GMS 6121 - Exam 4

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? E, the vaccine effective against transmission number. 100% The basic reproduction number, R0. (R0 - 1)/R0, where R0 is the basic reproduction number. Vaccination can only protect individuals, not populations.

(R0 - 1)/R0, where R0 is the basic reproduction number.

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.

Haemophilus influenzae type b (Hib) vaccine

infant-child meningitis, epiglotitis type b capsule coupled to tetanus toxoid or N. meningitidis protein to elicit IgG against antiphagocytic capsule to opsonize/lyse; should induce sIgA

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

Encephalitis definition

infection of brain parenchyma

Meningitis definition

infection of meninges

Myelitis definition

infection of spinal cord

The primary cause of damage during meningitis is: cytotoxicity from toxins cytotoxicity from intracellular replication inflammation autoimmune reactions with antibodies autoimmune reactions with T cells

inflammation

L. monocytogenes host damage

inflammation triggered by peptidoglycan, fluid accumulation, etc.

Haemophilus influenzae type b host damage

inflammation, LPS, Protein D - ciliated epithelium (glycophosphodiesterase)

Fungal immune response

inflammation, PAMPS: glucans, mannans, chitin; adaptive immunity (Th-1, IgG)

Meningitis damage

inflammation, PMNs, vasogenic edema, impaired blood flow, ischemia, cell death

N. meningitidis damage & vaccine

inflammation; mix of most prevalent capsular Ag's, not group B; conjugated to protein to induce IgG to protect blood

S. penumoniae damage

inflammation; peptidoglycan; pneumolysin toxin that binds to cholesterol on host cell membranes

Schistosoma damage

inflammatory and fibrotic response to eggs in tissues S. mansoni & japonicum - intestinal & liver symptoms S. haematobium - urinary symptoms, bladder cancer correlation

Rhabditiform larva

immature form of hookworm

Which of the following most accurately states the increasing severity of skin infections? impetigo - folliculitis - cellulitis - fasciitis cellulitis - folliculitis - carbuncle - gangrene x impetigo - furuncle - cellulitis - erysipelas x follicilitis - impetigo - fasciitis - erysipelas x carbuncle - furuncle - folliculitis - fasciitis x

impetigo - folliculitis - cellulitis - fasciitis

common skin infections

impetigo, abscesses: folliculitis, furuncles (boil), carbuncles (coalesced furuncles); local spreading: erysipelas, cellulitis, fasciitis, gangrene; systemic: toxic shock, sepsis

Adjuvants in vaccines

improve immune response; keep Ag in tissue longer; stimulate cytokines; activate and recruit APCs

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

Cysticerosis

inappropriate infection by pork tapeworm only; asymptomatic to mental problems

SIRS/Sepsis host mediators

inflammatory cytokines, chemokines, prostaglandins, leukotrienes, etc.; TNF-alpha, IL-1,6,8; fever, low BP, increased capillary permeability & blood flow, mobilization/infiltration/activation of neutrophils & platelets; activation of coagulation cascade (coags used up, leading to uncontrolled internal bleeding)

Vaccine - Ag drift and shift

influenza virus each year

Malaria symptoms

influenza-like; paroxysms (fever, chills, rigors) every 36-48hrs; sickle cell trait provides resistance to Plasmodium falciparum

Taenia solium (pork tapeworm) encounter, entry

ingest meat with larvae of worm (cysticercus); oral-larvae mature to adult in intestine; NO spread

Encounter: What are the usual circumstances of the encounter by a human? inhalation direct contact with skin ingestion sexual contact vertical - in uero

ingestion

what are the usual circumstances of encounters for humans

ingestion

Taenia solium (pork tapeworm) encounter, entry

ingestion of egg in human feces (Mexico); eggs hatch in stomach releasing onchosphere; autoinfection (regurgitate eggs from intestines back into stomach)

Echinocandins

inhibit UDP glucose glucan synthase, component of cell wall, capsofungin

What is the mechanism of action of tetanus toxin? killing inhibitory neurons stimulating inhibitory neurons inhibiting neurotransmitter release of inhibitory neurons killing all neurons stimulating all neurons

inhibiting neurotransmitter release of inhibitory neurons

Flucytosine

inhibits pyrimidine synthesis

Goal-Directed Therapy for Sepsis

initiate fluid resuscitation; obtain blood, urine, etc.; administer empiric broad spectrum antimicrobial and hydration therapy - all within 1 hour

IgG goal of vaccine

injected; extracellular+toxins, intracellular

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

IgA goal of vaccine

mucosal surface; without spread

If we want to eradicate a pathogen from the world, each of the following must be true EXCEPT: only a human reservoir x must be treatable by antibiotics infected people should be easily identified x must not have a latent infection x must have an effective vaccine given to minimal levels of the population

must be treatable by antibiotics

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

R0-1/R0

need the proportion of vaccinated individuals to be greater than this value.

Neisseria meningitidis vaccine factors

new vaccine available

Taenia solium (pork tapeworm) treatment

niclosamide

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

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 high mortality difficult or no treatment or prevention (vaccination) high public panic factor None of the above.

no special public health required to deal with infection

Hymenolepis nana symptoms

none or nausea, weakness, loss of appetite, diarrhea, abdominal pain, pruritis ani (itchy bottom); kids might also have headache and trouble sleeping

Staph aureus encounter & entry

normal flora skin, nost; direct contact or fomite; nosocomial; catheters, skin, wounds after surgery, fibronectin binding proteins

S. pneumoniae transmission

normal flora; via contaminated droplets or saliva

Taenia solium (pork tapeworm) damage

onchosphere develops into cysticercus, which cannot develop further ---> calcification and inflammation in brain, muscle, eye, heart, and lung

Taenia solium (pork tapeworm) spread and multiplication

onchosphere penetrates intestines and migrates in blood to tissues; humans are dead-end host - no multiplication in humans

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.

