Acute Gastroenteritis - Royal Children's Hospital · PDF file– sudden onset self limiting acute diarrhoea ... • Most common cause outbreaks gastro – Adults ... Inflammatory enteritis

November 06Jim Buttery- RACP lectures 2006

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Acute Gastroenteritis


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Overview

• Acute gastroenteritis (AGE)– Epidemiology– Aetiology– Pathophysiology– Therapy and prophylaxis

• Traveller’s diarrhoea • Toxin mediated diarrhoea


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AGE mortality

• Kills ~1.5 million each year <5 years– One death every 21 seconds– Largely due to lack of access to

• Oral rehydration therapy• Clean water• Health care• Immunisation (measles)• Nutrition (vitamin A)

• Improved over last 15 years


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Rotavirus impact• Ubiquitous• Many animal species

– Swap genes with human

• Almost all infected by 2y• Developing countries

mortality• Developed countries

hospitalisation and costs

452000 deaths

2.3 million admissions

24 million OP visits

114 million episodes


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Definitions:

• Gastroenteritis– sudden onset self limiting acute diarrhoea

• increased stool frequency with alteration of stool consistency

• Invasive– Blood or mucous – More likely to be due to bacteria, esp

• Shigella, Camp, Salmonella– More abdominal pain


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Differential Dx AGE

• Systemic infection– UTI, pneumonia– sepsis, meningitis

• Surgical conditions– appendicitis– intussusception– partial bowel obstruction, Hirschsprung’s

enterocolitis• Other

– DM, antibiotic associated diarrhoea, HUS


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Reconsider if…..

• Vomiting bile or blood • severe abdominal pain• toxic, high fever• Abdominal signs:

– distension, tenderness, guarding, mass, hepatomegaly

• neonate• failure to thrive


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AGE Aetiology - Australia

1. Rotavirus2. Norovirus (NLV/SRSV) =caliciviruses3. Adenovirus 4. Astrovirus5. Campylobacter jejuni6. Salmonella sp7. EPEC, EAEC, EHEC, sapoviruses8. Protozoa: Giardia lamblia, cryptosporidia


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AGE aetiology

Developed countries• Rotavirus• Norovirus • Astrovirus• Adenovirus• Campylobacter jejuni• Salmonella sp• EPEC, EAEC, EHEC• Sapoviruses• Protozoa

Developing countries• Rotavirus• Campylobacter sp• EHEC/EAEC/EPEC/ETEC• Shigella sp• Salmonella sp• Vibrio sp• Aeromonas?• Noro, astro, adenovirus• Protozoa incl Entamoeba


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Why the change in aetiology?

• RT-PCR and PCR- ?down to 10 pfu/ml– More sensitive than:

• EM ~105/ml• ELISA ~104/ml• Latex agglutination ~105/ml• culture

• Environmental change: e.g. DCC, hygeine• Food preparation and transport• …


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Epidemiology- developed• 1 in 5 have infectious intestinal disease (IID) each year• 1 in 6 of these present to GP• 18% children <5yrs present with IID each year

– UK data• Wheeler et al, BMJ 1998

• 20,000 AGE admissions each year in Australia– 10,000 rotavirus admissions

• NT: Aboriginal children x10 more likely to be admitted– Darwin aex: EAEC, rotavirus, enteropathogenic E. coli,

Salmonella spp, Cryptosporidium parvum and Strongyloides• Kukuruzovic,R. et al PIDJ 2002


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Viral pathogenesis

• Infect enterocytes jejunum and ileum– Cell destruction day 1

• Transduction of fluid into lumen• Net loss of water and salt in faeces

– Day 2-5 adjacent villi fuse• Reduce surface area =>decrease fluid loss

– Day 6-10 architecture restored• Rotavirus NSP4 enterotoxin- ?role


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Rotavirus- virology• dsRNA virus• Segmented chromosome

– Enables reassortment• Potential new serotypes

• G1-4 main serotypes 95%– worldwide– Until recently in Australia

• G9 predominant last 3 years• Does cause viraemia**

• Lancet- 2003

VP7 – codes G type

VP4- codes P type


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Rotavirus epidemiology

• Winter/spring peaks in temperate climates• Less predictable tropical climates• Peak infection 6-24 months• 1st infection most severe• Most infections asymptomatic• Increased in:

– Day care centres (x2)– Hospitals (?15%)


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Rotavirus transmission

• Diarrhoea up to 1010 fcfu/g• ?infective dose 101 fcfu/g • Faeco-oral• But….detected in/on:

