1. DIARRHEA HOSSEIN SANEIAN HOSSEIN SANEIAN Ped. Gastroenterologist Ped. Gastroenterologist شهریور 1391

2. Definition In epidemiological studies diarrhoea is defined as: Passage of three or more loose or watery stools in a 24-hour period, a loose stool being one that would take the shape of a container.

3. Definition In Pediatrics, Diarrhoea is an increase in the: Fluidity Volume Number of stools relative to the usual habits of each individual.

4. Stool output > 10 g / kg / day, > 200ml per m² BSA/d, >150-200 gr per m² BSA/d.

5. Importance of Diarrhoea In under five children Diarrhoea is a leading cause of: Mortality Morbidity Severe malnutrition

6. High Childhood Morbidity 2.5 billion episodes/year 3.6 episodes/baby/year In children under 5 years of age

7. High Childhood Mortality In children under 5 years of age 3.2 million deaths/ year 5 million per year in 1980 to less than 2 million in 1999 5 million per year in 1980 to less than 2 million in 1999

8. اسها ل = 18% مرگ ومیر کودکان دومین علت مرگ ومیر کودکان. 1/5 میلیون مرگ در سال روتا ویروس =527000(deaths=29%) ETEC=300000-500000 شیگلا =160000

9. Major Contributor to Malnutrition DIARRHOEA MALNUTRITION, اختلالات روانی تکاملی و شناختی

10. Diarrhea attack rate / 100 child / year Guatemala,1968

11. Acute Watery Diarrhoea Constitutes 80% of cases of diarrhoea Begins acutely, lasts less than 14 days (most episodes last less than 7 days), Involves passage of frequent loose or watery stools without visible blood. Vomiting may occur,Fever may be present Main sequelae: Dehydration that can be fatal Contributes to malnutrition

12. Dysentery (Bloody Diarrhoea) Constitutes 10% of cases of diarrhoea Diarrhoea with visible red blood in the stools Main sequelae: Anorexia Rapid weight loss Damage to the intestinal mucosa

13. Persistent Diarrhoea Constitutes 10% of cases of diarrhoea Diarrhoea that begins acutely as watery diarrhoea or as dysentery and lasts for 14 days or more. Should not be confused with chronic diarrhoea which is recurrent or long-lasting diarrhoea due to noninfectious causes.

14. Etiology: Fecal-Oral Transmission Water Food Infected animal Infected Person فقر – بهداشت نامناسب

15. Etiology of Diarrhoea Identification of the etiology of diarrhoea on clinical grounds alone is not usually possible except in epidemics or if there is history of contact with a diagnosed case. With the availability of modern laboratory techniques, causative pathogens could be identified in >75 % of cases of diarrhoea.

16. Etiology of Diarrhoea The majority of diarrhoeas occur as a result of infection with a few pathogens which tend to recur again and again. The most important causes of acute diarrhoea in developing countries are: Rotavirus Enterotoxigenic Escherichia coli Shigella Campylobacter jejuni Cryptosporidium

17. Etiology of Acute Diarrhoea Percent 15-25%10-20% 5-15% 10-15% 5-15%

19. Enteropathogens that are infectious in a small inoculum (Shigella, enterohemorrhagic E. coli, Campylobacter jejuni, noroviruses, rota virus, Giardia lamblia, Cryptosporidium parvum, Entamoeba histolytica) can be transmitted by person-to-person contact, others, such as cholera: Are generally a consequence of contamination of food or water supply.

20. Food-borne outbreaks of bacterial diarrhea in the United States are most commonly due to: Salmonella, E. coli, Clostridium botulinum, Clostridium perfringens, Staphylococcus aureus

21. PATHOGENESIS OF INFECTIOUS DIARRHEA: organisms have preformed toxins (S. aureus, Bacillus cereus),? produce secretory toxin(cholera, E. coli, Salmollella, Shigella) Adherence and/or translocation by bacteria. cytotoxic toxin (Shigella, S. aureus, Vibrio parahemolyticus, C. difficile, E. coli, C. jejuni) invasive Multiple

22. (protein NSP4 acts as a viral enterotoxin)

23. Pathogenesis of Rotavirus Diarrhoea Rotavirus invades the absorptive enterocytes of villi but spares crypt cells. The viruses replicates and infected enterocytes are destroyed

24. Rotavirus Rotavirus inside enterocyte Rotavirus

25. Pathogenesis of Rotavirus Diarrhoea 1 2 1- Infected absorptive ente-rocytes are killed causing patchy epithelial cell destruc-tion and villous shortening 2- Destroyed absorptive cells are rapidly replaced by cells that migrate from the crypts. So, affected villi become temporarily covered with immature non-absorptive crypt-like secretory cells having no brush border and no brush border enzymes (e.g. lactase) 1

26. Effects of Rotavirus

28. Pathogenesis of Secretory Diarrhoea 1- Enterotoxigenic Bacteria secrete an Enterotoxin that stimulates the production of C-AMP (cyclic adenosine mono-phosphate) 2-Increased C-AMP leads to: Inhibition of absorption of Na+ & Cl- from the cells of villi Stimulation of secretion of Cl- from crypt cells

31. Entero-Adherent E. Coli Entero-Adherent E. Coli adherent to enterocyte of small intestine (electron microscope X 20 000)

33. RISK FACTORS FOR GASTROENTERITIS: 1- environmental contamination and increased exposure to enteropathogens. 2-young age, 3-immunodeficiency, 4- measles, 5- malnutrition, 6- lack of exclusive or predominant breast-feeding. 7- nutritional deficiencies

34. Zink deficiency مرگ و میر ناشی از اسهال و پنومونی ومالاریا را 21-13% افزایش میدهد Vitamin A deficiency مرگ و میر ناشی از اسهال و سرخک ومالاریا را 24-20% افزایش میدهد

35. clinical manifestations Symptomatic, Asymptomatic C. jejuni Infections

36. clinical manifestations There is considerable overlap in the symptomatology. are related to the infecting pathogen and the dose or inoculum development of complications (e.g., dehydration and electrolyte imbalance)

37. Usually the ingestion of preformed toxins (e.g., those of S. aureus) is associated with: the rapid onset of nausea and vomiting within 6 hr, with possible fever, abdominal cramps, and diarrhea within 8-72 hr.

38. Watery diarrhea and abdominal cramps after an 8-16 hr incubation period are associated with enterotoxin- producing e. perfringens and B. cereus.

39. Abdominal cramps and watery diarrhea after a 16-48 hr incubation period can be associated with noroviruses, several enterotoxin-producing bacteria, Cryptosporidium, and Cyclospora and have also been a notable feature of influenza virus HINI infections.

40. Several organisms, including Salmonella, Shigella, c. jejuni, Yersinia enterocolitica, enteroinvasive or hemorrhagic (Shigatoxin-producing) E. coli, and V.parahaemo/yticus, produce diarrhea that can contain blood as well as fecal leukocytes in association with abdominal cramps, tenesmus, and fever;

41. COMPLICATIONS: Most of the complications associated with gastroententIs are related to delays in diagnosis and delays in the institution of appropriate therapy. 1-dehydration 2- prolongation of the diarrheal episodes 3-malnutrition 4- secondary infections 5-In developing countries and HIV-infected populations, associated bacteremias are well-recognized complications in malnourished children with diarrhea. 6-micronutrient deficiencies (iron, zinc).

42. Extra-intestinal complications Specific pathogens are associated with extra intestinal manifestations and complications These are not pathognomonic of the infection, nor do they always occur in close temporal association with the diarrheal episode