Micro NBME

Viral Skin pathogens

Rubeola virus/measles Rubella virus Human herpes virus (HHV 6,7 Parvo B19 virus Varicella-Zoster virus Coxsackie A Pox Virus Herpes virus type 1 and 2 Human papilloma virus Molluscum contagiosum Orf Virus

Chlorhexidine

Salts dissociate and release the positively charged chlorhexidine cation. The bactericidal effect is a result of the binding of this cationic molecule to negatively charged bacterial cell walls. At low concentrations of chlorhexidine, this results in a bacteriostatic effect; at high concentrations, membrane disruption results in cell death.

Diagnosis of anthrax

Sample - respiratory secretions, pus from lesion, blood Microscopy: Gram stain: Gram positive large rods (Non motile), in chains, No spores from tissues DFA- to detect capsule M'Fadyean methylene blue stain/India ink-for capsule Culture: blood agar plates - non hemolytic. white-grey rough colonies, look like ground-glass/Medusa Head PCR: for rapid diagnosis

Diagnosis of Rabies

Sample: Saliva, serum, CSF, skin biopsy -Detection of rabies antigens- DFA -RT PCR (reverse transcriptase) Brain biopsy on autopsy: Negri bodies (inclusion bodies) Mann's, Giemsa, or Sellers stains

Blood agar

Sheep Blood agar- enriched and differential media Enriched: with blood Differential: hemolytic character (alpha, beta and gamma/non)

Viroids

Single circular RNA, no protein coat; identified only in plants

Bacterial cell size

Size ranges between 0.2-5 µm The smallest bacteria, Mycoplasma = largest virus (Pox virus), measures about 0.1µ to 0.2µ m in diameter

Transmission of Parasitic Disease

Source: Exogenous (from out side) Mode of transmission Ingestion: Contaminated water or food with human/animal waste Raw or undercooked beef/pork/fish Direct penetration: Arthropod borne, larval-directed skin penetration Transplacental Sexual contact

Categorization of Gram Positive Rods

Special techniques for endospore staining include the Schaeffer-Fulton stain (uses malachite green and safranin; spores appear green) and the Moeller stain (uses carbol fuchsin and methylene blue, spores appear red)

Diagnosis of Typhoid Fever

Specimen: blood, bone marrow, urine, stool (chronic) Culture : selective and differential media - Hektoen media: Serology/ Widal test: a test tube agglutination: detect antibody against specific O and H antigen in patient sera. Treatment: Multi drug resistance common: broad spectrum, fluoroquinolones, ciprofloxacin or ceftriaxone

Enzyme test

Spot test: rapid colorimetric assays Detect Beta lactamases; eg. ESBL (Nitrocef test) Chloramphenicol modifying enzyme-Chloramphenicol acetyltransferase Faster

Esophagitis

Symptoms: Dysphagia (difficulty swallowing), Odynophagia (pain on swallowing) Heartburn, acid regurgitation Etiology: Most often it is caused by non-infectious conditions gastroesophageal reflux. Less frequently by infectious agents The most common is: Candida: immunocompromised patients Cytomegalovirus (CMV) in immunocompromised HSV type 1: immunocompromised and immunocompetent Type and position of lesions: vary among the pathogens -CMV infection present with a single, deep ulcer as opposed to the multiple shallow ulcers seen in herpes esophagitis. -HSV commonly associated with small, superficial ulcers -Candida : White plagues

Clostridium botulinum

Tennis racket like structure - General properties: Gram positive spore forming rods, strict anaerobe Reservoir: Part of the colon normal flora of humans and animals. Widely spread in nature. Neutral and alkaline soils. Transmission: ingestion of preformed toxin; trauma and wound infection, ingesting spore by infants, inhalation Risk Factors/High Risk Populations: -Eating canned foods, especially home processed. -Eating fermented fish: Alaska outbreaks -Improperly sterilized commercial canned foods such as alkaline vegetables - green beans, peppers, mushrooms, smoked fish. -Drug addicts - sniffing of black tar heroin -infants < one year old fed with honey.

Family Rickettsiaceae Treatment

Tetracycline, chloramphenicol. Never give Sulfonamides because these drugs promote the growth of these group of organism.

Inclusion Bodies

The Negri body is an accumulation of rabies virions (belongs to Rhabdoviridae) in cytoplasm of neural cells Intranuclear inclusion body: From lesion of CMV (belongs to herpesviridae) infection-Cowdry type A (Owl' s eye)

Hyphae

The branching, threadlike tubes that make up the bodies of multicellular fungi

Acne

The chronic inflammatory condition that usually includes both comedones and inflamed papules and pustules (pimples).

Spheroplast

The complexity of the Gram negative cell wall results in innate resistance to enzymatic destruction of cell wall. Thus, Gm -ve bacteria with damaged cell walls become Spheroplasts i.e, they assume spherical shape even in a non-isotonic medium because of their resistance to differences in osmotic pressure between the extracellular and intracellular compartments.

Coccidioidomycosis

Valley Fever/ Desert Rheumatism Pathogenesis and Clinical Disease: most virulent among all human fungal pathogens Inhaled arthrospores convert to spherules in the lungs, produce endospores which again develop into more spherules - rupture, release endospores and disseminate Within 1 to 3 weeks flu-like symptoms develop symptoms include cough, malaise, chest pain After 6 wks: Pulmonary cavitary lesions that may calcify as they heal 1% may have disseminated disease may involve any organ, CNS, bone, skin (eruptions), soft tissue Formation of granuloma in different tissues Erythema nodosum/desert bumps (due to DTH response), and arthralgias (Due to immune complex formation) CNS, Bone, Skin+

Human T-cell lymphotropic virus 1

The only human oncogenic retrovirus identified, uses more subtle mechanisms of leukemogenesis. It encodes a protein (TAX) that transactivates gene expression, including genes for growth-stimulating cytokines (e.g., interleukin-2 [IL-2]).

HAV Pathogenesis

Virus, not-cytolytic. No direct killing, leaves infected cell by exocytosis Virus does not cause cytopathic effect on hepatocytes. Tissue damage: immune response Attack by T cytotoxic cells and NK cells Antibody, complement, ADCC No chronic infection, Life long immunity

Viral classification

Viruses are classified on the basis of their genome, capsid structure, envelope and replication strategy: Based on Genome: DNA: dsDNA; Gapped dsDNA; ssDNA; RNA: dsRNA; (+) ssRNA; (+) ssRNA with iDNA; (-) ssRNA. Based on Capsid Structure (capsid symmetry): Helical Icosahedral Complex Based on the presence/absence of Envelope Enveloped Non enveloped (naked)

Oncogenic human viruses

Viruses associated with human cancer

Naked viruses

Viruses that lack an envelope Naked with Icosahedral capsid: Capsomeres arranged in 20 triangles that form a symmetric figure - polyhedral e.g. poliovirus, adenovirus, hepatitis A virus Naked with Helical capsid: capsomeres arranged in a hollow coil that appear like a rod e.g. tobacco mosaic virus. So far no human viruses with this structure are known

Bubonic Plague Pandemics and Outbreaks

Three recorded pandemics: 6th,14th and 19th century In some places, no one was left alive to bury the dead!!! Outbreaks: First half of 20th Cent. in India; 1960s and 1970s- Vietnam war Most recent outbreak: 2014 - 2017 Madagascar (Africa): 1 August to 22 November 2017, a total of 2348 confirmed cases with 202 deaths (case fatality rate 8.6 %)

HBV antigens

Three viral antigens of importance HBsAg (surface antigen) - is detected in serum as particles (polymerizes) - can be detected by EM. HBcAg (core antigen, capsid) HBeAg (capsid Ag mainly secreted from infected cells to into the blood)

Ringworm

Tinea: The classic pattern -Ring shaped erythematous raised border, may contain papules and vesicles or scales -Lesions are usually pruritic; strong inflammatory response -Immune response, infection with zoophilic and geophilic species; strong inflammation Named after the affected area Tinea corporis, body Tinea capitis, scalp (T. tonsurans, T. rubrum) Tinea pedis, foot Tinea barbae, beard Tinea cruris: Groin Tinea unguium (onychomycosis), nails

Tissue Nematodes

Toxocara canis/ T. cati/Baylisarcaris procyonis - dogs/cat/racoon worms Ancylostoma caninum Dracunculus medinensis Filarial worms: Wuchereria bancrofti Brugia malayi Onchocerca volvulus Loa loa

Scarlet fever

"2nd disease" childhood exanthema Associated with pharyngitis Mediated by streptococcal pyrogenic exotoxin A (Spe A)/ Erythrogenic toxin, which is a super antigen) - produced by lysogenized strains Diffuse erythematous rash beginning on chest/neck and spreading to the trunk, extremities; with fever Strawberry tongue, skin desquamation-seen in tips of fingers and toes

Transduction

Transfer of bacterial genetic information using bacteriophage as the vehicle Bacteriophages Ds DNA viruses Complex structure, tadpole shaped-hexagonal head and cylindrical tail Head-icosahedral capsid with DNA 2 types: Virulent or lytic phage Temperate or lysogenic phage The phage coat protects the DNA in the environment so that transduction, unlike transformation, is not affected by nucleases in the environment. Not all phages can mediate transduction. In most cases gene transfer is between members of the same bacterial species. However, if a particular phage has a wide host range then transfer between species can occur. The ability of a phage to mediate transduction is related to the life cycle of the phage.

Generalized sequence of the stages of infection

Transmission from an external source into the portal of entry Evasion of primary host defenses such as skin or stomach acid Adherence to mucous membranes, usually by bacterial pili Colonization by growth of the bacteria at the site of adherence Disease symptoms caused by toxin production or invasion accompanied by inflammation Host response, both nonspecific and specific immunity, during steps 3,4 and 5 Progression or resolution of the disease

Risk factors for Pneumocystis jiroveci

Transmission: Respiratory; Inhalation of spores/cysts; Exact source-unknown. High Risk Populations: Low CD4 count (<200 cells/mm3) Most common opportunistic infection in patients with AIDS. Other people with impairments of cellular immunity such as primary immunodeficiencies, steroid treatment, organ transplantation and cancers are at risk

Non Arboviral Zoonotic Infections

Transmitted by Inhalation, or contact (do not require arthropod vectors) 1. Ebola virus 2. Hanta virus Haemorrhagic (Asia) Pulmonary (Americas) 3. Arenavirus Lymphocytic choriomeningitis virus (LCM) Lassa fever virus: Tropical Africa Junin fever virus Machupo haemorrhagic fever virus.

Structural Components of Bacteria

1. Cell Wall 2. Plasma Membrane 3. Cytoplasm 4. Ribosomes 5. Nucleoid 6. +/- Plasmids 7. +/- Capsule 8. +/- Biofilms 9. +/- Pili/Fimbriae 10. +/- Flagella 11. +/-Axial Filaments 12. +/- Spores

Growth requirements for bacteria

1. Essential elements: Hydrogen, Oxygen, Carbon, Nitrogen, Phosphorus and Sulphur 2. Mineral sources: K, Mg, Fe, Cu, Co, Mn, Mb, Zn 3. Organic growth factors: Growth factors or bacterial vitamins May be essential or accessory Vitamins: thiamine, riboflavine, nicotinic acid, pyridoxine, folic acid and vitamin B-12

Pandemic Strains of Influenza

2003 - 2013: Avian H5N1 - birds to humans, 637 human cases, First in China - spread to Europe, Africa April 2013 - avian H7N9- birds to humans, China - confirmed cases until April 2013, 400 confirmed with more than 125 deaths No human to human transmission yet

Protein Synthesis inhibitors

30s Aminoglycosides Tetracyclines 50s Macrolides Chloramphenicol Lincosamides Oxazolidinones Streptogramin

Bacterial Plasma membrane

4 important functions: Active transport of molecules into the cell Energy generation by oxidative phosphorylation Contains polymerizing enzymes for synthesis of cell wall Secretion of enzymes and toxins Components Phospholipid bilayer: similar to eukaryotic cells: Except that sterols are absent Some integral and/or peripheral glyco/lipoproteins participate in transport and/or metabolism

Viral Composition

A Complete virus is called a virion or a viral particle Genome + capsid = Nucleocapsid

Quellung test

A biochemical reaction in which anticapsular antibodies bind to the capsule of a bacterium, resulting in the capsule to swell or become more visible, especially under the microscope.

Gas Pak system

A commercial product, available in the form of a disposable packet of aluminium foil containing pellets of sodium borohydride and cobalt chloride and of citric acid and sodium bi-carbonate, is now widely used for preparing anaerobic jars. The chemicals generate hydrogen and carbon di oxide inside the jar when water (10ml) is added. Hydrogen combines with Oxygen in the presence of a catalyst (eg. Alumina pellets coated with palladium) present in the undersurface of the lid of the jar. After the inoculated plates are placed inside a large air-tight jar, it is incubated at 370 C. The gas pak technique is simple and effective.

Reservoir host

A host in which the infectious agent normally lives and multiplies. It acts as the source for transmission of infection to humans.

Parasite

A living organism requiring intimate prolonged contact with another living organism to meet some of its basic nutritional needs. It refers to eukaryotic pathogens.

Pathogen

A microbe that has the ability to cause disease

Infrared combustion technology

A mobile thermal processing system that uses electrically-powered silicon carbide rods to heat organic wastes to combustion temperatures. Waste is fed into the primary chamber and exposed to infrared radiant heat (up to 1,850 °F) provided by silicon carbide rods above the conveyor belt. A blower delivers air to selected locations along the belt to control the oxidation rate of the waste feed. Any remaining combustibles are incinerated in an afterburner.

Diagnosis of dengue fever

Travel history to endemic areas Serology: ELISA Dengue-specific IgM antibody (more than 5 days after onset of fever) Four fold increase of anti-dengue IgG (acute vs.convalescent sera) Real Time RT PCR Assay: DENV-1-4 Treatment: Supportive treatment only. Prevention: No effective vaccine yet - in progress Vector control, infected persons should avoid mosquito bite to limit spread

PYR test

A rapid colorimetric method for presumptive identification of certain groups of bacteria based on the activity of the enzyme pyrolidonyl arylamidase (also called pyrolidonyl aminopeptidase). L-pyrrolidonyl- β-naphthylamide (PYR) is impregnated into the test disk and serves as the substrate for the detection of pyrolidonyl arylamidase. Hydrolysis of the substrate yields beta-naphthylamide which combines with the PYR Reagent (p-dimethylamino-cinnamaldehyde) to form a bright pink to cherry red color. A positive PYR tests allows for the presumptive identification of group A streptococci (Streptococcus pyogenes) and enterococci

Antimetabolites

A substance that interferes with the normal metabolic processes within cells, typically by combining with enzymes or mimic an important or a required metabolite Inhibition of Folic acid Synthesis Sulfonamides (several derivatives) Trimethoprim Para-aminosalicylic acid (PAS) Dapsone

Antiseptic

A substance/chemical that can be applied to tissue and inhibits the growth of microorganisms.

Non-Gram-staining bacterium

Acid Fast: Mycobacterium Cell wall less: Mycoplasma Atypical cell wall: Chlamydia, Chlamydophila, Orientia, Ehrlichia and Anaplasma, Rickettsia Spirochetes: Treponema Borrelia Leptospira

Non permissive EBV infection

Additional Diseases associated with the virus : Leukemia/Hodgkin's lymphoma: In people with T cell deficiency or under immunosuppressive treatment Burkitt's lymphoma: tumor of B cell, Jaw and face, (in Africa), enhancement by malaria infection Nasopharyngeal carcinoma: cancer of epithelial cells (In Asia) Oral hairy leukoplakia: AIDS patient - wart like growth on tongue, EBV multiply in epithelial cells

Pathogenesis of Enterococcus faecalis/faecium

Adhesion and production of biofilm Antibiotic resistance - inherently resistant to commonly used antibiotics, eg. Oxacillin, cephalosporins Resistance also by acquired genes Eg. Aminoglycosides and Vancomycin- mediated by plasmids/Transposon - source for other bacteria Clinical Disease: Soft tissue infections/peritonitis after colon surgery, trauma; usually polymicrobial Other diseases: UTI-Cystitis and Pyelonephritis. Bacteremia; and endocarditis (previously damaged heart valve) Biliary tract infection

Treatment of Cyclospora cayetanensis

Trimethoprim/sulfamethoxazole Prevention and Control Increased sanitation and hygiene practices Warn travelers not to visit regions where the coccidian parasites are endemic Treatment with chlorine or iodine is unlikely to kill Cyclospora oocysts. No vaccine for cyclosporiasis is available

Trypanosoma

Trypanosoma brucei 2 subclasses Trypanosoma brucei gambiense Trypanosoma brucei rhodesiense African Sleeping sickness Trypanosoma cruzi --American trypanosomiasis, Chagas disease

Phase variation (conversion)

Also known as programmed gene rearrangement Switch genes on/off: results in phenotype switching that is faster than mutation Transcriptional regulation of alternative genes. This is not mutation: no gene is changed, Only the direction of the promoter or position of a gene is changed. There are several ways this is achieved The changes may affect host cell binding and virulence Eg. Pili of Neisseria gonorrheae Several genes encoding proteins with the same or similar functions and the ability to express only one of the these genes at a time. In effect this is achieved by maintaining only one active promoter at a time and/or moving genes to a position downstream of an active promoter.

Hairy Oral Leukoplakia

An Epstein Barr virus infection of the mouth seen in AIDS patients, Wart like growth that develops on the tongue, Multiplication of the virus in epithelial cells

Vector

An arthropod or other living carrier that transports a pathogenic organism from an infected to a non-infected host. Mechanical vectors: are non essential to the life cycle of the pathogen Biological vectors: serve as the site of some developmental events in the life cycle of the parasite

Cytochrome oxidase

An enzyme found in some bacteria that transfers electrons to oxygen, the final electron acceptor in some electron transport chains. Thus, the enzyme oxidizes reduced cytochrome c to make transfer of energy. Presence can be detected through the use of an Oxidase Disk which acts as an electron donator to cytochrome oxidase. If the bacteria oxidize the disk (remove electrons) the disk will turn purple, indicating a positive test. No color change indicates a negative test.

Lymphogranuloma venereum (LGV)

An infection of the lymphatic system caused by three strains of the bacterium Chlamydia trachomatis L1, L2, L3, transmitted sexually

Fungal Diseases

Two categories: 1. Infectious : Mycosis (plural-Mycoses) 2. Non infectious most common site is the skin, - dermatophytes -candida

S. aureus disease

Two categories: I. Pyogenic infections: direct organ invasion - involves several organs. II. Toxin mediated disease Scalded skin syndrome(SSS) caused by EFT (exfoliative toxin) Toxic shock syndrome (TSS): caused by TSST Food poisoning (will be presented with other food poisoning in GIT): caused by enterotoxin

Treatment of Enterobiasis

Two doses of albendazole, mebendazole or pyrantel pamoate two weeks apart give a very high cure rate. The drugs are effective against adults The second dose is to kill new worms hatching from eggs (retroinfection) The entire family should be treated, to avoid reinfection. Bedding and underclothing must be sanitized between the two treatment doses Prevention and control Good personal hygiene; prompt Rx of infected persons

Metazoa (helminths)

Two groups 1. Platyhelminthes - flat worms: two forms- a) Cestodes: segmented body, (proglottids), no alimentary tract, head has suckers &/or hooks for attachment, hermaphroditic b) Trematodes: leaf shaped, oral/ventral suckers, blind alimentary tract, usually hermaphroditic 2. Nemathelminthes/Nematodes—round worms, long with true alimentary tract, oral attachment device possible, produce eggs/ larvae, separate sexes

Cryptococcus spp

Two species C. neoformans and C. gattii Purulent Meningitis in the Immunocompromised/competent Most common cause of fungal meningitis

Fluorescence Microscope

An optical microscope that uses fluorescence and phosphorescence instead of, or in addition to, reflection and absorption to look at organisms on a slide. Up to 2000x magnification.

Human Immunodeficiency Virus (HIV)

Two types HIV-1, world wide, HIV-2 (mainly west Africa). Acquired Immunodeficiency Syndrome (AIDS) Belongs to Retroviridae, Lentivirus

Serological analysis

Antibody detection/titer ELISA Heamagglutination inhibition assay Neutralization tests: block cytopathic effects Western blot Rapid tests eg, for HIV Neutralization (prevention of cytopathic effect) Hemagglutination inhibition assay

Subcutaneous nodules

Are rarely seen and are usually associated with severe carditis. They are usually located over extensor surfaces of the knees, wrists and elbows

Antimicrobial Susceptibility Testing

Are used to make the best drug of choice to treat infections Diffusion Tests Dilution Tests Automated Tests Phenotype testing/Enzyme testing Molecular tests: Genotype testing

Atypical measles

Atypical rash without koplik's spots acute, more intense presentation; fever, pneumonia, petechiae, purpura or urticaria, starts from the extremities Occurs in people vaccinated with the killed vaccine, but did not develop sufficient immune response and when they get infected with a wild-type virus

Chlamydoconidia

Become larger than the hypha, are round and thick-walled , borne usually on the terminal end of the hyphae or along side.

Antihelminthic transport disruption

Benzimidazole - Mebendazole, Albendazole Broad spectrum anthelmintic Multiple paths: inhibits glucose transport and fumarate reductase, disrupts microtubules

Tegument

Between capsid and envelope-containing viral proteins and enzymes for replication

Vegetative reproduction

Budding: Budding by constrictions results in Blastospores (Blastoconidia) If cells do not separate, they form pseudohyphae Fragmentation of hyphae: results in Arthrospores (Arthroconidia)

Diagnosis of Clonorchis sinensis

By identification of eggs in the stool Egg- oval shaped, bile stained a convex operculum, that rests on visible "shoulders," at the smaller end of the egg. a small knob or hook-like structure at the opposite (larger, abopercular) end, Approx. 30 ×15µm

La Crosse encephalitis

California sero-group (LAC) Infectious agent : Bunyavirus.: Env, ssNeg sense RNA, helical Epidemiology: Reservoir: Forest Rodents- chipmunks and squirrels Vector: Aedes mosquito, Distribution: Suburban or rural environment, woody area, widely distributed in the U.S. 80-100 cases/year Risk population: highest attack rate age 5-18 year old Disease: Viral encephalitis Abrupt onset of encephalitis, frequently with seizures

Live attenuated influenza vaccine

Called FluMist (in the form of nasal spray), uses a temperature-sensitive mutant that can be reassorted with any new virulent influenza strain that appears. The reassorted virus will have the genes for the internal proteins from the attenuated virus (and hence will be attenuated) but will display the surface proteins of the new virulent antigenic variant.

Molecular fungal diagnosis

Clinical sample: PCR: Amplification of Fungal DNA In situ hybridization: detection of fungal DNA in tissue biopsy Culture: use of DNA probes to identify fugal culture; PCR

Viral Hepatitis Diagnosis

Clinical signs and symptoms Evaluation of the patient's blood for elevations in ALT, AST, and bilirubin Serology: Confirmatory diagnosis detection of antibodies against viral antigens viral antigen

Other STD Skin Pathogens

Commonest in the US are genital herpes (HSV2), syphilis and warts (human papiloma virus)

Smallpox (Variola) virus

Complex Structure Ds DNA, enveloped Complex appearance: brick like external structure and complex internal structure

Integumentary system

Covering- Skin and appendages Skin: Largest organ Epidermis Dermis Subcutaneous tissue Skin appendages - hairs, sebaceous glands, sweat glands

Lab Diagnosis of Hymenolepis nana

Demonstration in stool of characteristic egg with six-hooked embryo and polar filaments

Diagnosis of Trichomonas vaginalis

Demonstration of characteristic trophozoite in vaginal and urethral discharge; (unstained smears or Giemsa, papanicolaou stained smear) On Microscopy of wet preparation, T. vaginalis, which is larger than Polymorphonuclear leukocytes but smaller than an epithelial cell, it is recognized by its usually rapidly moving flagella, the rippling movement of undulating membrane and the jerky movement of the organism.

Diagnosis and treatment of chiggers

Demonstration of chiggers in skin scrapings Treatment: Antipruritics, Antihistaminics and Steroids Prevention and Control- Person going to chigger infested areas-insect repellents (eg.DEET)

Subacute Sclerosing Panencephalitis (SSPE)

Develops 1 to 10 years after the initial infection. Rare but Extremely serious Progressive, usually fatal CNS disease and those who survive are severely impaired mentally and physically. Occurs when a defective measles virus persists in the brain. The virus replicate slowly and move from cell to cell, not released. Risk factors include acquiring primary measles at an early age (usually under two years).

Treatment for Bedbugs

Diagnosis: Detection of tiny spots of blood from dead insects on bedding Observation of pattern and location of bites Treatment: Calamine lotion to relieve itching Antihistaminics Prevention and control Proper hygiene Malathion or lindane to treat mattresses and beds

Amoebic Liver Abscess

Diagnostic aspiration: Aspirated pus examined for the presence of trophozoites (Not cysts!!!!) Or, Liver biopsy Along with examination of stool, Serological tests Radiological examination PCR and DNA probe assay

Differential Diagnosis Urethritis/Cervicitis

Differences in Discharge Microscopy and Culture

Diagnosis of Echinococcosis granulosus

Difficult; x-rays, CT scans, MRI, serology detect antigens, skin test (Casoni's reaction)-An immediate hypersensitivity reaction. Intradermal injection of 0.2 ml of a fresh sterile hydatid fluid produces within half an hr, in all positive cases, a large wheal (5 cm in diameter) with multiple pseudopodia. It fades in an hour. Hydatid fluid from human cases (removed by operation) or from animals is used as antigen.

UV microscopy

Direct Fluorescent Antibody Staining (DFA) Detection and identification of viruses in patient's tissue/specimen or viral culture

Capnocytophaga canimorsus

Dog bite A thin Gram-negative rod, found in the normal oral flora of dogs Clinical infections Usually fulminant septicemia, peripheral gangrene or meningitis, DIC Risk factors: Splenectomy, alcohol abuse and immunosuppression have been associated with a number of cases

Diagnosis of Infective Endocarditis

Duke Criteria Duke University standardised criteria for assessing patients with suspected endocarditis Include -Predisposing Factors -Blood culture isolates or persistence of bacteremia -Echocardiogram findings with other clinical & laboratory findings

Hymenolepis nana

Dwarf tapeworm Epidemiology: worldwide, most often seen in Children (with poor hygiene)/day care centers Most common tapeworm infection in US. Infects humans, rodents and arthropods. Intermediate host not essential for human infection (but can pass through intermediate host as well) Transmission: fecal-oral, autoinfection, ingestion of arthropods (e.g beetles) in contaminated grain/flour Morphology Embryonated eggs (contain embryophore with 3 pairs of hooklets & polar filaments) Larva: Cysticercoid (attach on small intestine) Adult worm (2-4 cm in length, thread like)

Antibiotic sensitivity test

E.g Optochin sensitivity for alpha hemolytic Streptococcus spp.

Escherichia coli causing diarrhea

Each group causes diarrhea by different mechanisms There are five categories Non-inflammtory diarrhea - in small intestine (remains lumenal) -Enterotoxigenic E. coli (ETEC) travelers and infant diarrhea in developing countries -Enteropathogenic E.coli (EPEC) -Enteroaggregative E. coli (EAEC)] Inflammatory diarrhea ( will be discussed later) -Enterohaemorrhagic E. coli (EHEC) -Enteroinvasive E. coli ( EIEC)

Treatment for mucormycosis

Early diagnosis is crucial Surgical removal of damaged tissue Amphotericin B-first line therapy Generally Azoles (except Posaconazole) and echinocandin not effective

Treatment of Lyme Disease

Early stages- Doxycycline or Amoxicillin effective; severe forms or later stage: ceftriaxone Prevention: Rodent control, Protective clothing, Insect repellants, examining the skin and early removal of the ticks, Disinfect tick bite with alcohol or iodine, water + soap

Lice life cycle

Egg, nymph, and adult (CDC) Eggs: Nits are head lice eggs. They are hard to see and are often confused for dandruff or hair spray droplets. Nits are laid by the adult female and are cemented at the base of the hair shaft nearest the scalp . They are 0.8 mm by 0.3 mm, oval and usually yellow to white. Nits take about 1 week to hatch (range 6 to 9 days). Viable eggs are usually located within 6 mm of the scalp. Nymphs: The egg hatches to release a nymph . The nit shell then becomes a more visible dull yellow and remains attached to the hair shaft. The nymph looks like an adult head louse, but is about the size of a pinhead. Nymphs mature after three molts and become adults about 7 days after hatching. Adults: The adult louse is about the size of a sesame seed, has 6 legs (each with claws), and is tan to grayish-white. In persons with dark hair, the adult louse will appear darker. Females are usually larger than males and can lay up to 8 nits per day. Adult lice can live up to 30 days on a person's head. To live, adult lice need to feed on blood several times daily. Without blood meals, the louse will die within 1 to 2 days off the host

Pathogenesis of Brucella spp.

Entry: skin, mucus membrane Engulfed by phagocytic cells, inhibit phagolysosome, resist killing; and spread. Localized in: reticuloendothelial system , induce granuloma and abscesses Periodic release of Brucella into the blood induces the recurrent chills and fever typical of Brucellosis

Entamoeba histolytica

Epidemiology: world wide, highest incidence in tropical and subtropical regions; Transmission by fecal oral route; homosexual men; asymptomatic carriage common; prevalence in US: 1-2% Biology: Amoeba;trophozoite and cyst (maximum 4 nuclei)

Toxicity of oxygen

Especially harmful to obligate anaerobes Obligate anaerobes lack superoxide dismutase and catalase and/or peroxidase, and therefore undergo lethal oxidations by various oxygen radicals when they are exposed to O2 Superoxide dismutases are a class of enzymes that catalyze the conversion of superoxide into oxygen and hydrogen peroxide. Catalase convert hydrogen peroxide to oxygen and water. Tolerant anaerobes with low catalase and peroxidase levels are known

Morphology of leishmania

Exist as flagellate (promastigote) and non flagellate form (amastigote form) Kinetoplast: a mass of mitochondrial DNA lying close to the nucleus

Pathogenesis of Mycoplasma pneumoniae

Extracellular pathogen Adhesion: surface P1 protein binds to sialic acid on ciliated respiratory epithelial cells Tissue damage: Produce hydrogen peroxide, superoxide radicals and cytolytic enzymes - killing cells, destroying ciliary action Also act as superantigens-massive release of cytokines Clinical disease: Generally mild illness but can progress to severe form Incubation time 2-3 weeks Pharyngitis Tracheobronchitis (most common clinical presentation); low grade fever, dry cough Pneumonia: Atypical/ walking pneumonia - low grade fever, patchy bronchopneumonia, dry cough Complications (Extra-pulmonary); include hemolytic anemia, neurologic abnormalities, Stevens-Johnson syndrome etc.

Plasmids

Extrachromosomal genetic material (circular, DsDNA) Non essential genetic information May have more than one copy of a single plasmid

Relapsing fever pathogenesis

Febrile episodes - afebrile episodes alternation due to Antigenic variation Symptomatic/Febrile stage: has "chill phase" high fever and shaking chills + other non specific symptoms " flush phase" : drenching sweats Death is due to cardiac failure, hepatic necrosis or cerebral hemorrhage Mortality: 40% for epidemic 5% for endemic,

Hepatitis C virus (HCV)

Flaviviridae The most common chronic blood-borne infection in the USA World wide: 185million infected 350,000 die each year General properties: + ss RNA, Enveloped; 6 genotypes with >70 subtypes, variation on envelope glycoproteins Reservoir: Humans & chimps. Transmission: Same as HBV, but greater potential for establishing persistent and chronic infection Risk Factors/High Risk Populations: transfusion or transplant from infected donor; Injecting drug use; Hemodialysis (yrs on treatment); Accidental injuries with needles/sharps; Sexual contact; Multiple sex partners; Birth to HCV-infected mother

Electron Microscope

Focuses a beam of electrons through the specimen or onto its surface TEM or SEM

Focus Assay

For viruses with oncogenic potential

Sporangiospores

Formed in a sac called a sporangium, easily broken to free the spores

Laboratory Diagnosis of mycotic disease

Four approaches 1. Direct Light Microscopic Examination 2. Culture 3. Immunological tests/Serology 4. Molecular: eg, DNA probe tests

Coccidioides immitis

General propeties : Dimorphic fungus; At 25 0C: Mold- septate hyphae with arthroconida and In tissue, it forms spherules (endospore containing)-thick walled Reservoir: Soil in hot, semi-arid areas of the US- Southern California and the desert Southwest; Central and South America Transmission: Inhalation of arthroconidia (arthrospores) Risk Groups/High Risk Populations: travel, Regional - people of Asian descent (particularly Filipino), African-Americans, pregnant women (3rd trim.) and immuno compromised

Fasciolopsis buski

Giant Intestinal fluke Largest trematode: approx. 5 cm by 1.5cm Epidemiology: worldwide, common in China and other countries in south-east Asia; humans as definitive host and snail as intermediate host; pigs, dogs and rabbits as reservoir host Transmission: consumption of contaminated (with metacercaria) aquatic vegetations (eg. water chestnuts)

E. Coli enteropathy

Gm -, lactose fermenter, indole +

Dracunculus medinensis

Guinea worm or fiery serpent Epidemiology: Tropical Africa Transmitted by consumption of water (from 'step wells') containing infected Copepod, Cyclops

Cutaneous anthrax

Hide Porter's disease (most common form in humans) from wound inoculation, begins as a pruritic papule or vesicle that enlarges and erodes (1-2 days) leaving a necrotic ulcer with subsequent formation of a central black eschar with raised edematous edges, painless

Medical Significance of Spores

Highly resistant to heat and chemicals Not killed by boiling, but are killed at 121 0C The spore coat is impermeable to many chemicals - Only few disinfectants can kill spores (sporicidal disinfectants) Can survive for many years in the environment - eg. soil Any thing that is contaminated in soil may contain spores tetanus and gas gangrene by spore forming bacteria Their use as sterilization controls: B. stearothermophilus: in autoclave B. subtilis and C. tetani: in hot air oven

Id Reaction (Dermatophytid)

Hypersensitivity reaction; response to circulating fungal antigens; vesicle on finger

Diagnosis of Hookworm infection

Identification of eggs in stool - thin walled eggs with segmented ovum Differentiation between two hook worms-by study of their adult/larval morphologies and buccal capsules (hook like teeth or chitinous plates) Occult blood test (guaiac test): to detect presence of blood in stool

Diagnosis of Paragonimus westermani

Identification of operculated eggs in sputum and stool; x-ray

Translation in prokaryotes

Unique microbial initiation, elongation, and termination factors 1st aa - N-formyl methionine ( fMet) (soluble PAMP = recognized by innate immunity as foreign) Targeted by antimicrobial agents Eg, tetracyclines, Macrolides etc. Most metabolic regulatory mechanisms involve control of transcription of the gene into messenger RNA, rather than control of translation of the messenger.

Genotypic diagnosis

Includes the cause, and use of laboratory tests (endophenotypic). Based in genetic make up

R group of penicillin

Increases resistance to stomach acids Increases absorption in the GI Resistance to penicillinases (beta lactamases) Increases spectrum of activity But no improvement in allergic reactions

Systemic candidiasis

Infection of bronchi, lungs, gastrointestinal tract; septicemia; endocarditis and meningitis

Inversion

Is a chromosome rearrangement in which a segment of a chromosome is reversed end to end Through the utilization of specific recombinases, a particular DNA sequence is inverted, resulting in an ON to OFF switch and vice versa of the gene located within or next to this switch. Many bacterial species can utilize inversion to change the expression of certain genes for the benefit of the bacterium during infection.

Black widow spiders

Latrodectus mactans General characters Round shiny black abdomen Characteristic orange or reddish hourglass marking on the ventral surface Produce potent peripheral neurotoxin (Latrotoxin) Epidemiology: Worldwide-temperate and tropical regions, western and southern US, Old wooden building, cellars, hollow logs and outside toilet At Risk: Small children and Immunocompromised people

Bactoprenol

Lipid carrier molecule that transports peptidoglycan precursors across the cytoplasmic membrane

Conidia

May arise directly from hyphae or from specialised stalk-like structures - conidiophore

Relapse of Malaria

May result from Recrudenscence: due to persistence of blood infection in which surviving population of erythrocytic forms are increased. Is a feature of P. falciparum infection Recurrence or true relapse: Persistence of exoerythrocytic forms in the liver in which erythrocytic schizogony commences again Is a feature of P. vivax, P. ovale and P. malariae infections

Viral size and shape

Measured in nm Ranges from 18 nm to 300nm Assume different shapes

Blood &Tissue Protozoa

Medically Important: Plasmodium spp. Babesia microti Toxoplasma gondii Leishmania spp. Trypanosoma spp. Naegleria fowleri Acanthamoeba castellani

Camouflage

Molecular mimicry: antigenic similarity with host Hiding within cells - intracellular growth

Pathogenesis of Leishmaniasis

Multiply inside macrophages and other cells. Kala-azar (Visceral form)/Black fever/Dumdum fever: asymptomatic to rapidly fatal disease affects organs of the reticuloendothelial system (RES) Liver, spleen and bone marrow IP: several wks to a year Gradual onset of fever, chills, sweating, diarrhea, anemia Hyperpigmentation of skin Persistence results in Post-Kala-azar dermal leishmaniasis: hypopigmented/nodular lesions Cutaneous and muco-cutaneous forms: pruritic lesions enlarge and ulcerate

Ducreyi Chancre

Nature of the ulcer: soft chancres Extremely painful Begins as papules progressing to pustules, ulcerate Initially the lesion is typically solitary but by autoinoculation multiple lesions develop Position of ulcer; glans or shaft, anus, vulva, vagina and cervix Tender inguinal lymphadenopathy: suppurative rupture and leave chronic fistulae

Pneumonic plague

Necrotizing hemorrhagic pneumonia; most serious form of the disease IP: 1-4 days Symptoms: rapid onset of fever, malaise, pneumonia, productive cough, DIC, meningitis. Terminal cyanosis - blackening of skin - due to lack of oxygen responsible for the term 'Black Death'. Mortality almost 100%

Types of Staining Methods

Negative staining: Stain the background, not the object of interest: which will be transparent against colored back ground Eg. Capsule staining (India ink) Simple staining - one dye is used; reveals shape, size, and arrangement Differential staining - use a primary stain and a counterstain to distinguish cell types or parts (examples: Gram stain, acid-fast stain and endospore stain)

Side effects of aminoglycosides

Nephrotoxic 8th cranial nerve damage Hearing loss and/or loss of balance drug level monitoring required These drugs are ineffective in abscess. Do not penetrate cell wall of Gram positives. They are generally given with cell wall inhibitors to treat an infection with them.

Treatment of Influenza Virus

Neuraminidase inhibitors: inhibit viral release, effective against type A and B: are given within 48hrs of onset of symptoms Oseltamivir (Tamiflu): oral Zanamivir (Relenza): inhaled Prevention of uncoating: block matrix proteins (M2), effective against type A only Amantadine Rimantadine Development of resistance to these drugs is of concern.

Common causes of bacterial meningitis

Newborns Group B Streptococcus, Streptococcus pneumoniae, Listeria monocytogenes, Escherichia coli Babies and children Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b (Hib), group B Streptococcus Teens and young adults Neisseria meningitidis, Streptococcus pneumoniae Older adults Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b (Hib), group B Streptococcus, Listeria monocytogenes

Hypersensitivity Mycotic Diseases

Non Infectious Airborne spores, hyphal fragments; Id reaction

Bacterial interference

Normal flora Prevent colonization of pathogen Competition of receptor /binding sites Competition for nutrients Antagonize other bacteria Mutual inhibition by metabolic, toxic products and antibacterial substances eg, fatty acids, peroxides, bacteriocins

Viral Non-inflammatory diarrhea

Norwalk (norovirus) virus Rotaviruses Adenovirus Astrovirus

Oxygen and Bacterial Growth

Obligate aerobes: require oxygen. Grow best at atmospheric concentration of oxygen. Microaerophiles: require oxygen at a lower concentration than the atmospheric conc. Facultative anaerobes: can grow in the presence or absence of oxygen. Aerotolerant anaerobes: They do not use oxygen but can grow in the presence of oxygen. Obligate anaerobes: Get inhibited by oxygen Examples: Obligate aerobes: Pseudomonas, Bacillus Micro-aerophiles: Helicobacter, Campylobacter Facultative anaerobe: Escherichia coli, Vibrio cholerae (They are generally aerobes but can grow in the anaerobically environment) Aerotolerant Anaerobes: Lactobacilli, Clostridium carnis, C. histolyticum, C. tertium etc. Obligate anaerobes: Clostridium tetani, Bacteroides.

Clinical manifestation of mumps

One third asymptomatic but contagious IP: 16-18 days Prodromal phase : fever, malaise and anorexia Parotitis (30-40%): swelling of all of any of the salivary glands, could be unilateral or bilateral, resolves in 1 week Orchitis: inflammation of the testicles: In post-pubertal males painful unilateral swelling of testes, if bilateral can cause sterility Oophoritis: inflammation of ovaries can mimic appendicitis if the right ovary is involved. Not associated with infertility in women. Meningitis or encephalitis Pancreatitis

Other gonococcal infections

Other than reproductive system Proctitis (rectal infection) Pharyngitis: oral sex Ophthalmia neonatorum : eye infection in newly born babies Conjunctivitis - adults : autoinfection Disseminated infections: follows untreated local infections Bacteremia, meningitis, endocarditis, Skin lesions: mostly on the extremities Septic arthritis: joint infection: a leading cause in sexually active adults

Heat

Physical Agent Denature proteins Dry heat: Incineration - sterilization by combustion Direct flaming : used to sterilize heat resistant materials for immediate use. Eg. Inoculating loop Dry hot air (Hot air oven): 160 oC for 1hr, used to sterilize heat resistant materials like glass ware Infrared combustion technology

Pathogenesis of BK Virus

Primary replication in URT, viremia, Seeds renal tissue and lymphoid organs: remains latent in lymphocytes, Immunosuppression - reactivation Viral shedding in urine Tissue damage results from a combination of direct viral cytolytic effects and inflammatory responses Clinical Disease: BK-associated nephropathy (BKAN) Occurs in 5% of renal transplant recipient -Hemorrhagic cystitis -Ureteral stenosis, difficulty urinating, pain or burning sensations -Tubulointerstitial nephritis: is inflammation of the spaces between renal tubules. -Renal failure - allograft dysfunction and failure

Virulence factor

Properties of a pathogen that help it cause disease

Neisseria gonorrhoeae

Properties: Gram negative, diplococci, covered with pili, bean shaped, facultative intracellular; oxidase and catalase positive, ferments glucose but not maltose Gonorrhea=Glucose Reservoir: Humans, asymptomatic carriers Transmission: Sexual transmission, auto-inoculation, neonatal transmission, Risk Factors/High Risk Populations: Sexual partners of infected, neonates; Deficiency in C6-C9 - risk for disseminated infections Pathogenesis : Several surface structures and IgA Proteases

Prokaryotes vs Eukaryotes

Protein synthesis in bacteria =n-formyl methionine as the first amino acid; in eukaryotes it is methionine

Prion

Proteinaceous infectious agent Composition: only protein - no DNA or RNA Encoded by host cell genes Forms from post translational modification of gene products Normal protein (PrPc ) - has alpha-helical form Abnormal protein (PrPsc )- has beta-pleated sheet Extremely resistant to usual sterilization techniques Cause slow fatal neurodegenerative diseases in human and animals transmissible spongiform encephalopathies - Eg Creutzfeldt-Jacob disease (CJD)

Exotoxins

Proteins secreted by many bacteria Three types: A-B Toxin Membrane damaging Toxins Superantigens

Thoracic mucormycosis

Pulmonary involvement include infarct of lung tissue, cavitation and fungus ball formation, local hemorrhage

Mucocutaneous candidiasis

Whitish lesions composed of epithelial cells, yeast and pseudohyphae -Oral Candidiasis/ Oral Thrush- White 'cottage cheese' like patches or pseudomembranous type, may extend to esophagus, intestine -Angular cheilitis -Vulvovaginitis or Vaginal thrush: thick yellow/white discharge

Anaerobic Culture

a. Gas Pak system b. Anaerobic chamber c. Reducing medium - Thioglycollate broth

Other STIs

no signs/symptoms on the genitals Human immunodeficiency virus (HIV) Cytomegalovirus (CMV) Hepatitis B and C*

Types of Enteric Infections

1. Watery Diarrhea, non inflammatory 2. Diarrhea Dysentery, inflammation 3. Systemic Involvement/with or without dysentery

Syncytia formation

A process wherein cells are caused by viruses to fuse together into giant cells. Multi-nucleated syncytial cells are often the result of infections by enveloped viruses that induce cell fusion.

Complex virus

A virus with a complicated structure, such as a bacteriophage. Unusual morphology e.g. Poxvirus (enveloped), bacteriophage

Toll like receptors

Can directly activate NK cells in case of viral infection

Fungal cell wall

Composed of Chitin,Glucan, Mannan and proteins Chitin: a polymer of N acetylglucosamine (provides rigidity) Major composition of fungal cell wall Glucan : a polymer of D-glucose - provide additional strength Mannan +protein: a polymer of the mannose sugar found linked to surface protein. May undergo antigenic variation, activate complement Glucan and Mannan = PAMP (induce innate immunity)

Mannitol Salt Agar

Contains a high concentration (~7.5%-10%) of salt (NaCl). It is also a differential medium for mannitol-fermenting staphylococci, containing carbohydrate mannitol and the pH indicator phenol red for detecting acid produced by mannitol-fermenting staphylococci. Selective - high osmotic pressure & % NaCl Differential - mannitol fermentation

Balantidium coli: life cycle

Cysts are the parasite stage responsible for transmission of balantidiasis . The host most often acquires the cyst through ingestion of contaminated food or water . Following ingestion, excystation occurs in the small intestine, and the trophozoites colonize the large intestine . The trophozoites reside in the lumen of the large intestine of humans and animals, where they replicate by binary fission. Trophozoites undergo encystation to produce infective cysts. Some trophozoites invade the wall of the colon and multiply. Some return to the lumen and disintegrate. Mature cysts are passed with feces.

Common Respiratory Viral Pathogens

DNA Viruses Non enveloped Adenovirus: Adenoviridae: ds DNA Enveloped Epstein-Barr Virus Herpesviridae: dsDNA RNA viruses Non enveloped Rhinovirus : Picornaviridae, ss + sense Coxsackie A: Picornaviridae, ss + sense Enveloped: Coronavirus: Coronaviridae, ss + sense Parainfluenza Virus: Paramyxoviridae, ss negative sense Metapneumovirus Paramyxoviridae, ss negative sense Respiratory Syncytial Virus: RSV Paramyxoviridae , ss negative sense, Influenza virus: Orthomyxoviridae, ss negative sense , 8 segments RNA

Tertiary or late syphilis

Decades later, 10-40 years Chronic inflammation with tissue destruction a non-contagious but highly destructive phase Different manifestations Gummatous (Gumma) syphilis: granulomatous lesion, painless a soft, non-cancerous growth Cardiovascular syphilis: affects aorta, and valve Neurosyphilis: include psychosis, dementia, myelopathy (tabes dorsalis), seizures, optic nerve dysfunction (Argyll-Robertson pupil ), loss of vision etc Destructive joint diseases

TB culture

Decontamination of sputum specimens with 2% sodium hydroxide to reduce contaminants Inoculate into egg/agar based media (Lowenstein-Jensen or Middlebrook) Grows slowly, generation time 18-20hrs Culture kept up to 8 weeks before reporting as negative

Diagnosis of T. Brucei

Demonstration of trypomastigotes in body fluids From primary lesion, blood, CSF

Streptogramins

Derivatives: Quinupristin, Dalfopristin Mechanism of Action: Both drugs given at the same time: synergistic action Inhibit protein synthesis: Dalfopristin - binds to 50s and prevent peptide chain elongation Quinupristin: causes premature release of peptide Pharmacology: bactericidal, Narrow spectrum: Gram positive Recommended for vancomycin resistant Staphylococcus and Enterococcus

Diagnosis of Enterobiasis

Detection of adult worms and eggs by: Peri-anal swab-method of choice Scotch tape Occasionally, stool specimens Eggs are thin walled and assymmetrical

Diagnosis of epidemic typhus

Detection of antigen: Direct fluorescence assay (DFA) on biopsy specimens: Detection of antibody (Serology): using Micro-immunofluorescence (MIF)- diagnostic method of choice Treatment: Antibiotics such as tetracycline/doxycycline Prevention: Louse control measure Tetracycline : post exposure Inactivated typhus vaccine is available - for people at risk

Treatment of Adenovirus

Diagnosis: Clinical presentation; immunoassay (fluorescent ab or ELISA) or PCR on samples; virus Isolation in cell culture. Treatment: There is no specific antiviral therapy Prevention: Hygiene - washing hands; Covering mouths/nose when sneezing or coughing Proper chlorination of swimming pools Vaccination: live vaccine (non attenuated) only for military recruits to prevent Adult Respiratory Distress Syndrome. Consists of live type 4, 7, and 21 in coated capsules (Monovalent),. Given orally

Diagnosis and Treatment of Molluscum contagiosum

Diagnosis: Clinical, virus can not be cultivated. Histology: large, eosinophilic, cytoplasmic inclusion bodies in epithelial cells. "molluscum bodies" Molecular: PCR Treatment: Spontaneous resolution in 2-12 months; Surgery (to shorten duration): Remove the nodules by curettage (scraping) or, Cryosurgery: application of liquid nitrogen (freeze and destroy lesions)

Urethritis

Discharge and burning pain (dysuria) during urination, fever absent

Pathogenesis of Malassezia furfur

Disease: Pityriasis versicolor (Tinea versicolor) -Superficial skin infection of the stratum corneum -Lesions- irregular but well demarcated macules of hypopigmentation or hyperpigmentation May be covered with fine scale, minimal itching, cosmetic importance -No inflammation -Interference with melanin production In dark skinned - hypopigmented Light skinned - hyperpigmented - pink/pale Appear mostly on upper trunk, face, neck, arms, or abdomen

Treatment of Fasciolopsis buski

Drug of choice-Praziquantel Prevention and Control: Education on safe consumption of aquatic vegetations, Chestnuts Use of molluscacides to control snails, Control of reservoir hosts, Early treatment of cases

Treatment of Trichuriasis

Drug of choice-albendazole/mebendazole Prevention: education, good personal hygiene

Skin Lesions

Due to alteration in the integumentary system or skin. Various types: either flat lesions, elevated or depressed lesions. solid or filled with pus or clear fluid localized as single or multiple Disseminated multiple lesions Lesions could be manifestation of systemic infections or of localized infections Macule, patch Papule, Nodule, Plaque (flat topped) Maculopapular Vesicles: clear fluid Bullae: big vesicle Pyoderma: skin inf. with formation of Pus Folliculitis, furuncles (boils), carbuncles; abscess, pustules Impetigo: vesicle with honey colored crust Petechiae: hemorrhagic spots-red/purple Purpura: coalescing petechiae Ecchymosis: large purpura Cellulitis Erysipelas: large raised red patches on the skin; involves dermis and superficial lymphatics Ulcer Granulomas Eschars: dead tissue that sheds Fasciitis/myonecrosis Warts: hard benign growth Tineas: Ringworm

Malarial Infection of RBC

During the erythrocytic stage of the parasite's life cycle, it uses intracellular hemoglobin as a food source. The protein is broken down into peptides, and the heme group is released and detoxified in the form of hemozoin Maurer clefts/dots: finely granular precipitates or irregular cytoplasmic particles that usually occur diffusely in red blood cells infectedwith the trophozoites of Plasmodium falciparum. They are membrane-limited vacuoles or sack-like structures in the cytosol of the erythrocyte, formed early after invasion by the parasite, visible as blue dots in Giemsa-stained blood smears. Their origin and functions remain still unclear.

Vaginosis Clue Cell

Epithelial cells with bacteria adhering to their surface and sometimes obscuring their borders. Rough cell membrane

Spontaneous mutation

Error during replication Mutation rate in viruses is high due to the poor fidelity of viral polymerases Mutation rate > in RNA than DNA virus because RNA viruses do not have error-checking mechanism Viruses are subject to the same type of mutations as other organisms Different types of mutations - resulting in variety of mutants Lethal mutant - due to inactivation of essential genes, can't replicate Defective mutant- deletion/mutation of gene/s: able to replicate with the help of other viruses Host range mutant - change of host/tissue specificity Attenuated mutant - causes less serious/no disease (vaccines) Conditional mutant: (eg temperature sensitivity of influenza live vaccine - can multiply at lower temp of URT but not LRT

Formol Ether Concentration Technique

Ether adsorbs fecal debris & floats. Formalin fixes/ preserves the specimen.

Laboratory Diagnosis of Intestinal Amoebiasis

Examination of stool: -Macroscopic examination: offensive, darkbrown semi-fluid stool mixed with blood and mucous -Microscopic examination: Demonstration of E. histolytica-Cysts/trophozoites Presence of Cellular exudate and Charcol-Leyden crystals Charcot-Leyden crystals are slender and pointed at both ends. They consist of Lysophospholipase (an enzyme synthesized by eosinophils) and are produced from the breakdown of eosinophils PCR and DNA probe assay

Serotyping

Further Identification of isolates: detection of expressed antigens Slide agglutination: identify antigens present on the surface of specific microorganisms Use of Fluorescent dye tagged antibodies - DFA

Treatment for Cytomegalovirus

Ganciclovir, (resistance has emerged Foscarnet : for ganciclovir resistant Prevention and control Safe sex Screening of blood and tissue donors Avoid seropositive donors Prevention of congenital and perinatal transmission difficult Seropositive mothers unlikely to pass the infection Passive immunization (CytoGam) To prevent disseminated infection in organ transplant patients

Ethylene oxide

Gas Bactericidal even against spores Great penetrating power because it is a gas Alkylates protein and nucleic acid Used to sterilize bulky stuff such as bedding materials heat sensitive medical materials, like plastic gloves, syringes Highly toxic, so need of special chamber

Diagnosis of H. pylori

Gastric Biopsy: invasive, not found in blood or stool. The only specimen to isolate it from gastric biopsy. Microscopy: gastric biopsy tissue staining and detection of Helicobacter Biopsy may be stained with hematoxylin-eosin, Gram stain, but The Warthin-Starry silver stain is most sensitive - almost 100%. But the procedure of taking biopsy is invasive. Urease detection: by placing gastric biopsy on urea containing medium - detect change in pH Culture: require enriched media and microaerophilic, require 2 weeks. (Bacteria not commonly found in stool or blood) Campy or Skirrow Antigen detection from stool Using monoclonal antibodies specific to HP Urease breath test: ingest radioactive urea - detection of radioactive CO2 in breath Serology: IgA and IgG: detects exposure, antibodies persist for many years, Nucleic acid detection: limited to research labs

Pasteurella multocida

General Properties: Gram negative capsulated small rod, bipolar staining (safety pin appearance) oxidase positive; sensitive to penicillin G Grows well in ordinary media (blood agar) at 37 0C, but not on MacConkey agar. Reservoir: normal flora of the oropharynx of healthy cats, dogs, other domestic animals and rodents Transmission: animal bite or scratch (primarily cats and dogs in the human population or lick an open wound Risk Population/Risk factor: Anyone; Sutures

Vibrio vulnificus

General Properties: Motile, Gram negative curved rod, facultative anaerobe, oxidase positive, halophilic Reservoir: warm estuarine or marine water, common in Gulf Coast states. A notifiable disease in the US (responsible for > 90% vibrio related deaths in US) Transmission: Direct contact with contaminated salt water (break, scratch) in skin or Consumption of improperly prepared shellfish (oysters)/sea food Risk Factors/Risk Populations: wound in any person (through direct contact). Immunocompromised, patients with chronic liver disease - Septicemia (through ingestion) Virulence and pathogenesis: - Capsule, cytolysin and numerous extracellular enzymes

Coxiella burnetii

General features: Pleomorphic- Gram negative rod (related to Legionella) or spherical cell (endospore-like structure), stable in harsh environment shows phase variation (Phase I: LPS intact, Phase II: O antigen missing) Epidemiology: Reservoirs: wide range of animals: farm animals (Cattle, sheep, goat), birds. High conc. in placenta, excreted in milk, urine and feces. Transmission: inhalation of airborne particles, or ingestion of unpasteurized milk or meat. (Not by arthropod!!!) Geographic distribution: worldwide. Reportable in the US since 1998. In 2017: 153 acute and 40 chronic Q fever cases Risk Group: exposure to livestock; Ranchers, veterinarians, abattoir workers, and few handlers. Q fever

Borrelia spp

General properties: Gram negative spirochete, show antigenic variation (upto 30) of surface protein Transmission: lice- epidemic; tick bite or via feces- Endemic Risk Factors/High Risk Populations: Epidemic RF- Conditions of overcrowding and social disruption (eg, refugee setting)/low socioeconomic status Endemic RF - hunters, campers and woodsmen, seasonal Few cases reported in US, In US, primarily linked to sleeping in rustic, rodent-infested cabins in the mountains & exposure to caves Bite of soft ticks is brief, usually lasting less than half an hour

Clostridium perfringens

General properties: Gram positive rod (rectangular) Anaerobe, spore former- but spores rarely seen in vivo or in vitro growth, several types: A-E. depending on what toxin they produce. Most human infections due to type A. Reservoir: Soil and human colon Transmission: Spores introduced into wounds Risk Factors/Risk Populations: Trauma (war, automobile accidents), septic abortions, Diabetics or others with poor peripheral circulation Septic abortion is serious uterine infection during or shortly before or after an abortion. Septic abortions usually result from induced abortions done by untrained practitioners using nonsterile techniques

Rhinovirus

General properties: Non-enveloped, icosahedral, ss +sense RNA, at least 100 serotypes are known Replication in the cytoplasm using RNA-dependent RNA polymerase (viral coded/not carried) resistant to drying, detergents Epidemiology: >half of all URTI, Early autumn and late spring, infants/children-high risk Reservoir: Humans and chimpanzees Transmission: direct contact (hands); inhalation of aerosols; by fomites

Noroviruses

General properties: Positive ss RNA, non-enveloped icosahedral , 'Star of David' like appearance. Reservoir: Human GI tract Transmission: Highly transmissible: person-to-person via oral-fecal food & water, including aerosols, as few as 10 virions; shedding of the virus may continue for 2-3 weeks after symptoms have ceased. Environmentally stable, Occurs year around (peaks Nov. April) Risk Factors/High Risk Populations: Outbreaks in group settings: schools, camps, hospitals, families. Outbreaks have plagued cruise ship populations; Schools in the US - Feb 2016

Adenoviridae

General properties: ds DNA virus, non-enveloped; Icosahedral capsid Capsid protein (capsomeres)-hexons and pentons Pentons at the apices- each consisting of a base and a protruding fiber which serves as an attachment protein and also a hemagglutinin More than 55 human serotypes based on antigenic variation on fiber Resist dryness, detergents, mild chlorine level May survive up to 90 days in poorly chlorinated pools Capsid consist of 252 capsomeres (240 hexons, 12 pentons) . The pentons make up the apices and possess projecting fibers. These are the only virus that have protruding fibers. The fibers are means of attachment and are hemagglutinin. Purified fibers are toxic to human cells.

Metapneumovirus

General properties: enveloped, ss negative sense RNA, family Paramyxoviridae, genus Pneumovirus Relatively recently recognized pathogen (2001) Almost all children by age 5 are seropositive At risk: Seronegative children, elderly and Immunocompromised May cause 15% of all children's colds May also cause bronchitis, bronchiolitis, pneumonia Diagnosed by RT-PCR.

Nucleoid

Genome not enclosed within a nuclear envelope Most bacterial chromosomes are single, circular, highly coiled and haploid Double stranded DNA No introns Ultrastructure: fine structure, especially within a cell, that can be seen only with the high magnification obtainable with an electron microscope. Has no histones (protein) in the chromosome

Treatment of Tularemia

Gentamicin-drug of choice Prevention: Avoid exposure to reservoirs safety precaution in lab Live Attenuated vaccine for high risk group eg. Lab personnel (Currently under FDA review)

Enteroinvasive Escherichia coli (EIEC)

Gm -, lactose fermenter, indole + Virulence: several genes on a plasmid mediated bacterial invasion (pInv) Invade colonic epithelial cells, escape from phagosome, multiply in cytoplasm, move to adjacent cells, like shigella But does not produce enterotoxin Disease: IP 12-72 hrs on Infective dose - 10 organisms Fever, cramping, watery diarrhea may progress to dysentery Primarily seen in under-developed countries, rare in the US

Diagnosis and treatment of Streptococcus viridans

Gram positive cocci, catalase negative, alpha hemolytic, lack Lancefield antigen, optochin resistant, bile insoluble not lysed in bile, non capsulated Treatment and prevention: Penicillin, increase in resistance

Klebsiella granulomatis

Granuloma Inguinale (Donovanosis) Gram-negative rod bacterium, obligate intracellular, infect mononuclear cells . Requires cell culture. Reservoir: Humans, gastrointestinal Transmission: Sexual transmission Risk Factors/High Risk Populations: Sexually active, found predominantly in Africa, Papua new guinea, India and the Caribbean, homosexual men in the USA and Europe. In the US - probably < 100 cases/year

Complicated UTI treatment

Guided by culture and susceptibility results, Empiric therapy should cover broad spectrum coverage

HSV Central nervous system infection

HSV I: encephalitis: acute/subacute- highly fatal Most common cause of endemic/sporadic encephalitis all seasons and all ages Necrotic lesion on temporal lobe General and focal signs of cerebral dysfunction HSV-2: meningitis/encephalitis

Complications of S. dysenteriae

HUS (Hemolytic Uremic Syndrome): Associated with Shiga toxin When toxin enters circulation causes acute hemolysis, renal failure, uremia, thrombocytopenia, and disseminated intravascular coagulation Primarily disease of infants and children (6 months to 4 years), ~ 15% mortality.

Leprosy

Hansen's Disease IP- Average 5-7 yrs (vary between 2-40 yrs ) A progressive, disfiguring disease Chronic infections of the skin, peripheral nerves, upper airway, eyes and testicles Two forms based on host immune response 1. Tuberculoid: strong cellular; weak humoral, few bacteria in tissue 2. Lepromatous: weak cellular, strong humoral, heavy bacterial burden These are the two extreme manifestation of the disease - with several intermediate stages

Naegleria fowleri life cycle

Has 3 stages in its life cycle: , ameboid trophozoites , flagellates, and cysts. The only infective stage of the ameba is the ameboid trophozoite. Trophozoites are 10-35 µm long with a granular appearance and a single nucleus. The trophozoites replicate by binary division . Trophozoites infect humans or animals by penetrating the nasal tissue and migrating to the brain via the olfactory nerves causing primary amebic meningoencephalitis (PAM). Trophozoites can turn into a temporary, non-feeding, flagellated stage (10-16 µm in length) when stimulated by adverse environmental changes such as a reduced food source. They revert back to the trophozoite stage when favorable conditions return. Naegleria fowleri trophozoites are found in cerebrospinal fluid (CSF) and tissue, while flagellated forms are occasionally found in CSF. Cysts are not seen in brain tissue. If the environment is not conducive to continued feeding and growth (like cold temperatures, food becomes scarce) the ameba or flagellate will form a cyst. The cyst form is spherical and about 7-15 µm in diameter. It has a smooth, single-layered wall with a single nucleus. Cysts are environmentally resistant in order to increase the chances of survival until better environmental conditions occur.

Lipopolysaccharide (LPS)

Has three distinct units: 1. O antigen: An outer polysaccharide consisting up to 25 repeating units of 3-5 different type of sugars 2. A core polysaccharide - five sugars attached to Lipid A - is common to all Enterobacteraeae 3. A phospholipid - Lipid A, positioned inside the layer- Lipid A - is an endotoxin - toxic shock, fever O antigen: antigenic determinant used in serotyping of bacteria

Bacterial ribosomes

Has two units Differ from eukaryotic cell ribosome in size and chemical composition Bacterial ribosome size -70s with 50s and 30s subunits Eukaryotic cell ribosome size - 80s with 60s and 40s subunits Site for antibiotic action The Svedberg unit (S) offers a measure of particle size based on the rate of the sedimentation in the centrifugation

Diagnosis of tularemia

Hazardous for lab people!! Microscopy: Gram staining insensitive even from samples from ulcer since bacteria are extremely small and stain faintly DFA staining-more sensitive and specific Culture: requires cysteine supplemented media Cysteine + Chocolate agar or Buffered Charcoal Yeast Agar (BCYE) agar (does not grow on blood agar); Grows slowly (3-5 days) Serology : Four fold increase of paired sera or single titer (1:160 or more). Antibodies can persist of long time. Positive Serology may not differentiate past and present infection

Human Herpes Virus (HHV) 6 and 7

Herpes viridiae (family) Beta-Herpesvirinae(subfamily) Roseolovirus (genus) Roseola/ exanthem subitum, 6th disease "Sudden rash" General properties: Same as -typical herpes virus. primarily infect lymphocytes, especially CD4 T cells cause latent infection in T cells and monocytes. Reservoir: Humans: adults almost 100% seropositive Transmission: transmitted via saliva as it replicates in the salivary glands Risk Factors/High Risk Populations: Infections occurs early in life, (highest peak 6-24months). Reactivation in immunocompromised

Varicella-Zoster Virus

Herpesviridae Family Alpha herpes virinae (subfamily) Varicellovirus (Genus) Chickenpox (Varicella) Shingles (Herpes Zoster) General properties: Enveloped, ds linear DNA, icosahedral neucleocapsid, member of the human herpes, Produce viral thymidine kinase (required for activation of antiviral drugs) Reservoir: Humans: Life long latent infection; 90% seropositive Transmission: highly contagious, Predominantly by Respiratory droplet; Also by contact with skin lesions (vesicles); No seasonality Risk Factors/High Risk Populations: Unvaccinated populations, children below 10 years (Chicken pox) >60 years (Shingles)

Histoplasma capsulatum

Histoplasmosis "Cave disease" General properties: dimorphic : mold at 250 C yeast at 370 C. Mold produces two types of asexual spores- important for identification Tuberculate macroconidia - thick walled with spike-like projections Microconidia - thin smooth walled, smaller Reservoir: Soil heavily contaminated with birds/bats droppings, alkaline soils Transmission: Aerosolization of fungal micro-conidia Excavation of soil during construction, Exploration of bat infested caves Risk Groups/High Risk Populations: Regional travel; highest incidence in Great lake river basins of US- Ohio, Missouri and Mississippi River valleys; Central and South America,

Fasciolopsis buski life cycle

Humans ingest the encysted larval stage (metacercaria) through contaminated aquatic vegetations (eg. water chestnuts). The metacercaria gets released from the husk due to chewing action, swallowed and develop into immature flukes in the duodenum. The fluke attaches to the mucosa of small intestine with its suckers, develops into adult worms and undergoes self-fertilization. Eggs production usually starts 3 months after ingestion of metacercaria. The operculated eggs released in feces reach water and free swimming larval stage (miracidium) is liberated through operculum. The miracidium penetrates the soft tissue of snail with the help of certain lytic substances it produces. In the snail tissue, the miracidium develops through a series of stages. The final stage (cercaria) in the snail is a free swimming form that, after release from the snail, encysts on the aquatic vegetations, becoming the metacercaria or Infective stage

Fungal Reproduction

I. Asexual A. Vegetative reproduction By budding (in yeast) or fragmentation of hyphae B. Formation of asexual spores: Anamorph Several types: important in identification II. Sexual: Formation of sexual spores: Teleomorph Not used for identification, but for taxonomy

DNA Viruses

I: ds DNA: replication is the same as for Eukaryotic DNA and can make mRNA from dsDNA, eg. Herpes virus use host DNAdep-DNApoly.(but varies) and DNA dependent RNA polymerase. _dsDNA viruses (e.g. Adenoviruses, Herpesviruses, Poxviruses) (Polyoma, papillomaviruses use host coded DNA polymerase whereas Adeno and Herpesviruses use viral coded DNA polymerases) II: ss DNA: replication passes through ds DNA then to mRNA, eg. parvovirus use a host DNAdep---DNApoly and DNA dependent RNA polymerase -ve strand or antisense ) DNA (e.g. Parvoviruses) VII: Partially ds DNA: replicate through RNA intermediate - Uses host DNA dep-RNA poly and code their own RNAdep-DNApoly. Eg. Hepatitis B (hepadnaviridae) VII: dsDNA-RT viruses (e.g. Hepadnaviruses i.e Hepatitis B virus)

Baltimore Classification

I: dsDNA viruses (e.g. Adenoviruses, Herpesviruses, Poxviruses) (Polyoma, papillomaviruses use host coded DNA polymerase whereas Adeno and Herpesviruses use viral coded DNA polymerases) II: ssDNA viruses (+ strand or "sense"/-ve strand or antisense ) DNA (e.g. Parvoviruses) III: dsRNA viruses (e.g. Reoviruses) IV: (+)ssRNA viruses (+ strand or sense) RNA (e.g. Picornaviruses, Togaviruses) V: (−)ssRNA viruses (− strand or antisense) RNA (e.g. Orthomyxoviruses (influenza virus), paramyxoviruses (measles, mumps, respiratory syncytial virus etc), Rhabdoviruses (rabies virus etc)] VI: ssRNA-RT viruses (+ strand or sense) RNA with DNA intermediate in life-cycle (e.g. Retroviruses) VII: dsDNA-RT viruses (e.g. Hepadnaviruses i.e Hepatitis B virus)

Diagnosis of E. coli meningitis

Identification E. coli serogroup K1: by Latex agglutination PCR

Diagnosis of Loiasis

Identification of adult worms in the eyes Identification of microfilariae in blood smears taken between 10AM and 2PM (Day time) Serology

The virulence of Haemophilus influenzae

IgA protease: facilitates colonization Pilli and non pillus adhesins Endotoxin - Lipo-oligosaccharide (LOS), similar to the Neisseria: adherence, toxic to ciliated cells, induce inflammation Difference between LPS and LOS: LOS lacks an O antigen Polysaccharide capsule: antiphagocytic Type b capsule is made up of polyribose-ribitol phosphate (PRP) - most invasive diseases are caused by H. influenzae type b (Hib)

Dark Field Microscope

Illumination comes from the sides, thus making the background appear dark, and the organism on the slide appear light(bright).

Immunological diagnosis

In Vitro: Serology; Antibody or Antigen. In Vivo: skin tests : eg. PPD test

Categorization of Gram Positive Cocci

In general, the following characteristics Cytoplasmic lipid membrane Thick peptidoglycan layer Teichoic acids and lipoids are present, forming lipoteichoic acids, which serve as chelating agents, and also for certain types of adherence. Peptidoglycan chains are cross-linked to form rigid cell walls by a bacterial enzyme DD-transpeptidase. A much smaller volume of periplasm than that in gram-negative bacteria.

Brudzinski's sign

In response to passive flexion of the neck towards the chest, both the knees and hips are flexed This reflex is due to exudate around the roots in the lumbar region.

Urinary Tract Infection statistics

In the US, UTI ranks second to respiratory infections in their incidence. Accounts for more than 10 million office visits and 1 million hospitalizations each year at a total cost exceeding 1 billion dollars. Most common nosocomial infections; 40% of all nosocomial infections are UTIs 75% of all nosocomial UTIs are associated with urinary catheter Up to 10% of UTIs result in serious complications such as Gram-negative sepsis or chronic pyelonephritis with loss of renal function.

Trichomonas vaginalis life cycle

In the United States, an estimated 3.7 million people have the infection, but only about 30% develop any symptoms of trichomoniasis. Infection is more common in women than in men Female- found in urethra and vagina, male- in urethra and prostrate gland Sexual transmission is the primary mode of transmission.

Treatment of T. Brucei

Indicated for all persons diagnosed Pentamidine for first stage T. b. gambiense infection is widely available in US Other drugs (suramin, melarsoprol, eflornithine, and nifurtimox) to treat Afr. Tryp. are available in the U.S. only from the CDC Prevention and Control Wearing long-sleeved clothes Inspection of vehicles before entering Avoiding bushes. Use of insect repellent

Gray baby syndrome

Infants skin appears gray with vomiting and shock- due to toxic concentration of Chloramphenicol. This occurs due to reduced glucuronyl transferase (responsible for detoxification of chloramphenicol) activity in infants.

Toxoplasma gondii congenital infection

Infection during pregnancy may lead to abortion, still birth, blindness and congenital defects of the fetus: Ocular: Chorioretinitis- blurred vision, photophobia, and eye pain Neurologic: Intracerebral calcification, hydrocephaly/ microcephaly, convulsions, mental retardation Cardiac: Cardiomegaly Intracerebral calcification. If a woman is infected for the first time during pregnancy the parasite can cross the placenta and cause fetal disease. Both the probability and severity of the disease depend on when the infection takes place during pregnancy. Early: low transmission, but severe disease Late: high transmission, more benign symptoms. Hydrocephaly.

Septic (infectious) arthritis

Infection of the surface of cartilage lining the joint and synovial fluid Most common cause: Staphylococcus aureus

St. Louis encephalitis (SLE)

Infectious agent : Flavivirus- Env, +ve sense ss RNA, icosahedral Epidemiology: Reservoir are birds House sparrow, pigeon, blue jay, and robin may infect horses, but no disease Vector: Culex mosquito Distribution: Predominantly urban area, 102 cases annually. Risk group: adults >40 years old Disease: Viral encephalitis, moderately severe encephalitis, with mortality rate of 10%, sequelae are uncommon

Dengue Fever

Infectious agent: Dengue virus (Flavivirus), Enveloped, ss + sense RNA: There are 5 serotypes (1-5) Reservoir: Monkeys and humans Vector: Aedes aegypti and Aedes albopictus breeds in urban areas, stagnant water Transmits the virus between people Risk Factors/high risk group: Everyone for infection; those with previous exposure are at increased risk of progression to Dengue Hemorrhagic Fever and Dengue Shock Syndrome Distribution: mainly tropics and subtropics - spreading. most common arbovirus infection worldwide 390 million infections annually worldwide, 1/3 of world population at risk,

Pathogenesis of HPV

Infects and replicates in squamous epithelial cells of skin and mucus membranes. Induce cell proliferation causing benign outgrowth - WARTS - Papillomas Hyperplasia of the prickle cells and an excess production of keratin (hyperkeratosis). Two types, 16 and 18 are oncogenic - cause carcinoma of the cervix , penis and anus Proteins encoded by two early genes, E6 and E7 of oncogenic strains inactivate tumor (growth) suppressor genes Protein E6 inactivates p53 gene Protein E7 inactivates p105RB (retinoblastoma gene)

Pathogenesis of Parvovirus (B19)

Infects cells undergoing mitosis so that they get the necessary enzymes for replication Infects immature erythroid progenitor in the bone marrow or erythroid leukemia cells (cancer) Binds to a blood group antigen (P antigen) Pathogenesis is due to direct killing of these cells and the subsequent immune complex deposition (rash and arthralgia) The disease has Bi-phasic course: 1. Lytic infectious phase with prodromal symptoms and viral shedding 2. Noninfectious/immunological phase (rash and arthralgia)

Pathogenesis of Varicella-Zoster Virus

Infects epithelial cells, fibroblasts, T cells and neurons After inhalation, primary infection begins in the tonsils & mucosa (respi. Tract), then virus to blood stream and lymphatics Infection of RES and secondary viremia Infects T cells which home to Skin epithelial cells Latent infection of sensory neurons Retrograde flow to the dorsal root and cranial nerve ganglia; reactivation, virus released along the entire neural pathway- Infection of skin Can form syncytia Two major diseases: Chicken-pox (Varicella)- primary infection, usually in childhood (mild); more severe in adults Shingles (Zoster)- a reactivation of an earlier varicella infection, later in life

Pathogenesis of Dengue Fever

Infects mono/macro, B/T cells, causes apoptosis of endothelial cells. Formation of immune complex by cross reacting antibodies leading to activation of monocytes/macrophage (Antibody-dependent enhancement, ADE) and complement. Life long immunity against same serotype

Pathogenesis of Anaplasma phagocytophilum

Infects the granulocytes: neutrophils, eosinophils, basophils Causes Human Granulocytic Anaplasmosis IP : 5-11 days, symptoms similar to human monocytic ehrlichiosis (rash in less than 10%) Complication: peripheral neuropathies (demyelinating polyneuropathy, facial palsy) Despite the severity, mortality is less than 1%

Listeria Pathogenesis and virulence

Infects various cells Facultative intracellular pathogen, can invade mononuclear phagocytic cells/GIT Cells (like salmonella) Facilitates rapid egress from phagosome into cytoplasm, thus evades killing Move from cell to cell without leaving the cells like Shigella Virulence factors: InIA, lysteriolysin O, phospholipase C, ActA Virulence factors clustered together and regulated by a single gene, prfA (positive regulatory factor gene) Internalins are surface proteins found on Listeria monocytogenes. They exist in two known forms, InlA and InlB. They are used by the bacteria to invade mammalian cells via cadherins transmembrane proteins and Met receptors respectively. The genes that code of for lysis, intracellular replication and directional movement are clustered together and regulated by a single gene, prfA or positive regulatory factor gene ActA; actin polymerization

Encephalitis

Inflammation of the brain; caused mainly by viruses Endemic/sporadic Herpes type 1 and 2 Varicella-zoster EBV, CMV, HIV Measles/Rubeola Coxsackie Echoviruses Polio virus Epidemic Arboviruses, several Seasonal and geographic distribution Most characteristic C/F: fever, headache, altered mental status, seizures and focal neurologic deficits Focal or diffuse neurologic signs confusion, delirious, unconsciousness, changed personality, behavioral and speech disturbances altered mental status paralysis seizures and coma

Hepatitis Syndrome

Inflammation of the liver due to infection of the hepatocytes, Starts with non-specific flu like symptoms Such fever, anorexia, nausea, vomiting, upper abdominal pain Hepatitis signs include -Blood bilirubin elevated -Icteric symptoms/Jaundice: not in all patients -yellowed skin, mucous membranes and eye-whites -Dark urine, pale (light colored) stools, itching Elevated transaminases -Alanine transaminase (ALT) and Aspartate transaminase (AST),

Reservoirs for Infuenza

Influenza type B: only humans Influenza type A: many species of animals birds, pigs, other animals. H5N1: from birds to humans, Assortment from pig, birds and human strains

Cleavage of rRNA

Inhibition of protein synthesis Removes adenine from specific sites on the 28s rRNA of the 60s ribosome Shiga/Vero toxin : Enterohemorrhagic E. coli and Shigella spp. In the intestine: Bloody diarrhea If it enters the blood: Hemolytic uremic syndrome (HUS) - death of RBC HUS, is a disease characterized by hemolytic anemia (anemia caused by destruction of red blood cells), acute kidney failure (uremia), and a low platelet count (thrombocytopenia).