Eosinophilia

only seen with tissue-invasive worms

Toxoplasma gondii encounter & entry

oocysts in cat (essential host) faces tissue cysts in meat pregnant women at risk in first trimester; ingestion of cysts or oocysts that then differentiate into tachyzoites and spread from blood to brain and/or to fetus

Candida albicans

opportunistic mycoses; normal flora, vaginal and oral thrush diaper rash, can be systemic, humans only; yeast (at both temp ranges) hyphae, and pseudohyphae, inflammation, septic shock, transmissable

Based on the pathogenesis of disease, which of the following would be an ideal typhoid fever vaccine (note - it might already be in use)? injection of killed whole cells oral admininstration of killed whole cells injection of live attenuated - Salmonella enterica serovar Typhi oral administration of live - attenuated Salmonella enterica serovar Typhi injection of Salmonella proteins

oral administration of live - attenuated Salmonella enterica serovar Typhi

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)

M. tuberculosis spread

phagocytosed by macrophages, wherein they are transported to draining lymph nodes where Ghon complexes form (inflammation of hilar lymph nodes); can cause bacteremia through hematogenous dissemination; can seed almost any tissue, but the lung is the most important

Protozoa

single-celled eukaryotes; intestinal, urogenital, blood & tissue

representative URT infections

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

Ancyostoma duodenale & Necator americanus host damage

skin penetration, lung migration, blood loss & anemia

Bioterrorism history

snakes from hannibal's forces, plague-ridden dead bodies during siege of kaffa, Native Americans given clothing contaminated with variola virus (smallpox) both in 15th Century and in 1763; anthrax spores USSR accidentally released, cult contaminates salad with Salmonella typhimurium to prevent election

C. tetani encounter and entry

soil, wound

Haemophilus influenzae type b Vaccine

stimulates IgG response for opsonization; type b carb conjugated to protein to make it T-dependent for infants since they have T-independent

How does the Haemophilus influenzae type b vaccine work? stimulates sIgA to prevent colonization stimluates Tc cells to activate macrophages stimulates cytotoxic T cells to kill infected cells stimulates IgG to protect the blood stimulate defenses within the brain

stimulates IgG to protect the blood

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

pharyngitis

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

SIRS

systemic inflammatory response syndrome; At least 2 of the following symptoms: high or low Temp, tachycardia, tachypnea, high PaCO2, high WBC, immature WBC forms (with bands)

What is Hymenolepis nana? fungus tapeworm bacterium virus insect

tapeworm

what type of organism is h. nana

tapeworm

Cestodes

tapeworms; scolex (head) & proglottids; hermaphroditic; absorb host's nutrients in intestines; complex life cycles; usually aysmptomatic, except passage of egg-containing proglottids , can be several meters long, nausea

C. tetani damage

tetanospasmin produced during sporulation: A-B toxin, binds to nerve, retrograde transmission to CNS and through blood

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)

Azoles

voriconazole, fluconazole; inhibit cytochrome P450 dependent enzymes involved in biosynthesis of cell memebrane sterols

Ancyolostoma braziliense encounter, entry, spread & multiplication

warm regions of USA; filariform larvae in animal feces in soil, larvae penetrate skin & migrate, cannot differentiate

Giardia lamblia encounter & entry

waterborne (cysts); human-human fecal-oral, sexual; entry by ingestion; cysts mature to trophozite in stomach acid, attaches to intestine with sucking disk

Killed vaccine

whole cell/organism; toxicity (bacteria); IgG

Helminths

worms: cestodes - tapeworms trematodes - flukes nematodes - roundworms

Cimex leticulares

Arthropod, bed bug: bites humans at night while sleeping sucks blood, leaves rash like mosquito bite, does not transmit disease, nuisance

Listeria monocytogenes

gram + rod, non-spore-forming, serogrouped by teichoic acid, motile

Bordetella pertussis

gram - rod (coccobacillus); causes whooping cough or pertussis (severe cough); fastidious, Bordet-Gengou plates

Pseudomonas aeruginosa

gram - rod aerobic forms biofilms; opportunistic; folliculitis, cystic fibrosis, eye, otitis externa (swimmers ear), burn patients

S. pyogenes (Group A) dissemination

hyalurinidase breaks down intracellular matrix; DNase B degrades DNA from lysed PMNS in mucous to aid in spread

localized TB

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

P. aeruginosa damage

usually fixed by PMNs; neutropenic, in CF patients, alginate polysaccharide, inflammation, Exotoxin A, T3SS, extracellular enzymes, self-limiting to lethal, not usually transmissable

Entry: Where does H.n. enter the body, and where does it initially set up infection? upper respiratory tract lower respiratory tract mouth - intestines skin - subcutaneous tissues genital tract - urethra

mouth - intestines

Erysipelas

usually group A strep

Is H. nana transmissible between humans? If so, how?

- Yes - Ingestion of eggs from human feces

does H. nana spread? If so, where?

- Yes - intestinal mucosa

Which form of H. nana is released? How is it released?

- eggs - feces

where does h. nana enter the body and where does it set up infection?

- mouth - intestines

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

H. influenzae type b Ab/infection trend

At beginning of exposure, low infection, high Ab then infection raises and Ab decreases ---> maternal IgG Ab's begin to decrease after birth

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

Acute bacterial meningitis causes

Neonates: Group B strep, E. coli K1, Listeria monocytogenes Infant to 2yo: Strep. pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b Adults: Strep pneumoniae, N. meningitidis

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

Pertussis toxin

A-B type toxin: B faciliates entry, A has toxin activity; ADP-ribosylates (like Diphtheria toxin) G protein increasing cAMP; Localized tissue damage; Systemic toxicity: hypoglycemia, leukocytosis, neurological damage

Agr gene

Accessory Gene Regulatory locus

Autoimmunity issues

Ag mimicry (sialic acid) cross-reactions (M-protein of S. pyogenes)

Polyenes

Amphotericin B: ergosterol, causes membranes to leak, also binds to cholesterol so severe side effects Nystatin: topical only

Which of the following is NOT a mechanism/site of entry to the skin tissues? bite burn surface contact hematogenous All of the above ARE routes of entry to the skin.

All of the above ARE routes of entry to the skin.

Which worm is most likely encountered through domesticated pets? Taenia solium Schistosoma mansoni Schistosoma japonicum Ancylostoma duodenale Ancylostoma braziliense

Ancylostoma braziliense

Malaria encounter & entry

Anopheles mosquito-borne sporozoites; enters circulatory system and travels to liver

C. diphtheriae Damage, Treatment, & Prevention

Antibiotics + antitoxin against Diphtheria toxin (A-B type toxin); toxoid vaccine

Which of the following is FALSE regarding entry of pathogens into the LRT? Any size of particle can be directly inhaled into the alveoli. 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.

Any size of particle can be directly inhaled into the alveoli.

