Infectious Diseases Exam 4

fungal morphology

yeast - encapsulated yeast - cryptococcus neoformans mold - hyphae (threads) making up a mycelium dimorphism - Many pathogenic fungi are dimorphic, forming molds at ambient temperatures but yeasts at body temperature molds can assume various forms, starting with the basic structure that can then differentiate into various reproductive structures (conidia and spores). two common molds, aspergillus and rhizopus species, that cause human infection are illustrated.

age related issues vaccines

infants and T independent immune responses infants cannot make T-independent immune responses carbohydrates conjugation to proteins --> t dependent haemophilus influenzae type b streptococcus pneumoniae

consequences of inflammatory cascade and sepsis

infection --> microbial PAMPs --> cell responses: PRR and NF-kB activation --> platelet activation, coagulation activation, oxidases, kinins complement, cytokines TNF, IL-1, IL-6 --> coagulopathy and vascular/organ system injury --> endothelial damage --> multi-organ failure --> death vasculature effects in sepsis - the release of interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) causes the outpouring of a number of cytokines and other effectors. in turn, that outpouring leads to intravascular coagulation, vasodilation, increased neutrophil adherence to vessel walls, and vascular leakage. increased expression of cellular adhesion molecules, release of reactive oxygen intermediates by PMNs, chemotaxis and adherence of PMNs. - NO= nitric oxide - PAF= platelet activating factor - PGE= prostaglandin E - PMN= polymorphonuclear leukocyte

Cysticerosis

inappropriate infection by pork tapeworm only asymptomatic to mental problems, depending on burden and site Encounter and Entry - ingestion of egg of Taenia solium (pork tapeworm) in human feces - prevalent in Mexico - eggs hatch in stomach releasing onchosphere - autoinfection by ingestion of eggs released by tapeworm infection or regurgitation of eggs into stomach from intestines - compare with ingestion of larval stage (cysticerci) in pork Spread - onchosphere penetrates intestines and migrates in blood to tissues Multiplication - none in human by this route (compare with tapeworm infection) - humans are dead-end host (unless someone gets eaten by someone or something!) Damage - onchosphere develops into cysticercus, which cannot develop further - calcification and inflammation in brain, muscle, eye, heart, lung Diagnsosis - eosinophilia, radiology Treatment - praziquantel, steroids, surgery

Host mediators of SIRS/Sepsis

inflammatory cytokines, chemokines, prostaglandins, leukotrienes, etc. TNF-alpha, interleukin-1, -6, -8 - fever - decreased blood pressure - increase in capillary permeability and blood flow - mobilization/infiltration/activation of neutrophils and platelets - activation of the coagulation cascade part of the normal and essential response to insults to the host- normally a good thing! in sepsis, it is too much of a good thing

appropriate protective immunity

mucosal surface - IgA - need mucosal immunization - common mucosal immune system - mucosal infection (live) best IgG - injected - about any antigen cell mediated immunity - systemic infection (live) best - Th1 - IFN-gamma: presented with MHC-II, antigen presenting cells - cytotoxic T lymphocytes: presented with MHC-I, infected cells of any type, antigen in cytoplasm

miliary TB

mycobacterial infection not controlled by immune system persistent dissemination occurs with primary disease and occasionally with reactivation see in patients with depressed cell-mediated immunity nonspecific symptoms - fever, malaise, anorexia, weakness, weight loss

defining upper and lower respiratory tract

no consistent definition I prefer: - upper = ciliated epithelium (everything down to bronchi) - lower = nonciliated epithelium (bronchoalveoli and alveoli) - rationale = URT can be cleared by the mucociliary escalator but LRT cannot others: - larynx, separated by normal aspiration or not. this will not be an exam question

Compensatory Anti-Inflammatory Response Syndrome (CARS)

normal response controls inflammation after insult anti-inflammatory cytokines - IL-4, IL-10, IL-11, TGF-beta hyporesponsive lymphocytes

do microbes directly cause sepsis?

not usually an example that does: staphylococcal toxin --> superantigen stimulates approximately 20% of T cells most of the time, it is an overly-exuberant host response

bacterial meningitis

one week after arriving at boot camp, Pvt. A experiences a precipitous onset of fever (40C) and headache. within hours, he felt pain in his neck upon movement of his head. he reported to the medical unit. lumbar puncture was performed after determining that pressure was only slightly elevated (220 mm H2O). CSF was cloudy and contained 5000 leukocytes/ul (75% PMNs), no RBCs, glucose- 15mg/dl, protein- 150mg/dl. A gram stain revealed gram negative diplococci with kidney bean appearance. patient was initiated on IV antibiotics. three days later, Pvt. B experienced similar course of illness and prompt treatment based on diagnosis of Pvt. A. other contacts within their unit were then placed on prophylactic antibiotics to halt the epidemic.

pertussis pathogenesis

outcome - transmissible- yes- mandatory - usually self limiting but can be fatal - treatment: antibiotics prevention- vaccine - original killed whole cell - neurological problems - current acellular vaccine - pertussis toxoid + FHA - safe but not optimal - requires booster for adults

Staphylococcus aureus

outcome - usually self limiting, but can be fatal - transmission to humans: yes, direct and fomite treatment - antibiotic resistance is problematic - methicillin resistant SA (MRSA- resistant penicillin binding protein) - vancomycin resistant SA (VRSA)

multiorgan system dysfunction

overlaps with septic shock clotting disorders or failure of renal, hepatic, cardiac, or cognitive function accumulation of products of metabolism that cannot be cleared (ex. lactic acidosis) this is being caused by organ failure which is being caused by some of the effects of the systemic inflammation

representative URT infections

sinusitis otitis media (middle ear) pharyngitis (sore throat) laryngitis bronchitis (chest) whooping cough diphtheria

TSST-1

structure - single secreted protein (not A-B) mechanism of action - interacts with MHC-II and VB T-cell receptors - stimulates the release of cytokines (IL-1, IL-2, and TNF-alpha) treatments - steroids to reduce inflammatory effects

cellulitis

subcutaneous tissue acute inflammation redness, induration, heat, tenderness indistinct borders lymphangitis possible s. aureus and s. pyogenes

mortality stratified by disease severity

survival rates: sepsis/severe sepsis with appropriate treatment (90%) sepsis/severe sepsis with inappropriate treatment (60%) septic shock and appropriate treatment septic shock and inappropriate treatment (20%)

pharyngitis

symptoms - fever, exudative tonsils, lymphadenitis - should not have cough, rhinorrhea

SIRS

systemic inflammatory response syndrome not necessarily due to infection. cancers can cause it, trauma can cause it, metabolic factors two or more of the following: - temperature >38 C (100.4 F) or <36 C (96.8 F) - heart rate >90 beats per min (tachycardia) - respiratory rate >20 breaths per min (tachypnea), or any that results in a PaCO2 <32mm Hg - WBC >12K, <4K, or >10% immature forms (bands)

APHIS plant pathogens, HHS select infectious agents, and USDA high consequence livestock pathogens or toxins

viruses - ebola viruses - foot and mouth disease virus - variola major virus (smallpox virus) and variola minor (alastrim) prion - bovine spongiform encephalopathy agents toxins - botulinum neurotoxins - ricin - staphylococcal enterotoxins bacteria - bacillus anthracis - ralstonia solanacearum race 3 - yersinia pestis fungi - coccidiosis immitis (southwest UK, inhaled)

sites of infection in severe sepsis

lung (35%) - pneumonia bacteria can get into the blood abdomen (25%) urinary tract (12%) soft tissues (10%) IV catheter (5%) other (15%)

localized TB

lungs pleura CNS lymphatic system genitourinary systems bones and joints about anywhere

pharyngitis

most pharyngitis is caused by viruses bacterial causes - streptococcus pyogenes - neisseria gonorrhoeae - corynebacterium diphtheriae (in unvaccinated)

recent examples of vaccine- preventable disease

102 measles cases in US january 2015 - person with measles at disneyland coming in contact with unvaccinated visitors - nearly 4-fold larger amish outbreak this year 12 influenza deaths at shands hospital (UF) 2014 - not in elderly - 11 unvaccinated pertussis outbreak in california- 2010 - 9,210 cases - 10 deaths

helminths- worms

Nematodes (roundworms) - Enterobius vermicularis (Pin worm) - Necator americanus & Ancylostoma duodenale (hookworms) - Ancylostoma braziliense (dog/cat hookworm) - Ascaris lumbricoides (Round worm) - Strongyloides stercoralis - Trichuris trichuria - Trichinella spiralis

History of Bioterrorism

6th century BC- assyrians poison the wells of their enemies with rye ergot 184 BC- Hannibal's forces hurl snakes on enemy ships 1346- during the siege of Kaffa, the Tartar army hurls plague ridden dead over the walls of the city 15th C- Pizarro presents native Americans with clothing laden with the various virus (smallpox) 1763- royal Americans present native Americans with blankets contaminated with smallpox 1925- geneva protocol bans biological weapons. extends the prohibition of chemical agents to biological agents. 1940- plague is dropped by Japanese planes at Ninpo, causing 99 deaths 1941-1943 - fort detrick, Frederick, MD developed as a site for biological R&D 1960s- vietcong use fecally contaminated spear traps during the Vietnam war 1972- order of the rising sun members arrested with typhoid cultures to poison the water supply in midwest cities. likely would have failed due to chlorination of the water supplies. 1972- biological weapons convention (aka convention on the prohibition of the development, production, and stockpiling of bacteriological and toxin weapons and on their destruction). it is eventually signed by 103 nations. 1978- London- Bulgarian exile Georgi Markov is injected in the leg with a still ball impregnated with ricin via a specially constructed umbrella. he dies. 1979- Sverdlovsk, USSR, accidental release of anthrax spores from a BW plant officially kills 40 people. could be as high as 100 1984- Oregon- the Rajneeshee cult contaminates salad bars of restaurants with salmonella typhimurium. over 750 are poisoned and 40 hospitalized. the purpose is to influence the outcome of a local election. 1995- Iraqi authorities acknowledge that they had botulinum toxin, anthrax, and aflatoxin bombs and Scud missile warheads 1995- Aum Shinrikyo attempts to disperse anthrax, botulinum toxin, Q fever, and Ebola against the mass population and authority figures in Japan. no reported infections occur. sarin gas attack in tokyo kills many. 1995- lab tech orders the plague bacterium from American type culture collection. 3 vials of yersinia pests are mailed to him using no more than a credit card and a false letterhead 9/11- US anthrax incident- 5 deaths- mad scientist?

