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Introduction• GI defenses• Normal flora
Mouth and Esophagus• Dental infections• Candida infection
Stomach• Helicobacter infection
Intestine• Food poisoning• Non-food-related diarrhea
LECTURE OUTLINE
Food Poisoning
• Main bug details• gram stain, morphology
• pathogenic features
• food of choice
• Clinical setting
• Diagnosis
• Frequency of food poisoning is increasing!• more fresh fruit/vegetables• more pre-cooked foods• more kinds of food
• 5,000 deaths, 325,000 hospitalizations, 76 million illnesses
• FDA resources can’t keep up!
Food Poisoning
E. coli
Clostridium
Staphylococcus
Campylobacter
Yersinia
Listeria
Vibrio
Salmonella
Bacillus
Eating
Contaminated
Stuff
Causes
You
Lots of
Very
Smelly
Barf
Food Poisoning
• Staphylococcus• Salmonella• Shigella• Campylobacter• E. coli• Yersinia• Vibrio• Bacillus• Listeria• Clostridium
The bugs:
Food Poisoning
• gram-positive cocci
• enterotoxins • made in food• survive high temps
• nose, skin
Staphylococcus
Food Poisoning
• gram-negative rod• motile • injects proteins, causing “ruffles”• replicates in host cells• sensitive to stomach acid
Salmonella
Food Poisoning
• gram-negative rod• microaerophilic • likes warm places• C. jejuni (diarrhea), C. fetus (sepsis)• cells eat bugs, then die• monocytes can carry bugs into blood
Campylobacter
Food Poisoning
• gram-negative rod• motile • EHEC strains• O and H antigens• cytotoxins damage vessels
E. coli
Food Poisoning
E. coli outbreak: raw spinach
• October 2006
• 3 died, over 200 became ill
• Traced to spinach grown in central California
• Grazing deer or water contaminated with cattle feces
E. coli outbreak: Taco Bell
• November-December 2006
• 70+ became ill
• Green onions vs. lettuce
• Contamination at packing plant?
• gram-negative rod• single flagellum • likes water• can tolerate acid• makes toxins
Vibrio
Food Poisoning
• gram-positive rod• heat resistant• hides out in host cell cytoplasm• mild GI illness in most• meningitis, sepsis in fetuses, elderly
Listeria
Food Poisoning
• gram-positive rod• anaerobic• spores• toxins• C. botulinum: progressive paralysis
• adults usually recover• babies may not
• C. perfringens: diarrhea
Clostridium
Food Poisoning
• enterocolitis• self-limited, usually• serious complications rare• incubation time varies• fever, tenderness on exam
Clinical
Food Poisoning
Introduction• GI defenses• Normal flora
Mouth and Esophagus• Dental infections• Candida infection
Stomach• Helicobacter infection
Intestine• Food poisoning• Non-food-related diarrhea
LECTURE OUTLINE
• Important cause of death worldwide
• Here, more bothersome than deadly
• Three categories: • secretory diarrhea• invasive diarrhea• antibiotic-associated diarrhea
Non-Food-Related Diarrhea
• loss of fluids, electrolytes from small intestine
• mild (traveler’s diarrhea) to severe (cholera)
Definition
Secretory Diarrhea
• Enterobacteriaceae (E. coli, others)
• Vibrionaceae (Vibrio, Campylobacter)
Pathogens
Secretory Diarrhea
Transmission
• fecal-oral route
• … feces, food, fluids, fingers, flies, fomites, fornication
• some bugs require only a small inoculum!
• No matter how clean we think we are…if sh*t was red, the world would be pink.
