chapter 39 - GI infections.pptx for mbbs

For mbbs and nursing

1. Gastrointestinal (GI) Infections

2. Learning objectives 2 At the end of the session, the students will be able to understand: Types of diarrhoeal diseases. Infections agents of acute diarrhea and the underlying mechanism. Identification features/ detection methods of common organisms causing acute diarrhea or dysentery and their pathogenic mechanisms

3. RESIDENT MICROBIAL FLORA 3

4. RESIDENT MICROBIAL FLORA 4 Human GIT is colonized by diverse group of normal resident microbial flora. Upper GIT contains only sparse flora (streptococci in oral cavity and lactobacilli in stomach). Lower GIT : The microbial load gradually increases towards lower part of GIT and is highest in the distal ileum (10 11 to 10 12 /g).

5. RESIDENT MICROBIAL FLORA (Cont..) 5 The large bowel comprises of both anaerobes and aerobes with a ratio of 1,000:1; with Bacteroides fragilis (most common) and Enterobacteriaceae such as E. coli, Klebsiella present predominantly Normal flora also comprises of yeasts (e.g. Candida ) and parasites (e.g. Entamoeba coli ).

6. DIARRHEAL DISEASES 6

7. DIARRHEAL DISEASES 7 Diarrheal diseases are one of the leading cause of illness globally; cause significant morbidity and mortality. Worldwide - 1.7 to 5 billion cases of diarrhea occur per year, with 1.26 million deaths; accounting for the second leading cause of death globally

8. Gastrointestinal infective syndromes 8 Diarrheal diseases Diarrhea Dysentery Traveler’s diarrhea Persistent (chronic) diarrhea Gastroenteritis Food poisoning Other gastrointestinal infective syndrome Acute vomiting Necrotizing enterocolitis Necrotizing enteritis Pseudomembranous enterocolitis Tropical sprue Peptic ulcer disease Infections of other GI structures such as appendicitis, diverticulitis and typhlitis

9. Diarrhea 9 Diarrhea - defined as passage of three or more loose or liquid stools per day, in excess than the usual habit for that person (World Health Organization). Caused by microbial infections, or as a result of other gastrointestinal diseases such as inflammatory bowel diseases, coeliac disease, etc. Acute diarrhea usually lasts for <14 days; most often caused by viral agents, followed by bacterial or parasitic agents

10. Dysentery 10 Dysentery is characterized by diarrhea with increased blood and mucus, often associated with fever, abdominal pain, and tenesmus (feeling of constant need to pass stools, despite an empty colon)

11. Infections agents of acute diarrhea and the underlying mechanism 11 Mechanism Features Examples of pathogens involved Non-inflammatory Location: Proximal small bowel Illness: Watery diarrhea Stool findings: No fecal leukocytes Fecal lactoferrin —not increased or mildly increased Bacteria (mostly enterotoxin mediated): Vibrio cholerae Escherichia coli: Enteropathogenic (nontoxigenic) Enterotoxigenic Enteroaggregative Clostridium perfringens Bacillus cereus Staphylococcus aureus Aeromonas hydrophila Plesiomonas shigelloides Parasites (Protozoa): Giardia lamblia Cryptosporidium parvum Cyclospora cayetanensis Cystoisospora belli Blastocystis hominis

12. Infections agents of acute diarrhea and the underlying mechanism (Cont..) 12 Mechanism Features Examples of pathogens involved Non-inflammatory Location: Proximal small bowel Illness: Watery diarrhea Stool findings: No fecal leukocytes Fecal lactoferrin —not increased or mildly increased Viruses: Rotavirus Norovirus Enteric adenoviruses- 40,41 Caliciviruses Astrovirus Fungi: Microsporidia Parasites (Helminths): Ascaris lumbricoides Hookworm Strongyloides stercoralis Enterobius vermicularis Trichinella spiralis Taenia saginata , T. solium Hymenolepis nana Dipylidium caninum Diphyllobothrium latum Fasciolopsis buski