Meningitis types

acute (bacterial, viral); subacute (slower organisms); chronic (fungi, mycobacterium)

Whooping cough disease

B. pertussis; infant to 2yo; "cough of 100 days;" 3 stages: Catarrhal, Paroxysmal, Convalescent; restricted to URT with NO spread; incubation 5-10d; can lead to pneumonia (4.9%) or death (0.2%)

M. tuberculosis vaccine

BCG: Bacille Calmette-Guerin, Mycobacterium bovis, live attenuated, not used in USA

C. dihtheria toxin

Bacteriophage encoded (example of lysogenic conversion); A-B type toxin; ADP ribosylates EF-2; inhibits protein synthesis; cytotoxic; Heart, nerve, kidney damage: Heparin-binding epidermal growth factor receptor; can kill

Impetigo

Staph aureus Strep pyogenes

R0

Basic reproduction number; amount of cases generated by a typical infectious individual when the rest of the population is susceptible

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.

TSST-1

Staph aureus toxic shock syndrome, single secreted protein NOT A-B; stimulates release of cytokines

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

M. tuberculosis transmission & entry

aerosol - droplet nuclei from infected person; resistant to drying; however, can dry to size <3um and be directly inhaled into alveoli (LRT); no URT colonization

characteristics of bioterrorism agents

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

Meningitis diagnosis

CSF, gram stain, leukocytes (>1000), mainly PMNs (>50%), low glucose (<30), high protein (>100)

S. pneumoniae vaccines

Carbohydrate conjugated to protein (like H. influenzae type b); stimulates IgG response to opsonize bacteria

Why are most of the carbohydrate capsule vaccines conjugate vaccines in which the capsule is chemically linked to a protein? Carbohydrates are not immunogenic by themselves. Carbohydrates are T independent antigens. It is economically beneficial to get two vaccinzations (the capsule and protein) from a single vaccine. Anti-capsule antibodies are not sufficient for protection. We need a second antigen from the bacterium for protection. Without coupling to a protein, the carbohydrate will be degraded in tissues too quickly.

Carbohydrates are T independent antigens.

Whooping Cough Stages

Catarrhal (1-2wks from onset): cough, rhinorrea Paroxysmal (1-6wks): coughing spasms, whoop, cyanosis, vomiting, groups of episodes with normalcy in between Convalescent (8-12wks, wks to mos): decreasing but continuing symptoms Communicable period lies within catarrhal and paroxysmal stages

CMI

Cell-mediate immunity: intracellular, systemic infection (live); Phagosome: Th1- IFN-gamma, presented with MHC-II; Cytoplasm: Cytotoxic T lymphocytes presented with MHC-I, any cells, Ag in cytoplasm

arthropods

Cimex lectularius (bed bug), ticks & mites

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

Vc

Critical vaccination level; proportion of population that must be vaccinated to achieve herd immunity threshold, assuming that vaccination takes place at random

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

DTaP vaccine

D - Diphtheria (Corynebacterium diphtheriae) toxin toxoid elicit IgG Ab to neutralize toxin in blood; bad: could induce sIgA against adhesins T - Tetanus (C. tetani) toxin toxoid elicit IgG to neutralize toxin in blood; bad: induce IgG aP - B. pertussis: whooping cough: pretussis toxin toxoid + FHA + pertactin +/- fimbriae to elicit IgG Ab to neutralize toxin, not very effective, should induce sIgA against these adhesins

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 cell-mediated immunity to stimulate macrophages. They are aimed at eliciting IgG to stimulate opsonization. They are killed whole cells. They are live-attenuated cells. They are capsule conjugated to pneumococcal proteins.

They are aimed at eliciting IgG to stimulate opsonization.

What do diphtheria toxin and pertussis toxin have in common? They bind to the same receptor and affect the same host cells. They have the same enzyme activity and cellular effects. They both cause death of affected cells. They both are single subunit toxins. They are both ADP-ribosylating toxins.

They are both ADP-ribosylating toxins.

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

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)

Hymenolepis nana

Dwarf tapeworm or cestode

In terms of pathogenesis (especially spread) and symptoms, which of the following most accurately compares intestinal protozoans to gastrointestinal bacteria? E. histolytica - Shigella; Giardia - Salmonella E. histolytica - V. cholerae; Giardia - Salmonella E. histolytica - Salmonella; Giardia - Shigella E. histolytica - EHEC; Giardia - Salmonella E. histolytica - Shigella; Giardia - V. cholerae

E. histolytica - Shigella; Giardia - V. cholerae

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

Intestinal Protozoa

Entamoeba histolytica; Giardia lamblia; trophozite form (replicating); cyst form (survival outside of host)

LRT Host defenses

Epiglottis, larynx, coughing up matter; lysozyme degrades peptidoglycan; lactoferrin binds Fe; alveolar TH-1 macrophages; complement (IgG)

Antibiotics to treat M. tuberculosis infection

Ethambutol, isoniazid, pyrazinamide, rifampin

Which form of immunity is most needed to prevent most infections but is least likely to be induced by most currently used vaccines? IgA IgG Th1 Cell-mediated immunity Cytotoxic T lymphocytes (CTLs)

IgA

vaccine target Ag functions

IgA - adhesins Toxins - B subunit Capsules - opsonization

Vaccine - Breadth of coverage of the pathogen

Haemophilus influenzae type b: type b capsular carbohydrate, 100% coverage; Streptococcus pneumoniae and Neisseria meningitidis: numerous capsule types, combine most prevalent forms

Diphtheria disease

Hallmark pseudomembrane; bull neck (lymphadenitis); sore throat, low grade fever, dysphagia; toxin: carditis, neurotoxicity, croup, etc. in larynx, renal tubular necrosis; Since 2000, 0-2 cases per year in USA

L. pneumonphila replication

Facultative intracellular: within amoeba and host macrophages

What is the typical result of infection with Mycobacterium tuberculosis in an otherwise healthy person? Flu-like symptoms followed by lifelong asymptomatic infection. Unchecked spread through the body with highly lethal consequences. Cavitary lesions of the apical portions of the lung with high transmission to other people. Focal infections at specific sites throughout the body with symptoms differing according to the infected site. Productive, bloody sputum, night sweats, fatigue, and weight loss.

Flu-like symptoms followed by lifelong asymptomatic infection.