HIV Infection Stage 1

Initial or primary infection (acute phase) and asymptomatic phase Acute phase -Incubation period of 1-3 weeks -no symptoms, OR any or all of the following -"mononucleosis-like symptoms": -Fever, headache, sore throat, malaise - myalgia, arthralgia, aseptic meningitis, Lymphadenopathy, -Rash - small pink papules or macules over much of the body, except the palms and soles (sero-conversion) -Symptoms usually disappear within a week to a month -Highly infectious stage - virus in large concentrations in genital fluids -Viremia - high level of p24 and viral RNA in serum during early phase After the acute phase - asymptomatic period: up to 10 year or more for adults; within 2 years in children Some virions are actively multiplying, infecting, and killing cells of the immune system in the lymphoid organs Some hide within infected cells and lay dormant During this time there is a gradual decline in the number of CD4 positive T (CD4+) cells as well as CD8 P24 and viral RNA level low in serum Antibody level high

Reassortment of genes

Interaction between two genetically different viruses The mixing of the genetic material of a species into new combinations in different individuals. In particular, occurs among influenza viruses, whose genomes consist of eight distinct segments of RNA. (Genetic Shift) : Major changes

Major Protozoan Parasites

Intestinal -Entamoeba histolytica -Giardia lamblia -Cryptosporidium parvum -Cyclospora cayetanensis* -Cystoisospora belli * -Balantidium coli * mostly in immunocompromised host Urogenital -Trichomonas vaginalis Blood and tissue -Plasmodium spp. -Babesia spp. -Toxoplasma gondii -Leishmania spp. -Trypanosoma spp. -Naegleria fowleri -Acanthamoeba castellani

Subcutaneous mycoses

Involves dermis, subcutaneous tissues, muscle, and fascia Sporotrichosis: Sporothrix schenckii Chromomycosis: several species Mycetoma: Several species

Capsid Assembly

Is assembled around the viral genome. In addition, viral-coded envelope glycoproteins are inserted in the host cell's membranes by the Golgi apparatus. The viral envelope will be added later as the virus buds from the membrane (eg. Cytoplasmic) of the host cell during the release stage.

Distribution of Blastomycosis

Is reportable - meaning physicians should report cases to local public health agencies - in some states, including Louisiana, Michigan, Minnesota, Mississippi, and Wisconsin Blastomyces dermatitidis is widely considered an extracellular pathogen, with little evidence for a facultative intracellular lifestyle

Bacteriophage Life cycles

Lytic Cycle Virulent phage Leads to generalized transduction Lysogenic Cycle Temperate phage Leads to specialized transduction

Diagnosis of Mumps

Mainly clinical presentation Viral detection: saliva, pharyngeal swab, urine, CSF: Viral isolation : cell culture Viral antigen/nucleic acid: Immunofluorescence, /RT-PCR, Serology: IgM or 4 fold increase in IgG

HEV Clinical Disease

Major etiologic agent of fecal-oral non-A, non‑B hepatitis (E-NANBH) worldwide IP: Avg 40 days, Range 15-60 days Signs and Symptoms: similar to HAV, causes only acute infection, mostly self limited Case-fatality rate: Overall, 1%-3% Pregnant women,15%-25% No chronic sequelae identified

Diagnosis of Lymphogranuloma Venereum

Microscopic: cytoplasmic inclusion bodies, cell culture, PCR, serology Treatment: Doxycycline, azithromycin Prevention: Treat sexual partners, Safe sexual practices

Diagnosis of Chagas Disease

Microscopy Blood - flagellate form only during acute form, Tissue biopsy: amastigote form Culture: Cell culture/culture in NNN medium Animal inoculation -intra-peritoneal inoculation, mice Serology Xenodiagnosis: Reduviid bug is allowed to feed on a patient, then parasites are detected in the bugs

A-B Toxins

Most bacterial toxins fall into this class Two units: A and B B unit binds to host cell receptor Determines the host cell specificity of the toxin After entering the cell the A unit cleaves or modifies a target molecule within the cell. The A unit is translocated through host plasma membrane after B binds (directly or through endocytosis).

HSV Congenital/neonatal herpes

Mostly HSV type 2 Encephalitis (fatal), kerato-conjunctivitis, body lesions Associated with active/asymptomatic infection of the mother.

Syncytia Formation

Multi-nucleated syncytial cells are often the result of infections by enveloped viruses that induce cell fusion.

Treatment of trichinosis

NO effective treatment, anthelmintic drugs cannot reach the larvae in tissue: Mebendazole halt new larvae production in intestine Steroids for treatment of inflammatory symptoms Prevention: Education regarding transmission Proper cooking of meat (pork/bear meat); Strict regulation regarding pigs feed- avoid feeding pigs with uncooked garbage.

Adenovirus

Naked with Icosahedral capsid Capsomeres- hexons and pentons 12 vertices (with pentons) and 20 triangular faces (with hexons). Each face has no.of capsomers. Peplomers (fibers) - projections

HIV prevention

No vaccine yet Safe sex Male circumcision HIV + mothers cesarean section, no breast feeding Prophylaxis antiretroviral Post exposure: needle-stick High risk occupation HIV infected expecting mothers and their babies Advanced AIDs patient: protection against common infections in HIV+ Antibacterial, antifungal drugs, anti-CMV (ganciclovir)

Bacterial Non-Inflammatory Diarrhea

Noninflammatory diarrhea, which is typically less severe than inflammatory diarrhea, causes large, watery stool with cramping but no blood; fecal leukocytes are absent.

Parvovirus (B19)

Parvoviridae Family: Parvovirus Genus 5th disease (Erythema Infectiosum) General properties of Parvovirus: Smallest of DNA viruses, Naked icosahedral capsid, ss linear DNA (negative or positive sense). Has limited genes, Requirement of growing cells or helper virus for replication; only one serotype (B19). Reservoir: Humans-only host, 65% of adults sero+ Transmission: Late winter and Spring Respiratory droplets and oral secretions-primary means; Also by blood and blood products, Transplacental Risk Factors/High Risk Populations: Children 4-15 years (Causes 5th disease), Pregnant woman (fetal infection), Persons with chronic anemia such as Sickle Cell Anemia (Aplastic crisis)

Prevention of HBV

Passive immunization: hyper-immune sera (pre or post exposure) Active immunization: Recombinant acellullar vaccine - HBsAg - cloned into yeast 95% seroconversion recommended all newborns, adults at risk and expecting mothers Other measures - screening of blood donors, blood and body fluid precautions. Hepatitis virus infection is a reportable disease in the US: determine isolated case or part of out break - preventative measure

Blastomycosis

Pathogenesis and Clinical Disease Inhalation of conidia initiates the infection and development into the yeast form Incubation time: weeks Pulmonary and extra pulmonary manifestation Pulmonary could be mild flu like symptoms or Acute, severe: resemble bacterial pneumonia - typical Acute onset, fever, cough with lobular infiltrates - respiratory failure may occur Chronic pneumonia - may resemble tuberculosis or lung cancer Extrapulmonary -2/3rd to skin and bone (hematogenous route) chronic cutaneous lesions : painless nodules which may ulcerate , usually in exposed part of the body.

Pathogenesis of Ebola Hemorrhagic Fever (EHF)

Pathogenesis: Infects cells - macrophages, dendritic cells, fibroblasts and endothelial cells Infection of the endothelial lining of the vasculature leads to hemorrhage Infection of mononuclear cells - cytokine storm - like septic shock Inhibit interferon production Mostly symptomatic - but presence of seropositive individuals indicate subclinical condition Mortality rates varies (25%-90%), Average of 50%

Treatment and prevention of GBS

Penicillin G Antibiotic at least 4 hrs prior to delivery 2 cornerstones to prevent newborn early-onset disease Test all pregnant women for group B strep bacteria late in pregnancy (35-37 weeks). rectal/vaginal swab culture Intrapartum (during labor) antibiotic administration to women With positive culture Previous neonate infected Intrapartum temperature of 38 0C or higher Urinary tract infection with GBS during pregnancy; Or Membrane rupture at least 18 hrs before delivery

Antifungal Drugs

Polyenes : Amphotericin B, Nystatin Affects integrity of plasma membrane: Inserts in fungal membrane next to ergosterol; causes pore formation, ion leakage Azoles : Eg. Ketoconazole, Fluconazole inhibit plasma membrane synthesis: by interfering with ergosterol synthesis Echinocandins : eg. Caspofungin inhibits cell wall synthesis - interfere with glucan synthesis Nikkomycins: Inhibit cell wall synthesis: interfere with chitin synthesis Flucytosine : Inhibits nucleic acid synthesis Griseofulvin: : Inhibits cell division: interfere with microtubules (disruption)

Molluscum Contagiosum Virus

Poxviridae (family) Mulluscipoxvirus (Genus) Properties: Same as Poxviridae (family) Reservoir: Humans; strictly human pathogen Transmission: Direct contact with the lesion, sexual contact, wrestling, or Indirectly via fomites eg. sharing towels, swimming pools and showers. Spread by autoinoculation High Risk Populations: More common in children, and incidence increasing in sexually active persons and immunocompromised

Epiglottitis

Signs and Symptoms An acute onset, fever, sore throat, 4 D's Dysphagia - difficulty in swallowing Dysphonia - hoarseness Drooling - unintentional production and dropping of saliva Distress - breathing problem Stridor - high pitched sound on inspiration cherry red, stiff, and swollen epiglottis. Diagnosis: imaging laryngoscopy Lateral X-ray of neck- 'thumb' sign

Protozoa

Single cells; eukaryotic cell structure Surrounded by either a plasma membrane alone or with an exterior flexible pellicle Extracellular and intracellular infections May have two or more forms/stages Trophozoite is the motile, metabolically active, replicating form Cyst is the dormant, non-replicating form that is adapted for survival in the environment. If it does not have a cyst form, it must be transmitted via a vector or direct contact

Bacterial skin pathogens

Skin and wound infection Gram positive cocci Staphylococcus aureus Streptococcus pyogenes Enterococcus faecalis Gram negative rods Pseudomonas aeruginosa Acinetobacter baumanii Vibrio vulnificus (curved) Gram positive rods Bacillus anthracis Anaerobic bacteria Gram Positive Clostridium perfringens Actinomyces israelii Propionibacterium spp. Gram negative Bacteroides fragilis Many other spp. Acid fast bacteria Nocardia asteroides Mycobacterium leprae Mycobacterium spp. (MOTTS= Mycobacteria Other Than Tuberculosis Zoonotic bacteria (Please see note below): will be covered later

Clostridium perfringens Clinical Diseases

Soft tissue infections: Cellulitis Suppurative myositis: pus accumulation, without muscle necrosis or systemic symptoms Myonecrosis = Gas Gangrene Painful rapid destruction of muscle tissue Gas accumulation under the skin results in crepitation in the tissue The gas is from microbial fermentation of host tissue - gives foul smelling Systemic spread Mortality about 30% when properly treated, 100% if not Other diseases: GI diseases: Food poisoning, Necrotizing enteritis knows as pigbel.

High Frequency Plasmids

Some F plasmids can be integrated into the host chromosome because they contain insertion sequences. These are called Hfr plasmids Can transfer chromosomal genes from the donor to the recipient

Diagnosis of Blastomycosis

Specimen: Sputum, lung biopsy, bronchoalveolar lavage, biopsy from nodules, drainage (exudate) Microscopy: wet (KOH) or stained: demonstrate broad-base budding yeast- definitive Culture: at 25 0C and 37 0C on standard media. Slow growth - up to 4 weeks. To confirm - Detect Broad-based budding yeast, or perform nucleic acid test -antigen detection in urine available Serology: Limited value

Diagnosis of Streptococcus pneumoniae

Specimen: aspirate from sinus or middle ear; Sputum, CSF, blood Gram stain: Gram positive diplococci, capsule Quellung test: capsular swelling by applying specific antibodies. Culture: Alpha-hemolysis on BAP, Optochin susceptibility Bile solubility: addition of bile salts to culture results in killing of cell - culture becomes less turbid. A rapid test to detect urinary antigen (C polysaccharide or C-substance) PCR and/or latex particle agglutination: mainly for meningitis.

Homologous DNA Recombination

Stabilizes linear genes after genetic transfer It is an exchange of piece of DNA: loss of old information, replaced by new Requires long region of homology and a series of recombination enzymes (recA, recB, etc)

Diagnosis of Trichuriasis

Stool examination- bile stained, barrel shaped egg with polar (mucous) plugs The eggs in the stool contain unsegmented ovum

Diagnosis of Ascariasis

Stool for eggs and parasite (occasional adult worms, usually eggs) Sputum, bronchoscopically obtained washing, and gastric lavage may reveal larvae of the Ascaris Imaging Studies: Patchy infiltrate on chest radiograph or worms seen in abdominal radiograph Infusion of the contrast medium barium sulfate, a radioopaque salt, coats the lining of the digestive tract, allowing accurate X-ray imaging of this part of the abdomen. Adult Ascaris may be seen as filling defects.

Dapsone and Para-Aminosalicylic Acid

Structure Similar to sulfonamides Mechanism of action Similar to sulfonamides Pharmacology Narrow Spectrum: Mycobacterium Mechanisms of Resistance Same as sulfonamides

Cephalosporins

Structure: 7-Aminocephalosporanic Acid Betalactam ring + Dihydrothiazine Ring (6 membered) R group: Change in R group - 1st, 2nd, 3rd, 4th, 5th generations Mode of action and uses: same as penicillins Ist generation: Cephalexin, Cefazolin, narrow spectrum: Gram +ve 2nd generation: Cefuroxime, cefoxitin: expanded spectrum to a few Gram negatives 3rd generation: Ceftriaxone, ceftazidime : broader spectrum, more Gram negative bacteria 4th generation: Cefepime, Cefpirome: extended spectrum, against Gram negative including Pseudomonas aeruginosa, also against Gram +ve 5th generation: ceftobibrole (powerful antipseudomonal activity), ceftaroline

Cestodes

Structure: Tape worms Ribbon like, segmented worms (size varies - some reach 25 meters) Do not have GIT - food absorbed from host GIT Anterior end: scolex- suckers with/out hooks for attachment Body: Strobilla Composed of proglottids (segments) Reproductive structures filled with eggs, are hermaphrodite Break off and pass out of body in stool use flame cells for excretion

Bacitracin

Structure: a large, complex cyclic peptide Mechanism of Action Binds to Bactoprenol and inhibits transportation of peptidoglycan precursors Bactericidal Pharmacology: narrow spectrum, Gram positive, nephrotoxic, Topical application Resistance: decreased penetration

Facet cells

Terminally differentiated superficial epithelial cells. E. coli adhere and enter these surface cells, multiply resulting in exfoliation - some of the bacteria released infect adjacent cells. Some may persist in underlying transitional epithelial cells in endosome (intracellular) - in a kind of dormant stage (quiescent). In this situation the bacteria are protected from antibiotic treatment. When the transitional epithelial cells gradually mature and come to the surface to replace the damaged facet cells - the quiscent form of the bacteria may start multiplying causing relapse of infection.

RNA Viruses

There are 13 families of RNA viruses (i.e more than DNA viruses) All RNA viruses replicate in the host cell cytoplasm except orthomyxo (e.g influenza) viruses (retroviruses in both the cytoplasm and nucleus) RNA of RNA viruses varies in its structure— ss or ds ssRNA is either positive (like mRNA) sense, negative sense Some may be segmented All negative sense RNA viruses are enveloped All negative sense RNA viruses carry an RNA dependent-RNA polymerase Only RNA viruses may be arthropod borne

Pathogenesis of Pertussis

This pathogen adheres and multiplies rapidly on the epithelial surface of the trachea & bronchi; and causes increased respiratory secretions; and interferes with ciliary action (clearance). Historically pertussis was a disease of children. But now a significant increase in adolescents and adults - due to waning of immunity.

Serotyping of Enterobacteriaceae

Three antigens are important O, K, H antigens 1. They all possess LPS : the terminal sugars of the LPS, O somatic antigen useful in identification 2. Some species possess a K (capsular) or Vi (virulence) antigen 3. If motile the flagellar, H antigens. Example : a strain E. coli with O55:K9:H6 Somatic O55 , Capsular K9, Flagella H6

Treatment of S. aureus

Treatment: Beta lactamase resistant drugs - Methicillin/Nafcillin/oxacillin MRSA Strains: >20% of isolates are resistant to Met/Naf -carry mecA gene (chromosomal gene), which encodes an alternative penicillin-binding protein, PBP 2a Cause outbreaks in hospitals; are multiple drug resistant; also community acquired For MRSA - vancomycin is the drug of choice Vancomycin resistant strains have emerged (VRSA), coded by VanA transposon gene carried on a plasmid For VRSA - quinupristin/dalfopristin Sterptogramins (protein synthesis inhibitors) Toxic shock syndrome: correction of shock-by fluid, removal of foreign body. Antibiotics Preventions: Treat Carriers: nasal spray with Mupirocin (Bactroban) and improved hygiene.

Vibrio spp.

Vibrio cholerae: watery diarrhea V. parahaemolyticus - watery but milder diarrhea than cholera V. vulnificus - skin and wound infection

Septicemic Plague

Yersinia pestis 50-75% infections progress to bacteremia, septic shock death within hrs or days. (with out treatment) About 5% of bubonic plaque may develop pneumonic plague.

Prevention of pertussis

vaccine: 2 types (Whole cell killed and acellular) DPT vaccine (diphtheria, pertussis, tetanus): Pertussis-whole cell inactivated, 80-85% effective, have side effect, not used in USA DTaP vaccine: for children (2months to 6 Years, 5 doses) Multivalent acellular vaccine-effective; less side effects Composed of several purified proteins- pertussis toxoid, hemagglutinin, pertactin, fimbriae (at least 2 components) The main immunogen is the pertussis toxoid - genetically engineered by introducing 2 amino acids to inactivate its enzymatic activity Tdap: as a booster for people vaccinated by DTaP - for adolescents (10-12 years); and adults (19-64 years) Erythromycin prophylaxis in close contacts if warranted Vaccinating pregnant (booster) women to protect infants. (In the latest epidemic: infants were more affected)

Mechanism of antibiotic resistance

1. Inactivation (cleavage) of antibiotics by enzymes 2. Active Efflux of drugs by membrane-bound multiple drug resistant (MDR) efflux pumps 3. Chemical Modification of the antibiotic: eg. transfer of acetyl group, methyl group 4. Decrease cell permeability of cell 5. Hyper-production of target 6. Mutation or post-translational modification of drug target 7. Formation of biofilm

HIV killing of CD4 T lymphocytes

1. by puncturing of cell membrane during viral release. 2. Formation of syncytia (merging of cells) 3. killing of infected CD4 cells by T CD8 cells. 4. Free gp120 binding to CD4 cells makes uninfected CD4 look like infected and may be targeted by complement mediated lysis.

Vibrio cholerae Virulence & Pathogenesis

140 recognized serotypes based on LPS O-specific antigens. O1 and O139 strains produce: Cholera toxin (CT): - similar to ETEC toxin (LT), binds to GM1 ganglioside increase: cAMP hyper-secretion of electrolytes and water, chloride ion out, Na ion not absorbed Toxin-co-regulated pilus (TCP) - adhesion Non-O1 and non-O139 lack these virulence factors. Additional Virulence Factors: Zonula occludens toxin (zot) is a protease: Degrade tight junctions - causes mild to moderate diarrhea; Accessory cholera enterotoxin (ace): activates a calcium dependent chloride channel.

Phenol

1st disinfectant used rarely used, replaced by phenol derivatives Act by dissolving lipid solvents - disrupts cell membranes Effective disinfectants but too toxic for antisepsis Not sporicidal, not effective against non-enveloped viruses

Granuloma Inguinale

90% of infected are symptomatic. An indurated papule on the penis, labia or anal margin Lesions are painless, ulcerate progressively Beefy-red open sores that slowly enlarges, mutilating ulceration, produce a foul-smelling discharge. Extra genital lesions are common on the face, lips and neck. Kissing lesions Pseudo-buboes: subcutaneous granulomas in the inguinal regions; they do not involve the lymph nodes Secondary infection may occur May result in extensive scarring and tissue damage

Meningococcal Meningitis risk factors

< 5 years, Age 15-25 years, elderly Associated with crowding as in military barracks, college dormitories, prisons, high schools. Inherited deficiency of Complement (C5-9) properdin or mannose-binding lectin (activator of complement without antibody) Asplenic patients

Mycobacterium

> 150 species, many are associated with human diseases. Grouped based on Rate of growth: Fast growers (˂7days) Slow growers (several weeks) Production of yellow pigment Scotochromogens: Pigment in the dark Photochromogens: Pigment only after exposure to light Nonchromogens : no color or slight tan color Mycobacteria with pulmonary manifestation M. tuberculosis - causes TB, strictly human pathogen M. bovis - from animals, transmitted via raw milk, TB M. avium complex (MAC) - TB like disease, mostly in HIV patients, found in soil and water M. kansasii -TB like disease mostly in HIV patients, found in soil and water Mycobacteria with skin manifestations M. leprae - causes leprosy, strictly human pathogen M. marinum - found in water, causes skin granuloma " fish tank granuloma", swimming pool granuloma" M. ulcerans - found in soil/water, causes skin infection known as buruli ulcer, tropical disease

Mycetoma

A localized chronic, granulomatous, infectious process involving cutaneous and subcutaneous tissues. It is characterized by formation of multiple granulomas and abscesses that contain large aggregates of fungal hyphae known as granules or grains) two types-Actinomycotic and Eumycotic Common etiological agents of Actinomycotic (Bacterial) mycetoma: Actinomadura, Nocardia, Streptomyces (S. somaliensis) Common agents of Eumycotic (Fungal) mycetoma: Madurella, Acremonium, Exophiala etc. (Eumycotic

Snapping division

A mode of cell division characterized by rapid horizontal division of an elongated cell with the two daughters finishing at an angle to each other. The daughter cells frequently remain in contact for a period of time

Diagnosis of Filarial Elephantiasis

A. Microscopy: demonstration larva (microfilariae) in Giemsa stained blood films (Blood collected at night) Buffy coat films Membrane filtration technique (blood mixed with saline and filtered) Differentiation between W. bancrofti and B. malayi is based on study of head and tail structure B. Serology: alternative to microscopy

Normal flora

AKA human microbiome, or indigenous flora Population of microorganism that inhabit the skin and mucous membranes of a healthy person; Two types- Permanent/resident flora- relatively fixed type of population found regularly in a site, and when disturbed can easily re-establish itself. Transient flora: occupy sites only temporarily, short duration, could be non-pathogens or pathogens Healthy carriers- certain % of the population harboring many pathogenic bacteria

Sulfonamide and Trimethoprim

Act in the same pathway toward the synthesis of folic acid and eventually to purines and DNA. Sulfonamides are structural analogue to PABA. Sulfas mimic para-aminobenzoic acid needed by bacteria for folic acid synthesis. Sulfas inhibit bacterial folic acid synthesis at the level of the enzyme dihydropteroate synthetase Trimethoprim impairs folic acid synthesis at the level of dihydrofolate reductase. Human cells are not affected by these drugs, because unlike bacterial cell human cells require preformed folic acid Pharmacology: Usually used together Broad spectrum Bacteriostatic Urinary tract infections Gastrointestinal tract infections Respiratory infections Mechanisms of Resistance Efflux pumps are proteinaceous transporters localized in the cytoplasmic membrane of all kinds of cells. Alteration (mutation) of enzymes dihydropteroate synthetase and dihydrofolate reductase Overproduction of PABA and or dihydrofolic acid Many bacteria, including those found in the human intestinal tract such as E. coli, generate PABA from chorismate, a biochemical intermediate. Folic acid dependency Decreased permeability

Innate Response Against Viruses

Activation of NK cells Infected cells produce interferon 1 Dendritic cells/macrophages produce IL-12, TNF alpha, etc. Toll like receptors TLR3 and TLR7, TLR8 found in NK cells: recognize viral PAMP These lead to activation of NK: which in turn results in -Killing of infected cells -Production of interferon gamma and IL-12 -favouring the development of Th1 (promote cell mediated immunity) -activation of CD8 and macrophages. Once NK are activated by either by IFN alpha/beta, IL-12, TNF alpha or by binding ssDNA/dsRNA through TLR3/TLR7/TLR8, they produce Interferon gamma which favour the development of Th1 and also activates CD8 and macrophages.

pathogenesis of norovirus gastroenteritis

Alters integrity of brush border of small intestine Acute gastroenteritis, self-limited Incubation Period - 1-2 days; Sudden onset of watery diarrhea, nausea and vomiting, abdominal pain Duration of disease - 2-3 days. Re-infection possible, weak immunity

Chronic HBV infection

AntiHBc and HBsAg positive AntiHBs negative. HBeAg may continue to be expressed until antiHBe appears Drugs reduce liver inflammation, could relapse 1. Interferon alpha: pegylated interferon alpha. 2. Antiviral drugs: nucleoside analogs or reverse transcriptase inhibitors such as : lamivudine Successful response to treatment will result in the disappearance of HBsAg, (appearance of AnitHBS) and seroconversion to antiHBe 3. Passive immunization: HBIG -Post exposure -Neonate: if mother is HBsAg and HBeAg positive

C. difficile clinical disease

Antibiotic Associated Diarrhea Vomiting, nausea, and diarrhea Onset 4 - 10 days after start of antibiotic, up to 2 weeks after termination Pseudomembranous colitis (pathognomonic for C. difficile) Severe abdominal pain, watery diarrhea, high number of neutrophils in stool Damage to colonic mucosa separate lesions coalesce Pseudomembrane - refers to yellowish/whitish plagues composed of fibrin, mucus with cellular debris that overlay the ulceration in the colonic mucosa.

Spiders

Arachnids; Produce venom Venomous spiders may cause: Systemic arachnidism (Neurotoxic disease) Black widow spiders and Tarantulas Intense pain and phase of agitation followed by stupor and somnolence No tissue necrosis Necrotic arachnidism (Dermonecrotic disease) Brown recluse spider Severe tissue necrosis

Cat-Scratch Disease

Bartonella henselae Immunocompetent, IP: 1-3 weeks after exposure Low grade fever Bump (papule) or blister (pustule) at site of injury, may last for a few weeks Extensive swelling of lymph nodes, especially around the head, neck and upper limbs Rarely: Muscle pain Conjunctival lesion may occur by autoinoculation Systemic infection leading to subacute endocarditis, encephalitis

Subtypes of Influenza virus

Based on variation on HA and NA antigens, only Type A has subtypes 16 HA subtypes (H1-H16) 9 NA subtypes (N1-N9) Many different combinations of these exist in birds, humans and other animals, eg. H1N1, H9N5 Human influenza subtypes are mainly composed of Four H types (H1, H2, H3, H5) And two N types (N1, N2)

Taenia saginata

Beef Tapeworm Epidemiology: worldwide; one of most frequent causes of cestode infections in US; intermediate host-cattle; human- definitive host Transmission: eating undercooked or raw beef (containing larval form i.e. cysticercus) Pathogenesis: infects intestines, mechanical obstruction, sharing food. (No cysticercus in human tissue) Clinical Disease: Taeniasis; most infections are asymptomatic, can cause mild vague abdominal discomfort Annoyance - passive passage of 1-6 proglottids Length of adult worms is usually 5 m or less for T. saginata (however, it may reach up to 25 m) and 2 to 7 m for T. solium

Diagnosis of parainfluenza virus

Best specimens are nasopharyngeal secretions. Antigen detection: Immunofluorescence Serology: Hemagglutination inhibition test, ELISA Isolation: Primary monkey kidney cells-syncytia formation X ray: steeple sign, narrowing the upper part of trachea Treatment Hospitalization: Treat symptomatically and monitor airway continuously Cold or Warm mist (humidification) - "croup tent" Oxygen - May have to be intubated May use IM dexamethasone (corticosteroid ) and/or inhaled epinephrine (pediatric) Prevention: No vaccine, re-infections common

Relapsing Fever

Borrelia Spp. Two types: I. Epidemic relapsing fever: louse borne Is caused by Borrelia recurrentis Transmitted by Pediculus humanus (louse) Human is the only host More severe than endemic II. Endemic relapsing fever - Tick borne (TBRF) At least 15 different Borrelia species. Borrelia hermsii, (Most common) Transmitted by different species of soft ticks (life span 10-20 years) Ornithodoros spp (common) Rodents are the reservoirs

Variations of Microscopes

Bright-field (eg, Compound microscope)- most widely used; specimen is darker than surrounding field; best for preserved and stained specimens Dark-field - brightly illuminated specimens surrounded by dark field; used to detect live and unstained specimens - mostly for spirochetes Phase contrast : Uses parallel beam of lights which passes through objects of different densities. The wavelength of one beam moves out of 'phase' relative to other beam of light. Used for detailed analysis of internal structure in living cells UV/ Fluorescent microscope: uses ultraviolet light and fluorescent compounds - mostly for immunofluorescent (eg. DFA) stained smear - for fast diagnosis Such as CSF, Tissue biopsy, culture isolate Electron microscope: uses beams of electrons - mostly used for viruses, Types- Scanning and Transmission EM

Diagnosis of Meningitis/Encephalitis

CSF : Gram stain, cell count, glucose and protein concentration measurement Culture: CSF and blood Head CT /MRI scan: looking for hydrocephalus, abscess or deep swelling Chest X-ray: to look for other sites of infection

Hepatitis E Virus

Caliciviridae family General properties: non-enveloped, ss positive sense RNA virus, one serotype; resistant to inactivation Reservoir: humans and primates, pigs Transmission: Fecal-oral (contaminated drinking water) Blood transfusion possible U.S. cases usually, but not always, have history of travel to HEV-endemic areas (Southeast and Central Asia, Middle East, North and West Africa, Mexico) Risk Factors/High Risk Populations: Similar to HAV but high mortality in pregnant women primarily in 3rd trimester

Infections of the mouth

Candidiasis: Cheilitis - lips Herpangina Candidiasis: Thrush - oral cavity Oral herpes

Slow pathogens of CNS

Cause CNS disease characterized by a long incubation period, gradual onset, and progressive, invariably fatal JC virus: Progressive Mutifocal Leukoencephalopathy (PML) Defective measles virus-Subacute Sclerosing panencephalitis (SSPE) Prions: Transmissible spongiform diseases

Vulvovaginal Candidiasis parthenogenesis and treatment

Clinical Disease: A thick, curd/cottage-cheese-like vaginal discharge Discharge contain epithelial cells and mass of yeast/pseudohyhae Intense pruritus of the vulva ,erythematous vagina and labia Other diseases caused by Candida: Thrush, skin rash in wet areas of the body - diaper rash Treatment: intra-vaginal antifungal drugs such as nystatin; no need to treat sexual partners Prevention: Judicious use of antibiotics, avoid invasive hospital procedures

Pathogenesis of Hymenolepis nana

Clinical Disease: No symptoms with few worms Heavy infections: diarrhea, abdominal pain, headache, loss of appetite, itchy sensation

Pathogenesis of Trichuriasis

Clinical disease: Mostly asymptomatic Heavier infections: chronic profuse mucus and bloody diarrhea with abdominal pain and edematous PROLAPSED rectum. may result in appendicitis, malnutrition, anemia, weight loss, growth retardation and sometimes death.

Pathogenesis of Cystoisospora belli

Clinical disease: Asymptomatic or mild to severe GI disease (similar to Giardiasis); malabsorption Watery diarrhea with foul smelling stools

Pathogenesis of Trichomonas vaginalis

Clinical disease: Trichomoniasis - more common in female Female- found in urethra and vagina, male- in urethra and prostrate gland Female: Inflammation of the vagina and cervix with itching and burning. Vaginal discharge which is scant, frothy, greenish-yellowish Strawberry red cervix Males: usually asymptomatic as reservoir May cause urethritis with discharge

Pathogenesis of Streptococcus pyogenes (GAS)

Clinical diseases: Pyogenic infections - local infections: include pharyngitis*, otitis media, pneumonia, skin and soft tissue infection Toxin mediated - scarlet fever*, toxic shock syndrome, necrotizing fasciitis Immune mediated : follows untreated pharyngitis/ skin infection Rheumatic fever*- (Skin manifestation?) Glomerulonephritis*

Diagnosis of Streptococcal Glomerulonephritis

Clinical, history of skin or throat infections, Serology- anti streptolysin O (ASO) and anti-DNase.

Q fever

Coxiella burnetii, considered rickettsial Pneumonia Inhale aerosols (generally aerosolized feces; no vector)

Drugs that inhibit cell wall synthesis

Cycloserine: an analogue to D-alanine: inhibits peptidoglycan synthesis Isoniazid (INH); prodrug; inhibits mycolic acid synthesis Ethionamide: derivative of INH, inhibits mycolic acid synthesis Pyrazinamide: prodrug; inhibits mycolic acid synthesis Ethambutol: Interferes with synthesis of arabinogalactan (part of the cell wall of acid fast bacteria), bacteriostatic All above drugs are used in the treatment of mycobacterial infections: (acid fast bacteria) First line essential: Rifampin, Isoniazid, Pyrazinamide, Ethambutol First line supplemental: Streptomycin, Rifabutin, Rifapentine Second line: Quinolones, Amikacin, Kanamycin, Capreomycin, Ethionamide, Para-aminosalicylic acid, cycloserine

Immunofluorecent staining of cell culture

DEAFF: detection of early antigen fluorescent foci Detection o viral antigens in cell culture Detection of early proteins (expressed at the early stage of viral replication) by monoclonal antibodies tagged with fluorescent dye This is a method used for the early diagnosis of CMV infection. In immunocompromised patients, The specimen is inoculated into cell culture which is examined 24 hours later by immunofluorescence for expressed CMV encoded early proteins. The monoclonal antibodies must be able to cover most, if not all strains of CMV.

Diagnosis and Treatment of lice

Demonstration of adult lice and eggs (nits) Treatment: Permethrin: treatment of choice Gamma benzene hexachloride (lindane) lotion Permethrin-both pediculicidal (kils adult) as well as ovicidal Prevention: Education and practice of hygiene Not sharing articles/clothing Shaving the hair of affected areas Treating brushes, combs and bedding with pediculicide

Diagnosis of Giardia lamblia

Demonstration of cyst or trophozoites Several stool samples may be necessary String test/ Entero test Usually a stool sample is tested first. A string test is done if the stool sample is negative. String test: a string with a weighted gelatin capsule is swallowed. Four hours later, it is pulled back out. Any bile, blood, or mucus (from small intestine) attached to the string is examined under the microscope for cells and parasites or parasite eggs.

Diagnosis of trichinosis

Demonstration of encysted worms (larvae) in muscle on biopsy, Serology Complement fixation, Bentonite flocculation test etc. Marked eosinophilia

Diagnosis of Fasciolopsis buski

Demonstration of large, golden, bile stained eggs with operculum (in stool)

Acid Fast Staining

Differential Staining Common method is Ziehl-Neelsen (Z-N) stain - used to stain Acid fast bacteria (AFB) Requires heating of a primary stain, decolorizing with an acid/acid-alcohol solution, and then pouring a secondary dye.

Treatment of Cystoisospora belli

Drug of choice: Trimethoprim-Sulfamethoxazole Prevention and Control: Maintaining personal hygiene and sanitary conditions

Kernig's sign

Each hip is flexed (so that it is at a right angle to the trunk), and then attempt is made to straighten the knee while keeping the hip flexed. In a meningitis, this movement is greatly limited by spasm of hamstrings - which in turn causes pain - due to inflammatory exudates around the roots of the lumbar theca.

Norovirus Trends in the US

Each year on average Causes 19-21 million cases of acute gastroenteritis Leads to 1.7-1.9 million outpatient visits and 400,000 emergency department visits, primarily in young children Contributes to about 56,000-71,000 hospitalizations and 570-800 deaths, mostly among young children and the elderly

Harmful effects of normal flora

Endogenous diseases Infective endocarditis (valvular heart disease)-Viridans streptococci UTI by Escherichia coli: Direct ascend Opportunistic infections in compromised host defense Diabetes Leukemia Chemotherapy etc. Some associated with a variety of chronic diseases: Inflammatory bowel disease, Autoimmune diseases; Ex. SLE Allergic conditions Obesity Psychiatric and neurological disorders. Brain-gut connection Can cause disease when Transferred to susceptible host When transferred to other host, they can cause disease Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, S.aureus- Resp. tract infection E.coli, Salmonella - GIT infection Possible source of carcinogens Normal intestinal flora may produce carcinogens from the compounds that an individual ingests e.g, Artificial sweetener, cyclamate (cyclohexamine sulphate) is converted to the active bladder carcinogen cyclohexamine by bacterial sulphatases. Competition for nutrients Bacteria in GIT get some of our nutrients before we are able to absorb them

Bacterial Toxins

Endotoxins and Exotoxins Note: Teichoic and lipoteichoic acid, peptidoglycan of Gram positive can cause fever, acute phase response similar to that caused by Endotoxin

Herpes virus

Enveloped with Icosahedral capsid ds DNA, tegument between capsid and envelope-containing viral proteins and enzymes for replication

HIV

Enveloped with helical capsid Genome: Segmented RNA, Two identical positive ss RNA strands Surface glycoproteins - for adhesion and entry Packed enzymes: Reverse transcriptase, integrase , and proteases

Paramyxovirus

Enveloped with helical capsid Non Segmented, negative sense RNA genome, carry RNA dep. RNA polymerase F: mediates cell entry by inducing fusion between the viral envelope and the cell membrane HN/ H, G: attachment proteins, with Hemagglutinin and/or neuraminidase activity

Rabies virus

Enveloped with helical capsid bullet shaped, negative sense ss RNA Virus

Cystoisospora belli (Formerly, Isospora belli)

Epidemiology: worldwide, healthy as well as immunocompromised patients, Transm. by ingestion of contaminated food or water Least common of 3 intestinal coccidian Biology: sporozoan (coccidian), both asexual (schizogony) and sexual (gametogony) reproduction The least common of all 3 intestinal coccidian (CDC)

Alcohols

Ethanol and isopropanol Dissolve lipids (cell membranes) and denature proteins Bactericidal against many, but not against spores and non-enveloped virus More effective at 70% than 100%, because more effective in presence of water Commonly used to disinfect skin, and items such as thermometers

HACEK group

Fastidious oropharyngeal GNBs -Haemophilus spp (H. aphrophilus or H. parainfluenzae) -Actinobacillus actinomycetemcomitans, -Cardiobacterium hominis, -Eikenella corrodens, -Kingella kingae Reside in oral cavity Either native or prosthetic valves Course: Subacute endocarditis Vegetations-large Slow growing, may require upto 30 days for culture

Pathogenesis of lice

Feeds on blood Injects saliva into the skin that induces hypersensitivity reaction Intense itching, pruritic red papules Excoriation (act of abrading or wearing off the skin) and secondary bacterial infection can occur

Endocarditis

Fever, Chills, A new or changed heart murmur — abnormal heart sounds made by blood rushing through your heart Fatigue, Aching joints and muscles, Night sweats, Shortness of breath, Paleness, Persistent cough, Swelling in your feet, legs or abdomen Unexplained weight loss Tenderness in the spleen — an infection-fighting In addition: Immune complex deposition may lead to nephritis (blood in the urine) arthritis, and skin lesions and petechaie Vegetation is composed of fibrin deposits, platelet aggregation, inflammatory cells, bacteria. May get detached and get deposited in small blood vessels (embolization) resulting in blockage of blood vessels and establish secondary site of infection. Osler's nodes — red, tender spots under the skin of your fingers, painful, red, raised lesions found on the hands and feet. Petechiae — tiny purple or red spots on the skin, whites of your eyes or inside your mouth Janeway lesions are non-tender, small erythematous or haemorrhagic macular or nodular lesions on the palms or soles only a few millimeters in diameter that are pathognomonic of infective endocar ditis

Prostatitis

Fever, shaking chills, decreased libido, perirectal pain, low back pain, cystitis symptoms, bladder outflow obstruction

Diphyllobothrium latum

Fish tapeworm Epidemiology: worldwide, cool lake regions (Northern hemisphere/North America) Reservoirs hosts: multiple fish eating wild and domestic animals Intermediate hosts: Crustaceans and fish Transmission: Ingestion of raw or undercooked fresh water fish Morphology: Adult up to 25 m long (largest tapeworm infecting humans), larva and operculated egg (diagnostic stage)

Pontiac Fever

Flu-like symptoms (Influenza like illness) Incubation period: 1-2 days , lasts 2-5 days Fever, chills, myalgia, malaise, headache (dry cough in few) No evidence of pneumonia Due to hypersensitivity reaction to bacterial endotoxins Self-limited, no antibiotic treatment

Botulism intoxication

Food borne Incubation time 18-72hrs - after ingesting toxin Recovery may take months to years Bilateral descending paralysis May include abdominal pain, either diarrhea or constipation If untreated may progress to cause paralysis of the arms, legs, trunk and respiratory muscles death due to respiratory failure Wound Botulism infection: Incubation period: 1-4 days, symptoms similar to food-borne

Salmonellosis

Gastroenteritis: Incubation time 6-48 hrs after consumption Inflammatory diarrhea with/without visible blood, Nausea, vomiting fever, abdominal cramps, myalgias, and headache lasts 2 - 7 days, usually spontaneously resolve. Systemic infection: May enter blood stream and cause septicemia, invade brain, bone, lungs causing meningitis, pneumonia, osteomyelitis (especially in among sickle cell patients)

Transformation

Gene transfer resulting from the uptake by a recipient cell of naked DNA from a donor cell. Certain bacteria (e.g. Bacillus, Haemophilus, Neisseria, Pneumococcus) can take up DNA from the environment and the DNA that is taken up can be incorporated into the recipient's chromosome. Successful gene transfer is dependent on the absence of restriction endonucleases Most important mechanism of genetic transfer in Gram positive microorganisms such as Streptococcus pneumoniae Cells must be competent Under the control of extracellular Competence Factor (CF) Uptaken DNA-Sensitive to endonucleases Occurs in nature and it can lead to increased virulence. In addition transformation is widely used in recombinant DNA technology.

Chigger mites

General Properties Chiggers (Larvae) have branched, feather like hairs Adult infest grass and bushes but their larvae (chiggers) attack humans and other vertebrates causing severe dermatitis The larvae are minute, barely visible, reddish dots attached to skin They use hooked mouth parts to ingest tissue fluids Epidemiology: Worldwide Medically important chiggers in US: larvae of Eutrombicula alfreddugesi and E. splendens Risk: Campers and picnickers

Chlamydia trachomatis

General properties:, Bacteria, obligate intracellular; require cell culture Has cell wall but lack muramic acid, Do not stain Gram staining, Energy dependent, biphasic growth cycle, Elementary body (EB) and Reticulate body (RB) EB = infectious stage, metabolically inactive RE= metabolically active stage Inclusion body: EB/and or RB inside a cell in a vesicle > 15 serotypes (A-L)

Types of Transduction

Generalized - transfer of any bacterial gene from the disrupted cell Specialized - transfer of specific genes after integration of phage into bacterial chromosome

Bacterial Genome

Genes on Chromosome and extra chromosomal element (if any) Chromosome Plasmid Prophage

Gram Positive vs. Gram Negative Bacteria

Gram positive to take a positive stain and associated with respiratory and soft tissue infections Gram negative to obtain a negative stain and associated with genitourinary or gastrointestinal tract infections

Diagnosis of Ducreyi

Gram staining may reveal chains of coccobacilli Dark-field exam to rule out syphilis Culture difficult PCR and antigen detection methods of choice -90% sensitive Treatment: penicillin resistance common Drug of choice cephalosporins Needle aspiration or incision and drainage of fluctuant lymphadenopathy may be required

Pathogenesis of Coxsackie A Virus

Herpangina (several cox A types) Vesicular Pharyngitis Sudden fever (38-400C), Headache Sore throat Dysphagia (difficulty swallowing) Malaise Ulceration and vesicular rash in the pharynx, tonsils, mouth Hand-foot &mouth disease (coxA 16) mild fever Vesicular lesion, hand, foot, mouth and tongue

Mycobacterium Cell wall structure

High concentration of lipids in the cell wall been associated with : Impermeability to stains and dyes Resistance to many antibiotics Resistance to killing by acidic and alkaline compounds Resistance to complement attack Resistance to lethal oxidations; and survival inside of macrophages Cord factor: (Trehalose dimycolate) Part of the surface lipid: +nt only in virulent strains Inhibits leucocyte migration; disrupts mitochondrial respiration and oxidative phosphorylation Responsible for serpentine appearance (parallel clumping) of mycobacterial cells in culture

Diagnosis of Osteomyelitis

Imaging studies: Plain radiographs Insensitive, especially in early osteomyelitis. May show periosteal elevation after 10 days, lytic changes after 2-6 weeks. Useful to look for anatomic abnormalities (e.g., fractures or deformities), foreign bodies, and soft tissue gas. 3-phase bone scan-Characteristic finding in osteomyelitis: increased uptake in all three phases of scan. Highly sensitive (~95%) in acute infection, CT-Limited role in acute osteomyelitis. In chronic osteomyelitis, excellent for detection of sequestra, cortical destruction, soft tissue abscesses MRI-As sensitive as three phase bone scan for acute osteomyelitis (~95%); detects changes in water content of marrow before disruption of cortical bone. High specificity (~87%), with good anatomic details. Procedure of choice for vertebral osteomyelitis because of high sensitivity for epidural abscess. Laboratory Culture: Blood culture If negative, culture of samples from needle aspiration of pus; or from a bone biopsy ESR and CRP-elevated

Peptidoglycan Cross-linking

In Gram negatives : cross linking between D-alanine and L-lysine is a direct covalent bond In Gram positives: 5 molecules of glycine make a bridge between D-alanine and L-lysine

Cytoadherence

In P. falciparum infections, membrane protuberances appear on the erythrocyte's surface 12-15 h after the cell's invasion. These "knobs" extrude a high-molecular-weight, antigenically variant, strain-specific erythrocyte membrane adhesive protein (PfEMP1) that mediates attachment to receptors on venular and capillary endothelium—an event termed cytoadherence.

Sulfur granules

In actinomycosis are named due to their similar appearance with sulfur but are not actually composed of sulfur. They are in fact, bacterial colonies-consisting of thin Gram positive filaments surrounded by antigen-antibody complexes (gives sunray appearance)

Clay pipe stem fibrosis

In fatal schistosomiasis caused S. mansoni, fibrous tissue, reacting to the eggs in the liver, surrounds the portal vein in a thick, grossly visible layer

Yellow Fever

Infectious agent: Flavivirus- ss+RNA, enveloped virus Reservoir: wild and domestic animals; Transmission: Mosquitoes as vectors Aedes aegypti Jungle cycle: non human primates Urban cycle: human to human Risk Factors/High Risk Populations: travel to endemic areas: Africa and S. America

Treatment of Taenia solium

Intestinal: drug of choice-niclosamide Cysticercosis: drug of choice- praziquantel or albindazole Prevention and Control Proper cooking pork Washing kitchen utensils after cutting pork. Hygiene maintenance Health education regarding transmission

Negri Bodies

Intracytoplasmic inclusion body in rabies Is an accumulation of components of rabies virions in cytoplasm of neural cells.

Cowdry type A

Intranuclear inclusion body in Herpes infection

Lab Diagnosis of Cryptosporidium parvum

Lab Diagnosis: Demonstration of oocyst in feces; unstained, acid fast or fluorescent staining

Tuberculous pleural effusions

Lymphocyte-predominant, exudative effusion - glucose <60 - pH <7.2

Immunological Methods

Measuring specific antibody levels against a particular pathogen - IgM - current infection IgG: paired sera- 4x increase OR : A single serum sample - determine titer and compare it with an upper limit of normal if it is established for that particular pathogen Detection of an antigen specific to a particular pathogen in a clinical (patient) sample in Vitro *Immunological techniques discussed in Immunological tools:

Conjugation

Mediated by the F factor, a plasmid that contain tra operons: (transfer region) where the genes coding for sex pili and other "fertility" factors are found Origin of transfer (OriT): where one of strands breaks and is transferred to the recipient Insertion sequence (For Hfr): a region that facilitate integration to the main chromosome Requires direct cell contact between 2 cells

Categorization of Gram Negative Rod

Medically relevant gram-negative bacilli include a multitude of species. Some of them cause primarily respiratory problems (Klebsiella pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa), primarily urinary problems (Escherichia coli, Proteus mirabilis, Enterobacter cloacae, Serratia marcescens), and primarily gastrointestinal problems (Helicobacter pylori, Salmonella enteritidis, Salmonella typhi).

Categorization of Gram Negative Cocci

Medically relevant gram-negative cocci include the four types that cause a sexually transmitted disease (Neisseria gonorrhoeae), a meningitis (Neisseria meningitidis), and respiratory symptoms (Moraxella catarrhalis, Haemophilus influenzae).

Klebsiella pneumoniae

Member of the Enterobacteriaceae Properties: Gram negative rods, lactose fermenter, non-motile, produces Urease Highly mucoid colonies because of large capsule Reservoir: Part of the normal flora GIT and URT Transmission: inoculation from feces or URT normal flora. One of the top ten nosocomial infections Risk Factors/High Risk Populations: hospitalized patients, catheter. Clinical Disease: Cystitis and Pyelonephritis Diagnosis: Clinical presentation; patient history, culture and biochemical Treatment: Appropriate antibiotics, multidrug resistance common Prevention: Personal hygiene, proper infection control, removal of catheters

Proteus species

Members of the Enterobacteriaceae Two species; P. mirabilis (sensitive to penicillin) P. vulgaris (highly resistant to antibiotics) Properties: Gram negative rod, non-lactose fermenter, H2s positive, urease +, peritrichous flagella, highly motile: swarming colonies -O antigens of certain strain of Proteus cross react with antigens of several Rickettsia. Thus, Proteus antigens used to detect antibody in Rickettsial infection (Weil-Felix reaction) Reservoir: Normal flora of colon Transmission: Auto-inoculation; nosocomial Risk Factors/High Risk Populations: any one

Blood and tissue samples

Microscopic examination Blood, CSF, biopsy Serologic examination Antibody response Antigen detection Nucleic acid hybridization PCR Detection - In situ Culture Imaging; detect presence of parasites in tissues Xenodiagnosis Blood differential cell count = increased eosinophils in parasitic infection

Diagnosis of Listeriosis

Microscopy: CSF typically show no organism - too few bacteria for detection Culture - Small zone of hemolysis on blood agar, catalase positive, CAMP test positive Culture isolation may be improved by "cold enrichment" (storage of specimen in the refrigerator for a prolonged period): while detecting Listeria in specimens contaminated with rapidly growing bacteria

Ectoparasite Neuromuscular manifestation

Neurotoxin mediated Ascending flaccid paralysis: Ticks Systemic arachnidism (Muscle spasm): Black widow spiders

Acid Fast Bacteria skin pathogens

Nocardia spp. Mycobacterium leprae MOTTS: Mycobacteria Other Than Tuberculosis

Katayama fever

Onset of oviposition results in a symptom complex featured by fever, chills, cough, urticaria, arthralgia, splenomegaly and abdominal pain

Fungal Respiratory pathogens

Opportunistic Rhizopus spp. Mucor spp. Aspergillus spp. Pneumocystis jiroveci Regional Histoplasma capsulatum Blastomyces dermatitidis Coccidioides immitis

Ectoparasites

Organisms found either on the skin or only in the superficial layer of skin Arthropods Ectoparasites causing human diseases-two categories: Insects (6 legged arthropods): Lice, Flies, Bed bugs Arachnids/chelicerates (8 legged arthropods): Mites, Ticks, Spiders

Scrub Typhus

Orientia tsutsugamushi Epidemiology: Eastern Asia, Australia, Japan, pacific islands Reservoir: Rodents Transmitted to humans by bite of mite larva (chigger), trans-ovarian transmission in mites Pathogenesis and clinical disease: IP: 10-12 days Severe headache, fever and myalgia Initial lesion, a necrotic eschar at the site of bite. Maculopapular rash (in 50%) starts in the trunk and spread centrifugally to the extremities Lymphadenopathy, splenomegaly, CNS invol. Treatment: Doxycycline Control: Avoid exposure to mites No vaccine

Psittacosis

Ornithosis/Parrot Fever After inhalation, infection of mucosal epithelial cells and macrophages; bacteria spread to RES of liver, spleen-focal necrosis From hematogenous spread, reaches lungs and other tissues Atypical pneumonia, bronchitis, pharyngitis, sinusitis (with high fever, chills headache), rarely causes death in healthy patients In severe cases it may involve other organs, hepato-splenomegaly, GI, CNS and eye infection.

Lab Diagnosis

Other lactose fermenters differ in 1. production of indole from tryptophan 2. decarboxylates lysine 3. use of acetate as sole carbon source 4. it is motile Lactose fermenter - MacConkey agar = pink colonies Eosin Methelene Blue (EMB) = green metallic sheen

Mumps virus

Paramyxoviridae Paramyxovirus Rubulavirus genus General properties: ssRNA, negative sense, helical nucleocapsid, pleomorphic envelope, It carries RNA dependent RNA polymerase One antigenic type only - long life immunity Reservoir: Humans Transmission: Worldwide distribution; Respiratory; person to person via respiratory droplets. Highly contagious - spread 7 days before on set of disease. Risk Factors/High Risk Populations: children under 15 years of age ( 95% of all cases). Unvaccinated, worldwide, peak winter and spring Envelope of paramyxovirus seems to be fragile, distorted on images Non- suppurative enlargement salivary glands

Respiratory Syncytial Virus

Paramyxoviridae Family Pneumovirus genus General properties: Negative-sense, enveloped ssRNA virus, surface spikes carry the F protein, (no hemagglutinin or neuraminidase). causes cells to fuse - multinucleated giant cells (syncytia); Has 2 subtypes (A &B) Subtype A - more severe clinical illnesses ; predominates in most outbreaks. Subtype B - asymptomatic strains affects the majority of the population Reservoir: Humans; (~everyone infected by age 3 years) Transmission: Inhalation of large droplet aerosols; infants and young children may shed the virus up to 3 weeks. Peaks in winter Risk Factors and High Risk Populations: Infants < 1 year/preemies/young children - more severe and involves lower respiratory tract- bronchiolitis and pneumonia- most common cause of acute, fatal respiratory tract infections Adults: Mild symptoms, common cold-like. Very few infections become life-threatening. Adults - re-infection

Enteroviruses

Picornaviridae (family) -Enterovirus: Poliovirus, Coxackievirus, Echovirus, Enterovirus General properties: + ssRNA, icosahedral, non-enveloped Resistant to harsh environmental condition and gastrointestinal tract Portal of entry : URT and intestinal tract But rarely cause enteric disease Exclusively human pathogen Mode of transmission: Faecal- oral Entry to host cell mediated by viral receptors that bind ICAM-1 - intercellular adhesion molecule CD55 - decay accelerating factor CD155 - (for polio virus adhesion)

Biotyping

Presence or absence of biochemical markers The formation of distinct biochemical end-products eg. carbohydrates fermentation Presence of certain bacterial enzymes and or toxins eg. Catalase, oxidase, hemolysins Use of specific nutrients - eg. E.coli using acetate as sole source of carbon Information from selective, differential media and enrichment media E.g Lactose fermentation and other colony characteristics

Pyelonephritis

Renal calculi (nephrolithiasis) Fever, flank pain, shaking chills, nausea, vomiting white blood cell casts and crystals May lead to septic shock - death

Treatment of gonorrhea

Resistance to common antibiotics Plasmid mediated beta-lactamase production, and tetracycline resistance Cephalosporins- third generation - drug of choice ceftriaxone, cefixime, cefotaxime Resistance increasing !!! GN is now a superbug!!! Sensitive only to carbapenem Plus doxycycline or erythromycin effective against possible co-infection with Chlamydia trachomatis Sex partners should be referred and treated. No vaccine antigenic variation Annual Screening: all sexually active women aged <25 years and for older women at increased risk for infection Chemoprophylaxis : To prevent ophthalmia neonatorum local application of either Silver nitrate (1%) - classical method Erythromycin (0.5%), Tetracycline (1%)

Carboxypeptidase

Restriction enzyme that cuts to the left of carboxy terminal Remove terminal D alanine from the pentapeptides in peptidoglycan Inhibited by penicillins

Roth spots

Retinal hemorrhage with white or pale centers caused by immune complex mediated vasculitis. Composed of coagulated fibrin including platelets, focal ischemia, inflammatory infiltrate, infectious organisms. They are typically observed via fundoscopy (using an ophthalmoscope to view inside the eye) or slit lamp exam. They are usually caused by immune complex mediated vasculitis. Roth's spots may also be observed in leukemia, diabetes,, pernicious anemia, and rarely in HIV retinopathy. Roth's spots are named after Moritz Roth

Rabies Virus

Rhabdoviridae (family) Lyssavirus (Genus) Properties: Bullet shaped, ssRNA, negative sense, enveloped virus with helical Nucleocapsid, has G protein spikes - neurotropic Reservoir: in the US: Wild animals, raccoons, bats Transmission: I. From the bite of rabid animals/bats II. Non bite exposure to body fluids from an infected animal Non-bite exposures include scratching or licking of an open wound or mucus membrane exposure to brain tissue or cerebrospinal fluid (CSF) of a rabid animal, handling of dead rabid animals and respiratory exposure (inhalation) from bat dropping. III. Organ (Cornea, solid organs) transplantation: Human to human transmission Risk Factors/High Risk Populations: Animal handlers, veterinarians

Normal flora in the colon

Rich in normal flora, mostly anaerobic Flow rate of food slows down No digestive enzymes More than 20% of feces is composed of bacteria 1011 - 1013 cells/g 500 species Comprises about 2 lb body weight of adult human being The most common members are Bacteroides fragilis : Gram negative strict anaerobe, associated with peritonitis as a result of perforation of the intestinal wall following trauma, appendicitis, colon surgery Escherichia coli: Gram negative, facultative anaerobe, most common cause of urinary tract infection Bifidobacterium, Lactobacillus - used as probiotics

Interferon Response

Secreted by infected cells bind to common interferon receptor on infected as well as non infected cells. The interferon receptor is linked to cytoplasm signalling molecules [Janus family of tyrosine kinases/Janus Kinase (JAK)] and which in turn is linked to STAT (Signal Transducer and Activator of Transcription). Activated STAT enters the nucleus and turns on several genes, including those proteins that help to inhibit viral replication. These include: -Oligoadenylate synthetase, activates an endoribonuclease (Rnase L) that degrades viral RNA. -The second gene activated by interferon is a serine-threonine kinase called PRK kinase - inactivates eIF-2 (an initiation factor) by phosphorylation, thus prevents protein synthesis, inhibits viral replication. -Another interferon induced protein called Mx protein, blocks viral transcription.

Eosin Methylene blue (EMB) agar and MacConkey agar

Selective and differential media Only Gram negative bacteria grow (Coliforms) Differentiate between lactose fermenter and non fermenter LF: Lactose fermenting colonies NLF: Non lactose fermenting colonies EMB agar: contains dyes that are toxic for Gram positive bacteria and bile salt which is toxic for Gram negative bacteria other than coliforms. EMB is the selective and differential medium for coliforms Lactose fermenters in EMB agar give a distinctive metallic green sheen (due to the metachromatic properties of the dyes) MacConkey agar: LF colonies: pink, NLF: gray/colourless

Treatment of Cryptosporidium parvum

Self limiting in healthy. No effective treatment, Immunocompromised may use paromomycin, nitazoxanide Prevention and control: Improved personal hygiene and sanitation, purification of water supply including filtration (since cysts are resistant to standard chlorination)

Treatment of Coccidioidomycosis

Severe - Amphotericin B, azoles

Diarrheal diseases

Small/large intestine caused by viruses, bacteria, parasites Three categories: Intoxications Non-inflammatory Diarrhoea Inflammatory Diarrhoea Intoxications Staphylococcus aureus Bacillus cereus Clostridium perfringens Clostridium botulinum

Treatment of RSV

Symptomatic: bronchodilators to help relieve chest congestion and wheezing; such as metaproterenol or albuterol For severe disease Use oxygen therapy, Aerosolized Ribavirin (a nucleoside analogue of guanosine) Hyperimmune globulin against RSV (RespiGam) Prevention: (Natural infection may still allow re-infection) Immuno-prophylaxis: For children <2 yrs who have chronic lung disease - Monoclonal ab against F protein - (Palivizumab) Hyperimmune globulin (RespiGam) against RSV

Infective Endocarditis Clinical features

Symptoms Fever, sweats, chills, back pain Anorexia, malaise, weight loss Signs Anemia (normochromic, normocytic) Splenomegaly Microscopic hematuria, proteinuria New or changing heart murmur, CHF Embolic or immunologic signs (Splinter hemorrhage, Janeway lesion, Osler's node, Roth spot) Hypergammaglobulinemia, elevated ESR, CRP, RF

Diagnosis of Septic Athritis

Synovial fluid analysis-WBC count, Gram stain, Culture Differentiate septic arthritis from non inflammatory and inflammatory (next slide) Blood culture Culture of pharyngeal, rectal, cervical or urethral specimens (on suspicion of Gonococcal Septic arthritis): Thayer martin media Imaging Plain X-Ray: expansion in joint space, edema around the joint Ultrasound- collection of fluid in the joint and aspiration CT- detection of associated osteomyelitis, joint fluid MRI- spread of joint infection to surrounding structures

Treatment of Mycoplasma pneumoniae

Tetracycline (doxycycline), Erythromycin and Quinolones Prevention: Covering mouth and nose while coughing and sneezing Hygiene Isolation of cases

Acid Fast Cell Walls

The cell envelopes of these organisms are considerably more complex than other bacteria. Mycolic acid (long, branch chained fatty acids) covalently bound via a polysaccharide to peptidoglycan. Other mycolic acid-containing compounds and other complex lipids form a thick waxy membranous layer outside the peptidoglycan layer. Components: Peptidoglycan Lipid based polymers woven through out, e.g, Mycolic acid Trehalose dimycolate Lipoarabinomannan Arabinogalactan Cell wall resists intracellular killing Examples Mycobacteria, Nocardia

Hepatitis B Virus Clinical Features

The incubation period for HBV infection is longer than that for HAV infection and is anywhere from 7 to 160 days in duration. Asymptomatic infections occur about 65% of the time. Early symptoms of acute infection include fatigue, anorexia, nausea, pain and fullness in the upper right quadrant, and fever. Manifestations that develop later may include arthritis, rash, and cholestasis (jaundice and icterus;, and tend to be more severe than in patients infected with HAV. Fulminant HBV hepatitis occurs in 1% of acutely infected individuals. Fulminant hepatitis results in altered brain function (hepatic encephalopathy), extensive jaundice, and massive necrosis of the liver. Manifestations are more severe and can be fatal. Patients have severe liver damage with abdominal ascites and bleeding; the liver shrinks rather than swells. Chronic HBV hepatitis occurs in 5-10% of patients and is more likely to occur in those that had a mild or in apparent initial infection. Chronic HBV hepatitis is defined at the presence of HBV surface antigen in the bloodstream for at least 6 months.

Viropexis

The process by which different classes of viruses, particularly picornaviruses and papovaviruses, enter the host cell in which they will be able to replicate. The hydrophobic structures of the capsid proteins may be exposed after viral binding to the cell (see VAP, viral attachment protein). These structures help the virion or the viral genome slip through the membrane.

Quorum sensing

The regulation of gene expression in response to fluctuations in cell-population density. Quorum sensing bacteria produce and release chemical signal molecules called autoinducers that increase in concentration as a function of cell density. The detection of a minimal threshold stimulatory concentration of an autoinducer leads to an alteration in gene expression. Gram-positive and Gram-negative bacteria use quorum sensing communication circuits to regulate a diverse array of physiological activities

Formation of asexual spores (Anamorph)

The shape, color and arrangement of asexual spores/spore forming structures are used in the identification of fungi Two basic forms: a. Conidia-naked spores, no sac, most common form ; different forms Eg, Chlamydoconidia, Microconidia, Macroconidia etc. b. Sporangiospores - contained in a sac like structure

Replication of paramyxoviruses

The virus binds to glycolipids or proteins and fuses with the cell surface. Individual messenger RNAs (mRNAs) for each protein and a full-length template are transcribed from the genome. Replication occurs in the cytoplasm. Proteins associate with the genome, and the nucleocapsid associates with matrix and glycoprotein-modified plasma membranes. The virus leaves the cell by budding. (−), Negative sense; (+), positive sense; ER, endoplasmic reticulum; RSV, respiratory syncytial virus

DNA Viruses

There are 7 families Genome/DNA structure varies Double stranded linear (eg, herpes virus) Double stranded circular (complete) [eg, human papilloma virus] Partially double stranded circular - only in hepadnaviruses Single stranded linear - only in parvoviruses All replicate in the host cell nucleus except for poxviruses All have a neoplastic potential since they have an intra- nuclear residence and might damage host DNA They may also cause latent infection

Lyme Disease

Though complete genome sequencing has been done, pathogenesis is not well understood Disease has three stages Primary: Early localized Secondary: Early disseminated Tertiary : Late disseminated

Strongyloides stercoralis

Threadworm First described in French troops stationed in modern day Vietnam during the late 19th century who were suffering from severe, persistent diarrhea. Epidemiology: Mostly tropical and subtropical climate and poor sanitation, warm moist soil. Sporadic cases in temperate regions 30-100 million infected persons worldwide; rural areas; often associated with agricultural activities. Transmission: penetration through the skin, similar to hook worm. Plus autoinfection Complicated life cycle - free living and parasitic form. Egg hatch into larva in the intestine. Mature larva (filariform) penetrate skin -goes through lungs - esophagus - intestine (like hookworm)

Surviving host defenses

To avoid immune attack by Interference: Camouflage: Antigenic Variation Coordinated expression of several genes (Pathogenicity islands) Camouflage: Disguise, concealment

Endemic syphilis/ Bejel

Transmitted by sharing drinking and eating utensils Skin lesion and around the oral mucosa, Bone and skin granuloma may occur later Found mostly in desert in Africa and Middle east

TORCH

Transplacentally transmitted pathogens T for Toxoplasma O for other (syphilis, group B streptococcus, Listeria monocytogenes ....) R for rubella C for cytomegalovirus H for HIV, herpes simplex and hepatitis B.

Treatment of Streptococcus pyogenes (GAS)

Treatment : Pharyngitis: Penicillin G/or amoxicillin , For allergic - Macrolides such as azithro/erythromycin. AGN and RF: after onset, antibiotics do not help Prevention: No vaccine available Early treatment of pharyngitis - prevent RF Persons having recovered from rheumatic fever are given monthly dose of benzathine penicillin to prevent further infection by strep and prevent recurrence of rheumatic fever.

Treatment of JC Virus

Treatment: No effective treatment; Currently, best treatment is reversal of the immune-deficient state. In the case of HIV-associated PML, immediately beginning anti-retroviral therapy will benefit most individuals. Prevention: not known

Treatment and prevention of listeriosis

Treatment: With bactericidal agents Combination of Penicillin/ ampicillin with aminoglycosides. OR Trimethoprim- sulfamethoxazole Resistance to several other antibiotics. Prevention: Pregnant women and immunocompromised should Avoid soft cheeses, raw or partially cooked foods of animal origin, unwashed raw vegetable. Follow CDC recommendation: http://www.cdc.gov/listeria/prevention.html

Pinta

Treponeme Direct contact with infected lesion Primary and secondary lesions , Limited to the skin and healed lesion leave skin depigmented area - white patches Found central and south America

Reduviid bugs (Triatomine bugs/kissing bugs)

Trypanosoma cruzi vector, feeding and defecating on the wound after taking a blood meal. The bug excretes the trypomastigote form along its feces while feeding. It enters the bite site or eye while the persons rub the site of infection and the eye.

Acute Post Streptococcal Glomerulonephritis

Usually follows localized skin infection by GAS Pharyngitis associated AGN-Acute glomerulonephritis may also occur Takes about 10-15 days after the skin infection Antigen antibody complex deposition (hypersensitivity type III) on the glomerular basement membrane triggers inflammatory reaction that leads to tissue damage and impairment of normal kidney function The major symptoms include hypertension, edema, hematuria, proteinuria , smoky urine

Non-specific tests for syphilis

VDRL: Venereal Disease Research Laboratory RPR: Rapid plasma reagin Cardiolipin as the antigen from beef heart immune flocculation test Easy, rapid, inexpensive Sensitivity: Primary stage - 70 - 85% positive, Secondary stage - 99% positive. Tertiary stage - 70-75% Specificity: False positive in diseases such as connective tissue diseases, Infectious mononucleosis, Malaria, Leprosy, Infective endocarditis - and non-conventional treponemas Titers decrease with effective treatment and in the late stage of the disease with/out treatment Therefore used to assess adequacy of therapy

Prevention of Rubella Virus

Vaccine: MMR- Live attenuated vaccine Recommended to 12-15 months and 4-6 years old , and non immune women - if they want to get pregnant (At least 1 month before conception. (Not for immunocompromised and pregnant women) Rubella test for women: pregnant or want to get pregnant- ELISA - determine ab level (a part of TORCH screening)

Prevention of measles

Vaccine: live attenuated - part of MMR (12-15 mo + 5-6 yr), SC Significant reduction in the incidence: only one type of virus and human as the only host

Tuberculoid Leprosy

Well defined cutaneous macular rash with erythematous borders and pigment loss in center; associated with areas of sensory loss (fine touch, pain, temperature) Lepromin skin test positive Result of a good T cell (TDTH) response Skin lesions: raised erythematous margin. Center- anaesthetic (loss of sensation)

Helix distortion mutations

When UV radiation induces dimerization of adjacent nucleotides, particularly thymines. Results cyclobutane ring in DNA, which prevents faithful replication

Complementation

When a defective virus is aided in its replication by a helper virus (complete virus/ or other defective virus) Can occur when either one or both of the two viruses that infect the cell have a mutation that results in a nonfunctional protein Non mutated virus (helper virus) complements the mutated one (defective virus) by making functional protein

Cyclospora cayetanensis : Life cycle

When freshly passed in stools, the oocyst is not infective (thus, direct fecal-oral transmission cannot occur; this differentiates Cyclospora from another important coccidian parasite, Cryptosporidium). In the environment , sporulation occurs after days or weeks at temperatures between 22°C to 32°C, resulting in division of the sporont into two sporocysts, each containing two elongate sporozoites . Fresh produce and water can serve as vehicles for transmission and the sporulated oocysts are ingested (in contaminated food or water) . The oocysts excyst in the gastrointestinal tract, freeing the sporozoites which invade the epithelial cells of the small intestine. Inside the cells they undergo asexual multiplication and sexual development to mature into oocysts, which will be shed in stools. The potential mechanisms of contamination of food and water are still under investigation.

Inhalation anthrax

Wool sorter's disease Most serious form Incubation time: week to 2 months (long latent period), during which alveolar macrophages engulf spores and carry them to mediastinal lymph nodes Initial symptoms are nonspecific: atypical pneumonia-like symptoms Progression to respiratory distress: Massive chest edema, hemorrhagic mediastinal lymphadenitis (widened mediastinum). Hemorrhagic pleural effusions, bacteremia and toxemia resulting in cyanosis, shock and death within 3 days in most cases; many patients also present with meningeal symptoms.

Polio eradication

World wide campaign to eradicate Polio started 1988 Today, only 3 countries (Afghanistan, Pakistan and Nigeria) remain polio-endemic (but all detected cases since 2017 have been in Afghanistan and Pakistan) down from more than 125 countries in 1988

Epidemiology of Influenza Virus

World wide: Isolates named by type, place, strain #, year, antigen (subtype) A/Fujian/411/2002/(H3N2) Only Type A and B cause epidemics. Type A- even pandemic Transmission: Respiratory transmission, aerosol droplets, fomites Risk Factors/High Risk Populations: any one unvaccinated, severe among elderly and children

Colony

a visible mass of microbial cells on solid/semisolid media that theoretically arose from one cell

Non-gonococcal urethritis and cervicitis

(watery discharge) caused by serotype D-K The most common bacterial STD in the US Many infected cases (up to 80%) are asymptomatic

MODS (Multiple Organ Dysfunction Syndrome)

Altered organ function that can not be normalized without intervention

Acinetobacter baumannii

'Iraqibacter' or Iraq bacillus due to its sudden emergence in military treatment facilities during the Iraq War It was primarily associated with blood stream infection, respiratory infection and wound infection at military medical facilities General properties: Gram negative coccobacilli (very small rods), non motile, aerobic, oxidase negative, Non fermenter, highly resistant to antibiotics Reservoir: Ubiquitous like Pseudomonas; exceptionally resistant to the environment, on dry surfaces also; found as normal flora in oropharynx of some people Transmission: Person-to-person contact or contact with contaminated surfaces High rate of transmission in hospital setting Risk Groups/High Risk Populations: Opportunistic pathogen, Patients with respiratory ventilation, catheterized patients (urine, dialysis), broad spectrum antibiotics, after surgery or trauma

Actinomyces israel Clinical Diseases

-Cervicofacial actinomycosis: most common form, Angle of jaw- "Lumpy Jaw" Nodule on the cheek or submaxillary region Feels hard/woody - uneven; lumpy Progresses to become suppurative (Abscess) Draining abscess/sinus tract (openings from underlying abscess to epidermis) PUS may appear orange/yellow color - Sulfur granules -Thoracic and abdominal forms after aspiration/swallowing -Pelvic inflammatory actinomycosis: intrauterine device related Other tissues: Hematogenous spread to other tissue areas - thighs, bone, CNS etc

Viral Isolation and Growth

1. Chicken eggs (Embryonated) - still used for some viruses 2. Animals - mainly for research purposes 3. Cell culture: Three types of cell lines: monolayer growth Primary cells - e.g. Monkey Kidney cells. These are essentially normal cells obtained from freshly killed adult animals. These cells have limited life span, and can only be passed (cultured) once or twice. Semi-continuous cells (diploid cell line)- e.g. Human embryonic kidney cells and skin fibroblasts. These are cells taken from embryonic tissue, and may be sub-cultured up to 50 times. Continuous cells - e.g. HeLa, Vero, Hep2, LLC-MK2, BGM. These are immortalized cells i.e. tumor cell lines and may be sub-cultured indefinitely.

Diagnosis of gonorrhea

1. Evaluation of the presenting symptoms and sexual history; 2. Microscopy: Gram stain of exudates from urethra, cervix, rectum, pharynx or conjunctivae 3. Culturing: sample collection: use calcium alginate swabs. Media: Thayer Martin/or New York City medium Chocolate agar + antibiotics to inhibit other organisms, Require 5% CO2 Biochemical test: Ferments glucose but not maltose 4. Molecular techniques: directly from sample swabs Antigen detection: immunoassay can be done at home, low specificity NAAT (Nucleic acid amplification tests) : PCR rapid: but no info. on antibiotic susceptibility

Anti-protozoal Drugs

1. Heavy metals: inhibits sylfhydryl group of enzymes and disrupt glycolysis Arsenicals: eg, Melarsoprol inhibits parasite pyruvate kinase (inactivates sulfhydryl groups) and causes decreased concentrations of ATP, pyruvate and phosphoenol pyruvate Antimonials: eg, Sodium stibogluconate 2. Inhibitors of DNA Replication Quinoline derivatives - Chloroquine, Primaquine Interfere with DNA replication and hemoglobin digestion Diamidines - Pentamidine: binds with DNA Nitroimidazoles - Metronidazole*- breaks DNA 3. Inhibitors of Folic Acid Biosynthesis: Inhibition of biosynthetic pathway Pyrimethamine inhibitis the enzyme dihydrofolate reductase (DHFR). Sulfonamides/Trimethoprim* 4. Inhibitor of pyruvate-ferridoxin oxidoreductase: Nitazoxanide: Inhibits anaerobic metabolism (protozoa and anaerobic bacteria) 5. Inhibitors of Protein Synthesis Paramomycins - Paramomycin (aminoglycoside) Tetracycline, clindamycin, spiramycin (macrolide) 6. Sesquiterpenes: Artemisinins, artemether React with heme moety causing free radical damage to parasite membranes Most effective antimalarial 7. Phosphocholine analogue: Miltefosine Act on key enzymes involved in metabolism of ether lipids present on the surface of parasite 8. Atovaquone-Proguanil (Malarone) Atovaquine inhibits electron transport chains of mitochondria of parasite Proguanil-antifolate (inhibits DHFR enzyme)

Pathogenesis of Typhoid Fever

1. Perforation wall of intestine 2. Fatty degeneration: accumulation of fat in cells resulting in enlarged spleen and liver, mesentric glands, kidney, heart 3. Inflammation of gall bladder 4. Skin- Rose spots 5. DIC: Thrombophlebitis - vein inflammation related to a blood clot

TB clinical disease

1. Primary tuberculosis: lower part of lung cavitary lung disease: Gradual onset, cough, bloody sputum, fever, chills, night sweats, weight loss 2. Latent tuberculosis: no clinical symptoms, bacteria remain alive inside granuloma 3. Reactivation tuberculosis: upper part of lung, similar symptoms as primary 4. Miliary (multiple foci) : disseminated, and extra-pulmonary disease of many tissues

HIV Treatment

1. Reverse transcriptase inhibitors - inhibit cDNA synthesis Nucleoside/Nucleotide NRTI Non-Nucleoside: NNRTI 2. Protease Inhibitors: PI inhibit viral protein cleavage 3. Binding and Fusion inhibitors: Enfuvirtide blocks action of gp41 mimics one section of gp41 Maraviroc blocks CCR5 4. Integrase inhibitors (IIs): Isentress - inhibit latency 5. Highly Active Anti-Retroviral Treatment (HAART) Multiple drug therapy: cocktail of drugs to minimize the emergence of resistance Virus mutate fast.

