Acute Gastroenteritis WAFA SAMA’N Pediatrics MD.

Incidence:- The second most common cause of death in children <5 years. Account for 1.5 million death of children/year globally.(13% of all deaths). Every child <5 years has 3.6 episode of diarrhea/year. Mortality due to diarrhea has declined cause of Rotavirus vaccine, improved nutritional status, better management of disease.

Etiology:- Feco-oral route transmission. Ingestion of contaminated food or water. Person to person transmission occur in pathogens infectious in small inoculum ,like Shigella,campylobacter,EHEC,Norovirus, Rotavirus, E.histolyticum and Giardia. Most common cause is viral like Rota,norovirus(Norwalk) then adenovirus and enteric viruses.

Bacterial causes like salmonella,Shigella and E.Coli. Waterborne outbreaks of diarrhea caused by cryptosporidium commonly and others like:-Shigella, E.coli, Norovirus and Giardia. Antibiotics associated pseudomembranous colitis is due to Clostridium defficile. Usually all children acquired Rotavirus, enterovirus and Giardia lamblia in the first 5 years of life.

Diarrhea Classification Pathophysiology Osmotic Secretory Exudation Abnormal motility Duration Acute (< 2 weeks) Chronic (> 2 weeks)

Mechanism of Diarrhea:- Non-inflammatory Enterotoxin/Adherence Inflammatory Invasion/cytotoxin Penetration Location Proximal Small Bowel Colon Distal Small Bowel Illness Watery Diarrhea Dysentery Enteric Fever Stool Examination No fecal leukocytes Mild or no lactoferrin Fecal Neutrophil lactoferrin Fecal mononuclear leukocyte Example V.cholera,E.coli (ETEC,EPEC,EAEC) ,Norwalk,Giardia,Staphaureus,Cl.perfringes. Shigella,E.coli(EIEC,EHEC) Salmonella enteritidis,Cl.defficile,E.histolytica. Salmonella typhi Yersina Enterocolitica

Osmotic diarrhea Def: Increased amounts of poorly absorped, osmotically active solutes in gut lumen Interferes with reabsorption of water Solutes are ingested magnesium sorbitol malabsorption of food (mucosal injury, lactase deficiency)

Secretory diarrhea Excess secretion of electrolytes, fluid across mucosa Usually coupled with decrease in absorption Watery, high-volume diarrhea with dehydration Enterotoxins: Cholera, E. coli, food poisoning, Rotavirus (?), Norwalk virus (?)

Osmotic/Secretory VOLUME OF STOOL <200ml/24 hrs >200ml/24 hrs Response to fasting Diharrea stops Diharrea continues Stool Na <70 mEq/l >70 mEqu/l Reducing substances Positive Negative Stool pH <5 >6

In secretory Diharrea enterotoxin produced by microorganism cause inhibition of Na-Cl pump but not(glucose-Na) pump. In inflammatory diharrea extensive histological damage,release of cytokines leads to increase crypt secretion of Chloride ion by increasing c-AMP.Uncoupling of both Na-H,Hco3-CL –and Na-Glucose uptake. In Shigellosis superficial invasion of colonic mucosa and phagocytic activation with apoptosis and inflammatory interleukins release leading to neutrophilic degranulation.

Risk Factors:- Environmental contamination of water and food. Young age. Immunedefficiency. Measles. Malnutrition. Lack of exclusive breast feeding. Vitamin A defficiency. Zink defficiency is known also to increase mortality in pneumonea,measles and diharrea.

Complications:- Dehydration. Prolongation of diharrea with resultant malnutrition Secondary infections. Micronutrient defficiency(Zinc,Iron). Extraintestinal manifestations like reactive arthritis,GuillianBarre(C.jejeuni),glomerulonephritis,HUS and erythema nodosum(salmonella,campylobacter).

Treatment:- ORS is considered the cornerstone in treatment because it has appropriate osmolality about 310 mos/Kg. ORS can’t be given in shock,ileus,vomiting,high stool output>10cclKG Home made remedies like carbonated beverages(soda),fruit juice are not suitable for rehydration or maintainance because of high osmolality and low Na concentration.