Hookworms - Ancylostoma duodenale and Necator americanus

700,000 infected in U.S. Symptoms - allergic reaction in feet upon entry through skin (temporary ground itch) - pneumonitis during migration through lungs - g.i. - nausea, vomiting, diarrhea - anemia due to feeding of adult worms in intestines Encounter and Entry - Filariform larvae in soil from human feces - Need warm, moist soil - southern U.S. - Penetrate intact skin (unusual fecal- cutaneous route) Spread and Multiplication - Circulation - Lungs - Coughed, swallowed - Adults intestines - Feed off blood - Eggs in feces Damage - skin penetration - lung migration - blood loss Move to new human host - yes Diagnosis - Observe characteristic eggs in stool Treatment - mebendazole; pyrantel pamoate Prevention - hygiene, sanitation, shoes

Pneumococcal pneumonia

>1,000,000 deaths worldwide predisposed populations - young - elderly - asplenic (sickle cell anemia) - complement deficiency - sickle cell encounter - humans only, by respiratory droplet - normal flora entry- colonization of the oropharynx - aspiration into lung spread - pneumonia- not necessary, but frequent - meningitis- blood to CNS - otitis media and sinusitis - not necessary multiplication - grows well in serous fluid in alveoli space evade defenses - extracellular - capsule- antiphagocytic - sIgA protease damage - inflammation: peptidoglycan - pneumolysin: toxin binds cholesterol in the host cell membrane stage of pneumonia - serous - early consolidation (numerous bacteria, few PMNs) - resolution (effective antibody response, macrophages clear debris) - no permanent damage outcome - transmission- droplet/saliva (between humans) - self resolving to fatal prevention - vaccines - IgG to opsonize - 23 valent polysaccharides - 7 valent polysaccharide conjugate vaccine (conjugated to a nontoxic diphtheria toxin) - 13 valent conjugated

parasitism

A relationship between organisms where one (the parasite) gains food and shelter from another (the host) which suffers from the relationship. This is opposed to mutualism where both benefit or commensalism where one gains but the other is not harmed. types of organisms protozoa - single celled eukaryotes - intestinal and urogenital - blood and tissue helminths (worms) - cestodes (tapeworms) - trematodes (flukes) - nematodes (roundworms) arthropods - Cimex lectularius (bed bug) - Ticks and mites

considerations in vaccinations

active vs passive - necessity/luxury of time - duration of protection live, attenuated vs killed vs subunit - risks, strength and duration of immunity who gets vaccinated - everyone vs specific risk groups - at what age(s)

parasitology importance

Billions of cases worldwide - lots of morbidity Malaria causes over 1 million deaths/year There ARE many parasitic diseases endemic to the U.S. Even for those that are not endemic - travelers and immigrants bring them here.

hospital mortality and adequacy of antibiotics

adequate therapy means broad spectrum coverage of gram positive and gram negative organisms adequate mortality rate = 30% (high) inadequate mortality rate = 60%

diagnoses of mycoses

Clinical presentation - History (risk factors) - Physical Exam (lesions, devices) Histopathology - KOH to accentuate fungal forms - Special stains (silver, calcofluor) - Mold or Yeast? - Septate hyphae? Culture of organism (days to weeks) - Special media - Problem - contaminating bacteria - Problem - Ubiquity of environmental fungi Serology - Antibody or Antigen tests - Problem - endemic exposure vs. infection Molecular Biology - PCR Skin infections - can occur in healthy people - Superficial infections (surface of skin). Versicolor (pigmentation), piedras - Cutaneous (invasion of outer layers of skin). Tineas - jock itch, ringworm, athlete's foot, etc. - Subcutaneous (deeper invasion and spreading). Sporothrix

characteristics of bioterrorism agents

affect large numbers of people be produced easily - no special training - compare with nuclear or chemical weapons small quantities sufficient

insects/arthropods

Cimex leticulares (bed bug) bites humans at night while sleeping sucks blood leaves rash similar to mosquito bite does not transmit disease nuisance pay attention at hotels/motels to not bring home

Ancylostoma braziliense (dog/cat hookworm)

Cutaneous Larva Migrans, creeping eruption, ground itch Encounter, Entry, Spread, Multiplication - found in warm regions of U.S. (here) - contamination of soil with animal feces containing filariform larvae - larvae penetrate skin and migrate - cannot differentiate Damage - create tracks of migration for weeks to months Diagnosis - clinical, eosinophilia Treatment - thiabendazole Prevention - pet owner education - cover the sandbox

review of bacterial vaccines used in the US

DTaP - given to infants and children (injection) - D = diphtheria (Corynebacterium diphtheriae): diphtheria toxin toxoid. elicit IgG antibodies to neutralize toxin in blood before it reaches systemic targets. efficacy is excellent. shortcoming - could induce sIgA against bacterial adhesins to better prevent colonization. - T = tetanus (Clostridium tetani): tetanus toxin toxoid. elicit IgG antibodies to neutralize toxin in blood before it reaches systemic targets. efficacy - excellent. shortcoming - induce IgG against cellular antigens to help fight the infection itself in tissues - aP = pertussis [whooping cough] (Bordetella pertussis): pertussis toxin toxoid + filamentous hemagglutinin + pertactin +/- fimbriae. elicit IgG antibodies to neutralize toxin in blood before it reaches systemic targets and elicit antibodies to adhesins. efficacy - not very good (85% initially but wanes). shortcoming - should induce sIgA against adhesins (FHA, pertactin, fimbriae) to better prevent colonization, but injection does not do this very well Haemophilus influenzae type b (Hib) - infant-childhood meningitis, epiglotitis - type b capsule coupled to tetanus toxoid or Neisseria meningitidis protein - elicit IgG antibodies against antiphagocytic capsule to opsonize/lyse the bacteria and elicit IgG to other pathogens (C. tetani or N. meningitidis) - efficacy - excellent - shortcoming - should induce sIgA against adhesins to better prevent colonization Neisseria meningitidis - Childhood/adult meningitis, sepsis - Mixture of 4 capsule types +/- coupled to genetic toxoid of diphtheria toxin - elicit IgG antibodies against antiphagocytic capsule to opsonize/lyse the bacteria - efficacy - excellent - shortcoming - should induce sIgA against adhesins to better prevent colonization Streptococcus pneumoniae - Childhood/adult meningitis, sepsis, pneumonia, (otitis media) - Mixtures of: 7 or 13 capsule types coupled to genetic toxoid of diphtheria toxin, 23 capsule types not conjugated - elicit IgG antibodies against antiphagocytic capsule to opsonize the bacteria in the alveoli and/or blood - efficacy - excellent - shortcoming - should induce sIgA against adhesins to better prevent colonization Mycobacterium tuberculosis - tuberculosis - Live/attenuated Mycobacterium bovis strain (BCG) injected, usually to children - elicit Th1 cell-mediated immunity to activate macrophages to kill the intracellular pathogen - efficacy - OK in children, not very good in adults - shortcoming - should not be given to immunocompromised, need more effective vaccine for adults

histoplasma capsulatum

Histoplasmosis - Dimorphic fungus - 90% infections asymptomatic - Pneumonitis, lymphadenopathy - Symptomatic disseminated disease in 1:200 - usually immunocompromised - Reticuloendothelial system Encounter - Soil in Mississippi and Ohio river valleys - From bird droppings - Caves - Conidia (mold form) inhaled - environmental temperatures Entry - Lung Multiplication: - Converts to yeast in body (37°C) Spread - From lungs throughout body in blood Evade defenses - Yeast survive within macrophages - Increase pH of phagosome - Th1 CMI important Damage - Cell-mediated immune response in tissues (granulomas) - In lung - bronchial obstruction - CNS infection - fatal Outcome - Usually self-resolving, but death possible in immunocompromised - Transmissible - no

candida albicans

Diseases - Vaginal and oral thrush, cutaneous infections (diaper rash), systemic infections Encounter: - Humans - Normal flora - Endogenous infection Entry: - Gastrointestinal tract, upper respiratory tract, oral cavity, and vaginal tract Spread - Skin and mucus membranes are normally an effective barrier. - Damage from catheters or intravascular devices can permit Candida to enter the bloodstream. - Epithelial damage from chemotherapy enables invasion. Multiplication: - Growth is normally suppressed by other microorganisms found in colonized areas (pH, glucose). - Broad spectrum antibiotics can lead to overgrowth. - In vitro (25C): mostly yeast - In vivo (37C): Yeast, hyphae, and pseudohyphae Evasion of defenses: - Hyphae are too big for phagocytosis but are damaged by PMNs and by extracellular mechanisms - Cytokine-activated lymphocytes can inhibit growth. - Resistance to invasive infection is mediated by phagocytes, complement, antibody, and T cell mediated immunity. - Patients with defects in phagocytosis function and myeloperoxidase deficiency are at risk for disseminated (even fatal) Candidiasis. Damage: - Overgrowth of the organism and erosion and ulceration of tissue. - Inflammation - systemic candidiasis - septic shock Outcome: - Transmissible - Yes Treatment: - Antifungals - Strength depends on severity of infection

opportunistic mycoses

Do not normally cause disease in healthy people Often cause disease in immunocompromised people - Inherited immunodeficiency diseases - Immunospuppresive drugs (cancer chemotherapy, corticosteroids, drugs to prevent organ transplant rejection) Radiation therapy Other infections (e.g., HIV) Cancer Diabetes Advanced age Malnutrition Most common infections: - Candida albicans (and C. glabrata) - Aspergillus fumigatus (among others) - Cryptococcus neoformans (and C. gattii) - Pneumocystis carinii - Zygomycosis (Rhizopus and Mucor)

parasitology pathogenesis

Encounter - Geographic distribution - regions of world as well as regions of U.S. - One or more hosts (notice difference between simple vectors versus replication within the non- human host) - Arthropod vectors - bites - Oral (food and water) - Direct penetration of intact epidermis (different from bacteria and viruses) - Some are human only - Occupational, activity relationships - Considered exogenous infections (although some are often asymptomatic, depending on conditions, not considered normal flora) entry - Oral, epidermis, bites, sexual - Specific adherence by protozoans just like bacteria - Worms- biting, sucking mouth parts spread - Some do, some don't - Some travel through body in a complex, orderly process - Tissue specificity often seen evade defenses - Most of these are chronic infections; therefore evasion of even specific adaptive immunity is important - Antigenic mimicry, Antigenic cloaking (masking), Antigenic variation - Nonspecific generalized stimulation of immunoglobulin multiplication - Often specific to different hosts, dependent on life cycle form - Inappropriate host causes special forms of disease - Not often cultured damage - Generally no toxins, except damaging enzymes - Parasite burden in tissue (migration, blockage, pressure) - Immunologic: Inflammation, Type 1: Hypersensitivity reactions, Type 2: Cytotoxicity, Type 3: Immune complex, Type 4: DTH - CMI - Bleeding and loss of blood - Cysts, etc. in tissues - Allowing spread of bacteria from gut - The infective dose often directly relates to severity of disease (e.g., a few worms is no big deal, many worms can be lethal) - Repeated encounter can be additive outcome: transmission - Direct human to human - Human to animal/vector to human - Human dead end (accidental) host diagnosis - Most often seeing organism in patient sample (macroscopic - worms, microscopic - others) - Feces, urine, blood, biopsy, endoscopic, Entero (string) test - Radiographic observation of damage - Eosinophilia - only seen with tissue-invasive worms - Serology - Nucleic acid-based coming soon treatment - Because eukaryotic and highly varied life forms - different sets of drugs - Some antibacterials still useful Anti-protozoals (inhibit replicating organisms, similar to bacteria) - Metronidazole - DNA - Entamoeba, Giardia, Trichomonas - Aminoquinolones (numerous targets) - chloroquine, primaquinine - Malaria - Trimethoprim, sulfa drugs - Folic Acid - Toxoplasma, Malaria - Heavy metals - arsenic and antimony - Leishmania - Protein synthesis - Malaria, Babesia, Entamoeba, Cryptosporidium - Quinolones - Ciprofloxacin - Malaria Anti-helminth (disrupt adults) - Mebendazole, thiabendazole - microtubule - broad spectrum - Niclosamide - oxidative phosphorylation - Cestodes - Praziquantel - muscle, tegument (Broad spectrum) - Pyrantel pamoate - muscle relaxant - Ascaris, Enterobius, Hookworm - Piperazine - muscular paralysis - Ascaris, Enterobius - Ivermectin - muscular - Filaria

immune response to fungal infection

Fungal pathogen associated molecular patterns (PAMPs): glucans, mannans, chitin Inflammation Adaptive immunity: - TH1 response is optimal - IgG can be helpful Evasion of the immunity: - antiphagocytic capsule - yeast to hyphal transition (hyphae are difficult to attack) - changing of surface glycoproteins - hydrophobins (small hydrophobic proteins) - survival in macrophage

cestodes (tapeworms)