Considerations in Diarrhea

1.Time frame relative to consumption : hours to days Rapid onset (hours) largely distinguishes rapid acting preformed toxins in food from infection 2. Signs and Symptoms (one or more may be present) -Nausea, vomiting, diarrhea - watery feces (3 or more in a 24 hrs period), frequency and volume -Fever -/+ -dysentery (gut pain, diarrhea, often bloody, containing inflammatory cells) 3. History: -epidemiology, (contact with other cases) -type of foods eaten -drugs (antibiotics, etc.) -travel, pets -clinical predispositions

Influenza virus segmented genome

8 ss neg RNA segments NS1-interferes with interferon response

Rectal prolapse

A condition in which the lower portion of the colon, just inside the anal canal, becomes turned inside out and protrudes outside the body. In a whipworm infection, the rectum loses its internal support because the worms bury their thin heads into the intestinal lining, loosening the elastic epithelium and weakening the surrounding muscles. In addition to it, increased peristalsis in whip worm infection also contributes.

Stages of Disease Progression

A primary infection refers to an infection you acquire for the first time A secondary infection is an infection that occurs during or after treatment of another pre-existing infection. It may result from the treatment itself or from changes in the immune system. For example, a vaginal yeast infection that occurs after antibiotic treatment of a bacterial infection is a secondary infection Types of infection: acute, chronic primary, secondary

Diagnosis of HCV

ALT = high in acute phase, later goes up and down Anti-HCV antibodies - does not differentiate acute Vs chronic, provide no immunity ( virus mutates at high rate) Detection of HCV RNA - may be intermittent throughout the infection : repeated test required to rule out infection with HCV ELISA (antibodies appear within 7 to 31 weeks of infection - does not differentiate acute/chronic past infection - gives no immunity Confirmation: false positive in ELISA occur, confirm using Western blot, (using 4 recombinant HCV antigens) RIBA = recombinant immnoblot assay RT-PCR for HCV RNA - diagnosis in acute phase, and confirmation and determination of viral load in monitoring the response to antiviral therapy. Repeated testing required

Hydatidosis

Abdominal cyst Treatment: Surgical excision-treatment of choice; If inoperable, high dose albindazole or praziquantel Prevention: Health education regarding the transmission of the parasite

Pathogenicity

Ability to cause disease

B. abortus

Abortion in cattle related to high concentration of erythritol in placental tissues- is a growth factor for brucella. Human placenta does not contain erythritol

Pathogenesis of Clonorchis sinensis

Adults live in the bile duct causing inflammation resulting in fibrosis and hyperplasia, narrowing or blockage of the bile ducts. In heavy infection eggs may enter the liver causing granuloma. Association with gall-bladder stone formation (picture-next slide) Clinical disease: Indigestion, epigastric discomfort, weakness and loss of weight. Heavy infections: liver enlargement, Chole-cystolithiasis, jaundice, edema, ascites and diarrhea.

Tinea nigra

Affects stratum corneum (traumatic inoculation) superficial mycosis of the stratum corneum. Infection is believed to occur as a result of inoculation from a contamination source such as soil, sewage, wood, or compost subsequent to trauma in the affected area. The fungus exhibits lipophilic adhesion to human skin; it is exclusively found in the stratum corneum and does not extend into the stratum lucidum. The fungus receives nourishment from its use of decomposed lipids. Its tolerance to an environment with a high salt concentration and a low pH allows the fungus to thrive in human skin. By Hortaea werneckii-Black (Dematiaceous) fungus-branched, septate hyphae with arthroconidia and elongated budding cells Brown to black macule- mostly on palm, due to production of melanin. Darkly pigmented macules with irregular edges The treatment is very simple and effective. Most cases resolve with only keratinolytic agents like urea, salicylic acid and Whitfield ointment, applied once or twice a day (for about 15 days)

Cytomegalovirus (CMV)

Affects various organs Belongs to human herpes virus (HHV5)

Multi-site mutations

Also known as Macrolesion. Alteration of DNA involving large no. of base pairs, More comprehensive changes in the DNA, involve loss (deletion), gain (addition), duplication or inversions

Morphology of Naegleria fowleri

Amoeba - protozoan, exists as Cyst (only in the environment, not in human body) Trophozote (have pseudopodia, reproductive stage) Flagellated form

Lipopolysaccharide (LPS)

Antigen - surface antigens on Gram negative bacteria Target for specific immune response Serotyping of bacteria Core polysaccharide - contributes to the integrity of membrane Conserved among related Gram negatives Lipid A - long fatty acid: Endotoxin: Inflammation, hypotension, shock some variation across species

West Nile Fever

Asymptomatic: majority Non neuro-invasive (Febrile illness). About 1/5 who are infected : a fever, headache, body aches, joint pains, vomiting, diarrhea, or rash. Most recover, but fatigue and weakness can last for weeks or months. Severe symptoms (neuro-invasive): < 1% encephalitis or meningitis, paralysis: Recovery may take several weeks or months. Or May lead to permanent neurological damage 10 percent of people who develop neurologic may die. Mortality: 5% of reported cases (1999-2018) in the USA

Sepsis

At least 2 signs and symptoms of SIRS + a documented site of infection

Complications of Campylobacter

Autoimmune diseases Guillain-Barre syndrome : Demyelination of the peripheral nerves Rapid ascending muscle weakness of the extremities, trunk, head and face. Immunological cross reactivity between O antigen (O 19) and peripheral nerve gangliosides. Reactive arthritis: Inflammation of joints, HLA-B27

Prevention of meningococcal meningitis

Avoid crowded condition prophylactic antibiotics, for exposed people Rifampin or ciprofloxacin - effectively secreted to the mucus membranes Vaccines: Three kinds of meningococcal vaccines (MCV) available in the United States Conjugate: Meningococcal conjugate vaccines (Menactra®, MenHibrix® and Menveo®): Polysaccharide + protein Polysaccharide: Meningococcal polysaccharide vaccine (Menomune®) Recombinant: Serogroup B meningococcal vaccines (4CMenB vaccine /Bexsero® and Trumenba®): Multicomponents Vacccine recommended for all preteens and teens; and some adults at risk

Bacillary Angiomatosis

Bartonella henselae in immunocompromized host Vascular proliferative (neo-vascular) lesions in the skin, under the skin, in bone, or in other organs Red cranberry-like papule- elevated, nodular lesions (satellite lesions common) Closer inspection shows lobular proliferations of small blood vessels May ulcerate and produce serous drainage with or without visible blood

Diagnosis of Balantidium coli

Demonstration of cyst and trophozoite in feces

Treatment of Fasciola hepatica

Bithionol is a chlorinated bis-phenol. It is suggested that bithionol is an uncoupler of oxidative phosphorylation. It has anthelmintic properties and is active against the trematodes Fasciola hepatica (sheep liver fluke) and Paragonimus westermani (lung fluke). Triclabendazole broad spectrum anthelmintic agent Prevention and control: Same as F. buski

Uses of botulinum toxin

Botox cosmetics - Treat spasmodic muscle disorders Relieve of chronic migraine pains, up to 3 months Most likely that botox inhibits the release of inflammatory cytokines by the nerves. Botox injections are to treat such problems as repetitive neck spasms (cervical dystonia), overactive bladder and some causes of crossed eyes.

Virulence of Klebsiella pneumoniae

Capsule - antiphagocytic, Endotoxin (LPS) - inflammation, septic shock Clinical Disease: Typical pneumonia: Hospital and community acquired, mostly upper lobes, 50% mortality. Necrotic destruction of alveolar spaces, cavity formation. Sputum thick, Blood tinged currant jelly sputum. May lead to septicemia. It also causes urinary tract infection (will be discussed under UTI)

Complications of Infective Endocarditis

Cardiac : valvular damage, infection beyond valve→ CCF, higher mortality A-V block pericarditis, tamponade or fistulae Systemic emboli mitral>aortic, high risk if >10 mm risk decreases once appropriate antimicrobial therapy started. Prolonged fever

Pathogenesis of Pasteurella multocida

Cellulitis and Soft Abscess not fully understood. It has capsule and endotoxin IP: less than 24 hrs after animal bite At the site of bite develops a rapidly spreading diffuse cellulitis Progression of disease results in a soft abscess with extensive edema and regional lymphadenopathy Bone infection - if the bite is deep (bite from Cat's sharp pointed teeth) Fever in about 20% of cases Immunocompromized Systemic infections The local abscess may lead to necrotizing fasciitis

Haemophilus ducreyi

Chancroid: Soft Chancre Gram negative rod, chain former, LOS cell wall; Grow on chocolate agar, is a capnophile (require CO2) Reservoir: Humans Transmission: Sexual transmission , few hundred cases per year in the USA, some times with outbreaks "You do cry with ducreyi"

Blueberry muffin rash

Characterized by widespread maculopapular lesions of reddish-blue or magenta color caused by persistent dermal erythropoiesis. In congenital rubella, the typical lesion can present at birth, during the first 48 h or, rarely some months later (This type of rash can also be seen in cytomegalovirus infection, hematological disorder etc.)

Treatment of Varicella-Zoster Virus

Children: supportive treatment For adults/ immunocompromised: to prevent dissemination Acyclovir/Famciclovir OR Passive immunization: Varicella immunoglobulin (VZIG) DO NOT USE ASPIRIN (Reyes Syndrome as sequelae) Pain control in post herpetic neuralgia

Treatment of Brown Recluse Bite

Cleansing bite wounds, tetanus prophylaxis and antibiotics for prevention of secondary bacterial infection Antivenom within 24 hours (early administration has better result) Prevention and Control: Similar to Black Widow Spiders

Pathogenesis of Streptococcus pyogenes (GAS)

Clinical diseases: Pyogenic infections -include pharyngitis, otitis media, pneumonia, skin and soft tissue infections Toxin mediated - scarlet fever, toxic shock syndrome, fasciitis Immune mediated (non suppurative): follows untreated pharyngitis/ skin infection Rheumatic fever Glomerulonephritis

Diagnosis of Salmonella

Colonial growth pattern displayed by cultured on a Hektoen enteric (HE) agar. Salmonella colonies grown on HE agar are blue-green in color indicating that the bacterium does not ferment lactose. However it does produce hydrogen sulfide, (H2S), as indicated by black deposits in the centers of the colonies

Transfer of Fertility factor

Conjugation occurs turning an F- cell into an F+ cell The F factor must be completely transferred to ensure a copy of the tra operon (transfer operon) present. The tra operon drives the conjugation process Maintaining the plasmid in the cytoplasm is energy requiring. If there is no external pressure to maintain the plasmid, it may be lost over time = Curing

Gram Positive Cell wall

Components: Thick multilayered peptidoglycan Teichoic acids (TA) Lipoteichoic acids (LTA) Pentaglycine aa bridge cross -linking of peptidoglycan layers Teichoic acid and lipoteichoic acid. (water soluble polymers that contain ribitol or glyceral phosphate) These are species specific; some may be conserved across a genus. They are immunogenic and trigger a specific immune response but they may also undergo antigenic variation.

Significance of Transposition

Consequence of integration: Disruption of normal gene sequence Insertion of new genetic information Can carry several genes (Pathogenicity Islands-several genes under the control of a single promoter)-Gene products include toxins, adhesins, antibiotic resistance, etc

Diagnosis of Shigella

Culture media: Selective and differential media, such as MacConkey, EMB may be used. non-lactose fermenter But Hektoen enteric agar favors the growth of the non-lactose fermenters (Shigella and Salmonella) over the other enterobacteriaceae Hektoen enteric (HE) agar - growth of non-lactose fermenter - faint green (non H2S producer)

Diagnosis of Brucellosis

Culture: repeated blood sample, bone marrow. Culture on blood agar/castaneda medium. Grow slowly: 2-4 weeks. Serology: Standard Agglutination test (SAT) four fold increase of Ab titer in paired sera; or single titer above 1:160 Treatment: Treat for 6 weeks with doxycycline with rifampin (WHO) (Doxy-replaced with Cotrimoxazole for pregnant ladies and children <8) Prevention: Drinking/eating only pasteurized cheese and milk . People handling meat should wear protective glasses and clothing. Vaccination of young animals/required in the US Detection and elimination of infected animals

Diagnosis of HAV

Current infection: HAV-IgM serum by ELISA Past Infection (i.e., immunity) HAV-IgG by ELISA Viral RNA: for epidemiological purposes

Virulence

Degree of pathogenicity; measured by (ID50) or (LD50) Infectious dose (ID50) number of a pathogen enough to cause disease Lethal dose (LD50): number of a pathogen enough to kill a host

Genotype test

Detect resistant gene: ex. Van A and Van B genes for Vancomycin DNA hybridization Sequencing PCR (Amplification) Rapid, detect presence of the resistant gene but it may not mean expression of the gene

Haemadsorption

Detection of viral peplomers (hemagglutinins on infected cells) Occurs as a consequence of the insertion of viral peplomers (that have the ability to bind to RBC) into the surface of infected cells, chicken RBCs can now bind to these peplomers on the surface of the infected cells phenomenon is particularly useful in detecting infection by viruses that cause little cytopathic effect. useful for enveloped viruses that express hemagglutinins (surface gp - binds to RBC)

Electron Microscopy

Detection of virus in specimens Study of Size, Morphology Detection and identification of virus can be enhanced by using virus specific ab (Ab agglutinate virus) or by immunofluorescence

Pathogenesis of Respiratory syncytial virus

Direct viral invasion of epithelial cells and form giant cells (syncytia), kills cells This is followed by immunologically mediated cell injury Necrosis and sloughing of the bronchiolar epithelium. Formation of plugs, containing mucus, fibrin, necrotic material obstructs the air pathway - the hallmark of bronchiolitis. Airway obstruction can be extremely dangerous, especially in infants and young children who have narrower airways than adults.

Urethritis

Discharge: Clear or purulent or mucopurulent Color varies: white, yellow, green, brown dysuria (painful urination) or urethral itching Odor change

Treatment of Paragonimus westermani

Drug of choice-triclabendazole (Benzimidazole): broad spectrum anthelmintic agent, acts by: 1] inhibition of fumarate-reductase of the parasite 2] inhibition of glucose transport, resulting in glycogen depletion, cessation of ATP formation and paralysis or death and 3] disruption of microtubular function and elimination of their motility Prevention & Control: Avoiding eating raw, pickled, smoked crabs and crayfish; Education; Proper disposal of human feces

Treatment for Ascariasis

Drug of choice: Albendazole or Mebendazole Prevention: Education, Improved sanitation and avoidance of human feces as fertilizer

Treatment of Enterococcus faecalis/faecium

Dual treatment with aminoglycosides + cell wall inhibitors. Resistance is increasing, plasmid gene, Resistance very common including vancomycin Prevention: Restricted use of antibiotics, proper infection control practices

Diagnosis of Ebola

ELISA- antigen detection, RT-PCR, requires high safety standard. Treatment, control and prevention; No antiviral drug Mainly supportive : balancing electrolytes, maintaining oxygen status and blood pressure. Interferon Passive transfer - heat treated convalescent sera Quarantine infected patients Destroy infected animals Vaccine: Under trial (Experimental vaccine : effective)

Diagnosis of Blood stream infection

Early diagnosis important to minimize complication Blood culture: Should immediately be obtained. A minimum of 2 sets of cultures is essential. Most likely to be positive if collected when the fever is rising. The yield increases with the volume of blood cultured. A 1 in 10 dilution (Blood in Broth) is usually optimal. Other specimens culture: based on suspicion of other organ involvement Urine, sputum, pus, would swabs, drain aspirate, throat swabs, joint aspirate, CSF, diarrheal stool may be cultured in appropriate circumstances

Morphology of Schistosoma spp.

Eggs, larvae (various stages) and adults Adults: The sexes are separate, the male and female live attached to each other. This ensures fertilization Males are shorter and stouter than females, lateral margins of males are folded to form gynaecophoric canal ('Schist') The female resides in the groove in the male [i.e, the gynecophoric canal ('Schist')] where he continuously fertilizes her eggs. There are 3 medically important species: can be distinguished by the appearance of their eggs in the microscope S. mansoni: have a prominent lateral spine S. japonicum: have a very small lateral spine S. haematobium: have a terminal spine Unlike other trematodes, Schistosoma eggs are bile stained but not operculated forked tailed cercariae are the infective form adults are not typical leaf like but more elongated have separate sexes

Source of CNS infection

Entry into the cranial cavity Hematogenous: Spread of distant foci or by insect bite mostly via choroid plexus Local: infection of skull, middle ear, nasal sinus or osteomyelitis Trauma to the head: Fractures eg. Fracture of cribriform plate during water diving Surgery: placement of cerebral shunts during medical intervention Via peripheral nervous system Some viruses and toxins can move from one place to another through nerve fibers - herpes, rabies, tetanus Via olfactory nerve endings - which are the only elements of the nervous system in direct contact with the exterior

Plasmids

Extra-chromosomal DNA, circular One or more in a cell, Can be lost or gained Replicate independent of the main chromosome Can integrate into the main chromosome (episome) Carries genes - for specialized function, but not essential for survival such as R-plasmid - antibiotic resistance gene

Transpeptidase

Facilitate formation of peptide cross-links between the amino acid layers of peptidoglycan to make the wall strong Inhibited by penicillins

Streptococcus pyogenes

Group A Streptococcus (GAS) General properties: Gram positive cocci in chains, catalase negative, beta hemolytic on blood agar plate, bacitracin sensitive, Lancefield group A, PYR +. Group specific carbohydrate (A antigen) and type specific proteins (M) in cell wall, Over 150 different strain of M types Reservoir: Humans, Transient colonization of URT and skin Transmission: Respiratory droplet and direct contact (exudates, fomites), winter-spring, especially with crowding Risk Factors/High Risk Populations: Mostly among children 5-15 years (pharyngitis) though infects all ages.

HIV -1

Has several groups and subtypes/clades Group M is the most common globally. Several clades predominate in certain regions. Eg. Clade B in Americas, Europe, and Australia Clade C in India and South Africa Clade A in West Africa

Transformative factors

Impaired immunity Transfer to susceptible sites Transfer to susceptible people Breach in the integrity of skin/mucous membrane due to trauma/surgery Aspiration/Intubation/catheterization Use of broad spectrum antibiotics

Congenital Rubella Syndrome

Infection during first trimester results in growth retardation and congenital birth defects Affects several organs but the Primary targets organs are -Heart: patent ductus arteriosus (PDA), other defects -Eyes: cataracts, glaucoma, blindness -Ear: Deafness (most common cause of congenital deafness) -CNS: microcephaly, mental retardation Fetal infection The risk of severe disease in neonates is the highest if the mother is infected within the first few weeks of pregnancy and declines as the pregnancy progresses. The virus first infects the placenta and then proceeds to infect the fetus. The effects of infection include the following: Hearing loss (most common), Congenital Heart Defects, Ophthalmic problems, Intrauterine growth retardation, Neurological Problems including mental and psychomotor retardation as well as microcephaly, Hepatomegaly, Splenomegaly, Bone lesions, Thrombocytopenia purpura, and pneumonitis. If the mother is non-immune and is infected within the first trimester, up to 80% of the neonates have sequelae.

Cutaneous Mycoses

Involves deeper layers of epidermis and its integuments (hairs and nails). Dermatophytosis (Tinea) : by Dermatophytes Microsporum spp. Trichophyton spp. (T. rubrum & T. mentagrophytes-80-90% of all dermatophytosis) Epidermophyton spp. Dermatomycosis: by non-Dermatophytes Many non-dermatophytic fungi (i.e dermatomycotic fungi) are associated with nail infections. The important fungi are Scopulariopsis spp Scytalidium spp Aspergillus, Fusarium, Candida etc.

Transposons

Jumping Genes Mobile genetic elements The smallest transposon carries Insertion sequences -minimal genetic information required for transport and replication Transposases- transport; Resolvase or recombinase (Rec) is a nuclease which is involved in DNA recombination Can integrate and excise and take their gene to another place while leaving itself behind Can move to and from any DNA--phage, plasmid, bacterial genomes May carry additional genes such as genes coding antimicrobial resistance

Immune Defense Mechanisms of the Integument

Keratinization - skin tough, water resistant; Sloughing of outer layers Sebaceous and sweat gland secretions- high salt, acidic Normal flora Resident macrophage in dermis Vascular supply in dermis (Plasma proteins, Ig, complement, WBCs)

Pathogenesis of Acanthamoeba castellani

Keratitis: associated with contact lens or eye trauma, Granulomatous amoebic encephalitis (GAE), plus Disseminated cutaneous and subcutaneous infections in HIV/immunocompromised patients

Brain abscess

Localized infection of the brain parenchyma. Signs and symptoms depends on the location of the abscess. -Streptococcus anginosus (viridans group): most common -Staphylococcus aureus -Gram negative rods: enteric bacteria -Fungi (mostly in immunocompromised) Aspergillus fumigatus Cryptococcus Candida

Normal Cellular Protein (PrPc)

Located on the cell membrane Alpha helical Protease sensitive Sensitive to heat and UV

HIV Pathogenesis

Lytic infection (killing) of CD4 T cells - leading to immunosuppression Syncytia formation - of infected cells - loss of function and eventually death of CD4 cells Killing of infected CD4 cells by T CD8 cells Reduction or loss of function of cells that depend on T CD4 cells for help (CD8, NK, macrophages) HIV reduces MHC I expression in infected cells - mediated by nef products - avoid attack by CD8 Persistent infection of macrophages and dendritic cells in lymphoid tissues - major reservoirs High rate of mutation of env gene (gp120) - difficult to design a vaccine.

Pathogenesis of Cytomegalovirus

Lytic infection of epithelial cells and others Latent state and persistent infection In T-cells, endothelial cells and monocyte/ macrophages Avoiding immune attack, eg. Inhibiting expression of MHC I and MHC II Usually subclinical in immunocompetent May shed the virus Reactivation - immunosuppression of cell mediated immunity

Treatment of Chlamydophila pneumoniae

Macrolide-first line, Tetracycline, fluoroquinolones also effective No vaccines, control of exposure difficult

Stool/urine sample

Macroscopic examination Microscopic examination Wet mount Permanent stains Stool concentrates Demonstrate: Cyst, trophozoite, egg, larvae, adult Culture

Biofilms (Glycocalyx)

Made of mucopolysaccharide surround populations of cells to provide: Adhesion (devices & even in tissue) Protection against: Phagocytosis Dehydration Antibiotic/antibodies penetration

Entamoeba histolytica Pathogenesis

Major virulence factors are Lectin/adherence protein Release of cytoxins and hydrolytic enzymes -Cytotoxin/Amoebapores (pore forming peptide): create pores in the target cell -Cysteine protease: (Thiol protease): degrades the extracellular matrix

Black water fever (dark urine)

Manifestation of falciparum malaria in previously infected subjects. Intra vascular hemolysis, fever, hemoglobinuria, Can result in acute renal failure and death In majority cases, parasites not detected in periph. blood.

Escherichia coli (Uropathogenic)

Member of the Enterobacteriaceae Properties: Gram negative rod, lactose fermenter, oxidase neg. Indole +, decarboxylates lysine, use ACETATE as sole source of Carbon, motile Reservoir: Human colon Transmission: Autoinoculation via fecal contamination of urethra, catheter Risk Factors/High Risk Populations: Women, catheterized patients, neonates

Semisynthetic Penicillins

Methicillin, nafcillin, oxacillin, ampicillin, amoxycillin Resistant to beta-lactamase Increased stability to stomach acid Increased spectrum of activity Activity - similar to natural penicillins with increased activity against Gram negative rods and beta-lactamase producing organism

Treatment for Entamoeba histolytica

Metronidazole followed by iodoquinol (quinoline derivative) Asymptomatic carriage: iodoquinol Prevention and Control Education Public and personal hygiene Use of boiled water/Protection of all food and drink from contamination by flies, cockroaches and rats Avoidance of raw vegetables and fruits Amoebicidal drugs: Tissue amoebicides (Trophozoites): Emetine, Dehydroemetine Luminal (Both trophozoites and cysts): Iodoquinol, Diloxanide Both Tissue and luminal: Metronidazole, Niridazole

Diagnosis of Leptospira interrogans

Microscopy: Not very sensitive due to low number Dark field microscopy or Giemsa stain, or DFA Culture: Blood or CSF, urine sample Fletcher, EMJH and Tween-80 albumin Media time-consuming due to slow growth (2-3 weeks) PCR: not widely used Serology: preferred diagnostic test - relatively sensitive Microscopic agglutination test (MAT) Treatment: Doxycycline Prevention: Vector control (RODENTS); vaccination of pets and livestock

Treatment of Babesia microti

Mild to moderate case: Atovaquine + Azithromycin Severe: Clindamycin+ quinine/Exchange transfusion Prevention and Control Use of protective clothing and insect repellants Prompt removal of ticks, minimize exposure time The Ixodes nymphs that typically spread B. microti are so small (about the size of a poppy seed) that they are easily overlooked. But they usually must stay attached to a person for more than 36-48 hours to be able to transmit the parasite.

Lyme Disease Tertiary stage

Months to years Pathogenesis not well understood Arthritis of large joints (eg, Knees) and Chronic progressive central nervous system diseases, Shooting pains, numbness, or tingling in the hands or feet, problems with concentration and short term memory

Tubercular arthritis

Mycobacterium tuberculosis 10-11% of extrapulmonary TB is bone/joint TB 1-3% of all TB cases Incidence ↑se- with ↑se in HIV prevalence Risk factors In endemic regions, children and young adults; in other parts elderly and immunosuppressed ones. Low socio-economical status, alcohol, i.v. drug use, immunosuppressive therapy, HIV infection, joint disorders Chronic granulomatous monoarthritis -Hematogenous spread after primary infection -A long latent period without sign & symptom Knee, hip, ankle -Fever may not be seen, a draining sinus can be observed Diagnosis: Synovial fluid analysis: Leukocytes 10 000-20 000/ml, Acid-fast bacilli (AFB)+ culture.........(80%) Synovial biopsy; AFB+ culture+ histology (90%) PCR Treatment: Anti-TB therapy; surgery-for periarticular abscess and reconstruction

Antibiotic terminology

Narrow spectrum: active against one or few types of pathogens Broad spectrum: active against a wide variety of pathogens Bactericidal: Kills the pathogen, irreversible Bacteriostatic: Inhibit the growth of the pathogen, reversible Empirical therapy: initial selection of antibiotics based on clinical findings Bacteriostatic drug: on withdrawal of drug - growth of agent. Assists the host defense by limiting the populations size

Escherichia coli Meningitis

Neonatal Purulent Meningitis Properties: Gram negative rod; lactose fermentor, pink colonies on MacConkey agar Reservoir: Colon/Urogenital tract of some patients Transmission: Mother to infant at time of delivery. Virulence: not all E.coli strains cause meningitis. Most stains that cause meningitis have capsular antigen K1 that cross reacts with Group B strep capsule. Risk Factors/High Risk Populations: neonates Clinical Disease: Neonatal meningitis. (E.coli and Group B strep are the leading causes of meningitis in new borns)

Family Rickettsiaceae Pathogenicity

Obligate intracellular pathogen of endothelial cells lining the small blood vessels (small arteries, veins and capillaries): escape from phagosome and multiply in the cytoplasm Vasculitis, thrombosis: generalized distribution Disease manifestation: Skin rash, Manifestation of CNS, heart, lungs, and kidney involvement

Diagnosis of Dracunculiasis

Observation of the lesions and recovery of the adult/larval worms while flooding the ulcer with water Radiological examination

Host

Organism harboring a parasite. Definitive host: Animal harboring the adult or sexually mature stage of the parasite. Intermediate host: Animal in which development occurs but in which adulthood is not reached.

Hydrogen peroxide

Oxidizing agent Attacks sulfydryl groups in proteins and modifies them kills most bacteria, kills spores Antiseptic - to clean wounds and contact lenses

HBsAg Complexes

Particles in Blood detected under electron microscope Intracellular build up of the filamentous forms gives Ground glass appearance of hepatocytes

Peptic Ulcer

Presentation is upper abdominal pain, feeling of fullness, indigestion, nausea and vomiting. About 80% remain asymptomatic In severe cases, bleeding into the GI

Herpes Clinical Diseases

Primary infection and reactivation Primary: Painful vesicular lesions due to infection of epithelial cells at the site of entry accompanied by fever, malaise, myalgia, regional lymphadenopathy Reactivation: Similar lesions as primary. Sensory nerve symptoms such as pain and tingling often precede the reappearance of recurrent lesions. Recurrent episodes are less severe than primary lesions May be asymptomatic but can shed the virus. Lesion heal without leaving scar I. Skin and Mucosal infection II. Central nervous system infection III. Congenital/neonatal herpes: mostly HSV type 2

Clostridium botulinum Virulence and pathogenesis

Produce invasive enzymes: lipases, gelatinase may contribute to wound infection Neurotoxin: 8 different serotypes (A,B,E are most common). Gene carried by phage, heat sensitive Highly potent - lethal dose is about 1-2µg/Kg Toxin type A and B associated with canned a variety of foods, Type E associated with fish products. It gets absorbed from the gut/wound to the blood stream It binds to the presynaptic neuron and cleaves a protein involved in the release of acetylcholine. SNARE proteins (synaptobrevin and syntaxin) This causes a bilateral flaccid paralysis, a weakening of muscles. Used in small amount to treat spasmodic muscle disorders, cosmetic to remove wrinkles and migraine

Replication

Protozoans: multiply inside the human body Intracellular or extracellular - depending on organism Helminths: most do not replicate inside the human body

UTI recurrences

Put on chronic suppressive therapy Continuous low-dose antibiotic prophylaxis - for six months Such as trimethoprim-sulfamethoxazole Self administered single dose prophylaxis on onset of symptoms

Epidemic typhus

R. prowazekii: Epidemiology: Reservoir: Human, (flying squirrels?), world wide, Incidence unknown in US, but sporadic cases occur in rural eastern part). Vector: human body louse (Pediculus humanus). Lice die quickly so no transovarian transmission. Organism excreted in the feces and transmitted when scratching the louse bite which introduces the infective feces into the skin puncture Risk population: people living in crowded unsanitary conditions, war, famine, poverty homeless people. Rural Eastern states associated with squirrels and flea bite

Nitrocef test

Rapid test for beta lactamase production are intended for the rapid testing of isolated colonies of Neisseria gonorrhoeae, Moraxella (Branhamella) catarrhalis, Staphylococcus spp., Haemophilus influenzae, Enterococcus spp., and anaerobic bacteria of the genera Bacteroides, Clostridium, Porphyromonas, Fusobacterium, and Prevotella. Disks are impregnated with nitrocefin (a chromogenic cephalosporin). As the amide bond in a beta-lactam ring is hydrolyzed by a beta-lactamase, nitrocefin changes color from yellow to red. Bacteria which produce beta-lactamase in significant amounts produce this yellow to red color change

Pathogenesis of Rhinovirus

Receptor on host cell - ICAM-1 - present on many cells Low Infectious dose (as low as 1 virion) Enter through nose, eye, mouth; replication primarily in nose Infected cells produce histamine and bradykinin - cause "runny nose" Replicates better at 33o C than at 37o C, Reason for preferring upper respiratory tract Acid labile (killed in stomach acid if swallowed), does not involve GI tract Disease: Common cold. Sneezing followed by rhinorrhea- runny nose; later-Nasal obstruction; Mild sore throat

Griffith's experiment

Reported in 1928 by Fredrick Griffith, was the first experiment suggesting that bacteria are capable of transferring genetic information through a process known as transformation Rough strain: Non capsulated (Non virulent) Smooth Strain: Capsulated (Virulent)

Pyelonephritis treatment

Require hospitalization - appropriate antibiotics

Culture Characteristics

Requirements: oxygen, Temp, pH, osmotic pressure, growth factors, etc Colony morphology: Appearance on culture media - Selective, differential, enriched Size, Texture (rough, smooth) hemolysis, pigment etc...

Onchocerca volvulus

River blindness Epidemiology: Africa; and Central & South America (Guatemala, Mexico, Colombia and Venezuela) Transmitted by black fly - Simulium damnosum, breeds along fast flowing water - rivers and springs Adults live in subcutaneous tissue, forming nodules. Larvae concentrate in dermis (easily picked up by black flies)

Urinary Tract Infection

Significant bacteriuria: presence of bacteria ≥ 105 CFU/ml in urine (Exceptions-next slide!) Complicated UTIs: UTIs arising in a setting of catheterization, instrumentation, anatomic or functional urological abnormalities, stones, obstruction, immunosuppression, renal disease or diabetes Asymptomatic bacteriuria: ≥ 105 CFU/ml in urine, but no symptoms Acute urethral syndrome: ≤ 105 CFU/ml - with symptoms Recurrent UTI: could be relapse or re-infection Pyuria: white blood cells in urine Dysuria: painful urination; often a burning sensation Hematuria: blood in urine Nephrolithiasis - stone in kidney

Major differences between C. cayetanensis and C. parvum

Size difference — C. parvum is smaller; Differing results from modified acid-fast staining -C. parvum has consistent red staining; and Autofluorescence under UV light — C. cayetanensis does, C. parvum does not.

Reactive (Inflammatory) arthritis

Sterile inflammatory process in the joint following a bacterial infection in distant site in a body Most common cause: Chlamydia trachomatis Others-Campylobacter jejuni, Yersinia enterocolitica, Shigella, Salmonella, Streptococcus

Genital Skin and Mucous Membrane Lesions

Syphilis Genital Herpes Warts (HPV) Common in the USA Chancroid Granuloma inguinale Lymphogranuloma Venereum Molluscum contagiosum

Hemagglutination

The red blood cells that are attached to virus particles form a lattice that coats the well

Mutations in Bacteria

They reproduce fast, some divide within 20 min. Thus the probability of mutation is high. Because of their haploid state, bacterial mutations are expressed quickly, no recessive or dominant pattern Can occur as Spontaneous mutation: polymerase enzyme errors or Induced mutations: caused by mutagens - chemicals, radiation

Leptospira interrogans

Weil's disease General properties: Gram negative thin spirochetes with numerous closely set coils and hooked ends. Best seen in dark field microscopy Grows slowly in culture Risk Factors/High Risk Populations: Farmers, veterinarians, hunters and meat handlers; sewer workers, people in water sports during summer (jet skiers) Infection can increase after hurricanes or floods

Malassezia furfur

Yeast and short mold form "Spaghetti and meatballs" General properties: Both yeast and short mold form found on skin. Appear like Spaghetti and meatballs, lipophilic (requires lipid for growth) Reservoir: Human skin Transmission: direct contact or indirect contact with infected persons Risk Factors: Young adults; world wide distribution, but more common in tropical and subtropical

Fungal Colony Morphology

Yeast colony: opaque, compact, mucoid/dry, bacteria like, alcoholic odor, grow well at room temp in 24 hrs Molds colony : Hairy, cottony, velvety texture, may be colored (dematiaceous-due to pigment production). Vegetative hyphae: extend into growth medium, absorb nutrition Aerial (reproductive) hyphae: extend from the agar surface and often have spores- useful in identifying the mold

Bubonic plague

Yersinia pestis Multiplication in regional lymph nodes Symptoms: Rapid onset of fever, headache, chills Painful swollen lymph nodes (called Buboes)- Site depends on entry site, neck, armpit, groin Hemorrhagic suppurative lymphadenitis seeding of the pathogen in the blood, lung and other organs

Epidemic typhus disease

also called "camp fever", "Epidemic louse-borne typhus," and "louse-borne typhus") IP ~ 8 days Clinical presentation: A sustained high fever, severe headache, myalgia, chills A macular rash begins on the chest about five days after the fever appears, becomes petechial and spreads to the trunk and extremities (Centrifugal, a pattern opposite to that of RMSF). Complication: Myocarditis; CNS dysfunction (stupor, delirium, coma); DIC; Gangrenous necrosis; sensitivity to light Mortality rate 20-30%

Infant Botulism

" Floppy baby" syndrome Most common in the US, infants < one year old Incubation period: 3-30 days Ingestion of spore - germinate and multiply in the gut - produce toxin - get absorbed to blood Associated with honey and dust inhalation Symptoms: Lethargy, weakness, constipation, poor feeding and sucking reflex, lack of facial expression. The differential diagnosis of infant botulism includes other causes of paralysis such as Guillan-Barré syndrome (symmetric ascending paralysis with an elevated CSF protein), poliomyelitis (asymmetric paralysis, fever, and presence of lymphocytes in CSF ), and myasthenia gravis (muscle fatigability with reversal or ptosis with tensilon Hidden botulism - in adults similar to infant botulism. This happens due to endogenous CB invasion of tissue when there is intestinal wall injury or damage such as after surgery.

Yersinia pestis

"Black Death" General properties: Gram negative rod with bipolar staining, Non motile, gives safety pin appearance, produces Coagulase, Stalactatic growth in ghee broth Reservoir: Urban plague-urban rats; dogs and cats vector: rat flea (Xenopsylla cheopis) Sylvatic plague -squirrels, field rats, rabbits vectors are fleas of reservoir animal Transmission: Flea bite, Contact: with contaminated fluid or tissue (animal/human) Respiratory droplets - person to person, animal (PETS) to human. Risk Groups/High Risk Populations: Contact with sick animals/person/rodents, camping, hiking, hunting in endemic regions

Fasciola hepatica

"common liver fluke" or "the sheep liver fluke'' Epidemiology: worldwide in sheep raising areas, rare in US but cases in travelers from endemic areas, Infect herbivores (mainly sheep & cattle) and humans; snail as intermediate host. Transmission: consumption of contaminated raw/undercooked Watercress/fresh water plant Morphology: Egg, Larvae, and Adult Fluke

Enterococcus faecalis and faecium

(Group D Lancefield antigen) Properties. Gram positive cocci in chains/pairs, catalase negative, bacitracin and optochin resistant, grow in 6.5% NaCl and 40% bile, hydrolyze esculin, PYR + (pyrolidonyl arylamidase), varied hemolytic pattern Reservoir: human colon, urethra, female genital tract. Endogenous or exogenous source of infection Risk Factors/High Risk Populations: Hospitalization, broad spectrum antibiotic treatment esp. with vancomycin; catheterization, Clinical Disease: Cystitis and Pyelonephritis Other diseases : Soft tissue infections after colon surgery/ trauma; usually polymicrobial. Bacteremia and endocarditis

Neisseria meningitidis

(Meningococcus) Ranks second to S. pneumoniae as a cause of bacterial meningitis but is the most common cause in teens and young adults in US Properties: Gram negative, diplococcus (coffee bean shape) - capsulated, facultative intracellular; Oxidase positive requires chocolate agar ferments maltose and glucose Reservoir: Human are the only natural host, Carriage in nasopharynx of healthy people (up to 40% of the population); Transient asymptomatic carriers Transmission: via. respiratory droplets (common in people living in CLOSE CONTACT)

Onchocerciasis

(River Blindness) Affects primarily, the eye, the skin, and lymph nodes Pathogenesis is mainly due to Direct invasion and immune reaction to migrating microfilariae (larva); Release of endotoxin like molecule by Wolbachia (rickettsia like bacteria as endosymbiont) Acute: fever, eosinophilia and urticaria Chronic: A. Ocular manifestation: microfilariae migrate to the surface of the cornea. Chronic infection leads to sclerosing keratitis - affected area becomes opaque. The entire cornea may become opaque = (River Blindness) B. Skin manifestations Nodules - known as Onchocercomata (contain - few adults) Intense itching, swelling, and inflammation. Scattered pruritic papules - small to large and may become keratinized Skin atrophy - loss of elasticity; thin and scaly skin - 'lizard skin' appearance Depigmentation - 'leopard skin' appearance, anterior lower leg. C. Hanging groin: lymph node enlargement and hanging down Mild to moderate lymphadenopathy particularly in inguinal and femoral areas where enlarged nodes may hang down in response to gravity due to loss of subcutaneous elastic fiber - "hanging groin''

Hantavirus

(Rodent borne or Robo virus) Bunyavirus, Enveloped, negative ss-RNA - SEGMENTED No matrix protein (unlike other negative sense RNA viruses) Reservoir: urban rodent, deer mice in USA Transmission: : Inhalation of aerosols of rodents' urine or feces. NOT from PERSON TO PERSON About 100,000-200,000 cases/year world wide. Pathogenesis: infects vascular endothelium of the lungs, kidney, heart, and lymphoid organs

Trichuris trichiura

(Whipworm) soil-transmitted helminths The adult worm measure 3-5 cm, resembles a whip-anterior three-fifth is very thin and hair like and the posterior two-fifth is thick and stout; resembling the lash and handle of a whip. The worm lives in large intestine Epidemiology: world wide Third most common roundworm of humans (worldwide) Southern United States Children at more risk Often seen in areas where human feces is used as fertilizer or where defecation onto soil happens No animal reservoir In the US: Whipworm infection in the rural Southeast, estimated 2.2 million people are infected･ Internationally: Whipworm infection is common in less-developed countries; more than 500 million people are infected worldwide Transmission: One of the soil transmitted helminths Fecal-oral

Axial Filaments

(endoflagella) For motility Flagellin covered by outer sheath (membrane) Only found in Spirochetes

Uptake of mobile genetic elements

(phages, virulence plasmids and pathogenicity islands), as well as the loss of chromosomal-DNA regions in different E. coli lineages, has enabled the evolution of separate clones, which belong to different E. coli pathotypes and are associated with specific disease symptoms. LEE, locus of enterocyte effacement; PAI, pathogenicity island; pEAF, enteropathogenic E. coli adhesion-factor plasmid; pENT, enterotoxin-encoding plasmids; Stx, Shiga-toxin-encoding bacteriophage.

Comedo

(plural for comedones) is a clogged hair follicle (pore) in the skin. Keratin (skin debris) combines with oil (from sebaceous gland) to block the follicle. Can be open (blackhead) or closed by skin (whitehead), and occur with or without acne. The word comedo comes from Latin to suggest the worm-like look of a blackhead that has been secreted.

Trachoma

(rough eye): Chlamydia Serovars A-C A chronic conjunctivitis/ inclusion conjunctivitis It turns the eyelashes inward causing irritation and corneal scarring Leads to blindness, affecting millions around the world Initially follicular conjunctivitis and inflammation

Platyhelminthes

*Cestodes (Tapeworms) -Diphyllobothrium latum (Fish tapeworm) -Echinococcus granulosus (Dog tapeworm) -Taenia saginata (Beef tapeworm) -Taenia solium (Pig tapeworm) -Hymenolepis nana (Dwarf tapeworm) *Trematodes (Flukes) -Clonorchis sinensis (Chinese or oriental liver fluke) -Paragonimus westermani (Lung fluke) -Fasciolopsis buski (Giant Intestinal fluke) -Fasciola hepatica (common liver fluke) -Schistosoma spp (Blood flukes)

Measles/Rubeola Virus Pathogenesis

-Inhalation, Virus enters cells of respiratory tract and replicates locally inside epithelial cells -Spreads to local lymph nodes , blood -Disseminates to skin and mucous membrane, eye, CNS, back to RT, Urinary tract, endothelial cells of small blood vessels The typical Maculopapular rash is caused by CD8 T cells attacking infected endothelial cells of small blood vessels. Giant cell formation and cell death Transiently depresses CMI; Infects B and T cells, Induces switch from Th1 to Th2 cells. Death due to pneumonia, diarrhea or encephalitis Recovery gives life long immunity

Secondary Syphilis

1-3 months Skin and mucous membrane lesions and systemic disease Patient is infectious Skin lesions: vary from macular, (flat), papular, (raised), occasional pustule (with pus) and nodular (hard). Painless Appear on the whole body including the palms and soles but excluding the face Condyloma lata lesion- wart-like- appear on moist areas of the skin, anogenital region, axilas and mouth

Virulence and Pathogenesis of C. difficile

1. Adhesion factors: surface-layer proteins 2. Toxin A is an enterotoxin increase cAMP hyper-secretion of fluid Induce inflammation - chemotactic for neutrophils and cytokine production, results in tissue damage leading to hemorrhagic necrosis 3. Toxin B is a cytotoxin Depolymerization of actin, loss of cytoskeleton - leading to cell death Toxins A and B act synergistically Toxin A damage to mucosal cells allows toxin B maximal effect Super C strain: Deletion of the toxin A and B regulatory gene (tcdC), produce 20x toxin

Protozoan Parasites

1. Amoeba (Sarcodina)—motile via pseudopods, divide by binary fission, exist as metabolically active trophozoites and inactive, resistant cysts. 2. Flagellates (Mastigophora)—motile via long whip-like flagellae, divide by binary fission, exist in trophozoite and cyst forms, exceptions exist 3. Ciliates (Cilliata)—motile via short, brush like cilia, divide by binary fission (may conjugate), exist as trophozoites and cysts 4. Sporozoa (Coccidia)—reproduce by sexual &/or asexual means, exist in diverse cellular forms, trophozoites, sporozoites, oocysts, gametocytes, etc. May be intracellular

Immunopathogenesis

1. Excessive immune response: innate, specific and inflammatory responses - Examples NK and CTLs - host cell death Activated neutrophils and macrophages: bystander damage Complement activation: anaphylatoxins, inflammation Granuloma formation: interfere with normal function 2. Molecular mimicry: Induction of autoimmune diseases: eg, M protein of Streptococcus pyogenes and heart protein (Rheumatic fever) 3. Immune complex deposition: In Bacterial endocarditis nephritis, arthritis, vasculitis

Rickettsia and Related Microorganisms

1. Family Rickettsiaceae has two genera A. Rickettsia B. Orientia 2. Family Anaplasmataceae has two genera A. Anaplasma B. Ehrlichia 3 . Family Coxiellaceae: Coxiella: is not a member of the above but traditionally has been discussed along with these group

Virulence and Pathogenesis of Salmonella

1. Local Invasion Ingestion of organisms→ Colonization of ileum and cecum (entry via M cells and other gut epithelial cells)→Mucosal invasion→ Acute inflammation→Shallow ulcers which may cause bloody diarrhea 2. Enterotoxins: activate adenylate cyclase→ increased cyclic AMP → Fluid production (large and small bowel) →Watery diarrhea 3. Systemic invasion Bacteria multiply within endosome/phagosome, resist killing Growth inside macrophages Get carried to lymphatics, blood stream

Diagnosis of cytomegalovirus

1. Microscopy: Histology + DFA ; demonstration of cytomegalic cell - enlarged cell that contains a dense central basophilic intranuclear inclusion body - known as "Owl's eye" 2. DNA probes: PCR Detection of virus DNA In newborns detection of the virus in urine, saliva, blood of neonates within 2-3 weeks indicates congenital infection 3. Serology: detect IgM or 4x increase paired sera 4. Viral culture: cell culture; helps in antiviral drug testing.

Diagnosis of HIV infection

1. Serology: Ab/Ag 2. Viral load: Nucleic acid testing (NAT): RT-PCR Detection viral nucleic acid or viral proteins; Large number of viral RNA or p24 in blood correlates with early or late infection Viral RNA - RT-PCR: Reverse transcriptase polymerase chain reaction. Viral isolation - not routine 3. CD4 count staging of disease follow up treatment Staging of the disease, used to determine treatment efficacy.

Toxicara canis/cati and Baylisarcaris procyonis

1. Toxocara canis: Associated with Dogs 2. Toxocara catis: Associated with Cats 2. Balisarcaris procyonis: Associated with Racoons Toxocariasis: neglected parasitic infection in US (but, under CDC's priority), Almost 14% US people infected Baylisarcariasis: Fewer than 25 cases reported in US Dog, cat and raccoon parasites, humans accidently infected, humans are dead end host Risk group: Young children are at risk as they are more likely to put contaminated fingers, soil, or objects into their mouths. Transmission: Ingestion of eggs from dog/cat/racoon feces

Gene Transfer

1. Transformation: - the transfer of "naked" DNA. (DNA fragment and or plasmid) 2. Conjugation: the passage of plasmids/genetic elements through direct physical contact between two bacteria 3. Transduction: the transfer of genetic information through virus (phage). 4. Transposition: the movement of small pieces of DNA called transposons to different locations in the genome and between plasmids. These are sometimes called "jumping genes."

Staphylococcus aureus intoxication

1. Virulence factors and pathogenesis Not infection Preformed toxin : 8 serotypes, A-E, G-I (type A most common) Heat stable - 100 oC for 30 min Resistant to gastric acid and digestive enzyme Dose: as little as 1 micrograms of toxin Emetic activity: stimulates vagus nerve endings in the stomach lining that control vomiting response. 2. Symptoms: Sudden onset (<1 - up to 6 hr) of severe nausea and vomiting, headache, diarrhea (watery, not always), sweating and headache 3. Duration of illness: Self resolving within 24-48 hrs

Environmental factors affecting growth

1. Water 2. Oxygen (obligate aerobes, microaerophiles, facultative anaerobes, aerotolerant anerobes and obligate anerobes) 3. Carbon dioxide 4. Temperature (Psychrophilic: below 20, meso-philic: 25-40, Thermophilic: 55-80 0 C) 5. Hydrogen ion concentration (optimal pH 7.2-7.4) 6. Light: Most prefer to grow in darkness except phototrophic 7. Osmotic pressure: Osmotically stabilized with 0.5% NaCl in growth media

Diarrhea

3 or more loose stools in a 24 hour period The most common cause of death in developing countries (1.5 million deaths/year. Over 211 million cases of di arrhea occur in United States every year. Source/entry: fecal-oral- contaminated water, food, fingers, person/animals to person Ingestion of a pathogen or preformed toxin infection may be limited to the intestinal mucosa Infection may go deeper to the draining lymph nodes, lymphatic, blood - systemic infection Some infections are self-limited: do not need antibiotic treatment Others may need treatment : the trick is knowing when and how to treat

Fungal Cell Structure

Are Eukaryotic cells, unicellular or multicellular and have membrane bound organelles, nuclear membrane, cytoskeleton Fungal Cell membrane: Phospholipid bilayer like mammalian cells, but differs in the nature of sterol- they have ergosterol instead of cholesterol Site of action for antifungal drugs Amphotericin B and azole

Clostridium perfringens Lipase Activity

A Nagler agar plate, containing 5-10% egg yolk, is used to presumptively identify strains which produce α-toxin. These strains produce a diffusable lecithinase which interacts with the lipids in egg yolk to produce a characteristic precipitate around the colonies. One half of the plate is inoculated with antitoxin to act as a control in the identification. Principle of test: Bacterial lecithinase breaks down the lecithin (a normal component of egg yolk) to an insoluble diglycerides resulting in an opaque halo, surrounding the colony when grown on the egg yolk agar medium. Clostridium perfringens will release the toxin and form an opacity, as seen in the upper right streak to form an opacity. The upper left streak shows lipase (Phospholipase) inhibition by antiserum. The lower streak—a lipase negative clostridium.

Lepromin test

A boiled (sterilized) extract of lepromatous tissue in isotonic saline. Test: When 0.1 ml of lepromin (containing 40 million dead lepra bacilli) in injected intradermally to an individual, it produces an area of nodular infiltration at the site of injection. It elicits 2 type of reactions: Early or Fernandez reaction: Erythema and induration of 10-30 mm appears after 24-48 hrs after injection Delayed or Mitsuda reaction: Erythematous nodular lesion of 3-5 mm develops at the site of inoculation after about 3 wks. Significance: 1. Classification of leprosy 2. Prognostic significance: prognosis is better in positive cases

Replication of herpes simplex virus

A complex enveloped DNA virus. The virus binds to specific receptors and fuses with the plasma membrane. The nucleocapsid then delivers the DNA genome to the nucleus. Transcription and translation occur in three phases: immediate early, early, and late. Immediate early proteins promote the takeover of the cell; early proteins consist of enzymes, including the DNA-dependent DNA polymerase (i.e viral coded); and the late proteins are structural and other proteins, including the viral capsid and glycoproteins. The genome is replicated before transcription of the late genes. Capsid proteins migrate into the nucleus, assemble into icosahedral capsids, and are filled with the DNA genome. The capsids filled with genomes bud through the nuclear and endoplasmic reticulum (ER) membranes into the cytoplasm, acquire tegument proteins, and then acquire their envelope as they bud through the viral glycoprotein-modified membranes of the trans-Golgi network. The virus is released by exocytosis or cell lysis. GA, Golgi apparatus (Please note: There is a controversy regarding how these viruses acquire envelope. Some researcher claim that these viruses are the only viruses acquiring envelope from nuclear membrane)

Burkholderia cepacia complex

A complex of 17 species General properties: Gram negative bacilli; aerobic non-fermenter; Oxidase positive; does not produce diffusible pigments Reservoir: moist environmental surfaces (like pseudomonas) Transmission: inhalation/Contact with contaminated surfaces/Person-to-person contact Risk Groups/High Risk Populations: Opportunistic pathogen, underlying chronic pulmonary disease, cystic fibrosis, chronic granulomatous disease, immunodeficient individuals

Zoonosis

A disease involving a parasite for which the normal host is an animal, and wherein man can also be infected Cryptosporidium, Trichinella etc are examples of zoonotic parasites that may be transmitted from animals to humans

Vaginal Environment

A dynamic ecosystem that contains approximately 10 billion bacterial colony-forming units. Normal vaginal discharge is clear to white, odorless, and of high viscosity. Normal bacterial flora is dominated by Lactobacilli : Gram positive rods - produce lactic acid potential pathogens may be present in some women. Acidic environment (pH 3.8-4.2) inhibits the overgrowth of bacteria Some lactobacilli also produce H2O2, a potential microbicide

Stool examination

A flotation media (for concentration) has a higher specific gravity than 1.20 to float many of the common parasite ova. Sheather's sugar solution has a specific gravity of 1.27 which is high enough to float any ova. Sedimentation use solutions of lower specific gravity Heavy eggs (Ascaris egg) Operculated eggs (Trematodes) Larvae (Strongyloides stercoralis) Cysts Floatation use a higher specific gravity than 1.20 Non Operculated eggs Trematodes (S. m.) Cestode Nematode(Hook worms) Cysts

Lac Operon

A gene system whose operator gene and three structural genes control lactose metabolism in E. coli Lactose is inhibiting the repressor, allowing the RNA polymerase to bind with the promoter, and express the genes, which synthesize lactase. Eventually, the lactase will digest all of the lactose, until there is none to bind to the repressor. The repressor will then bind to the operator, stopping the manufacture of lactase The gene product of lacZ is β-galactosidase which cleaves lactose, a disaccharide, into glucose and galactose. LacY encodes lactose permease, a protein which becomes embedded in the cytoplasmic membrane to enable transport of lactose into the cell. Finally, lacA encodes galactoside O-acetyltransferase.

Antigenic drift

A gradual change in antigenicity due to point mutations that affect major antigenic sites on the glycoprotein. - gives rise to seasonal flu strains Yearly outbreaks, epidemics is due to point mutations. Influenza virus genes, made of RNA, are more prone to mutations than genes made of DNA

Suppression mutation

A mutation (second) that restores the function of a gene inactivated by previous mutation (first): Example ATA to AAA causes Tyr to Phe AAA to ATA causes Phe back to Tyr

Peplomers (spikes)

Are proteinaceous projections that extend from the capsid; or viral glycoproteins inserted on envelope Importance of Peplomers Attachment of the virus to host cells, act as viral attachment proteins (VAPs), Determine tissue and host specificity Some may have enzymatic activity to aid entry or exit of the virus Antigens - target for the immune system Have other useful properties—as antigens useful in classification, hemagglutination

Neurocysticercosis

A person gets cysticercosis by swallowing eggs (Remember! Not with LARVAE) found in the feces of a person who has an intestinal tapeworm. People living in the same household with someone who has a tapeworm have a much higher risk of getting cysticercosis than people who don't. People do not get cysticercosis by eating undercooked pork (i.e containing larvae). Eating undercooked pork can result in intestinal tapeworm if the pork contains larval cysts. Pigs become infected by eating tapeworm eggs in the feces of a human infected with a tapeworm (CDC)

Prophage

A phage genome that has been inserted into a specific site on the bacterial chromosome.

Lysogenic Cycle

A phage replication cycle in which the viral genome becomes incorporated into the bacterial host chromosome as a prophage and does not kill the host.

One step viral growth curve

A single cycle of virus growth can be studied by determining the titer of infectious virus (e.g. by plaque assay) over time. Viral titer is stable during the brief period of virus attachment. Following attachment, viral titer declines precipitously as the virus undergoes disassembly, transcription, translation, and genome replication. That interval is termed the eclipse. Viral titer begins to increase as progeny virions, which are fully infectious, are assembled. Eclipse phase: corresponds to the period during which the input virus becomes uncoated. As a result, no infectious virus can detected during this time (any infectious virus detected is simply virus that is still stuck on the cell membrane) (Time period between entry and assembly/maturation) Latent period. During this period, no extracellular virus can be detected. (Time period between entry and release) Burst size : amount of infectious virus produced, per infected cell

Latent syphilis

A positive serological test for syphilis in the absence of any clinical disease symptoms. Some may heal spontaneously, others may get relapse to the 20 stage, others enter the 30 stage

Varicella (Chickenpox)

A primary infection, IP- 14 to 16 days Prodrome: Flu like symptoms Rash: on skin and mucosal area Itchy, papulo-vesicular, appear in successive crops and finally form crusts. Starts on Face and trunk and moves outward The rash is due to replication of virus Interstitial pneumonia and encephalitis: fatal, especially in immunocompromised

Sigma Factor

A protein that associates with RNA polymerase that facilitates its binding to specific promoters a protein for initiation of RNA synthesis May associate with the RNA polymerase before binding to the promoter region or it may bind to promotor and act as a docking station for the polymerase. The specific sigma factor used to initiate transcription of a given gene will vary, depending on the gene and on the environmental signals needed to initiate transcription of that gene. Some sigma factors are inserted into the plasma membrane to "sense" the environment - may be targets for the adaptive immune system Turns on or off genes DNA- dep - RNA polymerase requires specific Sigma factors for accuracy and affinity of binding to the promoter New sigma factors allow new phenotypic expressions

Autoclave

A sophisticated pressure cooker. In its simplest form, it consists of a chamber in which the air can be replaced with pure saturated steam under pressure. Air is removed either by evacuation of the chamber before filling it with steam or by displacement through a valve at the bottom of the autoclave, which remains open until all air has drained out. The latter, which is termed a downward displacement autoclave, capitalizes on the heaviness of air compared with saturated steam. When the air has been removed, the temperature in the chamber is proportional to the pressure of the steam; autoclaves are usually operated at 121°C, which is achieved with a pressure of 15 pounds per square inch. Under these conditions, spores directly exposed are killed in less than 5 minutes, although the normal sterilization time is 10 to 15 minutes to account for variation in the ability of steam to penetrate different materials and to allow a wide margin of safety. The use of saturated steam in the autoclave has other advantages. Latent heat equivalent to 539 cal/g of condensed steam is immediately liberated on condensation on the cooler surfaces of the load to be sterilized. The temperature of the load is thus raised very rapidly to that of the steam. Condensation also permits rapid steam penetration of porous materials such as surgical drapes by producing a relative negative pressure at the surface, which allows more steam to enter immediately. Autoclaves can thus be used for sterilizing any materials that are not damaged by heat and moisture, such as heat-stable liquids, swabs, most instruments, culture media, and rubber gloves

Yaws

A treponeme skin disease Person to person by contact of open ulcers, lesions, Later develop to gummas (granuloma develop on skin and bones Found in tropical and desert of South America and Africa and Asia Affects 50 million people

Viral neuraminidase

A type of neuraminidase found on the surface of virus (eg. Paramyxo virus, orthomyxovirus ) that enables the virus to be released from the host cell. Neuraminidases are enzymes that cleave sialic acid groups from glycoproteins and are required for influenza virus replication.

Lytic cycle

A type of viral (phage) replication cycle resulting in the release of new phages by lysis (and death) of the host cell. Eclipse phase: Entry of nucleic acid into the cell and first appearance of infectious intracellular phage particle Latent phase: Time interval between infection of a cell to the first release of infectious phage particles.

Amoebic ulcer of the penis

A very rare clinical entity. We report a case of amoebic ulcer of the glans penis in a 47- year-old male homosexual, symptomatic with severe pain and foul-smelling hemopurulent discharge of acute onset. He had received systemic antibiotics like ciprofloxacin and azithromycin prior to presentation with no improvement. Diagnosis was confirmed by wet mount microscopic examination of the discharge. The patient responded well to a course of metronidazole.

Chlamydial trachomatis serovars and disease

A, B, C Hand to eye, fomites, flies leads to Trachoma/ blindness D-K Sexual, intrapartum, hand to eye leads to Genital infection, Inclusion conjunctivitis Infant pneumonia L1, L2, L3 Sexual Genital ulcer: lymphogranuloma venereum

Activation of G protein

A-B toxin causes ADP ribosylation Increase in adenylate cyclase activity - Increase in cAMP In the respiratory epithelium, the high levels of cAMP results in increased respiratory secretions and mucous production and contributes to coughing. 1. Cholera toxin (Vibrio cholerae)/Heat labile toxin (Escherichia coli) - Act on small intestine Cause watery diarrhea/secretory diarrhea 2. Pertussis toxin (Bordetella pertussis): Respiratory epithelium pathogen The high levels of cAMP results in increased respiratory secretions and mucous production and contributes to coughing.

Inactivation of EF-2

A-B toxin causes ADP ribosylation Leads to Inhibition of protein synthesis 1. Diphtheria toxin: Corynebacterium diphtheriae Upper Respiratory tract pathogen; results in cell death. Toxin can enter circulation and affect heart, kidney, nerves Toxin gene carried by temperate phage 2. Exotoxin A: Pseudomonas aeruginosa Pneumonia in cystic fibrosis patients

Virulence of Meningococcal Meningitis

A. Capsule: a polysaccharide capsule - prevents from phagocytosis several serotypes the most common- A, B, C, Y, W135 (cause 95% of cases) Type A mostly in developing countries of Africa, causing epidemics B,C,Y main forms in USA (B strain most common) capsule is immunogenic: except type B capsule B. LOS - lipooligosaccharide - lacks O antigen but has Lipid A (endotoxin) Induces strong inflammatory cytokine production: C. Surface proteins: several, Factor H binding protein (fHbp) inactivates C3b - no membrane attack and phagocytosis D. Adhesion proteins: pili E. IgA protease.

Virulence of Streptococcus pneumoniae

A. Colonization and Migration: IgA proteases - disrupt secretory IgA activity Surface protein adhesins Pneumolysin: cytotoxin-binds cholesterol in cell-creates pores B. Tissue destruction Teichoic acid and peptidoglycan - activate alternative complem. Pneumolysin: activate classical complem. pathway-inflammation Phosphorylcholine : unique to SP, + in cell wall - binds to receptors (for PAF) expressed on many cells - bacteria "hide" inside the non-professional phagocytes - spread of infection C. Phagocytic survival: Polysaccharide capsule (90 serotypes) -Antiphagocytic

Dermatophytic Hair Infections

A. Ectothrix infection--hyphae within the hair shaft and round spores are on the outer hair surface B. Endothrix infection--hyphae and spores within the hair shaft C. Favic infection--bubbly empty air spaces inside hair, hyphae and spores also present - "honey comb" appearance - cause hair loss

Intrinsic Resistance

Bacteria lacking the target - e.g, lack of peptidoglycan. Cell wall less: Mycoplasma, Ureaplasma Cell wall without typical peptidoglycan: Chlamydia, Chlamydophila,Orientia, Ehrlichia and Anaplasma, Rickettsia The antimicrobial cannot enter the bacterium eg. Gram negative bacteria due to the outer membrane; Acid fast bacteria due to mycolic acid

Streptococcus pyogenes skin infections

A. Impetigo : similar to S. aureus impetigo, confined, purulent infection, Vesicles progresses to pustules, rupture honey colored crust with erythema B. Erysipelas: (red skin): infection of the skin (upper dermis and superficial lymphatics), localized pain, and inflammation Regional lymph node swelling, systemic symptoms. The involved skin is typically raised and has demarcated margins. On face or legs follows URT or skin infection C. Cellulitis: inflammation of the skin and subcutaneous tissues No distinction between infected and non infected area D. Endometritis (Puerperal fever): a serious infection of pregnant women

Listeriosis

A. In adults: Immunocompetent : mostly asymptomatic, flu-like symptoms, with/w out GI symptoms Acute self limited gastroenteritis (Cx by IP: 1 day followed by 2 days of symptoms such as watery diarrhea, fever, nausea, headache, myalgias and arthralgias) Pregnant women: Most infection during 3rd trimester (when CMI is most impaired), typically fever and other non specific symptoms, can lead to fetal complications (next slide) Immunocompromised: Severe gastroenteritis disseminated, bacteremia, hypotension and meningitis Most common cause of meningitis in renal transplant patients and adults with cancer B. Neonatal Disease: outcome depends on the stage of infection Early onset: acquired transplacentally (within 10 days): Can lead to abortion, still birth or premature birth Granulomatosis infantiseptica: severe form of early onset listeriosis sepsis, pyogenic granulomas in multiple organs - high mortality rate unless treated promptly Late onset: acquired at or soon after birth from fecal exposure Disease is seen 2-3 weeks after birth Meningitis or meningoencephalitis with septicemia

Increase of antibiotic resistance

A. Increased use of antibiotics Selects for antibiotic resistance phenotypes. Administration of antibiotics without need 1/3 of outpatient prescriptions for antibiotics are unneeded Unregulated prescriptions Use of broad-spectrum antibiotics Use of antibiotics in agriculture Bystander effect on normal flora Serve as a link to pass on resistance genes When the antibiotics attack pathogenic (disease causing) bacteria, they also affect benign bacteria (innocent bystanders) in their path. They eliminate the drug susceptible bystanders that could otherwise limit the expansion of the pathogens and they simultaneously encourage the growth of resistant bystanders. Propagation of these resistant non pathogenic bacteria increases the reservoir of resistant traits in the bacterial population as a whole and raises the odds that such traits will spread to pathogens. In addition, sometimes the growing populations of bystanders themselves become agents of disease. B. Increased mobility of world's population C. Hospital setting: Selection and maintenance of antibiotic resistance genes

GBS infection

A. Neonates Early Onset Neonatal Disease: 1st week of life infection acquired in utero or during delivery: sepsis, pneumonia , meningitis Late Onset Neonatal Disease: infection acquired from exogenous source - eg other infected infants develops between 1 week to 3 months. Sepsis and meningitis (less often fatal compared with early infection) B. Infection in Pregnant women: postpartum endometritis, wound infection, and urinary tract infection C. Infections in Men and Non pregnant women (Old and with debilitating condition): bacteremia, pneumonia, Bone and joint infections, skin and soft tissue inf.

Hyphal morphology (In molds)

A. Non septate or septate Non-septate or coenocytic : no separation of cells, mutinucleated Septate—cells separated by septa (cell wall) B. Dematiaceous (dark colored) or hyaline (colorless)

Pathogenesis of Ascariasis

A. Pulmonary manifestation: - pneumonitis (Loeffler's syndrome) Caused by the larvae migration through the lungs Results in accumulation of eosinophils in the lung Signs and symptoms: Dry nonproductive cough, fever chest pain, wheezing, dyspnea, rales (crackling sound) on auscultation Chest X-ray shows infiltrates B. Intestinal manifestation:- GI symptoms resulting from mechanical irritation include vague abdominal complaints - cramping, distended abdomen, intermittent loose stool and occasional nausea and vomiting. Heavy infection - Entanglement of large no. of parasite Small bowel obstruction (mostly in children) May lead to perforation, intussusception, volvulus (bowel twisted on itself) C. Adult worm migration: bile duct - cholecystitis; pancreatic duct - pancreatitis; and appendix- appendicitis

Pathogenesis of Strongyloides stercoralis

A. Skin manifestation: Ground itch - at site of penetration Migratory larva: Larva currens (Racing larvae), is a serpiginous (wavy) urticarial rash that creeps 5-15 cm/hr (i.e rapid migration) up the body B. Pulmonary manifestation: pneumonitis (Loeffler's synd.) migrating larvae- cough, dyspnea, wheezing, fever C. Intestinal manifestation: abdominal cramping, chronic bloody diarrhea, epigastric pain D. Hyper infection syndrome: autoinfection results recurring episodes for years, in immunocompromised pts. E. Disseminated strongyloidiasis: in immuncompromised pts (eg. AIDS). Any organ involvement- pulmonary, neurologic complications, shock, even death

Infectious Mycoses

A. Superficial mycoses: superficial limited to outermost layers of the skin and hair. No inflammation B. Cutaneous mycoses: may extend into epidermis, invasive; hair and nail involvement C. Subcutaneous mycoses: involve dermis, subcutaneous tissues, muscle, and fascia - usually requires traumatic implantation D. Systemic mycoses: Start with localized infection such as in the lung (by inhalation); may disseminate to skin and other organs. E. Opportunistic mycoses: often normal flora or ever-present in environment, special conditions allow disease: -Suppression of normal flora: by antibacterial therapy -Diabetes -Immuno-suppression *HIV infection, use of immunosuppressive drugs etc.

Cell and tissue damage

A. Toxic products: Hydrolytic enzymes, cytolytic enzymes B. Mechanical Damage: blockage, pressure, migration of larva through tissue C. Immunopathology : Type I hypersensitivity (IgE mediated hypersensitivity): mast cell and eosinophil degranulation Type II and III type hypersensitivity: tissue damage and inflammation and scarring Type IV hypersensitivity: cell mediated; granuloma Type I: Helminthic infection, African trypanosomiasis Type II: Trypanosoma cruzi infection Type III: Malaria, Schistosomiasis, Trypanosomiasis Type IV: Leishmaniasis (Kala-azar), Schistosomiasis, Trypanosomiasis Competition for nutrition (malnutrition), cause loss of blood

HIV Infection Stage 2

AIDS Related Complex : ARC : symptomatic CD4 count 500-200 cells/ul Persistent fever, weight loss, fatigue, night sweats lymphadenopathy, may include opportunistic or reactivation infections Diarrhea lasting >1 month, Shingles, Candidiasis: Oropharyngeal candidiasis (thrush), vulvovaginal candidiasis, Hairy leukoplakia oral,(EBV+HIV), The gradual decline of CD4 T cells increases susceptibility to opportunistic pathogens, especially those controlled by CD4 T cells, activated macrophages, CD8 T cells and DTH response. Such infections include yeast, herpes, other DNA viruses, and intracellular bacteria.

Types of viral infection

Abortive: in non-permissive cells; replication does not occurNon permissive cell: may lack a receptor, important enzyme pathway, transcriptional activator or express an antiviral mechanism that will not allow replication of the virus Viral mutants, which cause abortive infections, do not multiply and disappear. In-apparent: little to no damage or rapid resolution eg. Cytomegalovirus in healthy Acute/Lytic : in permissive cells: host cell death - eg. Adenovirus Persistent: starts with acute phase, remain long A. Chronic (productive): Hepatitis B virus B. Latent (limited viral macromolecular but no virus synthesis): eg, Herpes virus C. Recurrent (periods of latency then virus production): eg, Herpes virus D. Transforming- Immortalization - oncogenesis - oncogenic virus eg. Papillomavirus

Trichinella spiralis: Life cycle

Acquired by ingesting meat containing cysts (encysted larvae) of Trichinella. After exposure to gastric acid and pepsin, the larvae are released from the cysts and invade the small bowel mucosa where they develop into adult worms (female 2.2 mm in length, males 1.2 mm; life span in the small bowel: 4 weeks). After 1 week, the females release larvae that migrate to the striated muscles where they encyst . Trichinella pseudospiralis, however, does not encyst. Encystment is completed in 4 to 5 weeks and the encysted larvae may remain viable for several years. Ingestion of the encysted larvae perpetuates the cycle. Rats and rodents are primarily responsible for maintaining the endemicity of this infection. Carnivorous/omnivorous animals, such as pigs or bears, feed on infected rodents or meat from other animals. Different animal hosts are implicated in the life cycle of the different species of Trichinella. Humans are accidentally infected when eating improperly processed meat of these carnivorous animals (or eating food contaminated with such meat).

Permissive EBV infection

Acute: Infectious mononucleosis ("Kissing disease"/MONO); IP: 4-6 wks Triad of exudative pharyngitis (sore throat), lymphadenopathy, and splenomegaly accompanied by high fever, fatigue, lasting for 1-4 weeks Heterophile antibody positive Chronic: Cyclic recurrent disease - fatigue (?chronic fatigue syndrome), may have low grade fever, headache and sore throat

Congenital Syphilis

Across the placenta or during birth, may result in Miscarriage, stillborn Children born alive may have birth defects or develop signs of congenital syphilis Early symptoms : Many (2/3) are asymptomatic at birth Symptoms appear between 2-6 weeks after birth Diverse presentation: include Hepatosplenomegaly, skin and mucous membrane lesions/rashes. Nasal discharge (snuffles), rhagades, Late (tertiary) syphilis: generally do not appear until after two years of age Early damage to developing structures, particularly teeth and long bones. Hutchinson's teeth, mulberry molars, Saber shins, saddle nose,

Uncomplicated UTI treatment

Acute cystitis and/or urethritis are usually treated for three days - targeting E. coli Trimethoprim-sulfamethoxazole (TMP-SMX), norfloxacin or ciprofloxacin.

Rhodesian sleeping sickness (East ASS)

Acute phase occurs very rapidly-fever, rigors, myalgia Lymphadenopathy Progresses to a fulminating, rapidly fatal illness CNS invasion early (within few wks)-lethargy, anorexia, mental disturbance, neurological problems Kidney damage, myocarditis and death

Treatment of HCV

Acute phase: Pegylated interferon alpha Chronic phase: antiviral (nucleoside analogues/RNA polymerases inhibitor/protease inhibitors (combination of drugs Prevention: Screening of blood, organ, tissue donors High-risk behavior modification/alcohol Blood and body fluid precautions No vaccine

Pathogenesis of Schistosomiasis

Acute phase; Swimmer's itch: within 12 hrs, common with non human schistosomes. immune reaction to penetrating cercariae (Type I HSR); Katayama fever: 2-3 weeks, onset of oviposition results in fever, chills, cough, urticaria, arthralgia, splenomegaly and abdominal pain Chronic phase: Presence of eggs; formation of granuloma as well as production of proteolytic enzymes by the eggs Mostly affected organs are the liver, spleen, wall of the gut or bladder. Eggs may enter blood and get deposited in any other organ such as brain, heart Eggs in the liver: periportal fibrosis and portal hypertension resulting in hepatomegaly, splenomegaly and ascites In the bladder: granulomatous lesions, hematuria and sometimes urethral occlusion. bladder cancers In the intestine: cause polyp formation which, in severe cases, may result in life threatening dysentery.

Pathogenesis of trichinosis

Adult lives in intestine, larvae in muscles in the same host Toxic secretions by migrating larvae-vasculitis Host reaction to large numbers of larvae and their metabolites in vital muscles The larvae promotes formation of collagenous capsule- Nurse cell The muscle fibers become enlarged, edematous and deformed. The paralyzed muscles are infiltrated with neutrophil, eosinophils and lymphocytes. Splinter hemorrhage beneath the nails: due to vasculitis resulting from toxic secretions of the migrating larvae

Pathogenesis of Taenia solium

Adult lives in the intestine, larvae can be found in many parts of the body Clinical Disease: Taeniasis Intestinal taeniasis: most infections are asymptomatic, mild abdominal discomfort. Cysticercosis: Associated with ingestion of eggs (through contaminated water or vegetations/salad). Cyst (cysticercus i.e larval stage) in tissue: Space occupying lesion. Immune response when the cyst dies; may calcify Symptoms depends on the tissue affected. In brain (NCC)- results in seizures, headaches, and vomiting. In Spinal cord - paralysis, In eyes - blindness

Pathogenesis of Scabies

Adult mites enter the skin, produce eggs-develop into larva and nymph stages Embedded in the stratum corneum Presence of mites and their feces/secretions cause type IV hypersensitivity reaction and intense itching Scabies/Mange/Itch Intense itching; short, slightly raised burrows; worsening at night Interdigital and popliteal folds, wrist, inguinal region, along belt line Occasionally, excoriation, crusts and secondary bacterial infection In immunodeficient people: more severe form-Norwegian scabies-generalized dermatitis with extensive scaling and crusting and presence of thousands of mites in the epidermis

Pathogenesis of Paragonimus westermani

Adult worm commonly lives in the lungs Pulmonary: asymptomatic to severe tuberculosis like/ chronic pneumonia Long term - pulmonary fibrosis, pleurisy: pulmonary pain, chronic bad/dry cough, bronchitis, blood in the sputum/rusty brown sputum. Extra-pulmonary: brain, spinal cord, intestinal wall etc

Ascaris lumbricoides: Life cycle

Adult worms live in the lumen of the small intestine. A female may produce approximately 200,000 eggs per day, which are passed with the feces. Unfertilized eggs may be ingested but are not infective. Fertile eggs embryonate and become infective after 18 days to several weeks , depending on the environmental conditions (optimum: moist, warm, shaded soil). After infective eggs are swallowed, the larvae hatch, invade the intestinal mucosa, and are carried via the portal, then systemic circulation to the lungs. The larvae mature further in the lungs (10 to 14 days), penetrate the alveolar walls, ascend the bronchial tree to the throat, and are swallowed . Upon reaching the small intestine, they develop into adult worms. Between 2 and 3 months are required from ingestion of the infective eggs to oviposition by the adult female. Adult worms can live 1 to 2 years. Geographic Distribution: The most common human helminthic infection worldwide. Highest prevalence in tropical and subtropical regions, and areas with inadequate sanitation. Occurs in rural areas of the southeastern United States.

