Infectious Diarrhea by Dr Arun Aggarwal Gastroenterologist

1. Infectious Diarrhea Dr. ArunAggarwal Gastroenterologist

2. Etiology • Diarrhea: noninflammatory and inflammatory. • Enteropathogens elicit noninflammatory diarrhea through enterotoxin production by some bacteria, destruction of villus (surface) cells by viruses, adherence by parasites, and adherence and/or translocation by bacteria. • Inflammatory diarrhea: caused by bacteria that invade the intestine directly or produce cytotoxins. By: Dr Arun Aggarwal Gastroenterologist

3. BACTERIA Aeromonas Bacillus cereus Campylobacter jejuni Clostridium perfringens Clostridium difficile Escherichia coli Plesiomonas shigelloides Salmonella Shigella Staphylococcus aureus Vibrio cholerae 01 and 0139 Vibrio parahaemolyticus Yersinia enterocolitica VIRUSES Astroviruses   Caliciviruses   Norovirus    Enteric adenoviruses  Rotavirus   Cytomegalovirus    Herpes simplex viruses Causative Agents of Gastroenteritis • Balantidium coli • Blastocystis hominis • Cryptosporidium parvum • Cyclospora cayetanensis • Encephalitozoon intestinalis • Entamoeba histolytica • Enterocytozoon b bieneusi    • Giardia lamblia • Isospora belli • Strongyloides stercoralis • Trichuris trichiura PARASITES By: Dr Arun Aggarwal Gastroenterologist

4. Chronic or persistent diarrhea lasting 14 days or more may be due to • an infectious agent such as Giardia lamblia, Cryptosporidium parvum, and enteroaggregative or enteropathogenic E. coli • any enteropathogen that infects an immunocompromised host • residual symptoms due to damage to the intestine by an enteropathogen after an acute infection. By: Dr Arun Aggarwal Gastroenterologist

5. Indications for stool examination for O & P • Pt have a history of recent travel to an endemic area, stool cultures are negative for other enteropathogens, and diarrhea persists for more than 1 wk • part of an outbreak of diarrhea • immunocompromised. By: Dr Arun Aggarwal Gastroenterologist

6. Epidemiology By: Dr Arun Aggarwal Gastroenterologist

7. Young age Immune deficiency Measles Malnutrition Travel to an endemic area Lack of breast-feeding Exposure to unsanitary conditions Ingestion of contaminated food or water Level of maternal education Attendance at a childcare center. Factors that increase susceptibility to infection with enteropathogens include: By: Dr Arun Aggarwal Gastroenterologist

8. Immune-Mediated Extraintestinal Manifestations of Enteric Pathogens

9. Specific Pathogens By: Dr Arun Aggarwal Gastroenterologist

10. Cholera • Gram negative, slightly curved rod. • V. cholera O1 and O139 are responsible for causing disease. • The two biogroups (or biotypes) of V. cholerae O1 are differentiated as classic and El Tor • V. cholerae O1 has two major O antigenic types (Ogawa and Inaba) and an unstable intermediate type (Hikojima). • V. cholerae O139 is closely related to the El Tor biotype By: Dr Arun Aggarwal Gastroenterologist

11. Epidemiology • Transmission is usually by fecal-oral spread with contaminated water. • Humans are the only known reservoirs of V. cholerae. • Colonization usually requires the ingestion of a large number of viable vibrios (>108 viable units), in part, because the organisms are killed by acid environments including the normal stomach. • The primary mechanism of fluid loss is activation of adenylyl cyclase at the cytoplasmic surface of the basolateral membrane by the enterotoxin, cholera toxin. By: Dr Arun Aggarwal Gastroenterologist

12. Clinical Features • Profuse, painless, watery diarrhea with a rice-water consistency and a fishy odor, sometimes with flecks of mucus but no blood. • Fecal leukocytes are not present because V. cholera does not invade the mucosa. • Diagnosis is primarily clinical. • The gold standard for cholera diagnosis remains stool culture on TCBS medium. By: Dr Arun Aggarwal Gastroenterologist

13. Treatment • Rehydration is the most important treatment. • Antibiotics are useful in shortening the duration of illness, reducing the period of excretion of the organisms, and decreasing the requirements for fluid replacement. • Doxycycline is drug of choice, Bactrim can be used for <8 yrs, quinolones are effective. By: Dr Arun Aggarwal Gastroenterologist