General characteristics - body segments: head = scolex, others proglottids - no intestines - absorb nutrients - hermaphroditic (don't need male and female in same host) - complex life cycles - pay attention to forms encountered by different hosts - usually asymptomatic, except passage of proglottids in stool, possible nausea

persons at higher risk of developing TB disease once infected

HIV infected persons taking anti TNF agents (TB drugs) recently infected persons with certain medical conditions

parasitology 1 quiz

In terms of pathogenesis (especially spread) and symptoms, which of the following most accurately compares intestinal protozoans to gastrointestinal bacteria? E. histolytica - Shigella; Giardia - V. cholerae. E. histolytica causes dysentery and invades the colonic epithelium like Shigella. Giardia doesn't invade and causes diarrhea like V. cholerae. What drug is used to treat amoebic dysentery and giardiasis? Metronidazole can be used to treat these two protozoal infections. Primaquine and chloroquine are for malaria. Trimethoprim and sulfa drugs are for Toxoplasma. Each of the following is a distinguishing feature of P. falciparum disease relative to P. vivax disease EXCEPT: has Schuffner's dots in infected RBCs. distinguishing features of P. falciparum disease relative to P. viva disease: numerous ring forms in RBCs, higher percentage of infected RBCs, increased adherence of infected RBCs to capillaries, more severe symptoms Which of the following most accurately describes the transmission and life cycle of Plasmodium in the humans? mosquito - blood - liver - blood - mosquito. After the mosquito bite, the organisms travel from the blood to the liver fo rthe initial exoerythrocytic phase. Then the organisms undergo repetitive cycles of blood infection not to return to the liver. They are ultimately taken up by mosquitoes in a blood meal. How does Toxoplasma gondii evade host defenses? Replicate in a specialized vacuole in macrophages. Like Mycobacterium tuberculosis, T. gondii is an intracellular pathogen of macrophages. It survives in the host for the lifetime of the host until CMI breaks down and the infection reactivates.

What is sepsis?

Inflammatory Spectrum - SIRS: systemic inflammatory response syndrome. There are both infectious and non infectious causes - Sepsis: SIRS + infection - Severe Sepsis: sepsis + organ dysfunction or hypotension (low blood pressure) - Septic Shock: sepsis + hypotension despite fluid resuscitation (you've lost your ability to manage it)

antifungal agents

Membrane sterol (ergosterol vs. cholesterol) - Azoles - Polyenes - Allylamines Target cell wall biosynthesis (caspofungin) Tubulin (griseofulvin) Nucleoside metabolism (flucytosine) Often insoluble and/or toxic targets of antimycotics Polyenes - Amphotericin B: high affinity for membrane ergosterol (sterol). making membranes leaky. also binds to cholesterol, with severe side effects Nystatin - topical only amphotericin binds ergosterol Azoles - Have 5-membered organic rings that contain either two (imidazoles) or three (triazoles) nitrogen molecules. - triazoles: voriconazole and fluconazole - Inhibit cytochrome P450- dependent enzymes involved in the biosynthesis of cell membrane sterols. Allylamines - block ergosterol synthesis - topical - used for dermatophytes (athlete's foot, etc.) - terbinafine Echinocandins - non-competitively inhibit UDP- glucose 1,3-β-d glucan synthase - necessary for the synthesis of 1,3-β-d glucan, an essential component of the cell wall of several fungi. - Limited toxicity - caspofungin Flucytosine (5-fluorocytosine) - inhibits pyrimidine synthesis - Activated by fungal cells to 5−fluorouracil

mycology conclusions

Most fungal infections affect our surface not our inside. A few dimorphic fungi can cause systemic infections in otherwise healthy people. - Endemic areas - Contact by inhalation Candida species inhabit our guts and usually stay there, but, given the right (wrong) conditions can disseminate to infect almost any organ. - Important nosocomial infection In immunocompromised people, any fungus can be a deadly pathogen Several types of antifungals take advantage of differences in structure and composition

systemic infections

Most infections are asymptomatic or self- limiting. Requires a large inoculum and a susceptible host Specific fungi often have specific endemic areas. In immunocompromised hosts (AIDS, cancer chemotherapy, BMT), infections can be fatal.

blood and tissue protozoa

Plasmodium species - we will concentrate on the most common (P. vivax) and most lethal (P. falciparum) malaria - complex life cycles with sexual and asexual cycles in different hosts over 1 million deaths/year - mainly Africa Incubation period - 8-30 days, depending on species influenza-like symptoms; paroxysms (fever, chills, rigors) every 36 to 48 hours, depending on species sickle cell trait - resistance to P. falciparum Encounter - Not endemic to U.S. (imported cases, but few mosquito-borne reported) - tropics, subtropics mosquito bite (Anopheles) with sporozoites (U.S. does have Anopheles); prevent encounter with mosquito Entry and Spread - circulatory system to liver Multiplication - liver (exoerythrocytic) - schizogony (asexual) - release merozoites into blood that infect RBCs (erythrocytic cycle - more asexual) - differentiation into gametocytes, blood meal for mosquitoes (sexual cycle) - P. vivax only invades young, immature RBCs - P. falciparum no specificity for RBCs (more infected cells, more severe disease) Evasion of defenses - intracellular shielding - antigenic variation of major surface protein (MSP-1) Damage - both - lysed hepatocytes, RBCs, plugged capillaries - P. falciparum - RBCs adhere to capillaries including brain, RBC lysis, kidney (blackwater fever); more deaths Diagnosis - microscopic examination of blood smears - P. falciparum - numerous rings/RBC and high number of infected RBCs, no Schüffner dots - P. vivax - single ring/RBC and lower number of infected RBC, has Schüffner dots Treatment - chloroquine and primaquine, among others

major impact on health: famine

Rice blast disease in 85 countries, causing 10-35% loss of harvest. Wheat stem rust is present on six continents, causing up to 100% crop loss. Microsporidian fungal infections are associated with bee colony collapse disorder and declining populations. self inflicted epidemic: fungal meningitis 2012 - exserohilum rostratum - 510 cases, 36 deaths

sepsis

SIRS plus proven or clinically suspected infection

prevention of TB

TB is strictly spread from person to person need to identify exposed individuals and prevent them from developing active disease screening tests can accomplish this task test only those in whom there is an identified risk - PPD - IGRA vaccine is not used in the US

Taenia solium

Taenia solium (pork) - rare in U.S. Taenia saginata (beef) - common in U.S. Diphylobothrium latum (fish)- common Encounter - ingest meat with larvae of worm (cysticercus) Entry - Oral - larvae mature to adult in intestine Spread - No Multiply - proglotids can mutliply to form chains several meters long - break off and are excreted in feces - also eggs in feces Damage - consumption of nutrients in intestines, some intestinal irritation Outcome: Transmission to new host - eggs ingested by pigs/cows, migrate into tissue and form larvae Diagnosis - eggs in stool Treatment - niclosamide Prevention - cook the meat - sanitation

focus on acute bacterial meningitis

agents vary depending on the age of the patient newborns/neonates - group B streptococci - E. coli K1 - listeria monocytogenes infants and children up to 24 months old - streptococcus pneumoniae - neisseria meningitidis - haemophilus influenzae type b adults - streptococcus pneumoniae - neisseria meningitidis

toxoplasmosis

Toxoplasma gondii - opportunistic pathogen - brain and heart infection of adults - congenital infection Encounter - cat feces - oocysts - meat - tissue cysts - cats are essential hosts - pregnant women who are seronegative at risk Entry - ingestion of cysts or oocysts - differentiate into tachyzoites Spread - blood to brain - to fetus Multiplication - maturation to tachyzoite Evade defenses - actively invades and survives in macrophages - parasitophorous vesicle - normally held in check (except congenital during first trimester) - survives for the lifetime of the host - immunocompromise enables reactivation Damage - encephalitis - especially bad during first trimester (mental retardation) Diagnosis - serology - brain imaging Treatment - antibacterials: trimethoprim, sulfa drugs

why is sepsis on the rise?

aging population increased awareness and diagnosis immunocompromised patients - atypical presentation - rapid progression invasive procedures (ventilators, catheters, prostheses) entryways for microbes resistant pathogens

bacterial meningitis quiz

The primary cause of damage during meningitis is: inflammation. Each of these is a characteristic of cerebrospinal fluid analysis for acute bacterial meningitis EXCEPT: low protein. It's elevated protein, not low protein. You cannot always see bacteria on the Gram stain, but it is possible, if not frequent. characteristics of CSF: low glucose, high protein, elevated white blood cells, presence of PMNs, organisms on a gram stain Which of the following most accurately describes the interaction of Listeria monocytogenes with host cells? Invasion, escape into cytoplasm, spread directly between cells. invasion, escape to the cytoplasm, and cell-to-cell spread is characteristic. Listeria does make some toxins, but they are ancillary. How does the Haemophilus influenzae type b vaccine work? stimulates IgG to protect the blood. Cell mediated immunity is irrelevant because this is an extracellular organism. IgG to the capsule will protect the blood and intercept the organisms should they invade. The defenses of the brain might be stimulated, but that is too late. Why are we not protected against Neisseria meninigitidis group B by the multivalent anticapsular vaccines? The Group B capsule is polysialic acid. Group B = sialic acid = antigenic mimicry, so it is not in the anticapsular vaccines. However, there is a new vaccine that uses an outer membrane protein that protects against Group B, as well as other groups.

LRT quiz

There are three vaccines to Streptococcus pneumoniae used in the U.S. What do these three vaccines have in common? They are aimed at eliciting IgG to stimulate opsonization. The vaccines all have carbohydrate capsule (2 are conjugated to non-pneumococcal proteins, one is pure capsule). They are aimed at eliciting IgG that will opsonize the bacteria in the blood and in the alveoli. How is immunity to Mycobacterium tuberculosis linked to pathogenesis? Th1 cell-mediated immune responses damage the lungs and other infected sites. It's a Th1 CMI response that stimulated macrophages to hold the infection in check. But because it is not effective, there is chronic infection and response leading to tissue damage. What is the typical result of infection with Mycobacterium tuberculosis in an otherwise healthy person? Flu-like symptoms followed by lifelong asymptomatic infection. 90% of primarily infected people have few initial symptoms, and they will never have problems for the rest of their lives. Immunocompromised people can experience miliary TB with highly lethal unchecked infection. Only 10% of people have secondary reactivation with either serious lung infection (cavitary lesions) or focal infections. How is Legionella pneumophila disease different from that caused by Streptococcus pneumoniae and Mycobacterium tuberculosis? The bacteria are from the environment only and are not transmissible between humans. Legionella is an environmental organism, whereas S. pneumoniae and M. tuberculosis are human only. L.p. is not transmissible, but the others demand transmission between people. L.p. is intracellular, but so is M.t. All three organisms can be cultured. All three can infection healthy people (Pontiac Fever for L.p.), but all three have a propensity for causing more severe disease in debilitated people. How does Legionella pneumophila interact with macrophages? It injects proteins and stimulates autophagy. L.p. uses type 4 secretion to inject proteins, stimulating autophagy that results in an endoplasmic reticulum-like vacuolar space in which the bacteria replicate.

