Gastroenteritis Acute Care Module Jonathan Bae, MD 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 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 Epidemiology Approximately 5 billion episodes of diarrhea/gastroenteritis occur worldwide annually In children <5 years old, there are 1-5 episodes per child-year – – 1 in 50 children are hospitalized during childhood due to acute gastroenteritis – – – 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 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 Transmission Fecal-oral route Contaminated food and water Daycare, school Respiratory tract inoculation? 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. 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) 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 Physical Exam 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 Laboratory Evaluation Elevated specific gravity on urinalysis Isotonic dehydration Metabolic acidosis Stool gram stain, culture, and electron microscopy (viruses), ova & parasites – Fecal leukocytes – – Labs routinely test for Salmonella, Shigella, and Campylobacter 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 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) Viral vs. Bacterial Viral gastroenteritis accounts for 70-90% of cases Bacterial gastroenteritis 10-20% 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 Gastroenteritis Rotavirus Calcivirus (Norwalk) Enteric adenovirus (serotypes 40 & 41) Astrovirus 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 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) Adenovirus Enteric subtypes 40 & 41 Similar to rotavirus but with longer course (>6 days) Common year round Typically affects older children Bacterial Gastroenteritis Campylobacter jejuni E. Coli Salmonella Shigella Yersinia enterocolitica Vibrio cholera C. Diff Staph Bacillus cereus 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 Escherichia coli 1. Gram-negative rod with four different subclasses named for distinct mechanisms of action Enterotoxigenic E. coli 2. Enteropathogenic E. coli 3. Infects and disrupts enterocytes Musty smelling stool w/o blood or mucous Enteroinvasive E. coli 4. Toxin similar to cholera Watery, large volume diarrhea 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) 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 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) 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 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 Other bacterial pathogens Clostridium difficile – – – – Staphylococcal – – – – – 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 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) Parasites Giardia lamblia – – – – – Entamoeba histolytica – – Ingestion of infected cysts resulting in loose, bloody, mucoid diarrhea May be complicated by hepatic abscess Cryptosporidium – – 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 Daycare settings, immunocompromised hosts (HIV) Frequent, watery stools Isospora – Common in HIV/AIDs 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 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 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 Assessment of Dehydration 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 Refeeding (Maintenance) AAP and CDC recommend resumption of an ageappropriate 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 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 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 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 Prevention Hand washing! – – 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 – – – Excretion can begin before symptoms and continue after symptoms resolve Asymptomatic infection common route of spread 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 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! 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.” UpTo-Date, 2008 Rudolph, A., et al. “Infectious Diarrhea.” Rudolph’s Fundamentals of Pediatrics, 3rd edition. 2002: 356-60.