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

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

Streptococcus pneumoniae

Gram + diplococcus; carbohydrate capsule; >90 sertotypes; alpha hemolytic; normal flora

Legionella pneumophila

Gram -, rod; causes Legionnaire's disease (pneumonia in immunocompromised patients) and Pontiac (Michigan) fever (flu-like in otherwise healthy individuals; environmental only (amoeba in water), fastidious, use silver stain; grow on BYCE media

Streptococcus pyogenes (Group A)

Gram+ coccus in CHAINS; fastidious; beta hemolytic on blood agar; Group A carbohydrate; M protein (fibrillar layer), >100 serotypes gives Ag variety; hyaluronic capsule (antigphagocytic); LTA (Lipoteichoic acid)

S. pneumoniae replication

Grows in serous fluid in alveoli space

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

Age-related issues

Haemophilus influenzae type b and Streptococcus pneumoniae: infants cannot make T-independent immune response: carb conjugated to proteins ---> T-dependent

M. tuberculosis host damage

Host CMI reaction; Delayed-type hypersensitivity; granulomas (tubercles); Caseous necrosis

S. pyogenes (Group A) host damage

Host response inflammation; hemolysins: Streptolysin O & S; pyrogenic exotoxins: super antigens; Spe toxin in Scarlet fever rash (phage encoded); Toxic Shock-like syndrome

Ancylostoma duodenale & Necator americanus

Human hookworms, 700,000 infected in USA

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.

How is the evasion of defenses of Histoplasma related to the damage that it causes during infection? Toxins that kill macrophages also kill lung cells. The way that it suppresses cell-mediated immune responses predispose the patient to opportunistic infections. Intracellular replication in macrophages causes granulomas in tissues. The fungi stimulate an autoimmune response. The antiphagocytic capsule is highly inflammatory.

Intracellular replication in macrophages causes granulomas in tissues.

Which of the following most accurately describes the interaction of Listeria monocytogenes with host cells? Invasion, escape into cytoplasm, spread directly between cells Lysis of cells from outside with cytotoxins Killing of cells from outside with toxins Replication within the phagosome Adherence to cells with pili, but remaining extracellular

Invasion, escape into cytoplasm, spread directly between cells

How does Legionella pneumophila interact with macrophages? Its cell wall waxes and lipids inhibit phagosome-lysosome fusion. It injects proteins and stimulates autophagy. It injects proteins and stimulates apoptosis. It kills macrophages via exotoxins to prevent uptake. Its capsule prevents phagocytosis.

It injects proteins and stimulates autophagy.

How is Candida albicans different from most other medically relevant fungi? It is normal flora of humans. It exists as a yeast in human tissues. Damage is caused by inflammation in tissues. It causes systemic infections. It can cause infections in otherwise healthy people.

It is normal flora of humans.

Which of the following is NOT an example of bioterrorism? Spreading Salmonella at a theme park to effect the local economy Putting botulinum toxin in milk to discourage people from using dairy products Killing your neighbor with ricin toxin because he shot your dog. Putting Vibrio cholerae into the water system to discourage people from moving near your ranch Putting anthrax spores in the mail to further incite public panic after terrorists crash jets into buildings

Killing your neighbor with ricin toxin because he shot your dog.

LRT

LRT bronchoalveoli to alveoli; no mucociliary escalator clearance; IgG (blood to alveoli); pneumonia, etc.

C. diphtheria toxin reaction

NAD + EF2 ---> EF2-ADP ribose + nicotinamide acts at diphthamide (modified amino acid residue of EF2)

Does Giardia lamblia spread?

NO

Does Taenia solium (pork tapeworm) spread?

NO

How does Staphylococcus aureus cause toxic shock syndrome? Infection of the blood Extensive infection of skin tissues with localized damage Localized infection with systemic toxin Autoimmune reaction to bacterial components in the skin Ingestion of a preformed toxin in food x

Localized infection with systemic toxin

S. pyogenes (Group A) methods of evading host defenses

M protein binds to factor H to inhibit complement; antiphagocytic hyaluronic acid capsule ; C5a peptidase cleaves C5a

Ancylostoma doudenale & Necator americanus treatment

Mebendazole

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

Giardia lamblia treatment

Metronidazole

Anti-protozoals

Metronidazole: DNA - Entamoeba, Giardia, Trichomonas Aminoquinolones: chloroquine, primaquinine - Malaria Trimethoprim, sulfa drugs - folic acid - toxoplasma

Which worm causes anemia by feeding on blood in humans? Ancylostoma braziliense Necator americanus Taenia solium Schistosoma mansoni Schistosoma haematobium

Necator americanus

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

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.

Antifungal agents

Often insoluble or toxic Ergosterol: Azoles, Polyenes, Allylamines targets cell wall biosynthesis: capsofungin Tubulin: griseofulvin Nucleoside metabolism: flucytosine

Plasmodium host damage

P. vivax & P. falciparum both lyse hepatocytes, RBCs, plug capillaries P. falciparum - RBCs adhere to capillaries including brain; RBC lysis; kidney (blackwater fever); more deaths

Primary form of tuberculosis

Primary: first exposure; flu-like symptoms, within 4-8 weeks bacteremia, Ghon complexes; CMI

Inflammatory Cascade & Sepsis

Pathogen Associated Molecular Patterns (PAMPs) recognized by cellular Pattern Recognition Receptors (PRRs): LPS recognized by TLR4 Peptidoglycan recognized by TLR2 & 6 Flagellin recognized by TLR5; this activates key master regulator transcription factor NF-kB, which facilitates transcription of cytokines (TNF, IL-1 &6), platelet activation, coagulation activation, oxidases, Kinins complement, vasodilators & vascular leakage => leads to coagulopathy and vascular/organ system injury (endothelial damage) => multi-organ failure => death

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

B. pertussis vaccine

Pertussis toxoid + FHA; acellular (original vaccine was optimal but killed whole cells)

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 Schistosoma mansoni Schistosoma japonicum Taenia solium Necator americanus

Schistosoma haematobium

Schistosoma multiplication

Schistosoma mansoni and Schistosoma japnonicum - eggs into intestines, liver Schistosoma haematobium - eggs into urinary bladder Shed eggs develop into miracidia that infect snails; snails release infectious cercaria

Flukes

Schistosomes: Schistosoma mansoni - S. America, Africa, Middle East Schistosoma japonicum - East Asia Scistosoma haematobium - Afirca, Middle East

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

Blood & Tissue Protozoa

Plasmodium species: most common - P. vivaz,most lethal - P. falciparum

Treatment: What is the standard of treatment for H.n. infection? Ampicillin Metronidazole Praziquantel Chloroquine There are no effective treatments.

