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Gastrointestinal Bacterial Infections

Gastrointestinal Bacterial Infections. Liliana Rodr í guez, MPH, RM (AAM), M(ASCP) UT Health Science Center at Houston Liliana.F.Rodriguez@uth.tmc.edu. Learning Objectives. Understand the definition of diarrhea and other gastrointestinal syndromes.

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Gastrointestinal Bacterial Infections

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  1. Gastrointestinal Bacterial Infections Liliana Rodríguez, MPH, RM (AAM), M(ASCP) UT Health Science Center at Houston Liliana.F.Rodriguez@uth.tmc.edu

  2. Learning Objectives • Understand the definition of diarrhea and other gastrointestinal syndromes. • Learn the classification of diarrhea and the microorganisms associated with each type. • Learn the mechanisms utilized by microorganisms to cause disease in the GI tract, and be able to list examples.

  3. Learning Objectives • Learn the definitions of endotoxin, exotoxin, enterotoxin and cytotoxin and be able to list examples of each. • Understand the mechanisms of defense in the GI tract and the role of the normal flora. • Understand the global impact of diarrheal disases.

  4. Learning Objectives • Understand the general morphology, physiology, and virulence factors of major bacterial pathogens of the GI tract. • Understand the molecular pathogenesis of the major GI bacterial diseases. • Learn the epidemiology, clinical features, diagnosis, basic treatment and prevention of GI bacterial infections.

  5. The Gastrointestinal Tract

  6. GI Tract (Enteric) Infections • Most common infections seen by primary care physicians in USA. • Leading cause of infant mortality worldwide, killing 2-3 million children/year. • In some countries, a 7 years-old or younger child’s chance of dying of a diarrheal illness can be as high as 50%. • 300 children die of diarrhea in the U.S. each year along with 4000 elderly, AIDS and transplant patients.

  7. GI Tract (Enteric) Infections • Diarrheal disease control is a major goal of the World Health Organization. • Traveler's diarrhea has a high economic impact. • GI Tract can be the major portal of entry but not prime target (Polio, hepatitis A, botulism), OR • Major portal of entry and prime target in most cases (Shigellosis, Cholera, Traveler’s Diarrhea).

  8. Clinical Features • fever • vomiting • abdominal pain • diarrhea • presence of these symptoms varies with different diseases, and the different stages of infection

  9. Definition of Diarrhea • An abnormally frequent discharge of semisolid or fluid fecal matter. • Usually involving increased fluid and electrolyte loss. • Can be watery or bloody. • Method by which the host forcibly expels the infecting microorganism(s).

  10. Classification of Diarrhea • Watery diarrhea • no blood or pus • caused by enterotoxins • small bowel (proximal or distal) • self-limiting • examples: Traveler’s diarrhea, cholera

  11. Classification of Diarrhea II. Bloody diarrhea • structural damage to the intestine • large bowel • invasion or damage to the mucosa by cytotoxins • usually requires treatment • examples: non-typhoid Salmonella, Yersinia and Campylobacter

  12. Classification of Diarrhea III. Dysentery - inflammatory disorder • frequent passage of stool, blood and pus • tenesmus, fever, cramps • colon • serious, requires antibiotic treatment • typically caused by Shigella, Entamoeba histolytica (amoeba) IV. Diarrhea can also be classified as acute (<2 weeks) and chronic (>6 weeks)

  13. Pathophysiology of Diarrhea • Impaired fluid absorption • Increased fluid production* • toxin-mediated • mucosal injury (adhesion to enterocytes) • Motor disturbances

  14. Important Terms • Gastroenteritis – A syndrome characterized by GI symptoms including nausea, diarrhea and abdominal discomfort. • Enterocolitis - Inflammation involving the mucosa of the small and large intestines • Enteric fever (typhoid fever) – Disseminated infection involving multiple organs. Associated with Salmonella typhi.

