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1. DIARRHEA AND HANDWASHING Module : Infectious Diseases Dr RUTAGANDA Eric, MD., Mmed ., MPH. Hepato -Gastroenterologist CHUK/ SoM -UR

2. I. ACUTE DIARRHEA

3. Diarrhea - Epidemiology

4. Background: What is abnormal?

5. Definition and Classification Diarrhea is defined as the passage of loose or watery stools, typically at least three times in a 24-hour period Acute diarrhea is defined as diarrhea of ≤14 days in duration Persistent Diarrhea : >14 days and ≤30 days Chronic Diarrhea : >30 days of diarrhea Invasive diarrhea , or dysentery , is defined as diarrhea with visible blood, in contrast to watery diarrhea . Dysentery is commonly associated with fever and abdominal pain

6. Physiology - Small Intestine Does most of the work of absorption nutrients fluid and electrolytes Designed for the task villus cells specialized for absorption crypt cells specialized for secretion

7. Physiology- Large Intestine

8. Physiology Stool and Water Balance Approximately 7-9L of fluid enter the bowel lumen per day 1.5 Liters from diet 90% of the water (and sodium) is absorbed in the small intestine 90% of the REMAINING water (about 1L) is absorbed by the colon

9. MECHANISMS OF DIARHEA 10

10. Osmotic diarrhea

11. Secretory Diarrhea Diarrhea due to a derangement of fluid and Electrolyte transport across intestinal mucosa. It is watery, Large volume fecal output >1 l/day, Painless, Persists with fasting, No fecal Osmotic gap Causes: Medications ( nonosmotic laxatives, antibiotics) Endocrine (carcinoid, gastrinoma , VIPoma, adrenal insufficiency, hyperthyroidism) Bile salt malabsorption (ileal resection, cholecystectomy) Noninvasive infections (giardiasis, cryptosporidiosis) Small intestinal bacterial overgrowth ( SIBO)

12. Inflammatory Diarrhea Diarrhea accompanying fever, pain and bleeding Stool analysis show leukocytosis Causes Inflammatory bowel disease (ulcerative colitis, Crohn disease, microscopic colitis) Malignancy (colorectal cancer, lymphoma) Invasive infections ( Clostridium difficile , cytomegalovirus,  Entameba histolytica , tuberculosis) Ischemia Radiation colitis/enteritis

13. Dysmotility Diarrhea Dysmotility: Rapid transit Causes: Postsurgical (vagotomy, dumping) Endocrine (diabetes mellitus, hyperthyroidism) Visceral neuropathy: Scleroderma

14. Inflammatory vs Noninflammatory Infectious Diarrhea

15. Steatorrhea Diarrhea Steatorrhea is defined as stool fat exceeding > 7 gm per day Fat malabsorption may lead to greasy foul smelling, difficult to flush diarrhea It is associated with weight loss and Nutritional deficiency of amino-acids and Vitamins ( ADEK) Causes Maldigestion (decreased bile salts, pancreatic dysfunction) Malabsorption (celiac disease, tropical sprue, giardiasis, Whipple disease, chronic mesenteric ischemia, short bowel syndrome, bacterial overgrowth, lymphatic obstruction)

16. Miscellaneous Irritable bowel syndrome Functional diarrhea: Frequent or loose or watery stools without abdominal discomfort in the absence of other identifiable causes Factitious Overflow common in Colorectal cancer Fecal incontinence more common in stroke patients. The DRE is important to evaluate the incontinence

17. Acute Diarrhea- The initial assessment The initial assessment should focus on Assessment of the severity need for hydration historical clues as to the cause in the patient. The decision to : test for a specific pathogen notify public health start empirical treatment

18. Acute Diarrhea-important points of assessment C haracteristics of the stool: bloody, water Associated symptoms: fever, tenesmus, vomiting U nderlying comorbidities T ravel history I ngestion of unfiltered water R ecent use of antibiotics R ecent contact with a sick individual D ietary history focusing on foods that are at high risk for transmitting diarrheal illness Employment: daycare worker, food handler, health care worker R esidence in a closed facility (e.g., long-term care facility)

19. Acute Diarrhea-important points of assessment Evidence of volume depletion is important to assess the severity of the illness. Reduced skin turgor and dry mucous membranes may reflect mild volume depletion. Tachycardia, an orthostatic drop in blood pressure, hypotension, changes in mental status are all suggestive of severe dehydration. Examination of the abdomen may reveal focal or diffuse tenderness. Rebound tenderness suggestive of peritoneal inflammation should warrant further assessment to rule out severe colitis or perforation

20. Acute Diarrhea-Differentials

21. Acute Diarrhea-Treatment

22. Consequences of Diarrhea Most common Dehydration>hypovolemia Electrolytes imbalance: Potassium deplation Metabolic acidosis Bacteremia>Sepsis>Septic shock Rectal prolapse Renal failure (Pre-renal AKI) Malnutrition (especially HIV) Less common Hemolytic uremic syndrome Guillain-Barré Reactive arthritis

