Gastroenteritis

1. Gastroenteritis Acute Care Module Jonathan Bae, MD

2. Objectives • To review epidemiology of acute gastroenteritis • To review common causes of gastroenteritis as well as clinical presentation • To differentiate between viral and bacterial/parasitic types of gastroenteritis • To discuss management strategies of gastroenteritis

3. Background • Gastroenteritis refers to an acute inflammation of the stomach and intestines resulting in vomiting and diarrhea • Gastroenteritis is one of the most common diseases affecting children • Second most common acute infection after URI • Viruses are the most common causes of acute gastroenteritis in developed and developing countries • Gastroenteritis is a substantial cause of morbidity in pediatric populations • Worldwide, acute gastroenteritis is the leading cause of illness and death for children

4. Epidemiology • Approximately 5 billion episodes of diarrhea/gastroenteritis occur worldwide annually • In children <5 years old, there are 1-5 episodes per child-year • Accounts for 15-25 million episodes of gastroenteritis annually resulting in 3-5 million doctor visits and 200K hospitalizations • Highest rate of infection occurs between 3-24 months of age • 1 in 50 children are hospitalized during childhood due to acute gastroenteritis • 95% occur less then 5 years of age • 3-5% of all hospital days and 7-10% of hospitalizations annually for patients <18 are due to viral gastroenteritis • 70-90% occur in winter • Gastroenteritis accounts for 15-30% of death in developing nations

5. Transmission • Fecal-oral route • Contaminated food and water • Daycare, school • Respiratory tract inoculation?

6. Pathogenesis • Viral: infect enterocytes leading to destruction  transudation of fluid into intestinal fluid • Bacterial: • Toxin production (Vibrio cholerae, Clostridium difficile, Staph)  secretory diarrhea • Bacterial adherence (E. Coli) release of mucinase, protease resulting in cell death  osmotic diarrhea • Invasion (Shigella) • Parasites: Invasion or adherence to bowel wall resulting in cell destruction Disruption of enterocytes leading to transudation/exudation of fluid, often with loss of ability to digest food (complex sugars) and absorb food until return of normal villous architecture.

7. Clinical Presentation • Diarrhea • Frequency, color, consistency, odor, blood, mucus, duration • Nausea/vomiting • Fever • Anorexia • Abdominal pain/cramping • Headache • Myalgias • Dizziness/lightheadedness • Daycare attendance • Recent antibiotic use • Dietary indiscretions; inadequate storage and preparation of food • Rapid onset • Travel • Animal exposure (domestic, wild, farm)

8. Risk Factors for severe manifestations or hospitalization • Children <4 years • Lower socioeconomic status • Poor capability of parents • First time infection • Malnutrition • Immunodeficiency • Change in serotype of infecting strain • Large inoculum size • Strain virulence • Loss of maternal immunity

9. Fever Weight loss Tachycardia Orthostasis Tachypnea Hypotension Somnolence/Level of consciousness Dry membranes Flat fontanel Loss of skin turgor Physical exam should focus on signs of clinical dehydration which helps to assess severity of illness Physical Exam

10. Laboratory Evaluation • Elevated specific gravity on urinalysis • Isotonic dehydration • Metabolic acidosis • Stool gram stain, culture, and electron microscopy (viruses), ova & parasites • Labs routinely test for Salmonella, Shigella, and Campylobacter • Fecal leukocytes • Nonspecific evidence of inflammation • Most common for bacterial/parasitic gastroenteritis  indicative of invasive diarrhea • Fecal blood  suggests invasive organism (hemorrhagic E. Coli) • Specific assays  rotavirus, C. diff

11. Differential Diagnosis • Extraintestinal infections (UTI, AOM, URI) • Lactose intolerance • Bacterial sepsis • Meningitis • Pyloric stenosis • Bowel obstruction • Intussusception • Diabetic ketoacidosis • Toxin ingestions • Antibiotic use • Overfeeding • Food protein allergy • Celiac disease • Inflammatory Bowel Disease • Malabsorption • Malignancy (neuroblastoma, carcinoid, VIPoma, gastrinoma)

12. Bacterial Tend to affect children >2 years of age Blood often present Fecal leukocytes often present May be associated with travel, exposure to animals, consumption of meat Viral Tend to affect children <2 years Blood absent Fecal leukocytes absent Not often associated with travel, animals, or meat Viral vs. Bacterial Viral gastroenteritis accounts for 70-90% of cases Bacterial gastroenteritis 10-20%

13. Viral Gastroenteritis • Rotavirus • Calcivirus (Norwalk) • Enteric adenovirus (serotypes 40 & 41) • Astrovirus

14. Rotavirus • The most common cause of acute gastroenteritis • 70-nm, double-stranded, segmented RNA virus • Fecal-oral route • Peaks in winter; common spread among daycare • Highest incidence ages 6 months to 2 years • Infects and destroys enterocytes in the small intestinge • Incubation for approximately 2 days • Vomiting and watery diarrhea x 3-8 days • May have associated fever and abdominal pain