  15. Other GI Clinical Syndromes • Gastric ulcers – H. pylori • Antibiotic-associated diarrhea – Cl. difficile • Food poisoning – Bacillus cereus, Clostridium perfringens, Cl. botulinum,S. aureus • In addition to bacteria, certain parasites and viruses are classified as enteric agents

  16. GI Defenses Against Infection • Mouth- flow of fluids, saliva • Esophagus – flow of liquids, peristalsis • Stomach – acid pH • Small intestine- peristalsis, bile, IgA, Peyer’s patches, shedding, normal flora • Large intestine- NF, peristalsis, shedding, mucus

  17. Normal Flora • 1011 to 1012 viable bacteria/gm of feces • Bacteriocins • Occupation of the mucosal surface • Immunogens • Vitamin K

  18. Distribution of Intestinal Flora Predominant Concentration Organisms (per gram) Obligate anaerobes Streptococci Staphylococci Neisseria >106 102 None Lactobacilli Streptococci <104 Anaerobes Bacteroides Coliforms E. coli Streptococci Candida Protozoa 106 109 1011

  19. Cast of Characters • Family Enterobacteriaceae • Escherichia coli (many serotypes) • Salmonella spp. (many serotypes) • Shigella spp. (4 species) • Yersinia enterocolitica (minor cause of diarrhea) • Family Vibrionaceae • Vibrio cholerae • Vibrio parahemolyticus • Family Campylobacteriaceae • Campylobacter jejuni

  20. Acquisition of GI Pathogens • Infections are acquired by the fecal-oral route (fecally-contaminated food, fluids, fingers, fomites, flies) • Infective dose • High, 10 6-8 (ETEC, Vibrio cholerae) • Intermediate 10 3-5 (Salmonella, Campylobacter) • Low,10-100 cells (Shigella, EHEC) • Evasion of host defenses

  21. Mechanisms of Pathogenesis A. Colonization 1. Adhesins fimbria or pili colonizing factor antigen (CFA) 2. Receptors glycoproteins D- mannose

  22. Pathogenesis B. Toxin Production • Endotoxin - LPS Gram-negative bacteria, extremely toxic to humans • Exotoxins –excreted • Enterotoxins - proteins that affect the small intestine without demonstrable histopathology. Vibrio cholerae, ETEC • Cytotoxins –produced by Shigella dysenteriae type 1 and certain E. coli serotypes; kill mammalian cells by inhibiting protein synthesis.

  23. Pathogenesis C. Invasion of Intestinal Mucosa Microbial cell Mucu Mucus Epithelial cell

  24. Enterobacteriaceae • Largest family of GNR • Found in soil, water, vegetation, humans, animals • Large rods, non-spore forming, facultative • Major reservoirs for R-factors • They ferment glucose • Most have surface pili for attachment • Oxidase negative

  25. Enterobacteriaceae (cont...) • Colon normal flora (E. coli, Klebsiella, Enterobacter). • Frank pathogens (Salmonella, Shigella, Yersinia, certain serotypes of E. coli). • Some typically encapsulated (K. pneumoniae). • Most are motile by peritrichous flagella except Shigella, Klebsiella and some E. coli. • Can cause disease in other organs, such as the urinary and respiratory tract.

  26. Classification Identification to species level by biochemical characteristics Below species level by ID of surface antigens, called serotyping cell wall antigens: O (somatic) flagellar antigens: H capsular antigens: K

  27. Production of fever by Lipid A

  28. Escherichia coli • Most abundant facultative bacteria in GI tract • Large rods, non-spore forming, facultative • Lactose fermenter (unlike Salmonella and Shigella) • Nornal flora of colon (human and many animals)

  29. Escherichia coli • Five groups cause intestinal disease. All share the property of adherence to the epithelium of the intestine. • Enterotoxigenic ETEC • Enteroaggregative EAEC • Enteroinvasive EIEC • Enteropathogenic EPEC • Enterohemorrhagic EHEC

  30. Enterotoxigenic E. coli (ETEC) • The most important cause of diarrhea in children in developing countries. • Main cause of traveler’s diarrhea. • Affects 50% of Americans traveling to Africa or Latin America. • Spread by contaminated water or food.