NF-kB: the master regulator

all end up here. key transcription factor moved to the nucleus, where it acts as a transcriptional activator, changing gene expression cytokines, proliferation signals, chemoattractants, adhesion molecules

specific agents and diseases- protozoa

Urogenital protozoa - Trichomonas vaginalis Intestinal protozoa - Entamoeba histolytica - amoebic dysentery, invasive disease - Giardia lamblia - non-invasive diarrhea There are numerous commensal (normal flora) intestinal amoeba (don't memorize names) Two cellular forms - trophozoites (replicating) and cysts (survival outside host)

sepsis quiz

What is the definition of sepsis? SIRS + infection What is the most frequent site of infection that leads to sepsis? lungs What are the major mediators of sepsis? cytokines and host effectors What is the initiating event that triggers the sepsis cascade? Pathogen Recognition Receptors interacting with Pathogen Associated Molecular Pattern molecules What is the most effective intervention in sepsis? antibiotics plus fluids

Hymenolepis nana

What type of organism is Hymenolepis nana? - tapeworm What are the typical symptoms of H. nana infection? - usually asymptomatic - diarrhea abdominal pain possible Encounter: What are the most common hosts other than humans? - beetles and mice Encounter: What are the usual circumstances of the encounter by a human? - ingestion Entry: Where does H.n. enter the body, and where does it initially set up infection? - mouth, intestines Spread: Does H.n. normally spread in the human body? If so, where does it go? - yes. it can invade the intestinal mucosa Multiplication: In the life cycle of H.n. in the human body, which form is released and how? - eggs, feces Multiplication: What is the non-adult form of the organism in the human intestines (there are adults there, too). - cysticercoid Outcome: Is H.n. infection directly transmissible between humans? If so, how (this is related to encounter). - Yes - ingestion of eggs from human feces. Outcome: What is the outcome of H.n. disease if untreated and treated? - self-limiting, discomfort Treatment: What is the standard of treatment for H.n. infection? - Praziquantel

vaccines quiz

Which form of immunity is most needed to prevent most infections but is least likely to be induced by most currently used vaccines? IgA. Most infections start at mucosal membranes where IgA is the only relevant form of adaptive immunity, but few of our vaccines are aimed at eliciting IgA. Why are most of the carbohydrate capsule vaccines conjugate vaccines in which the capsule is chemically linked to a protein? Carbohydrates are T independent antigens. Carbohydrates are T-independent antigens, and infants cannot make good immune responses to Ti antigens. Adults can do just fine, though. If we want to eradicate a pathogen from the world, each of the following must be true EXCEPT: must be treatable by antibiotics. We don't have to be able to treat infected people, as long as they do not remain chronically infected. There was no treatment for small pox. You either died or cleared the infection and got better. eradicating a pathogen from the world: only a human reservoir, infected people should be easily identified, must not have a latent infection, must have an effective vaccine given to minimal levels of the population According to the concept of herd immunity, how many people in a population must be effectively vaccinated to prevent epidemic spread of the infectious disease? (R0 - 1)/R0, where R0 is the basic reproduction number. If the proportion of vaccinated individuals is (R0 - 1)/R0 or greater, the epidemic cannot be sustained. E is a measure of effectiveness and will determined how many people will need to be vaccinate to generate a protected individual (e.g., for an effectiveness of 0.5, you'd need to vaccinate 2 people for 1 protection). Of course, vaccination protects populations as well as individuals. Based on the pathogenesis of disease, which of the following would be an ideal typhoid fever vaccine (note - it might already be in use)? oral administration of live attenuated Salmonella enterica serovar Typhi. A live attenuated strain given orally would induce all relevant branches of the immune system (IgA, IgG, CMI). Injection of the live attenuated strain would not do a good job with IgA. Oral dead cells would not be as effective. Injecting killed cells (current vaccine) and injecting proteins would only elicit primarily IgG.

URT quiz

Which of the following describes differences between the upper respiratory tract (down to bronchi) versus the lower respiratory tract (bronchoalveoli and alveoli)? URT has mucociliary escalator and IgA. The mucociliary escalator and IgA are limited to URT as defined in the lecture and question. Which of the following is FALSE regarding entry of pathogens into the LRT? Any size of particle can be directly inhaled into the alveoli. Only particles <3 microns can be directly inhaled to the alveoli. true regarding entry of pathogens: Some organisms colonize the URT then are aspirated, Some organisms colonize the URT then migrate down the mucosa, Some organisms get into the alveoli from the blood, Some organisms take advantage of impariment of the mucociliary escalator. What is the difference between regular pharyngitis and scarlet fever? Scarlet fever is caused by a locally produced, systemically active toxin. It is a systemically active toxin that is encoded on a bacteriophage (not a human virus). Immune manifestations of disease are rheumatic fever and glomerulonephritis. What do diphtheria toxin and pertussis toxin have in common? They are both ADP-ribosylating toxins. They both are ADP-ribosylating toxins, but they ADP-ribosylate very different cellular targets with very different effects. Diphtheria toxins halts protein synthesis and kills host cells, while pertussis toxin increases cAMP, which is not cytotoxic. They are both A-B toxins. What do Corynebacterium diphtheriae and Bordetella pertussis have in common? They cause non-spreading infections with systemic effects. These are local infections with systemic toxins. Only C.d. is G+. Only B.p. has TCT. There are <10 cases of diphtheria, but hundreds-thousands of cases of whooping cough. Only B.p. has adhesins in the vaccine.

mycology quiz

Which of the following is NOT a direct target of clinically used antifungal agents? protein synthesis. There are no antifungals that directly affect protein synthesis. Flucytosine can affect RNA that eventually leads to protein synthesis problems. direct targets of anti fungal agents: pyrimidine synthesis, tubules, ergosterol synthesis, and cell wall synthesis Which pair of antifungal agents have the most similar mechanism of action? Voriconazole and terbinafine. Voriconazole and terbinafine both inhibit ergosterol biosynthesis, albeit at different steps. Amphoericin binds to ergosterol while vorconazole inhibits its synthesis. This may seem trivial, but it has a huge impact on the toxicity of these drugs. Flucytosine and fluconazole may sounds similar, but they have nothing to do with each other. What is the cause of damage in the cutaneous infections by dermatophytes? exoenzymes and inflammation. It's exoenzymes that break down keratin and our inflammatory response to the organisms. The dermatophytes do not make any toxins that I know of, nor do they induce apoptosis. They definitely do not get inside macrophages. How is the evasion of defenses of Histoplasma related to the damage that it causes during infection? Intracellular replication in macrophages causes granulomas in tissues. The yeast form of the fungus replicates in macrophages. Just like with TB, the inefficient cell-mediated immune response contributes to damage. How is Candida albicans different from most other medically relevant fungi? it is normal flora of humans. Candida is normal flora of humans and can be spread from person to person. The other fungi are environmental. Candida is mostly a mold in people, although it can also be a yeast. Most, but not all, other fungi are molds in the environment and yeasts in people. Most fungi cause damage by inflammation. Many other fungi like Histoplasma cause systemic infections, too. Many other fungi can infect healthy people, but others like Aspergillus require a severely compromised host.

bioterrorism and zoonoses

Which of the following is NOT an example of bioterrorism? Killing your neighbor with ricin toxin because he shot your dog. Killing your neighbor with a biological toxin is not bioterrorism because you are not trying to affect public policy or behavior. This is just plain murder. All of the other acts are designed to bring about societal or economic changes. Which of the following would you expect to see in a Risk Group 2 category C select agent? no special public health required to deal with infection. RG2 and category C are the least virulent of the select agents, so they would require little to no special public health measures. All of the other characteristics are for highly virulent pathogens. Which of the following most accurately describes the urban cycle of plague? bite of flea from a rat - bubonic plague - pneumonic plague - inhalation - pneumonic plague. Which of the following explains the relationship of Bacillus anthracis with phagocytes? The spores survive intracellularly and the capsule prevents phagocytosis. The spores survive and germinate inside of macrophages. Then the vegetative cells express the polyglutamate capsule to be extracellular. The symptoms of the tertiary phase of Lyme disease are caused by: host immune responses. As is the case for syphilis, the tertiary phase symptoms are either immune responses to bacterial antigens or autoimmune reactions stimulated y the bacteria. Note that B. burgdorferi does not have LPS.

skin and wound infections quiz

Which of the following most accurately states the increasing severity of skin infections? impetigo - folliculitis - cellulitis - fasciitis routes of entry into the skin: bite, burn, surface contact, hematogenous. How does Staphylococcus aureus cause toxic shock syndrome? Localized infection with systemic toxin. It's a locally produced superatigen toxin (TSST-1) with systemic effects. Which of the following is LEAST likely to be caused by Pseudomonas aeruginosa? gastroenteritis. Although P.a. can be found in food and can colonize the gut, it does not cause gastrointestinal disease. What is the mechanism of action of tetanus toxin? inhibiting neurotransmitter release of inhibitory neurons. It is inhibiting neurotransmitter release by inhibitory neurons that results in spastic paralysis (opposing muscles work against each other).

parasitology 2 quiz

Which of the following worms does NOT depend on fecal shedding from humans of some form of the worm for transmission to a new host?Schistosoma haematobium. it is released from humans via the urine. depend of fecal shedding: Schistosoma mansoni, Schistosoma japonicum, Taenia solium, Necator americanus Which of the following would LEAST likely result in eosinophilia? Taenia solium after ingestion of pork. Taenia solium encountered through ingestion of pork never invades or leaves the intestines, so it will least likely induce eosinophilia. All of the other worms and their encounters result in invading worms, which will induce eosinophilia. Which worm is most likely encountered through domesticated pets? Ancylostoma braziliense. Which worm causes anemia by feeding on blood in humans? Necator americanus For which of the following worms does the number of adults increase in the human body continue to increase after all of the larvae have initially matured (i.e., there is a complete life cycle in the human body)? none. None of these worms has a complete life cycle in the human body. Once the larvae mature into adults, no more adults are generated in the human body.

physical findings

abnormal temp (high or low) hypotension (low BP) mental status change renal dysfunction: oliguria or anuria tachypnea (RR > 20) or respiratory failure edema decreased capillary refill or mottling of skin vascular occlusion

entamoeba histolytica

amoebic dysentery: abdominal pain, cramps, diarrhea, dysentery, blood stools, colitis Liver and systemic infection - fever, leukocytosis, rigors Encounter - worldwide - temperate - developing (5-10% carriers); U.S. (1 - 2% carriers) - fecal-oral (hygiene, sanitation), cysts in stool, trophs in intestine and tissues Entry - Ingestion of cysts - trophs in large intestine - specific adhesin Spread - Yes - invasive of gut epithelium - even to liver and elsewhere Evasion of defenses - Killing of PMNs and macrophages - IgG/IgA Trophozoite with ingested RBCs Damage - Cytotoxin - Flask-shaped ulcers in gut - Secondary bacterial infection from invasion - Liver abscess Outcome - Move to new hosts - yes - cysts in feces Treatment - metronidazole Diagnosis - microscopy: Cysts in stool, biopsy, ingested RBCs definitive - serology in U.S.