15. Calcivirus (Norwalk) • Described after an outbreak among school children in Norwalk, Ohio in 1972 • 27-nm RNA virus • Incubation 1-2 days • Fecal-oral transmission • More common in older children and adults • Vomiting, diarrhea +/- fever, abdominal pain • Outbreaks after ingestion of contaminated shellfish, salad (cruise ships)

16. Adenovirus • Enteric subtypes 40 & 41 • Similar to rotavirus but with longer course (>6 days) • Common year round • Typically affects older children

17. Bacterial Gastroenteritis • Campylobacter jejuni • E. Coli • Salmonella • Shigella • Yersinia enterocolitica • Vibrio cholera • C. Diff • Staph • Bacillus cereus

18. Campylobacter jejuni • Curved gram negative organism • Most commonly isolated bacterial fecal pathogen • Less common: C. fetus, C. abortus • Common in summer • Affects large bowel • Grossly bloody diarrhea, fever, abd pain; may mimic appendicitis • Animal reservoirs include dogs, cats, wild birds, poultry

19. Escherichia coli • Gram-negative rod with four different subclasses named for distinct mechanisms of action • Enterotoxigenic E. coli • Toxin similar to cholera • Watery, large volume diarrhea • Enteropathogenic E. coli • Infects and disrupts enterocytes • Musty smelling stool w/o blood or mucous • Enteroinvasive E. coli • Similar to shigella • Enterohemorrhagic E. coli • Cytoxins result in destruction of enterocytes • Bloody diarrhea • O157:H7 subclass associated with hemolytic uremic syndrome (acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia, fever)

20. Salmonella • Non-lactose fermenting, motile GNR • S. enteritidis, S. choleraesuis, S. typhi • Late summer, early fall • Enterocyte invasion in small bowel\ • Foul smelling, soft stool +/- blood, mucus; stool leukocytes • Fecal-oral route, contaminated food, reptiles (turtles), eggs/poultry  needs large inoculum size • May have asymptomatic carrier state or be complicated by bacteremia, osteomyelitis

21. Shigella • Non-lactose fermenting, nonmotile GNR • S. sonnei, S. flexneri (more common in US); S. dystenteriae (developing countries) • Most common in fall • Enterocyte invasion in large bowel • Watery, bloody, or mucous stool with fruity or vinegary smell; stool leukocytes • Associated with fever, abdominal pain, tenesmus, headache • Daycare, contaminated food/water  only requires small inoculum • Complications include toxic megacolon, cholestatic hepatitis, HUS, Reiter syndrome, seizures • Rx with IV 3rd generation cephalasporins (Ceftriaxone)

22. Yersinia enterocolitica • Nonlactose fermenting, aerobic, motile gram negative coccobacillus • Most common in winter • Affects small bowel (ileum)Loose bloody, mucous diarrhea; fecal leukocytes • Complications include erythema nodosum, reactive arthritis, terminal ileitis, mesenteric adenitis (may mimic appendicitis), meningitis, myocarditis, hepatitis, glomerulonephritis

23. Vibrio cholerae • Aerobic, motile, curved, gram-negative • Occurs in epidemics • Affects small bowel via enterotoxin • Attaches with flagella and release cholera toxin which causes rapid and severe fluid loss • Large voluminous, explosive diarrhea; crampy abdominal pain • Complicated by severe hypovolemia and death • Uncooked crustaceans, mollusks (oysters, crabs, shrimp); requires large inoculum

24. Other bacterial pathogens • Clostridium difficile • Colitis results in overgrowth after antibiotic administration (ampicillin, clindamycin, cephalosporins) with subsequent toxin production  pseudomembranous colitis (lined with gray plaque-like lesions) • Symptoms may not appear for weeks after abx • Abdominal pain, fever, blood/mucous stool; fecal leukocytes • Rx with flagyl or vancomycin • Staphylococcal • Disease mediated by enterotoxin • Produces primarily nausea, vomiting, and retching followed by diarrhea • Brief incubation period (3-5 hrs) • Contaminated food (mayonaise) • Antibiotics of no help  toxin mediated • Bacillus cereus • Soil dwelling, gram positive rod • Heavy vomiting, retching, abdominal pain • Toxin mediated symptoms, often resulting from contaminated food with bacterial spores “Fried Rice Syndrome” (improperly refrigerated cooked rice)

25. Parasites • Giardia lamblia • Flagellated protozoan; cyst form is the infectious agent which infest the duodenum via fecal-oral route • Contaminated fresh water streams, day care centers • Flatulence, abdominal pain, mucous diarrhea • Higher risk for severe disease with IgA deficiency or cystic fibrosis • Diagnosed by direct inspection of stool or ELISA • Entamoeba histolytica • Ingestion of infected cysts resulting in loose, bloody, mucoid diarrhea • May be complicated by hepatic abscess • Cryptosporidium • Daycare settings, immunocompromised hosts (HIV) • Frequent, watery stools • Isospora • Common in HIV/AIDs

