Infectious Diarrhea

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Infectious Diarrhea

• Charles S. Bryan, M.D.
• November 27, 2007

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Overview

• Worldwide the greatest single cause of morbidity
  and mortality
• Decisive role in world history
• Third most common syndrome seen in general
  practice in the United States

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Enteric host defenses

• Age
• Personal hygiene, physical barriers
• Gastric acidity
• Intestinal mobility
• Enteric microflora
• Specific immunity phagocytes, B-cell, T-cell
• Intestinal receptors

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Infectious doses of enteric pathogens

• Shigella 101-2
• Giardia lamblia 101-2
• Entamoeba histolytica 101-2
• Campylobacter jejuni102-6
• Salmonella 105
• E. coli 108
• Vibrio cholerae 108

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Old and new pathogens bacteria

• Old Salmonella, Shigella, invasive E. coli,
  Vibrio cholerae, Clostridium perfringens, S.
  aureus
• New Toxigenic E. coli, enterohemorrhagic E.
  coli, E. coli 0157H7, Yersinia, Vibrio
  parahemolyticus, Vibrio vulnificus,
  Campylobacter, Clostridium difficile, Aeromonas,
  Plesiomonas shigeloides

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Old and new pathogens viruses

• Old viral diarrhea
• New Reovirus, parvovirus, Norwalk agent,
  rotavirus, calcivirus, adenovirus, astrovirus,
  coronavirus

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Old and new pathogens parasites

• Old Entamoeba histolytica, Giardia lamblia
• New Cryptosporidium parvum, Isospora belli,
  Blastocystis hominis, Microsporidium

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Low-versus high-volume diarrhea

• Low volume (low water) colonic
• High volume (high water) small bowel
• OSMOTIC DIARRHEA high-volume diarrhea in which
  the measured fecal osmolality is less than 2 Na
  K
• SECRETORY DIARRHEA high-volume diarrhea in which
  the measured fecal osmolality equals 2 Na K
  
  

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Small- versus large-bowel diarrhea

• Small bowel (the runs) large, watery, less
  frequent, painless stools. Blood and WBCs are
  rare. Proctoscopy is normal. Pain is
  mid-abdominal.
• Large bowel (the squirts) small, often mucoid,
  more frequent, painful stools. Blood and WBCs are
  common. Proctoscopy is abnormal. Pain is
  lower-abdominal (left lower quadrant)

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Fecal leukocytes

• Shigellosis
• Enteroinvasive E. coli
• Clostridium difficile
• Salmonella enteritidis
• Vibrio parahemolyticus
• Ulcerative colitis
• Ischemic colitis

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Pathophysiologic mechanisms of infectious diarrhea

• Toxin production
• Enteroadherence
• Mucosal invasion
• Systemic infection

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Toxin production (examples)

• Preformed toxin Bacillus cereus, Clostridium
  perfringens, Staphylococcus aureus
• Enterotoxin Aeromonas species, enterotoxigenic
  E. coli, Vibrio cholerae
• Cytotoxin Clostridium difficile, E. coli 0157H7

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Enteroadherence (examples)

• Cryptosporidiosis (Cryptosporidium parvum)
• Cyclospora species (?)
• Enteroadherent and enteropathogenic E. coli
• Helminths
• Giardiasis (Giardia lamblia)

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Mucosal invasion

• Minimal invasion Norwalk virus, Rotavirus, other
  viruses
• Variable invasion Aeromonas sp., Campylobacter
  sp., Salmonella sp., Vibrio parahemolyticus
• Severe invasion Entamoeba histolytica,
  enteroinvasive E. coli, Shigella species

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Systemic infection

• Legionellosis
• Listeriosis
• Measles
• Psittacosis
• Rocky Mountain spotted fever
• Toxic shock syndrome
• Septicemia
• Viral hepatitis

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Enteric infection

• Noninflammatory (enterotoxin) proximal small
  bowel, watery diarrhea, no fecal leukocytes
• Inflammatory (invasion, ? cytotoxin) colon,
  dysentery, fecal polymorphonuclear leukocytes
• Penetrating distal small bowel, enteric fever
  syndrome, fecal mononuclear leukocytes

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Noninflammatory (enterotoxin) diarrhea