zoonoses

animal reservoir we usually exclude domestic food animals (exclude food born pathogens like salmonella) some possible bioterrorism encounter/entry - bite of an arthropod vector - animal bite - inhalation of contaminated materials or animal droppings - ingestion (note domestic animal exclusion) - direct contact

causes of sepsis

bacteria (and fungi) in food. viruses could also lead to sepsis not all bacteremia leads to sepsis - transient from tooth bushing, defecation, etc. certain pathogens with virulence factors invasion through skin, mucosa granulocytopenia (low count of a type of white blood cell) and PMN dysfunction complement defects adaptive immunity defects (Ig and CMI) splenic dysfunction

review of infectious diseases (most likely bioterrorism agents)

bacteria (toxins) viruses fungi parasites - worms - protozoa - arthropods

mycobacterium tuberculosis and tuberculosis

basic bacteriology and pathogenesis - acid fast - cell wall waxes and lipids - slow growth- doubling time= 15-20 hours - obligate aerobe - unique set of antibiotics: ethambutol, isoniazid, pyrazinamide, rifampin - resistance is a problem encounter - humans only - 1/3 of world population infected - in US, mainly from immigrants - aerosol- droplet nuclei from actively infected people - resistant to drying: small desiccated respiratory droplets disease burden - in 2008, 8.8 million new cases world wide, 1.4 million deaths - estimated 2 billion people in the world infected (at any given time) - 10-15 million persons in US infected (doesn't mean they have active disease just means bacteria are inside their body) - without intervention, about 10% will develop TB disease at some point in life entry - inhaled directly into alveoli - no upper respiratory tract colonization - not aspiration pneumonia spread - yes - phagocytosed by alveolar macrophages - transported to lymph nodes - Ghon complex- inflammation of hilar lymph nodes - can cause bacteremia (hematogenous dissemination) - seed about any tissue - lung single most important site of infection phagocytes carry bacilli from alveoli to node. T cells access node through postcapillary venule. macrophages/dendritic cells present tubercle antigens to T cells from blood as they meet in paracortical areas of nodes. phagocytes carry bacilli from infected node to blood. multiplication - slow (doubling time can be a day) - intracellularly in macrophages: facultative intracellular (as opposed to obligate) - lipid metabolism - in areas with high oxygen - cultured on special agar- has unusual colony morphology evade defenses - intracellular pathogen of macrophages - cell wall components important - inhibits phagolysosome acidification - usually limited by initial cell mediated immune response, but organisms persist for life - immunity measured by PPD skin test or interferon gamma release assay - cel mediated immunity is required for intracellular pathogens of macrophages - activated T cells secreting IFN-gamma, other cytokines - stimulate macrophages - vaccine: bacille Calmette-Guerin (BCG), mycobacterium bovis, live-attenuated, not used in US (used overseas) damage - host cell mediated immune reaction - delayed type hypersensitivity - granulomas (tubercles). phagocytes and lymphocytes show up at the site of infection trying to fight it. - caseous necrosis - initial symptoms mild to non existent outcome - reactivation in only 10% of initially infected people - reactivation in first 2 years= 5% - remaining life= 5%. based on decreased immunity (ex. AIDS) - decreased immune status- miliary TB. uncontrolled infection. highly lethal. infection in alveoli --> bacilli multiply and move to the tracheobronchial lymph nodes --> little or no hypersensitivity; tuberculin negative --> progressive systemic disease and death infection in alveoli --> bacilli multiply and move to the tracheobronchial lymph nodes --> delayed type hypersensitive and cell mediated immunity; tuberculin positive --> disease is contained; bacteria live but fail to replicate --> Ghon complex appears 5 years or so later in 25% of cases --> 91% no disease, 6% clinical TB, 2% pulmonary, 3% extrathoracic, 1% both, 3% progressive systemic disease and death

damage of sepsis cardiovascular system

hypotension and capillary leak - decreased perfusion - impaired oxygen delivery - accumulation of toxic metabolites (lactic acidosis) - dysfunction, necrosis, and failure of vital organs (brain, lungs, kidney, liver, and gastrointestinal tract) neutrophil survival is prolonged and rates of apoptosis are reduced, organ failure disseminated intravascular coagulation (DIC)

clostridium tetani- tetanus

basic microbiology - gram positive rod, obligate anaerobe - spore former encounter - environment - spores in soil - also in intestinal tract entry - wound contamination with spores spread - yes, by definition- it's a wound multiplication - wound becomes anaerobic - other bacteria consume oxygen evade defenses? you don't hear a lot about this because it's not necessary damage - tetanospasmin - lethal dose = 1ng/kg - produced during sporulation - A-B toxin - binds to nerve - retrograde transmission to CNS - also through blood tetanospasmin - protease- cleaves synaptobrevin - inhibition of neurotransmitter release - vesicles cannot fuse in inhibitory synapses - no inhibitory signal - opposing muscles locked on - spastic paralysis - death by respiratory failure outcome - death by respiratory failure - transmission- none treatment - antitoxin - antibiotics - debridement prevention - vaccine- tetanus toxoid - IgG to neutralize toxin - immune globulin if too late - disease is slow, so time to boost (but not prime) after exposure

streptococcus pyogenes (group A strep)

basic microbiology - gram postive coccus in chains - beta hemolytic - major surface components= group A carbohydrate, M protein (fibrillar layer, over 100 serotypes, antigenic variety, different diseases) - hyaluronic capsule - lipoteichoic acid diseases - suppurative infections (causing pus): pharyngitis (scarlet fever rash from Spe toxin) - pneumonia - skin infections (wide range): superficial (impetigo), deep (necrotizing fasciitis) - streptococcal toxic shock syndrome: systemic symptoms from toxin - nonsuppurative secondary complications: rheumatic fever, glomerulonephritis, immunologically mediated sequellae

pertussis toxin

binding, internalization of S1, dissociation of enzymatic portion, reduction of disulfide bond and activation of S1 tracheal cytotoxin (TCT) peptidoglycan building block derivative loss of ciliated cells stops mucus flow makes patients susceptible to secondary infection adenylate cyclase toxin

yersinia pestis

biologist dies of plague in arizona: man performed necropsy on infected mountain lion gram negative rod diseases - bubonic plague: swollen, painful lymph nodes, fever, septic shock - pneumonic plague: flu like illness, mucoid, bloody sputum, dyspnea, cyanosis, rapidly fatal encounter/entry - sylvatic cycle: bites of fleas from prairie dogs, deer, mice, or rats . <50 cases per year in western US - urban cycle: none in US. bites of fleas from rats (bubonic). human too human (pneumonic). respiratory droplet. highly communicable (requires isolation) spread - draining lymph nodes causing buboes (swollen, painful) - through blood throughout body - lungs can become infected by septic emboli for pneumonic plague evade defenses, multiplication - after flea bite grows within macrophages - then becomes extracellular damage - endotoxin, shock like symptoms - high fever, myalgia outcome - bubonic usually fatal if untreated - pneumonic 100% fatal if untreated - transmission to humans - pneumonic plague diagnosis - culture - stain of tissue/sputum - serology

other issues vaccines

breadth of coverage of the pathogen - heamophilus influenzae type b: type b capsular carbohydrate, 100% coverage - streptococcus pneumonia and neisseria meningitidis: numerous capsule types, combine most prevalent forms antigenic drift and shift - influenza virus year to year function of target antigen - adhesins for IgA - toxins (B subunit) - capsules (opsonization) - other virulence factors - surface molecules for opsonization - viral proteins that get expressed on the cell surface autoimmunity issues - antigenic mimicry (sialic acid) - cross reactions (M protein of streptococcus pyogenes)

sepsis summary

cases are increasing caused by host response: recognition of PAMPs by PRR mediated by host cytokines and effectors effects mainly at vascular endothelium goal directed therapy is key: hydration and antibiotics early and appropriate antimicrobial therapy is crucial

meningitis

clinical presentation - acute (bacteria, some viruses) - subacute (slower organisms) - chronic (fungi, Mycobacterium) etiology epidemiology - community acquired vs nosocomial - sporadic vs epidemic

dermatophytes (cutaneous mycoses)

commonly called ringworm, jock itch, athlete's foot, etc. technically "tinea" + location: - tinea pedis (foot), tinea capitis (scalp), tinea cruris (groin), tinea unguium (nails) some preference by sex, age Three genera - Microsporum, Trichphyton, Epidermophyton encounter - soil, animals, or human only - moist environments (shower floors) entry - on broken epidermis from contact spread - through stratum corneum - superficial - Ring at edge of growth (ringworm) multiplication - multiplies as mold in tissues - Best at 25°C - Balance between growth and stimulation of host response damage - Keratinlytic exoenzymes - inflammation outcome - resolves with treatment diagnosis - histology treatment - terbinafine, itraconazole

molecular basis of inflammation

conserved features of microbes recognized by host cells are called "pathogen associated molecular patterns" or PAMPs host cells express proteins that recognize these conserved microbial features: "pattern recognition receptors" or PRR - toll like receptors - NOD proteins gram negative bacterium TLR4- LPS TLR6, TLR2- peptidoglycan TLR5- flagellin

vaccine ethical issues

cost vs benefit to society and individuals letting others take risks but relying on the benefit urban legends, myths, quackery, anecdotes societal standards - rotavirus story: rare intussusception caused halt to vaccine worldwide, thousands of babies died as a result vs few intussusception- legal concerns

anatomy

cranium- skull meninges - 3 membranes that surround the brain brain - cerebrum - cerebellum - brain stem blood brain barrier at vascular endothelium ventricles spinal cord the brain is located within a closed space, surrounded by the meninges (pia mater, arachnoid mater, and dura mater) in close approximation to mucosal surfaces containing commensal flora (the nasopharynx)

skin and wound infections

encounter - contact with humans, animals - bites of humans, animals, arthropods, - trauma entry - skin (pores, hair follicles) - wounds (scratches, cuts, burns, surgery, catheters...) - insect and animal bites - hematogenous (vibrio vulnificus) diseases - localized infections - localized infections with systemic effects - systemic infections multiplication - surface sparse, except oils - subcutaneous lipids damage - cytotoxins: locally produced, produced elsewhere (toxic shock syndrome) - exoenzymes - inflammation - intracellular infection: vascular endothelium

vaccine self study

current vaccines for cholera: Vaxchora is the only cholera vaccine approved by the FDA, the agency said. Two other oral cholera vaccines, Dukoral and ShanChol, are available elsewhere, but they require two doses and can take weeks to confer protection, according to the Centers for Disease Control and Prevention (CDC). VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR. current vaccines for typhoid fever: Inactivated typhoid vaccine (shot) One dose provides protection. It should be given at least 2 weeks before travel to allow the vaccine time to work. A booster dose is needed every 2 years for people who remain at risk. Vivotif (Typhoid Vaccine Live Oral Ty21a) - Also known as 'typhoid pills', Vivotif is made from attenuated live bacteria. The vaccine provides up to five years' protection and is approved for use in individuals over six-years-old. Vivotif is taken orally over the course of four doses. Typhoid Vaccine (Injectable) - Made from inactive bacteria, the injectable typhoid vaccine provides protection for up to two years. This vaccine is approved for use in individuals over two-years-old. ideal vaccine: The ideal vaccine is discussed under three headings. 1. The major requirements of the vaccine. This includes primarlly safety and efficacy and a number of other desirable features if the vaccine is to control a disease of global importance. These include cost, easy administration (e.g. orally), thermal stability, multivalency and long-lived immunlty 2. The nature and persistence of the immune responses which, as judged by model systems, are probably generated by the most effective viral vaccines in current human usage. 3. Approaches for developing future 'simplified" vaccines with similar levels of safety and efficacy so that these objectives are achieved.