Pathogenesis of Loiasis

Adults live and migrate through the subcutaneous tissue, muscles, and in front of the eye Clinical manifestations: Skin: Calabar/fugitive swelling. When the worms migrate through subcutaneous tissues, they create pruritic nodules as a result from allergic reaction. Transient, common in extremities, 5 to 10 cm in diameter Eye: Eyeworm: migration of worm under the conjunctiva- irritation, painful congestion, edema of eye lids; (loss of vision-rare)

Schistosoma spp. and habitat in humans

Adults live in urinary or mesenteric (i.e GIT) blood vessels, life expectancy, 10 to 25 years Three spp: Schistosoma mansoni, Schistosoma japonicum Live in mesenteric blood vessels of human and baboons, domestic animals, rodents Schistosoma haematobium - lives in veins draining the urinary bladder (Venous plexus of bladder), human is the only host

Hookworm morphology

Adults: Male and Female separate, ≈1cm. ♀is slightly larger than♂ Male's posterior end is expanded in an umbrella like fashion to form a copulatory bursa. Larvae: Rhabditiform and filariform Eggs: 60×40 µm, oval in shape, shell is thin and colorless (not bile stained), contains a segmented ovum, usually with 4 blastomeres, clear space between the egg shell and segmented ovum

Enterobius vermicularis: Life cycle

After ingestion the embryonic eggs (i.e, with larvae), they hatch in the duodenum and reach adolescence in jejunum and upper ileum. Adult worms descend into lower ileum, cecum and colon and live there for 7 to 8 weeks. After mating the male dies. The gravid females, containing more than 10,000 eggs migrate, at night, to the perianal region and deposit their eggs there. It then secretes a substance that causes a very strong itching sensation, inciting the host to scratch the area and thus transfer some of the eggs to the fingers. Eggs mature in an oxygenated, moist environment and are infectious 3 to 4 hours later. The eggs can be found in underclothes, bedding material, they can be carried in the air and contaminate any other house holds, such as curtains, floors. The eggs can survive from 2 to 3 weeks on their own outside of the human body Retro-infection can also occur, that is the migration of newly hatched larvae from the anal skin back into the rectum Reported up to 1000 females on the scotch tape + 50000 eggs Female goes out at night to the oxygenate environment to release her eggs. Diagnosis under microscope looking at the eggs (Asymmetrical in shape (plano-convex)

Trichomoniasis

Agent: Trichomonas vaginalis, flagellated protozoan, Symptoms: Itching and burning, watery, foul-smelling, greenish foamy vaginal discharge Cervix may show tiny spots of micro hemorrhages: Strawberry urethritis; dysuria both men/women Diagnosis: Microscopy: wet mount in warm saline: Motile flagellates Or stained prep. PCR: available Treatment: Metronidazole

General Characteristics of Enterobacteriaceae

All are Gram negative non-spore forming bacilli Are facultative anaerobes can ferment glucose Are oxidase negative Nitrate reductase positive : reduce nitrate to nitrite Classification is based on biochemical tests -Carbohydrate fermentation (with/out gas) -Lactose fermentation -Amino acid decarboxylases -Hydrogen sulfide production Antigenic properties of O antigen (LPS), capsular and flagellar antigen: share the core antigen Flagella: motility test

Itch Mites

Arachnid; Small sack like body Medically important (Sarcoptes scabiei), General Properties 300-400µm length 1st and 2nd pairs of legs widely separated from 3rd and 4th. Epidemiology: Worldwide, Global prevalence of nearly 300 million cases, obligate parasite of domestic animals (eg, dogs, cats) and humans Transmission: Personal contact or by fomites causes scabies

Treatment of blastomycosis

Amphotericin B, Itraconazole

Treatment of Aspergillosis

Amphotericin B, voriconazole; Surgery if possible

Antigenic shift

An abrupt change due to genetic reassortment with unrelated strains. Gives rise to pandemic flu. This occurs when two strains infect one cell simultaneously and RNA pieces of one strain is mixed with that of other strains giving rise to a new combination of RNA genome.

Dermatophytide

An allergic rash caused by an inflammatory fungal infection (tinea) at a distant site. The rash is usually itchy like dermatitis, with bumps or blisters scattered on face, trunk and/or limbs.

Urea Breath Test

An effective diagnostic method for H. pylori. They are also used after treatment to see whether it worked. In the doctor's office, the patient drinks a urea solution that contains a special carbon atom. If H. pylori is present, it breaks down the urea, releasing the carbon. The blood carries the carbon to the lungs, where the patient exhales it. The breath test is 96 percent to 98 percent accurate.

Trypanosoma cruzi Life Cycle

An infected triatomine insect vector (or "kissing" bug) takes a blood meal and releases trypomastigotes in its feces near the site of the bite wound. Trypomastigotes enter the host through the wound or through intact mucosal membranes, such as the conjunctiva. Common triatomine vector species for trypanosomiasis belong to the genera Triatoma, Rhodnius, and Panstrongylus. Inside the host, the trypomastigotes invade cells near the site of inoculation, where they differentiate into intracellular amastigotes . The amastigotes multiply by binary fission and differentiate into trypomastigotes, and then are released into the circulation as bloodstream trypomastigotes . Trypomastigotes infect cells from a variety of tissues and transform into intracellular amastigotes in new infection sites. Clinical manifestations can result from this infective cycle. The bloodstream trypomastigotes do not replicate (different from the African trypanosomes). Replication resumes only when the parasites enter another cell or are ingested by another vector. The "kissing" bug becomes infected by feeding on human or animal blood that contains circulating parasites . The ingested trypomastigotes transform into epimastigotes in the vector's midgut . The parasites multiply in the midgut and differentiate into infective metacyclic trypomastigotes in the hindgut . Trypanosoma cruzi can also be transmitted through blood transfusions, organ transplantation, transplacentally, and also by laboratory accidents.

Molecular Version of Koch's Postulates

An organism under investigation should be a member of pathogenic strains; and gene in question should be found in all pathogenic strains but absent from nonpathogenic strains The gene(s) coding for the responsible virulence factor(s) must be expressed during infection Inactivation of the gene (s) associated with virulence should lead to measurable decrease in pathogenicity Reversion of the inactivated gene/s should lead to restoration of pathogenicity. originally described by Dr.Stanley Falkow

Cutaneous larva migrans

Ancylostoma caninum & braziliense The lesions are erythematous, serpiginous (spreads by creeping), pruritic (extremely itchy), cutaneous eruption. IP: 1-5 days or long; Lasts for 2-10 weeks This is separate from the similar cutaneous larva currens which is caused by strongyloides.

Ancylostoma caninum & braziliense

Ancylostoma caninum : dog hookworm Ancylostoma braziliense: cat hookworm Larva can penetrate human skin, migrate under the skin, but does not complete its life cycle - human is a dead end host Children (exposure to soil contaminated with dogs and cat feces) are at risk In humans they cause severe erythematous and vesicular reactions- cutaneous larva migrans (CLM)literally means "wandering larvae in the skin", creeping eruption or ground itch (Differentiation from Larva currens- plz. see note) With A. brazilense- migration through lungs causes transient pulmonary infiltrates with peripheral eosinophilia (Loeffler's syndrome)

Treatment of Legionella

Antibiotic must penetrate human cells Macrolides (azithromycin or clarithromycin ), or fluoroquinolones (ciprofloxacin, or levofloxacin) Prevention and control: Identify source and eliminate aerosols Use of high temperature (Superheating) and hyperchlorination of water supply Copper-Silver ionization of water supply may be necessary

Significance of conjugation

Antibiotic resistance, R Plasmids Plasmid carrying multiple antibiotic resistance genes Rapid spread The whole process of conjugation takes about 100 min Virulence genes Pili genes that mediate adherence to epithelial cells Exotoxins genes can be transferred.

Diagnosis of RMSF

Antigen detection: Direct fluorescent staining on skin biopsy: rapid, specific Serology: Antibody detection (four fold increase in acute and Convalescent serum) Microimmunofluorescence (MIF test)/Indirect immunofluorescence assay (IFA); reference serological test Weil-Felix test: agglutination using Proteus antigens - (cross reacting antigens) - used in the past - not recommended any more due to poor sensitivity and specificity. Nucleic acid based tests : Cell culture or embryonated eggs: only in research labs

Evasion of immune system

Antigenic variation - within one life stage or due to different life stages (eg, African trypanosomiasis, Plasmodium, Babesia spp, Giardia) Encystation - uses the host response to wall itself off Antigenic mimicry: eg, Plasmodium spp, Trypanosomes, Schistosomes Antigen masking: Shistosoma mansoni Antigen shedding: Trichinella Masking/camoflage - uses discarded host antigens to hide by pasting them to their surface or molecular mimicry (eg, Hydatid cyst, filaria, Trypanosomes) Intracellular location Ig and/or complement proteases some produce DAF like molecule and destabilize C3b, others bind to C9 and prevent it from forming MAC (eg. Protease by Malarial parasite) Immunosuppression - diversion of the host immune response to ineffective immune response: Extracellular developmental stage secretes chemicals that down regulate a humoral (Th2) immune response Intracellular developmental stage secretes chemicals that down regulate a cell mediated (Th1) immune response Others suppress the immune system by producing antioxidant - interfere with macrophage killing

Treatment of Malaria

Antimalarial drugs Chloroquine or quinine; For chloroquine resistant cases: mefloquine± artesunate, artemether-lumafantrine, atovaquone-proguanil Prevention and Control Chemoprophylaxis for traveler to endemic areas: Chloroquine (P. falciparum sensitive areas) Mefloquine or doxycycline (chloroquine resist. P. falciparum endemic areas) Eradications of infections Vector control: control of mosquito breeding Protection of individuals by screening/window screening, netting, protective clothing and insect repellants

Treatment of Infective Endocarditis

Antimicrobial therapy: bactericidal regimen Use a recommended (American Heart Association) regimen Repeat blood cultures until blood is demonstrated to be sterile Streptococci/Enterococci Penicillin +/- aminoglycoside Vancomycin +/- aminoglycoside Cefotaxime/ceftriaxone HACEK Group: Cefotaxime/ceftriaxone Staphylococci Native valve Flucloxacillin +/- aminoglycoside Vancomycin +/- aminoglycoside/ rifampicin Prosthetic valve Flucloxacillin + aminoglycoside + rifampicin Vancomycin + aminoglycoside + rifampicin Surgery Prevention Antimicrobial prophylaxis is given to at-risk-patients when bacteraemia-inducing procedures are performed Follow guidelines (FYI only) American Heart Association. Circulation 1997; 96: 358-366 British Society for Antimicrobial Chemotherapy. Journal of Antimicrobial Chemotherapy 1993; 31: 347-438

Serologic determination of HIV

Antiviral antibodies ELISA : For screening antibody/ antigen detection "Combo HIV test" IgM, IgG against HIV-1 and HIV-2 and detection of p24 Repeated Positive Results Rapid antibody tests: version of ELISA (several) using urine, saliva or spot of blood Western blot/IFA confirmation of positive ELISA detects antibodies against several viral antigens: Positive = at least bands for gp41 + gp120/160 or p24 + gp120/160

Culture medium

Any material that contains the required nutrition and supports the growth of the microbes and is prepared in laboratory. It could be in liquid form - broth Solid/Semisolid - broth + a solidifying agent (agar)

Filarial worms

Any of a group of parasitic worms of the family Filariidae (phylum Nematoda) that usually require two hosts, an arthropod (the intermediate host) and a vertebrate (the primary/definitive host), to complete the life cycle. The larval phase occurs within the body of a biting insect. The mature (reproductive) phase occurs in the body of an animal bitten by the insect. Require 2 hosts: an arthropod (Intermediate host) and a vertebrate (Definitive host) Wuchereria bancrofti/ Brugia malayi - Elephantiasis Onchocerca volvulus - River blindness Loa loa - eye worm

Soil transmitted helminths

Ascaris Hookworm Whipworm Risk groups Preschool/School aged children; Women of childbearing age (including pregnant women in the second and third trimesters and breastfeeding women). Recommendation Periodic treatment with anthelmintic (deworming) drugs Prevalence over 20%- treatment once a year Prevalence over 50%-treatment twice a year

Assembly and Release

Assembly The site of assembly depends on the site of replication of genome Assembly can be in the nucleus or cytoplasm Nucleocapsid assembly Procapsid formation - empty capsid proteins assemble first then gets filled with the genome OR, Capsid proteins assemble around the genome. Release Naked viruses: released by cell lysis or exocytosis Enveloped viruses: Viral proteins are delivered to cellular membranes. Nucleocapsid moves underneath the membranes (nuclear, golgi, or cell membrane) with viral proteins; and leave by budding.

Romana's sign

Associated with the acute stage of Chagas' disease. It is unilateral painless periorbital/lymphoid swelling which occurs when the T. cruzi enters through the conjunctiva. Not to be confused with a chagoma (A chagoma is an inflammatory nodule at the bite site of the reduviid bug)

Dengue Fever Clinical Diseases

Asymptomatic Febrile virus illness - flu-like symptoms Uncomplicated Dengue fever (DF): Break-bone Fever Fever + two or more of the following: 1. Retro-orbital or ocular pain, headache, rash, leukopenia, 2. Mild bleeding manifestations: eg. tourniquet test +, petechiae, purpura/ecchymosis, nose or gum bleeding, easy bruising, blood in vomitus, urine, or stool; or vaginal bleeding 3. Deep bone pain and muscle pain (break- bone) Dengue Hemorrhagic Fever (DHF) Signs of DF plus evidence of plasma leakage, pleural effusion, or ascites or hypoproteinemia, thrombocytopenia Dengue Shock Syndrome (DSS) Signs of DHF plus circulatory failure, hypovolemic shock

Cystoisospora belli Life cycle

At the time of excretion in stool, the oocyst is immature and usually contains just one sporoblast (sometimes, two) . During further maturation after excretion, the sporoblast divides into two (the oocyst now contains two sporoblasts); the sporoblasts secrete a cyst wall, thus becoming sporocysts; and the sporocysts divide twice, resulting in four sporozoites per each of two sporocysts . Infection occurs by ingestion of mature (fully sporulated) oocysts: the sporocysts excyst in the small intestine and release their sporozoites, which invade the epithelial cells and initiate schizogony (asexual reproduction). Upon rupture of the schizonts, merozoites are released, which invade epithelial cells and continue the cycle of asexual multiplication. Trophozoites develop into schizonts, which contain multiple merozoites. After a minimum of one week, the sexual stage begins, with the development of male and female gametocytes . Fertilization results in the development of oocysts, which are excreted in the stool

Pathogenesis of Ticks

Attach at any point at the body but favor-scalp, hairline, ears, axillae, groin; Take blood meal Minor consequence-generally limited to small erythematous papule Serious consequence: Releases through saliva a neurotoxin that blocks acetylcholine release at the neuromuscular junction (action similar to botulinum toxin), requires at least 4 days contact Ascending flaccid paralysis (from legs to head within hours) resembling Gullain-Barre syndrome: Early signs-ataxia, symmetrical paralysis, fever Respiratory failure and death Recovery can occur within 24 hours of removal of tick

Pathogenesis of Fasciolopsis buski

Attachment of flukes in the small intestine produces inflammation, ulceration and hemorrhage, obstruction, abdominal discomfort, mal-absorption, diarrhea

Adenovirus replication

Attachment: by penton fiber protein Receptors on host cell: CAR: Coxsackie adenovirus receptor -glycoproteins belonging to Ig super family CD46 (membrane cofactor protein) MHC class I Integrin Sialic acid Receptor mediated endocytosis Replication in the nucleus Early protein synthesis, followed by replication and then late protein synthesis

Diagnosis of Taenia saginata

By detection of eggs/proglottids or entire worm in the stool (eggs similar to that of T. solium) Differentiation between T. solium & T. saginata based on their scolices and gravid segments Treatment: praziquantel, niclosamide Control & Prevention; proper cooking of beef, washing kitchen utensils after cutting meat.

Pathogenesis of Chiggers

Attack the areas where clothing is tight Saliva injected into the skin at the time of mite attachment produces and intense pruritic erythematous marks- may persist for wks. Mite larva visible at the center of the reddened swollen area Severe irritation may cause fever and sleep disturbance Excoriation and secondary bacterial infection can occur The stylostome is a funnel or channel-like structure formed by trombiculid mites. The formation is not caused by the mouthparts of the mites, because these mites do not have needle-like mouthparts, but have chelicerae, which only pierce the skin. The tube is formed by the digestive enzymes in the saliva, which is the same salivary secretions that break down cells that is causing the surrounding tissue to harden. As the mite feeds longer, the saliva seeps farther down, and digesting more tissue, therefore causes the stylostome to penetrate to lower layers of skin.

Mycobacteria Other Than Tuberculosis (MOTTS)

Atypical mycobacteria since they differ in certain aspects from the prototype, M. tuberculosis: For example, they are widespread in the environment and are not pathogenic for guinea pigs, whereas M. tuberculosis is found only in the humans and highly pathogenic for guinea pigs. Lung infection similar to MTB Mycobacterium avium-intracellulare most common mycobacterial disease in AIDS patients in US. (When CD4 count is less than 200 /microliter) Mycobacterium kansasii Skin infection Mycobacterium marinum Mycobacterium ulcerans Mycobacterium chelonae

Legionnaires' disease

Atypical pneumonia-severe form Incubation time 2-10 days Risk factor: Immunodeficiency Severe toxic pneumonia: rapid onset, starts with flu-like symptoms, high fever, chest pain, dry cough (non productive) Initially patchy interstitial infiltration with a tendency to develop into consolidation and micro-abscess May involve multi-organs - CNS, GI, liver, kidney Hyponatremia (serum Na≤ 130 mEg/L) Mortality rate may reach 15% in previously healthy, and 75% in patients with predisposing factors Acquired its name in 1976 when an outbreak of pneumonia occurred among persons attending a convention of the American Legion in Philadelphia. The bacterium causing the illness was named Legionella in 1977. It infected 221 people and killed 34. This type of bacteria was likely around before 1976, but unrecognized. More cases of Legionnaires' disease are being detected because we now look for this disease whenever a patient has pneumonia.

Direct Microscopic Detection of TB

Auramine rhodamine staining Mycobacteria stained with auramine -rhodamine and viewed with fluorescence microscopy (acid fast bacilli appear as glowing yellow rods) If positive, should be followed by Z-N staining Ziehl-Neelsen stain (Acid fast staining) Requires heating of a primary stain, decolorizing with an acid alcohol solution, and then a secondary dye. M. tb retains the primary dye

pathogenesis of gonorrhea

Avoid immune attack by IgA proteases - evade mucosal immunity Antigenic heterogeneity: programmed gene rearrangement Existence in multiple varieties: Pili (>100), Por (18-28), Opa (>100), LOS ( >8) Antigen switching (phase variation): from one type to another type Pili and Opa : switch from one type to another in the same isolate Repeated infection is common Lack of protective immunity - due to antigenic variation Primarily attacks epithelial cells of mucosal membranes, genitourinary tract, eye, rectum, throat characterized by a marked local neutrophil response purulent discharge. Lower genitourinary tract system infections Urethritis Discharge - thick creamy grey/white/greenish, pain during urination Cervicitis: Vaginal discharge thick grey/white, bleeding between menstrual periods, painful intercourse (bleeding after intercourse)

Microscopy of Malaria

Blood smear (thick/thin) examination after Giemsa staining-infected red blood cells, ring form, and gametocyte form. P. falciparum, can be differentiated from the others by multiple ring form per cell and crescent shaped gametocyte Thick films contain 10 to 20 times more blood than thin films, correspondingly providing increased sensitivity for malaria screening

Streptococcus pyogenes Necrotizing fasciitis

Bacteria entering through break in skin Myonecrosis/Streptococcal gangrene Deep tissue infection, with extensive destruction of muscle and fat, severe toxicity- Surgical debridement needed May progress to septic shock, 20% fatality Caused by Streptococcal exotoxin B (SpeB), a protease that destroys tissue Certain strains produce large amount of the toxin " flesh eating streptococci"

Bacterial Growth

Bacteria grow in size and number. Growth in number - population growth Population size increases by cell division They divide by binary fission A single cell divides to give two identical daughter cells The number of cells (population size) = 2n (n = generation number) This is exponential growth The doubling time - generation time varies Escherichia coli - 20 min Mycobacterium tuberculosis - 24 hrs

Shigella Clinical Disease

Bacillary dysentery/ Shigellosis; Watery followed by dysentery bloody diarrhea incubation period of 36-72 hours, initial non-specific symptoms fever (39-39 C) and cramping abdominal pain Profuse watery diarrhea: due to enterotoxin usually appears after 48 hours after the onset of the non-specific symptoms, Dysentery: invasion and damage of colonic mucosa Lower abdominal cramps, tenesmus (crampy rectal pain) with pus, mucus and bloody (red) stools; vomiting, dehydration, and convulsions Severity depends on the shigella sp. and host (malnutrition ). Children and the elderly more severe

Most common UTI pathogens

Bacteria Gram negative Escherichia coli Klebsiella pneumoniae Proteus spp. Pseudomonas aeruginosa Serratia marcescens Morganella spp. Gram positive Staphylococcus saprophyticus Enterococcus faecalis Group B Streptococcus Fungi Candida albicans Viruses Adenovirus (type 11 and 21) BK virus CMV

Common Pathogens of Digestive Tract

Bacteria Gram positive: Streptococcus (viridans group) Staphylococcus aureus Bacillus cereus Clostridium perfringens Clostridium botulinum Clostridium difficile Listeria monocytogenes *** Gram negative Escherichia coli (5 types) Vibrio spp. Shigella spp. Salmonella spp. Salmonella typhi Campylobacter jejuni Yersinia spp. Helicobacter pylori Viruses Mumps virus Noroviruses (Norwalk) Rotavirus Adenovirus 40/41 Asterovirus Herpes virus type 1 * Cytomegalovirus ** Fungi Candida albicans* Parasites: * Several of them *presented with skin and wound ** will be presented in STD *** will be covered with CNS

Categories of Infectious Agents

Bacteria - Prokaryotes, unicellular Virus - acellular, has either DNA or RNA Fungi - eukaryotes, unicellular/multicellular Parasites - eukaryotes, unicellular/multicellular Prions - abnormal proteins/ proteinaceous infectious agents, no nucleic acid

Pathogenesis of bacterial meningitis

Bacteria are transported across epithelial cells in membrane-bound vacuoles to the intravascular space or invade the intravascular space by creating separations in the apical tight junctions of columnar epithelial cells. Once in the bloodstream, bacteria are able to avoid phagocytosis by neutrophils and classic complement-mediated bactericidal activity because of the presence of a polysaccharide capsule. Bloodborne bacteria can reach the intraventricular choroid plexus, directly infect choroid plexus epithelial cells, and gain access to the CSF Some bacteria, such as S. pneumoniae, can adhere to cerebral capillary endothelial cells and subsequently migrate through or between these cells to reach the CSF. Bacteria are able to multiply rapidly within CSF because of the absence of effective host immune defenses. CSF contains few white blood cells (WBCs) and relatively small amounts of complement proteins and immunoglobulins. Many of the neurologic manifestations and complications of bacterial meningitis result from the immune response to the invading pathogen rather than from direct bacteria-induced tissue injury. As a result, neurologic injury can progress even after the CSF has been sterilized by antibiotic therapy. The lysis of bacteria with the subsequent release of cell-wall components into the subarachnoid space is the initial step in the induction of the inflammatory response and the formation of a purulent exudate in the subarachnoid space .

Coiling phagocytosis

Bacteria attach to the surface of the phagocyte and get rolled into a single fold of the plasma membrane, forming a pseudopod coil. The phagocyte forms multiple folds of the plasma membrane around the bacterium, which eventually leads to engulfment of the bacterium. Legionella produces various enzymes such as phosphatases, lipase and nuclease within the phagosome, destroys it; eventually kills the host cell.

Naturally Cell Wall-Less

Bacteria that do not produce peptidoglycan, but have unusual form of cell wall. These are Chlamydia, Chlamydophila, Ehrlichia, Orientia and Anaplasma. Are resistant to antimicrobials which target peptidoglycan synthesis Components: (Picture) No peptidoglycan present Assume a variety of shapes Sterols within a phospholipid Bi-layer membrane; Maintain fluidity Cannot be stained using the Gram stain procedure Resistant to antibiotics that target cell wall Examples of Cell Wall-Less Bacteria: Mycoplasma spp. Ureaplasma spp.

Non-inflammatory diarrhea

Bacteria: Escherichia coli Enterotoxigenic (ETEC) Enteroaggregative (EAEC) Enteropathogenic (EPEC) Vibrio spp. Viruses: Noroviruses (Norwalk virus) Rotaviruses Adenovirus 40/41 Astroviruses Protozoan: Giardia lamblia Cryptosporidium parvum Cyclospora cayetanensis Isospora belli

Nervous system Syndromes and Agents

Bacterial meningitis (purulent) Streptococcus pneumoniae Neisseria meningitidis Group B streptococci E. coli Listeria monocytogenes Haemophilis influenzae Viral meningitis (aseptic)* Coxsackie virus Echoviruses Chronic meningitis Cryptococcus neoformans Mycobacterium tuberculosis Treponema pallidum (STD) Acute primary amoebic meningitis Naegleria fowleri Granulomatous amebic encephalitis Acanthamoeba castellanii Viral encephalitis Arbovirus, many other viruses Space occupying lesions Taenia solium Echinococcus granulosus African Sleeping Sickness: Trypanosoma brucei Tetanus: Clostridium tetani Botulism: Clostridium botulinum (GI pathogens) Leprosy: Mycobacterium leprae (skin infection) Rabies: Rhabdovirus Polio: Polio virus Progressive multifocal leukoencephalopathy (PML): JC Virus Prion disease: Prions SSPE: Measles virus Brain abscess Various organisms eg. Streptococcus anginosus (viridans), Staph. aureus, Streptococcus pyogenes, Enterococcus faecalis and anaerobic bacteria

Vaginal/urethral discharge Pathogens

Bacterial vaginosis Mixed anaerobic bacteria Gardnerella vaginalis Vaginitis/Vulvovaginitis Trichomonas vaginalis* Candida albicans Urethritis/Cervicitis Neisseria gonorrhoeae Chlamydia trachomatis Mycoplasma sp. Trichomonas vaginalis* PID: Pelvic Inflammatory Disease Complication of cervicitis caused by certain pathogens

Types of Culture Media

Basal (Simple) Media: contains peptone, meat extract, NaCl & H20 eg., Nutrient agar Enriched Media: contains additional substances like in blood, serum, eggs or extracts from animal tissue that encourage the growth of organism eg, Blood agar, Chocolate agar Selective media: allows growth of only the desired microbes. The purpose is to inhibit the growth of unwanted organisms eg, LJ medium for M. tuberculosis Enrichment media: purpose same as selective media but liquid eg, Selenite F broth for Shigella Differential Media: are used to distinguish among different organisms eg. MacConkey agar, EMB agar Transport media: eg. Stuart's medium for Gonococci

Nutritional classification of bacteria

Based on their energy requirements and on their ability to synthesize essential elements Autotrophs: can synthesize all their organic compounds Photo-autotrophs: derive their energy from sunlight Chemo-autotrophs: obtain their energy from chemical reactions Heterotrophs: Unable to synthesize their own metabolites and depend on preformed organic compounds Majority of the pathogenic bacteria are heterotrophs

Diagnosis of Lyme Disease

Based primarily on Clinical features & H/O exposure to ticks; Laboratory-for confirmation Microscopy: During early stage with skin lesion : biopsy of rash; DFA. Serology (CDC's recommendation-next slide) ELISA and Immunofluorescence assay Detect IgM Fourfold increase of IgG in paired sera False positive: rheumatoid arthritis and other infections Western blot: for confirmation DNA probes - are available Culture: grows in special media, but not for diagnostic purposes.

Bacterial Cell Morphology

Basically there are three shapes Rods/bacilli (Coccobacilli) Cocci Spiral (spirochete, spirilla) Some show variation of these three basic structures Most bacteria are monomorphic Few are pleomorphic (many-shaped)

Cell Wall Synthesis Inhibitors

Beta Lactams -Penicillins -Cephalosporins -Carbapenems -Beta Lactamase Inhibitors: are structural analogues of penicillins/cephalosporins and have little antibacterial activity but bind strongly to beta lactamases thus protect penicillins/cephalosporins. Vancomycin Bacitracin For t/t of mycobacterial infection Cycloserine Isoniazid (INH) Ethionamide Ethambutol Pyrazinamide

Penicillin resistance

Beta-lactamase production: Genes carried on plasmids : spread easily Betalactamase activity: have various degree of spectrum Penicillinase : inactivates penicillins Cephalosporinase: Inactivates cephalosporins, Extended-spectrum batalactamase (ESBL); inactivates both drugs (P+C) Carbapenemase: against Penicillins + Cephalosporins + Carbapenems + Monobactems Alteration of Penicillin Binding Protein (form PBP 2A) Eg. By Methicillin resistant Staphylococcus aureus (MRSA) (mec A gene mediated: alter target)

Penicillin

Betalactam Antibiotic Structure: Nucleus: 6-Aminopenicillanic Acid Beta Lactam Ring Thiazolidine Ring (5 membered) R group R group altered in Semisynthetic Penicillins Access of beta lactamase enzyme to the beta lactam ring of semisynthetic penicillin is blocked by modification of the side chain with the addition of large aromatic rings, containing bulky methyl or ethyl groups.

Diagnosis of Enterococcus faecalis/faecium

Bile Esculin agar - Bile resistant hydrolyse esculin turns media black differentiate them from Streptococcus Bile Esculin Agar (Bile salts are the selective ingredient, while esculin is the differential component) is used primarily to differentiate Enterococcus from Streptococcus. Members of the genus Enterococcus are capable of growing in the presence of 40% bile and hydrolyzing esculin to glucose and esculetin. Esculetin combines with ferric ions to produce insoluble iron salts, a black complex (i.e, blackening of the medium).

Adhesion Factors

Binding specific molecules on host cells Determines tissue/ host specificity Pili, capsule, biofilm Cell wall structure: lipoteichoic acid Proteins on the cell wall Eg. Escherichia coli - urinary tract infection - has P fimbriae binds to Gal-Gal dimer on P antigen found on uroepithelial cells F protein found on cell wall of Streptococcus pyogenes - binds to fibronectin

Bacterial Classification

Binomial nomenclature: Genus and species: Staphylococcus aureus Classification/taxonomy: based on- Phenotype: based on morphology, staining properties, biochemical properties (biotyping), Genetics: DNA studies Antigenic variation: serotyping Phage typing : Sensitivity to bacteriophage

Diagnosis of Borrelia spp.

Blood - taken in the febrile period Microscopy: stained with Giemsa or Wright stain spirochetes do not stain well with Gram staining Treatment: Tetracycline, Penicillin, Erythromycin Prevention: Avoidance or elimination of arthropod vectors, insecticides, Personal hygiene

Schistosoma spp.

Blood flukes Schistosomiasis Bilharziasis Snail fever The disease is often associated with water resource development projects, such as dams and irrigation schemes, where the snails, intermediate hosts of the parasite, breed. Has low mortality but high morbidity rate. Epidemiology: World wide; affecting millions (approx.250), 2nd most prevalent tropical disease (after malaria) often associated with water resource development projects, such as dams and irrigation schemes; Transmission- skin penetration by cercaria (larva) : Eggs, larvae (various stages) and adults Adults: The sexes are separate, the male and female live attached to each other. This ensures fertilization

Transglycosylase

Enzymes facilitate formation of glycosidic bond to link peptidoglycan monomers

Diagnosis of JC Virus

Clinical observation of a progressive course of the disease Brain biopsy with histopathological examination PCR: in urine and in spinal fluid. Imaging: magnetic resonance image (MRI) demonstrate lesions.

Dilution test

Can measure MIC: Minimal inhibitory concentration MBC: Minimal bactericidal concentration Can be automated - results in few hrs Series of dilutions of the drug in broth media - inoculate same number of bacteria in every tube and determine the lowest concentration of drug that inhibits the growth of a particular bacteria, Minimum inhibitory concentration (MIC) = eg (below) 3.1 g/mL Does not mean this kills the bacterial isolate, only inhibits Minimal bactericidal Concentration (MBC) = 6.2 µg/ml that kills at least 99% of the bacteria For some infections -e.g, endocarditis- it may be necessary to determine amount of antibiotic that kills the bacteria, and also immunocompromised patients should be given a dose that would kill -the bacteria Bactericidal drugs usually have an MBC equal or very similar to the MIC, whereas bacteriostatic drugs usually have an MBC significantly higher than the MIC (Ref: Levinson)

Fungal arthritis

Candida spp, Cryptococcus spp, Aspergillus spp In otherwise healthy people: due to penetrating trauma with/out foreign substance In patients with chronic disease/immune suppression: trauma and hematogenous spread Antifungal treatment and surgery

Interference

Capsule: antiphagocytic Biofilm: prevent complement and antibodies Avoid killing: Inhibition of phagosome function or escape into the cytoplasm Killing of phagocytic cell by producing toxins Avoiding Ig mediated opsonization; bind Fc of IgG -Protein A of Staphylococcus aureus and -M protein of Streptococcus pyogenes Cleavage of antibodies/complement IgA proteases, C5a proteases

Virulence of Bacillus anthracis

Capsule: poly- glutamate- antiphagocytic Anthrax toxin: A-B toxin coded by genes on a plasmids 3 components- PA (protective antigen), EF (edema antigen, and LF (lethal factor) PA: Binding unit and mediate entry EF: is an adenylate cyclase that elevates cAMP resulting in edema LF: is a Zn-dependent protease that inhibits several kinases resulting in cell death

Bartonella henselae

Cat Scratch Disease General properties: Small Gram negative rod- pleomorphic, fastidious, grow slowly-2 to 6 wks, difficult to isolate Reservoir: Many animals but cats are the main reservoir; about 40% of all cats are infected Transmission: Bite, scratch, lick from an infected animal Risk Factors/Risk Populations: Anyone for Cat Scratch fever (disease); CSD - more common in children Immunocompromised for Bacillary Angiomatosis (BA) Two types of diseases 1. Cat Scratch Disease (CSD) 2. Bacillary Angiomatosis

Catalase test

Catalase producing organism (colonies) + H2O2= O2 (bubble)+water Hydrogen peroxide is a by-product of respiration and is lethal if it accumulates in the cell. Catalase is an enzyme that can degrade the hydrogen peroxide in the cell before it can do any cell damage. It splits the H2O2 to free oxygen and water.

Opportunistic pathogens

Cause disease in immun-ocompromised individuals or when normal flora enter body site other than normal site or overgrowth Microbes with small IDs have greater virulence. True pathogens (primary pathogens): cause disease in immuno-competent individuals

Wuchereria bancrofti and Brugia malayi

Cause Elephantiasis Epidemiology: tropical, subtropical Transmitted by mosquito, (feeds in night) For W. bancrofti-No animal reservoir For. B. malayi: animal reservoirs (Cats and Monkeys)

Streptococcal toxic shock syndrome

Caused by Streptoccal pyrogenic exotoxin SpeA and SpeC (super antigens). Mostly due to GAS serotype M1 and M3 Usually follows soft tissue infections (Erythema, swelling) with GAS Abrupt pain, fever, chills, malaise, N &V, diarrhoea Rapid demise, 50% fatality, due to septic shock and multi-organ failure Risk factors: Immunocompromised patients- with cancer, diabetes, HIV IV drug abusers

Plasmodium spp.

Causes Malaria Five species of medical importance P. falciparum (most serious form of malaria) P. vivax P. malariae P. ovale P. knowlesi: Infects primarily long-tailed & pig-tailed macaques human cases in Malaysia & other South east Asian countries)

Sporothrix schenckii

Causes Sporotrichosis General properties: Dimorphic fungi Mold at 25oC; septate hyphae with conidia in groups- "rosette" Yeast -at 35-37oC (body temperature) oval or elongated to give Cigar shaped appearance Reservoir: environment - soil, vegetation, rose or plum tree thorns Transmission: traumatic introduction of fungi, commonly by thorns Risk Factors/Risk Populations: Forest employees, gardeners, florists, people with other soil-related occupations and some outdoor leisure activities

Mechanisms of viral transformation

Cell growth is controlled by the maintenance of a balance in the external and internal growth activators (accelerators) and by growth suppressors, such as p53 and the retinoblastoma (RB) gene product (brakes). Oncogenic viruses alter the balance by removing the brakes or by enhancing the effects of the accelerators.

Syphilis virulence and pathogenesis

Cell wall: endotoxin Posses additional outer sheath - made of glycosaminoglycan: covers TP surface antigens Posses hyaluronidase: spreading factor Cross reacting antigens: Cardiolipin Immune response responsible for tissue damage It infects the endothelium of small blood vessels causing endarteritis and periarteritis - lesions

Adaptive Response Against Viruses

Cell-mediated: CD4 Th1 and CD8 Tc: killing infected cells, targets the intracellular phase of the virus Humoral immunity: primarily targets extracellular phase/cell surface expressed antigen Antibodies against viral attachment proteins (VAP): prevent infection Opsonization complement activation by antibody against virus Elimination via ADCC by NK cells (Ab provides specificity) Neutralization: Prevents spread by blocking extracellular virus particles

Point mutations

Change in single nucleotide Base pair substitution (Transition-most frequent, Transversion) Silent mutation: does not produce obvious effect Also called microlesion, changes in single nucleotides, may not necessarily result in detectable change in protein synthesis. Generally reversible. Two classes: I. Base pair substitution: Single base pair is substituted for another pair Transition-Substitution of one base pair but the purine, pyrimidine orientation is preserved. Happen by replacement of one pyrimidine by another pyrimidine, and one purine by another purine. Most frequent type of mutation Transversion: Pyrimidine is replaced by purine and vice versa, less frequently observed II. Silent mutation: It is a change at the DNA level only that does not result in any change of amino acid in the encoded protein. This is because more than one codon may encode an amino acid eg. GGT to GGA still gives proline.

Prevention and control of TB

Chemoprophylaxis : isoniazid (INH) or rifampin (RIF) recommended for people at risk (such as HIV +) if they get exposed to the MTB. Or for people exposed to MDR-TB Immunoprophylaxis BCG vaccine (Bacille Calmette-Guerin), a live attenuated bovine strain (i.e., M. bovis) is used in many countries with high incidence of TB, but not in the USA In the US, Recommended for children with close contact of TB patients; and Military personnel Active surveillance: identification of cases and contacts, directly observed treatment short course - DOTS

Clonorchis sinensis

Chinese or Oriental liver fluke/Opisthorchis sinensis Epidemiology: oriental region, one of the most frequent infection seen among Asian refugees, fresh water fish and snail- intermediate hosts; Dogs, cats and fish eating mammals as reservoir hosts Transmission : eating raw freshwater fish, undercooked fish Morphology Egg Larva: various stages Adult

Lymphogranuloma Venereum (LGV)

Chlamydia trachomatis Type L1-L3 Infectious Agent: Chlamydia trachomatis, Type L1-L3 Bacteria, obligate intracellular; cell wall lack muramic acid, do not stain Gram stain, energy dependent, biphasic growth cycle, Elementary body and Reticulate body, Reservoir: Humans, genital tract Transmission: Sexual contact, few hundred cases per year in the USA. Increasing among MSM. More common in hot climates Clinical symptoms: Genital ulcer: small painless lesion : may not be noticed, (usually a single lesion). Location: penis, urethra, scrotum, vaginal wall, vulva, cervix. Inguinal lymphadenopathy: Extensive swelling and redness of inguinal lymph nodes, painful, ulcerative Inflammation lymphatic channels, drainage problem Proctocolitis: anal, rectal and colon inflammation Hemorrhagic rectal discharge Swelling of lower limbs (elephantiasis-like) due to blockage of lymph circulation

Pathogenesis of Haemophilus influenzae

Clinical Disease: Non invasive/opportunistic infection- Mostly by non-Hib and non typable strain: Otitis media, sinusitis, Lower respiratory tract infection (pneumonia in elderly adults with chronic respi. disease) Invasive infection: Mostly by Hib Meningitis and epiglottitis, bacteremia, arthritis and cellulitis Epiglottitis: cellulitis and swelling of supraglottic tissue complete airway obstruction; life threatening medical emergency death not treated quickly; Children 2-4 yrs mostly affected

Pseudomonas

Clinical Disease: Respiratory infection: varies in severity; asymptomatic to Tracheobronchitis and Necrotizing bronchopneumonia; One of the most common causes of nosocomial pneumonia severe invasive infection in cystic fibrosis patients (Biofilm forming strains) Bacteremia and endocarditis: skin manifestation- Ecthyma gangrenosum, may lead to shock & death Ear infections: External otitis (Swimmer's ear)-malignant form in Diabetic/ elderly people (malignant external otitis); Chronic otitis media Other diseases. Skin: burn wounds, folliculitis (from conta. water-hot tub) Eye infection (corneal): after trauma with contact lens Urinary tract infection : through indwelling catheters Most common cause of osteochondritis of foot after penetrating injury

Poliomyelitis

Clinical Disease: IP 10-14 days Asymptomatic : Most (~90-95%) infections are asymptomatic with viral shedding Abortive poliomyelitis: (~5%), a 3-4 day long mild nonspecific febrile illness, headache, sore throat, nausea, vomiting. Most recover spontaneously. Non-paralytic polio (~2%) or aseptic meningitis. The virus reaches the meninges and cause aseptic meningitis with fever, headache, stiff neck in addition to symptoms of minor illness - some may recover spontaneously

Pathogenesis of Moraxella catarrhalis

Clinical Diseases: otitis media (3rd most common), sinusitis in children and bronchitis and pneumonia in elderly.

Pathogenesis of legionella

Clinical diseases: community/hospital acquired Asymptomatic common Symptomatic: Two types of diseases Pontiac Fever and Legionnaires disease Facultative intracellular pathogen, infects alveolar macrophage, monocytes and alveolar epithelial cells. C3b deposition in outer membrane protein facilitates phagocytosis but no fusion between phagosome and lysosome thus avoid intracellular killing and survive inside macrophages produce proteolytic enzymes and kill host cell infected macrophages produce inflammatory cytokines causing robust inflammatory response - typical of this pathogen

Direct Light Microscopic Examination

Clinical sample: sputum, lung biopsy, skin scraping Wet mount or stained smears -Wet mount: KOH: Treat the sample with 10% KOH to clear debris; Stains -Gram stain: in suspected yeast infection, Candida may stain as G +. -Indian ink (negative staining): for detection of capsulated fungus -Calcofluor white stain: is fluorescent and binds to chitin -Other stains: Periodic acid Schiff (PAS), Gomori methanamine silver (GMS), Giemsa, Hematoxylin and eosin, immunofluorescent staining Determine Morphology: yeast or mold; hyphal structure, asexual spores

Diagnosis of cholera

Clinical: Rice water, acute diarrhea Microscopy: RARELY USED Culture: Selective media Thiosulfate Citrate Bile Salts Sucrose Agar (TCBS): yellow colonies Biotyping, determine species Serotyping- agglutination test using polyvalent sera anti-O1 type and O139 Report to health authority if O1 or O139 are detected

Diagnosis of HEV

Clinically indistinguishable from HAV Detection of antibody: not well established Rule out A and B serologically; RT-PCR: Electron microscopy: Confirm with (DFA) immunoflourescent staining in feces Treatment: supportive Prevention and control measures: Avoid drinking water, uncooked shellfish and fruit/vegetables Passive immunity: IG from donors in Western countries does not prevent infection (exposure being low) No vaccine

Botulinum toxin

Clostridium botulinum toxin blocks/inactivates SNARE proteins needed for acetylcholine release causing flaccid paralysis

A-B toxins neurotoxins

Clostridium botulinum: toxin inactivates proteins [SNARE proteins (synaptobrevin and syntaxin required for the release of acetylcholine] Synaptobrevins are small integral membrane proteins of secretory vesicles Tetanus toxin affects anterior horn cells of the spinal cord and brain stem. Cleaves synaptobrevin and blocks release of inhibitory transmitter from inhibitory terminals produces hyperflexia and spasms of skeletal muscles.

Pig-Bel

Clostridium perfringens infection Diarrhea and Necrotizing enteritis. Under cooked Pig meat/sweet potatoes /malnutrition Associated with C. perfringens type C that produce beta-toxin - cause necrotic lesions progress to necrotizing enteritis Acute abdominal pain, bloody diarrhea, vomiting, ulceration of the small intestine, perforation of the intestinal wall Affects especially the jejunum but also the ileum. Associated with eating pork with sweet potatoes which contain heat resistant trypsin inhibitor. This protects the toxin from inactivation by trypsin. Common in Papua New Guinea. Fatal disease Not common in the US

Tetanospasmin

Clostridium tetani: Blocks release of neuro inhibitor (glycine and gamma amino butyric acid) causing spastic paralysis--tetanus

Virus

Comes from the Latin word for "poison" Submicroscopic - measured in nm - electron microcopy Acellular - inert, not considered to be "living" Incapable of self-replication They are obligate intracellular infectious agent Must encode any required processes not provided by the host cell Replicate by assembly of individual components within host cell 1890s - First identified as filterable infectious agents (passed through filters that removed bacteria) - It was suggested that the infection might be caused by a toxin produced by bacteria (The agent is now known as tobacco mosaic virus) 1901 - first human virus discovered - Yellow Fever Virus 1909 - poliovirus, 1933 - influenza virus, 1963-hepatitis B virus

Operons

Clusters of co-regulated genes: with a promoter, operator and structural genes These genes are regulated such that they are all turned on or off together. Grouping related genes under a common control mechanism allows bacteria to rapidly adapt to changes in the environment. Prokaryotic genes to be regulated in the same manner are grouped together in operons, under the control of a single promoter and operator. Transcription of an operon is dependent upon whether or not the repressor (encoded by a nearby gene) binds to the operator region. Inducible or Repressible

Inclusion bodies

Collections of replicating virus particles either in the nucleus or cytoplasm: Have diagnostic importance Examples of inclusion bodies include the negri bodies and cytomegalic inclusion bodies found in rabies and CMV infections respectively.

Treatment of Pseudomonas

Combination of antibiotics: anti-pseudomonal Beta lactams plus aminoglycosides or fluoroquinolones Multidrug resistance common; inherent resistance to multiple antibiotics. Prevention: Institution of antibiotic policies and infection control practices in hospital Prevention of contamination of sterile equipment (eg, ventilators, dialysis machines). Chlorination of hot tubs

Treatment of anthrax

Combination of drugs: Ciprofloxacin or doxycycline plus one or two other drugs (rifampin, vancomycin, penicillin, imipenem, clarithromycin etc) Prevention: Post-exposure prophylaxis for inhalation anthrax for 60 days Vaccine - partially purified protein (PA antigen) - available for people at risk and for animals; Multiple doses, annual boosters can be given Control of animal disease Vaccination of animals and Incinerating animals that die of anthrax, rather than burying them.

Treatment and Prevention of H. pylori

Combination of drugs: Initial treatment Proton pump inhibitors (eg. Omeprazole) Reduce gastric acid secretion 2. Macrolides (eg. clarithromycin) 3. Beta-lactam (eg. amoxicillin) 4. Metronidazole Drug resistance is common - susceptibility test recommended in treatment failure Prevention: Improved hygiene - reduction in prevalence

Zoster (Shingles)

Common in the USA (1:3) Reactivation of latent virus in immunocompromised, >60 years, Stress Painful vesicular skin lesions within dermatomes Post Herpetic Neuralgia; pain due to nerve damage may persist for months to years after the rash disappears The reactivated virus generally causes a vague burning sensation or tingling over an area of skin. Painful rash appear two to five days after the first symptoms. A cluster of small bumps (1)Turns into blisters (2) that resemble chickenpox lesions. The blisters fill with pus, break open (3),Crust over (4), and finally disappear. This process takes four to five weeks. Post-herpetic neuralgia can sometimes occur- thought to be caused by damage to the nerves (5), and can last from weeks to years after the rash disappears.

Pili (Fimbrae)

Commonly on Gram Negatives For adhesion and/or transport of bacterial material (sex pili) Fimbrins, adhesins, pilins - capable of inducing a specific immune response Adhesins in pili may be species specific and some are capable of undergoing antigenic variation; avoid immune response and/or bind to different host cells Bacteria are constantly losing and reforming pili as they grow in the body and the same bacterium may switch the adhesive tips of the pili in order to adhere to different types of cells and evade immune defenses

Protoplast

Complete Removal of the cell wall of a Gram positive bacteria results in the formation of protoplasts, which lyses unless it is osmotically stabilized

Severe necrotizing fasciitis

Complication of S. aureus infection skin and soft tissue infection, starting acute/abrasions, very painful Caused by MRSA that produce Panton Valentine leukocidin (P-V leukocidin), the gene of which is located in lysogenic phage This toxin kills phagocytic cells - releasing their toxic contents. fast spreading, occur within 24 hrs of infection Mortality: About 30% Usually community acquired, thus known as CA-MRSA . Occur within the first 24 hours of infection. They often include a combination of the following: Increasing pain in the general area of a minor cut, abrasion, or other skin opening. Pain that is worse than would be expected from the appearance of the cut or abrasion. Redness and warmth around the wound, though symptoms can begin at other areas of the body. Flu-like symptoms such as nausea, fever, dizziness, weakness, diarrhea, and general malaise.

Gram Negative Cell Wall

Components: Outer membrane: Phospholipid bilayer Lipopolysaccharide ( LPS) Porins proteins Lipoprotein Thin layer of peptidoglycan Periplasmic space: contain enzymes, such as nutrient transport enzymes

Satellite/defective viruses

Composed of protein and nucleic acid Mutation or deletion of part of their genome makes dependent on other viruses for replication Adeno-associated virus - replicates only in cells infected with adenovirus Delta agent - naked strand of RNA expressed only in the presence of hepatitis B virus

Peptidoglycan Monomer

Composed of: NAM: N-acetylmuramic acid NAG: N-acetylglucosamine * L-lysine could be replaced by another amino acid; D-aminopimelic acid (unique to bacteria) Unique to bacteria are NAM D forms of aa and D-aminopimelic acid Lysozyme: breaks the glycosyl bond - the bond that joins the two sugars Synthesized in the cytosol of the bacterium where they attach to a membrane carrier molecule called bactoprenol

Genus Streptococcus

Consists of several species which are medically important Gram positive cocci, Catalase negative, in chains or pairs Important features used to subgroup the genus include Hemolytic patterns: alpha, beta and gama Serologic properties: Lancefield grouping based cell wall carbohydrate antigen, 20 groups (A-H and K-V) but now primarily used for A-G Antibiotic sensitivity profile - bacitracin and optochin Biochemical properties Streptococcus pyogenes Streptococcus pneumoniae These two species of Streptococcus cause RT infections.

Bacterial growth curve

Consists of the following phases: I. Lag phase: No appreciable multiplication of cells although they may increase considerably in size and show marked metabolic activity (total count remains same) This initial period is the time required for adaptation to the new environment during which necessary enzymes and metabolic intermediates are built up in adequate quantities for multiplication to proceed II. Log or exponential phase: Cells start dividing by binary fission and their number increase exponentially or by geometric progression with time Linear relationship between time and the logarithm of no. of cells Cells at this phase are smaller and stain uniformly Many antibiotics are effective at this stage III. Stationary phase: Cell division comes to halt due to depletion of nutrients and accumulation of toxic products The no. of progeny cells formed is just enough to replace the no. of cells that die Viable count remains stationary (However, total count is more) Cells are Gram variable and show irregular staining Sporulation occurs at this stage Also, many bacteria may produce exotoxins. IV. Phase of decline: Decrease in population due to death of cells Cause may be: nutritional exhaustion, toxic accumulation, action of autolytic enzymes etc. Involution forms (irregular, atypical form) are common

Paramyxoviridae

Contains three genera, some cause RT infections Paramyxovirus: parainfluenza and mumps Pneumovirus: respiratory syncytial virus and metapneumovirus Morbillivirus: measles Paramyxoviridae are enveloped, negative sense ssRNA viruses Non segmented RNA, helical nucleocapsid F peplomer for fusion. Replication is like other negative sense ssRNA viruses Envelope of paramyxovirus seems to be fragile, distorted on images

Diagnosis of GBS

Culture on blood agar Beta hemolytic, weaker than GAS Bacitracin resistant Lancefield grouping: B CAMP test- positive produce a diffusible, extracellular compound that will, in conjunction with a specific beta-hemolysin of Staphylococcus aureus, cause complete lysis of sheep red blood cells in an agar medium. Hydrolyse hippurate action of the enzyme hippurate hydrolase, can hydrolyse sodium hippurate to benzoic acid and glycine. DNA probe : PCR for rapid diag.

Pathogenesis of Coronavirus

Conventional type limited to upper respiratory tract - (optimum temp 33-35 0C). SARS - Cov: infects and kills alveolar cells (receptor-ACE 2) MERS-Cov: nonciliated bronchial epithelial cells (Receptor-CD 26) Clinical disease: Common Cold: 2nd to rhinovirus (10-15%) and long IP (3 days) SARS-CoV: Severe acute respiratory syndrome A form of atypical pneumonia High fever (>380 C), chills, rigor, cough, difficulty breathing, myalgia 20% may have diarrhea China, spread to the world by travelers, 8098 cases, 774 deaths (≈10% mortality) MERS-CoV: more severe complications than SARS-CoV: ARDS + renal failure/ multi-organ failure, diarrhea Mortality rate 30% (higher in patients with underlying cond.

Regulation of Gene Expression

Coordinated gene expression may be obtained by I. Operons: Clusters of co-regulated genes: with a promoter, operator and structural genes Operons could be Inducible or Repressible II. Sigma factor: a protein for initiation of RNA synthesis III. Quorum sensing: gene expression depends on population size Most metabolite regulatory mechanisms involve control of transcription of the gene into messenger RNA, rather than control of translation of the messenger RNA In order to adapt quickly and effectively to changes, bacteria have developed mechanisms to coordinate and regulate the expression of multicomponent genes. Quorum sensing is the regulation of gene expression in response to fluctuations in cell-population density.

Pathogenesis of Dracunculiasis

Creation of vesicles and ulcers in the skin (Most commonly lower body parts; Also seen in arms, trunk, buttock, scrotum, head, neck and female breast) Site of ulceration-erythema, pain and allergic reaction Complications: Abscess formation and secondary bacterial infection Resulting in tissue destruction and sloughing of skin Generalized infection (sepsis) Joint infections (septic arthritis) that can cause the joints to lock and deform (contractures) At the site where worm dies- calcification and nodule formation

Clinical findings of Parainfluenza virus

Croup, Laryngotracheobronchitis Usually Causes mild cold-like upper respiratory infections May extend to larynx, trachea and bronchial tree causing croup, bronchiolitis, and even pneumonia Type 3: most commonly isolated from children with LRTI in US Type 1 and 2: major causes of croup Croup: breathing difficulty, hoarseness, A sharp SEAL BARK cough, due to subglottal swelling of the airway; Inspiratory stridor Symptoms worse on Laying down Can be life threatening

Diagnosis of Genital Mycoplasma

Culture on A8 agar, "fried egg" : enriched media Yeast extract and horse sera: source of sterol Isolation of U. urealyticum /M. hominis may have little value - as they are part of the normal flora, Other possible causes of urethritis and cervicitis should be ruled out. Treatment: Doxycycline

Diagnosis and treatment of P. aeruginosa

Culture on blood agar or enteric media MacConkey agar- grey colonies - non-lactose fermenter Oxidase positive: presence of cytochrome C oxidase On colorless media, produce pigments, blue, green-yellow mucoid colonies and fruity odor Treatment: Multidrug resistance common; inherent resistance. Combination of antibiotics: anti-pseudomonal Beta lactams plus aminoglycosides or fluoroquinolones Prevention: Hospital Infection Control, Chlorination of hot tubs

Diagnosis of Campylobacter

Culture on selective media: Campy-BAP or Skirrow media contain antibiotics , vancomycin, polymyxin B and trimethoprim, that reduce the growth of other enteric microorganisms. Microaerophilic and grow best 42oC; Antigen detection; from stool immunoassay Treatment: Supportive for diarrhea: usually self limited. Antibiotics when deemed necessary (if symptoms persist more than a week and severe). Antibiotic recommended for systemic infection; resistance uncommon Prevention: Food and water safety; pets - make it difficult to control.

Pure Culture

Culture with only one type of microbe. Pure culture techniques : several Streak plate: most commonly used

Diagnosis of Strep Pharyngitis

Culture: Throat swab, beta-hemolytic on blood agar, bacitracin sensitive, catalase negative, Gram positive cocci in chains Lancefield grouping - slide agglutination - group A antigen Rapid Strep antigen detection - ELISA Throat swab sample These tests use monoclonal antibodies to detect the streptococcal group A cell wall carbohydrate antigen. specificity - around 95% sensitivity - 70-90%) takes about 15 minutes

Lab Diagnosis of EHEC

Culture: on Sorbitol MacConkey agar E . coli O157:H7 is non sorbitol fermenter- grey colonies other E. coli ferment sorbitol - pink colonies Detect shiga toxin - on cell culture : destruction of cells - Or ELISA

Diagnosis of Haemophilus influenzae

Culture: Chocolate agar-Tiny, gray colonies; : Blood agar with S. aureus streak - Satellite growth Antigen Detection: latex agglutination- Rapid PRP capsular antigen for H. influenzae type b only Specimens recommended: Direct needle aspirate in case of otitis or sinusitis Sputum in pneumonia Blood in epiglottitis, cellulitis and arthritis Blood/CSF in meningitis

Diagnosis of Rheumatic fever

Cultures are usually negative in rheumatic fever Diagnosis based on serological findings + clinical presentation (see next slide) - Jones Criteria A rise in the titer of antibodies to several extracellular products of Group A strep (UPPER LIMIT OF NORMAL TITER) The most commonly used is detection of antibodies against streptolysin O (ASO)- one of the hemolysins

Ecthyma gangrenosum

Cutaneous manifestation of severe, invasive infection Usually among immunocompromised and critically ill patients Erythematous vesicles changing to hemorrhagic, necrotic and ulcerated form Presents as a round or oval lesion, 1 cm to 15 cm in diameter, with a halo of erythema. A necrotic center is usually present with a surrounding erythematous edge, representing where the organism invades blood vessels and causes infarctions

Lepromatous Leprosy

Cutaneous nodular lesions associated with areas of sensory loss and concurrent upper respiratory congestion. Widespread dissemination due to specific immune anergy Involvement of the nasal mucosa may lead to crusting, obstructed breathing and epistaxis (nose bleed) Ocular involvement leads to iritis and keratitis Lepromin skin test negative T cell anergy; B cells responsive

Entamoeba histolytica: life cycle

Cysts and trophozoites are passed in feces . Cysts are typically found in formed stool, whereas trophozoites are typically found in diarrheal stool. Infection by Entamoeba histolytica occurs by ingestion of mature cysts in fecally contaminated food, water, or hands. Excystation occurs in the small intestine and trophozoites are released, which migrate to the large intestine. The trophozoites multiply by binary fission and produce cysts, and both stages are passed in the feces. Because of the protection conferred by their walls, the cysts can survive days to weeks in the external environment and are responsible for transmission. Trophozoites passed in the stool are rapidly destroyed once outside the body, and if ingested would not survive exposure to the gastric environment. In many cases, the trophozoites remain confined to the intestinal lumen (: noninvasive infection) of individuals who are asymptomatic carriers, passing cysts in their stool. In some patients the trophozoites invade the intestinal mucosa (: intestinal disease), or, through the bloodstream, extraintestinal sites such as the liver, brain, and lungs (: extraintestinal disease), with resultant pathologic manifestations. It has been established that the invasive and noninvasive forms represent two separate species, respectively E. histolytica and E. dispar. These two species are morphologically indistinguishable unless E. histolytica is observed with ingested red blood cells (erythrophagocystosis). Transmission can also occur through exposure to fecal matter during sexual contact.

Giardia lamblia: life cycle

Cysts are resistant forms and are responsible for transmission of giardiasis. Both cysts and trophozoites can be found in the feces (diagnostic stages) . The cysts are hardy and can survive several months in cold water. Infection occurs by the ingestion of cysts in contaminated water, food, or by the fecal-oral route (hands or fomites) . In the small intestine, excystation releases trophozoites (each cyst produces two trophozoites). Trophozoites multiply by longitudinal binary fission, remaining in the lumen of the proximal small bowel where they can be free or attached to the mucosa by a ventral sucking disk. Encystation occurs as the parasites transit toward the colon. The cyst is the stage found most commonly in nondiarrheal feces . Because the cysts are infectious when passed in the stool or shortly afterward, person-to-person transmission is possible. While animals are infected with Giardia, their importance as a reservoir is unclear.

Membrane Disrupting Toxins

Cytolysins /cytolytic toxins Promote leakage of water and ions, disrupting cell function or cell lysis Two actions: 1. Pore (channel) former Eg, Streptolysin O produced by Streptococcus pyogenes 2. Destruction of phospholipid bilayer Eg. lecithinase (alpha toxin) produced by Clostridium perfringens (gas gangrene) Some are known Hemolysins, leukocidins Some are known as RTX or CDC pore formers RTX - because they have repeats of amino acid sequence CDC - cholesterol dependent cytolysins

Diagnosis of Ancylostoma caninum & braziliense

Demonstration of larvae in skin biopsy Along with clinical appearance of tunnels and history of contact with dog and cat feces

Diagnosis of Onchocerciasis

Demonstration of microfilariae in skin snips or blood Usually skin snips is taken from the infrascapular or gluteal region. Sample is obtained by raising the skin with a needle and shaving the epidermal layer with a razor. The specimen is incubated in saline for several hours and is then observed in dissecting microscope for the presence of non sheathed microfilariae

Diagnosis of Cystoisospora belli

Demonstration of oocyst (Approx.25 × 15µm) Concentrated stool specimens and Iodine mount or Modified Acid fast stained smears

Laboratory Diagnosis of Cyclospora cayetanensis

Demonstration of oocysts by Modified Ziehl-Neelsen (acid-fast) staining of formol-ether concentrated stool samples The oocysts are variably acid-fast. Demonstration of autofluorescence: The oocysts are refractile spheres which exhibit blue autofluorescence under ultraviolet light. Molecular: PCR

Diagnosis of Naegleria fowleri

Demonstration of organism in sterile tissue or fluid (CSF, nasal discharge) Detection of trophozoite by: Wet mount: live motile trophozoites Staining: Giemsa-staining, H & E staining or Florescent staining PCR Culture in a plate covered in bacteria, at 420 C The amoebae can be grown in culture to increase the likelihood of detection

Diagnosis of Acanthamoeba castellani

Demonstration of parasite in corneal scraping/CSF/biopsy from Sinus (H&E stain) Culture: Xenic and axenic culture Treatment: miltefosine Prevention & Control Proper care of eye lenses Steps to prevent GAE: unclear

Diagnosis of Diphyllobothrium latum

Demonstration of proglottids & bile stained operculated eggs (with knob) in stool Operculum - lid/covering opened at maturity

Diagnosis of Toxoplasma gondii

Demonstration of the organism as trophozoites/ cysts in tissues and body fluids: definitive method of diagnosis A. Trophozoite (Tachyzoite) stage: typically crescent shaped with a prominent, centrally placed nucleus B: Toxoplasma gondii cyst (Bradyzoites) in brain tissue stained with hematoxylin and eosin (100×). C: Zoom of Image B, T. gondii cyst Serology: Toxoplasma gondii Serologic profile (TSP): measure IgM, IgG, IgA and IgE To diagnose congenital toxoplasmosis Amniotic fluid (obtained by Amniocentesis): PCR- test of choice during prenatal (before birth) diagnosis Detection of IgM and IgA antibodies in new born

Heavy metals

Denature proteins Silver nitrate: used to prevent eye infection in new born babies from gonococcal infections

Aldehydes

Denature proteins and modify nucleic acids Glutaraldehyde: in 2% solution (Cidex) used as sterilant for heat sensitive instruments Formaldehyde - disinfectant, preservative; toxicity limits use formalin - 37% aqueous solution

GI Clinical Syndromes

Dental plaque - Streptococcus viridans group Stomatitis: - Inflammation of the mucosal surfaces of mouth, the lips and the tongue; etiologic agents were discussed with skin and soft tissue infections) Thrush - Candida albicans Cheilitis - Candida albicans Herpangina - Coxsackie group A Oral herpes - Herpes simplex virus Inflammation of the salivary glands Mumps - mumps virus Esophagitis: Candida albicans, herpes simplex virus and cytomegalovirus (will be present with STD) Peptic and duodenal ulcer: Helicobacter pylori

Bacterial Cell Group Arrangement

Depends on the line of consecutive cell divisions and the tendency of daughter cells to remain attached to each other after cell division

Rifamycin

Derivatives: Rifamycin, Rifampin/Rifampicin, Rifabutin Mechanism of Action Inhibits DNA-dependent RNA polymerase - prevents RNA synthesis Pharmacology Bactericidal, Broad spectrum Mycobacterium tuberculosis, Gram positives, some Gram negatives (but not all) Mechanism of Resistance Alteration of RNA polymerase

Lincosamides

Derivatives: Clindamycin (mainly), Lincomycin Mechanism: bind to the 23S rRNA of the 50S ribosomes and cause premature dissociation of the peptidyl-tRNA Bacteriostatic: effective against Gram positive cocci and against Gram -ve anaerobes. Inactive against Gram negative aerobes Resistance: methylation of the 23S rRNA Side effects: suppression of normal flora of GIT increases the risk of Clostridium difficile colitis

Carbapenems

Derivatives: Imipenem, meropenem Mechanism of action: Inh. cell wall synthesis Pharmacology: Bactericidal, broadest spectrum compared to penicillins and cephalosporins, Effective - Gram negative and positives; and also strict anaerobes Active against most beta-lactamases producing organisms including Extended spectrum beta-lactamase producers 'Drugs of last resort' against bacteria resistant to multiple antibiotics Resistance: Enzymatic inactivation by Carbapenemase (a form of beta-lactamases); resistant Gram negative rods on the increase. Klebsiella pneumoniae and Escherichia coli Strains are Multidrug resistant Outbreak with CRE in US in 2015

Quinolones and fluoroquinolones

Derivatives: several Nalidixic acid - original drug not in use any more, resistance high Ciprofloxacin, Ofloxacin, Norfloxacin, Mechanism of Action Inhibits bacterial DNA topoisomerases II (gyrase) and topoisomerases IV. Topoisomerases are required for DNA replication, recombination and repair. Fluoroquinolones are derivatives of the Quinolones because they have fluorine . Not recommended for children and pregnant women, affects bone and cartilage. Pharmacology: Bactericidal - broad spectrum Oral administration Mechanisms of Resistance Alteration of target site: bacterial DNA gyrase/topoisomerases Decreased permeability: Alteration of outer membrane proteins Export through efflux pumps

Microscopy of syphilis

Detection of the spirochete (primary/secondary) Dark field microscopy: unstained live spirochetes Bright field microscopy: Silver staining technique Direct immunoflourescence (DFA-TP) - highly specific

Diagnosis of BK Virus

Detection of virus may take the several months after transplant Urine sample: urine cytology, infected cells (decoy cells) with intranuclear inclusion bodies Renal biopsy ; cytopathic changes - not specific Needs to be confirmed immunohistochemical stains, in situ-hybridization, PCR Treatment: decrease immunosuppression as much as possible without causing rejection cidofovir (nucleotide analog) may help Prevention: Unknown

Immunodiffusion test

Detects precipitating antibodies by forming two bands: M and H Presence of both the H and the M band indicates active histoplasmosis. The presence of the M band alone indicates early or chronic disease The main components of HMIN to which antibody responses occur are the C, M, and H antigens. The C antigen is a carbohydrate (galactomannan) that is largely responsible for the cross-reactions observed with other fungal species . The M antigen is a catalase and the H antigen is a β-glucosidase. Due to their higher specificity to H. capsulatum, antibodies against the M and H antigen are particularly useful in diagnosis.

Guaiac test

Detects the presence of fecal occult blood (blood invisible in the feces). Occult blood in the stool indicates gastro intestinal bleeding that may be because of Helminth infestation (e.g, hookworm infection), colon cancer, polyps (abnormal growths) in the colon/rectum etc Principle of the test: When the hydrogen peroxide is dripped on to the guaiac paper (containing alpha-guaiaconic acid), it oxidizes the alpha-guaiaconic acid to a blue colored quinone. Normally, when no blood and no peroxidases or catalases from vegetables are present, this oxidation occurs very slowly. Heme, a component of hemoglobin if present in the sample, catalyzes this reaction, giving a result in about two seconds. A quick and intense blue color change of the film indicates positive test.

Rubella virus diagnosis and treatment

Diagnosis : Clinical presentation of German Measles; Molecular: Detection of viral RNA by RT-PCR Serology: Best Identification is by Serology (IgM) or four fold increase of IgG in paired sera (Acute & Convalescent) Treatment: Supportive- antipyretics and fluids as indicated

Diagnosis and Treatment of Staphylococcus aureus intoxication

Diagnosis: Normally a clinical diagnosis and history. ELISA to detect toxin in food, vomitus. (for outbreaks) Treatment: Rehydration, self-limited, not infection - toxin Prevention: Education of food handlers Proper cooking/storage of foods; Reheating food does not help Food handlers with opens hand wounds should either cover them completely or be excused from food preparation; Anyone with upper respiratory infections should be excused from food preparation/handling

Jones Criteria for Rheumatic fever

Diagnosis of initial attack of rheumatic fever : Carditis (mitral valve most commonly affected) Polyarthritis- inflammation in large joints starting with legs and moving to arms, transient (3 days per joint, and 3 weeks total) Sydenham's Chorea - non rhythmic involuntary movement Erythema marginatum - Non-pruritic erythematous rings on trunk, transiently appear and disappear over months Subcutaneous Nodules - Small painless nodules on extensor surfaces Arthralgia - joint pain Elevated Sedimentation Rate (ESR) The normal sedimentation rate (Westergren method) for males is 0-15 millimeters per hour, females is 0-20 millimeters per hour. If the ESR is elevated, it is typically a result of globulins or fibrinogens Elevated acute phase reactants, C-Reactive Protein (CRP) Prolonged PR interval on Electrocardiogram (ECG)

Diagnosis and treatment of Dermatophytes

Diagnosis: Microscopy: (KOH prep) demonstrates conidia - macro/microconidia Wood's lamp test: UV lamp - around 365 nm Microsporum - positive for wood's test Not all dermatophytes fluoresce Culture: SDA, colonies- various types Identified by LPCP mount Treatment: Topical and oral antifungals

Diagnosis and treatment of Nocardia

Diagnosis: Microscopy: Multiple sputum specimens, pus from skin lesions: Gram and acid fast stains Acid-fast staining: weakly acid fast, not uniform i.e beaded appearance Culture: Grow on most media; Selective media-BCYE agar (on suspicion of contamination with normal flora) Slow growth, may take a week, Colonies are waxy, may look like MTB; aerial hyphae on colonies under dissecting microscope Treatment: trimethoprim-sulfamethoxazole -drug of choice. Prolonged treatment, up to 12 months Prevention: Proper wound cleansing and drainage for cutaneous infection.

Diagnosis and treatment of Clostridium perfringens

Diagnosis: Microscopy: Gram stain of smears of tissue and exudate samples (spores may not be seen from tissue): Gram positive rods, no inflammatory cells Culture: blood agar -anaerobic culture, double zone of hemolysis Detection of toxin (alpha toxin) in culture - in egg yolk agar - produce opacity of the media (Nagler reaction) Treatment: Surgical debridement and High dose penicillin, Hyperbaric oxygen Prevention: Proper wound care and judicious use of prophylactic antibiotics

Diagnosis and treatment of Actinomyces israelii

Diagnosis: Microscopy: organism unevenly distributed in the affected tissue - concentrated in Sulfur granules - After collection of granules - crush them between microscopic slides - Gram stain Culture: Anaerobic culture (Starch casein agar or Actinomycetes Isolation Agar): takes at least 2 weeks for growth: irregular, rough, colonies, white to yellow pigment, molar tooth appearance Treatment: Drainage or surgical debridement Penicillin G-drug of choice. (TREATMENT MUST BE SUSTAINED FOR WEEKS TO MONTHS) Prevention: Good dental hygiene, antibiotic prophylaxis before surgery

Diagnosis and Treatment of Candidiasis

Diagnosis: Microscopy: Wet mount (KOH) or Gram staining of scrapings/ swab demonstrate budding yeast/ pseudohyphae Culture Grow in most common bacteriological media - colonies look like bacterial colonies - round and smooth CHROMagar: differentiation among mixed species candida (e.g, C. albicans-green, C. tropicalis-blue colonies) Cornmeal agar: Chlamydospore formation: differentiates from other species Germ tube test: Inoculation into animal serum at 37 0C for 2hr: develop elongated germ tubes Treatment: Imidazoles (topical and oral), Nystatin; Amphotericin B for systemic disease

Diagnosis and Treatment of E. coli diarrhea

Diagnosis: Culture on differential media, Lactose positive, MacConkey, EMB, Biotyping requires several biochemical tests (API). Indole production use of acetate as carbon source Decarboxylates lysine Motility Immunoassay detect toxin: Treatment: Rehydration, self limiting in general Prevention: Food safety, personal and public hygiene

Diagnosis and Treatment of Acinetobacter baumannii

Diagnosis: Culture: grows well on Blood agar Identified biochemically Treatment: difficult, Multidrug resistance common. Some strains are resistant to all known antibiotics Prevention and control: Infection control procedures, such as hand hygiene and environmental cleaning

Treatment of Prions

Diagnosis: EEG (electroencephalogram), CT scan, MRI, brain biopsy - spongiform and amyloid. Western blot of brain tissue Treatment: Currently no specific treatment Prevention: Avoid exposure Proper sterilization of neurosurgical tools and electrodes Chemical sterilization 5% hypochlorite solution 1.0 M NaOH Autoclave (121 0C for 1 hrs) (Note: Prions not inactivated by Ordinary autoclaving!!!!)

Treatment of Coronavirus

Diagnosis: Labs-Usually not done for conventional CoV For SARS-CoV and MERS-Cov- use of RT- PCR; ELISA for antibodies Treatment: Interferon and Ribavirin - promising Prevention and Control: Care in covering mouths, isolation of infected patient, screening of travelers (contact with cases)

Diagnosis and treatment of Malassezia furfur

Diagnosis: Microscopy- KOH preparation of skin scrapping- yeast and occasional short mold; Also H & E stain and PAS stain Culture: Fungal media with olive oil (source of lipid), yeast like colony Treatment: spontaneous resolution, takes time Ketoconazole/other azoles, topical selenium sulfide

Diagnosis and treatment of HPV

Diagnosis: Microscopy: Pap Smear (scraping from the opening of the cervix) and demonstration of typical cytopathic effect in infected cells: Koilocytes with vacuolated cytoplasm - round and occur in clumps Molecular: PCR/DNA probe- method of choice Treatment: Cutaneous may be self limiting; May require removal by surgical excision, cryotherapy (freezing), electrocautery (heat using electricity) chemical removal: use of Podophyllotoxin (Podofilox)

Diagnosis and Treatment of Chromomycosis

Diagnosis: Microscopy: Detection of muriform cells (Sclerotic bodies, Medlar bodies), sometimes pigmented hyphae in tissue- (KOH or tissue stains like H & E stain) Muriform cells are divided by internal septation and appear as cells with vertical and horizontal lines within the same or different plane Muriform cells (Sclerotic bodies, Medlar bodies) are found -extracellularly or within macrophages/giant cells in tissues Culture: Grow as mold (with annelids) or as yeast Treatment: Itraconazole/terbinafine

Diagnosis and treatment of Propionibacterium spp

Diagnosis: By Culture- growth on common media (2-5 days) Treatment: Topical Benzoyl peroxide; Erythromycin/clindamycin Benzoyl peroxide has a bactericidal effect on Propionibacterium acnes associated with acne and does not induce antibiotic resistance

Diagnosis and Treatment of C. perfringens gastroenteritis

Diagnosis: Clinical and history. Lab test usually not done. Isolation of pathogen from suspected food. Lab. Test - since Clostridium perfringens, is part of the normal flora - Isolation of this pathogen from the stool of a patient is not helpful in diagnosis. The toxin may also be produced in large intestine and a person may not show symptoms - as the toxin affects the small intestine, which happens when a person ingests the organism and they multiply in the small intestine. Treatment: Supportive care, antibiotics not indicated. Prevention: Refrigeration to prevent the bacteria from proliferating or production of enterotoxin Adequate reheating to kill vegetative cells and destroy the toxin.

Smallpox diagnosis and treatment

Diagnosis: Clinical presentation and history of- exposure/no vaccination; biopsy to demonstrate inclusion bodies (Guarnieri bodies-intracytoplasmic) in infected cells; DFA and PCR Treatment: Symptomatic relief, passive immunization

Diagnosis and Treatment of Noroviruses

Diagnosis: Clinical; Electron microcopy, Molecular - RT-PCR, serology to detect viral antigen , ELISA; Treatment: No specific antiviral treatment; prevent dehydration with ORF; disease self-limiting Prevention: Hand washing; sanitation, disinfect contaminated surfaces after outbreak, Resistant to 60oC, pH 3, detergent and even chlorination. Asymptomatic shedding -makes prevention difficult Immunity not long lasting, re-infection or infection with another genotype

Diagnosis and Treatment of Sporotrichosis

Diagnosis: Culture at 25 oC and 35-37 oC-growth in 2-5 days Confirmation by subculture at 37 oC (mold to yeast) or exoantigen test Treatment: Drug of choice: Itraconazole

Diagnosis and treatment of Vibrio vulnificus

Diagnosis: Culture: Grows on blood agar, MacConkey agar. Special selective media: TCBS (Thiosulfate Citrate Bile Salts Sucrose) agar- blue-green colonies Treatment: Doxycycline and a third-generation cephalosporin Prevention: avoid wound exposure to seawater and proper cooking of seafood.