– Resp secretions– Air of hosp rooms infected

immunosuppressed patients– Fomites/toys


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Norovirus (NLV)• Recently renamed as norovirus• ssRNA virus, in Caliciviridae, was Norwalk• Most common cause outbreaks gastro

– Adults– Health care outbreaks– Cruise ships

• Food borne outbreaks, e.g. oysters• Airborne spread in vomitus as well as faeco-oral• ?persistence on fomites- Alaskan cruises• Previous exposure no long term protection


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Astrovirus

• ssRNA virus• milder clinically• DCC outbreaks

Adenovirus• DNA virus• Enteric types 40 and 41


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Viral AGE features

F-OYes3AllWinterAstro

F-O, foods, water, resp

No1-4AllAllNoro/ Calici

F-OYes6-9ChildSummAdeno

F-O, ?respYes5-76 -24m

Winter/ Spring

Rota

ModeLactIntol

DaysAgeSeasonVirus


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Clinical features- hospitalised

32%49%Pharyngitis

77%95%- Isotonic40%80%Dehyd9%18%Cx LN9%19%Red TM

22%26%Rhinitis33%31%Fever >3958%96%Vomiting

Hrs-days1-3dIncubNon-rotaRotavirus Feature


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Clinical spectrum- viral

• Most asymptomatic• Up to 20 vomits/d• Up to 20 episodes diarrhoea/d• More severe it is: more likely rotavirus


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Inflammatory enteritis

Suggested by:• Fever• Abrupt onset diarrhoea• Onset diarrhoea before vomiting• >4 stools per day• Blood or mucus in stool


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Inflammatory enteritisMucosal damage and release inflammatory mediators

– Cytotoxins and/or mucosal invasionBacterial

– Shigella spp., EIEC, EHEC, Campylobacter jejuni/coli, Salmonella spp., EAEC, EPEC, Yersinia enterocolitica, Aeromonas hydrophila

Parasitic– Cryptosporidium, Entamoeba histolytica, Strongyloides

stercoralis, SchistosomaViral

– CMV, enteroviruses


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Bacterial pathogens

Shigella– sonnei most common of 4 species– Low infectious dose 102 cfu– Person-person, food-borne– seizures

Campylobacter jejuni– Dysentery and enteritis– Bacteraemia/dissemination rare– Bird GITs reservoir

• Food-borne outbreaks mainly


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Bacterial pathogensSalmonella spp.

– Wide spectrum of severity from mild diarrhoea to dissemination, enteric fever

– Predom food-borne• Usually contaminated animal products

Yersinia enterocolitica– ac diarrhoea to septicaemia (esp infants and

immunosuppressed)– Mesenteric adenitis– Post-infectious: Reiter’s, arthritis, GN, erythema

nodosum


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Bacterial pathogensE coli:• ETEC - watery diarrhoea infants and travellers• EIEC - sim to Shigella sonnei• EPEC - ac and chr watery diarrhoea• EHEC - haemorrhagic colitis/ HUS

– Australia O139 mainly, US 0157– Shiga-like toxin production

• EAEC - ac and chr watery diarrhoea– More developing conditions (NT)


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DehydrationMILD3-5%

Thirsty, alert, restlessOtherwise normal

MODERATE5-7%

Thirsty, restless, lethargic, irritableRapid pulse, normal BPSunken eyes & fontanelleDry mucous membranesDecreased skin turgor (1-2 sec)Decreased urine output

SEVERE>7%

Drowsy, Limp, Cold, Sweaty,Cyanotic limbsRapid feeble pulse, low BPSunken eyes & fontanelleDry mucous membranesDecreased skin turgor (>2 sec)No urine output


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Management viral AGE (1):

• ABC• Treat shock if present• Assess dehydration

– Mild 3-5%– Mod 5-7%– Severe >7%

• Rehydrate ASAP– ORT orally or NGT vast majority

• Vomiting not a contraindication to either


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Management viral AGE (2):

• Investigations rarely needed– Stool

• Blood mucus not present (if yes =>inflammatory)• WC tests negative• pH<6, reducing sugars• Virology: EIA rota/adeno standard assays at RCH• Culture: only if suspect bacteria

– U&E occasionally indicated if severe dehydr• >7% dry, neonates, prolonged illness• beware hypernatremia


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Oral Rehydration Therapy

• Rehydrate rapidly – Deficit plus maintenance (incl ongoing losses)– Replace over 6 hours

• Reintroduce solids as soon as feel like it– Starchy if possible

• Continue breast feeding• Formula/milk …..• No anti-diarrhoeal agents in childhood


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Rehydration solutions

drink Na K Cl citrate Glucose %Cola 2 0 27 No-bicarb 5 to 15Apple juice 1 20 ? yes 10 to 15Chicken broth 250 5 250 ? 0Tea 0 0 0 yes 0Gatorade 20 3 17 yes 5WHO 90 80 80 10 2gastrolyte 60 20 60 10 2


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ORT plus?