why do we vaccinate?

decrease morbidity and mortality increase quality of life economic benefits to society vaccines more than pay for the costs of their development in prevented health costs and lost economic output

staphylococcal scalded skin syndrome (SSSS)

dermonecrotic toxin (exfoliative toxin) bullous exfoliative dermatitis

pulmonary anthrax

diagnosis - history, epidemiology, culture, chest X ray

relationship between infection, SIRS, and sepsis

diagram on slides SIRS- other, trauma, burns, pancreatitis infection mixed with SIRS= sepsis infection can be bacteremia which overlaps with sepsis fungemia, parasitemia, viremia, and others overlap with sepsis severe sepsis- organ dysfunction septic shock- when you can't resuscitate the blood pressure by giving fluids

why care about mycology

fungi are a leading cause of nosocomial infections fungal infections are a major problem in immune suppressed people the incidence of fungal infections is increasing (re-emerging pathogens) fungal infections are often mistaken for bacterial infections, with fatal consequences

Corynebacterium diphtheriae- Diphtheria

diphtheria- Greek "leather" pseudomembrane gram positive non-sporeforming rod asymptomatic carriers possible clinical manifestations - 85-90% sore throat - 50-85% low grade fever - 26-40% dysphagia - 50% pseudomembrane bull neck toxin mediated manifestations - 2/3 with carditis - neurotoxicity in severe disease - larynx: croup, asphyxia - renal tubular necrosis epidemiology - early 1900s among leading cause of death in infants - 1920s: 200,000 cases per year, 13000 deaths - immunization- 19,000 cases in 1945 - since 2000: 0-2 cases per year reported in the US - still endemic in multiple areas of the world - significant illness and death in developing countries where vaccination coverage is low - soviet union 1991-1998: >200,000 cases with >5000 deaths pathogenesis - encounter: humans only, inhalation - entry: restricted to URT - spread: none - multiplication: fastidious (use serum tellurite) - evade defenses: not much to deal with in URT - damage: diphtheria toxin - outcome: transmission to humans (yes, mandatory), can be fatal if untreated (5-10%), treatment (antibiotics and antitoxin), prevention (toxoid vaccine)

classification of fungi

domains: archaea, bacteria, eukarya eukarya kingdoms: planta, animalia, mycota (mycetae)

laboratory findings

elevated creatinine (acute renal failure) abnormal WBC (leukocytosis/-penia) abnormal platelet count (thrombocytosis /-penia). the platelets will be consumed to the point that they can't be replenished coagulopathy (consumptive) lactic acidosis elevated C-reactive protein and erythrocyte sedimentation rate hyperglycemia (increased sugar in the blood)

diphtheria toxin

encoded on bacteriophage (lysogenic conversion) A-B type toxin - ADP ribosylates EF-2 - inhibits protein synthesis - cytotoxic - damaging heart, nerve, and kidneys, etc. - heparin-binding epidermal growth factor receptor - death from heart/nervous system damage target of vaccine - chemical or genetic toxoid NAD + EF2 --> EF2-ADP ribose + nicotinamide acts as diphthamide- modified amino acid residue of EF2 1. diphtheria toxin's receptor binding domain (B) binds host membrane 2. membrane bound toxin (A+B) enters by endocytosis 3. catalytic subunit A is cleaved but held to the B subunit by disulfide bonds. endoscope vesicle acidifies. the disulfide bonds are reduced. 4. the transmembrane domain facilitates passage of the catalytic A peptide through the vesicle membrane 5. the catalytic A domain ADP ribosylates elongation factor 2 (EF2). this halts protein synthesis and kills the cell.

pertussis pathogenesis

encounter - human only- inhalation - highly transmissible among unvaccinated (90%) - infected adolescents/adults are the source for infants and children (get vaccinated if contact with infants) entry - restricted to URT - adherence to ciliated epithelium - filamentous hemagglutinin (FHA) (part of current vaccine) - pili/fimbriae - pertactin spread- none multiplication- fastidious - bordet-gengou plates evade defenses - not much in URT in non-immune - ciliated epithelium - mucociliary escalator - affected by TCT damage - pertussis toxin - A-B type toxin - ADP ribosylates G protein increasing cAMP - localized tissue damage - systemic toxicity: hypoglycemia, leukocytosis, neurological damage

general pathogenesis - respiratory infections

encounter - most are human only - some are from animals enter - inhalation to URT first - inhalation all the way down to LRT - aspiration to LRT - descent down mucosa - hematogenous to alveoli - direct penetration (rare) spread - some do= into blood, go deeper (brain) - some don't= possible systemic effects multiplication - many are fastidious: require chocolate agar or special agars - some can be isolated on special agars - very fast (Staphylococcus) to very slow (mycobacterium tuberculosis) evade defenses - in non immune host, defenses are mainly physical. mucociliary escalatory of URT. - particle exclusion. large particles get caught in hairs or get thrown against mucus by inertia. <3 um can make it to LRT. - epiglottis, larynx, and cough reflex - chemical: lysozyme (degrades peptidoglycan) and lactoferrin (binds Fe) - alveolar macrophages (PMNs with inflammation) - complement in LRT aerodynamic factors include the presence of vibrissae in the nasal passage and abrupt changes in the direction of flow of the air column. the epiglottis and cough reflex prevent introduction of particulate matter into the lower airway. the ciliated respiratory epithelium propels the overlying mucus layer upward toward the mouth. in the alveoli, macrophages, humoral factors (including immunoglobulins and complement), and neutrophils (when inflammation is present) assist in preventing or clearing infection. IgG + C --> alveolus , alveolar macrophage IgA synthesis evade defenses - in immune host: sIgA in URT, IgG in LRT (not sIgA as opposed to book), CMI (CTLs throughout, TH1-macrophages in LRT for intracellular) very often the organisms take advantage of a debilitated or compromised host - chronic obstructive airway disease - physical obstruction (foreign object) - impairment of glottal/cough reflex (drugs, alcoholism) - mucociliary elevator (smoking, alcoholism) - viral infection - loss of consciousness damage - toxins (some act locally, some act systemically) - inflammation - intracellular replication - adaptive immune response outcome - self limiting to death - transmission to humans: usually yes, some are dead end

relationship of pathogenesis to appropriate immune defenses

encounter --> direct injection --> yes --> complement phagocytes --> intracellular (phagosome CMI- Th1 or cytoplasm CTL- Th1) or extracellular + toxins (IgG - Th2) if not direct injection then mucosal membrane sIgA --> spread --> yes (look above) or no (sIgA)

inhalation anthrax (wool sorter's disease)

entry at lung flu like illness progresses rapidly to - respiratory distress - cyanosis - edema of neck and chest - shock - fatal if untreated transmission to humans - No

cutaneous anthrax

entry at skin papule progressing to - vesicle - ulcer - ultimately an eschar (black lesion) and edema - malignant pustule - rarely fatal

skin

epidermis - stratum corneum- major physical barrier, only some worms can break this layer - langerhans cells- phagocytic defenses - hair follicles, sweat glands, sebaceous glands are weak points for entry basement membrane dermis - collagen, elastin - blood vessels, lymphatics subcutaneous fat superficial fascia muscle defenses - exfoliation: shedding of dead surface cells mandates renewal of microorganisms - dry: usual infection sites are wet areas, skin folds, armpit, groin - acidic: pH of 5 - temperature less than 37C: most pathogens grow best at 37C - lysozyme and toxic lipids: pore, hair follicles, sweat gland - resident microflora: manila gram positive - skin associated lymphoid tissue (SALT)

erysipelas

ery- red raised, bright red plaques with sharply defined borders usually group A streptococci

Burden of disease (sepsis)

estimates are compromised by lack of both standard definitions and cohort studies ~240-300 cases of sepsis per 100,000 persons economic burden - $22,100 per case - $20 billion nationally overall mortality rate of ~18% (very bad) - septic shock > severe sepsis > sepsis - 260,000 deaths in the US - 9.3% of all deaths that year 14 day mortality septic shock has a survival rate of ~58% meaning mortality rate is greater than 40% severe sepsis and sepsis have a mortality rate of approximately 20% (survival rate approximately 80%) sepsis in perspective - huge burden - around 300 cases per 100,000 (higher amount than AIDS, colorectal CA, breast CA, and CHF increasing incidence of sepsis - nearly tripled since 1979 - men have a higher rate than women

characteristics of fungi

eukaryotic, non-vascular organisms reproduce by means of spores (conidia), usually wind-disseminated both sexual (meiotic) and asexual (mitotic) spores may be produced, depending on the species and conditions like plants, may have a stable haploid & diploid states Vegetative body may be unicellular (yeasts) or multicellular molds (composed of microscopic threads called hyphae). cell walls composed of mostly of chitin and glucan cell membranes have a unique sterol, ergosterol instead of cholesterol Tubule protein - different heterotrophic - must feed on preformed organic material - not autotrophic (not photosynthetic) - digest using exoenzymes then ingest (we ingest then digest) glucose stored as glycogen - like animals - unlike plants - starch No Chlorophyll - Fungi are closer to animals than to plants or protists. - Fungi do not depend on light and can occupy dark habitats. - Fungi can invade the interior of the substrate with filaments

furuncles (boil)

extension of folliculitis carbuncle - coalesced furuncles

primary TB

first exposure inhalation followed by a flu like illness bacteremia develops can silently seed multiple sites in the body the bacteria take hold in specific sites in the body 4-8 weeks cell mediated immunity may see a Ghon complex (in different parts of the body)

goal-directed therapy for sepsis

first six hours - initiate fluid resuscitation - dopamine or norepinephrine for persistent hypotension - obtain blood, urine, and other appropriate cultures - administer empiric antimicrobial therapy - perform appropriate imaging studies- remove potentially infected foreign bodies - all interventions should be undertaken simultaneously and initiated within 1 hour