14. Complications • Lethargy, seizures, altered consciousness, fever, hypoglycemia, hyperglycemia, and death. • Inadequate fluid and electrolyte replacement may lead to acute tubular necrosis. • Hypokalemic arrhythmia can cause sudden death. • Children with low potassium levels can develop paralytic ileus and abdominal distention that can make oral rehydration impossible. • Pulmonary edema occurs in some children, probably because of fluid overload during rehydration. By: Dr Arun Aggarwal Gastroenterologist

15. Vaccine • Phenol-killed organisms administered parenterally as a two-dose primary series followed by boosters every 6 mo to maintain immunity. • Vaccine has about 50% efficacy by 3–6 mo after vaccination, does not protect against O139 vibrios, and is highly reactogenic (i.e., pain, erythema, local induration, fever, headaches). • Vaccine should be used only in very high-risk persons (e.g., those with achlorhydria) with a very high probability of exposure. • It is not recommended for children <6 mo of age. By: Dr Arun Aggarwal Gastroenterologist

16. Salmonella By: Dr Arun Aggarwal Gastroenterologist

17. Gram negative rod, don’t ferment lactose, grow aerobically. • Poultry and poultry products (mainly eggs) cause about half of the common-source outbreaks. • Meats, especially beef and pork, cause about 13% of the outbreaks, and raw or powdered milk and dairy products are the source of about 5% of the outbreaks. • The estimated number of bacteria that must be ingested to cause disease is 106–108 organisms. • Ingested Salmonella organisms reach the stomach, where acid is the first protective barrier. • Achlorhydria, buffering medications, rapid gastric emptying after gastrectomy or gastroenterostomy, and a large inoculum enable viable organisms to reach the small intestine. By: Dr Arun Aggarwal Gastroenterologist

18. In the small and large intestines, salmonellae have to compete with normal bacterial flora to multiply and cause disease; prior antibiotic therapy disrupts this competitive relationship. • After multiplication within the lumen, the organisms penetrate through the Peyer patches, typically at the distal part of the ileum and the proximal part of the colon. • Children with sickle cell disease are prone to Salmonella septicemia and osteomyelitis. By: Dr Arun Aggarwal Gastroenterologist

19. Clinical manifestations • The most common clinical presentation is acute enteritis. • After an incubation period of 6–72 hr (mean, 24 hr), there is an abrupt onset of nausea, vomiting, and crampy abdominal pain primarily in the periumbilical area and right lower quadrant, followed by mild to severe watery diarrhea and sometimes by diarrhea containing blood and mucus. • Fever (temperature of 101–102°F [38.5–39°C]). • The stool typically contains a moderate number of polymorphonuclear leukocytes and occult blood. • Symptoms subside within 2–7 days in healthy children. By: Dr Arun Aggarwal Gastroenterologist

20. Conditions That Increase the Risk of Salmonella Bacteremia During Salmonella Gastroenteritis • Neonates and young infants (≤3 mo of age) • AIDS, chronic granulomatous disease, and other immuno deficiencies • Malignancies, especially leukemia and lymphoma • Immunosuppressive and corticosteroid therapy • Hemolytic anemia, including sickle cell disease, malaria, and bartonellosis • Collagen vascular disease • Inflammatory bowel disease • Gastrectomy or gastroenterostomy • Achlorhydria or antacid medication use • Impaired intestinal motility • Schistosomiasis • Malnutrition By: Dr Arun Aggarwal Gastroenterologist

21. Diagnosis: stool culture, rectal swab, latex agglutination, serological assays • Treatment: correction of dehydration and electrolyte disturbances. • Antibiotics: ampicillin, bactrim, cefotaxime, ceftriaxone, quinolones By: Dr Arun Aggarwal Gastroenterologist

22. In patients with gastroenteritis, antimicrobial agents do not shorten the clinical course, nor do they eliminate fecal excretion of Salmonella. • By suppressing normal intestinal flora, antimicrobial agents may prolong the excretion of Salmonella and increase the risk of creating the chronic carrier state. • Antibiotics therefore are not indicated routinely in treating Salmonella gastroenteritis. • They should be used in infants (≤3 mo of age) and other children who are at increased risk of a disseminated disease . (previous table) By: Dr Arun Aggarwal Gastroenterologist