Praziquantel

what is the standard of tx for H. nana?

Praziquantel

Hymenolepis nana treatment

Praziquantel (antihelmintic), fluid & electrolyte therapy => prognosis good; if left untreated, can lead to dehydration

How does Toxoplasma gondii evade host defenses? Kill phagocytes with a toxin Replicate in a specialized vacuole in macrophages. Antigenic variation of surface antigens Antigenic cloaking by binding host proteins Antigenic mimicry

Replicate in a specialized vacuole in macrophages.

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

Most common Hymenolepis nana hosts other than humans

Rodents; intermediate: beetle, flea, mealworm arthropods

Human only pathogens

S. pneumoniae

Pharyngitis

S. pygoenes (Group A); fever, exudative tonsils, lymphadenitis; NO cough or rhinorrhea; URT

Scarlet Fever

S. pyogenes (Group A); Pharyngitis + red diffuse rash with "sandpaper feel;" strawberry tongue; red cheeks and lips; human only; URT

Necrotizing fasciitis

S. pyogenes, V. vulnificus

Sepsis

SIRS + (proven or clinically suspected) infection; mainly due to host inflammmatory immune response; ~300,000 cases per year; on the rise mainly due to aging population; mostly in response to Gram+ bacteria, ie. Staphylococcal toxin super Ag (~20% T cells)

Inflammatory Spectrum

SIRS > Sepsis > Severe Sepsis > Septic Shock

What is the difference between regular pharyngitis and scarlet fever? In pharyngitis the infection is limited to the URT, but in scarlet fever the infection spreads to the skin. Scarlet fever is an autoimmune manifestation of pharyngitis via cell mediated immunity. Scarlet fever is an autoimmune manifestation of pharyngitis via antibodies. Scarlet fever is caused by a locally produced, systemically active toxin. Scarlet fever is cause by a human virus that co-infects with Streptococcus pyogenes.

Scarlet fever is caused by a locally produced, systemically active toxin.

Secondary form of tuberculosis

Secondary: Reactivation (10%) within apical O2-rich portion of lung; cough worsens; sputum produced sometimes with blood (hemoptysis); low grade fever, night sweats, fatigue, weight loss; cavitary disease (holes in lung filled with bacteria) which is very infectious due to coughing up aerosol droplets (isolate patient)

Septic Shock

Sepsis + Hypotension despite fluid resuscitation; requires "pressors" like norepinephrine to raise BP; severe lactic acidosis

Severe Sepsis

Sepsis + organ dysfunction (distant from site of infection) or hypotension or hypoperfusion; Lung is primary site of infection; ie. sepsis+ acute renal failure/ hypoxic respiratory failure/ low BP

Stages of pneumonia (S. pneumoniae)

Serous: fluid build up in alveoli space (bacterial multiplcation) Early Consolidation: high bacterial count, low PMN count Late Consolidation: high PMN count Resolution: if survive, effective Ab response, macrophages clear debris with no permanent damage

M. tuberculosis replication

Slow; facultative intracellular: in vivo, intracellular in macrophages, in vitro can grow on special agar in "knobby" colonies

Most common cause of Community-acquired pneumonia (40%).

Streptococcus pneumoniae

Common LRT disease-causing organisms

Streptococcus pneumoniae, Mcyobacterium tuberculosis, Legionella pneumophila

Streptococcus pyogenes (Group A) diseases

Supperative: pharyngitis, scarlet fever (pharyngitis + rash); penumonia, impetigo, necrotizing faciitis; TSS (Toxic Shock Syndrome) Nonsuppurative secondary: rheumatic fever, glomerulonephritis, immunological sequellae

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

Which of the following would LEAST likely result in eosinophilia? Necator americanus encountered through the soil Ancylostoma brazilienze encountered through the soil Taenia solium after ingestion of pork Taenia solium after ingestion of food contaminated with human feces Schistosoma mansoni encountered through contact with water

Taenia solium after ingestion of pork

How is immunity to Mycobacterium tuberculosis linked to pathogenesis? A failure to make an antibody response enables the bacteria to replicate in the alveolar fluid. An antibody response to the bacteria causes immune complex-mediated damage throughout the body. Th1 cell-mediated immune responses damage the lungs and other infected sites. No immune response is generated, so the bacteria replicate without inhibition in all infected patients. Cytotoxic T lymphocytes lyse infected alveolar cells causing lung damage.

Th1 cell-mediated immune responses damage the lungs and other infected sites.

Why are we not protected against Neisseria meninigitidis group B by the multivalent anticapsular vaccines? There are no Group B N. meningitidis strains in the U.S. They are found only in Europe. The Group B antigen is a toxin. The Group B capsule cannot be coupled to proteins. The Group B capsule is polysialic acid.

The Group B capsule is polysialic acid.

How is Legionella pneumophila disease different from that caused by Streptococcus pneumoniae and Mycobacterium tuberculosis? It is intracellular and the others are extracellular. It is extracellular and the others are intracellular. It cannot be cultured and the others can be cultured. It only infects debilitated/compromised people and the others infect otherwise healthy people. The bacteria are from the environment only and are not transmissible between humans.

The bacteria are from the environment only and are not transmissible between humans.

Bordetella pertussis methods of evading host defenses

Tracheal cytotoxin (TCT) affects ciliated epithelium mucociliary escalator, pertussis toxin, adenylate cyclase toxin

TCT

Tracheal cytotoxin; peptidoglycan building block derivative, loss of ciliated cells, stops mucus flow

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.

Which of the following explains the relationship of Bacillus anthracis with phagocytes? The bacteria are strictly extracellular throughout the disease process. The bacteria are strictly intracellular throughout the disease process. The bacteria only infect neutropenic patients. The spores survive intracellularly and the capsule prevents phagocytosis. The bacteria evade phagocytes by living within endothelial cells.

The spores survive intracellularly and the capsule prevents phagocytosis.

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.

What do Corynebacterium diphtheriae and Bordetella pertussis have in common? They are both gram-positive rods. x They both produce peptidoglycan subunit toxins. There are less than 10 cases of each in the US each year now. x They cause non-spreading infections with systemic effects. Both of their vaccines have adherence components.

