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Infectious Diarrheas - Overview

Infectious Diarrheas - Overview. Greatest cause of morbidity and mortality worldwide Scope of disease: 1993,1999 - E.coli 0157:H7 1996-7 - Cyclospora 1998 - Vibrio parahaemolyticus 1993 - Cryptosporidium. GI Infectious – Factors increasing risk. Food-borne Travelers

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Infectious Diarrheas - Overview

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  1. Infectious Diarrheas - Overview • Greatest cause of morbidity and mortality worldwide • Scope of disease: • 1993,1999 - E.coli 0157:H7 • 1996-7 - Cyclospora • 1998 - Vibrio parahaemolyticus • 1993 - Cryptosporidium

  2. GI Infectious – Factors increasing risk • Food-borne • Travelers • Institutionalized settings

  3. GI Infections – Epidemiologic Factors • WHO you are • WHERE you are • WHEN it occurs

  4. GI Infections - Transmission • Fecal – oral route • Can include sexual transmission • Infectious inoculum

  5. GI Infections Host Defense Mechanisms • Hygiene • Gastric acidity • GI motility • Normal flora • Non-specific intestinal immunity • Mucosal associated antibody production

  6. GI Infections Microbial Virulence Factors • Adhesion • Toxins • Enterotoxins • Cytotoxins • Neurotoxins • Invasiveness

  7. Infectious Diarrheas Pathophysiologic Mechanisms • Enterotoxin-mediated - secretory • Vibrio cholera, enterotoxigenic E.coli • Inflammatory – cytotoxin-mediated • Systemic syndromes

  8. Infectious Diarrheas Enterotoxigenic E. coli (ETEC) • Adherence • Toxins • Heat labile toxin • Heat stable toxin

  9. Infectious Diarrheas – Clinical SyndromeEnterotoxin-mediated Gastroenteritis • History – Risk Factors • NO fever, systemic findings • Profuse watery stools NO fecal WBC’s • Small bowel • Often normal gross exam and histopathology

  10. Infectious Diarrheas – Pathophysiologic Mechanisms • Enterotoxin-mediated: secretory • Inflammatory: cytotoxin-mediated • Shigella, shiga-toxin producing E. coli, Clostridium difficile • Systemic syndromes

  11. Infectious Diarrheas – Shiga-toxin producing E. coli (STEC) • Food and water borne illness with high morbidity and mortality • Association with Hemolytic Uremic Syndrome (HUS) and Thrombotic Thrombocytopenic Purpura (TTP) • 25% hospitalized • 6% (15% children) develop HUS • 1% fatal • Shiga toxin production

  12. Infectious Diarrheas – Shiga Toxin • AB Toxin • Recognizes gal-1,4-gal residues • Blocks protein synthesis • Role in Hemolytic Uremic Syndrome (HUS) and Thrombotic Thrombocytopenic Purpura (TTP)

  13. Infectious Diarrheas – Clinical SyndromeInflammatory/Cytotoxin-mediated gastroenteritis • History • Dysentery • Risk Factors • Physical Exam/Labs • Fever, abdominal pain • Volume loss less prominent • Leukocytosis • WBCs and RBCs in stool • (+) toxin in stools

  14. Infectious Diarrheas – Pathology Inflammatory Cytotoxin-mediated gastroenteritis • Colon, large bowel • Limited to GI mucosa • Erosions, ulcerations

  15. GI Infections – Pathophysiologic Mechanisms • Enterotoxin-mediated - secretory • Inflammatory cytotoxin-mediated • Systemic syndromes • Salmonella, Yersinia

  16. GI Infections – Salmonella spp. • Typhoid fever, gastroenteritis • Typhi vs. non-typhi

  17. GI Infections – Salmonella Pathogenesis • Uptake by cells • Multiplication in mononuclear cells • Hematogenous dissemination • Replication in liver and spleen • Excretion in bile • Secondary bacteremia and entry into gut lumen

  18. GI Infections Salmonella Virulence Factors • Invasins – SPI-1 - Type III secretion system • Intracellular pathogen • Resistance to defensins • Survival in phagocytes - phoP/phoQ • Resistance to oxygen radicals • Resistance to low pH

  19. GI Infections Salmonella Virulence Factors • Systemic dissemination – SPI-2 (Type III secretion system) • Resistance to complement-mediated cytotoxicity • Long O antigen • rck – outer membrane protein • Capsular polysaccharide – Vi antigen

  20. GI InfectionsSalmonella – Clinical Syndrome • History – Risk Factors • Systemic illness Diarrhea often not prominent • Laboratory • Anemia, leukopenia, elevated liver function studies • (+) Blood cultures • (+) Stool cultures

  21. Infectious Diarrheas – Viral • Rotavirus • Caliciviruses/Norwalk-like viruses • 40% cases infectious diarrhea in U.S. • No toxin identified but produce histologic changes and alterations in fluid/electrolyte absorption/secretion • Small bowel; no fecal WBCs

  22. Infectious Diarrheas - Diagnosis • History • Risk factors •  Systemic symptoms • Character of stool • Physical Exam • Direct stool exam • Gross description • Fecal leukocytes • Exam for parasites

  23. Infectious Diarrheas - Diagnosis • Immunoassays for toxins, viruses • Stool culture • May be of limited use for E. coli • Not routinely performed for viruses • Blood culture • Only useful for systemic infections e.g. Salmonella

  24. Infectious Diarrheas - Treatment • Fluid and electrolyte replacement • Antibiotic therapy • Contra-indication?: Shiga-toxin producing E. coli • Epidemiologic considerations

  25. Infectious Diarrheas - Prevention • Adequate water, sanitation facilities** • Hygiene • Food handling • Vaccines

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