Enteral feeding should be continued during recovery from episode of diarrhea. Although brush border of intestine is affected ,still satisfactory absorption of CHO,protiens and fats can occur. Once rehydration is complete food should be reintroduced to replace ongoing losses by emesis or diharrea. Breast feeding or non diluted formula should be given. Food like rice soup,vegetables,fruits and yogurt can be given in the recovery period. Fatty food or food high in simple sugars should be avoided. Energy given should be 100 Cal/Kg/d and proteins 2-3glKg/d. Acute lactose intolerance is seen in some patients ,so they should be given Lactose free formula like replacing some of milk requirements with yogurt or milk free diet like comminuted chicken or elemental milk.

Oral rehydration solutions

Additional therapy:- Zinc supplement reduce duration ,severity and prevent recurring diharrea. Probiotics like non-pathological bacteria,can restore beneficial intestinal flora,decrease proinflammatory cytokines and increase anti-inflammatory factors Lactobacillus bifidobacterium and lactobacillus rhamenosus reduced duration in Rota.

Additional therapy:- Anti-motility(Loperamide) NO Role. Anti-emetics like phenothiazine, no role. Ondansetron is a selective anti 5HT receptors and a safe anti-emetic can be given as a single dose before ORS if there is vomiting. Antibiotics should not be given routinely because indiscriminate use lead to bacterial resistance and may prolong bacterial shedding

Prevention:- Promotion of exclusive breast feeding so no other fluid or food should be given in 1st 6 months. Improved complementary feeding preparation with hygenic practice. Vit-A supplement. Rota virus immunization.oral live attenuated pentavalent vaccine.

Viral causes of gastroenteritis Rotavirus Calcivirus(Norwalk) Enteric Adenovirus Astrovirus Others Torovirus,Coronavirus and Pesivirus

Rotavirus Mostly in infants between3-24 months. Low infection inoculum size so person-person spread is common. All children exposed by age 4-5 years Double stranded RNA virus Several groups (A-E ) Most common cause of viral diarrhea

Rotavirus

Pathogenesis Selectively infects &destroys villous tip cells in small intestine ,gastric mucosa is not affected. Villi have absorptive &digestive functions so both are affected in Rota viral infection. Viral enteritis enhance mucosal permeability to macro molecules leading to increase incidence of food allergy. Infants are more prone to infection because of decrease intestinal reserve , gastric acidity and lack of specific immunity.

Transmission Fecal-oral Contaminated water supplies Poor hygiene Food Fomites

Clinical manifestations:- Incubation period <48 hrs. Low grade fever,vomiting followed by diharrea lasting<one week,usually watery,no blood or white cells. Infants commonly develop dehydration. Malnourished children develop severe &prolonged illness. Newborns usually are asymptomatic some may develop NEC outbreaks in nurseries.

Diagnosis of rotavirus Electron microscopy Small intestine Stool Antigen in stool commercial ELISA PCR, nucleic acid probes No RBC or WBC in stool

Rotavirus Clinical Syndromes Asymptomatic carriers Diarrheal illness 2-3 day incubation period diarrhea, vomiting fever 3-7 days high infectivity Complications dehydration chronic diarrhea dissemination NEC

Prevention of Rotavirus Natural immunity 93% protective (sIgA) Good hand washing&isolation . Vaccine Was licensed in 1998 for infants 2,4,6 mo. offered 80% protection.

Norwalk virus

Norwalk virus “winter vomiting disease” 1968, Norwalk Cause 40% of nonbacterial epidemics Explosive epidemics camps, cruise ships, nursing homes Food borne illness raw shellfish

Norwalk virus: Clinical Features 24-48 hour incubation period vomiting prominent diarrhea 1-3 days less severe than rotavirus Small 27-35-nm single stranded RNA virus Most common cause of GE outbreaks in older children &adults Similar to staph food poisoning

How does Norwalk virus cause diarrhea? Infection affects proximal small bowel Patchy mucosal injury Malabsorption ? Excess secretion

Other viruses causing gastroenteritis Adenovirus Enteric serotypes 40,41 80-nm single stranded DNA Do not cause respiratory symptoms Common cause of GE in children and adults Prolonged course 10-14 days Astrovirus Second common cause of viral GE Single stranded RNA 30-nm diameter Similar to Rota infection but milder

Bacterial Etiology:- Salmonella Two main species with many different serotypes(S.Enterica S.bongori)Serotypes are divided according to somatic O antigen and flagella H antigen. G-ve flagellated rods killed by heat. Transmitted by raw poultry,eggs,vegetables contaminated water. Person-person spread uncommon because of large inoculum size.