They cause non-spreading infections with systemic effects.

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

Which of the following describes differences between the upper respiratory tract (down to bronchi) versus the lower respiratory tract (bronchoalveoli and alveoli)? URT has IgG and complement URT has mucociliary escalator and IgA LRT has IgA and PMNs LRT has mucociliary escalator and complement Only URT has Th1 CMI, Only LRT has CTLs

URT has mucociliary escalator and IgA

URT

URT is largest mucosal surface with direct access to/from outside; ciliated epithelium; mucociliary escalator; bronchi; sIgA; pharyngitis (S. pyogenes, N. gonorroeae, C. diphtheria), whooping cough, diphtheria, etc.

Haemophilus influenzae type b dissemination

URT to blood across BBB to CNS

Ancylostoma duodenale & Necator americanus symptoms

allergic reaction in feet upon entry through skin (temporary ground itch); pneumonitis during migration through lungs; GI symptoms; anemia due to feeding of adult worms in instestines

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)

Atypical pneumonia

Usually Mycoplasma pneumoniae; also called "walking pneumonia;" slower onset; less severe; non-productive cough; chest X-ray shows patchy interstitial infiltrates

Typical pneumonia

Usually caused by S. pneumoniae; acute, rapid onset; more severe; productive cough; sputum; Chest X-Ray shows dense consolidation

E

Vaccine effectiveness against transmission; reduction in transmission of infection to and from vaccinated compared with control individuals in the same population.

Which pair of antifungal agents have the most similar mechanism of action? Amphotericin B and voriconazole Griseofulvin and flucytosine Capsofungin and nystatin Voriconazole and terbinafine Flucytosine and fluconazole

Voriconazole and terbinafine

Category B

West nile, Hep A Salmonella, Ricin toxin

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.

M. tuberuclosis incidence

Without intervention, about 10% will develop the disease in life, 5% of which will occur in 1st 2 years of infection

Outcome: Is H.n. infection directly transmissible between humans? If so, how (this is related to encounter). Yes - sexually Yes - ingestion of eggs from human feces. Yes - direct contact with skin. Yes - sexually. No, it is not transmissible directly between humans without an intermediate host.

Yes - ingestion of eggs from human feces.

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.

Spread: Does H.n. normally spread in the human body? If so, where does it go? Yes. It can invade the bloodstream. Yes. It can invade to the liver. Yes. It can invade to the brain. Yes. It can invade the intestinal mucosa. No. It does not spread.

Yes. It can invade the intestinal mucosa.

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.

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)

M. tuberculosis diagnosis

acid fast stain (Zeil Nielson); slow growing; Nucleic acid amplifcation; PPD skin test; Interferon Gamma Release Assay (IGRA)

Mycobacterium tuberculosis

acid fast; waxes and lipids in cell wall; slow growing; obligate aerobe; likes O2 rich areas; humans only

skin defenses

acidic (pH 5); less than 37C; lysozyme and toxic lipis; resident microflora; SALT: skin-assoc lymphoid tissue

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

Toxoplasma gondii treatment

antibacterials: trimethoprim, sulfa drugs

Schistosoma evasion of host defenses

antigenic cloaking by binding host proteins

Fungal evasion of host defenses

antiphagocytic capsule; yeast to hyphal (difficult to attack) transition; change surface glycoproteins, hydrophobins; survive in macrophages

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

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

Encounter: What are the most common hosts other than humans? dogs and cats pigs and cows fish beetles and mice Humans are the only hosts.

beetles and mice

what are the most common hosts other than humans

beetles and mice

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

Which of the following most accurately describes the urban cycle of plague? bite of flea from wild animal - bubonic plague bite of flea from wild animal - bubonic plague - transmission to other humans via fleas bite of flea from a rat - bubonic plague - transmission to another human via flea - bubonic plague bite of flea from a rat - bubonic plague - pneumonic plague - inhalation - pneumonic plague inhaling bacteria from a rat - pneumonic plague

bite of flea from a rat - bubonic plague - pneumonic plague - inhalation - pneumonic plague

Allylamines

block ergosterol synthesis, topical, used for dermatophytes like athlete's foot, terbinafine

Plasmodium falciparum diagnosis

blood smear; numerous rings/RBC and high number of infected RBCs

Plasmodium vivax diagnosis

blood smear; single ring/RBC and lower number of infected RBCs; Schuffner dots

Route to CNS

blood to BBB to brain (most frequent); direct trauma, surgery); via nerves (ie. rabies)

toxin agents

botulinum, ricin, staph enterotoxins

livestock pathogens prion

bovine spongiform encephalopathy

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)

Y. pestis

bubonic: buboes, pneumonic plague: bloody sputum, rapidly fatal; sylvatic cycle: rat flea bites human (bubonic)' human to human pneumonic respiratory droplet 100% fatal if untreated

S. pneumoniae diseases

can cause pneumonia (immunocompromised patients, etc.), otitis media and sinutitis

Neisseria meningitidis methods of evading host defenses

carbohydrate capsule: Group B - polysialic acid (Ag mimicry) to LOS ; factor H binding protein (fhbp)

Malaria

caused by Plasmodium vivax & Plasmodium falciparum; >1 billion deaths per year; endemic in tropics & subtropics, not endemic in USA

Neisseria meningitidis

causes adult meningitis & septicemia; gram - diplococcus, serogrouped by carbohydrate capsule; likes CO2

Corynebacterium diphtheriae

causes diphtheria, Gram + non-spore-forming rod; fastidious; serum tellurite

Haemophilus influenzae type b

causes infantile meningitis; gram - rod, encapsuled (type b Ag); fastidious, chocolate agar

Toxoplasma gondii

causes toxoplasmosis; opportunistic; infects adult brain & heart; can be congenital

Plasmodium treatment

chloroquine, primaquine, etc.

Ancylostoma duodenale & Necator americanus spread & multiplication

circulation, lungs, cough, swallowed, adults intestines, feed off blood, eggs in feces

meningitis

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

Ancylostoma braziliense diagnosis

clinical, eosinophilia

Staph aureus evasion of host defenses

coagulase (clumping factor) fibrinogen > fibrin; superAgs disrupt immune response, chronic granulamatous diseases, protein A binds IgG backwards

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

Hymenolepis nana transmission & entry

contaminated food, water, soil; fecal-oral route; infects intestinal lumen; can transmit from human-to-human by fecal shedding

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)

Ancylostoma braziliense host damage

creates tracks of migration for weeks to months

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.