Diagnosis and Treatment of Eumycotic Mycetoma

Diagnosis: Differentiation from actinomycotic mycetoma essential Clinical: gives some clues (Next slide) Laboratoy Microscopy: Examinn of grains/granules by KOH or tissue stains Culture: in fungal media for definitive identification Treatment: difficult; Terbinafine/voriconazole; May need amputation

Diagnosis and Treatment of Rotaviruses

Diagnosis: For outbreaks - ID of the virus in the patient's stool EIA or latex agglutination for antigen RT-PCR to detect and identify strains rotaviruses Treatment: no antiviral drug Passive immunity for children with immunodeficiency: rotavirus-specific immunoglobulin preparation, administered orally to decrease shedding and ameliorate disease Prevention: hygiene; hand washing; Vaccine: 2 types : Recombinant attenuated live vaccines RotaTeq (2006) and Rotarix (2008)

Diagnosis and Treatment of myiasis

Diagnosis: Generally by clinical findings Laboratory needed only for confirmation of larvae Treatment: Surgical removal: most common mode of treatment Manual extraction of larvae Petroleum jelly: Anoxia induces larvae to migrate to surface Prevention: Limiting exposure to flies Wearing long sleeved clothes, mosquito netting, insect repellants

Treatment of coxsackievirus

Diagnosis: Mainly on clinical presentation Isolation of virus in cell culture or suckling mice Treatment: Symptomatic, Self limiting - takes 4-7 days Prevention: no vaccines. Proper hygiene, such as boiling of eating utensils and other items that touch the mouth or saliva of an infected person or using disposable utensils.

Measles diagnosis and treatment

Diagnosis: Mostly Clinical presentation Respiratory specimens and blood Detection of virus: DFA, RT-PCR Serology: Detection of IgM or 4 fold increment of antibody titre between acute and convalescent sera Treatment: Supportive: antipyretics and fluids

Diagnosis and Treatment of Bacillus cereus

Diagnosis: Normally a clinical diagnosis and history Toxin detection: stool, food Culture: isolation of B. cereus from food, Treatment: Self Limiting; Rehydration Prevention: Proper cooking/storage of foods; education of food handlers

Treatment of Tetanus

Diagnosis: Primarily on the basis of clinical presentations. Culture and toxin detection: low sensitivity Treatment: Surgical debridement; Metronidazole Passive immunization with Antitoxin; Supportive; Prevent muscle spasm (spasmolytic drug such as diazepam) Prevention: Adequate wound cleansing; Passive immunization (human tetanus immunoglobulin): post exposure Active vaccination: Tetanus toxoid (TT): Childhood: conjugated with diphtheria toxoid and pertussis (DTaP), 5 doses 2, 4, 6 and 15-18 months, a booster dose at 4-6 years-highly effective. Neonatal - TT vaccination during pregnancy/child bearing age women

Diagnosis and treatment of Bacteroides fragilis

Diagnosis: Specimens-abscess fluid, wound swab Gram stain: weak Gram negative appearance, can be missed Culture: Anaerobic culture, special media with 20% bile salt, Esculin and gentamicin Bacteroides Bile Esculin agar (BBE)-enriched, differential and selective media Esculin - gets hydrolized to give black coloration Gas chromatography to identify the fatty acids produced by B. fragilis Treatment: Metronidazole is drug of choice. Antibiotics with the best activity against gram negative anaerobes are Metronidazole, Carbapenems and Beta-lactam-Beta lactamase inhibitors (eg. Piperacillin-Tazobactam) Produce beta-lactamases: - Anaerobic infection are usually polymicrobial, more than one antibiotics are used. Wound drainage and hyperbaric oxygen Prevention: Prophylactic antibiotics- Metronidazole prior to surgery involving the abdominal and pelvic regions

Diagnosis and treatment of Klebsiella pneumoniae

Diagnosis: Sputum - Gram stain, Culture and biochemical identification. Pink colonies on selective and differential media - MacConkey - lactose fermentation Treatment: very difficult due to antibiotics resistance, multidrug resistance common; 3rd gen ceph + Aminoglycoside Prevention: proper infection control practices.

Parvovirus (B19 Virus) diagnosis and treatment

Diagnosis: Usually based on clinical presentation; Viral detection: PCR, Serology: IgM and IgG by ELISA Treatment: No specific antivirals Supportive in healthy person. Blood transfusion for aplastic anemia Prevention: No vaccine available Infection provides long lasting immunity

Treatment of Rhinovirus

Diagnosis: by clinical presentation; lab diagnosis rarely done Viral isolation: from pharyngeal swabs, saliva, and nasal aspirates. Serology can be used to confirm the virus as the cause of infection and for the assessment of immune status. Are grown in human diploid fibroblast cell lines Treatment Usually self-limited No antiviral drugs effective Relieve symptoms-Nasal vasoconstrictors; Nasal decongestants: eg. Pseudoephedrine, phenylephrine, Naphazoline etc. Inhalation of HOT STEAM Control: Hand washing and disinfection practice No vaccine- many serotypes

Diagnosis and Treatment of Botulism

Diagnosis: clinical symptoms; history, detection of toxin in patients sera and/or left over suspected food. For babies - stool can be a good source of the toxin Treatment: Supportive care, ventilatory support. Passive immunization antitoxin ( types A, B, E) Antibiotics for wound infection Antibiotics not recommended for infants, as it may worsen Prevention: Proper preparation and packing of canned food, Heating of canned food before eating to inactivate toxin. Do not feed honey to infants Every case of foodborne botulism - is treated as public health emergency, because the responsible food might still be available for consumption

Lab Diagnosis of E. faecalis/faecium

Diagnosis: culture and biochemical test Bile Esculin slant/agar) - hydolysis of esculin and bile resistance - turns media black Bacitracin resistance Lancefield Group D positive PYR + pyrolidonyl arylamidase grow in 6.5% NaCl and 40% bile Treatment:. Dual treatment with aminoglycosides and a cell wall active antibiotics. Resistance is increasing: via plasmid gene, Resistance very common including vancomycin (VRE) Prevention: Restricted use of antibiotics, proper infection control practices

Diagnosis and treatment of Leprosy

Diagnosis: most commonly based on C/F; Confirmation by lab: Samples from diff. sites- Slit skin smear (SSS): collect tissue pulp Microscopy -Acid fast staining: Acid fast bacilli in dermal macrophages Lipid laden macrophages- 'foam cells' Skin and nerve biopsy Culture - Not possible Serology: IgM against phenolic glycolipid-1 (not for tuberculoid) Lepromin test (Intradermal injection)- Skin Test: Useless in lepromatous form Treatment: Dapsone + rifampin for tuberculoid; Clofazimine added for lepromatous Prevention: Isolation of lepromatous patients; chemoprophylaxis with dapsone for exposed children

Pathogenesis of Yersinia

Diarrhea (watery/bloody) inflammatory, fever, may last for 1-2 weeks, may become chronic Mesenteric adenitis: Infection of mesenteric lymph nodes, causing severe abdominal pain lower right quadrant mimicking appendicitis, Enteric fever: Prolonged fever/systemic infection associated with diarrhea Complications: Reiter's syndrome: reactive arthritis of peripheral joints/HLA-B27 Diagnosis: stool culture, "cold enrichment" or 2-4 weeks. Samples kept of refrigeration temp - increase in number Treatment: Diarrhea - self-limited - no antibiotic, patients with under lying disease - antibiotics recommended to avoid enteric fever

Non-Inflammatory Diarrhea

Diarrhea ± vomiting -Watery diarrhea - often large volume, usually with out blood -No fecal lymphocytes -Abrupt onset, brief duration, -Fever and systemic symptoms usually are absent -Enterotoxins that affect function epithelial cells in the small intestine -Microbial adherence/superficial invasion affecting cell function directly or via action of induced cytokines -Proximal small bowel mainly Bacteria Escherichia coli ETEC, EPEC, EAEC Vibrio spp Protozoan Giardia lamblia Cryptosporidium parvum Cyclospora cayetanensis Isospora belli Viruses Norwalk virus Rotaviruses Adenovirus Astrovirus

Stoke's Method

Diffusion test Müeller-Hinton agar plate is inoculated by streaking the control strains evenly across the upper and lower thirds of the plate,and the test strains between the control ,leaving a distance of not more than 5mm on each side of the control strain. Measure the radius of the inhibition zone from the edge of the disc to the edge of the zone. Sensitive (S): Zone radius is wider than or equal to,or not more than 3mm smaller than the control. Intermediate (I): Zone Radius is > 2 mm but smaller than the control by > 3mm. Resistant (R): No zone of inhibition or zone radius measures 2mm or less

Kirby-Bauer method

Diffusion test Place paper disks impregnated with known conc. of antibiotics on a smear of culture on semisolid/solid media (eg, MHA: Mueller-Hinton agar), measure zone of inhibition in mm The size of the zone is compared with standard zone of inhibition to determine the sensitivity of the organism to that drug Report as: Resistant (R) -equal to or less than 14 mm Intermediate (R) -15-16 mm Sensitive (S)- equal to or more than 17mm Zone of inhibition measured in the test is compared with the standard given by CLSI guidelines Cheap, easy, but not quantitative

Gram Staining

Differential Staining A process by which components of bacterial cell walls are bound to Gram's stain. Depending on the amount of peptidoglycan in their cell walls, bacteria stain differently and are classified as Gram-negative or Gram-positive.

Diagnosis of Chlamydophila pneumoniae

Difficult Direct detection from clinical specimen- not sensitive. Does not get stained with tissue staining, DFA not sensitive Culture: Grow in HEp-2 cell line (not available in all lab) DFA staining to detect inclusion bodies in infected cells Nucleic acid testing: available, but not well established Serology: best method. Microimmunofluorescence (MIF - indirect immunofluorescent assay), or Complement fixation test Detect single IgM titre (> 1:16) or four fold increase in IgG titre

Virulence of Corynebacterium diphtheriae

Diphtheria toxin (DT): A-B exotoxin Gene carried by Phage (Beta) - lysogenization Binds to heparin-binding epidermal growth factor (HB-EGF) found on many cells, such as respi. epthelial, heart and nerve cells Inhibits protein synthesis via ADP ribosylation/ inactivation of EF-2 Regulation via DTxR (iron dependent repressor) protein on the chromosome which responds to tissue iron levels Low levels of iron: the protein de-represses toxin gene - toxin production High levels of iron: the protein is activated and represses the gene - no toxin production De-represses: removes repression i.e, in other words, LOW IRON LEVELS - TOXIN PRODUCED HIGH IRON LEVELS - TOXIN NOT PRODUCED

Coxsackie Virus & Echoviruses Pathogenesis

Disease: Aseptic meningitis, upper respiratory infections, febrile illness with/out rashes. Responsible for 90% of all viral meningitis Other diseases: Cox A: vesicular lesion - herpangina, hand-foot-mouth disease Cox B: Myocardial and pericardial infections: severe/fatal Bornholm disease (chest muscle): self-limited Cox A and B polio-like paralytic disease

Flies

Disease: Myiasis (caused by larvae/maggots): Transmission: Deposition of eggs which hatches to larvae Directly on wounds/abrasions or nostrils, conjunctiva, lips and even on unbroken skin Via mosquitos (eg. Bot fly) Specific myiasis: by flies which require a host for larval development eg. Human botfly: Dermatobia hominis Epidemiology: Worldwide, Tropical areas Infects humans as well as many animals

Superficial Mycoses

Diseases: -Pityriasis versicolor (Tinea versicolor) (most common superficial fungal infection in USA): by Malassezia furfur -Tinea nigra: by Hortaea werneckii -White piedra: by Trichosporon spp. -Black piedra: by Piedraia hortae

Pathogenesis of BV

Disruption of the balance between the normal flora resulting in an overgrowth of certain bacteria Clinical manifestation: White/gray vaginal discharge with milk-like consistency, unpleasant odor (gets stronger after having sex), minimal pre-vaginal itching or irritation Complications: pregnancy, increased preterm delivery, increases risk to STD, PID

Lyme Disease Secondary stage

Disseminated stage - IP: several months to years later Spirochetes move to the skin, nervous system, heart and Joints Multiple skin lesions (Additional EM rashes on other areas of the body) Arthralgia/Arthritis (60%) Cardiac complications (5%) Neurologic (10-20%) aseptic meningitis, cranial nerve palsy (Bell's palsy): Bilateral (highly suggestive)

Antibiotics and the colon

Disturbance of normal flora with antibiotic treatment leads to proliferation of antibiotic resistant members: Enterococcus spp Pseudomonas spp Candia spp Clostridium difficile : spore former- causes pseudomembranous colitis

Pathogenesis of TB

Does not produce exotoxin & endotoxin, has no capsule Survive inside macrophages by: preventing formation of phagolysosome (fusion of phagosome and lysosomes): by exported repetitive protein (ERP); and sulfatides and sulpholipids that hydrolyze into sulfuric acid preventing oxidative killing Primarily affects the lungs but may spread to other organs Upon first exposure to the bacilli a person has no specific immunity Inhaled bacteria are nonspecifically taken up by alveolar macrophages (innate immunity) The bacteria resist intracellular killing inside macrophages The infected macrophages secrete IL-12 and TNFα which recruit inflammatory cells Infected macrophages present the antigen to T lymphocytes Differentiation of Th to Th1 occurs Th1 secrete INF-gama which activates the macrophages to kill the bacteria Progression to active disease depends on infectious dose and the host's immune competence No disease: In the majority cases (about 90%) the infection may be arrested within the granuloma. Bacteria eliminated Primary infection: bacterial replication is not arrested Miliary tuberculosis: tubercle lesion may rupture, bacteria spread to several organs, extra-pulmonary tuberculosis Latent infection: bacteria remain viable in the granuloma Secondary infection: An impairment of the immune system may cause reactivation of TB from a granuloma and the bacteria spread to other part of lung and miliary tuberculosis

Echinococcus granulosus

Dog tapeworm Epidemiology: worldwide; Definitive host: dog (commonly) Intermediate host: sheep, human (Human is an accidental host) Transmission: Fecal-oral: food, water, fingers contaminated with dog's feces Morphology: Eggs, larvae and Adult Adult-only three proglottids, in the intestine of dogs, Larvae in tissue of sheep/human: big fluid filled cyst (hydatid cyst)

Plasmodium Species Differentiation

Done on Thin Films P. falciparum: infects RBC of all ages P. vivax and P. ovale: young RBCs P. malariae: old RBcs P. falciparum demonstrates no selectivity in host erythrocytes and invades any red blood cell (RBC) at any stage in its existence. Also, multiple merozoites can infect a single erythrocyte. Thus three or even four small rings may be seen in an infected cell. P. falciparum is often seen in the host cell at the very edge or periphery of the cell membrane, appearing almost as if it were "stuck" on the outside of the cell. This is called the appliqué or accolé position and is distinctive for this species (Murrary)

Bacterial chromosome

Double stranded DNA Single chromosome, circular Haploid No introns No nuclear membrane Highly coiled into supercoils Two enzymes DNA gyrase (Topoisomerase II) Topoisomerase IV In haploid organisms a mutation on a gene has profound effect than in Eukaryotes. Role of DNA gyrase and Topoisomerase and action of Flouroquinolones: In Gram negative organism: DNA gyrase becomes the primary target for Flouroquinolones In Gram positive organism: Topoisomerase IV is the primary target, DNA gyrase remains as a secondary target

Bacterial DNA

Double-stranded molecule twisted into a helix (similar to a spiral staircase). The two strands are comprised of a sugar-phosphate backbone and attached bases. 4 nucleobases, sugar, phosphate Thymine - Adenine, 2 Hydrogen bonds Guanine - Cytosine 3 Hydrogen bonds Genetic code; same like eukaryotic cells The smallest bacteria - Mycoplasma - 0.58 x106 base pairs and carry 475 potential genes A typical bacteria, Escherichia coli, 4.639 x 106 base pairs and carry 4288 potential genes

Treatment of Septic Athritis

Drainage of purulent exudate by arthroscopy or surgery Antibiotics: Non gonococcal: same as in osteomyelitis (3-4 wks as opposed to 4-6 wks in osteomyelitis) Gonococcal: Oral cefixime, fluoroquinolones (eg, Ofloxacin) Prevention Non gonococcal: Avoiding trauma Timely treatment of infections such as UTI, pneumonia, soft tissue infections that may lead to bacteremia Gonococcal: Avoiding sexual partners having gonorrhea, safe sex Identification and Early treatment of gonorrhea cases

Treatment of Leishmaniasis

Drug of choice for all forms-sodium stibogluconate (Antimonial/heavy metal) Alternatives For Visceral : Amphotericin B (liposome formulation), oral miltefosine, paromomycin, sitamaquine Cutaneous: Miltefosine plus fluconazole, Amphotericin B Muco-cutaneous: Amphotericin B Prevention and control Prompt treatment of cases Control of vector and reservoir host Use screening and insect repellents Vaccination under trial

Treatment of Filarial Elephantiasis

Drug of choice- Diethylcarbamazine (DEC) stimulates cholinergic receptors. Causes muscular paralysis, enhances adherence of leucocyte on parasite -targets larvae, No effective drugs for adult worms Supportive and surgical therapy may be needed Prevention and Control: Education, vector control, insect repellents and early treatment of infected cases

Treatment of Clonorchis sinensis

Drug of choice- praziquantel Prevention & Control: Avoid eating raw, pickled, smoked fresh water fish; Education regarding mode of transmission of parasite and proper disposal of human feces

Treatment of Loiasis

Drug of choice-Di-ethylcarbamazine (DEC)-effective for adults and microfilariae Corticosteroid may be added: to control the severe allergic reactions resulting from the destruction of the parasites Surgical removal after application of 10% cocaine Prevention and Control Health education Protection from fly bites using screening, appropriate clothing and insect repellents Early treatment of cases

Treatment of Schistosomiasis

Drug of choice-Praziquantel Prevention: Destruction of snail habitat: Clearing water plants where the snail lives (they breed on vegetables along the sides of freshwater bodies) Elimination of snails: chemicals Avoid swimming in endemic areas

Treatment of Ancylostoma caninum & braziliense

Drug of choice-albendazole Prevention and control Health education to pet owners to treat for worm infections in their pets Hygiene and sanitation Wearing shoes and sandals in endemic areas

Treatment of Hookworm infection

Drug of choice-albendazole/ mebendazole Prevention: Education Sanitation Not walking barefoot in areas where hookworm is common; wearing shoes By not defecating outdoors and by effective sewage disposal systems.

Treatment of Diphyllobothrium latum

Drug of choice-niclosamide a phenol, has selective activity against intestinal tapeworms. It acts by uncoupling oxidative phosphorylation in mitochondria, resulting in a loss of helminth ATP, that causes immobilization of the parasite and expel it with the feces. Prevention: avoiding insufficiently cooked fish; proper disposal of human feces

Treatment of Strongyloides stercoralis

Drug of choice: Ivermectin Interacts with chloride channel resulting in hyperpolarization, paralysis and death of the parasite Alternative: Albindazole/mebendazole Prevention and Control Similar to Hookworm infection

Treatment of Trichomonas vaginalis

Drug of choice: Metronidazole Prevention and control Safe sexual practices Personal hygiene Avoidance of sharing toilet articles

Treatment, Prevention and Control

Drug of choice: Tetracycline Prevention and control similar to amoebiasis When traveling to endemic tropical countries, Balantidium coli infection can be prevented by following good hygiene practices. All fruits and vegetables should be with clean water when preparing or eating them, even if they have a removable skin.

Treatment of Burkholderia cepacia

Drug of choice: Trimethoprim-sulfamethoxazole less resistant to antibiotics compared to Pseudomonas. Prevention and control:: Difficult to control due to ubiquitous presence, Careful monitoring/cleaning of respiratory equipment

Treatment of Hymenolepis nana

Drug of choice: praziquantel ) has broad spectrum of activity-effective against various cestodes and Trematodes. It is a calcium agonist. Increase in calcium level results in tetanic muscular contractions and destruction of tegument. It acts synergistically with the host immune system. The drug causes disruption of the parasite surface and tegument, allowing antibodies to attack parasite antigens not normally exposed on the surface. Prevention and control: proper hygiene, treatment of cases

Treatment for Shigella

Drug resistance common Shigellosis is usually a self-limited disease Does not cause severe dehydration - thus oral rehydration could be enough. Water and electrolyte therapy; antibiotics shortens course and should be used in individual cases if warranted by the severity of the disease or to protect contacts; Antidiarrheal compounds which inhibit peristalsis, are not recommended Prevention: Personal and public hygiene, shigellosis is a disease that can easily spread to other people; It is a reportable disease in the US

T. brucei (African Trypanosoma): Life cycle

During a blood meal on the mammalian host, an infected tsetse fly (genus Glossina) injects metacyclic trypomastigotes into skin tissue. The parasites enter the lymphatic system and pass into the bloodstream. Inside the host, they transform into bloodstream trypomastigotes , are carried to other sites throughout the body, reach other blood fluids (e.g., lymph, spinal fluid), and continue the replication by binary fission . The entire life cycle of African Trypanosomes is represented by extracellular stages. The tsetse fly becomes infected with bloodstream trypomastigotes when taking a blood meal on an infected mammalian host. In the fly's midgut, the parasites transform into procyclic trypomastigotes, multiply by binary fission , leave the midgut, and transform into epimastigotes . The epimastigotes reach the fly's salivary glands and continue multiplication by binary fission, producing metacyclic trypomastigotes . The cycle in the fly takes approximately 3 weeks. Humans are the main reservoir for Trypanosoma brucei gambiense, but this species can also be found in animals. Wild game animals are the main reservoir of T. b. rhodesiense.

Onchocerca volvulus life cycle

During a blood meal, an infected blackfly (genus Simulium) introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound . In subcutaneous tissues the larvae develop into adult filariae, which commonly reside in nodules in subcutaneous connective tissues . Adults can live in the nodules for approximately 15 years. Some nodules may contain numerous male and female worms. Females measure 33 to 50 cm in length and 270 to 400 μm in diameter, while males measure 19 to 42 mm by 130 to 210 μm. In the subcutaneous nodules, the female worms are capable of producing microfilariae for approximately 9 years. The microfilariae, measuring 220 to 360 µm by 5 to 9 µm and unsheathed, have a life span that may reach 2 years. They are occasionally found in peripheral blood, urine, and sputum but are typically found in the skin and in the lymphatics of connective tissues . A blackfly ingests the microfilariae during a blood meal . After ingestion, the microfilariae migrate from the blackfly's midgut through the hemocoel to the thoracic muscles . There the microfilariae develop into first-stage larvae and subsequently into third-stage infective larvae . The third-stage infective larvae migrate to the blackfly's proboscis and can infect another human when the fly takes a blood meal.

W. bancrofti and B. malayi Life Cycle

During a blood meal, an infected mosquito introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound. They develop in adults that commonly reside in the lymphatics . The female worms of W. bancrofti measure 80 to 100 mm in length and 0.24 to 0.30 mm in diameter, while the males measure about 40 mm by .1 mm (The adult worms of B. Malayi are smaller. Female worms measure 43 to 55 mm in length by 130 to 170 μm in width, and males measure 13 to 23 mm in length by 70 to 80 μm in width). Adults of W. bancrofti produce microfilariae measuring 244 to 296 μm by 7.5 to 10 μm (microfilariae of B. malayi, measuring 177 to 230 μm in length and 5 to 7 μm in width), which are sheathed and have nocturnal periodicity. The microfilariae migrate into lymph and blood channels moving actively through lymph and blood. A mosquito ingests the microfilariae during a blood meal . After ingestion, the microfilariae lose their sheaths and some of them work their way through the wall of the proventriculus and cardiac portion of the mosquito's midgut and reach the thoracic muscles . There the microfilariae develop into first-stage larvae and subsequently into third-stage infective larvae . The third-stage infective larvae migrate through the hemocoel to the mosquito's proboscis and can infect another human when the mosquito takes a blood meal .

ADCC (antibody-dependent cell-mediated cytotoxicity)

During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell. Antibodies can then bind to these viral proteins. Next, the NK cells which have Fc Receptors will bind to that antibody, inducing the NK cell to release proteins such as perforin and proteases known as granzymes, which causes the lysis of the infected cell to hinder the spread of the virus

Maturation

During this time, viral coded envelope glycoproteins are inserted in the host cell's membranes by the Golgi apparatus. Viruses that will be released by exocytosis obtain their envelopes by budding from the nuclear membrane, the endoplasmic reticulum, and/or from the Golgi complex. These enveloped viruses are then packaged in exocytic vesicles for release from the host cell by exocytosis. Matrix proteins for negative stranded RNA viruses line and promote the adhesion of nucleocapsid with glycoprotein-modified membrane. As more interaction occur, the membrane surrounds the nucleocapsid, and the virus buds from the membrane.

Inflammatory Diarrhea

Dysentery Bacteria Shigella spp. Escherichia coli Enteroinvasive (EIEC) Enterohaemorrhagic (EHEC) Salmonella spp. Campylobacter jejuni Yersinia sp. Clostridium difficile Enteric Fever Salmonella typhi - typhoid fever Parasites: Entamoeba histolytica Several helminthes

Five categories of pathogenic E. coli

EPEC: (Infant) tight adhesion and destruction of microvilli. Formation of filamentous actin pedestals or cup like structure. Enteroaggregative E. coli (EAEC)- Involves three stages that include; 1. Adherence to the mucosa, 2. Enhanced mucus production that encases the bacteria forming a biofilm, 3. Followed by elaboration of a cytotoxin, which damages the intestinal cells. They may have the ability to colonize both the small and large intestine. Regardless of this the symptoms of this infections are similar to most small intestinal infections. ETEC (Traveler's Diarrhea) strains colonize the small intestine and produce a cholera-like (heat-labile; LT) toxin and a heat stable toxin (ST). Both toxins ultimately stimulate the secretion of chloride by the host cells resulting in a watery diarrhea. Large Intestine EIEC Invade colonic epithelial cells, escape from phagosome, multiply in cytoplasm, move to adjacent cells, like shigella But does not produce enterotoxin EHEC Shiga Toxin Escherichia coli Verotoxin

Treatment of Blood stream infection

Early Stabilization: ABCs maintenance Rapidly clearing of micro-organism from blood: Antimicrobials Treatment of original focus: Removal of foreign bodies, Drainage of pus, Debridement of gangrenous tissues Prevention: Avoiding trauma Use of prophylactic medications in children with leukemia, in patient with burns Care of indwelling catheters Screening of pregnant woman for colonization of S. agalactiae

Treatment of Diptheria

Early administration of the diphtheria antitoxin (passive immunity) Penicillin or erythromycin Respiratory support Prevention Vaccine (DPT; Now 4 combinations-DTaP, DT, Tdap, Td) (plz see note below for explanation): series followed by boosters Contacts to known cases who have not been immunized (complete series or boosters) should receive a booster

Treatment of RMSF

Early aggressive treatment: Doxycycline: drug of choice Sulfonamides - contraindicated for all Rickettsial infections Prevention: Rodent control, Tick control - insecticides, not effective on eggs Repeated treatment of environment needed treating dogs for ticks, prompt removal of ticks; Doxycycline for post exposure prophylaxis

Treatment of Plague

Early treatment important Streptomycin, tetracycline or gentamicin Prevention and Control Keep rats and fleas (including form pets) off around your house Wear gloves while handling suspected animals Avoid contact with dead wild animals Do not allow dogs or cats to roam Prophylactic antibiotic after exposure - tetracycline/doxycycline Quarantine of infected individuals for 72 hrs after antibiotic therapy started No vaccine available Infection leads to life long immunity

Life cycle of Schistosoma spp.

Eggs are excreted with feces or urine. Under optimal conditions the eggs hatch and release miracidia , which swim and penetrate specific snail intermediate hosts. The stages in the snail include 2 generations of sporocysts and the production of cercariae. Upon release from the snail, the infective cercariae swim, penetrate the skin of the human host , and shed their forked tail, becoming schistosomulae . The schistosomulae migrate through several tissues and stages to their residence in the veins . Adult worms in humans reside in the mesenteric venules in various locations, which at times seem to be specific for each species . For instance, S. japonicum is more frequently found in the superior mesenteric veins draining the small intestine , and S. mansoni occurs more often in the superior mesenteric veins draining the large intestine. However, both species can occupy either location, and they are capable of moving between sites, so it is not possible to state unequivocally that one species only occurs in one location. S. haematobium most often occurs in the venous plexus of bladder , but it can also be found in the rectal venules. The females (size 7 to 20 mm; males slightly smaller) deposit eggs in the small venules of the portal and perivesical systems. The eggs are moved progressively toward the lumen of the intestine (S. mansoni and S. japonicum) and of the bladder and ureters (S. haematobium), and are eliminated with feces or urine, respectively . Pathology of S. mansoni and S. japonicum schistosomiasis includes: Katayama fever, hepatic perisinusoidal egg granulomas, Symmers pipe stem periportal fibrosis, portal hypertension, and occasional embolic egg granulomas in brain or spinal cord. Pathology of S. haematobium schistosomiasis includes: hematuria, scarring, calcification, squamous cell carcinoma, and occasional embolic egg granulomas in brain or spinal cord.

Paragonimus westermani life cycle

Eggs excreted in the sputum and sometimes in the stool Eggs are excreted unembryonated in the sputum, or alternately they are swallowed and passed with stool. In the external environment, the eggs become embryonated , and miracidia hatch and seek the first intermediate host, a snail, and penetrate its soft tissues . Miracidia go through several developmental stages inside the snail : sporocysts , rediae , with the latter giving rise to many cercariae , which emerge from the snail. The cercariae invade the second intermediate host, a crustacean such as a crab or crayfish, where they encyst and become metacercariae. This is the infective stage for the mammalian host . Human infection with P. westermani occurs by eating inadequately cooked or pickled crab or crayfish that harbor metacercariae of the parasite. The metacercariae excyst in the duodenum , penetrate through the intestinal wall into the peritoneal cavity, then through the abdominal wall and diaphragm into the lungs, where they become encapsulated and develop into adults (7.5 to 12 mm by 4 to 6 mm). The worms can also reach other organs and tissues, such as the brain and striated muscles, respectively. However, when this takes place, completion of the life cycles is not achieved, because the eggs laid cannot exit these sites. Time from infection to oviposition is 65 to 90 days. Infections may persist for 20 years in humans. Animals such as pigs, dogs, and a variety of feline species can also harbor P. westermani. Crustaceans like crabs, cray fish contain larva (metacercaria)- ingestion of which lead to human infection.

Diagnosis of Schistosomiasis

Eggs in urine or stool or biopsy, Serology (ELISA) Schistosoma japonicum egg- contain a miracidium enclosed in a shell , have a lateral spine but is inconspicuous, smaller than that of S. mansoni (70-100 ×55-65 µm ) S. haematobioum egg- presence of terminal spine, S. mansoni- Prominent lateral spine, eggs are 115-175 ×45-70 µm

Hymenolepis nana- life cycle

Eggs of Hymenolepis nana are immediately infective when passed with the stool and cannot survive more than 10 days in the external environment . When eggs are directly ingested by humans (in contaminated food or water or from hands contaminated with feces), the oncospheres contained in the eggs are released. The oncospheres (hexacanth larvae) penetrate the intestinal villus and develop into cysticercoid larvae . Upon rupture of the villus, the cysticercoids return to the intestinal lumen, evaginate their scolices , attach to the intestinal mucosa and develop into adults that reside in the ileal portion of the small intestine producing gravid proglottids . Eggs are passed in the stool when released from proglottids through its genital atrium or when proglottids disintegrate in the small intestine. When eggs are ingested by an arthropod intermediate host (various species of beetles and fleas may serve as intermediate hosts), they develop into cysticercoids, which can infect humans or rodents upon ingestion and develop into adults in the small intestine. An alternate mode of infection consists of internal autoinfection, where the eggs release their hexacanth embryo, which penetrates the villus continuing the infective cycle without passage through the external environment . The life span of adult worms is 4 to 6 weeks, but internal autoinfection allows the infection to persist for years. H. nana is one of the exception to the general rule that the helminths do not multiply inside the body of the definitive host.

Human Monocytic Ehrlichiosis

Ehrlichia chaffeensis Pathogenesis and Clinical disease: Infects monocytes and macrophages Progressive infection leads to lysis of the infected cells, release of bacteria and subsequent infection of new cells IP : 1-3 weeks, flu like symptoms with fever, malaise and myalgia. Late onset Rash develop in about 30-40% (more common in children). Leukopenia, thrombocytopenia, elevated liver enzymes Mortality rate low (2-3%), but most require hospitalization

Disinfection

Elimination of disease producing (pathogenic) Micro-organism. Frequently toxic to apply to tissue but are commonly used on inanimate surfaces.

Clonorchis sinensis life cycle

Embryonated eggs are discharged in the biliary ducts and in the stool . Eggs are ingested by a suitable snail intermediate host ; there are more than 100 species of snails that can serve as intermediate hosts. Each egg releases a miracidia , which go through several developmental stages (sporocysts , rediae , and cercariae ). The cercariae are released from the snail and after a short period of free-swimming time in water, they come in contact and penetrate the flesh of freshwater fish, where they encyst as metacercariae. Infection of humans occurs by ingestion of undercooked, salted, pickled, or smoked freshwater fish . After ingestion, the metacercariae excyst in the duodenum and ascend the biliary tract through the ampulla of Vater. Maturation takes approximately 1 month. The adult flukes (measuring 10 to 25 mm by 3 to 5 mm) reside in small and medium sized biliary ducts. In addition to humans, carnivorous animals can serve as reservoir hosts.

Pseudomonas aeruginosa

Encapsulated, Gram-negative, rod-shaped bacterium Aerobe Multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistance mechanisms, Citrate, catalase, and oxidase positive. Can secrete a variety of pigments, including pyocyanin (blue), pyoverdine (yellow and fluorescent), pyorubin (red), and pyomelanin (brown).

Pelvic Inflammatory Disease (PID)

Endometritis : Inflammation of the inside lining of the body of the uterus) Salpingitis : Inflammation of the fallopian tubes) Tubo-ovarian abscesses: Abscesses in the tubes and ovaries) Pelvic peritonitis : Inflammation inside of the abdominal cavity surrounding the female reproductive organs Signs and Symptoms -Moderate fever (generally above 99°F), -Bilateral lower abdominal pain that is maximal in the region of the fallopian tubes, may get aggravated by body movement -Tenderness on cervical motion, -Increased vaginal discharge, -Irregular bleeding, -Purulent endocervical discharge, -Nausea and vomiting

LPS (lipopolysaccharide)

Endotoxin Lipid A component of LPS of the cell wall of Gram-negatives Released after the bacteria die Activates several aspects of the immune system including the coagulation system. Acts as PAMP : activates macrophages, PMN, mast cells, endoth. cells, platelets Activates complement: alternative pathway B cell polyclonal activation Effects Low concentrations signal inflammation necessary for clearing infection High concentrations: Endotoxic shock, " SIRS"- systemic inflam. response syndrome Symptoms: Fever, Hypotension and DIC (disseminated intravascular coagulation) , inflammation, multi-organ failure, death

Amoebiasis (amoebic dysentery)

Entamoeba histolytica Intestinal (large intestine) - IP: 4-5 days: dysentery (bloody diarrhea), abdominal pain, cramping; Severe case: numerous bloody stools/day Asymptomatic carriage Extra intestinal: liver abscess: seen approx. 5% of intestinal inf. pain and tenderness in right hypochondrium, fever, hepatomegaly (lower border of the liver palpable), transmission to other regions Spleen and cutaneous amoebiasis brain abscess Genital abscess - (in homosexual men)

Intestinal Nematodes

Enterobius vermicularis - Pin worm Ascaris lumbricodes - *S Giant worm (round worm) Ancylostoma duodenale/*S Necator americanus Hookworm Trichuris trichiura- Whip worms Strongyloides stercoralis* Threadworm Trichinella spiralis - * Pig worm *Have tissue stages as well *Soil transmitted helminths

Shigella Toxins

Enterotoxins: produced by all four spp. ShET1 and ShET2: - Blocks absorption (uptake) of electrolytes, glucose, and amino acids from the intestinal lumen watery diarrhea Shiga toxins (AB toxin) - produced by S. dysenteriae Cytotoxin - Stx = shiga - (vero) toxins inhibits protein synthesis by inactivating 60S subunit of ribosome kills intestinal epithelial and endothelial cells synergizes with LPS to produce inflammatory cytokines, causing damage to endothelium lining the blood vessels causing bloody diarrhea

Pathogenesis of osteomyelitis

Entry of Microorganisms into bone: by hematogenous dissemination by spread from a contiguous focus of infection, or by a penetrating wound. Trauma, ischemia, and foreign bodies enhance microbial invasion. Phagocytes attempt to contain the infection and, in the process, release enzymes that lyse bone. Bacteria escape host defenses by adhering tightly to damaged bone, by entering and persisting within osteoblasts, and by coating themselves with biofilm. Pus spreads into vascular channels, raising intra-osseous pressure and impairing the flow of blood; As the untreated infection becomes chronic, ischemic necrosis of bone results in the separation of large devascularized fragments (sequestra). When pus breaks through the cortex, subperiosteal or soft tissue abscesses form, and the elevated periosteum deposits new bone (an involucrum) around the sequestrum. The distinguishing feature of chronic osteomyelitis is necrotic bone with absence of living osteocytes and mononuclear cells

Arenavirus

Env, sandy appearance, two ss RNA Rodent borne: Contact or inhalation Lymphocytic choriomeningitis virus (LCM) Source: house mice and hamsters, reported in the US. Transmission : inhalation of aerosol contaminated with droppings Disease: febrile illness with/out meningitis, encephalitis, but NO haemorrhagic fever, Pregnancy and LCM: congenital infection - miscarriage, birth defects 2. Lassa fever virus - causes haemorrhagic fever in west Africa. 3. Junin haemorrhagic fever virus endemic in Argentina. 4. Machupo haemorrhagic fever virus endemic in Bolivia.

HIV Structure

Envelope glycoproteins gp120= binds to CD4 and CCR5/CXCR4 gp41= mediates fusion Enzymes Reverse transcriptase: viral RNA to viral DNA Integrase = integrates viral DNA to host DNA - creates latency Protease = cleaves precursor polypeptides Capsid protein: P24 used in diagnosis - detection of viral antigen Nucleic acid: + sRNA - two copies, replicate via DNA intermediate Anti-HIV drugs targeting; gp41 (fusion), proteases, reverse transcriptase, integrases

Viral Structure

Envelope: lipid bilayer from host cell and viral glycoproteins Peplomers/Spikes: viral glycoprotein, binding to host cell Matrix protein- mediate attachment of capsid with the envelope Packaged enzymes: facilitate initial viral replication (polymerases, proteases). May be located inside the nucleocapsid or in the space between the capsid and envelope (tegument) Other proteins: structural proteins: part of virion non-structural proteins: not in virion, involved in early events of replication

Enveloped vs Naked Viruses

Enveloped Environmentally labile: Spread - must stay wet, large droplets, secretions, blood and organ transplant Enter cells by fusion with cytoplasmic membrane lipids Usually released by budding through the cell membrane with no cell death Cell to cell spread by syncytia may occur Naked Environmentally stable, Easily spread by water, dust, food, hand to hand, small droplets, fomites, etc. Naked viruses usually enter cells through receptor mediated avenue Naked viruses most often exit host cells by lysis and death of the cell

Influenza virus

Enveloped with helical capsid Segmented, negative sense ssRNA genome Peplomers: 1. Hemagglutinins - binds and agglutinate RBC 2. Neuraminidase: an enzymes ; splits polymers of sialic (acetylneuraminic) acid to get released RNA dep. RNA polymerase

Mechanisms of Aminoglycosides Resistance

Enzymatic Modification of the drug: -Acetylation by acetyltransferases -Adenylation by adenyltransferases -Phosphorylation by phosphotransferases Transport Interference: decreased uptake Mutation of ribosomal binding Site Accelerated Export of Drug

DNA Replication in Prokaryotic Cells

Enzymes & proteins required for bacterial replication are similar to those found in eukaryotic cells but different enough to be targets for specific antibiotics Replication requires uncoiling of supercoiled DNA. Antibiotics of class flouroquinolones bind to DNA gyrase (topoisomerase II) and inhibit uncoiling of supercoiling.

Loeffler's syndrome

Eosinophilic pneumonia caused by the parasites Ascaris lumbricoides, Strongyloides stercoralis and the hookworms (Ancylostoma duodenale and Necator americanus). Although Löffler only described eosinophilic pneumonia in the context of infection, many authors give the term "Löffler's syndrome" to any form of acute onset pulmonary eosinophilia no matter what the underlying cause is.

Brill-Zinsser disease

Epidemic typhus The pathogen may remain dormant for many years & reactivate A form of recurrent disease from reactivation of latent disease acquired earlier during world war II; milder presentation and rash may be absent, diagnosis-difficult; Serve as reservoir

Typhus Group

Epidemic typhus (louse borne typhus): R. prowazekii Endemic typhus (murine typhus): R. typhi Scrub typhus: Orientia tsutsugamushi

Infective Endocarditis

Epidemiology Incidence: 2 cases/100,000 in US Male > Female Risk Factors: Structural heart disease Rheumatic, congenital, aging Prosthetic heart valves Injected drug use Invasive procedures (eg for intracardiac pacemaker, AV Fistula) Indwelling vascular devices History of infective endocarditis Other infection with bacteremia (e.g. pneumonia, meningitis) Immunocompromised states

Anaplasma phagocytophilum

Epidemiology: Reservoirs: small rodents, deer, sheep, Transmitted by ticks (Ixodes spp, hard tick) Geographic distribution: worldwide. In the US, most common in the northern and central mid-western states and north east and central Atlantic states

Ehrlichia chaffeensis

Epidemiology: Reservoirs: deer, dogs and other canines, transmitted by ticks (hard ticks, Amblyomma americanum) Geographic distribution: worldwide. In US, most common in the southeastern, mid Atlantic, mid-western and south-central states.

Arboviral Encephalitis

Epidemiology: They are seasonal, occur mostly in summer when the vectors are active Have specific geographical distribution Incidence in the US: varies with occurrence and intensity of epidemic transmission; usually 150-3,000 cases/year Diagnosis: Clinical, travel history, serology CSF/serum ELISA (IgM), or a rise in titer, RT- PCR Treatment: No specific therapy; supportive treatment. Prevention: Vector control, no vaccine for humans. Except for yellow fever. vaccine for horses available for EEE, WEE and WNV

Loa loa

Epidemiology: Equatorial rain forests of central and west Africa, infects human and other forest animals, such as monkeys Transmitted by mango fly (deer fly)-Chrysops spp

Babesia microti

Epidemiology: Found where Borrelia burgdorferi (Lyme disease) is found, North east US. Reservoir: Rodents; deer, cattle transmitted by tick (Ixodes dammini); or by blood transfusion Morphology: Sporozoan Exists in different forms - sexual and asexual reproduction. Pathogenesis: Infective form: Sporozoites (pyriform bodies) Infect and lyse RBC Clinical disease: Malaria like syndrome Incubation Period: 1-4 wks, General malaise, Fever without periodicity, headache, chills, sweating, fatigue, hemolytic anemia; hepatosplenomegaly in severe case

T. brucei (african sleeping sickness)

Epidemiology: Transmitted by Glossina (Tsetse fly) - T. b. gambiense: humans as the main host (vector prefers shaded stream banks proximity to human dwellings)-98% infection T. b. rhodesiense : human and cattle, and antelopes (Vector prefers brush land rather than stream banks)-2% infection Morphology: flagellate

Naegleria fowleri

Epidemiology: Ubiquitous in nature Reservoir: Warm water bodies such as heated swimming pools, hot tubs, hydrotherapy and medicinal pools, aquariums and sewage Transmission: Acquired during warm summer months from contaminated lakes - or in hot tubs, via the olfactory mucosa and nasal tissues Risk Factors/High Risk Populations: Mostly young children

Toxoplasma gondii

Epidemiology: World wide, two hosts - definitive host - cat family, intermediate host: man, cattle, rodents. Transmitted by: a) oral route: fecal (cat feces)-oral; or consumption of meat with cyst; b) blood transfusion or organ transplantation; and c) Transplacental route Morphology and life cycle: Sporozoan; 3 important forms: Oocyst, Tachyzoites and Bradyzoites; undergo sexual (Intestinal) and asexual (extra-intestinal) reproduction

Cyclospora cayetanensis

Epidemiology: Worldwide but common in tropical and subtropical regions; Also infects animals Travelers, indigenous persons living in developing countries and immuno- compromised (particularly, HIV infected) person Transmission: by ingestion of food/vegetables/fruits/water contaminated with sporulated oocyst, outbreaks in US since 1990s Biology: Single celled coccidian parasite, both sexual and asexual reproduction

Trypanosoma cruzi (Chagas Disease/ American trypanosomiasis)

Epidemiology: infects human, domestic cats, dogs, wild rats, raccoon and even armadillo and opossums Transmitted: by insect vector Reduviid bugs (Triatomine bugs/kissing bugs); across the placenta (congenital); and by blood transfusion/organ transplantation Geographic distribution: Rural areas of South and Central America: endemic Migrants in the USA, Europe, Australia, Japan Morphology: exists as a flagellate and non flagellate

Acanthamoeba castellani

Epidemiology: ubiquitous in nature; water bodies, warm climate, hot tub Transmission: by contaminated water/soil through damaged skin, corneal abrasion; inhalation Risk factors: improper contact lens care and contact with nonsterile water during wear. Rare disease; incidence in developed countries: approx. 1 to 33 cases per million contact lens wearers Morphology: free living Amoeba (Protozoan), exists in two stages, cysts and trophozoite

Cryptosporidium parvum

Epidemiology: world wide, infects human and animals, millions of Crypto parasites shed in stools. Transmission by fecal- oral route, Approx. 748, 000 cases every year in US Biology: Sporozoan (coccidian) - exists in different forms, sexual and asexual reproduction. Acid fast oocyst (infective stage and diagnostic stage) Pathogenesis and Clinical disease: Adheres on the epithelial cells of the small intestine AIDS associated diarrhea, non bloody diarrhea, chronic, up to 50 stools Infects healthy persons as well.

Balantidium coli

Epidemiology: world wide, mostly tropical and subtropical, rare in US - infects animals - Risk factors: working with animals (pigs farm) and immune-compromised status fecal-oral route Outbreak associated with contaminated water supplies with pig feces. Biology: ciliate - cyst and trophozoite Trophozoite-covered with cillia (aid in motility), funnel like mouth (cytostome), has 2 nuclei - macro and micro nuclei, 50-200× 40-70 µm Cyst: refractile wall, single nucleus, 40-60µm (diameter)

E-test

Epsilometer test MIC determined from the test is compared with the standard given by CLSI guidelines A strip of paper with decreasing concentration of antibiotics Advantage : quantitative: measures Minimum Inhibitory Concentration (MIC)

Parvovirus (B19) Clinical Disease

Erythema Infectiosum (Fifth Disease); IP 8-11 days Prodrome: fever, coryza, headache, and sore throat Slapped Cheek Syndrome: 2 to 5 days later, the classic slapped-cheek macular rash appears on the cheek and spread mostly to exposed skin of arms and legs (Lace like rash) Arthralgia: infection in adults, mostly women; small joints (hands and feet) Aplastic crisis: Life threatening reticulocytopenia may occur in patient with underlying hemolytic anemias such as sickle cell anemia. May require transfusion for survival Hydrops fetalis: Congenital infection (2nd trimester), virus infects the fetus and kills RBC precursors, causing anemia and congestive heart failure. fluid accumulation in several tissues (stillbirth/miscarriage)

Blood stream infection

Etiology ˃50% of Sepsis: By Gram negative bacteria Slightly ˂ 50%: Gram Positive bacteria Less common cause: Fungi, viruses (eg. HIV), and Protozoa Differs based on age group: Neonate: ˂ 1month: Streptococcus agalactiae followed by E. coli Pediatric: S. pneumoniae, Neisseria meningitidis, Staphylococcus aureus Adults: Epidemiology Sepsis causes 9.3% of all deaths in US each year 400,000 cases diagnosed each year, approx. 50% progressing to septic shock Source of infection The most frequent source: Pneumonia, Peritonitis, and UTI Others: Skin and soft tissue, GIT, Instrumentation sites Risk factors: Patients with underlying diseases eg, Neutropenia, AIDS; Antecedent surgery or instrumentation: catheters, prosthetic devices Prior immunosuppressive drugs Men above 50: Benign prostatic hyperplasia-Cystitis/pyelonephritis-Sepsis Sexually active women aged 20-45 years Childbirth, trauma, widespread burns

Roseola Pathogenesis

Exanthem Subitum (abrupt high fever foll. by rash) Presence of infected T cells or activation of DTH in the skin may be the cause of rash It is the most common cause of febrile seizures in childhood (6-24 months). HHV-6 infection occurs very early in life. The virus replicates in the salivary gland, is shed, and transmitted in saliva. HHV-6 primarily infects lymphocytes, especially CD4 T cells. HHV-6 establishes a latent infection in T cells and monocytes but may replicate on activation of the cells. Cells in which the virus is replicating appear large and refractile and have occasional intranuclear and intracytoplasmic inclusion bodies the replication of HHV-6 is controlled by cell-mediated immunity. Similar to CMV, the virus is likely to become activated in patients with AIDS or other lymphoproliferative and immunosuppressive disorders and cause opportunistic disease The presence of infected T cells or the activation of delayed-type hypersensitivity T cells in the skin may be the cause of the rash Diagnosis: mainly clinical, Lab tests seldom done Treatment and prevention or control methods: None

Antigenic Variation

Existing in multiple types Antigenic/phase variation: programmed gene rearrangement Switch genes on/off : NO MUTATION but results in phenotype switching Transcriptional regulation of alternative genes. Help the bacterium evade the host immune system.

Invasion or Spreading Factors

Exoenzymes : act on the extracellular matrix Tissue degrading enzymes Examples : Proteases, phospholipases hyaluronidase, collagenase, fibrinolysin (streptokinase) Induction of phagocytosis and spread without leaving the cell: Eg. Shigella and Listeria

Secretion systems

Exotoxins are released through special apparatus Some transport the toxins directly into the extracellular spaces Others inject the toxin directly to the target host cell via structures that serve as "molecular syringe " Eg of bacteria with Type III secretion system: Pseudomonas, Shigella, Salmonella, Yersina pestis Bacterial secretion system are named as Type I, II, III, IV, V and VI. Type I, II, V deliver the toxin to the extracellular space. Type III, IV, and VI are syringe like apparatus

Fitz-Hugh-Curtis syndrome

Extension of PID - in women -Acute perihepatitis which occurs as the infection spreads from fallopian tube to the liver capsule and overlying peritoneum Severe pain in the upper right part of the abdomen, over the gallbladder, hepatic tenderness, peritoneal inflammatory signs. laparoscopy may show signs of "violin string" adhesions between liver capsule and the peritoneal cavity

Pathogenesis of Trypanosomiasis

Extracellular - multiply in body fluids Programmed gene rearrangement (Antigenic variation)/ about 1000 gene varieties Lesion at the site of insect bite (Chancre) Gambian sleeping sickness (West ASS): IP-few days to weeks, can progress to chronic disease-fatal Early (hemolymphatic phage): Fever (intermittent/weekly), myalgia, arthralgia and lymphadenopathy (Posterior cervical lymphadenopathy-Winterbottom's sign), Rash Chronic (Neurologic phage): CNS involvement (usually after 1-2 year )-lethargy, daytime sleepiness with night sleep disturbance, tremors, meningoencephalitis, mental retardation, convulsions, hemiplegia, coma and death

Coxsackie A Virus

Family Picornaviridae Genus Enterovirus General Properties: positive sense ssRNA, non enveloped. Reservoir: Humans Transmission: Person to person, primarily by fecal-oral but also by respiratory aerosols, contaminated objects. Risk Factors/High Risk Populations: Primarily infants and young children (2 weeks to 3 years), predominates in summer and fall seasons.

Rhinocerebral mucormycosis

Fatal form Begins in nasal mucosa or sinuses and progresses to the orbits, palate and the brain Signs and symptoms: orbital cellulitis (infection of eye socket), bulging of the affected eye (proptosis). Destruction of the palate, facial bones, septum. Seizures, partial paralysis and coma

Rabies clinical disease

Fatal unless vaccinated Incubation period is usually 30-90 days. Suspicion of rabies is clear when a history of an animal bite is given; however, because a history of animal bite is obtained in less than one half of US cases, diagnosis is problematic. Presentation of a patient in the rabies prodromal stage without a clear exposure history is so nonspecific and rare that making the diagnosis in the ED is essentially impossible. Rabies progresses over 7-14 days, and the mean time between initial presentation and death is 16.2 days. After prodrome, neurologic phase of the rabies manifests as either of two forms: furious (encephalitic) or dumb (paralytic form) A. Furious (encephalitic) form: occurs in about 80% cases. They common symptoms are agitation, delirium, seizures and hydrophobia (an aversion to swallowing water because of painful spasm of the pharyngeal muscles.). B. Dumb (paralytic) form: The symptoms of furious forms do not occur. Rather, the spinal cord is primarily involved and an ascending paralysis occurs. Death almost invariably occurs following both the forms.

Diagnosis and treatment of Ticks

Finding of a tick or a history of exposure + clinical features Treatment: Early removal of ticks Prevention and control: Wearing of protective clothing that cover extremities Application of insect repellents Inspection of people and pets for ticks after visits to tick infested areas

Maurer dots

Finely granular precipitates or irregular cytoplasmic particles that usuallyoccur diffusely in red blood cells infected with the trophozoites of Plasmodium falciparum. They are membrane-limited vacuoles or sack-like structures in the cytosol of the erythrocyte, formed early after invasion by the parasite, visible as blue dots in Giemsa-stained blood smears. Their origin and functions remain still unclear.

Diphyllobothrium latum: life cycle

Fish tapeworm: crustaceans (also called copepods which includes Cyclops/ and Diaptomus spp) and fish are intermediate hosts Immature eggs are passed in feces . Under appropriate conditions, the eggs mature (approximately 18 to 20 days) and yield oncospheres which develop into a coracidia . After ingestion by a suitable freshwater crustacean (the copepod first intermediate host) the coracidia develop into procercoid larvae . Following ingestion of the copepod by a suitable second intermediate host, typically minnows and other small freshwater fish, the procercoid larvae are released from the crustacean and migrate into the fish flesh where they develop into a plerocercoid larvae (sparganum) . The plerocercoid larvae are the infective stage for humans. Because humans do not generally eat undercooked minnows and similar small freshwater fish, these do not represent an important source of infection. Nevertheless, these small second intermediate hosts can be eaten by larger predator species, e.g., trout, perch, walleyed pike . In this case, the sparganum can migrate to the musculature of the larger predator fish and humans can acquire the disease by eating these later intermediate infected host fish raw or undercooked . After ingestion of the infected fish, the plerocercoid develop into immature adults and then into mature adult tapeworms which will reside in the small intestine. The adults of D. latum attach to the intestinal mucosa by means of the two bilateral groves (bothria) of their scolex . The adults can reach more than 10 m in length, with more than 3,000 proglottids. Immature eggs are discharged from the proglottids (up to 1,000,000 eggs per day per worm) and are passed in the feces . Eggs appear in the feces 5 to 6 weeks after infection. In addition to humans, many other mammals can also serve as definitive hosts for D. latum.

Coxsackie A16 virus

Foot-hand-mouth disease Member of Picornaviridae, Genus Enterovirus Positive sense ssRNA, non enveloped

Treatment of Toxocariasis and Baylisarcaris

For Toxocariasis Visceral: antiparasitic agents-albindazole or mebendazole Ocular- difficult to treat, measures to prevent further damage Antiparasitic agents for early infection; Corticosteroid For Baylisarcaris infection-No effective drugs; EXTREMELY FATAL Prevention and Control: Eradication of worms by the pet owners; Hygiene and sanitation; Proper disposal of pet's feces Discouraging keeping of raccoons as pets

Western blot

For detection of antiviral antibodies: The viral antigens are separated by electrophoresis, then transferred onto nitrocellulose membrane. The membrane is now reacted with the patient's serum containing the specific antiviral antibodies. The antibodies are now detected by secondary enzyme labeled antibody and substrate.

Flagella

For motility Gen. in rod shaped bacteria Flagellin proteins Variation in aa sequence - antigenic variation provides serologic classification Capable of being regenerated Number and position vary Generally found in many Gram negative bacteria. However, some of the Gram positive organisms like Vagococcus, two species of Enterococci (Enterococcus casseliflavus and E. gallinarum) have flagella

Life cycle

For survival and reproduction, many parasites evolve through a number of morphologic stages and several environments or different hosts. The sequence of morphologic and environmental stages is referred to as the life cycle.

Immunological fungal diagnosis

For systemic mycosis Dermal hypersensitivity testing (like tuberculin test) Serology: Detection of antibody (4x increase of paired sera) Detection of fungal antigens in patient's sample

Superantigens

Form bridges between the MHC II (beta chain) of macrophages or other APCs and TCR of T cells Rate of T cell activation: 1/5 versus 1/10,000 to 100,000 (Superantigen Vs Other antigens) High levels of cytokines in circulation (cytokine storm) - Toxic shock syndrome - life threatening multi organ involvement. Examples: Toxic Shock Syndrome Toxins, TSST (Staphylococcus aureus) Streptococcal pyrogenic exotoxin (Spe) A and C (Streptococcus pyogenes) Toxic shock syndrome can affect most organ systems in the body, including the skin, lungs, liver, kidneys, blood, GI, and pancreas. Fever, rash, low pb etc

Pathogenesis of Echinococcosis granulosus

Form cyst (larvae) inside tissues - and grows - mechanical destruction & space occupying lesions Type I Hyp. rxn due to leakage of cyst contents/fluid- Anaphylaxis, shock and DEATH Daughter cysts also develop and escape to other organs - liver, lung, and brain Clinical Disease: Hydatid disease or hydatidosis Cyst grows and develops over 5 - 30 years. Pressure on the organs; scarring/loss of function - liver, lung, brain; Cysts can calcify over time, or may rupture & disseminate

Viral Nomenclature

Formal names: 1. Family names end in - viridae, e.g Orthomyxoviridae, Reoviridae 2. Genera names end in virus eg. Myxovirus, Reovirus Common names based on; 1. Target tissue—Rhinovirus, hepatitis virus 2. Geography—St. Louis encephalitis virus, Coxsackie virus 3. Shape—Coronavirus 4. Transmission--Arboviruses (arthropod borne) viruses

Fungal Sexual Reproduction

Formation of sexual spores (Teleomorph) 4 classes based on sexual spore formation Zygomycetes: have non septate hyphae, produce zygospores as sexual spores (They also produce sporangiospores as asexual spores) Ascomycetes: Include both yeasts and filamentous fungi (Septate), form ascospores (sexual spores) Basidiomycetes: Basidiospores on a basidium or base Deuteromycetes: Also called as Fungi imperfecti Provisional group whose sexual phase not identified Contains most fungi of medical importance

Acanthamoeba castellani Life Cycle

Found in soil; fresh, brackish, and sea water; sewage; swimming pools; contact lens equipment; medicinal pools; dental treatment units; dialysis machines; heating, ventilating, and air conditioning systems; mammalian cell cultures; vegetables; human nostrils and throats; and human and animal brain, skin, and lung tissues. Unlike N. fowleri, Acanthamoeba has only two stages: cysts and trophozoites , in its life cycle. No flagellated stage exists as part of the life cycle. The trophozoites replicate by mitosis. The trophozoites are the infective forms, although both cysts and trophozoites gain entry into the body through various means. Entry can occur through the eye , the nasal passages to the lower respiratory tract , or ulcerated or broken skin . When Acanthamoeba spp. enters the eye it can cause severe keratitis in otherwise healthy individuals, particularly contact lens users . When it enters the respiratory system or through the skin, it can invade the central nervous system by hematogenous dissemination causing granulomatous amebic encephalitis (GAE) or disseminated disease , or skin lesions in individuals with compromised immune systems. Both cysts and trophozoites of Acanthamoeba spp are found in tissue

Koch's Postulates

Four criteria designed to establish a causative relationship between a microbe and a disease

Leishmania spp.

Four species L. donovani : causes kala-azar (visceral leishmaniasis) L. tropica L. mexicana L. braziliensis: mucocutaneous Leishmaniasis Epidemiology : World wide with restricted distribution. Favor arid, dry warm environment. Also infects animals (dogs and rodents). Transmitted by Sand fly, Phlebotomus spp. The second-largest parasitic killer in the world (after malaria) An estimated 1.3 million new cases and 20 000 to 30 000 deaths occur annually (WHO).

Zoonotic viruses

From animals to humans 1. Insect bite: Arboviruses: arthropod vector (arthropod borne = arboviruses). OR 2. Inhalation, or contact with infected excretions, or by direct contact with infected animal/human Three major diseases; 1. Epidemic viral encephalitis Inflammation of the brain tissue Fever, headache, and clouding of consciousness together with seizures and focal neurology May lead to coma Neurological sequelae may occur among those who survive 2. Febrile viral diseases Fever, muscles aches, joint pains, fatigue and headache, sometimes associated with rash 3. Viral hemorrhagic fevers (VHF) A severe multisystem syndrome: Acute febrile disease in which hemorrhage and shock are the major clinical characteristics There is some overlap of symptoms between the diseases caused by various virus types

Pathogenesis of Leptospira interrogans

From the skin or eye it reaches blood, then to CNS, visceral organs--liver, kidney Infects endothelial cells damaging blood vessels Extensive vasculitis, involving many organs Meninges, liver, kidney, lung- hemorrhages Initial phase of the disease due to bacteria Second phase - mostly due to immune response - immune complex deposition Leptospirosis; Weil's Disease, (swamp or mud fever) IP: 2 days to 4 weeks (CDC) Two phases: Initial phase (Bacteremic): Mild flu-like symptoms, fever, chills, muscle pain, GI symptoms; remit after a week or may progress to Second phase (Immune): more severe aseptic meningitis, jaundice, conjunctival suffusion (reddening of the eye) Weil's disease : Most severe form Hepatic and renal failure, meningitis, myocarditis and vascular collapse. mortality (10%)

HIV Infection Stage 3

Full-blown AIDS CD4 T cells < 200/µl in peripheral blood Viral load of peripheral blood > 75,000 copies/ ml (P24 and viral RNA level high in serum) HIV-AIDS related conditions and symptoms -Lymphadenopathy and fever -Opportunistic infections ( see next slide) -Malignancies: such as Kaposi sarcoma - skin cancer associated with HSV type 8 , EBV related lymphomas -AIDS related dementia: HIV infection of microglial cells

Fungi as Infectious Agents

Fungi are widely distributed in nature Only few are associated with disease True/primary pathogens can cause disease in a healthy, immunocompetent host Opportunistic pathogens are fungi with weak/nonexistent virulence or invasiveness, cause disease in immunocompromised host Increase in incidence - 10% of all hospital acquired infections

Giardia lamblia

G. duodenalis/G. intestinalis Epidemiology: world wide; In US, Giardia infection is the most common intestinal parasitic disease Also Infects other animals (beavers and muskrats) Transmission: fecal oral- mostly via contaminated water (such as streams, rivers); food and fingers; oral-anal sexual Risk factors-travel to known endemic areas, consumption of inadequately treated water, day care centers and oral-anal sexual practices Biology: flagellate - cyst and trophozoite Cyst: oval, 4 nuclei, axostyle/axoneme Trophozoite: Tennis/badminton racket appearance, two nuclei, 4 pairs of flagella, axoneme, sucking disc on ventral surface, 'Falling leaf' motility

Family Rickettsiaceae

General Features Very small rods/coccobacilli (0.3x1-2 um) bacteria Structurally their cell wall resembles that of gram-negative rods, but stain poorly by Gram staining Rickettsia: thin peptidoglycan + LPS (weak endotoxicity) Orientia: do not have peptidoglycan and LPS Best stained with Giemsa or Gimenez stains and can be seen under light microscope Obligate intracellular pathogens Depend on the host cell for several metabolic pathways Energy parasite - use ATP produced by the host cell Cultivated in cell culture, embryonated eggs or experimental animal Transmitted by arthropods: ticks, mites, fleas, body lice Most infections with tick vectors have a restricted geographic distribution Are zoonotic except one species, R. prowazekii

Trematodes

General Properties Small flat, leaf-like worms Measures in mm Have suckers for attachment The sexes of the parasites are not separate (monoecious). Except in one genus - Schistosoma All use freshwater snails as intermediate host

Lice

General Properties: 2-4 mm long Two species: Pediculus humanus- elongated body: two subspecies: P.h.capitis (head louse) P.h.corporis (body louse) Pthirus pubis (pubic louse)short body Nits - eggs of lice- attached to hair shaft Lice do not have wings unlike other insects Epidemiology: Worldwide, Common in US Transmission: Head lice: By sharing of hair brushes/combs, hats and towels; common in children Body lice: By personal contact or by clothing Pubic lice: By sexual contact

Ticks

General Properties: Arachnids Female ticks require blood meal for maturation of their eggs Found in grassy woodland areas and attracted by CO2 and warmth from humans Comprise 2 large families Ixodidae (hard tick): hard dorsal plate or scutum, mouth parts visible from above Argasidae (soft tick): leathery body that lacks hard covering (scutum), mouth parts ventrally Epidemiology: Wooded and rural areas worldwide Ticks of medical importance in US: Hard ticks: Dermacentor variabilis (American dog tick)-More common in Eastern US D. andersoni (Rocky mountain wood tick)-More common in Western US Ixodes dammini (deer tick) Soft ticks: Ornithodorus spp. Risk factors: Exposure in wooded areas, staying in rural cabins inhabited by small rodents (which serve as host for ticks)

Blastomyces dermatitidis

General characteristics : Dimorphic. But extracellular. Yeast - heavy, double walled yeast, broad-based bud. Mold -septate hyphae with microconida Reservoir: Moist soil, rich in decomposing organic debris. Endemic in areas of the United States and Canada surrounding the Ohio and Mississippi River valleys and the Great Lakes Central and South America and parts of Africa It causes disease in dogs as well Transmission: Inhalation of airborne conidia (spores); through skin Risk Groups/High Risk Populations: with exposures to wooded sites such as farmers, forestry workers, hunters, and campers. Cases in adult males > females; 1-2 cases per 100,000 population in endemic areas

Candida albicans

General characteristics: Yeast like fungus, reproduce by budding; produce pseudohyphae (elongated yeast), thick-walled chlamydoconidia; positive for germ tube test Reservoir: Normal body flora in skin, mouth, rectum, vagina; Also found on skin and mucosa of many animals Transmission: Endogenous- overgrowth of normal flora: due to alteration of physiological conditions: pH, increased sugar, decreased normal flora (antibiotic treatment). Exogenous- associated with medical intervention Risk Factors/ Risk Populations: Diabetes or weakened immunity Moist, warm areas of the body are the initial sites of infections

Family Anaplasmataceae

General features: Obligate intracellular bacteria, survive in cytoplasmic vacuoles of granulocytes OR monocytes Two morphological forms: Small Elementary bodies and Large reticulate bodies Intracellular growth protects bacteria from immune defenses Cell wall similar to Gram negative, but lacks peptidoglycan and LPS Transmitted by ticks, but no transovarian transmission

Mycobacterium tuberculosis

General features: Acid fast bacilli, obligate aerobe non spore forming bacteria Facultative intracellular pathogen High guanine + cytosine (G+C) contents in DNA Weakly Gram positive Cell wall similar to Gram positive bacteria, but is rich in complex lipids made up of long chain fatty acids with up to 70-90 carbon atoms Nonchromogen, Slow grower, generation time up to 24 hrs Produces niacin- differentiation from other species of related Mycobacterium

Bedbugs

General properties Cimex lectularius: most common bedbug in US About 5 mm long, oval and brownish body, long folded proboscis Resides in mattresses and in the crevices of wooden beds in the day time Feed at night Pathogenesis and Clinical findings Bite in a linear fashion in the trunk, take blood meal Hypersensitivity reaction leading to a pruritic wheal Occasionally, sleeplessness in children and adults

Chlamydiaceae

General properties Obligate intracellular Bacteria, do not grow on artificial media, requires cell culture for growth has cell wall but lack peptidoglycan (muramic acid ) do not stain with Gram stain energy dependent, biphasic growth cycle, Elementary body (EB) and Reticulate body (RB) EB = infectious stage, metabolically inactive RB= non infectious, metabolically active stage, Inclusion body: EB/and or RB inside a cell in a vesicle, important for making diagnosis Reservoir: Humans respiratory tract Transmission: Respiratory droplets Risk Groups/High Risk Populations: All ages at risk, but most common in school-age children. In US, about 50% of adults have evidence of past infection by age 20.

Hepatitis D (Delta) Virus

General properties : Enveloped, ss circular negative sense RNA genome; which codes for only HDAg. Defective - cannot replicate on its own because it does not have the gene for its envelope protein (s antigen). Replicate only in cells infected by HBV and uses the HBsAg - use it for binding to hepatocytes. Reservoir: Humans Transmission: mainly parenteral Risk Factors/High Risk Populations: patients with chronic HBV infection are at more risk to develop serious diseases. Co-infection with HBV - infection at the same time Super infection in HBV chronic infection - more severe

Streptococcus pneumoniae

General properties: Gram +ve, encapsulated, lancet-shaped (elongated) paired cocci or short chains, alpha hemolytic; optochin sensitive, bile sensitive, autolysis. No Group specific cell wall carbohydrate , >90 capsular serotypes - vaccine antigen

Poxviridae Family

General properties: Largest viruses, Enveloped Brick shaped Internally: complex structure Disk shaped core Has ds DNA Replicate in the host cell cytoplasm. Carry its own DNAdep—RNA polymerase to make mRNA which is translated to early proteins which include DNA dep DNA polymerase Potential Biowarfare agent

Aspergillus spp

General properties: Monomorphic fungus (mold) with septate hyphae; dichotomous branching at 45o angles (V- shaped). Several species -A. fumigatus. A flavus, A niger A. fumigatus most common. Spore: Conidia in extending chains Reservoir: Ubiquitous saprophytes in the environment - soil and decaying vegetation. Transmission: air borne spores - inhalation Risk Groups/High Risk Populations: severe invasive in immuno compromised patients (neutropenic or with cytotoxic or steroid therapy). less invasive in healthy persons

Vibrio cholera

General properties: Comma-shaped (curved) bacilli, Gram negative, oxidase +. Motile with single polar flagella Reservoir: Human asymptomatic carriers in endemic areas. Contaminated water, consumption of undercooked crabs/shrimps, or raw oysters. Transmission: fecal oral, acid sensitive - high dose. >108 V. cholerae spread by contaminated water & food; Risk Factors/High Risk Populations: anyone, during natural disaster - flooding outbreaks/epidemics Clinical Disease: Cholera - tremendous loss of water, rice water diarrhea

Actinomyces israelii

General properties: Filamentous -resemble fungi but are bacteria - Gram positive anaerobe; non acid fast. Forms sulfur granules - yellow/orange color Reservoir: Normal flora - oral cavity, gut, female genital tract. Transmission: Endogenous Risk Factors/Risk Populations: low virulence potential - disruption of mucosal surface - Trauma, dental work or surgery, intrauterine device Pathogenesis Chronic granulomatous lesions that form abscesses in connective tissue Sinus tract formation Areas of suppuration surrounded by fibrosing granulation tissue-hard/woody consistency

Streptococcus pneumoniae

General properties: Gram +ve, encapsulated, lancet-shaped (elongated) paired cocci or short chains, alpha hemolytic; optochin sensitive, bile soluble, autolyses. No Group specific cell wall carbohydrate, >90 capsular serotypes - vaccine antigen Reservoir: Humans, nasopharyngial carriage; 5 to 10 % adults, 20 to 40 % in children, serotype varies Transmission: Respiratory droplet spread, aspiration of normal flora Risk Factors/High Risk Populations: -Children and elderly -Lowered immune defense in RT -Antecedent viral RT infection, such as post- influenza infection -Alcoholics, smoking, asthma, chronic pulmonary disease, congestive heart failure (aspiration) -Asplenic/splenectomy patients=sepsis/bacteremia -Trauma/leakage of CSF to the nose= meningitis

Haemophilus influenzae

General properties: Gram negative coccobacilli (Pleomorphic); capsulated; Fastidious, require growth factors- factor X (hemin) and factor V (NAD) or grow on chocolate agar or near S. aureus on blood agar (Satellite growth). Catalase and Oxidase positive, Several capsular types (a-f). Type b (Hib) most virulent Reservoir: Humans only, nasopharynx, capsular type b carrier rate 2-4%. Non typable strains 50-80% carrier rate. Transmission: Respiratory droplets Risk Factors and High Risk Populations: Anyone; unvaccinated children between 2-4 years old more at risk, severe disease. Type b is the most virulent type. Non typable usually are normal flora but, may cause non invasive disease. Type b capsule has a unique chemical structure, containing pentose sugars-ribose and ribitol instead of hexoses and hexosamines as in other 5 serotypes.

Legionella pneumophila

General properties: Gram negative coccobacilli (but very pleomorphic), motile, hard to stain, best seen using Dieterle silver stain, obligate aerobe Fastidious growth (high nutritional demands)—cysteine (essential) and iron (accessory) Special medium BCYE, Buffered Charcoal Yeast Extract Agar for best isolation Reservoir: Aquatic habitat - survives inside amoebae in natural waters, cooling towers, A.C, showers, water misters, hot tubs, decorative fountains. Fairly resistant to chlorine in water. Can grow at 45 degrees C Transmission: through inhalation of contaminated aerosols. No person-to- person transmission Risk Groups/High Risk Populations: Middle age or >55 yrs, immunocompromised, alcoholics, smokers, Patients with COPD/ diabetes/ transplant; may occur as outbreaks (Most occur in late summer and autumn

Helicobacter pylori

General properties: Gram negative curved rod /spiral, highly motile with polar flagella, urease positive, catalase and oxidase positive. Microaerophilic (increased CO2and reduced O2). Require enriched media (Campy or Skirrow media) Reservoir: Humans as primary reservoir, life long colonization if not treated. Estimated that 70-90% of populations in developing countries are colonized before the age of 10 . In the US and other industrialized countries - Estimated 40% Transmission: Person to person spread important - oral-fecal route. Infection life long unless treated. Risk Factors/High Risk Populations: world wide/poor hygiene

Moraxella catarrhalis

General properties: Gram negative diplococci (bean shaped), family Neisseriaceae, oxidase positive. Does not ferment glucose, maltose and sucrose. A large number of Gram negative (red) cocci are seen and many appear to be attaching to or residing within the PMNs. PMNs - neutrophils Reservoir: normal pharyngeal flora in children and adults (40-50%) Transmission: respiratory droplets Risk Factors/High Risk Populations: emerging pathogen in children/elderly (in the elderly with underlying condition- may cause lower respiratory tract infection)

Haemophilus influenzae type b

General properties: Gram negative rod coccobacilli; capsulated. require growth factors, factor X (hemin) and factor V (NAD) or grow on chocolate agar or near S. aureus on blood agar (Satellite growth). Virulence factors: Polysaccharide capsule: Type b capsule is made up of polyribose-ribitol phosphate (PRP) LOS: similar to Neisseria; endotoxin Vaccine: Hib Vaccine: directed to type b capsular polysaccharide; conjugated to diphtheria toxoid or tetanus toxoid

Campylobacter jejuni

General properties: Gram negative, comma or S-shaped rod with polar flagella, motile, microaerophilic, grow best at 42 oC Three species: C. Jejuni (most common), C. coli, and C. fetus Reservoir: Zoonotic; healthy cattle, chickens, birds, pets, human Transmission: Oral fecal route, water and food contaminated with animal excreta, animal food products - such as poultry, meat, milk. Pets - especially children Risk Factors/High Risk Populations: Severe among young children, immunocompromised; decreased or neutralized stomach acids (anti-acids, milk, etc) is a risk factor; high infectious dose required (104 ). Sensitive to stomach acid, Most common cause in US and UK (1 in 100 each yr.). Can cause systemic infection among immunocompromised.

Staphylococcus aureus

General properties: Gram positive cocci, catalase & coagulase positive. Growth at 7.5% NaCl, mannitol fermentation Reservoir: Human nose, skin, low levels in colon and vaginal tract. Transmission: Consumption of contaminated foods; usually from food handler; growth in carbohydrate and protein rich foods, custards, creamy dishes, mayonnaise, salad dressings, potato egg salad, ice cream Processed meat, salted ham Risk Factors/High Risk Populations: Outbreaks in warmer months where people consume foods not kept refrigerated

Bacillus cereus

General properties: Gram positive spore forming rod; aerobic, Reservoir: Ubiquitous in nature; Transmission: Consumption of contaminated food with soil, cooked and kept warm. Such food include rice, grains, root vegetables Risk Factors/High Risk Populations: Usually occurs because heat-resistant endospores survive cooking or pasteurization and then germinate and multiply when the food is inadequately refrigerated. Clinical Disease: Two distinct food poisoning syndromes: 1. Emetic (strict intoxication) - 2. Diarrheal (infection/intoxication)

Clostridium perfringens

General properties: Gram positive, spore forming rod, anaerobic, serotype Type A most common Reservoir: Ubiquitous in nature; normal inhabitant of the large intestine of human beings and animals Transmission: Ingestion of large number of bacteria grown on pre cooked and not refrigerated meat dishes. Risk Factors/High Risk Populations: Eating pre - cooked foods (not properly stored). as meat products, poultry, gravy. Clinical Disease: Food Poisoning - toxico-infection, toxin acts on small intestine.