• Cholera
• Toxigenic E. coli
• Food poisoning syndromes Clostridium
  perfringens, Bacillus cereus, Staphylococcus
  aureus
• Viral rotavirus, Norwalk agent
• Parasitic giardiasis, Cryptosporidium
• ? Salmonella, ? Vibrio parahemolyticus

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Noninflammatory diarrhea

• Neonates enteropathogenic E. coli rotaviruses
  many other agents
• Healthy adults in temperate climates viruses,
  food poisoning, parasites
• Travelers enterotoxigenic E. coli others
• Adults in areas of poor sanitation cholera,
  entertoxigenic E. coli
• Hospitals Cl. difficile viruses Salmonella
• Chronic cases giardia, sprue, other

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Enteric bacterial toxins

• Neurotoxins Usually ingested preformed
  (examples Cl. botulinum, S. aureus, B. cereus)
• True enterotoxins Direct effect on intestinal
  mucosa to elicit fluid secretion (examples E.
  coli, V. cholerae Salmonella others)
• Cytotoxins Mucosal destruction causing
  inflammatory colitis (examples Shigella, E. coli
  0157H7 Clostridium difficile)

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Inflammatory diarrhea

• Colon
• Dysentery
• Fecal polymorphonuclear leukocytes
• Examples Shigella invasive E. coli Salmonella
  enteritidis Clostridium difficile Vibrio
  parahemolyticus ? Campylobacter jejuni

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Penetrating bowel infection (enteric fever)

• A systemic febrile illness originating from the
  distal small bowel with some combination of
  sustained fever, headache, rash, splenomegaly,
  positive blood cultures, and fecal mononuclear
  leukocytes, and mimicked by many diseases
• Examples Salmonella typhi Yersinia
  enterocolitica (yersinosis) ? Campylobacter fetus

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Syndromes of salmonellosis

• Gastroenteritis
• Enteric fever
• Bacteremia with or without metastatic disease
• Asymptomatic carrier state

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Nontyphoidal Salmonella

• Widely disseminated in nature, intimately
  associated with animals
• Contaminate 1/2 of chickens in U.S. also eggs
  unpasteurized milk fruits and vegetables
  marijuana reptiles (e.g., turtles, rattlesnakes)

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Salmonella required inoculum

• Dogma gt 105 needed to cause disease
• Recent outbreaks as few as 103
• Volunteer study placement of as few as 25
  organisms in the nose caused disease
• Required inoculum is reduced by raising gastric
  pH (atrophic gastritis antacids H2 blockers

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Bacteremia in salmonellosis

• Usually transient and inconsequential
• Sickle cell disease osteomyelitis
• Atherosclerosis mycotic aneurysm
• Underlying heart disease endocarditis
• Young children ? meningitis

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Salmonella carrier state

• 3 of cases of typhoid fever (recall Typhoid Mary
• 0.2 to 0.6 of symptomatic nontyphoidal
  infections (relevant especially to foodhandlers)
• High association with biliary tract disease and
  gallstones

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Shigellosis

• Highly communicable 10 to 40 of cases of
  diarrhea worldwide, especially small children
• Virulent strains involve colonic mucosa S.
  dysenteriae type 1 (Shiga bacillus) is the worst
• Often biphasic (large stools, then dysentery)
• Complications DIC, hemolytic-uremic syndrome

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E. coli diarrhea

• Enterotoxigenic watery diarrhea
• Enteropathogenic diarrhea with mucus
• Enteroinvasive dysentery with blood and mucus
• Enterohemorrhagic (E coli 0157H7) copious
  bloody diarrhea sometimes with the
  hemolytic-uremic syndrome
• Toxigenic ? mild diarrhea

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Shiga-toxin E. coli(0157H7 and other serotypes)

• Usually transmitted by beef, but many other foods
  transmit
• Low infectious dose (as few as 100 bacteria)
• Crampy abdominal pain, often disproportionate to
  physical findings
• Complications include hemolytic-uremic syndrome,
  thrombotic thrombocytopenic purpura

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Clostridium difficile

• 1970s Found to be the cause of enterocolitis
  related to the antibiotic clindamycin
• Pseudomembranous colitis with yellow-white
  plaques can progress to toxic megacolon
• At least two toxins (A and B) cause necrosis of
  epithelium
• Nosocomial transmission

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Clostridium difficile

• Colonization rate is 2 to 3 in healthy adults
  20 to 40 in hospitalized patients
• Widespread contamination of hospital environments
• Infection control measures including handwashing
  and gloves have been shown to reduce infection
  rates