Ancylostoma braziliense symptoms

cutaneous larva migrans - creeping eruption, ground itch

Multiplication: What is the non-adult form of the organism in the human intestines (there are adults there, too). rhabditiform larva filariform larva spore hyphae cysticercoid

cysticercoid

What is the non- adult form of the organism in the human intestines?

cysticercoid

immature form of Hymenolepis nana

cysticercoid (formed from oncosphere, which is a hexacanth larvae)

Entamoeba histolytica diagnosis

cysts in stool, biopsy, ingested RBC's are definitive, serology

Giardia lamblia diagnossis

cysts or trophs in stool

Entamoeba histolytica host damage

cytotoxin, flask-shaped ulcers in gut, liver abscesses

C. tetani outcome & treatment

death by respiratory failure as you cannot breathe, no transmission, antitoxin; tetanus toxoid vaccine stimulates IgG

H. influenzae type b outcome

death, neurological sequellae, transmission via droplet/saliva to new host

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

Histoplasma capsulatum

dimorphic, most asymptomatic, pneumonitis, lymphadenopathy, bird droppings, caves, conidia (mold form) inhaled into lungs, can spread throughout body, yeast survive within macrophages, CMI, granulomas

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)

Anti-helminths

disrupts adults Mebendazole, thiabendazole - microtubule - broad spectrum Niclosamide - oxidative phosphorylation - Cestodes Praziquantel - muscle, tegument - broad spectrum

Ancylostoma braziliense

dog/cat hookworm

classification of fungi

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

Miliary tuberculosis

due to uncontrolled infection; persistent dissemination occurs all over body; depressed CMI; fever, malaise, anorexia, weight loss, weakness, fatigue

livestock pathogens virus

ebola, foot and mouth, variola major

Note that I have skipped asking about evasion of defenses and damage. There is little known or little necessary to know since this is relatively benign. Multiplication: In the life cycle of H.n. in the human body, which form is released and how? eggs - feces adults - feces eggs - urine larvae - urine larvae - genital secretions

eggs - feces

Ancylostoma duodenale & Necator americanus diagnosis

eggs in stool

Toxoplasma gondii host damage

encephalitis; mental retardation in newborn

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.

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

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

Listeria monocyotgenes transmission & entry

environment (soil), foodborne, genital tract of mother, oral and transplacental

Pseudomonas aeruginosa encounter & entry

environment, water-borne; lung, intestine, wound, biofilms, pili

Taenia solium (pork tapeworm) diagnosis

eosinophilia, radiology

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)

Neisseria meningitidis dissemination

epithelium to blood across BBB to CNS

erysipelas

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

Which of the following is LEAST likely to be caused by Pseudomonas aeruginosa? burn wound infection lung infection of a cystic fibrosis patient eye infection gastroenteritis folliculitis

gastroenteritis

Staphylococcus aureus

gram + coccus in CLUMPS; impetigo, folliculitis, foruncles, carbuncles, cellulitis, necrotizing fasciitis, TSS, septic arthritis, scalded skin syndrome, food inTOXIcation; MRSA, VRSA

Clostridium tetani

gram + rod obligate anaerobe spore forming

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

What is the cause of damage in the cutaneous infections by dermatophytes? exoenzymes and inflammation intracellular replication within macrophages toxins that kill the epidermis toxins that kill the subcutaneous tissues apoptosis of skin cells

exoenzymes and inflammation

Plasmodium life cycle

exoerythrocytic in liver; asexual reproduction called schizogony; release merozoites into blood that infect RBCs (ertythrocytic cycle - more asexual); differentiate into gametocytes - blood meal for mosquitoes (sexual cycle); P. vivax only invades young, immature RBCs; P. falciparum has no specificity for RBCs

furuncles (boil)

extension of folliculitis carbuncle - coalesced furuncles

H. influenzae methods of evading host defenses

extracellular, antiphagocytic capsule, can add sialic acid or phosphorylcholine to LOS (lipooligopolysaccharide) to evade IgG; binds complement factor H; IgA protease

S. pneumoniae methods of evading host defenses

extracellular; antiphagocytic capsule; sIgA protease

Ancylostoma duodenale & Necator americanus encounter & entry

fecal-cutaneous; filariform larvae in soil from human feces; needs warm, moist soil (southern USA); penetrate intact skin; fecal-cutaneous route - unusual

Entamoeba histolytica encounter & entry

fecal-oral route: cysts in stool, trophozites in intestine and tissue; entry by ingestion of cysts, trophs go to large intestine

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)

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

Category C

flu, SARS, rabies, tuberculosis

L. pneumophila tramission & entry

from environment only, through amoeba in water (air conditioning, ie. hospitals, etc.); direct inhalation into alveoli (LRT); does not usually spread

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

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

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)

Each of these is a characteristic of cerebrospinal fluid analysis for acute bacterial meningitis EXCEPT: low glucose low protein elevated white blood cells presence of PMNs organisms on a Gram stain

low protein

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

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

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

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

Entamoeba histolytica spread

gut epithelium, liver & elsewhere

folliculitis

hair follicles microabscess s. aureus

Each of the following is a distinguishing feature of P. falciparum disease relative to P. vivax disease EXCEPT: numerous ring forms in RBCs higher percentage of infected RBCs has Schuffner's dots in infected RBCs increased adherence of infected RBCs to capillaries more severe symptoms

has Schuffner's dots in infected RBCs

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

Meningitis symptoms

high fever, headache, stiff neck, irritability in children, lethargy, confusion, sleepiness, vomiting

Category A Agents

high mortality, public panic, easy to spread ie. anthrax, plague

SIRS/Sepsis symptoms

high or low temp, hypotension, mental status change, renal dysfunction (oliguria, anuria), tachypnea or respiratory failure, edema, decreased capillary refill or skin mottling, vascular occlusion Lab results: high creatinine - acute renal failure abnormal WBC (leukocytosis/-penia) abnormal platelet count (thrombocytosis/-penia) coagulopathy (consumptive) lactic acidosis high Crp & ESR hyperglycemia