13. Infections agents of acute diarrhea and the underlying mechanism (Cont..) 13 Mechanism Features Examples of pathogens involved Inflammatory (invasion or cytotoxin ) Location: Colon or distal small bowel Illness: Dysentery or Inflammatory diarrhea Stool findings: Fecal pus cells ( polymorphonuclear leukocytes)—increased Fecal lactoferrin —markedly increased Predominantly dysentery: Shigella species Campylobacter jejuni Enterohemorrhagic E. coli Enteroinvasive E. coli Vibrio parahaemolyticus Predominantly inflammatory diarrhea: Non- typhoidal salmonellae Yersinia enterocolitica Listeria monocytogenes Clostridioides difficile Plesiomonas shigelloides Klebsiella oxytoca Parasite: (predominantly dysentery) Entamoeba histolytica Balantidium coli Trichuris trichiura Schistosoma mansoni Schistosoma japonicum

14. Infections agents of acute diarrhea and the underlying mechanism (Cont..) 14 Mechanism Features Examples of pathogens involved Penetrating Location: Distal small bowel Illness: Enteric fever Stool findings: Fecal mononuclear leukocytes (↑) Salmonella Typhi , (enteric fever) Yersinia enterocolitica (typhoid like illness)

15. Traveler’s Diarrhea 15 Most common travel-related infectious illness. Clinical presentation: Most cases begin within the first 3–5 days; characterized by a sudden onset of abdominal cramps, anorexia, and watery diarrhea. The illness is generally self-limited, lasting for 1–5 days

16. Traveler’s Diarrhea (Cont..) 16 Overall, enterotoxigenic Escherichia coli is the most common agent, followed by enteroaggregative E. coli. Campylobacter jejuni - more common in Asia. Norovirus diarrhea - associated with traveling on cruise ships.

17. Agents causing traveler’s diarrhea 17 Etiologic agent Comments Bacteria ( 50–75%) Enterotoxigenic E. coli (10–45%) Single most important agent Enteroaggregative E. coli (5–35%) Emerging enteric pathogen with worldwide distribution Campylobacter jejuni (5–25%) More common in Asia Shigella , Enteroinvasive E.coli Major cause of dysentery Non- typhoidal salmonellae Common agent in India Others Including Aeromonas , Plesiomonas , and Vibrio cholerae

18. Agents causing traveler’s diarrhea (Cont..) 18 Etiologic agent Comments Viruses (<20%) Norovirus (<10%) Associated with cruise ships Rotavirus (<5%) Common among children Parasites (0–10%) Giardia lamblia , Cryptosporidium , Entamoeba histolytica , Cyclospora

19. Persistent and Chronic Diarrhea 19 Diarrhea that lasts for ≥ 14 days (usually 2-4 weeks) is considered persistent. Chronic diarrhea usually lasts for >4 weeks. May result from infections due to various organisms. Parasites (e.g. Cryptosporidium, Cyclospora, Entamoeba histolytica , Giardia ) account for a major cause of chronic diarrhea

20. Persistent and Chronic Diarrhea (Cont..) 20 Bacteria (e.g. Aeromonas , Campylobacter, Clostridium difficile, Plesiomonas ) Viruses - cytomegalovirus, common in immunocompromised host Fungi - microsporidia, common in immunocompromised host.

21. Gastroenteritis 21 Gastroenteritis or infectious diarrhea - defined as inflammation of the mucous membrane of the stomach and intestine resulting in combination of diarrhea, vomiting and pain abdomen with or without mucus or blood in stool, fever or dehydration.

