Cholera, campylo, helico Flashcards
Cholera pathogenesis
Sensitive to gastric acid but some survive
TCP = toxin coregulated pilus
-> autoagglutination -> colonization of epithelium
Cholera toxin (CT) - secreted -> GM1 ganglioside -> endocytosis
- bacteria also secretes neuraminidase -> stimulates more GM1 -> more toxin binding
-> adenylate cyclase -> cAMP ->
villus cells - less NaCl absorption
secretory cells - inc Cl, HCO3 secretion
-> painless, watery, odorless diarrhea -> hypovolemic shock
Vibrio cholera characteristics
Gram negative
Comma shaped ("vibrio")
Motile - polar flagellum
Fermenter - yellow opaque colonies on TCBS medium
- no growth on EMB, enteric media
Strain O1 causes all epidemics
- classic
- El Tor - most recent (7th) epidemic since 1961
(also more virulent -> hemolytic)
Antigens: O, H, endotoxin (LPS), exotoxin (cholera toxin)
Cholera treatment
Death due to volume loss (10-15 L/d)
Measure volume loss Replace with oral rehydration or IV Antibiotics reduce duration to 1-3 d - doxycycline for adults - azithromycin - pregnancy, children
Cholera epidemiology
Only humans
Water, food - prevent with cooking, chlorination
- ID50 (infective dose) varies with food (yellow rice, shellfish) - 10’2-10’9
Endemic in Asia -> spread to Africa, South America
Current pandemic (7th) = El Tor O1, increasing/spreading world-wide
John Snow = father of epidemiology
- made a map -> removed pump handle -> cases fell -> proved water transmission
Vibrio pathogens
V cholera
V parahaemolyticus: shellfish -> invasive gastroenteritis
V vulnificus: seawater, shellfish -> wounds
- only if you have liver failure
Cholera vaccines
Toxoid - should be effective but isn’t
Parenteral kills - ineffective
Oral:
- killed cells + CT-B subunit - 50% efficacy, widely used but not in US or for travellers
- Shanchol - new killed whole cell - 70% efficacy - in use in Haiti
- live attenuated - works in US but not other populations
Campylobacter epidemiology
Zoonosis - transmitted to humans via food (human-human rare)
- 70% of poultry are contaminated!
- also unpasteurized milk
- cases peak in summer, fall
Most common cause of diarrhea
- infants in developing world, infants-young adults in developed
- not identified, cultured until 1970s
Low infectious dose (<500 organisms, one drop of chicken juice)
Campylobacter pathogenesis
C jejuni, C coli
Low infectious dose -> invades apical surface -> exocytosis on basolateral -> inflammation -> malaise, diarrhea
Specific humoral immunity develops
Rare
- bacteremia (C fetus in immune compromised)
- autoimmune vs PNS = Guillaim-Barre
Campylobacter identification
Campylobacter = curved, microaerophilic
Stool culture -> selective media (campy BAP, 5-10% O2, 42 C)
- mimics body temp, conditions of chickens
- cephalothin to suppress other flora
- can’t withstand freezing or drying
- 10’6-10’9 to diagnose (may be present without disease)
Small size - can filter (0.45 microns) -> non-selective media
C jejuni is hippurate + -> turns purple (other Camp. are hipp negative)
Tx: supportive
- erythromycin, ciprofloxacin
Helicobacter virulence factors
Urease -> NH3, HCO3 = alkaline Adhesins -> epithelial lipids, carbs - BabA -> Lewis B antigen CagA (from cag pathogenicity island = cagPAI) - injected into epithelium -> disrupts cytoskeleton, adhesion, signalling, polarity, etc VacA = vacuolating - injected into epithelium -> damage Flagella LPS
Helicobacter pathogenicity
Gastric acid -> secretes protective mucous, NH3, HCO3 (urease)
Adhesins -> direct damage to gastric (CagA, VacA)
Recruits WBCs -> can’t penetrate mucous -> release superoxides -> destroy gastric cells
-> gastritis -> ulcer -> gastric cancer (6x risk of MALT lymphoma)
Helicobacter epidemiology
Transmission:
- fecal-oral
- gastro-esophageal reflux -> kissing (GROSS!)
Worldwide prevalence 50% - highest in developing
-> most stomach ulcers, half of gastric cancers
Infectious dose unknown, 10,000 for primates
Helicobacter diagnosis
Spiral, Gram negative
Radiolabeled urea -> urease cleaves -> C14 released as aerosol
- non-invasive, sensitive
Stool culture - use Campylobacter medium (Campy-BAP)
- follow with urease test (Camp is urease negative)
Seroconversion - often positive
PCR - stool or dental
Endoscopy -> biopsy, culture and sensitivity = definitive
Helicobacter treatment
Variety of antibiotic regimens
- often combined with bismuth salts (PeptoBismol)
- ex metronidazole + tetracycline + bismuth
- also amoxicillin, clarithromycin
- usually not prolonged unless relapse
No treatment for asymptomatic!
No vaccine