  31. ETEC: Epidemiology • High infecting dose • Worldwide distribution • All ages affected • No seasonal incidence • Infects only humans • Affects small intestine • 80,000 cases/yr in the US

  32. ETEC: Virulence Factors • General type 1 pili bind to D-mannose • Colonization factor antigens (CFA), bind to glycoproteins in the host’s cells

  33. LT - Heat-labile Similar to choleragen Immunogenic Plasmid-mediated LTI and LTII ST- Heat-stable Non-immunogenic Plasmid-mediated ST-a and ST-b ETEC: Enterotoxins

  34. ETEC: Clinical features • Watery diarrhea. • No white or red cells in stool. No inflammatory process in the gut. • Incubation period 1-4 days. • Abdominal cramps, nausea, profuse diarrhea for 3-4 days. • No fever. • Immunity mediated by sIgA antibodies against LT-toxin.

  35. Enteropathogenic E. coli (EPEC) • Major cause of diarrhea in poor countries • Infects primarily infants • Fever, nausea, vomiting and self-limiting watery diarrhea • Small intestine • Also called enteroadherent • 12 species identified by serotype (O111:H2, O55:H6)

  36. EPEC O:111 in small intestine

  37. EPEC: Pathogenicity • Attachment to enterocytes through bundle-forming pili (Bfp) • Proteins inserted into the cell membrane • Effacement of microvillus • No enterotoxin • Diarrhea from malabsorption Attachment-Effacing Lesions

  38. Enteroaggregative E. coli (EAggEC) • Cause of persistent diarrhea in developing countries • Affects mainly infants • Small intestine • Patients suffer of vomiting, low grade fever, watery (sometimes bloody) diarrhea and dehydration

  39. EAggEC: Pathogenicity • Adherence to enterocytes • Cytotoxin (?) • Secretion of mucus and trapping of the bacteria in a biofilm • Shortening of the villi, mononuclear infiltration and sometimes hemorrhage

  40. Enteroinvasive E. coli (EIEC) • Classical serotype O29:H- • Able to invade and destroy colonic epithelium • Food-borne disease • Important cause of pediatric diarrhea in developing countries

  41. EIEC: Epidemiology • Infects only humans • Associated with travel • Infections restricted to children under 5 years of age living in poor conditions • One outbreak in USA traced to contaminated imported cheese

  42. EIEC: Pathogenesis • Similar to Shigella • Attachment to the large intestine mucosa (plasmid-mediated) • Invasion of cells after endocytosis • Lysis of the endocytic vacuole, multiplication and spread to adjacent cells

  43. EIEC: Clinical Features • Resembles shigellosis, but less severe • From mild, watery diarrhea, to severe bloody diarrhea • Fever • Cramps • Blood and leukocytes in stool

  44. Enterohemorrhagic E. coli (EHEC)

  45. EHEC: Historical Perspective • 1982- First identified as a pathogen • 1985- Associated with HUS • 1990 outbreak in Missouri. • 1991 outbreak in Massachusetts. • 1993 - Multistate outbreak, 731 cases linked to hamburgers.

  46. EHEC: General Characteristics • About 50 serotypes • Also known as Verotoxin E. coli (VTEC) • The most important are O157:H7 O111:NM, O26:H11, O104, O45 • Acquisition of the Shiga-toxin gene?

  47. EHEC: Epidemiology • Outbreaks or sporadic zoonosis • Main reservoir: GI tract of cattle • Worldwide outbreaks • Most prevalent in warmer months; greater incidence among children <5 • Person-to-person infection common • Very low infective dose (~100 cells) • Sources: beef, unpasteurized milk, apple cider, untreated water

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