23. Diarrhea – unique complications Reactive arthritis - Salmonella, Shigella, Campylobacter Guillain Barre syndrome - Campylobacter HUS/TTP - Shiga toxin producing E coli (0157), Shigella Bacteremia – non typhoidal salmonella, Campylobacter, shigella (more common in HIV infected individuals)

24. II. CHRONIC DIARRHEA

25. CHRONIC DIARRHEA-CLASSIFICATION

26. History and Physical examination

27. History and Physical examination

28. Diagnostic studies

29. Stool studies In cases of chronic diarrhea without an underlying diagnosis , a nalysis of stool includes: fecal weight stool electrolytes fecal pH, fat content fecal calprotectin presence of blood and leukocytes. In watery stools, fecal electrolytes can be used to calculate the fecal osmotic gap: 290 – (2 × [stool sodium + stool potassium]) An osmotic gap of less than 50 mOsm /kg (50 mmol/kg) suggests secretory diarrhea A gap greater than 100 mOsm /kg (100 mmol/kg) suggests osmotic diarrhea. The presence of blood or leukocytes in the stool suggests an inflammatory cause. A positive 72-hour stool collection for fecal fat confirms steatorrhea.

30. Small Intestine studies Evaluation of the small intestine may include: imaging with small-bowel radiography, CT enterography, or MR enterography to identify conditions that could lead to bacterial overgrowth, such as small intestinal diverticular disease, inflammation, or strictures. Upper endoscopy is indicated when small-bowel mucosal disease (such as celiac disease or chronic infection) is suspected. Capsule endoscopy can be used to visualize the small intestine but does not allow for sampling.

31. Colon studies Colonoscopy is the primary diagnostic tool for evaluating causes of diarrhea related to the colon, IBD, microscopic colitis, chronic colonic infections, and malignancy. By definition, colon biopsies of the right and left colon are required to exclude microscopic colitis. Colonoscopy is especially important in patients with rectal bleeding and/or age older than 45-50 years.

32. Diarrhea Initial Stool Analysis Stool Testing ( options to consider) F ecal leukocytes if positive, think bacterial causes, Inflammation causes if negative, think viral, giardia, cryptosporidium Culture antigen or toxin detection Camp, Shigella , Salmonella, E Coli 0157, Yersinia Giardia, E. histolytica , Strongyloid (by antigen), Cryptosporidium Stool Microscopy (parasites)

33. Additional studies I n immunocompromised patients (including HIV testing) and patients with secretory diarrhea. Patients found to have a small-bowel tumor in the setting of diarrhea should be considered for : R adioimmunoassays for peptides and/or 24-hour urine 5-hydroxyindoleacetic acid measurement for carcinoid tumors. Testing for carcinoid tumors should be limited to patients with chronic diarrhea and flushing.

34. Management of Chronic Diarrhea

35. CONDITIONS ASSOCIATED WITH CHRONIC DIARRHEA Celiac Disease Small Intestine Bacterial Overgrowth: SIBO Carbohydrate Malabsorption Inflammatory Bowel Disease: IBD Irritable Bowel Syndrome: IBS HIV/AIDS

36. Celiac Disease: Gluten Sensitivity Celiac disease is an immune-mediated disease that primarily affects the small intestine in response to dietary gluten. It is one of the most common causes of malabsorption It only affects individuals who are genetically predisposed. The immune reaction leads to destruction of the small intestinal villi starting in the proximal duodenum.

37. Celiac Disease Gastrointestinal symptoms of celiac disease typically include chronic diarrhea, bloating, and weight loss, but may also include atypical symptoms, such as constipation and dyspepsia. Other manifestations include iron deficiency anemia, bone loss, abnormal liver aminotransferase levels, neurologic symptoms, and dermatitis herpetiformis   Patients may also be asymptomatic. Ideally, testing for celiac disease should be done while the patient is on a gluten-containing diet. The combination of tissue transglutaminase IgA antibodies and anti- endomysial antibodies has a positive predictive value for celiac disease approaching 100%.

38. Small intestinal bacterial overgrowth (SIBO) C auses impaired motility strictures (for example, in Crohn disease) blind loops (for example, small-bowel diverticula). SIBO is defined by the presence of >10 5  colony-forming units per mL of jejunal aspirate. Glucose and lactulose breath tests have acceptable specificity (around 80%) but poor sensitivity (30%-40%) for diagnosing SIBO. Treatment consists of antibiotic therapy and often requires repeated courses if the underlying condition cannot be resolved.

39. Carbohydrate Malabsorption Carbohydrates are: monosaccharides (glucose, fructose) disaccharides (lactose, sucrose) oligosaccharides ( maltodextrose ) polyols (sorbitol, mannitol). These short-chain carbohydrates are osmotically active and can lead to increased luminal water retention and gas production through colonic fermentation. These two actions can cause gastrointestinal symptoms, including gas, bloating, and diarrhea. Lactose malabsorption is commonly due to loss of the brush border lactase enzyme in adulthood.

