12: Infectious Diarrhea

Question 1

What is diarrhea?

Answer 1

• Passage of 3+ loose/liquid stools per day or bowel movements more frequently than is normal for the individual
• Infectious = enfectious etiology
• Acute: episode = 14 days
• Persistent: episode >14 days
• Chronic: >30 days

Question 2

Name the three enteric infections and their locations.

Answer 2

• Watery: small intestine
• Bloody (dysentery): colon
• Enteric fever: systemic

Question 3

For watery diarrhea:

1. Mechanism
2. Location
3. Pathogens

Answer 3

1. Non-inflammatory (enterotoxin or neurotoxin)
2. Proximal small bowel
3. Vibrio cholerae, ETEC, Clostridium perfringens, bacillus cereus (toxin only), staph aureus (toxin only)

Question 4

For bloody diarrhea (dysentery):

1. Mechanism
2. Location
3. Pathogens

Answer 4

1. Inflammatory (invasion or cytotoxin)
2. Colon or distal small bowel
3. Shigella, salmonella, campylobacter jejuni, EHEC, clostridium difficile

Question 5

For enteric fever:

1. Mechanism
2. Location
3. Pathogens

Answer 5

1. Penetrating systemic infection
2. Distal small bowel
3. Salmonella typhi/paratyphi, Yersinia enterocolitica

Question 6

Which bacterial pathogens are spread easily person-to-person?

Answer 6

Shigella spp.

Salmonella typhi/paratyphi

Question 7

Describe the pathogenic mechanisms of diarrhea.

Answer 7

• Toxin production
  
  • Enterotoxins: act directly on secretory mechanism in intestinal mucosa (vibrio cholerae, ETEC, clostridium perfringens)
  • Cytotoxins: destroy mucosal cells and assoc’d w/ inflammatory diarrhea (shigella dysenteriae [shiga toxin], EHEC [shiga-like toxin])
  • Neurotoxins: act directly on central/peripheral nervous system (s. aureus, bacillus cereus)
• Invasion (shigella, salmonella)

Question 8

Describe the pathogenic mechanisms of neurotoxins.

Answer 8

• Staphylococcus aureus enterotoxin
  
  • Heat stable (incubation 2-4 hours)
  • Increases peristalsis by autonomic activation –> vomiting & diarrhea
• Bacillus cereus enterotoxin
  
  • Emetic (heat stable, elaborated in starch foods such as fried rice): incubation 1-6 hours
  • Diarrheal: Incubation 10-12 hours

Question 9

Describe vibrio cholerae

Answer 9

• Curved gram negative facultative
• O1 and O139 serogroups associated with epidemic and pandemic cholera
• To cause cholera, must have ~20 genes divided between two vibrio pathogenicity islands (VPI)
  
  • Cholera toxin (CT)
  • Colonizing factor (toxin-corgulated pilus [TCP])
• Virulence regulated by transmembrane protein ToxR
• Sx: 1L/hr fluid lose, afebrile
• Treat with doxycycline, but hydration key

Question 10

Describe shigella.

Answer 10

• Small, non-motile GNR; member of enterobacteriaceae
• S. dysenteriae type A1 most potent producer of Stx (shiga toxin): disrupts protein synthesis and produces endothelial damage
• Invasion of intestinal epithelial cells (small–>large intestines); ulceration and abscess formation
• Enterotoxin and cytotoxin elaboration
• Penetration beyond mucosa rare
• Pathogenesis
  
  • Invades M cells
  • Taken up by macrophages
  • Avoids phagosome
  • Multiplies in cytoplasm
  • Activates caspases causing macrophage death
  • Ipa (invasion plasmid antigens) injected into epithelial cells via type III secretion system
  • Cell actin reorganize, allowing bacteria to move from cell to cell
  • Ruffles membrane, invades and inflames epithelium
• Onset ~ 12 hours
• Sx: initially water diarrhea and fever –> bloody mucoid stools, tachycardia, abdominal pain
• Duration ~ 7 days
• Rx: ciprofloxacin (decr. transmission)

Question 11

Describe escherichia coli.

Answer 11

• Lactose-fermenting GN rods, pili, flagella, many toxins (STX-1,2)
• Human GI tracts of many animals (main reservoir for EHEC)
• Enterotoxigenic (ETEC): traveler’s diarrhea; tx w/ abx
• Enterohemorrhagic (EHEC O157:H7)
  
  • Hemorrhagic colitis
  • Produces STX-1,2
  • Hemolytic uremic syndrome (HUS) in children
  • Type III secretion apparatus secretes proteins which disrupt & reorganize host cell actin
  • Outbreaks: ground beef, water, apple cider, spinach

Question 12

Describe salmonella.

Answer 12

• Gram negative, facultative anaerobic rod
• S. enterica has 2500+ serotypes
  
  • S. enterica serovar typhimurium: nontyphoidal salmonella; colonizes virtually all animals, so transmission through contaminated food
    
    • Gastroenteritis (nausea, voiting, diarrhea 24 hours after ingestion)
    • Bacteremia
    • Tissue invasion/localized infections
  • S. enterica serovar typhi/paratyphi: strict human pathogens, fecal-oral transmission
    
    • Enteric (typhoid) fever 5-21 days after ingestion; persists 4-8 weeks if untreated; rose spots & hepatosplenomegaly
    • Complications: death, intestinal perforation, abscesses, endocarditis, relapse
• Pathogenesis similar to salmonella
• For typhoid, tx = ciprofloxacin

Question 13

Identify the common food vehicles for specific pathogens/toxins.

Answer 13

1. Undercooked chicken: salmonella, campylobacter
2. Eggs: salmonella
3. Unpasteruized milk: salmonella, campylobacter, yersinia
4. Water: campylobacter
5. Fried rice: bacillus cereus
6. Shellfish: vibrio
7. Sushi: campylobacter
8. Beef/gravy: salmonella, campylobacter, EHEC