• Rice based ORT– Reduced faecal output– eg. Gastrolyte-R

• Lactobacillus GG– Reduced faecal output in rotavirus AGE– Effect mainly developed world, hospital– Less impressive in developing countries

• Benefit restricted to non-breast fed


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Mx Inflammatory Enteritis

• Stool– M/C/S– Microscopy concentrate + stain for

crypto/?Giardia– OCP if suspect parasites– WBC >5 per high power field in >80%

• Not in ETEC, EPEC, Giardia• Variable in Salmonella, Yersinia

• rehydrate


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Mx Inflammatory enteritis

• ?antibiotics- MINORITY ONLY– Effective treatment

• Shigella, EIEC– Decreases excretion

• Shigella, EIEC, Yersinia, Campylobacter– In some hosts only (eg imm-supp)

• Salm, Camp, EPEC, ETEC, C. diff, Yersinia– Contra-indicated

• EHEC


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Mx Inflammatory enteritis

• Cotrimoxazole– Resistance emerging developing world

• Shigella

• Quinolones*– Not licensed for children


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Travellers diarrhoea

• ETEC• Shigella• Salmonella• Campylobacter• Entamoeba histolytica• Giardia

• Many take cotrimox & metronidazole or quinolones away


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Toxin mediated disease

• Predominantly vomiting, within hours of ingestion. Also diarrhoea. Food derived

• Staph aureus enterotoxins A-L– wide variety food– can function as superantigens

• Bacillus cereus– Classically rice left at RT– other ‘grainy’ foods possible


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Antibiotic associated diarrhoea• More common broader spectrum antibiotics

– including augmentin• Mx- Stop antibiotics, (probiotics)• little yield routine faeces MCS once in

hospital >72 hours– Clostridium difficile toxin assay only bacterial test

indicated• Rx metronidazole (1st), oral vancomycin (2nd line)• NB: C difficile carriage common in well newborns

(30%)


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Risk factors

• Beef: EHEC, salmonella• Poultry: Campylobacter, Salmonella• Pork: Yersinia, Salmonella• Water: Shigella, salm, Camp, Crypto• Seafood: norovirus, Vibrio parahaemolyticus• Unpasteurised milk: Salm, Camp, Yers• DCC: most things incl Shig, Giardia, crypto


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Prevention

• Clean water– Esp dysentery and cholera

• Breast feeding• Measles vaccination• Vitamin A• ?hygeine- ??no impact on rotavirus• vaccines


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Vaccines• Few enteric vaccines• Salmonella typhi

– Vi polysaccharide vaccine– Live oral vaccine

• Cholera vaccine• Rotavirus vaccines….• Other viruses

– hard to grow: astro, adeno– impossible to grow: noro


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Rotavirus protection and vaccine

• 1st infection homotypic (same G type)• 2nd infection heterotypic infection• 1997-8 RRV-TV G1-4• Withdrawn 1998

– Intussusception– Peak d3-7 post dose 1– ?no community increase– Increased risk if older with 1st dose

RRV1 RRV2 RRV3 RRV4

HU2HU1 HU4

RRV3


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Rotavirus vaccines

• Do they cause intussusception?– No! ☺ !!

• Development ?>$500 million USD– Sample sizes biggest ever to detect IS– Recoup costs and make profit – Will they cover new serotypes, eg G9?

• Will they get to those who need them?


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Rotavirus Vaccines: NEJM 5 Jan 06• Rotarix (GSK) Human monovalent G1 P[8]

– Safe, effective, 2 doses– 85-100% efficacy against severe disease– *excretion up to 10 days– Licensed

• Rotateq (Merck) Reassortant G1-4,6 P[5]– Bovine-human reassortant– Safe, effective, 3 doses– 96% efficacy against severe disease– Minimal excretion– Safe and efficacious in prems– Licensed

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Acute Gastroenteritis - Royal Children's Hospital · PDF file– sudden onset self limiting acute diarrhoea ... • Most common cause outbreaks gastro – Adults ... Inflammatory enteritis