Gastrointestinal Infections

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Gastrointestinal Infections
Clinical Correlation Conference Med Micro Course
2008

• Sangita Dash, MD
• November 21, 2008

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Overview

• On the global scale, diarrheal diseases are the
  leading cause of childhood death
• Third most common syndrome seen in general
  practice in the US
• The frequency, type, and severity of these
  infections depend on
• Who you are
• Where you are
• When you are there

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Host factors

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

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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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Toxin production

• Neurotoxins (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

• 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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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 large volume, watery, less
  frequent, painless stools. Blood and WBCs are
  rare. Proctoscopy is normal. Pain is
  mid-abdominal.
• Large bowel small volume, 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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Noninflammatory vs inflammatory

• Noninflammatory diarrhea pathogens act primarily
  on small intestine to induce fluid secretions
• Voluminous watery diarrhea, nausea, vomiting,
  abdominal cramps, low grade fever
• Inflammatory diarrhea induce inflammation by
  invasion or cytotoxins
• Stools of small volume, fever, blood and mucus,
  tenesmus, abdominal cramping

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Overview of Infectious diarrhea

• ACUTE (symptoms ? 14 days)
• Community-acquired
• gram-negative bacterial pathogens
• Viral pathogens
• Norovirus family clusters, winter outbreaks
• Rotovirus children, seasonal peak in winter
• Protozoal pathogens
• Entamoeba Histolytica acute colitis with fever
  and dysentry
• Nosocomial ( gt 3 days after hospitalization)
• Clostridium difficile
• Travelers
• ETEC

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Overview of Infectious diarrhea

• PERSISTENT (symptoms gt 14 days)
• Parasitic Girdia lamblia, Cryptosporidium
  parvum, Cyclospora, Isospora belli
• Immunocompromised host also consider
  microsporidium, MAC, and CMV

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FoodNet Data, CDC 2005Incidence of Various
Pathogens per100,000 Population in U.S.

• Salmonella 14.55
• Campylobacter 12.72
• Shigella 4.67
• Cryptosporidium 2.95
• STEC (EHEC) O157H7 1.06
• Yersinia 0.36
• Vibrio 0.27

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Gram-negative Bacteria Associated with Diarrhea

• Campylobacter
• Salmonella
• Shigella
• Escherichia coli
• Yersinia enterocolica
• Vibrio
• Aeromonas

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Campylobacter jejuni

• Curved gram-negative rods
• Zoonotic infection and carried in GI tract of
  animals
• Poulty common source of infection
• Disease caused by ingestion of contaminated food
  or water
• Incubation period 1-7 days
• Two-thirds present with fever, headache, myalgias
  followed by abdominal pain and bloody diarrhea

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Campylobacter jejuni

• Fecal leukocytes
• Antibiotic therapy reserved for immunocompromised
  and those with severe symptoms
• Reactive arthritis 1 of patients. 1-2 weeks
  after diarrhea
• Associated with Guillain-Barre, usually 1-3 weeks
  after diarrhea. 20-40 GBS cases are attributable
  to antecedent C. jejuni infection

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Salmonella gastroenteritis

• Non-lactose fermenting gram-negative bacilli
• Non-typhoidal strains seen in the US (S.
  enterica) serovars S. typhimurium, S.
  enteritidis, etc
• Found in GI tracts of mammals, birds, reptiles
• Acquired from ingestion of contaminated poultry,
  eggs, meat and exposure to pet reptiles
• Fever, abdominal cramping, nausea, vomiting,
  diarrhea with fecal leukocytes
• Untreated diarrhea lasts 4-10 days

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Other syndromes of Salmonella

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

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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 (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

• Non-lactose fermenting gram-negative rod
• Four species
• S. dysenteriae
• S. flexneri
• S. boydi
• S. sonnei
• Highly infectious infectious dose lt 200
• Incubation period 1-7 days
• Symptoms can develop 12 hours after ingestion

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Shigellosis

• Presents as fever, abdominal pain, tenesmus,
  bloody diarrhea
• Bacteremia 4 of patients
• Reactive arthritis 1-2, 1-2 weeks (S. flexneri)
• S. dysenteriae can be associated with HUS
• Antimotility drugs have been associated with
  toxic megacolon
• self-limited but treatment recommended to prevent
  secondary spread to contacts

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E. coli gastroenteritis

• Enterotoxigenic watery diarrhea (travellers
  diarrhea)
• Enteropathogenic diarrhea in infants common in
  developing countries
• Enteroinvasive dysentery with blood and mucus
• Enterohemorrhagic (E coli 0157H7) copious
  bloody diarrhea sometimes with the
  hemolytic-uremic syndrome
• Enteroaggregative

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Enterohemorrhagic E. coli(0157H7)

• Most common strain in developed countries
• Usually transmitted by beef, but many other foods
  transmit. Associated with petting zoo
• Low infectious dose (as few as 100 bacteria)
• Shiga-toxin
• Crampy abdominal pain, often disproportionate to
  physical findings along with bloody diarrhea with
  little or no fever
• Complications include hemolytic-uremic syndrome
  in children, thrombotic thrombocytopenic purpura
  in adults

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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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Endoscopic view of multiple scattered, yellowish
plaques consistent with pseudomembranous colitis.
(From Iseman DT, Hamza SH, Eloubeidi MA.
Pseudomembranous Clostridium difficile colitis.
Gastrointest Endosc. 200256907.)
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Abdominal radiograph demonstrating markedly
dilated colon, wall edema, and loss of
haustration in a patient with Clostridium
difficile-associated pseudomembranous colitis
complicated by toxic megacolon. (From Agnifili A,
Gola P, Manno M, et al. The role and timing of
surgery in the treatment of pseudomembranous
colitis A case complicated by toxic megacolon.
Hepatogastroenterology. 199441394-396.)
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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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Yersinia enterocolitica

• Carried in GI tract of pigs, cattle, rodents,
  sheep, dogs and cats
• Infection acquired by inadequately cooked pork,
  unnpasteurized milk, contaminated water
• Diarrhea, fever, abdominal pain
• Mesenteric adenitis/terminal ileitis fever, RLQ
  pain, leukocytosis
• Reactive polyarthritis, often with erythema
  nodosum
• 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 ceacum, 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

• Bacterial
• Enterotoxigenic E. coli (ETEC)
• Shigella
• Salmonella
• Campylobacter
• Protozoa
• Giardia, Entamoeba, Cryptosporidium
• Virus
• Norwalk, rotavirus, enterovirus

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Enterotoxigenic E.coli

• Most common cause of travelers diarrhea
• Acquired by ingestion of fecally contaminated
  food or water
• Occurs 3-14 days after ingestion
• Causes watery diarrhea, abdominal cramps
  occasionally nausea and vomiting
• Self-limiting lasts 1-5 days

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Staphylococcal food poisoning

• Common food borne illness
• Infections originate from asymptomatic carriers
  of staphylococcus aureus
• Can contaminate processed meats, potato salad,
  ice-cream
• Preformed toxin (enterotixin) in food rather than
  from direct effect of organism
• Incubation period about 4 hours.
• Symptoms last lt 24 hours (no new toxin produced
  by ingested bacteria)
• Severe nausea and vomiting along with abdominal
  pain and diarrhea. No fever

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Helicobacter pylori

• 70-90 of population in developing countries.
  Almost 45 in developed countries
• Associated with gastritis, duodenal ulcer,
  gastric ulcer, gastric adenocarcinoma, MALT
  lymphomas
• Fecal-oral transmission