Secretory Diarrhea
Pathogenesis
• proximal small intestine• different bugs have different mechanisms
Secretory Diarrhea
V. cholerae
• virulence genes switch on in intestine• cholera toxin binds to epithelium, gets eaten• toxin activates adenylate cyclase cAMP → Na+ absorption, Cl- excretion• water moves into gut by osmosis, leading to diarrhea
Secretory Diarrhea
ETEC
• Enterotoxins change fluid transport in the gut…• …so instead of absorbing, the gut is secreting.• like cholera toxin, but less serious
Secretory Diarrhea
EPEC
• complex mechanisms – no toxin
• actin-rich pedestals
• beyond that, unclear mechanisms
Secretory Diarrhea
Clinical
• most cases acute, self-limiting• except V. cholera and EPEC illnesses,
which can be fatal
Secretory Diarrhea
Stool culture
• selective media• differential media Further testing
• strains, virulence factors• useful for epidemiology
Secretory Diarrhea
Definition
• cause: bugs that invade the intestine• result: bloody diarrhea or dysentery• bugs: Shigella and EHEC
Invasive Diarrhea
Shigella: characteristics
• gram-negative rod
• species: S. dysenteriae (dysentery) S. flexneri S. boydii S. sonnei (secretory diarrhea)
Invasive Diarrhea
Shigella: pathogenic features
• changeable phenotype!• Acid-resistant in stomach, invasive in intestine• Pure selfishness: whatever works best. • Acidity turns on the genes for acid resistance!
Invasive Diarrhea
• Approach.
• Sneakiness.
• Eating.
• Prodding.
• Escape.
• Finger.
• Ulcer.
Shigella: pathogenic features
Invasive Diarrhea
• Shiga toxin stops protein synthesis• decreases Na+ absorption (watery stools)• damages endothelial cells (bloody stools)• worst result: HUS
Shigella: toxin
Invasive Diarrhea
Diseases caused by E. coli:
• Diarrhea• Urinary tract infection• Neonatal sepsis• Gram-negative sepsis
E. coli transmitted in DUNG-contaminated water
Invasive Diarrhea
Enterohemorrhagic E. coli (EHEC): characteristics
• gram-negative rod
• many strains cause invasive diarrhea
• O (cell wall) and H (flagellar) antigens
• O157:H7 most common
Invasive Diarrhea
EHEC: pathogenic features
• toxins (inactivate RNA, like Shiga toxin)• endothelial damage (toxin + cytokines)• end result: bloody diarrhea and/or HUS
Invasive Diarrhea
EHEC: diseases• GI complications
• sometimes, asymptomatic• often, bloody diarrhea (hemorrhagic colitis)• usually resolves in a week
• HUS• 1 in 10 people with severe diarrhea get HUS• #1 cause of acute renal failure in children• triad: MAHA, thrombocytopenia, renal failure• can be fatal (especially in children, elderly)
Invasive Diarrhea
• Common in hospitalized patients!
• Broad-spectrum antibiotics:• reduce normal flora• interfere with carb breakdown
• Clostridium difficile underlies most cases
Antibiotic-Associated Diarrhea
Mnemonic for C. difficile infection:
It’s difficult to be in a closet with someone having
explosive foul-smelling diarrhea,
because it smells and there is no air in there.
Antibiotic-Associated Diarrhea
Bug characteristics
• gram-positive rod
• obligate anaerobe
• forms spores
• hard (‘difficile’) to grow!
• makes exotoxins
Antibiotic-Associated Diarrhea
Pathology
• exotoxins cause cell death, shallow ulcers, pseudomembranes
• early lesions superficial
• may eventually invade
Antibiotic-Associated Diarrhea
Epidemiology
• 30% of hospitalized patients!
• elderly at greater risk
• associated with antibiotics
• also with chemotherapy, enemas, enteric feeding
• spread patient to patient by hospital personnel
Antibiotic-Associated Diarrhea
Disease severity
• wide spectrum
• asymptomatic to fulminant colitis
• usually: just diarrhea
• amount of toxin is unrelated
Antibiotic-Associated Diarrhea
Forms of disease
• Diarrhea
• Pseudomembranous colitis
• Osmotic diarrhea
• Fulminant colitis
Antibiotic-Associated Diarrhea
Diagnosis
• stool smear
• forget culture
• toxin detection
• scope dangerous
Antibiotic-Associated Diarrhea