Presentation Salmonellosis(acute enteritis): Incubation period 6-72 hrs. Nausea,vomiting,abdominal pain ,fever diharrhea,usually watery but st bloody. Rarely septicimia and septic shock. Extraintestinal manifestations like osteomyelitis,septic arthritis,meningitis Usually self limiting disease like food poisoning.

Treatment:- Correct dehydration Antimotility drugs are contraindicated because they increase incidence of perforation Antibiotics are not used in simple enteritis because they increase resistance prolonged bacterial shedding &carrier state.

Treatment:- Antibiotics are indicated in infants <3 months In patients with immune deficiency In patients with typhoid fever In septicimia and localized infection In chronic carrier before cholycystectomy

Shigella:- There are 4 species (S.dysenteriae S.sonnei S.flexneri S.bodyii) Aerobic non-motile G-ve rods Transmitted by contaminated water and food Person-person is common ,because the inoculum size is only 100 bacteria Invasion of colonic mucosa with production of enterotoxin

Complications:- Acute bloody diarrhea( tenesmus,crampy pain with fever) Hemolytic uremic syndrome(acute renal failure,hemolytic anemie,thrombocytopenia) Neurological complications (lethargy,coma and convulsions) Reiter syndrome(conjunctivitis urethritis and arthritis)

Treatment:- Fluid and electrolyte correction Antibiotics treatment in all children with shigellosis. Antibiotics are given to shorten duration of illness so the child will not be infectious Prolonged course if untreated with resultant malnutrition Ceftriaxone is drug of choice

Pseudomembranous Colitis :- Clostridium difficile is the causative bacteria It is found in colon as inactive spore form Antibiotics disrupt normal flora in intestine so dormant spores are activated They produce toxin that damage the colonic mucosa with production of membrane Antibiotics implicated mostly Clindamycin,Ampicillin,amxycillin Oral metronidazole or Vancomycin is drug of choice

Amebiasis Two species that are genetically identical E.histolyticum and E.dispar E.dispar usually asymptomatic carrier E.histolytica in 90% of cases are asymptomatic cyst passer Infection transmission is by cyst because they are resistant to cold and chlorination Trophozoites are not infectious Person-person transmission can occur

Symptoms Amebic dysentery with colicky abdominal pain frequent bowel motions,bloody diarrhea and tenesmus No general signs and symptoms Low grade fever May invade intestinal mucosa to cause abscess in liver and rarely in brain Chronic amebic colitis indistinguishable from IBD

Treatment All individuals with cyst or trophozoites in their stool whether symptomatic or not should be treated Metronidazole is the drug of choice for invasive amebiasis Iodoquinol and paromomycin is the treatment of choice for amebic cyst

Giardia lamblia Flagellated protozoan infects the duodenum and proximal jejunum It is found as cyst and trophozoites form 10-100 cysts are enough to cause infection Water and food borne infection Person-person infection is common Most common intestinal parasite Cysts are resistant to chlorination but killed by boiling

Symptoms Acute infectious diarrhea no mucus or blood in stool Chronic diarrhea leading to malabsorption and failure to thrive with fats and sugar in stool Most infections are asymptomatic No extra intestinal spread Diagnosed by stool analysis or duodenal aspirate and biopsy

Treatment Asymptomatic carriers are not treated Albendazole treatment for 5 days Others like metronidazole,furazolidone and paromomycin are effective treatment Infections in pts who have agammaglobulinemia should be treated

Antimicrobial Therapy:- Organism Antimicrobial Agent Indications for Rx Campylobacter Erythromycin/Quinolones Early in the course of disease Clostridium difficile Metronidazole/Vancomycin Moderate to severe disease E.coli TMP/SMZ Severe or prolonged illness Nursery epidemics Salmonella Cefotaxime/Ceftriaxone Ampicillin/TMP/SMX Bacteremia,suppuration Infants<3mon,typhoid fever Shigella Ampicillin,Ceftriaxone Ciprofloxacin All cases +ve stool Giardia lamblia Metronidazol/albendazol Entamoeba hisolyticum Metronidazol/iodoquinol Trophozytes/cyst

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