22. Food Poisoning 22 Food poisoning refers to an illness acquired through consumption of food or drink contaminated either with microorganisms, or their toxins

23. Pathogenic Mechanisms 23 Inoculum Size Adherence Toxin Production Invasion

24. Pathogenic mechanisms of diarrheal agents 24 Toxin production Enterotoxins Cholera toxin Vibrio parahaemolyticus E. coli LT and ST of ETEC EAST of EAEC VT of EHEC Clostridioides difficile (toxin A) Aeromonas Rotavirus (NSP4) Campylobacter jejuni Cytotoxins Shigella dysenteriae type 1 Enterohemorrhagic E. coli Clostridioides difficile (toxin B) Neurotoxins Staphylococcus aureus enterotoxin Bacillus cereus toxin Clostridium botulinum toxin

25. Pathogenic mechanisms of diarrheal agents (Cont..) 25 Attachment within or close to mucosal cells Invasion of intestinal epithelium E. coli Enteropathogenic Enterohemorrhagic Cryptosporidium species Cyclospora species Cystoisospora species Rotavirus Norovirus Shigella species Enteroinvasive E. coli Campylobacter jejuni Yersinia enterocolitica Plesiomonas shigelloides Entamoeba histolytica Balantidium coli

26. Predisposing Factors 26 Suppression of the normal flora Neutralization of gastric acidity Inhibition of intestinal motility Age and location Antibiotic-associated Impaired host immunity Genetic determinants

27. Laboratory Diagnosis 27 Specimen Collection: Fecal specimen (containing mucus flakes) - collected in a sterile screw capped wide mouthed container. In carriers - a rectal swab may be collected. Specimens should be transported to the laboratory within 1 hour If a delay of longer than 1 hour is anticipated - fecal specimen should be collected in transport media

28. Laboratory Diagnosis (Cont..) 28 Macroscopy: Color of the specimen Consistency of the specimen—formed, semiformed or liquid Presence of blood (suggestive of dysentery), mucus or pus (suggestive of inflammatory diarrhea) Presence of adult parasitic forms, e.g. Enterobius , Ascaris , or Taenia segments.

29. Laboratory Diagnosis (Cont..) 29 Microscopy: Wet mount preparation Hanging drop preparation Gram stained smear Modified acid fast staining Electron microscopy

30. Laboratory Diagnosis (Cont..) 30 Bacterial Culture: Culture media Identification Antimicrobial susceptibility test

31. Laboratory Diagnosis (Cont..) 31 Tissue Culture: This is carried out for the detection of enteric viruses and also for some diarrheagenic E. coli. Enterotoxigenic Escherichia coli (ETEC) penetrates HeLa and HEp-2 cell line, whereas verocytotoxin of enterohemorrhagic Escherichia coli (EHEC) is detected by its cytotoxic effect on Vero cell line.

32. Laboratory Diagnosis (Cont..) 32 Antigen Detection: ELISA is available for detection of rotavirus antigen in Stool Rapid tests - immunochromatographic test is available for simultaneous detection of antigens of three parasites Entamoeba histolytica , Giardia and Cryptosporidium in stool Latex agglutination test - available to detect E. coli O157 antigen in stool Rapid test - available to detect C. difficile antigens (glutamate dehydrogenase and toxin A/B) in stool.

33. Laboratory Diagnosis (Cont..) 33 Molecular Methods: Polymerase chain reaction (PCR) assays can be carried out for the detection specific genes of enteric pathogens BioFire FilmArray : Fully automated commercial nested multiplex PCR. Its gastrointestinal panel is used to detect common bacterial, viral, parasitic diarrheal pathogens.

34. Laboratory Diagnosis (Cont..) 34 Other Methods: Methylene blue preparation Fecal lactoferrin

35. Identification features/ detection methods of common organisms causing acute diarrhea or dysentery. 35 Enteric bacteria Presentation Identification features Vibrio cholerae Watery diarrhea Darting motility Coma-shaped gram-negative bacilli in culture smear TCBS agar: Sucrose fermenting yellow colored colonies Identification: By conventional biochemical tests or automated methods like VITEK or MALDI-TOF Agglutinates with Vibrio cholerae O1 antisera and ogawa antisera (this is the most common pattern; though other serotypes are also present) Shigella Dysentery Gram-negative bacilli, non-motile MAC or DCA: Non-lactose fermenting translucent colonies XLD: Red colonies without black center Identification: By conventional biochemical tests or automated methods like VITEK or MALDI-TOF Agglutinates with Shigella polyvalent antisera and specific monovalent antisera