Giardia lamblia

flagellate asymptomatic to mild diarrhea to severe diarrhea (cramps, gas, smell, steatorrhea), 10- 14 days or longer Encounter - worldwide including U.S. - sylvatic from animals - human-human fecal-oral, hygiene, sanitation, sexual - cysts in water Entry - stomach acid - cyst to trophozoite - attach to small intestine with sucking disk - Spread - none Damage - malabsortion diarrhea Outcome - Move to new hosts - yes - fecal-oral, sexual Treatment - Metronidazole Diagnosis - Cysts or trophs in stool

necrotizing fasciitis

flesh eating infection highly invasive highly destructive s. pyogenes vibrio vulnificus

meningitis of adults- neisseria meningitidis

gram negative diplococcus serogrouped by carbohydrate capsule meningitis, septicemia encounter - human only (5-10% colonization- normal flora) - respiratory droplets - can cause epidemics entry - upper respiratory tract - adherence- type IV pili - opacity proteins (Opa, Opc) spread - through epithelium into blood - ciliary stasis and death - crosses blood brain barrier - infects central nervous system evasion of defenses - carbohydrate capsule - numerous serogroups - group B= polysialic acid (antigenic mimicry) - lipooligosaccharide (LOS) sialylation - factor H binding protein (FHBP) - complement deficient patients susceptible multiplication - fragile organism (chocolate agar) - likes elevated CO2 (candle jar) - reaches extremely high levels in blood damage - inflammation vaccine - mixture of most prevalent capsular antigens - not group B. that would be antigenic mimicry - linked to protein - induce IgG to protect blood

pseudomonas aeruginosa

gram negative rod aerobic green pigments biofilms antibiotic resistance diseases - opportunistic pathogen - local infections: folliculitis (hot tub dermatitis), cystic fibrosis lungs, eye (contact lenses), otitis externa (swimmer's ear), urinary tract, cellulitis, osteomyelitis - systemic infections: immunocompromised, burn patients encounter - environmental: water, soil, air, food (you can't bring flowers to patients) - catheters - endotracheal tubes entry - lung, intestine, wound - biofilms - pili spread - yes, in immunocompromised or with burns, wounds multiplication - simple - can grow on diverse substrates. even in disinfectants and cleaning materials - easy to contaminate stuff, especially in hospitals evade defenses - usually held in check by PMNs - so serious infections usually in neutropenic - no defenses at surface - toxins can kill phagocytes - in cystic fibrosis- strains mutate to produce alginate polysaccharide- mucoid damage - inflammation - exotoxins: exotoxin A (similar to diphtheria toxin), type 3 secreted toxins, extracellular enzymes outcome - self limiting in healthy people - can be lethal in immunocompromised and burn patients - not normally transmitted between people prevention - no vaccines - in hospital- vigilant infection control - clean wounds - for otitis externa keeps ears dry treatment - antibiotics - highly resistant to numerous antibiotics

noenatal meningitis- listeria monocytogenes

gram postive rod non spore forming serogrouped by teichoic acid motile newborn meningitis, septicemia, abortion opportunistic encounter - environmental- soil - food borne outbreaks: meat, dairy - genital tract of mother entry - oral - transplacental spread - invade non-phagocytes (InIA-E cadherin) - lyse the phagosome (listeriolysin O [LLO]) - escape into the cytoplasm - use host actin to spread from cell-to-cell (ActA) - invade through the mucosal surface into the bloodstream - crossing the blood/brain barrier - inflammation can contribute to leakiness evade defenses - intracellular - infects macrophages: escapes vacuoles - peptidoglycan deacetylation (TLR2) damage - inflammation - triggered by peptidoglycan - fluid accumulation - increased intracranial pressure, hydrocephalus, and brain damage outcome - highly lethal if not treated - other than mother to baby, not transmitted

Legionella pneumophila

gram negative rod - stains irregularly - use silver stain - difficult to identify in 1970s diseases - Legionnaire's disease: pneumonia of predisposed (smokers, older, drinkers) - Pontiac fever: flu like in anyone encounter - environment only - amoeba in water - natural as well as air conditioning entry - inhalation - directly into alveoli - no initial URT sources of legionella for human disease - surface water source (L. pneumophila + protozoa) - water treatment plant surviving pneumophila - bacterial growth in hot water heaters - biofilms within residential and institutional water systems - evaporative cooling towers, fountains, showers = infectious aerosols - faucets = microaspiration spread - not usually multiplication - fastidious - special medium: BCYE buffered charcoal yeast extract - made initial identification difficult - replicates within amoeba in the wild - replicates within macrophages: replicative and transmissible forms evade defenses - facultative intracellular of macrophages - treats them like amoeba - uses type 4 secretion (injection) - blocks phagolysosomal fusion - stimulates autophagy - creates endoplasmic reticulum-like space - cell mediated immunity is required damage - host response - alveolar inflammation outcome - can be fatal - treatable with antibiotics - debilitated hosts problematic - is NOT transmissible between humans (from environment, water)

Bordetella pertussis- whooping cough- pertussis

gram negative rod (coccobacillus) whooping cough - pertussis= severe cough - primarily in infants and children - cough of 100 days clinical course (in weeks) - incubation period (typically 5-10 days, max 21 days) - onset - catarrhal stage (1-2 weeks) - communicable period (onset to 3 weeks after start of paroxysmal cough) - paroxysmal stage (1-6 weeks) - convalescent stage (weeks to months) catarrhal - cough - rhinorrea paroxysmal - coughing spasms - whoop - cyanosis - vomiting - groups of episodes - OK in between convalescent (recovering phase) - decreasing but continuing symptoms

types of microbes involved in sepsis

gram negative, gram positive, and fungi fungi are opportunistic and their numbers have been slowly rising gram negative bacteria used to lead but now gram positive bacteria have overtaken them

staphylococcus aureus

gram postive coccus, usually in clumps many different strains produce different diseases - skin infections (impetigo, folliculitis, furuncles (boils), carbuncles, cellulitis, necrotizing fasciitis) - toxic shock syndrome - scalded skin syndrome (neonates) - abscess - septic arthritis, osteomyelitis - sepsis - pneumonia - endocarditis - food intoxication (food poisoning, not infection) encounter - humans only (some animals, pets) - normal flora of skin, nose - direct contact or fomite - nosocomial entry - skin - catheters, devices - wounds (surgery) - MSCRAMMS (microbial surface components recognizing adhesive matrix molecules): fibronectin binding proteins spread - yes, through tissues multiplication - grows quickly, especially in food - salt resistant evade defenses - coagulase (clumping factor) fibrinogen > fibrin - superantigens disrupt immune response - panton valentine leukocidin - capsule - catalase - chronic granulomatous disease patients at risk (shows relevance of PMNs and oxidative defenses) - protein A (binds IgG backwards) damage - pyogenic = inflammation - peptidoglycan, lipoteichoic acid (LTA) - toxic shock syndrome: local infection (systemic effects), toxic shock syndrome toxin (TSST-1), certain enterotoxins, superantigens - staphylococcal scalded skin syndrome: local infection (systemic effects), exfoliative skin toxin (protease, desmosomes) - hemolysins - exoenzymes (ex. lipase)

streptococcus pneumoniae

gram postive diplococcus carbohydrate capsule serotyping, >90 serotypes, important for vaccines alpha hemolytic diseases - pneumonia - sepsis - sinusitis - meningitis - otitis media

bacillus anthracis

gram postive rod, aerobic spore former disease - anthrax: cutaneous, inhalation, ingestion - few cases of cutaneous in US each year encounter - exposure to stable spores (not vegetative cells) entry - lungs - breaks in skin - GI tract spread - throughout blood with inhalation and ingestion - possible with cutaneous evasion of defenses - poly-glutamate capsule - exception to carbohydrate rule - antiphagocytic - toxins inhibit phagocyte function multiplication - spores germinate in macrophages - vegetative cells replicate extracellularly damage - potent cytotoxic A-B exotoxins - B portion = protective agent (PA) - A portions = lethal factor (LF, protease, interferes with signal transduction), edema factor (EF, adenylate cyclase, interferes with PMN motility) - holotoxins: PA + LF = lethal toxin, PA + EF = edema toxin

folliculitis

hair follicles microabscess s. aureus

symptoms (meningeal symptoms)

high fever headache stiff neck irritability (children) neurologic dysfunction - lethargy - confusion uncharacteristic sleepiness vomiting diagnosis of bacterial meningitis - cerebrospinal fluid analysis (lumbar puncture) - gram stain, presence of or elevated leukocytes, with predominant PMN, decreased glucose, elevated protein - blood culture treatment - prompt antibiotic therapy - anti-inflammatory agents - reducing intracranial pressure

pertussis complications

hospitalization (16%) pneumonia (4.9%) seizures (0.7%) encephalopathy (0.1%) death (0.2%) reported NNDSS pertussis cases: 1922-2011 - have gone down since DTP vaccine was put on market in late 1940s - DTaP and Tdap - spikes caused by failure to vaccinate

usual composition of cerebrospinal fluid in various central nervous system infections

leukocytes- normal is 0-6 - acute bacterial meningitis is >1000 % neutrophils- normal is 0 - acute bacterial meningitis is >50 red blood cells (per mm^3)- normal is 0-2 - acute bacterial meningitis is 0-10 glucose (mg/dL)- normal is 40-80 - acute bacterial meningitis is <30 protein (mg/dL)- normal is 20-50 - acute bacterial meningitis is >100

types of vaccines

live, attenuated - longest lasting immunity - most relevant forms of immunity (IgG, IgA, CMI) - greatest risk: reversion, virulence in immunosuppressed killed whole cell/organism - toxicity (bacteria) - IgG subunit/toxoids - safe, defined, stable - shorter lasting immunity - IgG

skin infections

local infections - impetigo- epidermis - abscesses: folliculitis (hair follicles), furuncles (boil, extension of folliculitis), carbuncles (coalesced furuncles) local spreading - erysipelas- dermal lymphatics - cellulitis- subcutaneous fat layer - fasciitis- very severe, fascia - gangrene (myonecrosis) - muscle layer systemic effect - toxic shock - sepsis

disadvantages of bioterrorism

maintain viability lack of containment or control - will the terrorists harm their own people? - the wind blows both ways

evaluation for TB

medical history - symptoms of disease - history of TB exposure, infection - past TB treatment physical examination chest radiograph PPD test/IGRA bacteriologic or histologic exam symptoms of TB - chronic - fever - chills - night sweats - appetite loss - weight loss - easy fatiguability pulmonary symptoms - productive, prolonged cough (duration of approximately 4 weeks or more) - chest pain - hemoptysis microbiological diagnosis of TB - Zeil Nelson acid fast stain - culture most sensitive and specific test - slow growing, up to 6 weeks - lowenstein-jensen medium- classic - newer media faster - nucleic acid amplification tests (PCR) - PPD - IGRA interferon gamma release assay