40. Inflammatory Bowel Disease: IBD IBD is an idiopathic chronic inflammatory condition of the gut that includes ulcerative colitis and Crohn disease. In addition, microscopic colitis is considered a type of IBD with distinct clinical and pathologic features. The pathogenesis of IBD likely involves host genetic predisposition and abnormal immunologic responses to endogenous gut bacteria. The primary risk factor for development of IBD is family history, with a risk of approximately 10% for first-degree relatives of affected patients. Tobacco smoking increases the risk for Crohn disease and is protective for ulcerative colitis. IBD has a bimodal age presentation, with an initial peak incidence in the second to fourth decades of life followed by a less prominent second peak in the seventh and eighth decades.

41. Irritable Bowel Syndrome: IBS IBS represents a heterogeneous group of functional bowel disorders defined by the presence of abdominal pain in association with defecation and/or a change in bowel habits. Abdominal pain may worsen or subside with defecation. The altered bowel habits may include constipation, diarrhea, or a mix of both types. Other commonly reported symptoms include abdominal bloating and abdominal distention. The exact cause of IBS remains unknown, and there are no all-encompassing pathophysiologic mechanisms to explain the symptoms. IBS is more common in women and adults younger than age 50 years, and is frequently seen in association with psychosocial disturbance.

42. Irritable Bowel Syndrome There are no specific anatomic or physiologic abnormalities, nor are there any reliable biomarkers to define IBS. The diagnosis of IBS ( Rome Criteria IV ) requires symptoms of recurrent abdominal pain at least 1 day a week for a period of 3 months, along with at least two of the following three additional criteria with regard pain : pain related to defecation change in stool frequency or change in stool consistency. IBS can then be further subtyped into: IBS with predominant constipation (IBS-C), IBS with predominant diarrhea (IBS-D), IBS with mixed bowel habits, IBS unclassified.

43. Chronic Diarrhea in HIV/AIDS Diarrhea can cause significant morbidity in patients with HIV It can be due to a multitude of etiologies from infectious pathogens to malignancy to medications. Diarrhea is also an independent predictor of reduced quality of life and, in the case of advanced HIV disease, increased mortality

44. Chronic Diarrhea in HIV/AIDS

45. Suggested Readings Uptodate.com: Evaluation of the patient with HIV and diarrhea Arasaradnam RP, Brown S, Forbes A, et al. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut. 2018;67:1380-1399.  PMID: 29653941  doi:10.1136/gutjnl-2017-315909 Keefer L, Drossman DA, Guthrie E, et al. Centrally mediated disorders of gastrointestinal pain. Gastroenterology. 2016 Feb 19. pii : S0016-5085(16)00225-0.  PMID: 27144628 Mearin F, Lacy BE, Chang L, et al. Bowel disorders. Gastroenterology. 2016 Feb 18. pii : S0016-5085(16)00222-5.  PMID: 27144627 Nikaki K, Gupte GL. Assessment of intestinal malabsorption. Best Pract Res Clin Gastroenterol. 2016 Apr;30(2):225-35.  PMID: 27086887 Schiller LR, Pardi DS, Spiller R, et al. Gastro 2013 APDW/WCOG Shanghai working party report: chronic diarrhea: definition, classification, diagnosis. J Gastroenterol Hepatol. 2014 Jan;29(1):6-25.  PMID: 24117999 Shepherd SJ, Lomer MC, Gibson PR. Short-chain carbohydrates and functional gastrointestinal disorders. Am J Gastroenterol. 2013 May;108(5):707-17.  PMID: 23588241 Smalley W, Falck- Ytter C, Carrasco-Labra A, et al. AGA clinical practice guidelines on the laboratory evaluation of functional diarrhea and diarrhea-predominant irritable bowel syndrome in adults (IBS-D). Gastroenterology. 2019;157:851-854.  PMID: 31302098

46. III. HANDWASHING

47. Hand transmission Hands are the most common vehicle to transmit healthcare associated pathogens Compliance rates are generally low (40-60%) but improve if alcohol rub is available To sustain awareness about and increase compliance with hand hygiene a multimodal approach is advocated. This includes A combination of multidisciplinary teamwork, education, supervision, and provision of acceptable hand hygiene products Role models and champions are also important Patient engagement also is effective. 50

48. For effective hand hygiene: Keep nails short Remove rings, wrist watches and bracelets No artificial nails or nail polish Roll up long sleeves or remove long-sleeved clothing

49. Hand hygiene is important in reducing transmission WHO 5 moments of hand hygiene can be adapted for any healthcare environment

50. Correct technique is important Six steps technique for handwashing with soap and water (40-60seconds) Source: Babeluk R et al . PLOS ONE 9(11): e111969 .

51. Hand hygiene technique with alcohol based hand rub (60-70% alcohol) - WHO recommended method

52. Note: areas that can be missed if poor technique is used

53. Hand hygiene in COVID-19/Infectious Outbreaks isolation units The 5 moments of hand hygiene must be observed Never remove any piece of PPE while in the isolation unit Perform hand hygiene on gloved hands Use ABHR(Alcohol-based hand Rub) Wash with soap and water or Use dilute chlorine solution (0.05%) only when soap and water are not available

54. Stop Infection spreading, clean your hands!