Bacillus anthracis

General properties: Large Gram positive spore forming bacilli, tendency for chain formation, poly-glutamic acid (polypeptide) capsule; Aerobic Reservoir: Ubiquitous around the world in soils, animals (Anthrax is primarily a disease of herbivores- such as sheep and cattle that acquire the pathogens from grazing) Transmission: by contact with infected animals/ their products or from soil (No person to person transmission) three ways of acquiring the disease (Entry of the spores) through injured skin - cutaneous anthrax inhalation : inhalation anthrax ingestion: gastrointestinal anthrax Risk Groups/High Risk Populations: abattoir workers, veterinarians, farmers, ranchers, tanners, taxidermists

Dermatophytes group

General properties: Monomorphic mold- septate hyphae. Macroconidia and microconidia (asexual spores). The shape of conidia differentiate the three genera Microsporum spp., Produces macroconida, pointed-ended (boat shaped), thick-rough walled with 4 to 8 cells (does not infect nails) Epidermophyton spp: Produces large, blunt-ended, smooth walled (Club shaped) macroconidia, in clusters of 4 to 8 cells (does not infect hair) Trichophyton spp.: Produce numerous spherical (teardrop shaped)/ peg shaped microconidia borne along the sides of hypha, single cell in each. Some species may produce microconidia as well as cigar shaped macroconidia. Reservoir: Soil (geophilic); Animals (zoophilic) such as cats, dogs and cows; Humans (anthropophilic). Transmission: Direct contact or indirect contact - introduction of spores (conidia) or hyphae Risk Factors: any one with exposure to animals - cats, dogs, cows, pigs, fowl; more common in hot humid climate

Pseudomonas aeruginosa

General properties: Motile Gram negative rod; in pairs; Oxidase positive non-fermenter (aerobic); Beta-hemolytic Produces diffusible pigments pyocyanin (blue), pyoverdin (yellow green). Some strains have capsule or slime layer- mucoid colonies and fruity, grape like odor. Reservoir: Ubiquitous in water, moist reservoirs such as- showers, hot tubs, air conditioner towers, respirators, floors, soil, ground water, even in disinfectant solutions; requires minimal nutrition. transient normal flora in some people Transmission: Inhalation of water aerosol/Contact with contaminated surface; Opportunistic pathogen from environmental sources Risk Factors/High Risk Populations: Immunocompromised people-severely neutropenic pt (Neutrophil count less than 500/µl) COPD or cystic fibrosis patients Hospitalized patients Patients on mechanical ventilation, broad spectrum antibiotics

Brucella spp.

General properties: Very small, Gram negative coccobacilli, strict aerobe. Facultative intracellular pathogen of epithelial cells and phagocytic cells - resist phagocytic killing 4 clinically important species Reservoir: B. melitensis (goats and sheep ), B. suis (pigs), B. abortus (Cattle), B. canis (dogs). Human disease in US is most commonly caused by B. melitensis Transmission: Ingestion of contaminated unpasteurized milk/ dairy products. Via contact with infected meat or the placenta of infected animals Risk Factors/High Risk Populations: Occupation such as slaughterhouse workers, farmers, and veterinarians. AND Consumption of unpasteurized animal products.

Pneumocystis jiroveci

General properties: formerly called as Pneumocystis carinii and previously classified as a protozoa. Currently, it is considered a fungus based on nucleic acid and biochemical analysis, but it lacks ergosterol (has cholesterol) and does not grow on fungal media and not sensitive to antifungal drugs. Like protozoa - has trophozoites and cysts Some authorities still classify this organism as a parasitic organism, but based on molecular typing it shares more similarity to fungi. But also shares similarities with protozoans - having a trophozoite stage and cyst stage Reservoir: Worldwide, in humans and animals. Sero-positivity almost 100% found in the lungs of mammals, where it resides in the alveoli without causing overt infection until the host's immune system becomes debilitated, causing the fungal infection

Picornaviridae Family

General properties: non-enveloped, positive sense ssRNA, resistant to detergents Two major groups Rhinoviruses: infects upper respiratory tract Enteroviruses: initial infection in the enteric tract Coxsackie virus (respiratory and intestinal tract) Poliovirus Echovirus Hepatitis A virus

Astroviruses

General properties: positive ss RNA, non-enveloped; 8 serotypes: serotype 1 causes 65% of infections Reservoir: Worldwide; Cause of infantile diarrhea second to rotavirus Transmission: person-to-person; fecal-oral Risk Factors/High Risk Populations: children < 2 years, elderly institutionalized patients; more serious in immunocompromised children and adults Clinical Disease: Gastroenteritis (milder than Rotavirus); IP 3 - 4 days; Duration < 5 days Mild illness in adults, often asymptomatic Treatment: Supportive Prevention: Food safety; Hygiene

Orthomyxoviridae

General properties: ss negative sense RNA, 8 segments of RNA, enveloped. Replicates in the NUCLEUS Has its own RNAdep—RNA polymerase Matrix proteins - important in uncoating Two separate peplomers: Hemagglutinin (HA) Neuraminidase (NA) Three types: influenza A, B, C based on variation on matrix (M) proteins and nucleocapsid (NP) proteins

Parainfluenza Virus

General properties: ss negative sense, non segmented RNA; enveloped, cytoplasmic replication; Buds from plasma membrane; pleomorphic morphology, HN and F peplomers 4 serotypes: Types 1,2, 3-second only to Respiratory syncytial virus to cause severe lower RTI Type 4-causes mild upper RTI Reservoir: Humans Transmission: Inhalation of large-droplet aerosols Risk Factors/High Risk Populations: Children 6 mth. to 12 yrs of age, Adults (re-infection); Short term immunity after disease

ETEC, EPEC, and EAEC

General properties:, Gram negative rod, lactose fermenter, Properties that differentiate E. coli from other lactose fermenters are 1. Production of indole from tryptophan 2. Decarboxylates lysine 3. Use of acetate as sole carbon source 4. Motile Reservoir: Most common facultative anaerobe gram negative bacilli in GI tract Transmission: Fecal-oral; autoinoculation Risk Factors/High Risk Populations: Anyone Clinical Disease: NON INFLAMMATORY DIARRHEA. Virulence factors : adhesion pili and secreted toxins Adhesion: Colonizing factor adhesions (CFA), Bundle forming pili (Bfp) and Aggregate Adherence Fimbriae (AAF) Exotoxins: Heat stable toxin (ST), heat liable toxin (LT), and Shiga like toxin (STx),

Corynebacterium diphtheriae

General properties:. Pleomorphic, Gram positive rods, often with clubbed ends, coryneform (club shaped). Arranged in pairs of V and L shapes. Formation of granules (volutin) - gives beaded appearance, exhibits metachromatism Reservoir: human is the only host: Normal habitat- nasopharynx, upper respiratory tract, GI, skin; normally harmless to humans, except when they acquire the toxin gene (tox)- from a phage (virus): lysogenized; Asymptomatic carriers Transmission: via Respiratory secretions/ person to person spread of the lysogenized bacteria Risk Factors/High Risk Populations: Unvaccinated, crowded condition, mostly children Incidence ↓sed with vaccine Clinical Disease: Diphtheria (Respiratory and Cutaneous) A confirmed case has not been reported in the U.S. since 2003. Diphtheria remains endemic in developing countries with low vaccination coverage. During the 1990s, the countries of the former Soviet Union reported >150,000 cases in a large epidemic.

Pathogenesis of Giardia lamblia

Giardiasis Adhere to the wall of small intestine Malabsorption of food (fats and fat-soluble vitamins) Intestinal: non-bloody diarrhea: bulky, greasy stool/steatorrhea (Incubation Period: average of 10 days)

HSV Skin and Mucosal infection

Gingivostomatitis: primary infection, more severe, in children, heal spontaneously Herpes labialis (Cold sores or fever blisters): mild, recurrent, Corner of mouth/next to lips, crops of vesicles that ulcerate Herpes Pharyngitis Keratoconjunctivitis: corneal ulcers and lesions on conjunctiva Herpetic whitlow (in finger-commonly in health personnel); Herpes gladiatorum (in body-commonly in wrestlers) Genital herpes: mostly by HSV type 2 lesions develop on the glans or shaft of the penis in men and on the vulva, vagina, cervix and perianal region of women. Urethritis in both sexes

Staphylococcus aureus

Gram positive cocci, cluster/grape like arrangement, catalase & coagulase positive. Beta hemolytic, Growth at 7.5% NaCl, and Ferments mannitol Reservoir: Human nose, skin, low levels in colon and vaginal tract. 20-30% nasal carrier in community, higher among hospital personnel (up to 90%) Transmission: Shedding from lesion and droplets from carriers or sick persons. Direct contact with skin Indirectly by fomites. Risk Factors/High Risk Populations: Broken skin -due to trauma/surgery, Presence of foreign body such as Tampons, Surgical packing, Sutures, Catheters Diabetes, intravenous drug abuse, Severe neutropenia, chronic granulomatous disease Post influenza infection

Diagnosis and treatment of Moraxella catarrhalis

Gram stain and culture Treatment and Prevention 95% of isolates in the US are beta-lactamase positive and penicillin resistant Amoxycillin+clavulanate (Augmentin), 2nd or 3rd generation oral cephalosporins, TMP/SMX

Streptococcus pyogenes

Group A Streptococcus (GAS) General properties: Gram positive cocci in chains, catalase negative, beta hemolytic on blood agar plate, bacitracin sensitive, Lancefield group A, PYR +. Over 150 different strains - M types Reservoir: Human oropharyngeal region, skin Transmission: Respiratory droplet and direct/indirect contact (exudates, fomites), especially with crowding Risk Factors/High Risk Populations: Infects all ages Virulence factors: Structural components: Capsule, M protein and F protein Toxins: Streptolysin S & Streptolysin O (Hemolysins), Pyrogenic exotoxins (Superantigens) Enzymes: Streptokinase, Streptodornases (DNase), Hyaluronidase, C5a peptidase

Streptococcus agalactiae

Group B Streptococcus (GBS) Neonatal Purulent Meningitis # 1 cause during first week of life in the US Properties: Gram positive cocci-in chains, capsulated, catalase negative, beta hemolytic, bacitracin resistant Lancefield Group B (GBS), CAMP positive, hippurate hydrolysis. Reservoir: Normal flora of URT, GI, and genitourinary tract, 10% - 30% of women Transmission: in utero, during birth, contact (other people) Risk Factors/High Risk Groups: Infants: prolonged rupture of membrane (lasting >18hrs), preterm delivery (<37weeks), maternal intrapartum fever Adults: with chronic liver disease, diabetes, cancers or HIV; Old age (> 65) Virulence factors: Capsule: Polysaccharide rich in sialic acid; antiphagocyctic & serves as adhesion to the meninges

Hepatitis B Virus Pathogenesis

HBV infects hepatocytes but does not cause direct cytopathic effect. Cell mediated immune lysis of infected cells produce symptoms and resolves the infection. Ineffective T cell response leads to mild symptoms - but - chronic disease HBsAg binding to anti-HBs can contribute to immune complex (vasculitis, arthritis, rash, etc.) Chronic HBV infection predisposes a person to more serious outcomes - cancer, or supper infection with HDV . Incubation period:Average 60-90 days Range 45-180 days Clinical illness (jaundice): <5 yrs ~<10% (weak CMI) >5 yrs ~30%-50% Acute case-fatality rate:0.5%-1% Chronic infection: <5 yrs ~ 30%-90% (weak CMI) >5 yrs ~ 2%-10% Premature mortality from chronic liver disease: 5%-25%

Hepatitis B Virus Serological Diagnosis

HBsAg - general marker of infection. HBsAb - indicates recovery and/or immunity to HBV infection. Anti-HBcIgM - marker of acute infection. Anti-HBcIgG - past or chronic infection. HBeAg - active replication of virus (patient infectious) indicates infectiveness of immune response or treatment Anti-HBe - virus no longer replicating. However, the patient can still be positive for HBsAg which is made by integrated HBV. HBV-DNA - indicates active replication of virus More accurate than HBeAg Used mainly for monitoring response to therapy.

CMV esophagitis

Has been reported in patients who have undergone transplantation, patients undergoing long-term renal dialysis, patients with HIV infection or AIDS, and patients with other debilitating diseases. Occasionally extending in the mid esophagus. Differential diagnosis: -Herpes - small multiple ulcers -Candida - white exudates

Origin of Normal flora

Healthy fetus : sterile Initial flora: during / after birth- environmental sources (air, dust, food, water, personal contact, clothing etc.) Stable flora in about 48 hours Numerous and diverse Influenced by a variety of factors such as age, diet, hormonal state, hygiene The human body has 10x more microbial cells (as normal flora) than self cells human cells- about 1013, Bacteria- about 1014 Culturable bacteria- only 10% of bacteria present (DNA recovery studies)

Pathogenesis of influenza virus

Hemagglutinin (HA): initiates infection by binding to sialic acid on epithelial cells It also agglutinates RBC Antibody against HA - prevent infection Neuraminidase(NA): cleaves sialic acid to release viral progeny. Also dissolves mucus layer Antibody against NA: prevents spread

Diagnosis of EBV

Hematological approach : Lymphocytosis (60-70% of WBC count) Atypical T lymphocytes (Downey Cells) T cells (CD8) which are larger with vacuolated cytoplasm with basophilic inclusions Serology: Heterophile antibodies (non specific IgM antibodies) bind to Paul-Bunnell antigens on RBCs of horse, sheep, goat, pig and cow MONOSPOT test (uses horse RBC) - quick test EBV specific antibodies tests; Active infection: IgM against Viral capsid antigen (VCA), or early antigen (EA). For chronic- IgG for VCA and EBNA

Hepatitis B Virus

Hepadnaviridae Enveloped, partially ds circular DNA; Replicate via RNA intermediate; Codes for reverse transcriptase Viral DNA can integrate with cell chromosome, but no integrase enzyme Reservoir: Humans, in the US 1-2.5 million carriers, 300 million global Transmission: Parenteral transmission; tattoo Sexual Mother-to-child transmission of HBV can occur via three modalities: intrauterine transmission (low) ; transmission during delivery (high); and postpartum transmission ( mainly due to close contact with the mother, beast feeding is highly unlikely) Risk Factors/High Risk Populations: Unvaccinated; injection drug users; neonates of chronic mothers, multiple sex partners, blood transfusion, medical personnel, travel to endemic areas

Prion Associated Diseases

Human Kuru (ingestion) Creutzfeldt-Jacob (CJD) (sporadic, inherited, acquired): most common of prion diseases in humans New Variant Cruetzfeldt-Jacob (vCJD) (ingestion) Gerstmann-Straussler-Scheinker (GSS) Syndrome Fatal Familial insomnia (FFI) Animal Scrapie (Sheep and Goats) Bovine Spongiform Encephalopathy (BSE) Chronic wasting disease (mule, deer, and elk) Transmissible mink encephalopathy

Cytomegalovirus

Human Herpes Virus 5; HHV-5 Properties: ds DNA virus enveloped, icosahedral. can cause lytic, persistent, and latent infection. Forms multinucleated (syncytia) and basophilic intra -nuclear inclusion body - "Owl's eye". Reservoir: Humans: (~80% of adults worldwide are sero-positive); CMV is found In all tissues and body secretions: saliva, tears, urine, stool, semen (highest conc.), vaginal and cervical secretions. Transmission: In adults: Saliva (oral), sexual route, transfusions, transplants. Mother to fetus/child: primary infection of mother Transplacental, intrauterine, birth canal, breast milk;. May excrete for many years in urine Risk Factors/High Risk Populations: fetuses, immunocompromised, AIDS, bone marrow transplant patients, people receiving chemotherapy

Ehrlichiosis

Human monocytic ehrlichiosis : Ehrlichia chaffeensis Human granulocytic anaplasmosis : Anaplasma phagocytophilum

Mode of Transmission

Human to human: Direct contact, No direct contact, Transplacental, Blood borne Non human to human: from soil source, water source, animal source, fomite source Major Routes of entry: 3I's + sexual + Mother to child Ingestion, Inhalation, Injection -deep wounds, arthropod , Sexual contact. In addition vertical transmission from mother to unborn fetus (transplacental) during delivery and after delivery via breast feeding.

Taenia spp: life cycle

Humans are the only definitive hosts for Taenia saginata and Taenia solium. Eggs or gravid proglottids are passed with feces ; the eggs can survive for days to months in the environment. Cattle (with T. saginata) and pigs (with T. solium) become infected by ingesting vegetation contaminated with eggs or gravid proglottids . In the animal's intestine, the oncospheres hatch , invade the intestinal wall, and migrate to the striated muscles, where they develop into cysticerci. A cysticercus can survive for several years in the animal. Humans become infected: by ingesting raw or undercooked infected meat. In the human intestine, the cysticercus develops over 2 months into an adult tapeworm, which can survive for years. The adult tapeworms attach to the small intestine by their scolex and reside in the small intestine . Length of adult worms is usually 5 m or less for T. saginata (however it may reach up to 25 m) and 2 to 7 m for T. solium. The adults produce proglottids which mature, become gravid, detach from the tapeworm, and migrate to the anus or are passed in the stool (approximately 6 per day). T. saginata adults usually have 1,000 to 2,000 proglottids, while T. solium adults have an average of 1,000 proglottids. The eggs contained in the gravid proglottids are released after the proglottids are passed with the feces. T. saginata may produce up to 100,000 and T. solium may produce 50,000 eggs per proglottid respectively. by ingestion of contaminated water or eating undercooked vegetables containing eggs of T. solium (Humans don't get infected with T. saginata in this way!!!)

Dracunculus medinensis Life Cycle

Humans become infected by drinking unfiltered water containing copepods (small crustaceans) which are infected with larvae of D. medinensis . Following ingestion, the copepods die and release the larvae, which penetrate the host stomach and intestinal wall and enter the abdominal cavity and retroperitoneal space . After maturation into adults and copulation, the male worms die and the females (length: 70 to 120 cm) migrate in the subcutaneous tissues towards the skin surface . Approximately one year after infection, the female worm induces a blister (due to release of toxic substances) on the skin, generally on the distal lower extremity, which ruptures. When this lesion comes into contact with water, a contact that the patient seeks to relieve the local discomfort, the female worm emerges and releases larvae . The larvae are ingested by a copepod and after two weeks (and two molts) have developed into infective larvae. Ingestion of the copepods closes the cycle .

Hookworm: Life cycle

Humans get infected when an infective larvae, filariform, penetrate the skin. From the skin they enter the venules and are carried to the heart and lungs where they grow and eventually break out into the alveoli and pass up the respiratory tree. After they are swallowed, they attach to the intestinal mucosa and become sexually mature in 5 to 6 weeks. Females deposit eggs that are passed in the feces. In the proper soil, under ideal conditions, the eggs hatch in 1 to 2 days. Temperatures between 25°C and 35°C and a shady, sandy, or loamy soil with vegetation favor larval development. The rhabditiform larvae that emerge feed on bacteria and organic debris, moult twice, and develop into slender, infective filariform larvae in 5 to 8 days. The filariform larvae do not feed; if they are unable to penetrate a host, they die in a few weeks. Most adult worms usually live for 1-2 years but longer longevity is possible.

Prevention of HAV

Hygiene: interrupt transmission: Good food/water and personal hygiene, proper chlorination water Vaccination: Passive (immune serum globulins) and active - may be given pre or post exposure Active immunization: -inactivated HAV Vaccine, 1995 ( there is only one serotype of HAV Recommended for all children at 2 years Adults at high risk, such as travelers to high endemic regions, men who sex with men Treatment: No antiviral drugs/ supportive care

Pathogenesis of Molluscum contagiosum virus

Hyperplasia of epithelial cells within which cytoplasmic inclusion bodies can be seen - wart like lesions Clinical disease: IP 2-8 weeks Nodular to wart like lesion Cutaneous Warts; appear in clusters Are small firm, white, pink, or flesh-colored, pearl-like bumps with a dimple or pit in the centre. White cheesy material may be expressed from the pit Usually painless. In adults; mostly on lower abdomen, Pubic region, genitalia or inner thighs In children; face, trunk or extremities

Ectoparasite Skin manifestation

Hypersensitivity reaction: Lice: pediculosis capitis/corporis/pubis Bedbugs: linear lesions Itch mite: Scabies/Mange/Itch Chigger mites: Severe dermatitis/trombiculosis) Myasis (Larval growth): Flies Necrotizing lesion: Necrotic arachnidism (Brown recluse spiders)

Virulence of bordetella pertussis

I. Adhesins: Filamentous hemagglutinin (FHA) and Pertactin Both bind to integrins on ciliated cells Both bind to CR3 (complement receptor) on macrophages and induce phagocytosis without initiating oxidative killing Result in intracellular growth in macrophages; protected from humoral immunity II. Toxins: 1. Pertussis toxin (PTx) - AB type toxin ADP ribosylation of Gi protein; increased cAMP level Increased respiratory secretion and mucus production Interferes with the early chemokine production/signal transduction Inhibits neutrophil chemotaxis Causes peripheral lymphocytosis 2. Tracheal Cytotoxin (Peptidoglycan subunit) Low conc: Cilliostasis High conc: Extrusion of ciliated cells, Interferes with DNA synthesis, kills ciliated respiratory cells 3. Adenylate cyclase toxin: Activated in host cell by calmodulin, causes conversion of ATP to cAMP, Effect same as above

Nervous system pathogens

I. Bacteria Neisseria meningitidis Group B streptococci Listeria monocytogenes Clostridium tetani Escherichia coli Streptococcus pneumoniae Haemophilus influenzae Clostridium botulinum Mycobacterium tuberculosis Treponema pallidum Mycobacterium leprae (Peripheral nervous system) II. Viruses Enteroviruses Coxsackie virus EchovirusesPoliovirus Rabies virus Herpes virus JC Virus Measles virus III. Fungi Cryptococcus neoformans Coccidiodes immitis IV. Parasites Naegleria fowleri Acanthamoeba castellanii Trypanosoma brucei spp Taenia solium Echinococcus granulosus V. Proteinaceous Infectious Agents Prions

Laboratory Diagnosis of Viral Disease

I. Direct microscopic examination of clinical specimen Light/compound microscopy: Cytopathic effect (CPE). UV microscopy: Detection of viral antigens by fluorescent Ab staining Electron microscopy, immunoelectron microscopy II. Culture: cell culture (sometimes, inoculation of eggs or animals) Identification: Assessment of Cytopathic effect (CPE), Hemadsorption and other characters Detection of viral antigens by UV microscopy Quantification: viral titer-plaque assay Assessment of oncogenic potential (focus assay) III. Serological analysis: antibody detection/titer ELISA, Hemagglutination inhibition assay Neutralization tests: block cytopathic effects Western blot IV. Detection of viral antigens in sample: ELISA, rapid tests etc. V. Molecular analysis of genetic material PCR and In-situ hybridization: in clinical specimen or in culture specimen

Strongyloides stercoralis: Diagnosis

I. Larva (not eggs!!!) detection in stool or sputum Larva detection in stool by Baermann funnel gauze method II. Culture: charcoal culture or agar plate method; rarely used Tracks/furrows with motile larvae III. Serology: detection of antibodies; screening test or as an adjunct for diagnosis If the fecal sample is left for a day or more under tropical conditions, the larvae of hookworm will also have hatched out and eggs might no longer be evident.

Common Causes of Endocarditis

I. Native Heart valve Viridans streptococci (e. g, S. bovis, S. mitis, S. anginosus), Staphylococcus, Enterococcus II. Prosthetic Heart Valve Early (less than 2 month post implantation) S. aureus, S. epidermidis, Aerobic GNB Late (more than 2 month post implantation) Viridans streptococci, S. epidermidis and S. aureus III. IV illicit drug users S. aureus and GNB (Pseudomonas most common among GNB) Others Fungi Candida species, Aspergillus species Coxiella burnetti (Q fever) Chlamydia Bartonella Legionella

S. aureus virulence factors

I. Structural components Protein A: antiphagocytic - binds to Fc region of IgG, prevents complement activation - no C3b deposition. Also prevents binding of phagocytic cells Capsule: antiphagocytic Cell wall components: lipoteichoic acid and peptidoglycan have endotoxin like activity- activation of macrophages and release of inflammatory cytokines induce septic shock. Adhesins: cell bound proteins II. Toxins: Cytolytic (membrane damaging) toxins: are the staphylolysin (hemolysin), leukotoxin and leukocidin [Panton-Valentine (P-V) leukocidin]. P-V kills phagocytic cells causing release of radicals and other enzymes which are responsible for extensive damage of tissue Exfoliative toxins- a protease that degrades desmoglein Toxic shock syndrome toxin-1: superantigens Enterotoxin: superantigens III. Enzymes: Staphylokinase/ Fibrinolysin : degrades fibrin clots, assists bacterial escape from clots Coagulase: also known as clumping factor- form fibrin clots. It is secreted as well as expressed on the surface Hyaluronidase dissolves inter-cellular cement allowing bacterial spread Abbreviations: TSST: Toxic shock syndrome toxin EFT: Exfoliative toxin SE: Staphylococcal enterotoxin Note: Leucocidin is a kind of leukotoxins, kills cells by formation of the pores.

Fungal Morphology

I. Yeasts—oval, unicellular, reproduce by budding (blastoconidia) eg, Cryptococcus neoformans II. Yeast like: yeasts but form pseudohyphae (chain of elongated yeast cells, not true hyphae) during invasion of tissue eg, Candida albicans III. Mold form: thread-like tubular multicellular hyphae, colonies have cottony or velvety surface. Intertwining mass of hyphae is known as mycelium eg, Aspergillus spp. IV. Dimorphic: exist in 2 forms-yeast (at 37 0C) and mold (at 25 0C) interconversion between them influenced by temperature - Thermal dimorphism. Eg, Histoplasma capsulatum

Pathogenesis of Tularemia

ID: 10-50 bacilli No identifiable exotoxins Has polysaccharide capsule Facultative intracellular, inhibits phagosome-lysosome fusion Can survive inside macrophages of the reticuloendothelial system Formation of granulomas Also known as rabbit fever, deer fly fever: morality rate 5-30% Clinical manifestation depends on site of entry, IP 3-5 days. Acute onset of fever, chills and malaise Ulceroglandular: (70-85% of tularemia); entry th' insect bite/skin Cutaneous ulcer with swollen regional lymph nodes. Papule ulcerates with necrotic center and raised border Most common manifestation Glandular: without ulcer Oculoglandular: Eye involvement and swollen cervical LN Oropharyngeal or Gastrointestinal tularemia: consumption of contaminated meat Pneumonic tularemia: Inhalation via aerosol, most serious Typhoidal tularemia: prolonged systemic signs of sepsis (febrile illness similar to typhoid fever)

RNA Viruses

III: dsRNA: have positive and negative sense RNAs; negative sense RNA is used as a template for mRNA synthesis, Carries RNAdep-RNApoly (viral) to make the mRNA and also the genome; eg. Rota virus IV: ss +ve RNA: can directly act as mRNA, but during replication of their genome, forms a negative strand RNA (template) and then mRNA; code (viral) RNAdep-RNApoly [picornavirus (eg.rhinovirus), toga virus (chickengungya virus) etc. V: ss -ve RNA: must bring (carry) RNAdep-RNApoly (viral) to make mRNA (which also acts as a template for replication of their genome); orthomyxovirus (influenza virus), paramyxo virus (measles), rabies virus etc. VI: ss +ve RNA passing through a DNA intermediate: use their reverse Transcriptase to make ds DNA and host DNA dep-RNApoly to make mRNA (retrovirus- HIV)

Yellow Fever Clinical Disease

IP - 3-6 days Sings and symptoms Sudden onset: febrile illness (may be self-limited) May progress; to involve the liver, kidney and heart Hepatitis like syndrome Hemorrhagic fever: GI hemorrhage : "Black vomit" Failure of multiple organs: Heart and kidney signs Shock 20-50% mortality rate (among the ones with severe disease),usually within 10-14 days Diagnosis: PCR detect virus, serology- IgM detection Treatment: Supportive Prevention: Vector control: destruction mosquito breeding sites Vaccine; Live attenuated vaccine, booster after 10 yrs. recommended/required for people traveling to/living in endemic area

Rocky Mountain Spotted Fever Clinical Disease

IP 2-14 days Rapid onset of symptoms, Triad: Fever (1020 F), Headache, Rash Other: malaise, myalgia, arthralgia Wide spread vasculitis: leads to GI symptoms, CNS symptoms (delirium, confusion, stiff neck etc); conjunctivitis (red eye) In severe cases: DIC, encephalitis, respiratory, renal, and cardiac failure RASH: Starts first on ankles and wrist usually appears 2-5 days after the onset of fever: as small, flat, pink, non-itchy spots (macules), progresses to petechial form Swelling of ankles and wrist then spreads to involve the trunk, palms and soles and face (Centripetal rash) Can become gangrenous Without treatment, death in 8 -15 days

Lyme Disease Primary stage

IP 3-30 days 70-80% of infected pts presents Typical rash at the site of bite : Erythema Chronicum Migrans, has a target or Bull's Eye appearance - size ranges from 5 -30 cm (expands gradually with time) red macule, with a clear center, painless, (may feel warm on touch) may be accompanied by flu like symptoms:

HPV clinical disease

IP 3-4 months (up to 2 years) Cutaneous warts: mostly caused by type 1-4 Ano-genital warts (Condylomata acuminata): Type 11 and 6 most common (90%) In women - within vagina, on the cervix, and around the anus or within the rectum. In men - on tip of penis, on scrotum, or around the anus. Oral and Laryngeal warts (Respiratory papillomas): Oral: New born babies; warts can develop in the mouth of a person who has had oral sexual contact with an infected person; stalked growth Laryngeal: most common benign epith. tumor of larynx; If infection of children during birth-life threatening Carcinoma of cervix, penis, and anus: caused by HPV type 16, 18 (most common), 31, and 45

Acute hematogenous osteomyelitis

IP: 1 or 2 days Children more at risk- single long bone: tibia (most common), femur, or humerus Source-inapparent in children but some with blunt trauma. Chills, fever, malaise, localized pain and tenderness, in many cases—restriction of movement or difficulty bearing weight. Overlying erythema and swelling- indicate extension of pus through the cortex

Endemic Murine Typhus pathogenesis

IP: 1-2 wks Abrupt symptoms: fever, severe headache, chills, myalgia (similar to epidemic typhus but milder) and Maculopapular Rash (not petechial) may appear (in 50% cases) late in the illness, typically restricted to chest and abdomen Course of the disease: generally uncomplicated, lasting less than 3 wks even in untreated pts Diagnosis: indirect fluorescent assay (IFA) level of antibody Prevention and control Avoid rats and rat fleas Tetracycline

Primary syphilis

IP: 10 days to 3 months Syphilitic chancres: One (most) or more at the site of entry Painless, hard ulcer with raised borders, which heals within 2 months Regional lymphadenopathy: Firm, nonsuppurative: may persist for months, despite healing of the chancre. Highly Infectious stage

HAV Clinical Disease

IP: 15-50 days Children: usually asymptomatic/milder Adults: asymptomatic/symptomatic with acute onset - resolve spontaneous Asymptomatic shed virus Prodrome followed by typical hepatitis Jaundice: may not be seen in all cases In less than 10% of children < 6 years of age, 40%-50% of older children, and 70%-80% of adults. Hepatitis fulminant hepatitis: up to 80% mortality rate Occurs in 1-3/1000

Acquired Toxoplasma gondii

IP: 5-23 days A. Immunocompetent persons Cervical lymphadenopathy: most common Single or multiple, usually non tender Fever [usually <40°C] Headache, malaise, fatigue, myalgia, sore throat B. Immunocompromised patients: rapidly fatal if untreated -CNS: Principal opportunistic infection of the CNS in persons with AIDS meningoencephalitis, and mass lesions. -Lungs: Toxoplasma pneumonia (dyspnea, fever and non productive cough) -Heart: usually asymptomatic, but may progress to heart failure

Measles Clinical Disease

IP: 7-13 days Starts with Prodrome: High Fever, and CCC and P, (Cough, Coryza, Conjunctivitis and Photophobia) - lasts for 4 days After 2 days of prodrome: Koplik's spots appear commonly on the buccal mucosa and throat small bluish-white to grey spots (lesions) on erythematous base in mucus membrane; lasts 24-48hrs Maculopapular skin rash; within 12-24 hrs of appearance of Koplik spots - starts from the neck, below the ears, spread to all over the body including face, palms and soles fever is highest and the patient is sickest on the day the rash appears The rash disappears in the way it starts Pneumonia: due to the virus or secondary bacterial super inf. Giant cell pneumonia without rash - in T cell deficient children Stillbirth (rather than only congenital abnormalities) if infects during pregnancy

Tetanus

IP: few days to weeks, strong muscle contraction (spastic paralysis) Generalized : most common Lockjaw or Trismus - (Masseter muscles) Risus sardonicus (spasm of facial muscle) i.e, characteristic sardonic smile Drooling, sweating, irritability Opisthotonos: Persistent back spasms Severe cases: cardiac arrhythmias, respiratory failure, BP fluctuations, dehydration, abdominal rigidity No loss of consciousness Localized: disease confined to musculature at the site of primary infection Neonatal: typically associated with infection of umbilical stump (mortality 90%) that progresses to become generalized; represents 50% of all tetanus cases in third world countries

Phenotypic mixing coat component

If two different viruses infect a cell, progeny viruses may contain coat components derived from both parents and so they will have coat properties of both parents. This is called phenotypic mixing. IT INVOLVES NO ALTERATION IN GENETIC MATERIAL, the progeny of such virions will be determined by which parental genome is packaged and not by the nature of the envelope.

Fasciola hepatica Life Cycle

Immature Fasciola eggs are discharged in the biliary ducts and in the stool. Eggs become embryonated in water, eggs release miracidia, which invade a suitable snail intermediate host. In the snail the parasites undergo several developmental stages (sporocysts , rediae , and cercariae). The cercariae are released from the snail and encyst as metacercariae on aquatic vegetation or other surfaces. Mammals acquire the infection by eating vegetation containing metacercariae. Humans can become infected by ingesting metacercariae-containing freshwater plants, especially watercress . After ingestion, the metacercariae excyst in the duodenum and migrate through the intestinal wall, the peritoneal cavity, and the liver parenchyma into the biliary ducts, where they develop into adult flukes .

Pathogenesis of Blood stream infection

Immune response to microbial triggers Microbial triggers to release cytokines: Gm -ve: endotoxin (LPS) Gm +ve: Toxins; most commonly superantigens eg, TSST and enterotoxin of Staph. Cytokines: TNF, IL-1, IL-12, IFN gamma, IL-6 Usually begins with nonspecific symptoms-Fever, chills, constitutional symptoms- fatigue, malaise, anxiety or confusion Organ dysfunctions: Lung-ARDS, tachypnea Kidney: acute renal failure and proteinuria Liver: ↑bilirubin, alkaline phosphatase GIT: nausea and vomiting, diarrhea, Ileus (obstruction) Heart: Impaired cardiac contractility Brain: confusion Skin: Petechiae or purpura (N. meningitidis/Rickettsia spp) Sunburn like rash (Generalised erythroderma-Staph or Strepto) Ecthyoma gangrenosum (P. aeruginosa)

Pyogenic S. aureus

Impetigo (pyoderma): confined to superficial skin; require break in skin; Starts with red macule, then pus filled vesicle (pustule) on erythematous base; Rupture and crusting (honey colored), fever absent mostly in young children, affecting primarily face and limbs Conjunctivitis: most common cause of bacterial conjunctivitis Folliculitis: is an infection of the hair follicle If on the eye-lid, it is known as stye Most common cause Furuncles (boils) are an extension of folliculitis, large, painful raised nodules; often in clusters or groups; may drain Carbuncles are coalesced furuncles, deeper, multiple sinus tracts, more severe symptoms due to systemic spread- chills, fevers Cellulitis: intense inflammation around an infected site, with systemic symptoms, involves the skin and subcutaneous tissue Abscess: Results commonly from wound infections after trauma/surgery (most common cause of post surgical infection)

Prevention of Typhoid

Improve personal and public hygiene Identify and treat carriers antibiotic treatment (fluoroquinolones) some carriers require removal of their gallbladder to cure them Vaccine: two types -Capsular vaccine: Vi antigen -Live attenuated vaccine: (Ty21a strain): taken orally: can reduce risk of disease for travelers in endemic areas: Vaccine not 100% protective

Monkey Pox

In early June 2003, was reported among several people in the United States. Most of these people got sick after having contact with pet prairie dogs that were sick with monkeypox. This is the first time that there has been an outbreak of monkeypox in the United States. In humans, the signs and symptoms of monkeypox are like those of smallpox, but usually they are milder. Another difference is that monkeypox causes the lymph nodes to swell. Cx-Characteristic Pustule/papules cx of Monkey pox symptoms milder + Lymphadenopathy compared to small pox

Upper reproductive tract gonorrhea

In men: Epididymitis: inflammation of epididymis ; leads to swelling of scrotum may lead to sterility In women: PID Endometritis, Salpingitis, tubo-ovarian abscesses, may also cause sterility, ectopic pregnancy

Immune Reconstitution Inflammatory Syndrome (IRIS)

In some patients with AIDS who are infected with Cryptococcus, treating the patient with highly active anti-retroviral therapy (HAART) causes an exacerbation of symptoms. The explanation of exacerbation of symptoms is that HAART increases the no. of CD4 cells, which increases the inflammatory response. Some patients have died as a result of cryptococcal IRIS. To prevent IRIS, patients should be treated for the underlying infection before starting HAART.

Echinococcus granulosus life cycle

In the normal life cycle of Echinococcus species, adult tapeworms (3-6 mm long) inhabit the small intestine of carnivorous definitive hosts, such as dogs, coyotes, or wolves, and echinococcal cyst stages occur in herbivorous intermediate hosts, such as sheep, cattle, and goats. A number of other suitable intermediate hosts, such as camels, pigs, and horses, are involved in the life cycle in many parts of the world. Humans also serve as the intermediate host. In humans, it is the presence of the cyst that cause disease - A small cyst might contain hundreds of protoscolices; a large cyst might contain tens of thousands! This tremendous reproductive potential poses a problem in the intermediate host including humans. The disease is most commonly found in people involved in raising sheep, as a result of the sheep's role as an intermediate host of the parasite and the presence of working dogs that are allowed to eat the offal of infected sheep. Most commonly affected organs are liver followed by lung. Space occupying lesion, if a hydatid cyst breaks open, the protoscolex (larvae) enter the blood stream, may reach any organ: Each protoscolex could grow into a new hydatid cyst. They may also reach the brain - Unrelenting headache

Paralytic poliomyelitis

In ~1% , 3-5 days after the minor symptoms disappear The virus attacks anterior horn cells of the spinal cord and motor cortex of the brain Paralytic poliomyelitis: asymmetric flaccid paralysis with no sensory loss May involve one leg, or both or four extremities . Bulbar poliomyelitis: infection of brain cells (motor cortex), more severe life-threatening respiratory paralysis of muscles of pharynx, vocal cords, lungs Iron lungs used to assist breathing before vaccination. Post-polio syndrome: a sequela of poliomyelitis occurring much later in life (30-40 years later) deterioration of the residual function of the affected muscles as a result of combined loss of neurons due to polio and to old age

Phenotypic Diagnosis

Includes the signs, symptoms, course, outcome, and response to treatment. Observable characteristics Isolation and characterization of pathogens Microscopic features - shape, size, staining reaction, cell structures Cultural Characteristics: Growth on artificial media; colony appearance; texture, size, shape, pigment, growth requirements Biochemical Characteristics - detection of presence or absence of particular enzymes or metabolic pathways Biotyping Serotyping: characterize based on antigen type Sensitivity to Antibiotics: for identification purpose

Clinical findings of influenza

Incubation of 1 to 4 days, Fever, headache, sore throat, severe muscle pain and dry cough may follow Recovery 7-10 days Complications: occur in the young, elderly, and persons with chronic cardio-pulmonary diseases Pneumonia caused by influenza itself Pneumonia caused by secondary bacterial infection, most commonly- S. aureus, S. pneumoniae, or H. influenzae Reye' s syndrome: acute encephalopathy and liver degeneration in children-associated with aspirin use, life threatening, follows many viral fevers in children

Cholera

Incubation period 2-3 days Abrupt onset of profuse watery diarrhea up to 14-20 liters/day Rice water stools (colorless feces, flecks of mucus) Electrolyte imbalance, massive fluid loss, Hypokalemia Loss of skin turgor and weak pulse. cyanotic (turning blue), sunken eyes and cheeks, a scaphoid abdomen, and weak or absent peripheral pulses. Death can occur from: Hypovolemic shock; Metabolic acidosis; Cardiac arrhythmia, renal failure

Insects Vs. Arachnids

Insects Pediculus humanus (lice) Dermatobia hominis (flies/maggots) Cimex lectularius (bed bugs) Arachnids Sarcoptes scabiei (Itch mites) Eutrombicula spp. (Chigger mites) Dermacentor variabilis (Ticks) Dermacentor andersoni (Ticks) Ixodes dammini (Ticks) Ornithodorus spp (Ticks) Latrodectus mactans (Black widow spiders) Loxosceles spp. (Brown recluse spiders)

Herpes Pathogenesis

Infection has three phases: 1. Initial lytic infection: Herpes viruses infect epithelial cells. Actively multiply and eventually kills the cells, form vesicles 2. Latent infection in neurons (sensory ganglion cells) trigeminal ganglia (facial area); lumbar or sacral ganglia (genital herpes) Remain inactive 3. Reactivation: by several factors (plz, see the note below!); comes out of the neurons and infect and kill epithelial cells - causes recurrent symptoms Rule of Thumb: HSV 1 = mostly oropharyngeal infection (above waist) HSV 2 = mostly genital infection (Below waist) Avoid immune attack - spreading by making cells to merge - creating multinucleated cells - syncytia

Black piedra

Infection of hair (scalp), associated with poor hygiene By Piedraia hortae-mold (Brown to black, dematiaceous), form asci and ascospores (sexual phase) Reservoir: soil Firmly attached dark nodules on hair shaft; asymptomatic Shaving or cutting the hair is the treatment of choice also treated by using oral terbinafine.

Pathogenesis of tetanus

Infection of wound by spores Germination of spores to bacilli Bacilli produce toxins (tetanospasmin) Toxin carried intra-axonally (retrograde to CNS) Toxin degrades synaptobrevin Inhibition of GABA/glycine (inhibitory neurotransmitters) Acetylcholine secreted continuously Muscle remains contracted

Rotaviruses

Infectious Agent: (rota means wheel), ds RNA (11 segments), non-enveloped, icosahedral nucleocaspid Several serotypes - 42 types Resistant to detergents, acids, drying Infective dose 10-100 infectious viral particles Reservoir: Human GI tract Transmission: Fecal-oral including aerosolization, stable over a wide range of temp and pH Risk Factors/High Risk Populations: Infants/children, < 2 years Seasonality: Marked; November to April - winter to spring

Vulvovaginal candidiasis

Infectious agent: Candida albicans, yeast with pseudohyphae Reservoir: Normal body flora in skin, mouth, vagina, intestines; found on skin and mucosa of many animals Transmission: Disease due to overgrowth: physiological conditions: pH, increased sugar, decreased normal flora Risk Factors/High Risk Populations: Diabetes, Immunocompromised, antibiotic use, pregnancy, birth control pills

Chikungunya Fever

Infectious agent: Chikungunya virus- Togavirus, enveloped, +ss RNA Infects endothelial cells, dendritic cells, macrophages, lymphoid organs, liver, CNS and muscle Reservoir: Humans, Monkeys Transmission: Mosquitoes (Aedes aegypti and Aedes albopictus) - the later is spreading to new geographic locations, bite mostly during the daytime. Risk Factors/High Risk Populations: Urban, living in endemic areas: Travel to endemic areas Diagnosis : Serology - IgM , Reverse Transcriptase PCR (RT -PCR) Treatment and Prevention: Symptoms are treated, e.g. with analgesics and anticonvulsants. Vector control No vaccine

West Nile Virus

Infectious agent: Flavivirus- Env, Pos sense SS RNA, icosahedral Epidemiology: Reservoir- major host birds, infects a wide range of animals, dogs and cats, horses. Kills animals (horses and birds) Vector: Culex mosquito: breeds in stagnant water Distribution: introduced to the US in 1999, now reported from almost all states. Caused several outbreaks involving animals and humans. The leading cause of arboviral encephalitis in the US Risk group; any one

Bacterial Vaginosis (BV)

Infectious agent: Polymicrobial: primarily anaerobic bacteria -Gardnerella vaginalis major one: found in all cases Gram variable, pleomorphic rods, -Others: include Mycoplasma hominis, Mobiluncus sp., and Prevotella sp Source: normal vaginal flora Transmission: Sexual controversial? sexually inactive and lesbians are also affected.. People at risk: mostly childbearing age, increased douching, increased number of sexual partners, Pathogenesis: disruption of the balance between the normal flora resulting in an overgrowth of certain bacteria

Ebola Hemorrhagic Fever (EHF)

Infectious agent:, Ebola virus- a Filovirus, enveloped, -ssRNA, filamentous and highly pleomorphic structure Four subspecies infect humans and primates - based on geographic distribution Reservoir: Bats (fruit bats) and monkeys. Pigs (different strain) Highly virulent in primates, and humans. Transmission: through skin abrasions or mucosal memb. (eye, nose, mouth) by contact with blood or secretions from infected person or animal (Sick or Dead) objects (such as needles and syringes) contaminated with body fluids from an infected person infected fruit bats or nonhuman primates (such as apes and monkeys) Semen from a man who recovered from EVD Aerosol- from experimental data (pigs) ?? Distribution: Limited areas in Africa, with a potential to spread, because the natural bat reservoir is widely distributed around the globe

Chromomycosis

Infectious agents: dematiaceous molds grow on soil and woody plants; Fonseca, Phialophora, Cladosporium spp. Transmission: Enter the body through trauma Risk factor: Tropics (warm, moist), rural Disease: Slow progressive granulomatous infection, -Common in legs and arms -Wart-like lesions with crusting abscesses along lymphatics; -some with cauliflower like growth, clustered within the same region -Can be highly destructive but do not cause systemic infection

Epstein Barr Virus

Infectious mononucleosis HHV-4 Herpesviridae Family Gamma Virus General properties: ds linear DNA, enveloped, belongs to human herpesviruses, type 4 (HHV 4) Reservoir: human, 90-95% are sero-positive, Asymptomatic shedding with saliva, lifelong infection Transmission: Person to person via oropharyngeal route - saliva; kissing, sharing toothbrushes, drinking glasses Risk Factors/High Risk Populations: Young adults - previously not infected. Infections in infants or early childhood are usually asymptomatic and gives life-long immunity. 50 % of infections in teens and older are symptomatic.

Pathogenesis of leprosy

Infects histiocytes, endothelial cells and Schwann cells PGL-1 (phenolic glycolipid 1) present in cell wall - resists macrophage killing; binds to Laminin of nerve fibre Lipoarabinomannan and Trehalose dimycolate : Role in intracellular survival Preference for lower temperature (skin, nasopharynx, eye, larynx, testicles, peripheral nerves) Nerve damage is the result of two processes- Damage caused by direct contact or, Damage caused by CMI attack on nerve

Pathogenesis of chlamydia

Infects non-ciliated columnar or cuboidal epithelial cells of mucosal layers. Intracellular Destruction of the cells and the host inflammatory response (granuloma formation) Different serotypes (A-L) associated with different diseases. In men causes urethritis, epididymitis, proctitis In women cervicitis, urethritis, pelvic inflammatory disease may lead to infertility or ectopic pregnancy, Fitz-Hugh-Curtis Infant pneumonia: 4-11 weeks after birth, interstitial pneumonia, typical staccato cough Inclusion conjunctivitis: Neonates (5-12 days) as well as adults Complications: Reiter's syndrome : risk HLA-B27

Meningoencephalitis

Inflammation of both the meninges and the brain tissues Signs and symptoms of meningitis Early -fever, -headache -stiff neck (nuchal rigidity) Late -photophobia -altered consciousness Plus encephalitis fever, headache, altered mental status, seizures and focal neurologic deficits

Meningitis

Inflammation of the meninges Signs and symptoms include Early -fever, -headache -stiff neck (nuchal rigidity) Late -photophobia -altered consciousness Changes in the CSF -Increased pressure -Change in glucose and protein level -Elevated white blood cell Bacterial Meningitis: S. pneumoniae, H. influenzae, N. meningitidis: capsule major virulence rarely infect the brain parenchyma. Viral meningitis: mainly by members of enteroviruses Chronic meningitis: Cryptococcus neoformans Mycobacterium tuberculosis Treponema pallidum (STD)

Rubella virus pathogenesis

Inhalation, Virus enters cells of respiratory tract and replicates locally inside epithelial cells Spreads to local lymph nodes (lymphodenopathy), liver, spleen Viremia, Disseminates to other organs (Skin, mucous membrane) Virus enters cells of respiratory tract, replicates locally, spreads to local lymph nodes, and disseminates hematogenously to skin and mucous membranes. Viral replication also occurs on skin and mucosa. -Virus is not cytolytic -Cell mediated immunity plays important role in resolving the disease -Rash is associated with immune complex mediated vasculitis -Infection gives life long immunity

Nucleic Acid antibiotics

Inhibit Nucleic Acid Synthesis and Function DNA Metronidazole Quinolones /Fluoroquinolones RNA Rifampin

Penicillins Mechanism of Action

Inhibit Peptidoglycan Synthesis-act on penicillin binding proteins (primarily transpeptidases) Transpeptidases Transglycosylase enzymes Carboxypeptidases Accumulation of peptidoglycan monomers (since they are unable to cross link in +nce of penicillin) leads to activation of autolytic Enzymes (Murine hydrolase): Lysis of cells Bactericidal in actively growing bacteria

Recombination

Integration of donor DNA to the recipient chromosome/genome Stabilizing genetic information after gene transfer This results in new combinations of genes on the chromosomes involved Types A. Homologous DNA Recombination B. Site-Specific Recombination

Recombination

Interaction between two genetically different viruses Exchange of genetic material between different but related viral strains, occurring when infecting a cell simultaneously. By 2 mechanisms: Either by crossing over within the regions of significant base sequence homology (common with ds DNA viruses eg, Herpes 1 and 2) or, By exchange of segmented genome Reassortment-when two viruses with segmented genomes are simultaneously present and segments are mixed in progeny capsid Role in emergence of Epidemic Influenza strains

Diagnosis of Taenia solium

Intestinal-demonstration of eggs/proglottids in stool Cysticercosis: X-ray, CT, MRI imaging, Biopsy Eggs of Taenia Spherical and brown in colour (bile stained) Measure approx. 30-40 µm in diameter The inner embryophore is brown, thick walled and radially striated Contains an oncosphere with 3 pairs of hooklets Doesn't float in saturated solution of common salt

Bacillus cereus Emetic syndrome

Intoxication Caused by ingestion of pre-formed heat stable toxin (survives 90 min at 126ºC) Associated usually with carbohydrate rich foods Boiled rice held for prolonged periods at ambient temperature, fried rice, pasta, Enterotoxin - (Cereulide) - similar to S. aureus - stimulates vagus nerve leading to emetic response Rapid-onset: 1-6 hrs incubation period; symptoms last ~24 hours Symptoms: Profuse vomiting, nausea, and abdominal cramps; Fever and diarrhea usually absent

Clostridium perfringens gastroenteritis

Intoxication and infection High infective dose required: 108 to 109 - ingestion of vegetative cells which release toxin on becoming spore in the small intestine. Toxin acts on small intestine, but not large intestine, Enterotoxin - heat liable similar B. cereus diarrhea toxin - increase in cAMP - watery diarrhea Incubation - 8-16 hours (could be longer); Duration - generally lasts 24 hours or less. In the elderly or infirm, symptoms may last 1-2 weeks. Signs and Symptoms - Abdominal cramps, watery diarrhea, nausea - no fever or vomiting

Bacillus cereus Diarrheal syndrome

Intoxication/infection Ingestion of preformed toxin or organisms and subsequent production of heat-labile toxin - 5 min 56ºC or 30 min 45ºC Mode of action: stimulates adenylate cyclase (cAMP) causing intestinal fluid secretion - causing diarrhea Associated with protein rich foods, such as meats, stews, gravies, vegetables dishes, puddings , vanilla sauce and milk Slower-onset: 6 -16 hrs incubation symptoms last 24-48hrs Symptoms: Watery diarrhea, nausea, abdominal cramps; vomiting, fever absent

Pathogenesis of Chlamydophila pneumoniae

Intracellular growth- infects respiratory epithelial cells; macrophages, endothelial cells of coronary artery, and smooth muscle cells Clinical disease: mostly asymptomatic but is associated with Pharyngitis, sinusitis bronchitis Atypical pneumonia similar to Mycoplasma (walking), Atherosclerosis, Alzheimer's disease, asthma, and reactive arthritis (however, their role not yet well understood)

Pathogenesis of Plasmodium

Intracellular parasite, infects red blood cells and hepatocytes, dormancy in hepatocytes (except P. falciparum) P. falciparum: The processes of cytoadherence, rosetting, and agglutination are central to the pathogenesis of falciparum malaria Sequestration of RBCs containing mature forms of the parasite in vital organs (particularly the brain) interfere with microcirculatory flow and metabolism Clinical disease: Malaria : Incubation period: approx. 2 wks after bite. Fever, chills and sweating, shows periodic cycle. Febrile paroxysm synchronizes with erythrocytic schizogony, Types of fever: A. Tertian fever (with 48 hr cycle): recurs every 3rd d B. Quartan fever (with 72 hr cycle): recurs every 4th d C. Quotidian fever: recurs every 24 hrs Hepatosplenomegaly and anemia.

Pathogenesis of Toxoplasma gondii

Intracellular parasite: infect macrophages, muscle cells, epithelial cells - in different tissues Toxoplasmosis: affect many organs Clinical manifestations based on type of infection: I. Acquired infection: Immunocompetent Immunocompromised: severe II. Congenital infection:

Pathogenesis of Q fever

Intracellular pathogen of monocytes and macrophages: cause diffuse granuloma in organs involved Clinical Disease : Q fever: No rash. Mostly asymptomatic Acute Q fever: Flu like symptoms with fever, Atypical pneumonia and hepatitis. Chronic Q fever Subacute Endocarditis - chronic - months to years can sometimes be superimposed on previous valve lesion

Pathogenesis of Chagas Disease

Invade and multiply inside: smooth muscle and ganglion cells in organs such as heart, walls of GIT; skeletal muscle cells or cells of RES Clinical symptoms: can be divided into: Acute phase: nodular lesion (chagoma) at the site of bite, Romana's sign, may include fever, lymphadenopathy Latent phase - asymptomatic, may last for many years Chronic phase - many years later; muscular degeneration and denervation of heart & GIT heart rhythm abnormalities that can cause sudden death; megaesophagus, megastomach, and megacolon

Generalized Transduction

Is transduction in which potentially any bacterial gene from the donor can be transferred to the recipient. Phages that mediate this process generally breakdown host DNA into smaller pieces and package their DNA into the phage particle by a "head-full" mechanism. Occasionally one of the pieces of host DNA is randomly packaged into a phage coat. Thus, any donor gene can be potentially transferred but only enough DNA which can fit into a phage head can be transferred. If a recipient cell is infected by a phage that contains donor DNA, donor DNA enters the recipient. In the recipient a generalized recombination event can occur which substitutes the donor DNA and recipient DNA .

Leishmania spp. Life Cycle

Is transmitted by the bite of infected female phlebotomine sandflies. The sandflies inject the infective stage (i.e., promastigotes) from their proboscis during blood meals . Promastigotes that reach the puncture wound are phagocytized by macrophages and other types of mononuclear phagocytic cells. Progmastigotes transform in these cells into the tissue stage of the parasite (i.e., amastigotes) , which multiply by simple division and proceed to infect other mononuclear phagocytic cells . Parasite, host, and other factors affect whether the infection becomes symptomatic and whether cutaneous or visceral leishmaniasis results. Sandflies become infected by ingesting infected cells during blood meals. In sandflies, amastigotes transform into promastigotes, develop in the midgut, and migrate to the proboscis

Progressive Multifocal Leukoencephalopathy (PML)

JC Virus Activation of latent infection: Is a fatal demyelinating disease of the white matter and involves multiple area of the brain Progressive weakness Visual, speech and sometimes personality changes, weakness, dementia, coma, death within 6 months Approx. 10% pts with AIDS develop PML PML appears grossly as irregular areas of granularity in white matter which bear some resemblance to the plaques of demyelination with multiple sclerosis.

Cell Wall Less Forms

L forms Produced by the action of Lysozyme Antibiotics: cell wall synthesis inhibitors (beta-lactam (penicillin) Protoplast: from Gram positive (Stable L forms) Spheroplasts: from Gram negative (retain the outer membrane). Unstable L forms : they can divide and revert back to make peptidoglycan if moved to antibiotic free environment Formation of L forms may lead to infection after antibiotic treatment. Stable L-forms: L-forms that are unable to revert to the original bacteria.

HIV genome

LTR-long terminal repeats; repetitive sequence of bases (contain promotoers, enhancers, and other gene sequences used for binding different cellular transcription factors) gag-group specific antigen gene, encodes viral nucleopcapsid proteins: p24, a nucleoid shell protein, MW=24000; several internal proteins, p7, p15, p17 and p55. pol-polymerase gene; encodes the viral enzyme, protease (p10), reverse transcriptase (p66/55; alpha and beta subunits) and integrase (p32). And protease env-envelope gene; encodes the viral envelope glyocproteins gp120 (extracellular glycoprotein, MW=120 000) and gp41 (transmembrane glycoprotein, MW=41000). tat: encodes transactivator protein, activation of transcription of viral genes rev: encodes a regulator of expression of viral protein, transport of late mRNAs from nucleus to cytoplasm vif: associated with viral infectivity,, enhances infectivity by inhibiting the action of APOBEC3G an enzyme that causes hypermutation of retroviral DNA (part of human innate immunity against retrovial) vpu: encodes viral protein U, enhances, viron release from cells vpr: encode viral protein R, transports viral core from cytoplasm into nucleus in non dividing cells nef: encodes a 'so-called' negative regulator protein, decrease CD4 and MHC class I in infected cells, induces death of uninfected cytotoxic T cells

Diagnosis of Proteus UTI

Lab Diagnosis: Culture (Swarming growth) and Biochemical tests Treatment: resistance vary among species - antibiotic sensitivity test required, appropriate antibiotics Prevention: Good personal hygiene, prompt treatment of cystitis, preventive therapy if the patient has a history of recurrent infections

Diagnosis of PCP

Laboratory Diagnosis: Specimen: bronchopulmonary secretions - induced sputum or bronchoalveolar lavage (BAL); transbronchial lung biopsy Microscopy: Staining - such as Giemsa, Silver, DFA demonstrate typical cyst: round/cup or crescent shape Molecular: PCR probes available Culture: no culture media Serology: has not been developed yet Bronchoscopy with transbronchial biopsy is a procedure in which a bronchoscope is inserted through the nose or mouth to collect several pieces of lung tissue. Globular cysts eventually form that have a thicker wall. Within these cysts, eight spores form which are released through rupture of the cyst wall. The cysts often collapse forming crescent-shaped bodies visible in stained tissue. Polymerase chain reaction (PCR) is also used to detect P. jirovecii DNA in clinical specimens. PCR can be particularly helpful in detecting silent P. jirovecii infections in HIV-infected patients.

Diagnosis and Treatment of Psittacosis

Laboratory Diagnosis: Serology: Complement fixation or microimmunofluorescence- 4 fold increase of titre in testing of acute and convalescent sera Treatment, Prevention, Control: Treatment - Doxycycline, macrolides, fluoroquinolones Control infections in domestic and imported pet birds by treating with chlortetracycline

Diagnosis of Granuloma Inguinale

Laboratory Microscopic Scraping from the base of the ulcer, tissue biopsy Demonstration of mononuclear cells with intra cytoplasmic vacuoles packed with the bacteria known as Donovan bodies Treatment Tetracycline

Diagnosis of Legionella

Laboratory diagnosis Microscopy: DFA staining: sensitivity 25 to 75% (due to intracellular nature), or Dieterle silver staining (tissue) Culture- Gold standard: on BCYE medium, with cysteine and iron- enriched and selective media, 5% CO2 Urine antigen test: Rapid method. immunoassay test for LP specific LPS antigens in patients urine - sensitivity 60-90% Antibody detection: by ELISA, or Indirect Fluorescent antibody test; four-fold increase OR, a level of 1:128 or greater Since Legionella is a relatively slow-growing bacterium, negative plates should be reincubated until 7 days postinoculation and then re-examined for Legionella (CDC) AFA: Direct fluorescent antibody Dieterle stain - a silver impregnation method for staining Legionella Role of charcoal is to neutralize toxic fatty acids in media BCYE: buffered charcoal yeast extract medium LP-Legionella pneumophila

Diagnosis of Pseudomonas aeruginosa

Laboratory diagnosis: Culture on blood agar or enteric media MacConkey agar- grey colonies - non-lactose fermenter Oxidase positive: presence of cytochrome C oxidase Motile Produce pigments on colorless media , blue, green-yellow mucoid colonies and fruity odor

Diagnosis of Coccidioidomycosis

Labortory diagnois: Specimen: sputum, biopsy - Microscopy: treat samples with KOH/Calcofluor white, H &E or specific fungal stains such as GMS or PAS demonstrate spherules - definitive Culture: (for safety reasons - not preferred). Grow at 25 0C and produce arthroconidia (highly infectious) Identity confirmed with nucleic acid probe or by exoantigen immunodiffusion (ID) test Culture does not demonstrate spherule Serology: IgM and IgG (Latex particle agglutination and Complement fixation tests)

Prion Pathogenesis

Lack of antigenicity, no immune response Lack of inflammation and interferon production Generation and accumulation of a pathologic form of the normal prion protein Formation of amyloid-like plaques and fibrils, vacuolation of neurons (spongiform) and Neuronal dysfunction Long incubation time - CJD and Kuru - up to 30 yrs General symptoms include loss of muscle control, shivering, myoclonic jerks, tremors, ataxia, behavioral changes, visual loss, dementia. Death in 7-9 month after onset

Herpesviridae

Large, enveloped, linear dsDNA viruses. May cause lytic, persistent or latent and transforming infections Three groups & several subgroups based on types of cells infected: 1. Alpha herpes viruses (primarily infect epithelial cells) herpes simplex viruses (HSV) 1: HHV 1 herpes simplex viruses (HSV) 2: HHV 2 varicella-zoster virus (HHV 3): HHV-3 2. Gamma herpes viruses (infect a variety of cells) Epstein-Barr virus (HHV 4)- only herpes covered in this chapter Kaposi sarcoma virus (HHV8) 3. Beta herpes viruses (infect mainly lymphoid cells) Cytomegalovirus (CMV), HHV5 Herpes lymphotropic virus, HHV 6 and 7

Herpesviridae Family- Human Herpes

Large, enveloped, linear dsDNA viruses. May cause lytic, persistent or latent and transforming infections Three groups & several subgroups based on type of cells infected: 1. Alpha herpes viruses (primarily infect epithelial cells) herpes simplex viruses (HSV) 1 herpes simplex viruses (HSV) 2 varicella-zoster virus (HHV 3) 2. Gamma herpes viruses (infect a variety of cells) Epstein-Barr virus (HHV 4) Kaposi sarcoma virus (HHV8) 3. Beta herpes viruses (infect mainly lymphoid cells) Cytomegalovirus (CMV), HHV5 Herpes lymphotropic virus, HHV 6 and 7

Treatment of Naegleria fowleri

Largely ineffective, early diagnosis critical Amphotericin B, New drug: Miltefosine Amphotericin B - considered investigational for this purpose Miltefosine is an experimental drug, which was initially developed for breast cancer but had shown some amoeba-killing capabilities in the lab. Amphotericin B is effective against N. fowleri in vitro, but the prognosis remains bleak for those who contract PAM, and survival remains less than 1% Therapeutic hypothermia: cooling the body below normal body temperature Only three known survivors Prevention: Avoid exposure to contaminated water: nose clip

Atypical Pneumonia Pathogens

Legionella pneumophila Mycoplasma pneumoniae Chlamydophila pneumoniae Chlamydophila psittaci Bacillus anthracis

Parasitic skin pathogens

Leishmania spp. Ancylostoma caninum Dracunculus medinesis Schistosoma Ancylostoma duodenale (Hookworm)

Mycobacterium leprae

Leprosy/Hansen's Disease: 216,108 new leprosy cases registered globally in 2016 (WHO) First bacterium to be described but it remains one of the least understood because it can not be grown in culture mediafirst bacterium to be described but it remains one of the least understood because it can not be grown in culture media Properties: An acid-fast rod (resist decolorisation- upto 5% H2SO4), cannot be grown in culture Reservoir: Humans are the only reservoir of significance; Armadillos in Louisiana and Texas have a similar disease Transmission: Person to person Exact mode of transmission unknown but is believed to be: Inhalation and prolonged close contact with respiratory secretions or wound exudate Risk Factors/High Risk Populations: Persons living with active cases over long periods of time; Children seem to be at increased risk in these households Rare in USA - cases in Southern states, Approx. 100 cases/year

Strongloides stercoralis life cycle

Life cycle differs from Hookworm in 3 aspects: A. Eggs hatch into larvae in the intestine and before they are passed in feces (i.e we do not see eggs of the parasite in stool examination) B. Larvae can mature into filariforms in the intestine and cause autoinfection C. Free living, non parasitic cycle can occur outside the human host Once Strongyloides enters the skin it follows the path similar to hook worms.

Plasmodium: Life Cycle

Life cycle involves two hosts. During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host . Sporozoites infect liver cells and mature into schizonts , which rupture and release merozoites . (Of note, in P. vivax and P. ovale a dormant stage [hypnozoites] can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later). After this initial replication in the liver (exo-erythrocytic schizogony ), the parasites undergo asexual multiplication in the erythrocytes (erythrocytic schizogony) . Merozoites infect red blood cells . The ring stage trophozoites mature into schizonts, which rupture releasing merozoites . Some parasites differentiate into sexual erythrocytic stages (gametocytes) . Blood stage parasites are responsible for the clinical manifestations of the disease. The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal . The parasites' multiplication in the mosquito is known as the sporogonic cycle . While in the mosquito's stomach, the microgametes penetrate the macrogametes generating zygotes . The zygotes in turn become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop into oocysts . The oocysts grow, rupture, and release sporozoites , which make their way to the mosquito's salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle.

Pathogenesis of EBV

Life long infection Types of cells infected: epithelial cells (oro - and naso-pharynx) and B lymphocytes Means of attachment: Viral glycoprotein gp350 attaches to complement iC3b receptor- CR2(CD21); and gp42 binds to MHC II Binding of EBV on B cell results in proliferation of B cells (EBV virus acts as B cell mitogen). Overgrowth of B cell is controlled by T cells - resulting in production of Atypical T lymphocytes.

Oxazolidinones

Linezolid Mechanism of Action Binds to 50S and interfere with the formation of the initiation complex. Pharmacology: bacteriostatic, Gram positive, reserved for Vancomycin resistant Enterococcus faecium (VRE/VREF) Methicillin resistant Staphylococcus aureus (MRSA)/VRSA

Prevention of smallpox

Live attenuated vaccine; contains genetically related Vaccinia virus (not small pox virus!!!) - thought to have originated from cowpox, but appears to be a hybrid of different poxviruses. -Disease declared eradicated in 1980 -Vaccine not given any more except for military personnel, smallpox response team, lab personnel working with smallpox

Prion Protein Scrapie (PrPsc)

Located in the cytoplasm or secreted Beta-pleated sheet Protease resistant Resistant to heat and UV

Attenuation

Loss of/decreased virulence

Pathogenesis of Streptococcus viridans

Low virulence: No toxins produced Adherence and formation of biofilm: produce dextrans or levans (large polysaccharides) from sucrose : enhance attachment Production of acid from sugars - glucose, lactose, sucrose - lower pH leads: leads to mineralization of enamel Dental caries, gingivitis, periodontitis The initiating organisms are the viridans group, but once the plague is formed others are involved (polymicrobial) Subacute endocarditis: enter blood - may settle on heart valves especially in a deformed heart valve, can form vegetation, May lead to immune complex deposition, kidney, joints, blood vessels, skin (skin lesions) Accounts about 40% of infective endocarditis Abscesses: Brain and liver abscesses especially by S. anginosus group

Brown recluse spiders

Loxosceles spp. General characters: Relatively long legs Characteristic: a dark fiddle ( 'violin') shaped marking on the dorsal cephalothorax; 3 pairs of eyes in semicircle Venom is necrotoxin which also may have hemolytic properties Epidemiology: Worldwide; South, Central and Western US

Paragonimus westermani

Lung fluke Epidemiology: World wide, refugees from southeast Asia, Approx. 3 million people infected, Shore feeding animals (wild boars, pigs and monkeys) serve as reservoir Transmitted by eating raw or undercooked crabmeat Morphology: Adult Larva: various stages Eggs

Borrelia burgdorferi

Lyme Disease: The leading vector-borne disease in the USA Each year, approx. 30,000 cases reported to CDC General properties: Spirochete - weakly staining Gram negative cell wall, axial filaments Reservoirs and vectors: White foot mouse, whitetail deer and tick vector; Ixodes spp- same vector as for Babesia and Anaplasma adult and nymph stage, takes 24-48hrs to feed Transmission: Tick bite, seasonal, late spring and early summer geographic limitation Risk Factors/High Risk Populations: Campers, Hikers

GAS M protein

M protein consists of two polypeptide chains complexed in an alpha helix. The protein is anchored in the cytoplasmic membrane, extends through the cell wall and protrudes above the cell surface. M types based on differences in the M protein divide the groups into numbered types, over 100, M1 and M3 most common, often identified by presence of emm gene with a gene probe rather than by serologic tests a. Aminoterminus amino acid sequence varies, is site of antigenicity, if varied, immunity to new type is needed b. Carboxyterminus sequence common to all types c. M protein is the key antigen to provoke immunity and is also considered as the most important virulence factor

Treatment of pertussis

Macrolides: Erythromycin or azithromycin for early stage of the disease Supportive - for late stage: suctioning (drawing out) of thick respiratory secretion, rehydration, oxygenation, anti-inflammatory agents

Treatment of histoplasmosis

Majority recover without treatment Amphotericin B, Itraconazole

Bacterial Spores

Means of survival Formed in response to adverse conditions Occurs in unfavorable conditions such as starvation, desiccation, presence of disinfectants and in extreme temperature DNA replicates and separates, spore septum begins to form Double membrane encloses the DNA and cytoplasm Double membrane matures and becomes core wall Mother cell swells Spore coat develops Exosporium basal layer develops It contains- DNA, cell membrane, cytoplasm, cell wall, surrounded by a Spore Coat : contains high concentration of calcium bound to dipicolinic acid, plus a keratin-like protein Dehydrated : It contains about 70% less water than the mother cell. No detectable metabolic activity - makes them resistant to unfavorable conditions. Produced by some Gram positive & one Gram neg. Bacteria I. Gram positive bacilli: Obligatory aerobic: Genus Bacillus eg, B. anthracis, B. subtilis Obligatory anaerobic: Genus Clostridia eg. C. tetanus, C. welchii, C. botulinum Cocci: Gram positive cocci: Sporosarcina II. Gram Negative: Bacilli: Coxiella burnetii

Pathogenesis of Fasciola hepatica

Mechanical irritations during migration of larva from the intestine to and through liver and its settlement in bile ducts, and Toxic secretions, hyperplasia of epithelium Clinical Disease In the acute phase (during migration of larva): nausea, vomiting, and abdominal pain/tenderness. Fever, rash, and difficulty breathing In the chronic phase (after the settlement of the parasite): inflammation and blockage of bile ducts, inflammation of the liver (hepatitis), gallbladder, and pancreas Halzoun is a painful pharyngitis caused by the presence of adult flukes on the posterior pharyngeal wall. The adult flukes are acquired by eating raw sheep liver.

Pathogenesis of Diphyllobothrium latum

Mechanical presence causes most symptoms; and malnutrition Clinical Disease: mostly asymptomatic. Since they can live for upto 25 years, symptoms vary: Intestinal : usually mild abdominal discomfort, bloating, diarrhea. Migrating proglottids: acute abdominal pain and intestinal obstruction, cholangitis (inflammation and obstruction of the bile ducts) and cholecystitis (inflammation of gallbladder) Megaloblastic anemia: With heavy load, B12 deficiency (the parasite absorbs lots of vitamin B12) Neurological sequelae of vitamin B deficiency

Filtration

Mechanical removal using filters Any particle bigger than the diameter of the filter pores gets trapped. The most common bacterial filters are nitrocellulose membranes with pore size of 0.22 micrometers Used for heat sensitive liquids, such as enzymes and solutions for intravenous administration Also used to sterilize air in safety cabinet

Metronidazole

Mechanism of Action: Nitro group is reduced in vivo to form the active drug that disrupts DNA under anaerobic condition Pharmacology Initially as anti protozoan (Trichomonas) Bactericidal, narrow spectrum Effective against anaerobes, not aerobes Sensitivity testing for anaerobes is not performed routinely. Therefore, resistance is under-reported. The proposed mechanisms of resistance 1. Decreased drug uptake or increased efflux 2. Decreased drug activation/change in the biological target 3. Increased oxygen scavenging capabilities (SOD/catalase/ peroxidase) 4. Enhanced activity of DNA repair enzymes

Resistance in General

Mechanism of Resistance Intrinsic resistance Bacteria lacking peptidoglycan Seven major pathogens Chlamydia, Chlamydophila, Mycoplasma, Ureaplasma, Orientia, Ehrlichia and, Anaplasma Mutation of porin proteins - decrease permeability among some Gram negatives Inactivating enzymes: on plasmids Beta lactamase, some have extended spectrum (ESBL) activity gene carried on plasmid - could carry genes for other drug resistance - Multidrug R plasmids Alteration of Penicillin Binding Protein (form PBP 2A) Eg. Methicillin resistant Staphylococcus aureus (MRSA) (mec A gene mediated: alter target)

Treatment of BV

Metronidazole oral Metronidazole/Clindamycin intravaginally Systemic treatment recommended for pregnant women. Recurrence common - normal flora fail to reestablish Acidification treatment: vaginal capsules with boric acid Probiotics treatment: vaginal capsules with Lactobacillus (normal flora) Treatment of sexual partner not helpful. Prevention: What causes the imbalance in the normal flora is not clear - no specific prevention method. Avoid using excessive douching

Adsorption/ Attachment to Target Cell

Mediated by molecular interaction between virus and target cell Viral attachment structures: Surface structures on the capsid or envelope -Viral attachment proteins (VAP)/peplomers/spikes -Determine host/tissue specificity -High mutation rate in VAP can result in change in host specificity or avoid immune response eg. Influenza virus - hemagglutinin (HA) HIV - glycoprotein (gp)120 Receptors on target cell: are proteins or carbohydrates on glycoproteins and glycolipids Examples -CD4 and CxCR4/CCR5 (a chemokine receptors) on T helper cells, and Macrophages - for HIV -ICAM-1 on epithelial cells for rhinovirus -Sialic acid on epithelial cells for influenza virus Permissiveness = allowing Entry + Replication

Meningococcal Meningitis Clinical Disease:

Meningitis: Abrupt onset of fever, intense headache, chills, vomiting, nuchal rigidity seen in 50%; Kernig's sign; Brudzinski's sign Meningococcemia : disseminated infection: hemorrhagic skin lesions (rash) - petechial (small) - rapid progression of disease as petechial coalesce (ecchymosis), progress to DIC, shock, coma and death in few hrs, mortality rate 100% if not treated Waterhouse-Friderichsen syndrome: adrenal destruction

HSV diagnosis

Microscopic: Tzanck smear: Demonstrate mutinucleated (Syncytia) cells with intranuclear inclusion bodies (Cowdry type A) in scraping of an ulcer base Not specific Tzanck cell:a multinucleated giant cell, formed by the fusion of acantholytic keratinocytes, that occurs in the lesions of chickenpox, herpes simplex, herpes zoster, and pemphigus vulgaris; such cells are seen in the Tzanck test. Cell culture : most definitive In HeLa cells Viral detection using direct immunofluorescence; or Tzanck test Molecular: PCR differentiates HSV 1 and HSV 2.