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

The symptoms of the tertiary phase of Lyme disease are cause by: host immune responses intracellular replication in endothelial cells lipopolysaccharide toxins produced by the bacteria There are no symptoms in the tertiary phase of disease.

host immune responses

L. pneumophila host damage

host response, alveolar inflammation; can be fatal, NOT transmissable between humans

Nematodes

human hookworms: Necator americanus, Ancylostoma duodenale dog/cat hookworm: Ancylostoma braziliense

Neisseria meningitidis transmission & entry

human only - mandatory (5-10% colonization, normal flora); respiratory droplet, can cause epidemics; URT, type IV pili adherence; opacity proteins (Opa, Opc)

Haemophilus influenzae type b transmission & entry

human only - mandatory, respiratory droplets or saliva; URT through nasopharynx, pili or fimbriae, Hap autotransporter protein for adhesion & penetration

Bordetella pertussis transmission & entry

human only - mandatory; inhalation; adherence to ciliated epithelium by filamentous hemagglutinin (FHA), pili or fimbriae, pertactin

C. diphtheriae transmission & entry

human only - mandatory; inhalation; restricted to URT with no spread

S. pyogenes (Group A) transmission & entry

humans only; URT; adherence: M protein binds fibrinogen; LTA; fibronectin-binding protein

Entamoeba histolytica

intestinal protozoa; causes amoebic dysentery: abdominal pain, cramps, diarrhea, dysentery, bloody stools, colitis; liver & systemic infection (fever, leukocytosis, rigors (shaking)); worldwide

Giargia lamblia

intestinal protozoa; flagellate; worldwide

M. tuberculosis methods of evading host defenses

intracellular in macrophages; cell wall components; inhibits acidification of phagolysosome; CMI response; activated T cells secreting IFN-gamma & other cytokines

Plasmodium evasion of host defenses

intracellular shielding, antigenic variation of major surface protein (MSP-1)

Listeria monocytogenes method of evading host defenses

intracellular; infects macrophages, escapes vacuole; peptidoglycan deacetylation (to avoid TLR2)

Hymenolepis nana spread

invades intestinal mucosa

Toxoplasma gondii evasion of host defenses

invades macrophages and lives in parasitophorous vesicle; lifetime; immunocompromised patients can have reactivation

Listeria monocytogenes dissemination

invades non-phagocytes by InlA binding to cellular E Cadherin, escapes into cytoplasm and uses ActA on cellular actin to propel it intracellularly from cell-to-cell; bloodstream; BBB to CNS

Schistosoma entry & spread

invasion of skin by cercarial forms; sometimes rash; into blood

Tinea pedis

keratinlytic exoenzymes; terbinafine, itraconazole, stratum corneum, can be systemic in immunocompromised patients

Entamoeba histolytica evasion of host defenses

kills PMNs and macrophages, IgG/IgA protease, trophozites ingest RBCs

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

Giardia lamblia host damage

malabsorption & diarrhea

Filariform larva

mature form of hookworm

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

Entamoeba histolytica treatment

metronidazole

What drug is used to treat amoebic dysentery and giardiasis? metronidazole primaquine trimethroprim sulfa drugs chloroquine

metronidazole

Which of the following most accurately describes the transmission and life cycle of Plasmodium in the humans? mosquito - blood - mosquito mosquito - liver - mosquito mosquito - liver - blood - mosquito mosquito - blood - liver - blood - mosquito mosquito - blood - liver - blood - liver - mosquito

mosquito - blood - liver - blood - mosquito

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

pharyngitis

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

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)

B. anthracis

poly-glutamate capsule, spores germinate in macros, vegetative cells replicate extracellularly, A-B exotoxins: B = Protective antigen PA, Lethal Factor, Edema Factor: PA+LF= LT, PA+EF=ET; wool sorters disease; cutaneous: eschar

Taenia solium

pork tapeworm; rare in USA

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

Taenia solium (pork tapeworm) treatment

praziquantel, steroids, surgery

Toxoplasma gondii diagnosis

serology, brain scans

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

Hymenolepis nana host shedding

proglottids contain eggs & break off & shed in feces

Meningitis treatment

prompt antibiotic therapy, anti-inflammatory agents

Tetanospasmin

protease that cleaves synaptobrevin; inhibits neurotransmitter release (so you say flexed); spastic paralysis

Which of the following is NOT a direct target of clinically used antifungal agents? pyrimidine synthesis x protein synthesis tubules x ergosterol synthesis x cell wall synthesis x

protein synthesis There are not antifungals that directly affect protein synthesis. Flucytosine can affect RNA that eventually leads to protein synthesis problems.

Staph aureus damage

pyogenic (inflammation), peptidoglycan, LTA, TSS1, superAg, Staph scalded skin syndrome

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

Parasitism definition

relationship bw organisms where parasite gains food and shelter from host who suffers.

AgrA

response regulator that, in its phosphorylated form, activates high-level expression of the agrACDB and RNAIII transcripts

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

Subunit/Toxoid vaccines

safe, shorter lasting immunity, IgG

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

What is the outcome of H. nana infection if left untreated?

self- limiting

Outcome: What is the outcome of H.n. disease if untreated and treated? death intestinal blockage weight loss from consumption of nutrients by the organism anemia from loss of blood by consumption by the organism self-limiting - discomfort

self-limiting - discomfort

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

L. pneumophila Methods of Evading host defenses

uses type IV secretion system; blocks phagolysosomal fusion; can stimulate autophagy; recruits intracellular organelles (ER) and replicates in ineffective lysosome; releases transmissive form from cell; CMI

Cellulitis

usually S. areus and S. pyogenes

What are the typical symptoms of H. nana infection? always asymptomatic usually asymptomatic - diarrhea abdominal pain possible upper respiratory - cough tracts under the skin neurological - cysts in the brain

usually asymptomatic - diarrhea abdominal pain possible

what are the typical sx of an h. nana infection

usually asymptomatic, diarrhea and abdominal pain are possible

Ancylostoma braziliense treatment

thiabendazole

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

Access to LRT

through inhalation to URT first; direct inhalation (<3um); aspiration; descend down mucosa; hematogenous spread to alveoli from blood; direct penetration

Parasite damage to host

tissue burden (migration, blockage, pressure); bleeding; Immunological: inflammation Type 1: hypersensitivity reactions Type 2: cytotoxicity Type 3: immune complex Type 4: DTH-CMI

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

KOH

used to accentuate fungal forms