26. Initial Assessment • Duration of illness • Number of episodes • Fever • Presence of blood or mucous in stool • Fluid intake • Activity level • Moisture of mucous membranes • Urine frequency • Ill contacts, travel, food • Underlying illness

27. Management • Mainstay of therapy is management of fluid and electrolyte abnormalities • Antibiotics rarely indicated • May result in prolonged shedding • No benefit to the use of antiperistaltic agents • Controversial benefit to probiotics and antiemetics

28. Hospital Admission • Shock • Severe dehydration • Seizures • Anuria > 12 hrs • Hematemesis, hematochezia • Metabolic imbalance • Mild-moderate dehydration if cannot ensure successful oral rehydration (intolerant, vomiting) • High frequency of stools or vomiting • Concerns about caregivers • Immunocompromised hosts • Prolonged diarrhea (> 7 days) w/no improvement

29. Assessment of Dehydration

30. Fluid resuscitation • Severe dehydration/hypovolemia • Rapid fluid resuscitation with isotonic fluid (normal saline or LR) • Mild to moderate dehydration • May replace with oral rehydration solutions given “little and often” (~ 5 ml q1-2 minutes) • Deficit should be replaced over 3-4 hours • If child is intolerant, may consider NG tube or parenteral administration

31. Refeeding (Maintenance) • AAP and CDC recommend resumption of an age-appropriate diet after completion of rehydration • Unrestricted diets shown to reduce stool output and duration of disease • Breastfeeding should continue through the rehydration phase • BRAT (Bananas, rice, applesauce, toast) and clear liquids well tolerated but restrictive and have suboptimal nutritional value

32. Antibiotics • Not indicated for viral gastroenteritis • If bacterial or parasitic causes of gastroenteritis are suspected, confirm with culture before initiation of antibiotics • If organism isolated, antimicrobial therapy may be indicated • May prolong shedding (Salmonella) • Refer to Red Book

33. Antiemetics & Antimotility Agents Antiemetics: use is controversial • Cochrane review: Reglan and zofran • Small number of trials showed some benefit in reducing the number of episodes of vomiting over placebo • There was increased incidence of diarrhea in antiemetic group, thought to be secondary to retention of fluid and toxins that would have been eliminated by vomiting. • May be of some benefit • Promethazine: no demonstrable benefit • Increased risk of respiratory depression (black box warning) and dystonic reactions • Not to be used <2 years Antidiarrheal agents (Loperamide) • No data to prove benefit • Potential for side effects: lethargy, paralytic ileus, toxic megacolon, CNS depression • Delays transit time  prolong course of bacterial diarrheas

34. Probiotics • Microbial cell preparations or components of microbial cells that have beneficial effects on human health • Lactobacillus • Compete for available nutrients and binding sites, thus acting against enteric pathogens • Cochrane review of 23 studies • Reduced risk of diarrhea and duration of illness • May be some benefit in acute infectious gastroenteritis in addition to rehydration therapy

35. Prevention • Hand washing! • Excretion can begin before symptoms and continue after symptoms resolve • Asymptomatic infection common route of spread • Rotavirus vaccine • Pentavalent vaccine administered orally at 2, 4, 6 mths of age; first dose b/w 6-12 wks (no later then 12 weeks) and all doses administered before 32 weeks • Will prevent 75% of rotavirus cases, 98% of severe cases, and 96% of hospitalizations due to rotavirus • 2, 4, 6 months • Diaper changing • Changing area should be separate from food preparation area • Diapers should be placed in occlusive bags • Cleaning solution • Water purification • More of an issue in developing countries • Boil water for 10 minutes or using chlorine containing tablets

36. Summary • Acute gastroenteritis is a leading cause of morbidity nationwide leading to dehydration, hospital admission, and rarely, death • Viral causes (rotavirus) predominate as the pathogen • Initial management rely on assessment of severity of dehydration and fluid resuscitation • Early refeeding after resuscitation is the goal for maintenance of hydration • Some possible benefit to probiotics and antiemetics (reglan, zofran) • Antibiotics rarely indicated • Prevention is key  HANDWASHING!

37. References: Alhashimi D, Alhashimi H, Fedorowicz Z. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD005506. DOI: 10.1002/14651858.CD005506.pub3. Allen SJ, Okoko B, Martinez E, Gregorio G, Dans LF. Probiotics for treating infectious diarrhoea. Cochrane Database of Systematic Reviews 2003, Issue 4. Art. No.: CD003048. DOI: 10.1002/14651858.CD003048.pub2. Armon, K., et al. “An evidence and consensus based guideline for acute diarrhoea management.” Arch Dis Child, 2001; 85: 132-142. Matson, David. “Epidemiology, pathogenesis, clinical presentation, and diagnosis of viral gastroenteritis in children.” Matson, David. “Prevention and treatment of viral gastroenteritis in children.” Up-To-Date, 2008 Rudolph, A., et al. “Infectious Diarrhea.” Rudolph’s Fundamentals of Pediatrics, 3rd edition. 2002: 356-60.