Diagnosis of Leishmaniasis

Microscopic examination Of bone marrow, spleen, liver or lymph node biopsy, Of scrapings from margin of lesions demonstrate parasites inside macrophages Serology: Direct Agglutination Test (DAT) rK39 test: Serologic test using the cloned antigen rK39 instead of whole Leishmania parasites. The rK39 antigen, which consists of 39 amino acid repeats of a kinesin-like gene found in L. chagasi, is used in an enzyme-linked immunosorbent assay (ELISA) format and rapid diagnostics Novy-MacNeal-Nicolle (NNN) medium is used to grow Leishmania. It consists of 0.6% sodium chloride (NaCl) added to a simple blood agar slope. NNN can also be used to grow Trypanosoma cruzi. leishmanin test (Also called as Montenegro test) is a delayed hypersensitivity test for cutaneous leishmaniasis, In this test, killed Leishmania antigens are injected intradermally. A positive reaction is indicated by the appearance of a palpable nodule in 48 to 72 hours

Diagnosis of Chlamydia

Microscopic: cytoplasmic inclusion bodies, cell culture, NAAT (nucleic acid amplification test), immunological assays (DFA, ELISA) Treatment: Doxycycline, azithromycin Prevention: Erythromycin for expecting mothers Treat sexual partners, Safe sexual practices Screening: all sexually active women aged <25 years and for older women at increased risk for infection

Culture

Method of multiplying microbial organisms by letting them reproduce in predetermined culture media Pure culture: culture with one type of bacteria, theoretically derived from a single cell

Treatment and prevention of Giardia lamblia

Metronidazole or nitazoxanide with furazolidone (Nitrofuran antimicrobial, works by crosslinking of DNA) Prevention and control: Personal and public hygiene Avoidance of contaminated water and food Boiling or filtration (water from streams/lakes) Proper filtration system in municipal water supplies (since cysts are resistant to standard chlorination) Avoidance of high-risk sexual behaviour

Diagnosis of mucormycosis

Microscopy - nasal discharge, sputum, BAL, paranasal sinuses biopsy, aspirate, etc. KOH Wet mount: Broad, non-septate, ribbon-like hyphae which branch at right angles, sporangium Histopathological staining: PAS and H&E Culture : Sabouraud Dextrose Agar (SDA): rapid growth COTTON CANDY appearance Identification by LPCB stain: morphological study

Diagnosis of Candidiasis

Microscopy: Direct from swab: wet mount or Gram stain demonstrate budding yeast/ pseudohyphae Germ tube test: Inoculate into animal serum at 37 C for 90 min- develop elongated germ tubes - Culture: grow in most common bacteriological media - colonies look like bacterial colonies - round and smooth

Diagnosis of plague

Microscopy: Giemsa stain of aspirates from the buboes: Bipolar staining, (safety pin appearance) Direct immunoflourescent staining Culture: Grow well on blood agar, MacConkey agar. Laboratory hazard to culture, performed in reference labs only

Diagnosis of Bartonella henselae

Microscopy: Biopsy, use of special staining Warthin-Starry's silver stain demonstration of the presence of the organism; Culture: Grow on enriched blood agar/chocolate agar- rarely used PCR Treatment: CSD is self limited - no antibiotics needed Needle aspiration of swollen lymph nodes Bacillary Angiomatosis: Prolonged course of an oral macrolide antibiotic such as erythromycin or azithromycin Prevention: Cleansing of animal bites/scratches

Diagnosis of Varicella-Zoster Virus

Microscopy: Detection of Cytopathic effect in infected cells in Tzanck smear (scraping of an ulcer base) multinucleated giant cells (Tzanck cells) - syncytia Cowdry Type A - intranuclear inclusion bodies Antigen detections: Direct immunofluorescence staining Genome detection: PCR

Diagnosis of S. aureus

Microscopy: Gram stain of smears from lesions/abscess - Gram + cocci in clusters Culture: Blood agar- beta hemolytic Mannitol salt agar - fermentation - yellowing of the media Biochemical: Coagulase test +, catalase test + Rapid hybridization technique: FISH- use of fluorescent labelled probe complementary to rRNA genes or, fluorescent DNA probe for rapid identification of coagulase gene Identification of highly drug resistant strains Detection of resistance coding genes (such as mec A, vanA)

Diagnosis of Pasturella multocida

Microscopy: Staining- bipolar appearance May be insensitive from direct patient sample due to low number of bacteria Culture: blood agar or chocolate agar Non-hemolytic mucoid (buttery) colonies due to capsule Musty odor (mold smell) due to indole production Treatment: Sensitive to a variety of antibiotics Penicillin G drug of choice; Alternatives-tetracycline and fluoroquinolones Prevention: properly clean wounds, bites and scratches. Not to suture animals bites, especially cat bites Ampicillin as post exposure prophylaxis.

Diagnosis of diphtheria

Microscopy: poor specificity Culture- three types of culture media Blood agar (Enriched) Cysteine- tellurite blood agar, Tinsdale medium (Selective) Loeffer's serum plate - for granule formation: revealed by metachromatic staining Cysteine-Tellurite blood agar: Selective medium, inhibits growth of most normal flora Corynebacterium diphtheriae produces gray-black colonies in 24-48 hours Blood agar: Colonies are small gray, irregular ones and may have small zone of hemolysis Toxin testing: Demonstrating toxin production Elek's test -principle of Ouchterlony; or PCR - detect toxin gene Toxin Testing 1. Immunodiffusion assay (Elek's test): gold standard for detection of diphtheria toxin; antitoxin (Ab) on strip of filter paper 2. PCR of toxin gene Ouchterlony, precipitin

Diagnosis of Malaria

Microscospy: Examination of thick & thin blood films Gold standard Demonstration of infected red blood cells; ring form, schizont and gametocyte form of parasite. Antigen detection by rapid diagnostic test (RDT): Aldolase enzyme (all Plasmodium) Lactate dehydrogenase (all Plasmodium & also specific to P. falciparum) Histidine rich protein-2 (specific to P. falciparum) Molecular: PCR based test

Trypanosoma cruzi in non-endemic countries

Migration routes from Latin America and estimation of the total number of infected individuals in non-endemic countries.

EHEC Diseases

Mild diarrhea to Hemorrhagic colitis; little or no fever, severe abdominal cramps, watery diarrhea followed by bloody diarrhea Hemolytic uremic syndrome (HUS): 0-15% patients if toxin reach circulation. kidney failure, hemolytic anemia, thrombocytopenia and neurologic symptoms most common in children under 5 years old and the elderly. Treatment: Use of antibiotics may contribute to progression to HUS - Shiga toxin and LPS are released from dying or dead bacteria

Determinants of Bacterial Pathogenesis

Mode of Transmission Adherence factors Ability to invade, spread and cause inflammation Toxin production: Products that kill or alter physiology of host cells Surviving host defenses Immunopathogenesis: Collateral damage due to host immune response or immune complication

Chemical Agents

Mode of action: disrupt cell membrane, denature proteins, break DNA. The rate of killing by a chemical depends on: Concentration of the chemical: Effectiveness usually is directly related to concentration. But not always E.g Alcohol - 70% is more effective than 95% Time of exposure Physiological condition of the microbe (eg. Vegetative Vs. spore) Presence of organic matter - affects exposure Population size - the number of bacterial cells Disruption of cell membranes: Alcohol, Detergents, Phenols (Acronym-ADP) Modification of proteins: 3H-Halogens (chlorine, Iodine), Heavy metals, Hydrogen peroxide; Alcohol, Aldehydes (Formaldehyde and Gluteraldehyde), Ethylene oxide Modification of nucleic acids: Aldehyde (formaldehyde and Gluteraldehyde), Ethylene oxide and Dyes (Crystal Violet, Malachite green)

CPE (Cytopathic Effect) on cell culture

Morphological changes of human corneal epithelial cells infected with a virus. A: Normal human corneal epithelial cells exhibited a cobblestone appearance. B: After cells were infected with HSV-1, the cytopathic effect could be seen at 8 h p.i. The space between infected cells increased for 12 h (C) and 24 h (D), the cobblestone appearance disappeared and many giant multinucleated cells could be seen. Magnification: 200X.

Fungal Growth

Most fungi are aerobic, some may be facultative anaerobic Are heterotrophic - require organic matter for growth Most grow best at room temperature 20 -40 0C Fungi will grow well on slightly acidic media, slightly drier, higher osmotic pressure where bacteria do not Common culture media - Sabouraud dextrose agar (SDA) Selective for fungi: pH 5.6, osmotic pressure: Does not support bacteria Cycloheximide may be added to SDA to suppress fast growing non pathogenic fungi -To favor growth of pathogenic one in a mixture of same. Thermal dimorphism : Yeast at 37 0C and mycelial form at room temp (25 0C) Fungi can withstand higher osmotic pressures than most bacteria

Treatment of Toxoplasma gondii

Most infections in immunocompetent: resolve spontaneously Disseminated infection: Pyrimethamine plus sulfadiazine, Alternative: clindamycin plus pyrimethamine Cerebral edema and ocular infection: corticosteroid added Prevention and control Routine serologic screening for patients before organ transplantation and early in HIV infection (For sero+, Trimethoprim-sulphamethoxazole) Screening of Pregnant women (a part of 'TORCH' screening) Pregnant women and immunocompromised: avoiding raw or undercooked food, avoiding exposure to cat feces

Cerebral malaria

Most severe neurological complication of infection with Plasmodium falciparum malaria; Coma; Only young ring forms and occasionally gametocytes peripheral blood Mortality high, surviving patients sustain brain injury- long-term neuro-cognitive impairments.

Normal flora in respiratory tract

Mouth: Viridans streptococcus, a heterogeneous group (alpha hemolytic) Dental plaque: Streptococcus mutans: Produces biofilm, lots of acid that demineralizes the enamel Bacterial endocarditis and abscess in brain, liver Due to entry in blood stream (eg.during Tooth extraction, scaling) S.salivarius, S. mitis, S. sanguis, S. anginosus etc.. Nose: Staphylococcus aureus - 20% carrier rate - source of outbreaks in hospitals. Throat: mostly viridans Streptococcus; Streptococcus pyogenes (beta hemolytic) (10-15%) - cause bacterial pharyngitis Other potential pathogens in the upper respiratory tract may also be found: Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae Lower Respiratory tract: larynx, trachea, bronchioles and lower air ways - sterile. Aspiration of upper tract flora - cause infection in the lung

Pathogenesis of Helicobacter pylori

Mucinase: enzyme that hydrolyzes mucopolysaccharide substances (mucins). Urease - Breaks urea to CO2 and NH3, neutralizes gastric acid Destruction of epithelial cells Phospholipases: hydrolyzes phospholipids Vacuolating cytotoxin A (VacA): damage epithelial cells by producing vacuoles. Cytotoxin-associated gene (CagA): destroy epithelial cell cytoskeleton Type IV secretion system: assist in injecting CagA to epithelial cells LPS: Inflammatory response: infiltration with PMN and mononuclear cells Further destruction of exposed epithelial cells with digestive enzymes and acid 1. H. pylori penetrate the mucus layer of host stomach and adhere the surface of gastric mucosal epithelial cells. 2. produce ammonia from urea by the urease, and the ammonia neutralize the gastric acid to escape from elimination. 3. proliferate, migrate, and finally form the infectious focus. 4. The gastric ulcer is developed by destruction of mucosa, inflammation and mucosal cell death.

Rhizopus and Mucor spp

Mucormycosis Rhizopus arrhizus (oryzae) is the most common cause of human mucormycosis General properties: Fungi; Rhizopus and Mucor species. Belong to the order Mucorales of the phylum Zygomycota. MONOMORPHIC, Non-septate hyphae with broad, irregular walls and branches - more or less at right angles. Root like structure - rhizoids in Rhizopus, but not in Mucor Asexual spores - sporangiospores within Sporangium Reservoir: abundant in nature worldwide, rotting fruit, old bread, air, water, soil Transmission: Inhalation of sporangiospores Risk Factors/High Risk Populations: Infections more common in immunocompromised, Diabetic ketoacidosis, neutropenia and corticosteroid treatment

Mucosal manifestation of secondary syphilis

Mucous patches: lesions in mucus membrane, an oval to round yellow/gray/white, snail track in mouth Systemic disease includes: flu-like, generalized lymphadenopathy, and many organs may be infected, such as liver, kidney, joints, brain

Treatment of TB

Multi-drug for several months - 6 to 9 months. There are several drugs available but the first line of treatment are Isoniazid (H) Rifampin (R) Pyrazinamide (Z) Ethambutol (E) Resistant strains have emerged MDR-TB: multi drug resistant—to isoniazid and rifampin XDR-TB: extensively drug resistant- to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin); not easy to treat

TORCH

Stands for: -Toxoplasma gondii, -Other viruses (HIV, measles, and so on), -Rubella (German measles), -Cytomegalovirus and -Herpes simplex. All these infectious agents are teratogens (agents that are capable of causing birth defects.

Family Coronaviridae

Named for solar corona like appearance Glycoprotein projections of their surfaces (corona = crown) General Properties: Enveloped, helical nucleocapsid, longest positive sense ssRNA Surface projections with club shaped glycoproteins Optimum temp. 33-350 C. Replicates in the cytoplasm Translates RNA dep RNA polymerase Peplomers: S and HE are for attachment Acquires envelope from Endo. reticulum Three strains: Coronavirus (conventional) , SARS-CoV , MERS-CoV

Pathogenesis of Brown Recluse bite

Necrotic arachnidism (Dermonecrotic disease) Bite painless initially Several hours later-itching, swelling and soreness in area of bite Vesicle or bleb formation General symptoms (chills, headache, nausea) Within 3-4 days: ulceration of the bleb and radiating necrosis Diagnosis: Clinical as well as identification of typical spiders

Genital Mycoplasma

Non-gonococcal/non-chlamydial urethritis/cervicitis Mycoplasma genitalium Mycoplasma hominis Ureaplasma urealyticum General properties: cell wall less, sterol in cell membrane, smallest free living organism Ureaplasma urealyticum is urease positive Reservoir: Found in genitourinary tract of sexually active adults Rarely found before puberty and sexually inactive adults Transmission: sexual contact (80% of individuals with 3 or more sexual partners) Clinical disease: Non-gonococcal /non-chlamydial urethritis/cervicitis. May also lead to PID. Postabortal /postpartum fever (Mycoplasma hominis) Urinary tract infection: Ureaplasma urealyticum

Viral Genetics

New viral strains with properties different from the parent/wild type can arise by Spontaneous mutation Mutants can be point mutants (one base replaced by another) or insertion/deletion mutants. Recombination enables a virus to pick up genetic information from viruses of the same type and occasionally from unrelated viruses or even the host genome and/or Interaction between two genetically different viruses that infect the same cell Recombination Phenotypic mixing Complementation

Treatment of Chagas Disease

Nifurtimox and benznidazole (FDA not approved) In the U.S., drugs available only through CDC Prevention and Control Improved housing and spraying insecticide inside housing to eliminate triatomine bugs Screening for Chagas disease during blood donations Early detection and treatment of new cases

Treatment of Mumps

No antiviral drugs, Analgesics, infection gives lifelong immunity Vaccine: live attenuated MMR/MMRV - since 1967, two doses recommended (12-15 months, 4-6 years old) (88% effective), 3rd dose recommended in 2017 In the US - outbreaks, mostly young people vaccinated at least once, some twice Vaccine should not be given during pregnancy since the virus can cross the placenta

Acute HBV Infection

No antiviral therapy -HBsAg, HBeAg, AntiHBc positive -Anti HBs and Anti HBe negative Window 4-5 weeks following HBV infection HBsAg, AntiHBs negative AntiHBc and AntiHBe positive Resolved/ convalescence 5-6 weeks following infection HBsAg negative, antiHBs and antiHBc positive

Pathogenesis of HCV

No virus induced cytophatic effect Cell death due to immune attach by CD8 cells No oncogene in viral genome - but virus causes hepatocellular carcinoma - due to chronic damage Alcoholism and other liver cirrhorsis enhances the rate of hepatocellular carcinoma in HCV patients. Clinical disease: IP Average 6-7 wks (2-26 wks) Three types of diseases -Acute hepatitis with resolution Rapid on set of cirrhosis -Chronic persistent infection - with possible progression to disease -Hepatocellular Carcinoma Immunity: No protective antibody response identified, virus mutates fast

Nocardia spp.

Nocardia asteroides Nocardia brasiliensis General properties: Gram positive, strictly aerobic, non spore former, branching rods; look like actinomycetes but differ from them Form aerial hyphae on culture and Weakly acid fast; cell wall contain mycolic acid similar to MTB , but shorter fatty acids compared to MTB. Cell wall contains trehalose dimycolate ("cord factor" ) Reservoir: Environment/soil rich with organic matter, standing water Transmission: Exogenous; airborne or traumatic implantation Risk Factors/Risk Populations: Those with weakened immune systems, traumatic injury

Rhizopus

Nodal rhizoids Short, non-branched brown sporangiophores Sporangia with sporangiospores Asexual fruiting structure, illustrating sporangium, sporangiophore, sporangiospores, coenocytic hyphae and rhizoids

Adenovirus diseases

Non exudative pharyngitis Common cold symptoms Fever, sore throat, coryza (runny nose), inflamed pharynx Young children Pharyngoconjunctival fever same as above plus conjunctivitis (pink eye) (depending on the type of adenovirus): associated with poorly chlorinated swimming pools; older children Acute Respiratory Disease (ARD) in Military Recruits Mainly caused by type 4, 7, 21 Usually appears during the third week of training among newly enlisted troops. Characteristic symptoms include fever, malaise, sore throat, hoarseness and cough. May have conjunctivitis. Pneumonia develops in around 10% of cases.

Etiology of Septic arthritis

Non gonococcal: S. aureus: most common (overall), Streptococcus spp -in about 20% cases, others (below) Gonococcal: Neisseria gonorrhoeae Risk factors: Previously damaged joints, joints with Rheumatoid arthritis, SLE, minor trauma, intra-articular injection of cortico-steroid

Calciviridae

Noroviruses (formerly Norwalk Viruses) "Winter vomiting disease" Named after an outbreak in a school in Norwalk Ohio, in 1969. Note the 'Star of David' image exhibited by individual virus particles. This is distinct from the star-like images exhibited by astrovirus particles. Bar = 50 nanometers.

Rheumatic Fever

Now rare in the US Pathogenesis Appear few weeks after pharyngitis (2-4 weeks) is an immune mediated inflammation in the heart, joints, blood vessels, and subcutaneous tissues Type II hypersensitivity Immunological cross reactivity with M protein Molecular mimicry Only certain M types are considered rheumatogenic School age children are most affected (5-15 year) Early treatment (within three days since the onset of symptoms) reduces incidence of RF Major clinical symptoms: Fever Migratory polyarthritis Erythema marginatum (skin rash) Subcutaneous nodules Carditis, damage of heart tissue Chorea - uncontrollable movement of limbs and face (Since it affects the nerves) Strains include M types 1,3, 6, 18

Molecular Methods

Nucleic acid based tests Highly specific, quite sensitive, safe, and fast Historically used for pathogens difficult to culture, highly contagious, nowadays for rapid diagnosis Most commonly used are Amplification: Polymerase chain reaction (PCR) - require primers Hybridization; Detection and localization in biopsy:- requires labelled probes DNA Probes labelled with enzymes or fluorescent compounds Sequence analysis: 16s RNA subunit used to identify bacteria

Orf

Occupational hazard From direct contact with lesions on the animal human infection with sheep/goat pox single nodular lesion-granulomatous

Cowpox

Occupational hazard From direct contact with lesions on the animal infection with pox virus solitary lesions or multiple localized lesions-hemorrhagic When lesions regress, leaves no scar Mistaken for anthrax

Cutaneous Candidiasis

Occurs in moist, warm parts such as -skin folds (below the breast, buttcrack, between digits), -nails (Onychomycosis), -nail folds (paronychia), Erythema, vesicles -Also causes Diaper rash in infants Interdigital candidiasis of the hands may develop particularly in persons whose hands are subject to continuing wetting, especially with sugar solutions or contact with flour. Interdigital candidiasis of the feet explains l% of cases of "athletes foot" and must be distinguished from tinea pedis caused by dermatophytes. Superficial candidiasis in an infant (nappy rash). Usually occurs under unhygienic conditions of chronic dampness and irregularly changed, unclean nappies. In several cases this condition may spread to the axillae, face, conjunctiva and other areas

Replicating virus

Often produce histological changes in infected cells. These changes may be characteristic or non-specific. Viral inclusion bodies are basically collections of replicating virus particles either in the nucleus or cytoplasm. Examples of inclusion bodies include the negri bodies and cytomegalic inclusion bodies found in rabies and CMV infections respectively. Although not sensitive or specific, histology nevertheless serves as a useful adjunct in the diagnosis of certain viral infection.

Mycoplasma pneumoniae

One of the common causes of community-acquired pneumonia Most common cause of Atypical pneumonia Most common cause of pneumonia in young adults General properties: Cell wall-less, pleomorphic, sterol in cell membrane, smallest free living organism (extracellular). Require cholesterol in culture, resistant to cell wall inhibitors Reservoir: human respiratory tract Transmission: respiratory droplet spread within family and to close contacts Risk Groups/High Risk Populations/Seasons: School age children (5-15) and young adults. Outbreaks occur in crowded military and institutional college settings Throughout year but more common in summer and fall (Unlike S. pneumoniae and viruses in winter)

Interferon-gamma release assays (IGRAs)

Patients blood (or purified peripheral mononuclear cells) is mixed with two M.tb specific antigens : ESAT-6 or CFP-10 Incubation 16-24 hours Measure amount of IFN-gama being produced (If the patients were infected, their Th1 specific to MTB would be primed and produce IFN-gama) Detection of IFN-gama with serological techniques- ELISA

Pathogenesis of Septic Arthritis

Organisms enter the joint by hematogenous route (bacteremia-most common), contiguous spread from infected periarticular tissue or direct inoculation Source for bacteremia-UTI, IV drug use, IV catheters, endocarditis, soft tissue infection Bacterial growth in the joint space and inflammation Damage of joint cartilage by cytokines and inflammatory products of neutrophils and certain virulence factors of pathogens (eg. proteases of S. aureus) Clinical manifestations In adults: knee joint most commonly infected followed by hip, shoulder, ankle and wrists In children: hip joint followed by knee Non gonococcal: pain & swelling of a single joint Gonococcal: triad of fever, joint pain and impaired range of motion, usually polyarticular involvement

Halogens

Oxidizing agents, Denature proteins kill the micro-organism by cross-linking essential sulfydryl groups in enzymes to form the inactive disulfide Chlorine: used in purification of water and as disinfectants on inanimate objects (Sod. hypochlorite) Iodine: Two forms, Tincture of iodine (2% solution of iodine and potassium iodide in ethanol) is used to prepare the skin prior to blood culture. Iodophores are complexes of iodine with detergents that are frequently used to prepare the skin prior to surgery because they are less irritating than tincture of iodine As antiseptics - to clean skin or disinfect wounds

Moist heat

Pasteurization: aim is to kill pathogenic bacteria in milk and some canned foods. 62 oC for 30 min followed by rapid cooling, or 72 oC for 15 seconds followed by rapid cooling 1350 C (275 0F) for 1 to 2 seconds- kills bacteria and most spores Boiling: at atmospheric pressure, 100 oC at sea level, can kill vegetative cells in 10 min. , but not spores. Not a means of sterilization. Tyndallization : intermittent boiling (three days in succession), can attain sterility, including spores. May be used for solutions that contain heat sensitive substance Exposure of 1000 C for 20 min on 3 successive days. Autoclaving: steam under pressure, 121 oC at 15 lb/sq inch for 15-20 min kills all microorganism including spores, but not prions 121 oC for 1 hr to destroy prions Sterilization control: Spores of Bacillus stearothermophilus

Burkholderia cepacia disease

Pathogenesis Weak pathogen, not pathogenic for healthy persons Mild bronchitis to necrotizing pneumonia similar to pseudomonas Urinary tract infection in catheterized patients

Histoplasmosis

Pathogenesis : Facultative intracellular Inhaled spores are engulfed by macrophages/neutrophils develop into yeast form - divide by budding Survive inside phagolysosomes by producing bicarbonate and ammonia to keep the pH alkaline - preventing the killing process. Carried to regional lymph nodes - may disseminate to liver, spleen etc. Dependent upon the intensity of exposure and immunologic status of the host. Asymptomatic infection occurs in 90% of individuals after a low-intensity exposure. In the event of an exposure to a heavy inoculum, however, most individuals exhibit some symptoms (Murray) In AIDS patients, pancytopenia and ulcerated lesions on the tongue are typical of disseminated histoplasmosis In immunocompetent people, Erythema nodosum (a sign that cell mediated immunity is active and the organism will probably be contained) can occur Erythema nodosum is a type of skin inflammation that is located in a part of the fatty layer of skin. Erythema nodosum results in reddish, painful, tender lumps

Pneumocystis pneumonia (PCP)

Pathogenesis and Clinical Disease interstitial pneumonia Extracellular pathogen Inflammatory response and damage to alveoli, frothy exudates, blockage of gas exchange. Major surface glycoprotein undergoes antigenic variation Pulmonary: fever, dry cough, shortness of breath, and fatigue. Chest radiography demonstrates bilateral infiltrate- "ground glass" like appearance Extra pulmonary lesions occur in a minority (<3%) of patients; involving most frequently lymph nodes, spleen, liver, and bone marrow (RES).

Smallpox

Pathogenesis and Clinical Disease -Virus replication in the upper respiratory tract and local lymph node and enters the blood -Dissemination to liver, spleen bone marrow and other organs -Secondary viremia and spread to skin IP: 7-17 days Prodrome - flu-like symptoms High Fever, abrupt onset of a rash - vesicular rash Begins as macular, progresses to vesicular to pustular, then crusts First evident on the mouth, spreads to face and extremities, then to trunk, can cover entire body within 24 hours Simultaneous eruption of Rash in smallpox differentiate it from that of chickenpox where the rash erupt in successive crops

Mucormycosis

Pathogenesis: an acute inflammation of soft tissue, usually with fungal invasion of the blood vessels, in particular the arteries of paranasal sinuses, lungs, gut, oral mucosa. Produce hydrolytic enzymes - tissue destruction. This results in thrombosis, infarction and ischemic necrosis of tissues distal to the blocked vessel. The disease can spread rapidly Involves the rhino-facial-cranial area, lungs, GIT, Skin

Coordinated expression of several genes

Pathogenicity Islands : Assemblage of several virulence genes in one or more contiguous DNA sequences Usually a transposon inserted into the chromosome or a plasmid Can be transferred as a unit and could be turned on by single stimulus Eg. Salmonella - 25 genes can be turned on by a change in pH in a phagocytic vesicle within macrophages

Filarial Elephantiasis

Pathogenicity: chronic and debilitating Acute phase: recurrent fever, inflammation of lymphatic channels (lymphangitis) and lymph nodes (lymphadenitis); Due to release of endotoxin like molecule by Wolbachia (rickettsia like bacteria as endosymbiont in Wuchereria) Chronic: presence of adult worms and host reactivity eventually obstructs the lymphatic vessels, causing edema in the extremities-arms and legs; lymph nodes enlarge Thickening & hypertrophy of the tissues- Affected part enormously enlarged: Filarial elephantiasis Males-hydrocele or swelling of the scrotum The stretched skin is susceptible to traumatic injury and bacterial infections may complicate Chyluria: escape of chyle through urine

Zoonotic Bacterial Pathogens

Pathogens Gram negative rods -Yersinia pestis Black death (bubonic & pneumonic plague) -Francisella tularensis Tularemia -Brucella spp. Brucellosis -Bartonella henselae Cat scratch disease, -Angiomatosis -Pasteurella multocida Bite wound (cat and dog) -Capnocytophaga canimorsus Dog Bite -Streptobacillus moniliformis Rat bite fever Spirochetes -Borrelia burgdorferi Lyme disease -Borrelia spp. Several spp. Relapsing fever -Leptospira interrogans Weil's disease

Typhoidal Salmonella Spp.

Pathogens: Salmonella typhi, Salmonella paratyphi Properties: Gram negative rod; non-lactose fermenter; produces H2S, motile Reservoir: human, no animal reservoir, colonization of gallbladder for up to one year in 1-5% of infected persons. Transmission: fecal-oral Risk Factors/High Risk Populations: poor public and personal hygiene: travelers to endemic areas, < 30 years old Virulence: Ability to multiply in monocytes, and LPS Clinical Disease: Enteric fever/Typhoid fever, severe multi-systemic illness characterized by classic prolonged fever, potentially fatal if untreated,

Rapid Group A Strep Test

Patients specimen, throat swab, is re- suspended in sterile buffer, transferred to cup on one end of the reaction tube shown above. As the organisms in the patient's specimen come into contact with the antibodies fixed to the reaction surface, bands will appear. The top band marked C indicates that the reagents and antibodies are still in good condition and that the test protocols have been adhered to. The bottom band marked T, if it appears, indicates the presence of Streptococcus pyogenes in the patient's specimen.

Naturally occurring Penicillins

Penicillin G Acid labile, Narrow spec Penicillin V Acid Stable, Narrow spec Active against Gram positive bacilli and cocci, Gram negative cocci, and spirochetes Poor activity against G -ve rods Side effects: allergic reaction Most clinical isolates have developed resistance to these drugs.

Treatment for S. Pyogenes

Penicillin G For severe systemic infection: Intravenous penicillin + protein synthesis inhibitors (clindamycin) Drainage and aggressive surgical debridement for soft tissue

Treatment of Streptococcus pneumoniae

Penicillin/erythromycin for most strains. Increasing resistance to penicillin. Don't produce beta-lactamases, but mutation of PBPs Alternative drugs- ceftriaxone or vancomycin Prevention: pneumococcal capsular vaccines; two types PPSV23/PPV23 (Pneumovax): 23 valent vaccine: T cell independent polysaccharide antigens. covers 88% of most frequent isolates, Recommended for all adults 65 years or older and for those children 2 years or older at increased risk for disease. PCV13 (Prevnar 13): 13 valent vaccine, conjugated to diphtheria toxoid, gives T dependent response. Recommended for use in infants and young children; and adults 65 years or older. Older children and adults younger than 65 years old who are at increased risk for getting pneumococcal disease may also need a dose of PCV1

Treatment and Prevention of syphilis

Penicillin: long acting benzanthine penicillin Allergic patients erythromycin, tetracycline Penicillin can cross placenta- Complications of therapy Jarisch-Herxheimer reaction Reactions due to sudden massive destruction of spirochetes by drugs and release endotoxins manifested by fever, hypotension, rigors and aggravation of the existing clinical picture Prevention: No vaccine, safe sex

Clinical diseases of H. pylori

Peptic Ulcer Chronic Superficial Gastritis Lyphoproliferative disease-MALT B cell lymphoma, due continuous activation of B cells Chronic Atrophic Gastritis Gastric adenocarcinoma is associated with Cag+ strains and high level of IL-1 production (host factor)

Types of EBV

Permissive (productive) infection: Virus replicate and lyses the infected cell. Infected cells have EA (early antigen), VCA (viral capsid antigen) and MA (membrane antigen) Non-permissive (latent) infection: acts as a B cell mitogen (transform and immortalize). EBV DNA is found in the nucleus but not integrated with the chromosome. Infected cells have EBNA (Epstein Barr Nuclear Antigen) and LMP (latent membrane protein) needed for immortalization and cell growth

Hepatitis A virus

Picornaviridae General properties: ss positive sense RNA, no envelope; member of the enterovirus - known as enterovirus 72 , only a single serotype Replication similar to other Picorna viruses (+ssRNA). Make their own RNA Dependent RNA polymerase Receptor mediated endocytosis : Entry Reservoir: Humans, 50-75% adults are seropositive in the US Transmission: fecal-oral, cont. fingers, water or sea food. Low infectious dose: 10-100 virus particles. Virus shed 2 weeks before symptoms appear. Stable at pH 1, detergents, 60 C, salt, drying. But sensitive to chlorination. Risk Factors/High Risk Populations: Unvaccinated; overcrowding with poor food hygiene Outbreaks such as summer campus, day care centers MSM Travelers to high HAV-endemic countries;

Taenia solium

Pig Tapeworm Epidemiology: worldwide, intermediate host- pigs, humans- definitive (sometimes, intermediate host) Transmission: Eating undercooked pork 'measly pork' (containing larvae) Fecal-oral (from infected persons)- by ingestion of contaminated water or eating undercooked vegetables infected with eggs. Morphology: Eggs, Larvae (Cysticerci), Adults

Trichinella spiralis

Pigworm Adult worms: female 2.2 mm in length, males 1.2 mm Epidemiology: Worldwide, infects a wide variety of animals- carnivores/ omnivores PIGS main source for humans. Estimated 10,000 cases of trichinellosis occur every year worldwide; Temperate, Tropical and Polar regions Transmission: consumption of undercooked pork or wild carnivores such as BEAR, SEAL, that contain the larvae embedded in muscle tissue.

Pathogenesis of E. coli UTI

Pili/ Fimbriae ( 2 types) - Adhesions -Type 1 fimbriae (FimH): Binds to mono-mannose residues on urothelial cells -P pili: (pyelonephritis Associated Pili, (PAP): binds to dimers of galactose (Gal-Gal) on the P1 antigens Hemolysin (HIyA): tissue damage Flagella: motility LPS : inflammatory response Staying dormant inside urothelial cells : recurrence

Bacterial conjunctivitis

Pink eye H.aegyptius is also called Koch-Weeks bacillus (found by Robert Koch, 1883 and Week, 1887). It is a contagious organism associated with acute purulent conjunctivitis. It can cause epidemics, commonly in warm months of a year. It also requires factors X and V.

Enterobius vermicularis

Pinworm Epidemiology: Worldwide - 500 million infections (estimated) Most common helminth infection in US; small children, crowding- day care centers, schools and mental institution; Most common in temperate region (cold weather); poor hygiene; No animal reservoir Transmission: fecal-oral, ingesting pinworm eggs either directly or indirectly. Autoinfection (Retrofection) Retrofection: infection with pinworms in which the eggs hatch on the anal skin and mucosa and the larvae migrate up the bowel to the cecum where they mature

Pathogenesis of Enterobiasis

Pinworm infection Mild to severe disease depending on worm burden; Severe type IV immune response to secretion of the female, itching/pruritus in skin around the anal area. Clinical Disease: IP: 1 to 2 months or longer Severe itching : perianal and vaginal irritation caused by the female migration or presence of egg and larvae. The itching results in insomnia and restlessness Secondary bacterial infection: due to scratching Gastrointestinal symptoms: pain, nausea, vomiting, etc. may develop. Adult worm enters appendix or genital tract in females leading to inflammation and granuloma. Eosinophilia and elevated IgE Type IV reaction to female laying eggs, just like it is poison oak

Colistin

Polymyxin B, and Polymyxin E Structure: Basic polypeptide Mechanism of Action Cationic detergent Disrupts cell membrane Pharmacology: Bactericidal, narrow spectrum Gram negative bacilli (not for Gram positives) Side effects include neurotoxicity and acute renal tubular necrosis

JC Virus

Polyomaviridae (previously under Papovaviridae Family) Progressive Multifocal Leukoencephalopathy (PML) (Loss of white matter) Properties: Naked, ds DNA (circular) virus , icosahedral capsid Reservoir: Humans; 80% are sero-positive Transmission: Close contact - respiratory droplets? Organ transplant mainly Kidney Risk Factors/High Risk Populations: Immunocompromised people, especially with impaired cell mediated immunity

Paramyxoviridae

Possess spikes: H- hemagglutinin, N - Neuraminidase on the same spike and F- fusion protein on a separate spike contains three genera, some cause RT infections Paramyxovirus: parainfluenza and mumps Pneumovirus: respiratory syncytial virus and metapneumovirus Morbillivirus: measles Enveloped, negative sense ssRNA viruses, carry RNA polymerase Non segmented RNA, helical nucleocapsid F peplomer for fusion. Replication is like other negative sense ssRNA viruses Envelope of paramyxovirus seems to be fragile, distorted on images

Treatment of Rabies

Post exposure prophylaxis (PEP) before signs and symptoms begin 1. Clean wound - soap inactivate virus 2. Passive immunization: Human rabies immunoglobulin (HRIG) or equine antirabies serum Around the wound and intravenous 3. Active immunization: Inactivated (killed) virus vaccine; IM HDCV (Human diploid cell rabies vaccine) and PCECV (Purified chick embryo cell vaccine) 4. Antiviral drugs: ribavirin, IFN-α, and ketamine PEP for Non-immunized people: HRIG + vaccine (Days 0, 3,7 & 14) +5th dose (Day 28) for immunocomprom. PEP for previously immunized people No HRIG + Vaccine (days 0 and 3)

Diagnosis and treatment of scabies

Potassium hydroxide (KOH) -preparation of skin scraping or skin biopsy -demonstrates mite or their eggs or fecal pellets Treatment: Permethrin (Elimite)Apply from head to toe, leave on for 8-14 hr, rinse; may reapply in 7 days if live mites reappear Single application usually curative -drug of choice, Alternative-1% gamma benzene hexachloride (Lindane) Prevention and control Treatment of close contacts of the patient Treating or discarding fomites

Prevention of Rabies

Pre-exposure prophylaxis: HDCV or PCECV- 3 doses (0, 7, and 21 or 28 days): frequent risk people-veterinarians, spelunkers, laboratory workers, and animal handlers. Vaccination of domestic cats and dogs: a live recombinant vaccinia virus expressing the G protein of rabies Wild animals: a live recombinant vaccinia virus expressing the G protein of rabies, put in bait and parachuted into forest, immunizes animals

Diagnosis of BV

Three of the four criteria should be positive -Thin homogeneous discharge -pH of vaginal discharge >4.5. -Whiff test: Mixture of vaginal discharge and 10% KOH liberates an "amine-like" or "fishy" odor -Clue cells in saline wet mount or Gram stain of vaginal discharge

Application of Cell Culture

Presumptive identification of virus: by study of Cytopathic effect, Hemadsorption (Infected cell with hemagglutinin expressed on its surface + RBCs= Adsorption of RBCs on the surface of infected cell) Hemagglutination (Virus with hemagglutinin +RBCs= Agglutination) Interference (with the formation of CPE) and Decrease in acid production by infected cells Definitive identification of virus (grown in culture): by Neutralization*, Hemagglutination inhibition*, (*will be discussed under serology-slide no. 23) Immunofluorescence, Complement fixation, ELISA Others: Plaque assay: quantification of viral particles, titration Focus assay: determine oncogenic potential

Pathogenesis of JC virus

Primary replication in respiratory tract/tonsils/GIT- infection of lymphocytes-then epithelial cells of kidney Latent infection in kidney cells, B cells, monocyte cell lineage Reactivation in T cell deficient pts (eg, AIDS) and viral replication-viremia and viral shedding in urine (but no nephritis) Reaches CNS, crosses the blood brain barrier by replicating in the endothelial cells of capillaries Infects oligodendrocytes and astrocytes (Neurons are unaffected) Causing loss of white matter - myelin

Pathogenesis of Enteroviruses

Primary site of infection is lymphoid tissue associated with the oropharynx and gut (GALT). Virus production at this site leads to a transient viremia, following which the virus may infect the CNS. Replication of the virus in the CNS occurs in the 'grey matter', particularly motor neurons in the anterior horns of the spinal cord and brain stem. Distinctive 'plaques' produced in the grey matter are due to lytic replication of the virus & probably inflammation caused by an over-enthusiastic immune response. Death of these cells results in paralysis of muscles innervated by these neurons.

Phenotypic mixing

Progeny virus acquiring coat components of both the viruses; or genome of one virus surrounded by capsids or both capsids and envelope of other virus May occur between related viruses, e.g. different members of the Picornavirus family, or between genetically unrelated viruses, e.g. Rhabdo- and Paramyxo- viruses. In the latter case the two viruses involved are usually enveloped since it seems there are fewer restraints on packaging nucleocapsids in other viruses' envelopes than on packaging nucleic acids in other viruses' icosahedral capsids.

Osteomyelitis

Progressive infection of bone/bone marrow Most common cause: Staphylococcus aureus Classification: Based on- Route of infection: Hematogenous or contiguous spread Duration: Acute, Subacute or Chronic Host response: Pyogenic or Granulomatous

Enterococcus faecalis/faecium

Properties. Gram positive cocci in chains/pairs, catalase negative bacitracin and optochin resistant, varied hemolysis grow in 6.5% NaCl and 40% bile hydrolyze esculin PYR + (pyrolidonyl arylamidase) Reservoir: human colon, urethra, female genital tract. Source of infection: Endogenous or exogenous Transmission: Nosocomial infections, Endogenous: commonly after perforation of bowel or surgery Risk Factors/High Risk Populations: Hospitalization, catheterization, surgery, broad spectrum antibiotic use, treatment with vancomycin;

Coxsackie & Echoviruses

Properties: + ssRNA, icosahedral, non-enveloped Coxsackievirus: type A and B. Echovirus has many types Reservoir: human Transmission: Coxsackie : fecal-oral+ aerosol, Echoviruses: fecal-oral, common in summer - early fall

Staphylococcus epidermidis

Properties: Coagulase negative, catalase positive, non-hemolytic, Mannitol non fermenter, lacks the classic virulence properties of SA, Novobiocin sensitive Source. Normal skin flora Virulence: Surface slime layer and biofilm formation, especially on surface of foreign implants ; makes treatment difficult, hide from immune response Diseases: Are almost always Nosocomial infection Endocarditis: Bacteremia followed by deposition on heart valve prosthetic heart valve or damaged native valve Catheter and prosthetic joint infections: Biofilm formation in indwelling catheters, prosthetic devices such as in dialysis patients

BK Virus

Properties: Family Polyomaviridae; Naked, ds DNA virus Reservoir: Humans; ~80% of adults worldwide are sero-positive for BKV, latent infection in kidney and lymphoid tissues no evidence that BKV causes disease in the immune competent population Transmission: Has not been definitively established Respiratory spread is most likely; Organ transplantation Risk Factors for Disease: Renal transplant, bone marrow transplant, immunocompromised, pregnancy, old age

Zika virus

Properties: Flavivirus, Env, ssPos sense RNA, icosahedral Reservoir: primates, humans (many animals including birds are seropositive) Transmission: Mosquitoes (Aedes aegypti and Aedes albopictus) - day and night biter. Mother to fetus and during birth Sexual contact: Men to Women (before and after symptoms) Blood transfusion: documented in Brazil Disease: Mostly asymptomatic, (80%) Symptomatic, mild fever, rash, joint pain, and conjunctivitis lasts for about a week Congenital: microcephaly Guillain-Barre : Syndrome Diagnosis: nucleic acid amplification , IgM Treatment: supportive

Serratia marcescens

Properties: GNB, member of enterobacteriaceae, ubiquitous, prefer for damp conditions: showers, toilet bowls, and around wetted tiles MOT: Direct contact Virulence factors involved in its pathogenicity type 1 fimbriae protein secreted factors: proteases, a nuclease, a lecithinase, and hemolysin Causes opportunistic infections: UTI and ocular lens infections. also associated with endocarditis, osteomyelitis, septicemia, wound and respiratory tract infections Lab Diagnosis: Culture produces a reddish-orange pigment called prodigiosin at room temperature

Clostridium difficile

Properties: Gm+, rod, anaerobic spore former Reservoir: Colonizes GI tract of some healthy individuals, 5%. carrier rate higher (30%) in hospital Transmission: Endogenous or via spores; fecal-oral (contaminated clothing, surfaces); aerosols; pass through stomach, bile acids Risk Factors/High Risk Populations: hospitalization -Long term antibiotics use: ampicillin, cephalosporins, clindamycin most commonly associated. -Hospitalized patients: 2 weeks hospitalization - 13% rate of acquisition, 50% of those hospitalized longer than 4 weeks Clinical Disease: Antibiotic Associated Diarrhea (AAD). Mild diarrhea to pseudomembranous colitis Most common cause of nosocomial diarrhea. Community acquired super bug since 2005

Klebsiella pneumoniae

Properties: Gram negative rods, Facultative anaerobe Lactose fermenter on MacConkey agar, member of the Enterobacteriaceae, non-motile, oxidase negative, Indole negative, urease positive Highly mucoid colonies because of large capsule Reservoir: Part of the normal flora GIT and URT Transmission: Endogenous infection- by aspiration; or Spread through person to person contact (eg, from patient to patient via the contaminated hands of health care personnel or other persons), or contamination of the environment. One of the top ten nosocomial infections Risk Factors/High Risk Populations: chronic lung disease, alcoholism, diabetes, respiratory equipment - more in men.

Staphylococcus saprophyticus

Properties: Gram positive cocci, catalase positive, coagulase negative, non-hemolytic, non-mannitol fermenter, grow at 7.5% NaCl, novobiocin resistant Reservoir: moist area of skin around the genitourinary tract Transmission: inoculation from the skin Risk Factors/High Risk Populations: young sexually active women, 95% between 16-35 years Clinical Disease: mostly acute urethral syndrome, cystitis and rarely pyelonephritis Lab diagnosis: Culture Prevention: Personal hygiene, douching/antibiotics after intercourse

Shigella

Properties: Gram-negative rods; Do not ferment lactose, H2S negative, non motile, Four species with multiple serotypes, based on O antigen S. dysenteriae, S. flexneri; S. sonnei; S. boydii Reservoir: Humans, no animal reservoir Transmission: Fecal-Oral transmission, 4 F's, low infectious dose (10 -100 cfu), survives stomach acidity. Risk Factors/High Risk Populations: Primarily pediatric disease (<15 yrs) Epidemics in daycare centers, nurseries, custodial institutions Endemic disease - homosexual males, households with infected children Virulence: invasiveness, moving to neighboring cells without leaving the cell; enterotoxins and Shiga-toxin (verotoxin), LPS. low infectious dose

Cryptococcus neoformans

Properties: Monomorphic yeast, spherical to oval surrounded by a wide polysaccharide capsule, Replication by budding from a relatively narrow base (Single/multiple buds) urease positive Reservoir: Ubiquitous in nature, soil enriched with pigeon droppings, eucalyptus trees Risk Factors/High Risk Populations: Immunocompromised (C. neoformans common): Such as with HIV/AIDS, Organ transplant; Pt taking Corticosteroid Pigeon breeders Transmission: Not from person to person Inhalation of aerosolized cells: lungs then to CNS, skin Cutaneous inoculation

Defective measles virus

Properties: a defective form of a measles virus persisting in the brain Measles belongs to : Paramyxovirus-negative ssRNA, enveloped Late neurologic sequelae found in 1 in a million measles patients People at risk: children infected with measles when younger than 2 years, disease appears app. 7 years later Sub acute Sclerosing Panencephalitis (SSPE) Symptoms include: personality, behavioral and memory changes, muscular jerks or spasticity, blindness

Polio Virus

Properties: ss +RNA, Naked virus, icosahedral (3 serotypes; most infections due to Type 1) Reservoir: Humans, other primates Transmission: fecal-oral Risk Factors/High Risk Populations: Unvaccinated, Infection during early child hood - mild infection, Infection during adolescent - severe disease It is NEUROTROPIC: Virus binds to CD155, (strictly found on primates including humans) Found on, epithelial cells in the gut and oropharynx motor neurons: located at spinal cord anterior horn cells, and cortex Initial replication URT/GIT Spread to brain via blood spread by retrograde transport along nerve axons Clinical symptoms: Muscle paralysis due to death of nerve cells

Propionibacterium spp

Propionibacterium acnes Propionibacterium propionicum General properties: Short, small, Gram positive rods, non-spore forming anaerobe, produce propionic acid from sugars (hence the name) Reservoir: human skin, conjunctiva, external ear, oropharynx and female genital tract Transmission: endogenous Risk Factors/Risk Populations: opportunistic pathogen Pathogenesis and Clinical Diseases Acne vulgaris: metabolic by-products of the bacteria induce inflammatory response in sebaceous glands Opportunistic infections in patients with prosthetic devices or IV lines

Prions

Proteinaceous Infectious Agents Transmissible spongiform neurodegenerative diseases Properties: proteins (PrP) - proteinaceous infectious agents No nucleic acid, resistant to heat, proteases, formaldehyde, radiation Normal PrP (PrPC)-cellular prion protein (encoded by normal cellular gene) found on cell membrane-protease sensitive Abnormal PrP (PrPSC , scrapie like prion protein) is an altered conformation of PrPC -protease resistant, aggregates into amyloid rods (fibrils), found in the cytoplasm or is secreted. Reservoir: Humans and animals Transmission: Inherited Acquired: Injection Contact with infected tissue or fomites/medical devices, Organ Transplantation Ingestion of contaminated animal products Risk Factors/High Risk Populations: Families with history of disease (genetic), Surgeons, Transplant and brain surgery patients, People eating beef People with cannibalistic custom

Capsid

Proteins made up of repeated subunits known as capsomeres covers and protects the nucleic acid may have special host cell attachment properties arrangement of capsomeres determine the shape of the virus Icosahedral or helical

Bacterial Cell Walls

Provides shape and helps cell to maintain its integrity under changing environmental conditions Importance from the medical point of view carries virulence factors It is a site of action for many antibiotics It is a site of action for body defense chemicals, such as lysozyme It is important in bacterial classification Gram positive, Gram negative, acid fast Made up of a polymer - Peptidoglycan (Murein) composed of multiple units of -N-acetylmuramic acid (NAM), with tetra-peptide chain (4 amino acids) coming off of the NAM. -N-acetylglucosamine (NAG) along with few other constituents

Chlamydophila psittaci

Psittacosis/Ornithosis/Parrot Fever General properties: as other Chlamydophila (chlamydiaceae) Reservoir: Any species of bird. The bacteria is present in tissues, feces, urine and feathers of infected bird, either sick or healthy one. Turkey- major reservoir in the US Transmission: by aerosolization of respiratory secretions or avian feces Not person to person Risk Groups/High Risk Populations: Abattoir workers, veterinarians, farmers, pet shop owners, zookeepers, or anyone in contact with an infected bird

Listeria monocytogenes

Purulent Meningitis in neonates and immunocompromised adults A particular threat to pregnant women because of its ability to cross the placental blood barrier. Properties: Facultative intracellular, Short Gram-positive rod, in pairs or short chains, tumbling motility, Cold growth, growth at broad temp range (1- 45 0C), withstands pasteurization temp. small zone of hemolysis CAMP test positive Reservoir: a ubiquitous organism found in the soil, vegetation, water, and in the gastrointestinal tract of animals/humans. Transient vaginal carrier among pregnant women (10-30%) Transmission: foodborne, vertical or across the placenta Ingestion of contaminated food (mostly dairy products, meat), vegetables, undercooked food stored in cold Vertical transmission or across the placenta (During delivery if the mother is infected) Risk Factors/High Risk Populations: Fetus, neonates Old patients (>65) Cancer patients Immuno-compromised persons/renal transplant patients Pregnancy : 3rd trimester (reduced CMI)

Antihelminthic Inhibition of Neuromuscular Action

Pyrazinoisoquinoline: Praziquantel Calcium agonist, tetanic muscular contraction as well as destruction of the tegument Tetrahydropyrimidine: Pyrentel pamoate- cholinergic agonist Piperazines - Diethylcarbamazine (DEC): stimulate cholinergic recep. Muscular paralysis, enhances adherence of leucocyte on parasite Avermectins - Ivermectin Interacts with chloride channel, blocks neuromuscular action Phenols-Niclosamide Acts by uncoupling of oxidative phosphorylation in mitochondria-loss of helminth ATP-Immobilization

Detergents

Quaternary ammonium salts "Surfactants" disrupt cell membrane Composed of a long-chain lipid soluble- hydrophobic end and polar hydrophilic end. Effective against Gram negative cell and enveloped viruses Used as skin antiseptics

Ricketssial pox

R. akari Epidemiology: urban distribution; Outbreaks in New York city. Reservoirs: Rodents (mice) and mites. Transovarian transmission. Vector: mice mites Humans accidental host Disease: Biphasic course First papule, then necrotic eschar (may be mis-diagnosed as anthrax) at a bite site, Later abrupt high fever, myalgia, chills, generalized rash with vesicles that dry and crust over Treatment: Disease is relatively mild, spontaneous healing. Doxycycline could be used

Endemic Murine Typhus

R. typhi Epidemiology: worldwide, warm, humid climate. Gulf states (esp. Texas) and southern California in the US. 50 to 100 cases in USA annually (during warm season) Reservoir: Rodents Vector: Rat flea (Xenopsylla cheopis): Principal vector, worldwide Cat flea (Ctenocephalides felis): common in US The organism is excreted in the feces of vector Transmitted to human after scratching the bite site

Mycobacterium marinum

Reservoir: Found in cold or warm, fresh or salted water Risk factor: people with recreational or occupational exposure to contaminated freshwater or saltwater Disease: fish tank granulomas At the site of abrasions usually presents as a localized granuloma but can evolve into an ascending lymphangitis that resembles sporotrichosis (fungal infection) and Nocardiosis, or can spread to deeper tissues Most often in cooler parts of body: elbows, knees, feet, knuckles or fingers

Cervicitis

Red inflamed Exudate: purulent or mucopurulent visible in the endocervical canal or in an endocervical swab specimen, abnormal vaginal discharge abnormal vaginal bleeding (e.g., after sexual intercourse). easily induced cervical bleeding

Replication Sites

RNA viruses replicate in the cytoplasm DNA viruses replicate in the Nucleus With a few exceptions Orthomyxo in the Nucleus and Poxviruses in the Cytoplasm In both compartments: Retroviruses and Hepadnaviruses

Treatment of bacterial meningitis

Rapid assessment and therapy is required Empiric treatment, within 30 minutes of assessment : intravenous Cefotaxime + Vancomycin. Ampicillin + Cefotaxime, Ampicillin + Gentamicin, Anti-inflammatory drug: dexamethasone for children to minimize reaction to free LPS, 10-20min prior or concomitant with the first antimicrobial dose. Change antibiotic - depending of antibiotic sensitivity test results

Pyrrolidonyl arylamidase (PYR) test

Rapid colorimetric method for presumptive identification of certain groups of bacteria based on the activity of the enzyme pyrolidonyl arylamidase. L-pyrolidonyl beta-naphthylamide is impregnated into the test disk and serves as the substrate for the detection of pyrolidonyl arylamidase. Hydrolysis of the substrate yields beta-naphthylamide which combines with the cinnamaldehyde reagent to form a bright pink to cherry red color. A positive PYR tests allows for the presumptive identification of group A streptococci (Streptococcus pyogenes) and group D enterococci.

Transmission of coronavirus

Reservoir: Coronavirus - human SARS-CoV strain (2002) - from bats to palm civet cat, raccoon, dogs to humans MERS-CoV: a new SARS like (nCov) virus emerged in the Middle East Since April 2012; Source- bats, camels Transmission: via airborne droplets to the nasal mucosa, fecal- oral route as well. winter/spring peak time. MERS-Cov - Close contacts, also by drinking camel milk and eating camel meat Risk Factors/High Risk Populations: Coronavirus: common cold mainly affects infants and children. SARS: anyone can be infected MERS-Cov- majority with underlying medical condition but healthy persons can also be infected

Diagnosis of Coxsackie Virus & Echoviruses

Rapid detection of viral RNA in CSF - PCR, Viral culture takes days Treatment: Supportive, no vaccine

Pathogenesis of Naegleria fowleri

Rare but fatal. Primary Amebic Meningoencephalitis (PAM). It starts with flu like symptoms, severe headache followed by Meningeal signs: high fever, stiff neck, vomiting; Olfactory hallucinations, focal neurologic deficits, and progresses rapidly (<10 days); and Coma and death.

Intestinal anthrax

Rare in humans. high mortality, animal infections from grazing and ingestion of spore

Kaposi's sarcoma

Rare malignancy of the blood vessels, Which has become common among AIDS patients, The malignancy results in purplish grape-like lesions in the skin, GI and other organs. A cancerous tumor of the connective tissue: the skin, lungs, gastrointestinal tract, and other organs. Associated with a weakened immune system, such as infection with HIV and the human herpesvirus-8 (HHV-8).

Complications of S. flexneri

Reiter's Syndrome (Reactive Arthritis) Autoimmune Incubation time: 2-4 weeks after infection Symptoms - a triad of arthritis, urethritis, and conjunctivitis, (Can't see, can't pee, can't climb a tree) Risk factor: men aged 20-40 years, HLA-B27

Transmission of HIV

Reservoir: Humans Requires HIV-infected cells: macrophages, lymphocyte or spermatozoa: transmission via free virus appears less likely Sexual contact, blood or blood product transfusion, IV drug use with shared needles Mother to child: Transplacental, (~25%) During delivery, (~50%) Breast Feeding: (~25%)

Pathogenesis of Balantidium coli

Release of proteolytic and cytotoxic sustances Causes invasion and ulceration Extraintestinal-rare Clinical disease: Abdominal pain and tenderness, tenesmus, Bloody diarrhea/dysentery similar to that of Entamoeba histolytica

Treatment of Dracunculiasis

Removing the whole worm and caring for the wound in general. No specific drug to treat or prevent GWD. Prevention and control: no vaccine to prevent GWD Global eradication program-safe drinking water and education, Expected to be eradicated in the near future Filtering drinking water, using a fine-mesh cloth filter like nylon

Pathogenesis of Parainfluenza Virus

Replicates inside epithelial cells, Adhesion mediated by hemagglutinin - binds to sialic acid, Form giant cell & cause cell lysis. F protein spike mediates merging of infected cells - multinucleated cell - syncytia Neuraminidase mediates release and cell lysis

Site-Specific Recombination

Requires no homology It is an integration not exchange Requires restriction endonucleases and sites for the endonucleases on both DNA Foreign DNA may be circular or linear End result is the sum of the existing genome plus the integrated DNA Three major roles: Conjugation: Integration of a fertility factor to make an Hfr cell Transduction: Integration of temperate phage DNA into bacterial chromosome to create a prophage Transposition: Movement and insertion of transposons

Transmission of Adenovirus

Reservoir: Humans, asymptomatic shedding Transmission: Aerosol, close contact, fecal - oral, fomites; crowded condition. Risk Factors and High Risk Populations: children <14 years, young adults in crowded areas, swimming clubs

Mycobacterium chelonae

Reservoir: Tap water and other water sources Risk factor: a growing problem for soft tissue infection related to medical procedures-eg., laser eye surgery; cosmetic practices-eg, tattooing Diseases non-healing wound, subcutaneous nodule or abscess May cause lung disease, joint infection, eye disease and other organ infections

Mycobacterium ulcerans

Reservoir: water bodies such as slow-flowing rivers, ponds, swamps, lakes Risk factor: Tropical and subtropical countries, Africa, Australia and Asia; broken skin Disease: Buruli ulcer (3rd most common mycobacterial infection) Mycolactone (a form of macrolide): toxic, major virulence factor IP: 1-2 weeks: Solitary, painless and sometimes itchy nodule of 1-2 cm In 1-2 months, the nodule may break down to form a shallow ulcer that spreads rapidly and may involve up to 15% of the patient's skin surface Severe infections may destroy blood vessels, nerves, and invade bone

Life Cycle of Arboviruses

Reservoirs: birds, mammals, reptiles, rodents Vectors: usually mosquitoes, few ticks Seasonal: Summer time (June -October) Togaviruses (genus Alphavirus): enveloped, +ssRNA, icosahedral Flaviviruses: enveloped, +ssRNA, icosahedral Bunyaviruses: enveloped, -ssRNA, segmented, helical nucleocapsid Arenaviruses: enveloped, -ssRNA, segmented, helical Nucleocapsid, pleomorphic structure Filoviruses: enveloped, -ssRNA, helical nucleocapsid, filamentous and highly pleomorphic structure

Yersinia pestis Virulence

Resisting phagocytic killing and suppress inflammation Capsule like F1 antigen = antiphagocytic and adhesion Plasminogen activator (Pla) protease gene: Degrades complement C3b and C5a; prevent opsonization and phagocytic cell migration Degrades fibrin clots - promote dissemination Type III Secretion System: suppress cytokine production and resist phagocytic killing Yops (Yersinia outer proteins): Several of them: diverse activities Some have direct destructive enzymatic activity on host cells Others are injected into host cells via Type III secretion system Disrupt signaling system: Once inside the cells Prevents phagocytosis, induce cytotoxicity by destroying actin filaments, blocks cytokine release, no signaling LPS: endotoxin

Clinical manifestation of diphtheria

Respiratory diphtheria Incubation time: 2-6 days (sore throat, fever, dyspnea) Local inflammation characterized by fibrinous exudates that forms tough, adherent gray/green/black - pseudomembrane, Exudate filled with neutrophils, necrotic epithelial cells, erythrocytes, and bacteria in a fibrin mesh Difficult to detach without damaging underlying tissue - bleeds when attempt is made to remove it located on tonsils (tonsillitis) and Pharynx Airway obstruction: Extension of the pseudomembrane to larynx, trachea, serious condition Bull neck appearance: due to enlarged anterior cervical lymph nodes and edema of soft tissues Skin diphtheria - skin ulcer if bacteria enters through the skin, more common than respiratory form.

CMV Clinical Diseases

Responsible for failure of many kidney transplantation. Mononucleosis CMV - similar symptoms like EBV but less severe. Heterophile antibody—Monospot test EBV is positive but not CMV. Heterophile antibodies or Paul-Bunnell antibodies : antibody reacts with certain unrelated antigens such as reaction with horse RBCs In Neonate jaundice hepatosplenomegaly thrombocytic purpura, petechia hearing loss, most common cause of non-heriditary congenital sensorineural deafeness seizures microcephaly Birth defects in neonates include - deafness, mental retardation. Babies infected during birth do not show symptoms the most prevalent viral cause of congenital disease. 15% of stillborn babies

Different types of mutations

Result in variety of mutants: Lethal mutant - due to inactivation of essential genes, can't replicate Defective mutant- deletion/mutation of gene/s: able to replicate with the help of other viruses Host range mutant - change of host/tissue specificity Attenuated mutant - causes less serious/no disease (vaccines) Conditional mutant: (eg temperature sensitivity of influenza live vaccine - can multiply at lower temp of URT but not LRT

German measles

Rubella Virus (Three Day Measles) In children: Low Fever, Maculopapular rash starts on face , moves to trunk/extremities and usually fades after three days, posterior auricular lymphadenopathy (characteristic) In adults: could be more severe, including arthralgia, arthritis and post infectious encephalopathy (immune mediated)

Pseudomonas aeruginosa skin infection

Risk Factors/High Risk Populations: Primarily opportunistic pathogen, immunocompromised state , burn patients, contact with contaminated water Clinical Diseases: A. Skin and Soft tissue infections Folliculitis: Due to immersion in contaminated water (e.g, hot tubs, swimming pools) Finger/ Nail infection. frequent exposure to water or frequent "Nail Salons" Nail turns green with secretion of pigment by microorganism, Proteases disrupt the integrity of the nail which crumbles overtime. Wound and burn infection: most common cause of burn infection green-yellow discharge due to pigment production : (Clue for fast diagnosis) Ecthyma gangrenosum. Cutaneous manifestation of severe, invasive infection Usually among immunocompromised and critically ill patients Erythematous vesicles changing to hemorrhagic, necrotic and ulcerated form

Spotted Fever

Rocky mountain spotted fever(RMSF): R. rickettsii Rickettsial pox: R. akari

Reoviridae

Rotaviruses Kills >1/2 million children annually worldwide Wheel-like appearance of the particles. The observance of such particles gave the virus its name ('rota' being the Latin word meaning wheel). Bar = 100 nanometers

Nematodes

Round worms Elongated, cylindrical, non-segmented worms, tapered on both ends Have complete digestive system The body is covered with a non cellular, highly resistant coating called cuticle. Separate anatomical sexes Female produces either eggs or larvae These eggs and larvae may be infective immediately or may require a period of development to reach the infective stage, influenced by weather and soil type Most common Nematode infection in US: Enterobiasis (pinworm infection)

Measles

Rubeola Virus Paramxyoviridae /Morbillivirus 1st disease Does not have Neuraminidase General properties: enveloped virus, Negative sense ssRNA-carries RNA polymerase, replication as of other negative sense ssRNA, only one type. Two spikes: H (hemaglutinin) glycoprotein: binds to CD46 (found in all cells) F (fusion) protein induces cell to cell fusion = Syncytium formation = multinucleated giant cells Reservoir: Humans- only host Transmission: Highly contagious by respiratory droplets produced by sneezing or coughing; Congenital Risk Factors/High Risk Populations: unvaccinated/malnourished, particularly children 2-5 yrs

Childhoold exanthema (a widespread rash)

Rubeola/ Measles-1st disease (Measles virus/Paramyxovirus) Scarlet fever- 2nd disease (Streptococcus pyogenes) Rubella/ German Measles-3rd disease (Rubella virus/ Togavirus) Erythematous infectiosum- 5th disease (Parvovirus B19/Parvovirus) Roseola infantum- 6th disease (Human Herpes virus 6 &7) Chickenpox-No number (Varicella zoster virus (VZV)/ herpes virus - 3 )

Pathogenesis of Cyclospora cayetanensis

Rupture of epithelial cells during release of oocyst Incubation Period: an average of 7 days Watery diarrhea (most common), loss of appetite, weight loss, cramping, bloating, increased gas, nausea, fatigue If not treated, persistent watery diarrhea lasting over several days Typically, patients who come in with a persistent watery diarrhea lasting over several days may be suspected of harboring the disease, especially if they have traveled to a region where the protozoan is endemic.

Toxic shock syndrome (TSS)

S. aureus toxin mediated disease caused by Toxic Shock Syndrome Toxins (TSST) which are superantigens, bind to MHC---TCR complex with massive release of IL-1, IL-6, TNFα and IFNγ. Initiated by localized infection followed by diffusion of toxin Systemic inflammation resulting in Septic shock with a potential fatal outcome. Signs and symptoms: rapid onset, fever, hypotension, a diffuse, macular, sunburn-like rash which later desquamate, and involvement of at least three organs- liver, GI, Kidney, CNS, muscle and blood; multi- organ failure, septic shock, possible death Risk factors: 5-25% of SA carry the TSST toxin. Tampon, nasal packing to stop bleeding; or localized wound infection

Shigella spp.

S. dysenteriae: most severe S. flexneri S. sonnei : most common in USA S. boydii The CDC estimates that 450,000 total cases of shigellosis occur in the United States every year. "Daycare center diarrhea"

Salmonella spp. (Non-typhoidal)

S. enterica subsp. enteritidis S. enterica subsp. typhimurium S. enterica subsp. choleraesuis Accounted for 50% of top 10 outbreaks of food borne illness In 2015 Properties: Gram negative rod; non-lactose fermenter; produces H2S, motile. Salmonella spp, which has many serotypes (over 2000). Reservoir: animal reservoir, colonize virtually all animals such as chickens, reptiles, birds, and humans. Transmission: fecal-oral; poultry, eggs, dairy products, reptile pets, contaminated veg. high infective dose (105), acid sensitive Risk Factors/High Risk Populations: Decreased stomach acid is a risk factor, young and old at more risk Diagnosis: Culture; Hektoen enteric Agar, H2S positive

Other pyogenic infections of S. aureus

Septicemia: Spread from focal site or IV catheters. One of the leading causes. Osteomyelitis and septic arthritis: Most common cause, Source- hematogenous origin or local infections; Sudden pain and high fever Pneumonia and Empyema: aspiration or hematogenous spread, Acute/typical pneumonia post-viral, post surgery, ventilator-associated. Necrotizing pneumonia caused by CA-MRSA strains, P-V leukocidin positive Acute Endocarditis (normal/prosthetic): common cause in IV drug abusers

Enterohemorrhagic Escherichia coli (EHEC)

STEC: Shiga Toxin Escherichia coli E. coli O157:H7 most common type, other strains: O26, O121, O111, O145 , Reservoir: No human carrier: Cattle (1%) carrier rate Risk Factors/High Risk Populations: Anyone, Children < than 5 years highest risk, eating improperly cooked meat (hamburger!!), vegetables and other food contaminated with animal feces Virulence factors: Bundle forming pili (Bfp) like EPEC; Attaching-effacing - wiping out of microvilli: watery diarrhea Shiga-like toxin (Verotoxin): inhibit protein synthesis and kill epithelial cells and endothelial cells by inactivating 60S subunit of ribosome May lead to bloody diarrhea Infective dose as small as 100 cells Binds tightly to cells and produces verotoxin

Fungal Culture

Sabouraud dextrose agar (SDA): a common culture media Slightly acidic, may contain antibacterial drugs to suppress bacterial growth Two cultures - at 25 oC and 37 oC - detect thermal dimorphism Not reported negative until 4 weeks Gross colony appearance such as color, texture etc.; and Pigmentation Microscopic examination: examine hyphal and spore structures Lactophenol Cotton Blue (LPCB) mount-commonly used Components of LPCB stain: Lactic acid: preservative Phenol: disinfectant Cotton blue: stain Glycerine: hygroscopic agent

Laboratory Diagnosis of parasites

Samples: based on suspicion of organ invasion Stool samples: a series of 3 specimens on alternate days (within 10 days) Urine sample Blood and tissue etc.

General Pathogenesis of Cestodes

Sequestering host's nutrients (due to adults residing in intestines) = malnourishment/developmental and/or physical retardation in young people Massive infections - blockage of the intestine Excreting toxic waste - immune response Space occupying lesions - larvae in tissue Some live for many years - tissue damage increases with time

Amendments to Koch's postulates

Serological: antibodies or antigens specific to the pathogen in question should be detected Molecular: nucleic acid specific to the pathogen in question should be detected

Diagnosis of Toxocariasis and Baylisarcaris

Serology (ELISA), demonstration of the larvae in the affected tissue Diagnosis of VLM, NLM and OLM is based on the clinical findings, the presence of eiosinophilia, known exposure to dogs, cats or raccoons, and serological confirmation/detection of larvae in the affected tissue.

Treatment of Salmonella

Self-limiting in most people. Treatment appears to prolong carriage of the bacteria and does not appear to shorten the course of the illness. However, certain patients at risk of developing systemic infections should be treated neonates, persons over 50 years of age, immunocompromised patients, patients with Sickle-cell disease, patients with prosthetic valves or vascular grafts. Antibiotic resistance is common, appropriate antibiotic depends on local resistance pattern Prevention: proper preparation of poultry & eggs, meat personal and public hygiene proper chlorination of drinking water

Septic shock

Sepsis induced hypotension despite fluid resuscitation, plus hypoperfusion abnormalities Hypotension, hypoperfusion abnormalities

Severe sepsis

Sepsis with organ dysfunction Signs and symptoms Hyppotension: ˂70mm mean arterial pressure Hypoperfusion-eg. Lactic acidosis, oliguria etc. Rususcitation with IV fluids restores normal level

Diagnosis of Cryptococcus neoformans

Serology : CSF/serum: Capsular antigen detection by latex agglutination or enzyme immunoassays. Microscopic; Indian Ink preparation - Thick capsule surrounding budding yeast Mucicarmine staining for identification in tissue Culture: blood agar or mycological media - urease positive Treatment: Amphotericin B; Flucytosine, Fluconazole (HAART may be associated with IRIS in AIDS patients) (see note below)

Diagnosis of HME or HGA

Serology determine antibody titer. DNA amplification. Presence of cytoplasmic inclusion bodies "morulae'' in peripheral blood. Ehrlichia chaffeensis in Monocytes from a case of Human Monocytic Ehrlichiosis; Anaplasma phagocytophilum in a Neutrophil of a patient with human granulocytic anaplasmosis Treatment; Doxycycline

Diagnosis of HDV

Serology, detection of HDVAg ( in acute phase, ¼ +) Antibody HDVAg (IgM). RT PCR - genome detection Treatment and Prevention: No vaccine, but HBV vaccine prevents Same measures taken to prevent/treat HBV

Diagnosis of Q fever

Serology: IFA-test of choice, ELISA PCR Treatment: Doxycycline Prevention: Whole killed vaccination for animals and humans at risk (successfully used in Australia but not commercially available in US (CDC))

Diagnosis of poliomyelitis

Serology: antibody detection Virus isolation: cell culture (eg. Monkey kidney cell culture) from Throat sample (during the few days of illness) Stool (for as long as 30 days) CSF (rarely) Treatment: mainly supportive, Iron lungs breathing machine

Adenovirus 40/41

Serotype associated with GI -diarrhea , enteric serotype General properties: ds DNA, non-enveloped; 12 protruding fibers (penton), several serotypes, Reservoir: Humans Transmission: person-to-person, fecal-oral, fomites, more common in late fall and winter Risk Factors/High Risk Populations: infants; asymptomatic to mild illness in older children/adults Clinical Disease: Infantile diarrhea; IP 7 - 8 days; Duration 8 - 12 days: Watery diarrhea, fever Diagnosis: For outbreaks - Monoclonal antibody assays; EIA for adenovirus 40/41 in stool specimens Treatment: supportive and symptomatic treatment Prevention: Hygiene

Penetration and Uncoating

Several mechanisms Enveloped viruses Fusion: Enveloped virus fuses with host cell membranes, pH dependent; At neutral pH- fusion on the surface and release of the genome takes place. Endocytosis: At acidic pH the whole viral particle is engulfed (Endocytosis) and release takes place in the cytoplasm Naked viruses Endocytosis : Naked viruses are taken up by receptor mediated phagocytosis or, Viropexis: direct penetration of the genome Naked virus binds to receptor sites on cellular membrane and inject the nucleic acid. Uncoating Capsid digested or opened up AND nucleic acid released

Eumycotic Mycetoma

Several spp. Madurella, Acremonium, Exophiala etc. Saprobes,tropical areas with low rainfall Transmission: Enter the body through trauma Disease: localized, chronic, granulomatous-commonly in legs granuloma and abscess that contain large aggregates of fungal hyphae - "granules or grains". deep draining sinuses with serous fluid extension to muscle, fascia and bone - destructive

Pathogenesis of Pseudomonas

Several virulence factors: Adhesins: pili, LPS, and capsule Exotoxin A (ETA): A-B exotoxin, an ADP ribosyltransferase-It reacts with EF-2 to inhibit protein synthesis similar to diphtheria toxin (but less potent) Pigments: Pyocyanin (blue) catalyses production of oxygen radicals-toxic to tissues, stimulates IL8-attracts Neutrophils; Pyoverdin: is a siderophore-binds iron Phospholipase C: digests lecithin, cell lysis Elastases damage elastin containing tissue e,g lung Capsule/slime layer; form biofilm (some strains) Endotoxin and antimicrobial resistance

Pathogens that cause hepatitis

Several viruses, bacteria and parasites may cause hepatitis, but liver is not the only organ they affect. The hepatitis viruses their main site of infection is the liver. Viruses Adenovirus, Coronaviurs Parvovirus CMV EBV Yellow fever Coxsackie Hepatitis viruses Bacteria Mycobacterium tuberculosis Treponema pallidum, Listeria monocytogens Leptospira spp. Salmonella spp. And others Parasites Entamoeba histolytica Plasmodium spp. Babesia microti Leishmania spp Toxoplasma spp Clonorchis sinensis Fasciola spp Fasciolopsis spp Schistosoma spp Ascaris spp Schistosoma spp

RSV bronchiolitis

Severe illness is due to small airway obstruction. Begins with mild symptoms of an URT infection and progresses to cough, wheeze, onset of dyspnea, increased respiratory rate (tachypnea), Rales (Crackles), fever, and retractions indicating LRT involvement (pneumonia) Diagnosis: Antigen detection assays (immunofluorescence, EIA); RT-PCR; Serology (ELISA): paired sera-4 fold or greater ↑ in Ab titre Cell culture: Cytopathic effect -multinucleated giant cells form

Bacillus cereus Eye infection

Severe keratitis, endophthalmitis, panophtahlmitis Risk Factors: Eye trauma, use of non-sterile contact lens solutions, intravenous drug users (eye infection after systematic infection) Pathogenesis: cytotoxins: Cereolysin (hemolysin) and phospholipase C (lecithinase) cause invasive infection Clinical symptoms: Rapidly progressive - within 12-48 hours of injury Corneal deterioration with infiltrates progressing to an abscess Loss of sight may occur within 48 hours Treatment: aggressive multiple antibiotic, surgery eye removal

Normal Flora on skin

Skin is acidic, salty, and dry. About 1000 -10,000 bacterial cell/sq cm Most of them localize superficially on stratum corneum, others are found in hair follicles, sebaceous glands Moist regions such as the axilla (arm pit), the perineum (groin) and the toe webs provide suitable condition yeast and mold prefer moist skin Dominated by Gram positive bacteria Staphylococcus epidermidis - associated with hospital infections where catheters are used, artificial heart valve/Prosthesis infection Propionibacterium acnes - found in the follicles, anaerobic bacteria associated with acne Staphylococcus aureus: enters blood stream through skin piercing site, infective endocarditis in drug addicts Candida albicans: yeast -enter circulation via IV catheters, IV drugs; infection of moist skin

Pathogenesis of Rotaviruses

Shortening and blunting of the microvilli and mononuclear cell infiltration Clinical Disease: Gastroenteritis - IP 1-3 days, duration 3-8 days Characteristic clinical triad: fever, vomiting, diarrhea; Frequent coryza and cough ; Dehydration is leading complication #1 cause of diarrhea in children (6 - 24 months of age) Mild in adults, Re-infection common throughout life

Bacterial meningitis

Signs and Symptoms: Include Acute onset Fever, headache, vomiting Stiff neck in 90% of patients. But may not be seen in children Altered mental status, seizure Bulging fontanelles - in infants Skin rash: In about 50% of meningococcal meningitis, widespread petechiae (skin rash) Brudzinski's sign and Kernig's sign CSF - Increased protein level, decreased glucose (hypoglycorrhachia), and increased cell count: PMN Most common bacteria that cause meningitis, S. pneumoniae and N. meningitidis,

Vaginosis/Vaginitis/Vulvovaginitis

Signs and symptoms: Abnormal Vaginal discharge, Unpleasant odor +/- irritation and/or itching, Suprapubic discomfort Dysuria may be present Pathogens/syndromes Bacterial vaginosis -Several anaerobic bacterial spp. -No inflammation Candidiasis -Candida albicans Trichomoniasis -Trichomonas vaginalis

Pathogenesis of Hookworm infection

Skin manifestation: ground itch - at site of penetration Pulmonary manifestation: migrating larvae (Loeffler's syndrome) Intestinal: Attaches to the intestinal mucosa, bleeding, anorexia Ulcer-like symptoms, and chronic intestinal BLOOD LOSS leading to anemia, diarrhea and abdominal discomfort. Huge appetite with PICA (desire to eat unusual substances, such as dirt, clay, paint)

Variola virus

Smallpox virus General properties: Same as Poxviridae (family), only one serotype - thus became possible to eradicate by vaccine Reservoir: Humans Transmission: Respiratory droplets or aerosolized fluid from skin lesions or direct contact with skin lesion or indirectly by contaminated fomites Risk Factors/High Risk Populations: Unvaccinated populations; Last case in 1977, Eradication acknowledged by WHO in 1980 Risk of Bioterrorism: stockpiles of Variola virus still available in labs (USA and Russia)

Ascaris lumbricoides

Soil-transmitted helminths Giant nematode (roundworm) Epidemiology: Worldwide -prevalent with poor sanitation; eggs survive in nature; persist in feces and sewage; No animal reservoir known (however, a swine species can infect swine farmers) The most common helminthic infection in the world - about ¼ of world population infected. More common in tropical and subtropical climate. Occurs in Southern USA Is regarded as the largest intestinal nematodes parasitizing man. Male: 15-25 cm, Female: 25-40 cm Male has curved posterior end with two copulatory spicules Transmission: fecal-oral; ingestion of eggs Soil transmitted helminth

Hookworm

Soil-transmitted helminths (parasitic worms) Ancylostoma duodenale - old world hook worm Necator americanus - new world hook worm Epidemiology: world wide; second most common roundworm of humans; infect nearly 1/5 of world's population, warm, shady, sandy soil; common in area where human feces are used as fertilizer Transmitted through direct skin penetration of skin by larvae in soil Risk factor: walking bare foot

Competence

Some bacteria are able to take up DNA naturally. However, these bacteria only take up DNA in a particular time during their growth cycle when they produce a specific protein called a competence factor. At this stage the bacteria are said to be competent. Other bacteria are not able to take up DNA naturally. However, in these bacteria competence can be induced in vitro by treatment with chemicals (e.g. CaCl2). The DNA first binds to the surface of the competent cells on a DNA receptor, and passes through the cytoplasmic membrane

Limitations of Koch's postulates

Some pathogens are found as normal flora in certain % of the population Not all microorganisms are cultivable, eg, Treponema pallidum, Mycobacterium leprae Finding an experimental animal model for all microorganism is difficult Some diseases have a synergistic etiology of two or more agents.