36. Identification features/ detection methods of common organisms causing acute diarrhea or dysentery (Cont..) 36 Enteric bacteria Presentation Identification features Group B Salmonella Inflammatory diarrhea Gram-negative bacilli, motile MAC: Non-lactose fermenting translucent colonies DCA: Non-lactose fermenting colonies with black center XLD: Red colonies with black center Identification: By conventional biochemical tests or automated methods like VITEK or MALDI-TOF Agglutinates with Salmonella poly-O antisera and serotype (O4) specific antisera Viral agents Diarrhea Agents: Rotavirus, Norovirus, Adenovirus 40, 41, etc. Detection of viral particles in stool specimen by electron microscopy Detection of viral antigen by ELISA or Detection of nucleic acid (RNA or DNA) by PCR in stool specimen

37. Identification features/ detection methods of common organisms causing acute diarrhea or dysentery (Cont..) 37 Intestinal parasites Presentation Stool microscopy detects Entamoeba histolytica Dysentery Trophozoites and/or quadrinucleated round cyst Detection of specific antigen (e.g. lectin)/specific genes in stool Giardia intestinalis Fatty diarrhea Trophozoites (tear drop-shaped binucleated ) with four pairs of flagella and/or Tetra-nucleated oval cyst with a central axoneme Trichuris Dysentery Barrel-shaped eggs with mucus plugs at both ends, bile stained Enterobius vermicularis Nocturnal anal pruritus Plano-concave egg containing larva, nonbile stained Ascaris lumbricoides Malabsorption Fertilized egg: Round-oval, thick albumin coat, floats in saturated saline, bile stained Unfertilized egg: Elongated, thin albumin coat, does not float in saturated saline, bile stained Hookworm Diarrhea, anemia Egg: Oval, contains segmented ovum with four blastomeres, nonbile stained Strongyloides Diarrhea Detection of rhabditiform larva in stool microscopy

38. Treatment of Diarrhea 38 Treatment depends up on the severity. Fluid therapy (rehydration) is the main stay of treatment Anti-motility agents and adsorbents may be considered in moderate-to-severe diarrhea Empiric antibiotic therapy is required only for severe diarrhea

39. Treatment of diarrheal diseases (adapted from Sanford guideline). 39 Types of diarrhea Definition Treatment Mild diarrhea 1–2 unformed stools per day Minimal symptoms No interference with daily routine activities Hydration: Fluids Lactose-free diet and avoid caffeine No antibiotics required Moderate diarrhea 3–5 unformed stools per day With/without symptoms, Interferes with daily routine activities Fluids + Anti-motility agents (loperamide) + Adsorbents (bismuth subsalicylate) No antibiotics required Severe diarrhea ≥6 unformed stools per day ± temperature ≥101ºF, tenesmus, blood or fecal leukocytes Empirical: Ciprofloxacin or levofloxacin for 3–5 days Alternatives: Azithromycin (for 3 days) for Campylobacter Metronidazole or vancomycin for 10–14 days (for C. difficile )

40. OTHER INFECTIVE SYNDROMES OF GIT 40

41. OTHER INFECTIVE SYNDROMES OF GIT 41 1. Acute Nausea and Vomiting 2. Necrotizing Enterocolitis 3. Necrotizing Enteritis 4. Pseudomembranous Enterocolitis 5. Tropical Sprue

42. OTHER INFECTIVE SYNDROMES OF GIT (Cont..) 42 6. Esophagitis 7. Gastritis 8. Appendicitis 9. Diverticulitis 10. Typhlitis 11. Whipple’s Disease ( Tropheryma whipplei )

43. Questions: 43 Q1. Single most important agent of travelers diarrhea: Enterotoxigenic E. coli Enteroaggregative E. Coli Campylobacter jejuni NTS

44. Questions: 44 Q2. Examples of bacterial pathogens causing inflammatory acute diarrhoea : Bacillus cereus Enteroaggregative E. Coli Norovirus NTS