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New epidemic strain of C. difficile(Bartlett,
Ann Intern Med 2006 145758-764)

• First recognized in Quebec now recognized as
  causing outbreaks in U.S.
• More serious and more refractory to therapy
• Increased rates of toxic megacolon, disease
  requiring colectomy, shock, and death
• Attributable mortality 17 (versus lt1! For other
  strains with therapy)
• Designated B1/NAP1

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Five features of C. difficile B1/NAP1

• Produces much larger quantities of toxins A and B
• Toxinotype III (based on analysis of a portion of
  the genome responsible for toxins A and B
• Shows deletion from its genome of tcdC, an 18
  base-pair sequence in the pathogenicity locus
  responsible for downregulation of toxin
  production
• Produces a binary toxin (unclear significance)
• Resistance to quinolone antibiotics

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Campylobacter infection

• Campylobacter fetus ssp. jejuni causes 5 to 7
  of cases of gastroenteritis contaminated food
  products are the most common source
• Symptoms diarrhea, cramps, anorexia, weight
  loss, nausea, dehydration
• Stool exam blood in 60, PMNs in 78
• Usually self-limited

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Yersinia enterocolitica

• Enterocolitis (2/3rds of cases) especially young
  children fever, diarrhea, abdominal pain
• Mesenteric adenitis/terminal ileitis fever, RLQ
  pain, leukocytosis
• Reactive polyarthritis, often with erythema
  nodosum (10 to 30 of adults in Scandinavia)
• Septicemia especially in children

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Yersinia pseudotuberculosis

• Mesenteric lymphadenitis resembling acute
  appendicitis
• Septicemia

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Vibrio parahemolyticus

• Seafood or raw shellfish
• Often in epidemics
• Diarrhea, abdominal cramps, nausea, fever,
  headache (42) may have fecal leukocytes
• Produces both an enterotoxin and an inflammatory
  reaction
• A halophilic (salt-requiring) vibrio readily
  isolated on TCBS agar

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Vibrio vulnificus

• Usually an extra-intestinal pathogen
• Septicemia, especially in persons with cirrhosis
  (ingestion of raw oysters is the classic vector
  history)
• Cellulitis after exposure of wounds to salt water

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Vibrio cholerae

• 01 serotype watery diarrhea, dehydration
  associated with residence in endemic areas
• non-01-serotypes diarrhea, fever, nausea,
  vomiting, blood in stool often associated with
  travelers diarrhea

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Aeromonas hydrophila

• Summer months
• Diarrhea and abdominal cramps
• Possibly both an enterotoxin and a cytotoxin
• Also causes severe cellulitis in wounds exposed
  to fresh water

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Entamoeba histolytica (amebiasis)

• Affects 10 of worlds population
• In the United States, affects up to 4
• Order of involvement cecum, ascending colon,
  rectum, sigmoid
• Flask-shaped ulcers
• Liver abscesses in up to 10

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Giardia lamblia (giardiasis)

• Waterborne
• Rocky Mountains Leningrad but also widespread
• Can cause diarrhea by several mechanisms
• Weight loss (62), cramps (61), steatorrhea
  (57), flatulence (35), vomiting (29),
  belching (26), fever (17)

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Cryptosporidium parvum

• Formerly best known as an animal pathogen
  infecting numerous species
• Severity and duration of human infection vary
  directly with immunocompetence
• Healthy adults self-limited diarrhea, usually
  lasting 10 to 14 days
• AIDS patients severe intractable diarrhea

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Rotavirus diarrhea

• Usually sporadic but can cause epidemics in
  institutions, including nursing homes
• Winter months in temperate climates usually
  infants and young children
• fecal-oral transmissions
• DNA virus with at least 2 sterotypes can be
  demonstrated with ELISA

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Norovirus diarrhea

• Typically epidemic, often traced to a common
  source
• Throughout the year
• Usually adults and school-aged children
• Often traced to contaminated food or water
• At least 3 serotypes can be demonstrated by
  immune electron microscopy or radioimmunoassay

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Travelers diarrhea

• E. coli the most common cause
• However, consider Salmonella, Shigella,
  Campylobacter, Amebiasis, Cholera, Vibrio
  parahemolyticus, Norwalk virus, others
• Many persons are infected by multiple pathogens