Stages of Viral Replication

Stages: Adsorption/Attachment - Adsorption: binding of virus to specific molecule on host cell Entry/penetration - the virus enters host cell Uncoating- the viral nucleic acid is released from the capsid Macromolecular Synthesis- viral components are produced Assembly- new viral particles are constructed Release - assembled viruses are released by budding (exocytosis) or cell lysis

Frame shift mutation

Sometimes, during replication, one or a few adjacent base pairs (nucleotides) have been inserted to or deleted from the DNA. Shifts reading frame. Missense mutation: base changes result in production of different amino acids but the resulting protein may be functional or non functional (which depends on the importance of area affected by the mutation) Non sense mutation: One or more of 3 non sense codons (UAG, UAA, UGA), normally cause termination of the polypeptide chain elongation. If a nonsense codon is formed within a gene by mutation of a sense codon, the protein synthesis is terminated prematurely and only partial polypeptide is produced

Pathogenesis of Fungi

Source Exogenous: Environmental exposure, spore or hyphal form can be infectious Some are geographically restricted Endogenous: Overgrowth of normal flora Route of Entry: respiratory, cutaneous, or through mucus membranes Virulence factors: Include -Cell wall components are inflammatory stimulants -Adhesion factors -Capsules -Survival inside macrophages -Hydrolytic enzymes (proteases, phospholipases) -Thermal dimorphism: ability to grow at 37oC -Mycotoxins: toxic metabolites produced in the environment; associated with mycotoxicosis Some fungi produce melanin which interfere with the oxidative killing inside macrophages.

Epidemiology of Mycobacterium tuberculosis

Source: human is the natural reservoir host Transmission: human to human: inhalation of fine droplets, can survive for 8 months in the air Risk factors: Economically disadvantaged people- homeless, malnourished, compromised immune system (eg. HIV), crowded conditions, drug or alcohol abusers Distribution: World wide distribution, 1/3 of world population infected Worldwide: In 2016, approx 10.4 million new cases and 1.7 million death In US: 9,272 TB cases in 2016 HIV increased the prevalence of TB world wide

Cholera cot

Space for buttocks with bucket underneath to measure fluid loss

Treatment of Black Widow bite

Specific antivenom- treatment of choice Muscle spasm: administration of calcium gluconate or muscle relaxants Prevention and Control Good housekeeping-dusting webs and removing debris from around homes and adjacent sheds Discouraging children from playing on woodpiles and in woodsheds

Myiasis

Specific myiasis: by flies which require a host for larval development eg. Human botfly: Dermatobia hominis Semi-specific myiasis: is caused by species which (i) usually deposit their eggs or larvae in decaying flesh or vegetable matter and at times deposit them on morbid tissue and (ii) are facultative parasites eg. Green bottle fly (Phaenicia spp.) Pathogenesis: Larvae in tissues induces an inflammatory response Clinical disease: Cutaneous myiasis-the most common one Others-nasal, oral, ocular, intestinal, genitourinary and cerebral forms (head trauma) The lesion is painful, erythematous papule Larva visible within a central pore Sense of movement

Diagnosis of Influenza Virus

Specimen - nasal/throat washings or swabs, sputum, endotracheal aspirate Viral detection: Antigen: DFA, ELISA Genome detection: RT-PCR - determine types and subtypes - fast, sensitive and specific Quick techniques (genome or antigen): less than30 min. more than 10 different types, used for screening during epidemics. Viral isolation and identification: Cell/egg culture: Hemagglutination or, hemadsorption assay to detect virus, but not specific. Apply specific tests for identification upto types/subtypes. Serology: measure antibody level (titer) in acute/convalescent sera-Hemagglutination inhibition assay, ELISA, complement fixation

Diagnosis of meningococcal meningitis

Specimen : CSF, Blood, puncture from petechiae Microscopy: Gram stain or DFA, Serology: latex agglutination: detect capsular antigen in CSF CSF analysis: Culture - Chocolate agar, provide 5% carbon dioxide Biochemical tests: Oxidase +, maltose+ and glucose+ with acid production Treatment: Penicillin G is the drug of choice (resistance not common) For allergic persons: chloramphenicol, cefotaxime or ceftriaxone

Diagnosis of bacterial meningitis

Specimen: CSF Chemistry: cloudy, increased protein level, decreased glucose (hypoglycorrhachia) Cell count: increased white blood cell, neutrophils Microbiological analysis Gram stain CSF - presence of any bacteria is significant Culture of CSF and Blood: isolation of etiological agent and their sensitivity testing CT- Scan

Cryptosporidium parvum Life cycle

Stages: several forms Oocyst (with sporozoites inside): inactive: Infective and diagnostic stage: Trophozoite; actively dividing Merozoite Gametes: micro and macro gamonts Gamete fusion - zygote Oocyst

Diagnosis of Mycoplasma pneumoniae

Specimen: bronchial washings (as sputum usually not produced) Culture - Slow, may take up to 6 weeks mulberry colonies on A8 agar (selective and enriched media) with animal serum to provide cholesterol, and antibiotics to inhibit other bacteria. Nucleic acid amplification and antigen detection : excellent sensitivity, specificity not defined Serology: Cold agglutinin test: Non specific, IgM antibodies bind to antigen on erythrocytes of O blood type at 4oC but not at room temp. Presumptive test, Sensitivity 65%, low specificity. A titre of 1:32 or higher is suggestive. ELISA - ∆sis confirmed by 4 fold ↑ or a single high titer (1:128), detect ab against P1 antigen

Diagnosis of Histoplasmosis

Specimen: bronchoalveolar lavage, tissue biopsy, bone marrow aspirates Microscopy: demonstrate intracellular yeast form within macrophages/neutrophils (Giemsa stain) Culture: Sabouraud agar, 37 oC- yeast, 25 o C - hyphal growth with two types of conidia: Tuberculate macrocondia and microconidia Detection of antigen in urine or sera by ELISA, especially for disseminated diseases Detection of antibodies: complement fixation or immunodiffusion assay (precipitation)

Syphilis Diagnosis

Specimen: primary/secondary lesions, CSF, blood for serology Direct detection: Darkfield Microscopy, PCR primary/secondary stage Serology: secondary, latency and tertiary stage; detection of anti-treponemal antibodies in patient sera. Two tests : based on the antigen used -Nonspecific tests: use of cardiolipin as an antigen VDRL or RPR -Specific Treponemal test: use treponemal antigens FTA-ABS; MHA-TP, TP-PA test, EIA (various)

Diagnosis of pertussis

Specimens: Saline nasal wash Nasal swabs (with calcium alginate swabs, not the cotton swabs) or, Cough droplets expelled onto a cough plate held in-front of the patient's mouth during a paroxysm Microscopy: Fluorescent antibody staining on aspirated specimens (false positivity high) Culture: standard and preferred method Bordet-Gengou, Charcoal-cephalexin blood agar OR Regan-Lowe Nicotinic acid added to support growth; charcoal, starch or blood are added to adsorb fatty acids/toxic substances Molecular Methodology: PCR, most often used today Serology : ELISA Titers against Pertussis toxin and Hemagglutinin using acute and convalescent sera

Labs for UTI

Specimens: 'Clean Catch' Mid-stream urine Suprapubic aspirate "straight," or "in and out" catheterized urine Urine from indwelling catheter To establish bacteriuria/pyuria 1. Direct microscopic examination: > 1 bacteria cell/ oil immersion field = significant bacteriuria 1 cell/3-4 oil immersion field = <104 bacteria/ml 2-3 WBC/hpf in centrifuged urine-consistent with UTI 2. Chemical Screening Tests (Dipsticks): Leukocyte esterase released from inflammatory cells Nitrate reductase, Nitrite produced by bacterial metabolism Limited to infections caused by Enterobacteriaceae Neither technique reliably detects bacteriuria below 105/ml 3. Culture methods: semi-quantitative/quantitative methods plate and 'dip slide' cultures Appropriate selective and differential culture media: Isolation and Identification of causative agent Comparison of growth on Dip Slide

Lymphocutaneous Sporotrichosis

Sporothrix schenckii "rose growers disease"- Chronic infection of the cutaneous or subcutaneous tissue which tends to suppurate, ulcerate and drain It is often seen in gardeners and begins with a thorn prick on the thumb. A pustule develops and ulcerates. It infects the lymphatic system and then the disease progresses up the arm with ulceration , abscess formation, break down of the abscess with large amounts of pus followed by healing. Progression usually stops at the axilla Primary Lesion: At site of infection, chronic nodules that may ulcerate Secondary lesions: a linear chain of painless subcutaneous nodules along the draining lymphatics lesions may ulcerate and discharge pus Resemble squamous cell carcinoma

Morphology of Plasmodium spp.

Sporozoan, exists in different forms (sexual and asexual reproduction). Sporozoites : infective to liver cells Trophozoites: early stages in liver/RBC Schizont - mature malarial parasite, contains many merozoites. Merozoites: infective to RBC Gametocyte: inside RBC

Rocky Mountain Spotted Fever (RMSF)

Spotted Fever Rickettsiosis (SFR) R. rickettsii Epidemiology: Most common Rickettsial disease in US, especially in the eastern states. Accounts for 95% of the rickettsial dis. in US, Over 1,000 cases occur each year Reservoirs: Rodents, wild and domestic animals (dogs) Vector: hard ticks (Ixodidae) (6 hrs or more exposure) Seasonality: highest in Spring and Summer High Risk population: Hunters, Hikers, Campers A) Female Rocky Mountain wood tick, Dermacentor andersoni B) female American dog tick, Dermacentor variabilis

Diagnosis of Burkholderia cepacia

Sputum or catheter specimens Culture on BAP (or BAP with Polymyxin to which it is resistant) Susceptible to Trimethoprim-Sulfamethoxazole (differentiation from Pseudomonas)

Diagnosis of Aspergillosis

Sputum/ biopsy Microscopy: treat sample with KOH, Giemsa staining Septate branching hyphae and conidia Culture: repeated cultures (false positive, ubiquitous) Sabouraud dextrose agar (SDA), with antibiotics (gentamicin or chloramphenicol but without cycloheximide) Slide culture-for species identification Galactomannan antigen positivity (using an Aspergillus EIA kit) can be detected 5-8 days before clinical signs develop (in 65.2% of patients), findings on chest X-ray are visible in 71.5% of patients and culture results become positive in 100% of patients. Because of their ubiquitous nature repeated positive cultures may be needed to indicate true disease and not simply the recovery of contaminants Cycloheximide : may be added to fugal culture media to suppress the fast growing mold so that they do not over grow and interfere with the growth of slow growing molds. Serology: Allergy: detection of specific IgE in serum—by RAST Radioallergosorbent test Invasive Infection: detection of galactomannan antigen in serum—by ELISA - rapid test Imaging: CXR, CT scan images

Role of Normal flora in health

Stimulation of immune system Maintain proper balance of TH1 and TH2 cells Low level of antibodies produced against normal flora cross react with related pathogens Stimulate development of caecum and certain lymphoid tissue such as Peyer's patch in the intestine Production of essential nutrients Synthesis of vitamin K and B by enteric and lactic acid bacteria Antibodies against normal flora of the intestine have been shown to cross react with antigens of meningococci polysaccharide - may have a protective role Therapeutic role Used as probiotics. Eg, fecal transplant

Diagnosis of Fasciola hepatica

Stool examination-operculated eggs To differentiate from F. buski: bile examination Eggs: broadly ellipsoidal, operculated, bile stained, and measure 130-150 μm by 60-90 μm.

Vertebral Osteomyelitis

Subacute or chronic Elderly (>45 yr): Lumbar vertebra (most common) followed by Thoracic vertebra IV illicit drug user-Cervical vertebra Sources of bacteremia-UTI, dental abscesses, soft tissue infections & infected IV lines back or neck pain (vague, dull pain gradually intensifies over 2-3 months) Atypical pain in chest, abdomen, or an extremity due to irritation of nerve roots fever-low or absent Tenderness, limitation of motion

Features suggestive of GAS Pharyngitis

Sudden onset Sore throat Fever Headache Nausea, vomiting, and abdominal pain Inflammation of pharynx and tonsils Patchy discrete exudates (not always!!!) Tender, enlarged anterior cervical nodes Patient aged 5-15 years of age Presentation in winter or early spring No cough Symptoms usually last for 3-5 days

Rat Bite fever

Streptobacillus moniliformis (North America) or Spirillum minus (Asia) -Gram negative rods Clinical disease: IP (3 days-3 weeks), Fever, rash (flat, red with small bumps), Joint pain or swelling (one or more joints) Accompanied by vomiting, headache and muscle pain Can lead to systemic complications: Abscess in abdominal cavity, hepatitis, nephritis, pneumonia, meningitis, endocarditis

Typical Pneumonia Pathogens

Streptococcus pneumoniae Haemophilus influenzae Klebsiella pneumoniae Pseudomonas aeruginosa Burkholderia cepacia Acinetobacter baumannii Staphylococcus aureus

Dental Plaque

Streptococcus viridans group General properties: Gram positive cocci, catalase negative, alpha hemolytic, lack Lancefield antigen (cell carbohydrate antigen used to classify streptococci into groups - A, B, C, D etc. F antigen may be found in some viridans group), optochin resistant, bile insoluble, non capsulated . Several species S. mitis, S. mutans, S. salivarius, S. sanguis, S. anginosus etc Reservoir and Transmission: normal flora of the mouth and upper respiratory tract and intestinal tract. Endogenous source Risk Factors/High Risk Populations: poor mouth hygiene, tooth extraction, oral surgery and trauma enter blood cause bacteremia

Virulence of Streptococcus pyogenes

Structural Virulence Factors Capsule: Hyaluronic acid - antiphagocytosis M protein: used for serotyping (>150 types) Antiphagocytic: binds to Fc region of IgG and IgA Adhesion factor: binds to collagen, fibrinogen, plasminogen etc. Avoids host immune response -due to antigenic variation F protein: binds to fibronectin Toxigenic and Enzymatic Virulence Factors Hemolysins: Streptolysin S and Streptolysin O O is immunogenic, S is nonimmunogenic Pyrogenic exotoxins: superantigens C5a peptidase: inactivates C5a Streptokinase: lyses blood clots; dissemination Streptodornase (DNase) - dissemination Hyaluronidase: degrades hyaluronic acid

Beta Lactamase Inhibitors

Structural analogues of beta-lactams: have little antibacterial activity but bind strongly to beta lactamase thus protect penicillins/cephalosporins. Given together with beta lactams Clavulanic Acid Augmentin=Clavulanic Acid+ Amoxycillin Sulbactam Unasyn=Sulbactam + Ampicillin Tazobactam Zosyn=Tazobactam + Piperacillin Avibactam Avycaz=Avibactam +Ceftazidime (Cephalosporin) Activity: improved against beta-lactamase producing bacteria

Aminoglycosides

Structure: Amino-sugars linked by glycosidic bonds to other sugar derivatives Various derivatives Streptomycin, Amikacin, Gentamicin, Tobramycin Neomycin, Kanamycin, Netilmicin Mechanism of Action Inhibit protein synthesis by interfering with the function of the 30S ribosome Inhibit initiation complex and cause misreading of mRNA Oxygen dependent uptake Pharmacology Bactericidal (binds irreversibly)- narrow spectrum Effective against aerobes- Gram negatives Streptomycin - Mycobacterium Poorly absorbed in GI Penetrate poorly in abscess (Penetration requires O2)

Macrolides

Structure: Large (13-16 Carbon) lactone ring and two sugars one or more deoxy sugars, usually cladinose and desosamine Derivatives: Erythromycin, Azithromycin, Clarithromycin Mechanism of Action Exert their effect by their reversible binding to the 23S rRNA of the 50S ribosomal unit. Binding to 50s ribosome Prevents the release of tRNA after formation of peptide bond Pharmacology: Bacteriostatic: Broad spectrum, Gram positive and negative, Chlamydia, and Mycoplasma Drug of choice for penicillin allergic patients Mechanisms of Resistance Alteration of 50S ribosomal subunit Enzymatic modification Side effects: GIT disturbances due to suppression of the normal flora

Vancomycin

Structure: Large glycopeptide Mechanism of Action: Inhibits cross linking of peptidoglycan by binding to terminal D alanines Pharmacology: Bactericidal, Narrow spectrum; effective against Gram positives ADR: Red man syndrome: Histamine released from mast cell/basophils Resistance: Van A and Van B genes replace last D alanine with a lactic acid - Gene carried on plasmids and transposon (multi-drug R) Resistant strains of Enterococcus spp (known as VRE) and Staphylococcus aureus problematic (known as VRSA) world wide VRE-Vancomycin resistant enterococci VRSA-Vancomycin resistant Staphylococcus aureus

Chloramphenicol

Structure: Nitrobenzene structure, no derivatives Mode of action: Binds to 50S: Inhibits protein synthesis by inhibiting peptidyl transferase or elongation stage Pharmacology: bacteriostatic Broad spectrum: including anaerobes Side effects: bone marrow toxicity- aplastic anemia; Gray-Baby syndrome Resistance: enzymatic modification and decreased permeability. Inhibits mitochondrial protein synthesis (mitochondria have 50s ribosome) in host cell - a reason for its toxicity in the bone marrow. Another explanation for toxicity is the drug acting as hapten.

Tetracyclines and derivatives

Structure: consists of four joined cyclic rings. Mechanism: binds to 30s - prevents binding of tRNA to mRNA Pharmacology: Bacteriostatic, broad spectrum- Many G+ve, G-ve bacteria; Mycoplasma, Rickettsia, Chlamydia -transported actively into prokaryotes but not into eukaryotes because of energy-dependent transport system present in prokaryotes, but not in eukaryotic cells. Side effects: Discoloration of teeth Calcium and Iron chelator - not for children under 8 and pregnant women Suppress Normal flora: Gastrointestinal, Vaginal tract Photosensitivity Mechanisms of Resistance Active efflux: most common Decrease permeability Alteration of ribosomal binding site Enzymatic modification (acetylation)

Fungal Skin Pathogens

Superficial Malassezia furfur several others Cutaneous (Dermatophytes group) Microsporum spp., Trichophyton spp., Epidermophyton spp. Subcutaneous Mycetoma group-several fungi Sporothrix schenckii Opportunistic Candida albicans

White piedra

Superficial infection of hair (groin and axilla), poor hygiene By Trichosporon spp. (hyphae, arthroconidia and blastoconidia) Reservoir: soils/human skin White to brown swelling along the hair strand, soft and easily removed Shaving or cutting the hair is the treatment of choice. Treated by using topical antifungals, including imidazoles, ciclopirox olamine, 2% selenium sulfide, 6% precipitated sulfur in petroleum, chlorhexidine solution, Castellani paint, zinc pyrithione, and amphotericin B lotion.

Fungal infection Syndromes

Superficial mycoses: limited to the outermost layers of the skin, and hair stimulate little or no immune response, non destructive, Cutaneous mycoses: involves deeper layers of epidermis and its integuments (hairs and nails). induce inflammatory response Subcutaneous mycoses: involves dermis, subcutaneous tissues, muscle, and fascia Opportunistic mycoses: occur almost exclusively in debilitated patients whose normal defense mechanisms are impaired. Range from mucocutaneous to serious disseminated infection

Treatment and Prevention of Onchocerciasis

Surgical removal of nodules (adults) Ivermectin (only kills the larvae; not the adult) Doxycycline (promising result, kills wolbachia-leads to death of adult) Use of insect repellant such as DEET WHO is close to eradicating it Suramin kills adult worms, but is quite toxic - given only for those with eye disease There is a promising new treatment using doxycycline that kills the adult worms by killing the Wolbachia bacteria on which the adult worms depend in order to survive (CDC).

Capsules (Slime layer)

Surround single cells Composition: Mucopolysaccharides Multivalent - poor immunogen in children <2 Polypeptides Multivalent - still a poor immunogen Function Adhesion Protection against: Phagocytosis Dehydration Antibiotic penetration Gycocalyx = capsule (means sugar coat) Multivalent antigens: having multiple binding sites for antibodies Glycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit. The repeating unit consists of a hexose (six-carbon sugar) or a hexuronic acid, linked to a hexosamine (six-carbon sugar containing nitrogen)

Treatment of Haemophilus influenzae

Suspected epiglottitis case should be hospitalized immediately Supportive treatment: Cricothyrotomy if necessary Antibiotic treatment : for severe cases - broad-spectrum cephalosporin - mild cases - amoxicillin, doxycycline Prevention: Immunoprophylaxis: Hib (PRP) Vaccine directed to type b capsular polysaccharide; conjugated to diphtheria toxoid or tetanus toxoid; multiple doses In the USA -95% reduction, the vaccine also reduces carrier rate Chemoprophylaxis : Rifampin to eliminate carriage in high risk groups or outbreaks of H. influenzae Type b

Treatment of EBV

Symptomatic, steroids to reduce inflammation about 95% recover without treatment Sometimes misdiagnosed and treated with ampicillin results in rash There is no specific treatment for infectious mononucleosis, other than treating the symptoms. No antiviral drugs or vaccines are available. Some physicians have prescribed a 5-day course of steroids to control the swelling of the throat and tonsils. The use of steroids has also been reported to decrease the overall length and severity of illness, Prevention: None, Lifelong infections

Treponema pallidum

Syphilis General properties: Spirochete, endoflagella (axial filament), cell wall like Gm -, but too thin to be seen under light microscope: dark filed microscope or require special staining technique. Does not grow on culture media, extracellular pathogen. Reservoir: Humans, strict human pathogen Transmission: Sexual contact, including oral sex Transplacental: from mother during first three years of her infection or during birth (80% chance of transmission) Contact through broken: skin or other mucus membrane Risk Factors/High Risk Populations: Sexually active, neonates from infected mothers

Pathogenesis of Black widow bite

Systemic arachnidism (Neurotoxic disease): by latrotoxin Shortly after bite-sharp pain, followed by local redness, swelling and burning Systemic signs and symptoms also within an hour- Latrotoxin stimulates release of acetylcholine (pre-synaptically) Severe pain and spasm in the extremities, chest pain, nausea, vomiting, intestinal spasms and visual difficulties Abdominal tetanic cramps produce a firm or 'boardlike abdomen'-highly characteristic Acute symptoms usually subside within 48 hours Severe case-Paralysis, coma, cardiac or respiratory failure Diagnosis: Clinical as well as identification of typical spiders

Clostridium tetani

Tetanus Properties: Gram positive, spore forming, motile, slender bacillus (tennis racket, or drumstick appearance due to terminal spores); Strict anaerobe Reservoir: Commonly found soils Transmission: Introduction of spores into puncture wound/Traumatic site; requires low tissue oxygen Risk Factors/High Risk Populations: trauma, deep wound, skin popping by drug addicts, unclean cutting of umbilical cord (neonatal tetanus); unvaccinated

Babesia: Life cycle

The Babesia microti life cycle involves two hosts, which include a rodent, primarily the white-footed mouse and a tick in the genus Ixodes. During a blood meal, a Babesia-infected tick introduces sporozoites into the mouse host . Sporozoites (pyriform bodies) enter erythrocytes and undergo asexual reproduction (budding) . In the blood, some parasites differentiate into male and female gametes, although these cannot be distinguished by light microscopy . The definitive host is the tick. Once ingested by an appropriate tick , gametes unite and undergo a sporogonic (sexual) cycle resulting in sporozoites . Transovarial transmission (also known as vertical, or hereditary, transmission) has been documented for "large" Babesia species but not for the "small" Babesia, such as B. microti . Humans enter the cycle when bitten by infected ticks. During a blood meal, a Babesia-infected tick introduces sporozoites into the human host . Sporozoites enter erythrocytes and undergo asexual replication (budding) . Multiplication of the blood-stage parasites is responsible for the clinical manifestations of the disease. Humans usually are dead-end hosts. However, human-to-human transmission is well recognized to occur via contaminated blood transfusions

HBsAg Rapid Test Principle

The Rapid Test is based on the principle of chromatographic immunoassay for qualitative detection of the surface antigen of hepatitis B virus (HBsAg) in human whole blood, serum, and plasma samples. Monoclonal and polyclonal antibodies are employed to identify HBsAg specifically. This HBsAg Rapid Test employs chromatographic lateral flow device. Colloidal gold conjugated monoclonal antibodies reactive to HBsAg are dryimmobilized onto a nitrocellulose membrane strip. When the sample is added, it migrates by capillary diffusion trough the strip rehydrating the gold conjugate. If present, HBsAg will bind with the gold conjugated antibodies forming particles. These particles will continue to migrate along the strip until the Test Zone (T) where they are captured by anti-HBs antibodies immobilized there and a visible red line appears.

Quorum sensing

The ability of bacteria to sense the presence of other bacteria via secreted chemical signals. Regulation of gene expression in response to fluctuations in cell-population density. Some genes are only turned on when bacteria are present in high concentrations. Many bacteria can use "quorum sensing" to detect presence of specific autoinducer chemicals used for measuring cell density. These autoinducers are specific peptides (Gram positive bacteria) or homoserine lactones (Gram-negative bacteria). Autoinducer is produced in low amounts by all cells, diffuses freely across membrane, so concentration inside and outside cell is same. As cell number increases, autoinducer conc. increases until it is sufficient to bind to activator, turn on transcription of specific genes. Example: some virulence genes of pathogens are controlled by quorum sensing. Until a sufficient density of cells is present, cells don't turn on these factors. Signal molecules produced by individual cells do not have an effect until the bacterial population density is sufficient to provide a concentration of molecules, which then cross cell membranes and activate the manufacture of such cellular products as toxins, enzymes or surfactants

Origin of PrPsc

The abnormal form PrPsc recruits the normal proteins and convert them to the abnormal protein (PrPsc ) and the abnormal protein number increases. How can this model explain the sporadic, acquired or inherited form of the disease? The conversion from the alpha helical to the beta-sheet form may occur spontaneously, though very rarely (sporadic). The conversion may be catalyzed by PrPsc that comes from some exogenous source (acquired). Germ line mutations may make spontaneous conversion more likely (inherited). Somatic mutations may make spontaneous conversion more likely (sporadic). In this case, the mutant form could start the process of conversion and the resulting PrPsc molecules would then convert the normal form from surrounding cells Prion formation and replication. Results in formation of aggregates as amyloid-like plaques in the brain

Aseptic

The absence of microorganisms in tissue

Hepatitis Viruses

The liver is the target organ. They differ in structure, mode of replication , mode of transmission, and in the time course and sequelae of the disease they cause.

Hydatid cyst

The cyst vary considerably in size depending on where in the body they are formed, which may be almost any organ of the body. In the liver (the most common organ affected) it may be approximately 20cm in diameter and those found in the peritoneal cavity may sometimes be very much larger, containing several litres of fluid. For example one case has been reported of a cyst 50cm in diameter, containing 16 liters of fluid. We have to remove the intact cyst to prevent type I hypersensitivity Hydatid (Echinococcus): Larval stage, i.e, a bladder which multiplies by budding and forms many daughter and grand-daughter bladders. On the wall of these cysts, brood capsules are produced, inside which lie scolices.

Enveloped viruses

The envelope is derived from the host cell membrane or nuclear membrane depending on the site of replication (cytoplasm or nucleus). The proteins on the envelope are viral proteins (rarely are host cell proteins found on the envelope). Enveloped with icosahedral capsid e.g. herpes virus, yellow fever virus, rubella virus Enveloped with helical capsid e.g. rabies virus, influenza virus, parainfluenza virus, mumps virus, measles virus

Gene flow in bacteria

The genetic information is stored as a continuous segment of DNA, and the messenger RNA can immediately direct the synthesis of the corresponding protein. In higher organisms, the gene is usually split, and the messenger RNA has to be processed by splicing before it can be translated into a protein. Unlike prokaryotes, most genes in higher eukaryotic cells contain large amounts - as much as 98% in the human genome regions called introns that are not part of the code for the final protein. These are interspersed among the coding regions or exons that actually code for the final protein.

Replication of human coronaviruses

The glycoprotein spikes interacts with receptors on epithelial cells, the virus fuses or is endocytosed into the cell, and the genome is released into the cytoplasm. Protein synthesis is divided into early and late phases, similar to that in the togaviruses. The genome binds to ribosomes, and an RNA-dependent RNA polymerase is translated. This enzyme generates a full-length, negative-sense RNA template for the production of new virion genomes and six individual mRNAs for the other coronavirus proteins. The genome associates with rough endoplasmic reticulum membranes modified by virion proteins and buds into the lumen of the rough endoplasmic reticulum. Vesicles that contain virus migrate to the cell membrane, and virus is released by exocytosis.

Pathogenesis of Toxocariasis and Baylisarcaris

The larvae from the intestine wanders in different organs and disintegrate causing inflammatory response, granuloma, and tissue damage. Larval form migrate to lungs, liver, heart, kidneys, CNS, eyes Toxocara species are the most common causes of VLM and OLM whereas Baylisarcaris procyonis is the most common cause of NLM Disease expression : depends on the organs affected Intestinal: initial manifestation fever, anorexia and abdominal discomfort (During larval penetration of GIT) Pulmonary: cough, wheezing Ocular: Blindness Death can occur due to respiratory failure, cardiac arrhythmias or brain damage

Intoxications

The major signs and symptoms are nausea, vomiting /diarrhea (watery), abdominal cramps, (fever usually absent). Often caused by ingestion of pre-formed toxins as a result of bacterial contamination of food with soil or human source In some cases toxin may be formed while the bacteria multiply in the lumen. Staphylococcus aureus Bacillus cereus Clostridium perfringens Clostridium botulinum

Human Papilloma Virus

The most common sexually transmitted infection in US (CDC). About 79 million Americans Properties: Ds circular DNA, non-enveloped, icosahedral, replicates in nucleus; Poor growth in cell culture; exist in several types, some types show tissue preference Reservoir: Humans; can be infected with more than one serotype at the same time; Transmission: Direct contact: skin to skin; Indirect-by fomites; Sexual; Mother to newborn during delivery. High Risk Populations: Genital HPV: unprotected sex with an infected partner; unvaccinated Skin warts more common among children and young adults.

Nutritional factors

The most important elements necessary for synthesis of bacterial structural components (Carbohydrate, lipid, protein, nucleic acid) are hydrogen, oxygen, carbon, nitrogen, phosphorus and Sulphur. Hydrogen and Oxygen are made available from water added to the culture medium. Carbon and Nitrogen: Carbohydrate (sugars) is the principal source of carbon which is degraded by the bacteria either by oxidation or by fermentation. The oxidation or fermentation process provides energy in the form of ATP. Nitrogen is a major component of protein and nucleic acids and its main source is ammonia, usually in the form of an ammonium salt Sulphur and Phosphorus: Sulphur forms part of the structure of several co-enzymes and cysteinyl and methionyl side chains of proteins. Most bacteria use sulphate as a sulphur source and reduce it to hydrogen sulphide. Phosphorus is required as a component of nucleic acids, ATP, co-enzymes NAD and flavins. Mineral sources: required in trace amounts. Can be provided in tap water or as contaminants of other medium ingredients.

Bacteroides fragilis

The most important strict anaerobic, non-spore-former causing clinical disease. It has a prominent capsule that is involved in pathogenesis since it is (i) anti-phagocytic and (ii) directly involved in abscess formation. This bacterium also produces an endotoxin which differs in composition from typical endotoxin and is of low toxicity. General properties: Gram NEGATIVE bacilli, has capsule, pleomorphic in size and shape; obligate ANAEROBE, 20% bile salt enhances growth, hydrolyzes esculin Reservoir: Humans: GI (Colon), Vagina (60% of women). Transmission: Endogenous, break of the mucosal surfaces (due to surgery or perforation) Risk Factors/Populations: Bowel surgery, penetrating abdominal wounds

Microbiological Overview of GI Tract

The normal flora of mouth may be associated with gingivitis/periodontal disease which is a ploymicrobial process caused by anaerobic bacteria. Members of the alpha hemolytic streptococcus, viridans group ( S.mutans) are associated with dental caries, and if they enter the blood may lead to endocarditis. Most common cause of mouth and tongue infections are Herpes Simplex virus 1 and 2 (gingiovostomatitis/cold sores) and Candida albicans (oral candidiasis). Bacteroides fragilis the most common bacteria in the colon, strict anaerobe - may be associated with post surgery/trauma abscesses in the colon. Escherichia coli the second most common bacteria in the colon.

Toxoplasma gondii life cycle

The oocyst/cyst is rapidly digested by the acidic-pH gastric secretions. Bradyzoites or sporozoites are released, enter the small-intestinal epithelium, and transform into rapidly dividing tachyzoites. The tachyzoites can infect and replicate in all mammalian cells except red blood cells. Once attached to the host cell, the parasite penetrates the cell and forms a parasitophorous vacuole within which it divides. Parasite replication continues until the number of parasites within the cell approaches a critical mass and the cell ruptures, releasing parasites that infect adjoining cells. Most tachyzoites are eliminated by the host's humoral and cell-mediated immune responses. Tissue cysts containing many bradyzoites develop 7-10 days after systemic tachyzoite infection. These tissue cysts occur in various host organs but persist principally within the central nervous system (CNS) and muscle. The development of this chronic stage completes the nonfeline portion of the life cycle. Active infection in the immunocompromised host is most likely to be due to the spontaneous release of encysted parasites that undergo rapid transformation into tachyzoites within the CNS. The principal (feline) stage in the life cycle takes place in the cat (the definitive host) and its prey. The parasite's sexual phase is defined by the formation of oocysts within the feline host. This enteroepithelial cycle begins with the ingestion of the bradyzoite tissue cysts and culminates (after several intermediate stages) in the production of gametes. Gamete fusion produces a zygote, which envelops itself in a rigid wall and is secreted in the feces as an unsporulated oocyst. After 2-3 days of exposure to air at ambient temperature, the noninfectious oocyst sporulates to produce eight (from 2 sporocysts, each with 4 sporozoites) sporozoite progeny. The sporulated oocyst can be ingested by an intermediate host, such as a person emptying a cat's litter box or a pig rummaging in a barnyard. It is in the intermediate host that T. gondii completes its life cycle.

Intestinal Amoeba differential diagnosis

The presence of commensals amoebas in the intestine may make microscopic diagnosis difficult. E. histolytica can be distinguished from the other amoebas by trophozoite and cyst morphology. Number of nuclei in the cyst - maximum 4. Shape of the nuclei - central karyosome. Presence of ingested RBC in trophozoite are characteristic of E. histolytica

Septic

The presence of microorganisms in tissue.

Transcapsidation

The situation where a coat is entirely that of another virus, e.g. a retrovirus nucleocapsid in a rhabdovirus envelope. This kind of phenotypic mixing is sometimes referred to as pseudotype (pseudovirion) formation/Transcapsidation. The pseudotype described above will show the adsorption-penetration-surface antigenicity characteristics of the rhabdovirus and will then, upon infection, behave as a retrovirus and produce progeny retroviruses. This results in pseudotypes having an altered host range/tissue tropism on a temporary basis.

RAST (radioallergosorbent test)

The suspected allergen is bound to an insoluble material and the patient's serum is added. If the serum contains antibodies to the allergen, those antibodies will bind to the allergen. Radiolabeled anti-human IgE antibody is added where it binds to those IgE antibodies already bound to the insoluble material. The unbound anti-human IgE antibodies are washed away. The amount of radioactivity is proportional to the serum IgE for the allergen

Trichuris trichiura (Whipworm): life cycle

The unembryonated eggs are passed with the stool. In the soil, under moist and warm condition the eggs develop into a 2-cell stage, an advanced cleavage stage and then they embryonate; eggs become infective in 15 to 30 days. After ingestion (soil-contaminated hands or food), the eggs hatch in the small intestine, and release larvae The larvae moves to the colon, establish itself and mature to adult form. The adult worms are fixed with the anterior portions threaded into the mucosa. The females begin lay eggs 60 to 70 days after infection. Each female worm shed between 3,000 and 20,000 eggs per day. The life span of the adults is about 1 year.

Loa Loa: life cycle

The vector for Loa loa filariasis are flies of the genus Chrysops. During a blood meal, an infected fly (day-biting flies) introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound. The larvae develop into adults that commonly reside in subcutaneous tissue . The female worms measure 40 to 70 mm in length and 0.5 mm in diameter, while the males measure 30 to 34 mm in length and 0.35 to 0.43 mm in diameter. Adults produce microfilariae measuring 250 to 300 μm by 6 to 8 μm, which are sheathed and have diurnal periodicity. Microfilariae have been recovered from spinal fluids, urine, and sputum. During the day they are found in peripheral blood, but during the noncirculation phase, they are found in the lungs . The fly ingests microfilariae during a blood meal . After ingestion, the microfilariae lose their sheaths and migrate from the fly's midgut through the hemocoel to the thoracic muscles of the arthropod . There the microfilariae develop into first-stage larvae and subsequently into third-stage infective larvae . The third-stage infective larvae migrate to the fly's proboscis and can infect another human when the fly takes a blood meal.

Pathogenesis of Mumps

The virus infects the upper respiratory tract and then spreads through the blood to infect the parotid glands, testes, ovaries, pancreas, kidney, eyes and in some cases the meninges Orchitis in post-pubertal males, which, if bilateral, can result in sterility. Post-pubertal males have fibrous tunica albuginea, which resists expansion (swelling during inflammation), there by causing pressure and necrosis of the spermatocytes.

Radiation

There are two types of radiation used in killing microbes- Ionizing and Non ionizing Ionizing radiation: X-rays, Gamma rays Have higher energy and greater penetrating power than ultraviolet light Create oxygen and hydrogen radicals from water Denature proteins and DNA Used to sterilize heat sensitive materials, such as gloves, syringes Non-ionizing radiation: UV light Destroy DNA by forming bonds between neighboring thymine molecule. Most lethal waves 240 nm-280 nm Poorly penetrate objects Used to sterilize air, operating theater (OT), surfaces Treatment of public water supply

Diagnosis of Babesia microti

Thin Smear: "Maltese cross" - intra-erythrocytic ring-shaped parasites in a thin blood smear. Inoculation of blood sample to hamsters Serology - IFA Detects Antibodies PCR

Pathogenesis of Adenovirus

Three type of infections: 1. Lytic: in permissive cells: results in host cell death: Target cell: muco-epithelial cells in respiratory tract (upper and lower), conjunctiva, GI, urinary tract. 2. Latent- in non permissive cells: cause recurrence in immuno compromised patients Target cells: lymphoid cells: tonsils, adenoid, Peyer's patches 3. Transforming infection: Cancer at the site of inoculation in hamsters only, NOT in HUMANS 1. E1A protein (early proteins) is an oncogene product that binds to hamster p105RB growth suppressor protein. 2. E1B protein is also an oncogene product that binds to hamster p53 growth suppressor protein Disease determined by tissue tropism of specific serotype: Immune avoidance: Inhibit interferon response Block apoptosis of infected cells Reduce MHC I expression

Influenza Virus Vaccine

Three types of vaccines: 1. The "flu shot": an inactivated vaccine (containing killed virus): mixture of 3 (trivalent) or 4 different strains (Quadrivalent) (A and B strains prevalent in the community): IM, SC Eg. Trivalent vaccine in 2010 -2011 in US: included- H1N1, H3N2, plus type B (current strain of type B) 2. Recombinant Vaccine: Injectable; made by inserting the gene encoding hemagglutinin (HA) into an insect virus (Baculo virus) and the HA protein is harvested from the insect cells and purified 3. The nasal-spray flu vaccine: LAIV - Live attenuated influenza vaccine. Reconstructed from a mutant strain and a virulent strain by reassortment. The mutant strains doesn't grow well above 250 C, cold adapted mutant.

Vibrio vulnificus Clinical Disease

Through Contact exposure: Bullae and Necrotizing Fasciitis: IP: 24 to 48 hours after exposure Present with erythema, edema, hemorrhagic bullae (blood filled lesions), ulcers, and may rapidly progress to necrotizing fasciitis and sepsis. Mortality rate 20-30% Through Ingestion: Septicemia - highly fatal (50%) characterized by fever and chills, vomiting, diarrhea, abdominal pain blistering skin lesions often present decreased blood pressure, septic shock

Rubella Virus

Togaviridae Family: Rubivirus Genus German measles General properties: Enveloped; ss Positive sense linear RNA, does not carry viral polymerases. only one serotype Reservoir: Humans only host Transmission: Respiratory secretions, transplacental (congenital): Virus shed days before the onset of the prodrome and during and after the symptomatic phase - Risk Factors/High Risk Populations: primarily in children ages 5-9; unvaccinated, not infected naturally; crowded situation fetus of unvaccinated mothers. In the US, endemic rubella declared eliminated in 2005. Few imported cases are reported.

Eastern and Western Equine Encephalitis

Togaviruses: Env, ss Pos sense RNA, icosahedral Epidemiology: Reservoir host: Birds are major host Humans and horses are dead-end hosts Cause disease and may kill horses Vector: Culex mosquitoes Distribution: Primary rural areas in USA, not common Disease: viral encephalitis EEE is rare but more severe with mortality rate up to 50%, neurological sequelae common WEE more common but less severe - mortality rate of 2% among adults.

Viral Plaque Assay

Titration of Infectious Virus/ quantification of viral particles Cells lyse upon virus release Virus infects neighboring cells Clear zone is created as infection spreads outwards Clear zones are called plaques

Virulence and pathogenesis of C. perfringens

Toxigenic/Enzymatic virulence factors: More than 12 toxins- lyse blood cells and destroy tissues. Most important is the Alpha toxin (Lecithinase - a Phospholipase) Destroys cell membrane: hemolytic/necrotic Kills RBC, platelets, white blood cells, endothelial cells, Leads to massive hemolysis, increased vascular permeability, tissue destruction Others are collagenases, fibrinolysins, etc. which cause tissue damage during infections

Diagnosis of C. difficile

Toxin detection: from stool directly or from C. difficile grown on culture (not all C. difficile produce the toxins Toxin assay for cytotoxins using tissue culture; rarely used Immunoassays, ELISA for Toxin A and B Treatment: Discontinuation of antibiotics; Metronidazole or Vancomycin for severe cases; Relapses common (20-30%); restoration of normal intestinal flora; -Feeding of Saccharomyces boulardii (yeast); -Fecal transplant: via colonoscopy or enema -or oral "A pill full of poop" (90% efficacy ) Prevention: Difficult to prevent, spores can be isolated from floors, bedpan and toilet in hospital room occupied by a patient with C. difficile infection. Hands and clothing of medical staff. No vaccine

Toxin mediated diseases

Toxin interrupt physiological functions. A. Mycotoxicoses: Results from ingestions of mycotoxins produced by fungi on food Ergot Alkaloids-by mold growing in grains (Claviceps purpurea) Causes ergotism- Hallucinations, GI-upset, dry gangrene and painful burning sensation: outbreaks Aflatoxin - produced by Apergillus flavus in moldy grains, peanuts carcinogenic toxin - induce mutation on p53 (growth suppressor gene) - causes liver cancer B. Mycetismus (Mycetism/Mushroom poisoning)results from eating poisonous mushrooms (Amanita spp) Amanitin/Phalloidin: Toxin resistant to heating - cooking does not inactivate May cause severe/fatal liver and kidney failure

Complications of diphtheria

Toxin may be carried to other organs, such as heart, liver, kidney and cause necrosis of tissues Myocarditis - arrhythmias and circulatory collapse Nerve weakness/paralysis: especially the cranial nerves Paralysis of the muscles of the soft palate and pharynx can lead to regurgitation of fluids through the nose Difficulties with vision, speech, swallowing or movement of legs and arms

Scalded skin syndrome (SSS or Ritter's disease)

Toxin mediated disease of S. aureus Caused by EFT (exfoliative toxin): serine protease that cleaves desmoglein 1, a cell adhesion protein Follows Localized infection, mostly nasopharynx - toxin diffuses to the body No attraction of leukocytes, so little or no inflammatory response. Signs and symptoms: (Next slide) Risk factor: neonates and young children Signs and symptoms: Acute onset Fever; erythema, skin blisters, skin desquamation all over the body; skin and hair may be lost; serous exudates, electrolyte imbalance . leaves no scar after healing.

Virulence and Pathogenesis of Campylobacter

Toxin production, invasion of epithelial cells, survival in monocytes - like Salmonella. Enterotoxin: Electrolyte movement - watery diarrhea Followed by inflammatory diarrhea Invasion of epithelial cells leads to ulcers in the bowel mucosa and induces an acute inflammatory response. Systemic - survival in monocytes Sign and Symptoms: Watery diarrhea followed by foul smelling bloody diarrhea (10 or more stools/day) intense abdominal pain, fever, vomiting, mimic like acute appendicitis. Self limited may last for weeks, In immunocompromised it may become chronic and be difficult to treat Systemic infection: survive in monocytes and carried to other parts of the body causing septicemia and dissemination to multiple organs - immunocompromised (mostly by C. fetus)

Macromolecular Synthesis and Replication

Transcription of most viruses results in synthesis of early and late mRNA transcripts. The early transcripts encode regulatory proteins and enzymes required for DNA replication. This proteins are catalytic and only few are needed. The late transcripts encode mainly structural proteins of the virion. Replication of the genome usually initiates the transition to transcription of the late genes. Initiation of nucleic acid synthesis precedes transcription of the late genes.

Specialized Transduction

Transduction is transduction in which only certain donor genes can be transferred to the recipient. Different phages may transfer different genes but an individual phage can only transfer certain genes. Specialized transduction is mediated by lysogenic or temperate phage and the genes that get transferred will depend on where the prophage has inserted in the chromosome. During excision of the prophage, occasionally an error occurs where some of the host DNA is excised with the phage DNA. Only host DNA on either side of where the prophage has inserted can be transferred (i.e. specialized transduction). After replication and release of phage and infection of a recipient, lysogenization of recipient can occur resulting in the stable transfer of donor genes. The recipient will now have two copies of the gene(s) that were transferred. Legitimate recombination between the donor and recipient genes is also possible. Phage genome may pop out of chromosome with the exact genomic information it entered with - it is then non-transducing phage Phage genome may pop out of chromosome with a piece of bacterial chromosome which was adjacent to the insertion site - then it is a transducing phage. Since there is a size limitation on the amount of genomic material which can be packaged into a capsid, it must leave some of the original genome behind

Treatment of of cholera

Treatment 1. Restore fluid and electrolyte balance immediately: - Intravenous infusion of a sterile, solution containing NaCl, KCl, NaHCO3. - Oral rehydration therapy (ORT) with boiled tap water containing the above salts plus 2% glucose. Glucose allows maximum absorption of sodium. - 25-50% of typical cases are fatal if untreated. 2. Administration of antibiotics (tetracycline) in severe cases Prevention and Control 1. Improved sanitation - Chlorination of water supplies; sewage treatment. 2. Vaccination: Current approved vaccine is a killed, whole cell suspension. Effectiveness ~ 50% for 3-6 months. Boosters 6 month intervals.

Treatment and prevention of HSV

Treatment: Antiviral agents relieve symptoms, shorten the course of disease but cannot eliminate latency. Several drugs available The most commonly used is Acyclovir - a guanosine analogue - inhibit viral DNA synthesis The drug is inactive until it reaches an infected cell phosphorylated by viral thymidine kinase Prevention: Avoid direct contact; C - section considered in active outbreak during parturition Screening (part of TORCH)

Genital Skin and Mucous Membrane Lesion Pathogens

Treponema pallidum : Syphilis Haemophilus ducreyi : Chancroid Chlamydia trachomatis: Lymphogranuloma venereum Kelbsiella granulomatis: Granuloma inguinale Herpes simplex virus:* Genital herpes Human papilloma virus*: Genital warts Klebsiella granulomatis : Granuloma inguinale Molluscum contagiosum* : condyloma

Non conventional treponemes

Treponema pallidum subspecies; morphologically and serologically indistinguishable from Treponema pallidum Cross react in VDRL/RPR Transmission not sexual, disease pattern different from syphilis, mostly disease of children and young adults Limited geographical distribution There are three of them -Endemic syphilis/ Bejel caused by Subspecies Endemicum: -Yaws: caused by Subspecies pertenue -Pinta : caused by Subspecies carateum

Adherence

Two types: specific or nonspecific Specific: molecular recognition Duffy antigen is binding site for Plasmodium vivax Non specific: Mechanical "Hooks" in hookworms nonspecific

Treatment of PCP

Trimethoprim-sulfamethoxazole is the drug of choice. Antibacterial not antifungal drugs effective

Epidemiology of Malaria

Tropical and subtropical, human to human via a vector- mosquito (Anopheles spp), by blood transfusions/organ transplant, also by IV drug use Malaria is one of the most severe public health problems worldwide. It is a leading cause of death and disease in many developing countries 1-5 billion febrile episodes and 1-3 million deaths annually. Approx. 1,500-2,000 cases every year in US Airport malaria: In Palm Beach County, Florida, during the summer of 2003, a cluster of eight cases of malaria was detected

Diagnosis of TB

Tuberculin/ Mantoux test/PPD Test : Delayed hypersensitivity test to tuberculin proteins (purified protein derivatives). For screening X-ray: used in conjunction with PPD - looking for tubercles, Ghon complexes, cavitary lesions Samples: Sputum/other specimens Staining and Microscopy : Acid fast staining (Ziehl-Neelsen staining / Kinyoun stain/ Fluorochrome staining with Auramin-rhodamine stain- acid fast bacilli in sputum (AFB) Culture - isolation of organisms in Lowenstein-Jensen (LJ) medium or Middlebrook 7H10 (may take up 2 to 8 weeks for results): Gold standard for laboratory confirmation Interferon-gamma release assays (IGRAs): measure IFN production by Th1 specific to MTB. Alternative to PPD, but more specific DNA probes: for identification

PPD Test

Tubercullin/ Mantoux test Delayed hypersensitivity reaction Detects exposure but does not differentiate past, latent or current infection Measure the diameter of the hard swelling (induration) Done for people at risk of exposure Interpretation depends on risk factors Three categories: 5 mm or more is positive in HIV-positive person, recent contacts of TB cases, persons with abnormal CXR 10 mm or more is positive in increased risk Recent migrants from high prevalence regions Residents of crowded institutions Health care workers Persons with other medical issues. 15 mm or more is positive in Persons with no known risk factors

Francisella tularensis

Tularemia General properties: Very small Gram negative rod, strict aerobe, Grows slowly, fastidious-needs cysteine and complex media such as buffered charcoal yeast extract (BCYE) agar; potential biowarfare agent Reservoir: Wild animals: rabbits, deer, hares, rodents Transmission: Direct contact; Ingestion of contaminated water; Inhalation of aerosols or agricultural dusts; Via Vectors (ticks, and deer fly); Laboratory exposure Highly infectious, Low infectious dose (Only 10-50 organisms required for infection) World wide distribution. In the US, Oklahoma, Missouri and Arkansas. Risk Factors/ Risk population: Outdoorsmen, hunters, trappers

Oocysts of Cyclospora cayetanensis

Twice as large in comparison with C. parvum and are not sporulated (do not contain sporocysts) upon excretion

Prevention of Varicella-Zoster

Two Live attenuated vaccines based on Oka strain Varivax - to prevent varicella (primary infection), Efficiency (70-90%), duration about 20 years, Two doses: children 12 months to 12 years: 2 doses (Min.3 month interval) adolescence (≥13 years) and adults: 2 doses-Min. 1 month gap Zostavax: to prevent Zoster (reactivation) for adults, single dose Passive immunization for immunocompromised: varicella-zoster immunoglobulin (VZIG)

SIRS (Systemic Inflammatory Response Syndrome)

Two or more of signs and symptoms Chills Alteration of body temperature ˃38°C or < 36°C Alteration of mental status Tachycardia ˃90 beat/min Tachypnea ˃20 respiration/min Altered WBC count ˃12,000 or, < 4000 cells/mm3 Left shift ↑ immature neutrophils/band cells (˃10%) Thrombocytopenia Decrease perfusion Increased blood glucose Petechiae and purpura

Herpes Simplex Virus (HSV)

Two strains: HSV-Type 1 & 2 Belongs to Herpesviridae family Ds DNA: linear Properties: large, enveloped, icosahedral; ds linear DNA, surface glycoprotein spikes for attachment. Replicates in nucleus; Derives envelope from nuclear membrane; Establishes latency Cytopathic effect: Change in nuclear structure and margination of chromatin Cowdry type A - Intranuclear inclusion bodies It also causes fusion of cells - Syncytia formation Reservoir: human mucosa/skin and ganglia (trigeminal/lumbar or sacral) Transmission: Contact: close contact with infected secretions or lesions, Contact with saliva (eg. kissing), Sexual contact; transplacental and during delivery of new born babies Life long infection - may result in asymptomatic shedding

Hantavirus Clinical Disease

Two types 1. Hemorrhagic Fever with Renal Syndrome (HFRS) also known as Korean hemorrhagic fever Endemic in Asia (but not in north America) Fever, headache, petechial haemorrhages, shock and renal failure 2. Hantavirus Pulmonary Syndrome (HPS): fatal disease New viral strain known as Sin Nombre virus Reported from North and South America (first outbreak in 1993) Acute influenza like symptoms followed by shortness of breath (due to pulmonary infiltrates and edema) and acute respiratory failure. No signs of hemorrhage A mortality rate of 30%. Diagnosis: Clinical + history of rodent exposure RT PCR Treatment: No specific treatment; respiratory support Control: Rodent control in and around the home

Endocarditis

Two types of manifestations (based on the onset of symptom) seen in endocarditis: Subacute and acute. Subacute endocarditis is more common and symptom develop over a longer period of time (Usually less than 2 wks). The symptom often are non specific. The Acute endocarditis has a rapid onset of action

Prevention of Poliomyelitis

Two vaccines: Inactivated and live polio vaccines available Salk Vaccine: (IPV)1955 Inactivated polio vaccine Safe, no mucosal immunity, more than one dose, duration of immunity not known Sabin Vaccine: (OPV) 1962 Attenuated oral vaccine, Easy to administer, Only one dose, Gives mucosal immunity, Sheded in feces for 6mo - Transfer to non vaccinated persons. Life long immunity Side effect - reversion to virulent strain WHO recommended all countries to switch to IVP by April 2016 complete cessation of OPV planned for 2019

Hemagglutination Assay

Two-fold serial dilutions of a virus are prepared, mixed with a specific amount of red blood cells, and added to the wells of a plastic tray. The red blood cells that are not bound by the virus sink to the bottom. The red blood cells that are attached to virus particles form a lattice that coats the well Used to quantitate viruses that express hemagglutinins on their surface Reading (Example) Sample A: titer of 256 B: no virus detected D: titer of 512

Enteric Fever

Typhoid fever Salmonella typhi Salmonella paratyphi Characterized by abdominal pain and fever Portal entry of the pathogen - gastrointestinal tract After a systemic phase, these infections may subsequently involve intestinal tissue and then manifest as one of the following 1. Enteric fever - characterized by sustained fever, headache, abdominal pain, bradycardia, splenomegaly, bacteremia, and occasionally skin rash 2. Mesentric adenitis: a syndrome that may mimic acute appendicitis

Pneumococcal Pneumonia

Typical Pneumonia - acute Community and Nosocomial. Most common cause of community acquired typical pneumonias Symptoms: Generalised bronchopneumonia (lobular) in children and elderly Lobar pneumonia (lower lobes) if aspirational Abrupt onset, fever, chills, rigors, cough, chest pain with rusty (blood tinged) sputum

Acinetobacter baumannii disease

Typical pneumonia, urinary tract infection, septicemia, infections in aged and ICU patients. Soft tissue infection - Gun shot wound infection in military personnel (Iraq bacillus) Pathogenesis: Virulence factors Outer membrane protein A-adherence Pathogenicity islands (coding for toxins, antimicrobial resistance) Biofilm formation

Brucellosis

Undulating Fever Incubation period 1-3 weeks Onset may be acute or gradual Non-specific symptoms with fever 39-40°C The fever occurs daily in undulating (rising and falling) fashion Especially with B. melitensis, the fever and drenching sweats recur in the late afternoon or evening. Granulomas and abscesses in reticuloendothelial system Undulant fever can continue for weeks to years Advanced disease: may involve Bone/joints, GIT, Respiratory or any organs

Virulence of Proteus species

Urease Urea is converted to NH3 + CO2, increase pH precipitation of magnesium ammonium phosphate struvite stones obstruct urine flow, bacteria can hide inside the stones: escape antibiotics cause recurrence alkaline makes it more favorable for other bacteria Urine high pH, or smell of NH3 of the urine is indicative of a Proteus sp. infection Clinical Disease: Cystitis and pyelonephritis, nephrolithiasis (kidney stone) Flagella; motility LPS: induce inflammation - tissue damage systemic symptoms.

Normal flora in the Genitourinary tract

Urethra; urine flow - low normal flora. May be colonized by flora of the skin and colon. Vagina: Influenced by hormone level Lactobacillus spp. dominate Produce acid - low pH - makes it unfavorable for invading organism Women taking antibiotic treatment for other infections - may develop candida (yeast) infection Group B Streptococcus: in 5-20% women Can cause sepsis and meningitis in new born children

Toxocara life cycle

Unembryonated eggs are shed in the feces of the definitive host . Eggs embryonate and become infective in the environment . Following ingestion by dogs, the infective eggs hatch and larvae penetrate the gut wall. In younger dogs, the larvae migrate through the lungs, bronchial tree, and esophagus; adult worms develop and oviposit in the small intestine (Similar to the route for Ascaris in humans). In older dogs, patent infections can also occur, but larval encystment in tissues is more common. Encysted stages are reactivated in female dogs during late pregnancy and infect by the transplacental and transmammary routes; the puppies in whose small intestine adult worms become established. Puppies are a major source of environmental egg contamination. Toxocara canis can also be transmitted through ingestion of paratenic hosts: eggs ingested by small mammals (e.g. rabbits) hatch and larvae penetrate and migrate into various tissues where they encyst . The life cycle is completed when dogs eat these hosts and the larvae develop into egg-laying adult worms in the small intestine. Humans are accidental hosts who become infected by ingesting infective eggs in contaminated soil or infected paratenic hosts . After ingestion, the eggs hatch and larvae penetrate the intestinal wall and are carried by the circulation to a wide variety of tissues (liver, heart, lungs, brain, muscle, eyes) . While the larvae do not undergo any further development in these sites, they can cause severe local reactions that are the basis of toxocariasis.

Risk factors for HIV

Unprotected sex, Neonate of HIV positive mother, inflammatory STD's - syphilis, gonorrhea, genital herpes, etc. Uncircumcised male Long term survivors and resistant: have mutated CCR5 a receptor for the virus Mutation rate varies among races. Certain HLA alleles: epidemiological and genome seq. Infected by a mutant strains, especially mutation in nef gene

Cystitis

Urgency, increased frequency, dysuria, suprapubic tenderness, small volume cloudy urine, smell, low back discomfort especially pre-and immediately postvoid. Low grade or no fever Hemorrhagic large quantities of visible blood in the urine

Specific Treponemal Tests

Use antigens specific to TP Remain positive for life: Not useful for follow-up of treatment. 3 tests FTA-ABS Utilizes indirect immunofluorescence and killed Treponema cells fixed to slide and serum previously absorbed to remove non-specific anti-treponemal antibodies (FTA-ABS) Agglutination tests: TP-PA test: Treponema pallidum particle assay: uses gelatin particles sensitized with T. pallidum antigens - micro-titer agglutination MHA-TP - Microhemagglutination assay Treponema pallidum RBC attached to TP specific antigens Microhemagglutination test in the presence of antibodies specific to TP Enzyme Immunoassays

Treatment of Osteomyelitis

Use of bactericidal agents has been recommended Debridement/Surgery: For chronic infection

Sterilization

Use of physical procedures or chemical agents to destroy all microbial forms, including the bacterial spores. Physical means: heat and radiation Mechanical means : filtration Chemical means: Alcohol, H2O2

Salmonella

Use phase variation to switch between different types of the protein flagellin. As a result, flagella with different structures are assembled. Once an adaptive response has been mounted against one type of flagellin, or if a previous encounter has left the adaptive immune system ready to deal with one type of flagellin, switching types renders previously high affinity antibodies, TCRs and BCRs ineffective against the flagella.

HBeAg test

Used to determine if a patient infected with HBV is infectious; patients with anti-HBeAg are not considered infectious. Patients who have chronic HBV hepatitis with HBeAg are infectious and usually have a much worse prognosis (chronic active hepatitis), whereas patients with chronic HBV infection and anti-HBeAg (chronic persistent hepatitis) are less likely to have serious infections and are not considered as infectious.

Light Microscopy of viruses

Used to monitor the cytopathic effect. Morphological change: Change in shape, such as the rounding of cells, aggregation, degeneration Loss of attachment to culture dish, loss of contact inhibition Syncytia formation (multinucleated cells) Inclusion bodies: aggregation of viral proteins or particles in the cytoplasm or nucleus, margination of chromatin Haemadsorption - cells acquire the ability to stick to mammalian red blood cells by expressing viral hemagglutinin antigens on their surface

Bright field Microscope

Uses the visible light source under the stage to produce a clear image. The Diaphragm adjusts the amount of light entering the stage. It consists of three objectives- the scanning power(usually 4x-6x), the low power(10-12x), and high power(40x). Maximum useful magnification: 1000-2000X eg, Compound Microscope

Viral arthritis

Usually begins suddenly Parvovirus-B19 (in developed countries) In children, fever, headache, rash, fatigue Polyarthralgia, most commonly Joints of the hands, wrists and knees Symmetrical joint pain In adults, rubella can cause viral arthritis Its rate decreases due to mass vaccination during childhood It involves small joints No erosion seen on joints Diagnosis: clinical/serological and polymerase chain reaction (PCR) Treatment: It resolves spontaneously within 2 weeks, In some (20%) female patients, arthritis may persist for 2 months

Prevention of HPV

Vaccines (Subunit): A. Gardasil - (2006) Contains capsid proteins from 4 HPV types (Quadrivalent)/ or from Nine types (Nonavalent): HPV 6, 11 - which cause 90% of all genital warts HPV 16 and 18 which cause 70% of all cervical cancers 3 doses (second and third dose 1-2 months and 6 months after 1st dose.), IM Routinely given at 11 or 12 years of age, but it may be given beginning at age 9 years through age 26 years. B. Cervarix: Bivalent vaccine (2009) against HPV 16 and 18 (age 9-26) 3 doses (0,2,6 month), IM

Viral Evasion of the Immune Response

Various ways: few examples Existence in multiple Antigenic variants: eg. Influenza virus Latency- wait until the immune response weakens Infection of immuno-privileged sites within the body e.g. HSV in sensory ganglia in the CNS Interfere with antigen presentation Down regulation of MHC I expression, e.g. Adenoviruses Down regulation of LFA-3 and ICAM-1. Eg EBV LFA3: Lymphocyte function-associated antigen 3 (CD58): is a cell adhesion molecule expressed on Antigen Presenting Cells (APC), particularly macrophages. It binds to CD2 (LFA-2) on T cells and is important in strengthening the adhesion between the T cells and Professional APCs Inhibit TAP Transporter associated with Antigen Processing proteins Interfere with KAL and KAR i.e with NK recognition and killing, Eg. CMV Direct infection of the cells of the immune system, eg HIV

Entry and Spread of the Rabies virus

Viral replicates in the muscle at the site of bite (minimal or no symptoms) Protein G binds to acetylcholine receptor of neurons Travels via retrograde axoplasmic transport to ganglion neurons, then to Purkinje and other cells of the CNS (Prodrome foll. By Neurologic phase) From these sites - disseminates to all of CNS Descending infection

Trichomonas vaginalis

Very common agent of STDs Epidemiology: world wide, prevalence in developed countries-5-20% women and 2-10% men; In US: 3.7 million people infected, Transmission: sexual transmission sharing shower materials, through mother's infected birth canal- infection of infants Biology: flagellate; Anerobic exists as trophozoite only (no cysts!!!) one nucleus, four flagella and undulating membrane, a locomotory organelle of certain flagellate (trypanosome and trichomonad) parasites, consisting of a finlike extension of the limiting membrane with the flagellar sheath; wavelike rippling of the undulating membrane produces a characteristic movement. Costa: Ribbon like supporting structure at the base of undulating membrane

Detection of viral antigens

Viral antigens can be detected in the patient's blood or body fluids UV microscopy: by use of florescent dye tagged antibodies Serology: ELISA (Most common) Detection of p24 antigen of HIV, HBsAg of Hepatitis B Rapid tests Eg, for HBsAg of Hepatitis B

Pericarditis

Viral pericarditis: Usually presents with sharp substernal chest pain that worsens upon inspiration and supine position. Therefore, patients with viral pericarditis tend to prefer to sit up and lean forward to lessen the pain (pain changes with body position, as opposed to heart attack pain/MI that is pressure-like, and constant with radiation to the left arm and/or the jaw) Purulent pericarditis: develop suddenly and include fever and dyspnea. Only 1/3rd patients presents with chest pain. Tuberculous pericarditis: has the most insidious clinical onset. The patient may have vague gradual pain, weight loss, night sweats, cough and dyspnea.

Enteropathogenic E. coli (EPEC)

Virulence Factors : adhesion factors Bundle forming pili (Bfp): Patchy adherence followed by Tir insertion and Intimin binding Forms cup-like pedestal structure composed of dense mat of actin fibers Attaching-effacing - wiping out of microvilli Destruction of the absorptive microvilli leading to malabsorption which leads to diarrhea Disease: Infantile diarrhea: cause of epidemics in newborn nurseries Watery diarrhea, fever, nausea, vomiting, Antimicrobial therapy important in "at risk" children

Enterotoxigenic E. coli (ETEC)

Virulence Factors and Pathogenesis An adhesion factor and 2 toxins: Genes encoded on transferable plasmids - all three gene may be on the same plasmid. A. Colonization Factor Adhesions (CFAs): are fimbriae that recognize specific host glycoprotein receptors, determine host specificity B. Heat-labile toxin (LT) Similar to cholera toxin, A-B type. Binds to GM1 ganglioside receptors on gut epithelial cells, Enter into the cytoplasm Interacts with membrane protein (Gs) that regulates adenylate cyclase C. Heat-stable toxin (ST) Sta and STb Small peptide binds to and activates membrane guanylate cyclase receptor on epithelial cells Results in excess of cGMP (not cAMP) - blocks ion transport into cells; so water moves into the lumen Disease - Secretory Diarrhea: Watery diarrhea, abdominal cramps, nausea, low-grade fever IP: 1-3 days, Duration of illness 3 to >7 days Major cause of traveler's diarrhea, and < 3 years old children in developing countries

Enteroaggregative E. coli (EAEC)

Virulence Factors and pathogenesis Aggregative adherence fimbriae, AAF (encoded by genes on a plasmid) Results in bacterial clumping into small aggregates, noninvasive, "Stacked Bricks" like - bacteria parallel rows via autoagglutination Stimulates mucus production; Mucus + bacterial aggregation form thick biofilm Produce ST-like toxin (EAST1) (heat stable) yields excess of cGMP - interfere with ion absorption A cytotoxin/hemolysin; Shortening of microvilli, decreased fluid absorption Disease: Persistent watery diarrhea, vomiting, dehydration Infantile chronic diarrhea - growth retardation under-developed/developing countries Also a cause of traveler's diarrhea, HIV patients

Pathogenesis of Bacteroides fragilis

Virulence Factors: Adhesion factors: Capsule (polysaccharide) and pili Antiphagocytic: Capsule, Succinic acid formed during anaerobic growth Induction of abscess formation: Capsule, must be strong PAMP Catalase and superoxide dismutase - inactivate O2 radicals - resist killing Modified LPS: LPS lacks phosphate group in lipid A - has little/no endotoxicity Clinical Disease: -Intra-abdominal Abscess, peritonitis (in 90% of anaerobic peritoneal infections), appendicitis -Genital infections and pelvic inflammatory disease (PID) in females, -Necrotizing fasciitis/Myonecrosis -Bacteremia - polymicrobial infections. -Metastatic abscesses by hematogenous spread to distant organs (eg. Brain abscess)

Aspergillosis

Virulence and Clinical Disease Obstructive aspergillosis: Sinusitis and bronchitis - colonization, formation of plugs composed of hyphal mass and mucus; common in patients with CF and chronic bronchitis Allergic bronchopulmonary aspergillosis (ABPA). Colonization plus allergy; in patients with underlying condition (Asthma, CF etc.), high IgE Pulmonary aspergilloma: colonization of preexisting cavity in lung, "fungus balls" in lungs, sinuses (may resemble TB lesions) Invasive aspergillosis (in immunocompromised) Vascular invasion - Pulmonary necrotizing aspergillosis, Disseminated to other organs - CNS, heart, liver etc Mycotoxicosis: Mold in grains/nuts produce aflatoxin - carcinogenic

Pathogenesis of Cryptococcus neoformans

Virulence and pathogenesis; Possession of Capsule, melanin production, the ability to thrive at body temperature Highly neurotropic (produce metalloprotease-breaks BBB and invades), Usually involve meninges and underlying tissue Clinical Disease: cryptococcosis: Chronic Course of dis. Depends on host immune status Pneumonia Meningitis/meningoencephalitis Disseminated infection include Cutaneous lesions: Appear like molluscum cont. Ocular infection Bone lesion fatal if not treated

Pathogenicity Islands (PAIs)

Virulence cassettes: Unique area in the bacterial genomes where several genes are clustered, favoring their co-inheritance and co-expression May contain virulence genes Antibiotic resistance genes

Pathogenesis of Nocardia

Virulence factors and pathogenesis Cord factor prevents phagosome-lysosome formation Catalase and superoxide-dismutase- avoid phagocytic killing Clinical diseases: Pulmonary: mostly by N. asteroides Primary pulmonary disease almost always in immunocompromised patients Slow onset; cough, fever, dyspnea Localised or diffuse pneumonia with cavitation Cutaneous nocardiosis: mostly by N. brasiliensis Acute: cellulitis, subcutaneous abscess Chronic: Mycetoma; resembles actinomycosis, but not in the face Lymphocutaneous infections (nodules along lymphatics) CNS: brain abscesses and chronic meningitis (hematogenous spread from lungs)

Hfr Conjugation (Hfr × F-)

When the F factor integrates with the main chromosome 1.An F+ plasmid inserts into the donor bacterium's nucleoid to form an Hfr male. 2. The sex pilus adheres to an F- female (recipient). One donor DNA strand breaks in the middle of the inserted F+ plasmid. 3. The sex pilus retracts and a bridge forms between the two bacteria. One donor DNA strand begins to enter the recipient bacterium. The two cells break apart easily so the only a portion of the donor's DNA strand is usually transferred to the recipient bacterium. 4. The donor bacterium makes a complementary copy of the remaining DNA strand and remains an Hfr male. The recipient bacterium makes a complementary strand of the transferred donor DNA. 5. The donor DNA fragment undergoes genetic exchange (recombination) with the recipient bacterium's DNA. 6. The recipient bacterium gain new genes from the donor, but does not receive tra operon, thus remain F negative-.

Bordetella pertussis

Whooping Cough (Pertussis) Major cause of childhood fatality prior to vaccination Worldwide: 16 million cases and 200,000 death/year Common (endemic) disease in the United States (CDC) General properties: Gram negative coccobacillus: strict aerobic, Capsulated, Non motile Requires enriched culture media, Bordet-Gengou media (potato-blood-glycerol agar with 20-30% blood) , Resistant to penicillin - so penicillin is added in the media to make media selective Reservoir: Humans only reservoir Transmission: Aerosol transmission/direct contact, highly contagious Risk Factors/High Risk Populations: unvaccinated children, increasing incidence in adults

Enterobacteriaceae

Widely distributed in nature, in soil, water, vegetables and GI of humans and most animals. Some are always associated with diseases, others are opportunistic pathogens. Gene exchange among the members is very common. Enterobacter, Serratia, Citrobacter, Morganella are associated with invasive procedures, intravenous catheterization , respiratory intubation and urinary tract manipulation. They are rare among immunocompetet Enterobacteriaceae Salmonella spp Shigella sp Yersinia spp Escherichia coli Klebsiella pneumoniae Proteus spp Others: - mostly hospital infections: Enterobacter, Serratia, Citrobacter, Morganella

Childhood Exanthema

Widespread skin eruption/rash occurring as a symptom of a generalized disease; accompanied by fever, malaise and headache. Mostly viral Pathogenesis: as a result of: a reaction to a toxin produced by the organism, or damage to the skin by the organism, or an immune response.

Yersinia Spp.

Yersinia enterocolitica and Yersinia pseudotuberculosis Properties; Gram negative rod, non-lactose fermenters, grow best at 25oC. Motile at 25oC not at 37oC Reservoir: GI of a wide variety of animals (swine, dogs, rodents, sheep, cattle, and cats) Transmission: contaminated food products (milk, meat, water) especially with pork products, (chitterlings), pet feces, and contaminated fingers, requires high infectious dose,( 108 - 109 ) Risk Factors/High Risk Populations: Any one, more common among children, prominent in northern climate Virulence and pathogenesis: Enterotoxin and invasion of the mucosa Inflammation and ulceration. It may extend to mesenteric lymph nodes.

A-B Toxins Mode of Action

a. ADP-ribosylation of Elongation factor-2 G-protein - increase in cAMP Intracellular signalling cAMP and G protein: G proteins (guanine nucleotide-binding proteins) are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell b. Cleavage of rRNA The ADP-ribosyl group is removed from the coenzyme NAD (see dashed line) and is covalently attached to a host cell target protein. This causes the inactivation/hyperactivation of that target protein. c. Interference with release of neurotransmitters (Neurotoxin)

HIV adhesion and penetration

gp120 on HIV recognizes and binds to the CD4 molecule In addition to CD4 molecules HIV binds to a chemokine (cytokine) receptor molecule CCR-5 found on macrophages, dendritic cells, and on CXCR4 - on T helper cells. The co-receptor used by variant of HIV that are associated with primary infection is CCR5. - such strains are known as R5. Later in the infection the virus mutates and prefers to bind to CXCR4 and are known as X-4 variants. Some variants may use both CCR5 and CXCR4. After binding to the host cell through CD4 and the chemokine receptor the viral envelope is fused to the cell membrane through its gp41 protein letting the viral particle inside the cell. One of the anti HIV drugs (Enfuvirtide) inhibits the this fusion).

Red man syndrome

in the past attributed to impurities found in vancomycin preparations, earning the drug the nickname 'Mississippi mud'. But reports of the syndrome persisted even after improvements in the compound's purity. Studies have shown that an unknown percentage of the population may be prone to releasing a large amount of histamine in response to vancomycin. The hypersensitivity reactions that can arise due to vancomycin are due to its effect on the mast cells. In tissue culture, vancomycin causes degranulation of peritoneal mast cells in rats. An anaphylactoid reaction (Vs. The anaphylactic reaction-which is mediated by IgE) is caused by the degranulation of mast cells and basophils, resulting in the release of histamine independent of preformed IgE or complement. The extent of histamine release is related partly to the amount and rate of the vancomycin infusion. The name comes from the red rash that develops on the face, neck, and torso (trunk) of affected people

Viral Genome

nucleic acid RNA or DNA (not both) Single (ss) or double-stranded (ds) Linear, circular ssRNA, either positive strand or negative strand RNA may be segmented Usually haploid, some diploid

Detection of Plasmodium antigens

pLDH (parasite lactate dehydrogenase) Rapid diagnostic test (RDT) is based on rapid immunochromtatographic lateral flow principle. Dye-labeled antibody, specific for target antigen, is present on the lower end of nitrocellulose strip or in a plastic well provided with the strip. Antibody, also specific for the target antigen, is bound to the strip in a thin (test) line, and either antibody specific for the labeled antibody, or antigen, is bound at the control line. Blood and buffer, which have been placed on strip or in the well, are mixed with labeled antibody and are drawn up strip across the lines of bound antibody. If antigen is present, some labeled antibody will be trapped on the test line. Excess-labeled antibody is trapped on the control line. The accumulation of microscopic dye particles on the thin band produces a visible line if sufficient antigen-labeled antibody complex is present.

Contiguous-Focus Osteomyelitis

~80% of all cases of osteomyelitis, Usually chronic Organism enter bone via penetrating injuries, such as bites, puncture wounds, and open fractures; surgical procedures; or direct extension of infection from adjacent soft tissues Occurs most commonly in adults Risk factors: generalized vascular insufficiency and the presence of a foreign body Osteomyelitis may become apparent only weeks or months later In Diabetic patient (adult), involves small bones of the feet. Pain, fever, inflammatory sign Sinus tract development, failure of surgical wound or fracture to heal Occasionally, pieces of necrotic bone