23. Shigella By: Dr Arun Aggarwal Gastroenterologist

24. Four species of Shigella are responsible for shigellosis: S. dysenteriae (serogroup A), S. flexneri (serogroup B), S. boydii (serogroup C), and S. sonnei (serogroup D). • Contaminated food (often a salad or other item requiring extensive handling of the ingredients) and water are important vectors. • Person-to-person transmission is probably the major mechanism of infection. • Shigellae require very low inocula to cause illness. Ingestion of as few as 10 S. dysenteriae serotype 1 organisms can cause dysentery. By: Dr Arun Aggarwal Gastroenterologist

25. The basic virulence trait shared by all shigellae is the ability to invade intestine. • The pathologic changes of shigellosis take place primarily in the colon. • Secretory IgA and serum antibodies develop within days to weeks after infection with Shigella. (protection is serotype specific). By: Dr Arun Aggarwal Gastroenterologist

26. Incubation period: 12 hr to several days. • Severe abdominal pain, high fever, emesis, anorexia, generalized toxicity, urgency, and painful defecation characteristically occur. • Physical examination may show abdominal distention and tenderness, hyperactive bowel sounds, and a tender rectum on digital examination. • The diarrhea may be watery and of large volume initially, evolving into frequent small-volume, bloody mucoid stools. By: Dr Arun Aggarwal Gastroenterologist

27. Neurologic findings occur in as many as 40% of hospitalized infected children. • Convulsions, headache, lethargy, confusion, nuchal rigidity, or hallucinations may be present before or after the onset of diarrhea. • The most common complication of shigellosis is dehydration. • S. dysenteriae serotype 1 infection is commonly complicated by hemolytic-uremic syndrome. • This syndrome is caused by Shiga toxin–mediated endothelial injury. By: Dr Arun Aggarwal Gastroenterologist

28. Diagnosis: clinical picture, stool examination, rectal swab, blood cultures • Treatment: fluid and electrolytes • Antibiotics: azithromycin, ampicillin, bactrim, cefixime, nalidixic acid, quinolones. By: Dr Arun Aggarwal Gastroenterologist

29. E. coli By: Dr Arun Aggarwal Gastroenterologist

30. By: Dr Arun Aggarwal Gastroenterologist

31. Camplylobacter By: Dr Arun Aggarwal Gastroenterologist

32. Human campylobacterioses most commonly result from ingestion of contaminated food or water, from direct contact with environmental sources (i.e., a pet), or from person-to-person transmission. By: Dr Arun Aggarwal Gastroenterologist

33. Patients may have loose, watery stools or bloody and mucus-containing stools (dysentery). • Fever, vomiting, malaise, and myalgia are common. • The abdominal pain is periumbilical. • Abdominal pain may mimic appendicitis or intussusception. • Persistent infection may mimic chronic IBD. By: Dr Arun Aggarwal Gastroenterologist

34. Diagnosis: stool culture, rectal swab, serological studies. • The optimum incubation temperature for C. jejuni and C. coli is 42 to 43ºC; as a result, the term "thermophilic" campylobacters is sometimes applied to these species. • Treatment: • Fluid replacement • Correction of electrolytes • Antibiotics: azithromycin, aminoglycosides, doxycycline, trimethoprim • Antibiotics are recommended for patients with the dysenteric form of the disease, high fever, or a severe course and for children who are immunosuppressed or have underlying diseases. By: Dr Arun Aggarwal Gastroenterologist

35. Yersinia By: Dr Arun Aggarwal Gastroenterologist

36. Y. enterocolitica is transmitted to humans through food, water, animal contact, and contaminated blood products. • The organisms most often enter by the alimentary tract and cause mucosal ulcerations in the ileum. Necrotic lesions of Peyer patches and mesenteric lymphadenitis occur. • Presentation: enterocolitis with diarrhea, fever, and abdominal pain. • Acute enteritis is more common among younger children, and mesenteric lymphadenitis that may mimic appendicitis. By: Dr Arun Aggarwal Gastroenterologist

37. Diagnosis: stool culture, rectal swab. • Treatment: self-limiting disease and no benefit of antibiotic therapy is established. • Patients with systemic infection and very young children in whom septicemia is common should be treated. • Yersinia strains are sensitive to trimethoprim-sulfamethoxazole, aminoglycosides, third-generation cephalosporins, and quinolones. By: Dr Arun Aggarwal Gastroenterologist

38. Patients on deferoxamine should discontinue iron chelation therapy during treatment for Y. enterocolitica, especially if they have complicated gastrointestinal infection or extraintestinal infection. By: Dr Arun Aggarwal Gastroenterologist