CNS disease

meningitis - infection of the meninges encephalitis- infection of the brain parenchyma brain abscess myelitis- infection of the spinal cord since the anatomy is contiguous, infections do not necessarily respect boundaries representative organisms of every microbiological form infect the CNS

introduction to respiratory infections

most common site for infectious diseases - by number of cases, but not by variety of organisms - largest mucosal surface area to outside defining upper and lower respiratory tracts usually self-limiting, but can be fatal secondary infections and effects beyond respiratory tract mostly viral, but also bacteria and a few fungi common are pneumonia and pharyngitis

randomized controlled trials of potential sepsis treatments

most have failed only hope with procoagulant pathway and hypoxia, early-goal induced therapy despite our understanding, we still don't have good treatment

scarlet fever

pharyngitis + rash symptoms - red diffuse rash (sandpaper feel) - strawberry tongue - red cracked lips - circumoral pallor (pale area around mouth) - red cheeks pathogenesis - encounter: human only, some evidence for dogs via bites - entry: upper respiratory tract, skin, adherence (M protein binds fibrinogen, lipoteichoic acid LTA, fibronectin binding protein) spread - YES! - hyalurinidase - breaks down intercellular matrix - DNAse B: DNA from lysed PMNS impedes movement of bacteria, helps spreading, antibody response used in diagnostics multiplication - fastidious - blood agar evade defenses - M protein- binds factor H to inhibit complement - hyaluronic acid capsule- antigenic mimicry, antiphagocytic - C5a peptidase- cleaves C5a to inhibit innate defenses damage - inflammation - hemolysins- lyse defense cells - streptolysin O- antibody response used in diagnostics - streptolysin S - Pyrogenic exotoxins (numerous)- superantigens, Spe- scarlet fever rash (phage encoded), toxic shock-like syndrome outcome - transmission- yes, highly contagious - clinical- highly variable depending on strain, patient, circumstances, treatment - pharyngitis self limiting except for rheumatic fever and glomerulonephritis - pneumonia- can be lethal - simple skin infections usually are self limiting, but can lead to glomerulonephritis - serious skin infections (necrotizing fasciitis) can be fatal or require surgery

lower respiratory tract infections

pneumonia - community acquired pneumonia: otherwise healthy, immunocompromised - hospital acquired: ventilator assisted pneumonia - different pathogens community acquired pneumonia- etiologies - S. pneumoniae: most common cause (40%) - atypical pneumonia: mycoplasma pneumoniae, chlamydia pneumoniae, respiratory viruses (influenza, adenovirus, parainfluenza, and RSV) - rarer causes: H. influenzae (more common in smokers), S. aureus (after influenza, very severe), legionella pneumophila (compromised), aspiration (mouth flora, anaerobes), gram negatives (klebsiella, pseudomonas), nosocomial (elderly in nursing homes, cystic fibrosis, HIV, alcoholics)

can vaccines eradicate infectious agents and their diseases?

possibly must be human only - cannot sterilize the environment - cannot clear animal reservoirs must be acute, not latent must be effective must achieve critical vaccination level best if infection is easily identified to enable public health intervention not many infectious diseases meet this

septic shock

sepsis with hypotension that persists despite adequate fluid resuscitation and therefore requires pharmacologic blood pressure support (pressers like norepinephrine) severe sepsis + 7 L normal saline + BP 70/40 = septic shock usually accompanied by perfusion abnormalities that manifest as severe lactic acidosis high mortality rate (over 40%)

how does vaccination work?

prevent initial infection in an individual prevent serious effects in an individual even if an initial infection occurs prevent the transmission of infections within the population herd immunity - protection of susceptible unvaccinated members of the population by achieving sufficient vaccination to disrupt transmission basic reproduction number R0- number of secondary cases generated by a typical infectious individual when the rest of the population is susceptible (ex. at the start of a novel outbreak) critical vaccination level Vc- proportion of the population that must be vaccinated to achieve herd immunity threshold, assuming that vaccination takes place at random vaccine effectiveness against transmission E- reduction in transmission of infection to and from vaccinated compared with control individuals in the same population (analogous to conventional vaccine efficacy but measuring protection against transmission rather than protection against disease) basic reproduction number, R0= 4 need the proportion of vaccinated individual to be greater than R0-1/R0 (exponential) in this example, the disease is minimally propagated if R0= 3, the epidemic would die off (because 3/4 people would be vaccinated)

clinical forms of TB

primary secondary or reactivation miliary localized

secondary TB

reactivation occurs in 10% of patients - 1/2 within 2 years of primary disease usually an apical lung infection slowly progressive (several months) worsening cough with sputum production low grade fever, night sweats, fatigue, and weight loss hemoptysis or pleuritic pain are rare cavitary disease very infectious isolation is important

vaccines learning objectives

relate microbial pathogenesis to the appropriate form of protective adaptive immunity relate the form of immunity to the composition and route of administration of the vaccine describe benefits and risks of the specific vaccines understand how specific examples of currently used vaccines function relate examples of current vaccines to their targeted populations

biological agents- classification

risk groups/ biological safety levels 1. non pathogens for healthy people (E. coli K12) 2. rarely serious, treatable, preventable (salmonella, influenza) 3. serious or lethal injection, treatment or prevention might be available (tuberculosis, HIV) 4. likely serious or lethal, no treatment or prevention (smallpox, ebola) classification of select agents - definition: any biological agent or toxin listed in 42 CFR part 73 (HHS) and 7 CFR part 331 and 9 CFR part 121 (USDA) - based on: ease of dissemination, mortality rate, public panic factor, public health preparedness - categories A, B, C - A highest, C lowest category A agents - easily disseminated - high mortality - high public panic - require special preparedness - anthrax- bacillus anthracis - botulism- clostridium botulinum - plague- yersinia pestis - smallpox- various major - tularemia- francisella tularensis - viral hemorrhagic fevers (ebola, marburg, etc.) category B agents - moderately easy to disseminate - low mortality rate - require enhancement of diagnostic and surveillance capability - west nile virus - caliciviruses - hepatitis A - ricin toxin - salmonella category C agents - available - easily produced and disseminated - low potential for mortality - little to no special public health needed - influenza - SARS - rabies - multi drug resistant mycobacterium tuberculosis - yellow fever - tick borne hemorrhagic fever

pathophysiology

route to the CNS: blood to BBB to brain - most frequent, especially for bacteria - penetration of BBB difficult (invasion, inflammation) direct - trauma, surgery, anatomical defects - most bacterial meningitis is nosocomial, not community acquired via the nerves - viruses (rabies) defenses of the CNS - low complement in cerebrospinal fluid - microglia- phagocytes damage - inflammation - PMNS - vasogenic edema - impaired blood flow - ischemia - cell death

impetigo

s. aureus and s. pyogenes

Flukes - Schistosomes

schistosomiasis: 200 million infections, 3 species Encounter - water - throughout world, but not in U.S. - S. mansoni - South America, Africa, Middle East - S. japonicum - East Asia - S. haematobium - Africa, Middle East Entry - invasion of skin by cercarial forms (some skin symptoms - rash) Spread • into blood - portal vein mating pairs migrate to terminal tissue - S. mansoni and S. japonicum - mesentery/intestines - S. haematobium - urinary bladder Multiplication - eggs released - nonspecific complaints during egg shedding (fever, chills, malaise, inflammation) - S.m. and S.j. eggs into intestines, liver - S.h. eggs into bladder Evasion of defenses - antigenic cloaking by binding host proteins Damage - inflammatory and fibrotic response to eggs in tissues - penetration damage - S. mansoni and S. japonicum - intestinal and liver symptoms - S. haematobium - urinary symptoms, bladder cancer correlation Outcome: Transmission to new host - indirectly - shed eggs develop into miracidia that infect snails - snails release infectious cercaria Diagnosis - eggs in stool or urine - eosinophilia Treatment - praziquantel, anti-inflammatories Prevention - sanitation

severe sepsis

sepsis plus organ dysfunction distant from the site of infection, or hypoperfusion (decreased blood flow through an organ), or hypotension (low blood pressure) for example: - sepsis + acute renal failure - sepsis + hypoxic respiratory failure - sepsis + BP 70/40 (low blood pressure)

What is bioterrorism?

the deliberate use of microorganisms or toxins from living organisms to induce death or disease FBI defines terrorism as "the unlawful use of force or violence against persons or property to intimidate or coerce a government, the civilian population, or any segment thereof, in furtherance of political or social objectives" in addition to human death and disease, also consider economic, agricultural, tourism, etc. targets

infant meningitis- heamophilus influenzae type b

they thought it was influenza. has nothing to do with the flu virus gram negative rod encapsulated (type b antigen). predominantly causes meningitis non-typeable and types a, c, d, e, f- less disease Hib was the primary cause of meningitis in children ages 6 months to 2 years vaccine all but eliminated Hib meningitis and invasive disease encounter - human only - respiratory droplet or saliva - can be endogenous (can be exogenous) entry - URT (upper respiratory tract) (nasopharynx) - adherence factors pili (fimbriae) - Hap (haemophilus adhesion and penetration) - autotransporter, large protein spread - invade from URT into blood, cross blood brain barrier then to CNS multiplication - fastidious, requires chocolate agar evade defenses - extracellular - capsule - phosphorylcholine decoration of LOS- anti-LOS IgG - sialylation of LOS - binds complement factor H (degradation of complement by host protein) - IgA protease inverse relationship between number of antibodies and frequency of disease maternal antibodies IgG present at birth (bacterial antibody titers) incidences rise rapidly around 6 months to a year cross reactive antibodies being generated by the normal flora damage - inflammation - LPS - protein D- ciliated epithelium (glycerophosphodiesterase) - lipooligosaccharide outcome - death - neurological sequellae - transmission to new host- droplet/saliva Hib Vaccine - humoral IgG to capsule prevents systemic infection by opsonization - composed of type b carbohydrate coupled to protein - drastically reduced meningitis by Hib - single serologic type of capsule associated with systemic disease makes single vaccine sufficient. other 5 serotypes don't cause significant disease. - part of the standard infant/childhood regimen - very successful

lyme disease

thousands of cases per year in US borrelia burgdorferi - gram negative spirochete - no LPS- lipoproteins instead - unusual genome - linear chromosome - numerous plasmids encounter/entry - deer tick bite - white footed mice are immediate reservoir - deer are essential for tick life cycle - need specific mice, deer, and tick (determines geographic location) spread - yes- through skin and body evade defenses - antigenic variation of surface proteins damage stage one - early infection, 3-30 days after bite - bull's eye rash- erythema chronicum migrans, painless - flu like symptoms - fever, chills, myalgia, fatigue, headache - secondary skin lesions possible - arthralgia - endothelial infection stage 2 - early dissemination- weeks to months later - neurologic involvement: numbness, pain, weakness, Bell's palsy, visual, stiff neck, headache - sometimes cardiac: congestive heart failure (cardiomyopathy) stage 3 - latent stage - chronic- arthritis of large joints - chronic progressiveness - neurological disease - immune response to persistent bacterial antigens? - autoimmunity? inoculation: after tick initiates feeding, bacterial replication and dissemination within tick (2-7 days), transmission into dermis stage 1: localized infection (days to weeks). expanding inflammatory skin rash = erythema migrans (antibiotic treatment) stage 2: disseminated infection (weeks to months). transient blood borne phase. colonization of diverse tissues (carditis, meningitis, arthritis) (antibiotic treatment) stage 3: late stage infection (months to years), long term survival of B. burgdoferi, arthritis, lyme encephalopathy, acrodermatitis chronic atrophicans (skin) (antibiotic treatment) outcome - transmission to new human hosts- no (dead end hosts) - vaccine- discontinued because of poor sales (concerns over safety) diagnosis - clinical presentation and serology

toxic shock syndrome

toxic shock syndrome toxin (TSST-1) - superantigen - produced by 5-25% isolates - tampon or infected wound - fever - rash - exfoliation of skin - shock (death rate 3%)

typical vs atypical pneumonia

typical - rapid onset - more severe symptoms - productive cough, purulent sputum - CXR dense consolidation atypical (slower) - subacute onset (slower) - less severe symptoms (walking pneumonia) - nonproductive cough, a little white phlegm - patchy interstitial infiltrates