39. C. difficile By: Dr Arun Aggarwal Gastroenterologist

40. C difficile–associated diarrhea, also known as pseudomembranous colitis or antibiotic-associated diarrhea, is a major cause of nosocomial diarrhea. • C. difficile is a ubiquitous spore-forming gram-positive anaerobic bacillus. • The organism produces two toxins: toxin A (enterotoxin) acts on the intestinal mucosa to produce diarrhea; toxin B (cytotoxin) increases vascular permeability in low doses and is lethal to experimental animals in high doses. By: Dr Arun Aggarwal Gastroenterologist

41. Virtually all known antibiotics have been implicated; penicillins, broad-spectrum cephalosporins, and clindamycin are the most frequent offenders. • Newborns are often colonized with C. difficile during the first weeks of life. Carriage decreases to the adult rate of 1–3% by 2 yr of age. • Illness is unusual in neonates and infants; the basis for this remains unknown. By: Dr Arun Aggarwal Gastroenterologist

42. The classic picture of pseudomembranous colitis is diarrhea with blood and mucus accompanied by fever, cramps, abdominal pain, nausea, and vomiting. Disease occurs during and as long as weeks after antibiotic therapy. • The diagnosis is confirmed by detecting C. difficile or its toxin in the stool. • Findings at sigmoidoscopy or colonoscopy include pseudomembranous nodules and plaques characteristic of toxin-related colitis. Fecal leukocytes are present in approximately one half of cases; occult or frank blood is common. By: Dr Arun Aggarwal Gastroenterologist

43. The first and essential step in treatment is the discontinuation of the current antibiotics, if possible. • If symptoms persist, antibiotics cannot be discontinued, or the illness is severe, then oral metronidazole (20–40 mg/kg/24 hr divided q 6–8 hr PO) or vancomycin (25–40 mg/kg/24 hr divided q 6 hr PO) should be given for a 7–10 day course. By: Dr Arun Aggarwal Gastroenterologist

44. The initial response rate is >95%, but 5–30% of patients have clinical relapse, usually within 1–2 wk of treatment. • These patients should be re-evaluated and treated again; most will respond to a second course of the original treatment. • A few patients develop multiple recurrences, with short-lived responses to repeated treatment. • Treatment strategies for these patients include oral cholestyramine, oral bacitracin, oral immunoglobulin, reconstitution of bowel flora with oral lactobacilli or baker's yeast, or instillation of fecal flora by tube feeding or enemas (faeces transplant). By: Dr Arun Aggarwal Gastroenterologist

45. Rota Virus By: Dr Arun Aggarwal Gastroenterologist

46. Rotavirus causes 3 million cases of diarrhea, 50,000 hospitalizations, and 20–40 deaths annually in the United States. • Disease tends to be most severe in patients 3-24 months of age. • Infants younger than 3 mo of age are relatively protected by transplacental antibody and possibly breast-feeding. By: Dr Arun Aggarwal Gastroenterologist

47. The virus is shed in stool at very high concentration before and for days after the clinical illness. • Very few infectious virions are needed to cause disease in a susceptible host. • The gastric mucosa is not affected despite the commonly used term “gastroenteritis. • Selective viral infection of intestinal villus tip cells thus leads to • an imbalance in the ratio of intestinal fluid absorption to secretion • malabsorption of complex carbohydrates, particularly lactose. By: Dr Arun Aggarwal Gastroenterologist

48. Clinical manifestations: incubation period: <48 hrs • mild to moderate fever and vomiting followed by the onset of frequent, watery stools. • Diagnosis: Enzyme immunoassays, which offer approximately 90% specificity and sensitivity, are available for detection of group A rotavirus and enteric adenovirus in stool samples. • Laboratory findings: Isotonic dehydration with acidosis. By: Dr Arun Aggarwal Gastroenterologist

49. Treatment • Avoiding and treating dehydration are the main goals in treatment of viral enteritis. • A secondary goal is maintenance of the nutritional status of the patient. • Controlled studies have shown no benefit from antiemetics or antidiarrheal drugs. • Therapy with probiotic organisms such as Lactobacillus species has been shown to reduce somewhat the intensity and duration of illness. • Vaccine By: Dr Arun Aggarwal Gastroenterologist

50. Amebiasis By: Dr Arun Aggarwal Gastroenterologist