Acute Gastroenteritis

Transcription

1 Acute Gastroenteritis 1

2 Overview Acute gastroenteritis (AGE) Epidemiology Aetiology Pathophysiology Therapy and prophylaxis Traveller s diarrhoea Toxin mediated diarrhoea 2

3 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 3

4 Rotavirus impact Ubiquitous Many animal species Swap genes with human Almost all infected by 2y Developing countries mortality Developed countries hospitalisation and costs deaths 2.3 million admissions 24 million OP visits 114 million episodes 4

5 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 5

6 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 6

7 Reconsider if.. Vomiting bile or blood severe abdominal pain toxic, high fever Abdominal signs: distension, tenderness, guarding, mass, hepatomegaly neonate failure to thrive 7

8 AGE Aetiology - Australia 1. Rotavirus 2. Norovirus (NLV/SRSV) =caliciviruses 3. Adenovirus 4. Astrovirus 5. Campylobacter jejuni 6. Salmonella sp 7. EPEC, EAEC, EHEC, sapoviruses 8. Protozoa: Giardia lamblia, cryptosporidia 8

9 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 9

10 Why the change in aetiology? RT-PCR and PCR-?down to 10 pfu/ml More sensitive than: EM ~10 5 /ml ELISA ~10 4 /ml Latex agglutination ~10 5 /ml culture Environmental change: e.g. DCC, hygeine Food preparation and transport 10

11 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 ,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

12 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 12

13 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 VP7 codes G type VP4- codes P type 13

14 Rotavirus epidemiology Winter/spring peaks in temperate climates Less predictable tropical climates Peak infection 6-24 months 1 st infection most severe Most infections asymptomatic Increased in: Day care centres (x2) Hospitals (?15%) 14

15 Rotavirus transmission Diarrhoea up to fcfu/g?infective dose 10 1 fcfu/g Faeco-oral But.detected in/on: Resp secretions Air of hosp rooms infected immunosuppressed patients Fomites/toys 15

16 16

17 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 17

18 Astrovirus ssrna virus milder clinically DCC outbreaks Adenovirus DNA virus Enteric types 40 and 41 18

19 Viral AGE features Virus Season Age Days Lact Intol Mode Rota Winter/ Spring 6-24m 5-7 Yes F-O,?resp Adeno Summ Child 6-9 Yes F-O Noro/ Calici All All 1-4 No F-O, foods, water, resp Astro Winter All 3 Yes F-O 19

20 Clinical features- hospitalised Feature Incub Vomiting Fever >39 Rhinitis Pharyngitis Red TM Cx LN Dehyd - Isotonic Rotavirus Non-rota 1-3d Hrs-days 96% 58% 31% 33% 26% 22% 49% 32% 19% 18% 80% 95% 9% 9% 40% 77% 20

21 Clinical spectrum- viral Most asymptomatic Up to 20 vomits/d Up to 20 episodes diarrhoea/d More severe it is: more likely rotavirus 21

22 Inflammatory enteritis Suggested by: Fever Abrupt onset diarrhoea Onset diarrhoea before vomiting >4 stools per day Blood or mucus in stool 22

23 Inflammatory enteritis Mucosal damage and release inflammatory mediators Cytotoxins and/or mucosal invasion Bacterial Shigella spp., EIEC, EHEC, Campylobacter jejuni/coli, Salmonella spp., EAEC, EPEC, Yersinia enterocolitica, Aeromonas hydrophila Parasitic Cryptosporidium, Entamoeba histolytica, Strongyloides stercoralis, Schistosoma Viral CMV, enteroviruses 23

24 Bacterial pathogens Shigella sonnei most common of 4 species Low infectious dose 10 2 cfu Person-person, food-borne seizures Campylobacter jejuni Dysentery and enteritis Bacteraemia/dissemination rare Bird GITs reservoir Food-borne outbreaks mainly 24

25 Salmonella spp. Bacterial pathogens 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 25

26 Bacterial pathogens E 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) 26

27 Dehydration MILD 3-5% MODERATE 5-7% Thirsty, alert, restless Otherwise normal Thirsty, restless, lethargic, irritable Rapid pulse, normal BP Sunken eyes & fontanelle Dry mucous membranes Decreased skin turgor (1-2 sec) Decreased urine output SEVERE >7% Drowsy, Limp, Cold, Sweaty, Cyanotic limbs Rapid feeble pulse, low BP Sunken eyes & fontanelle Dry mucous membranes Decreased skin turgor (>2 sec) No urine output 27

28 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 28

29 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 29

30 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 30

31 Rehydration solutions drink Na K Cl citrate Glucose % Cola No-bicarb 5 to 15 Apple juice 1 20? yes 10 to 15 Chicken broth ? 0 Tea yes 0 Gatorade yes 5 WHO gastrolyte

32 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 32

33 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 33

34 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 34

35 Mx Inflammatory enteritis Cotrimoxazole Resistance emerging developing world Shigella Quinolones* Not licensed for children 35

36 Travellers diarrhoea ETEC Shigella Salmonella Campylobacter Entamoeba histolytica Giardia Many take cotrimox & metronidazole or quinolones away 36

37 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 37

38 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%) 38

39 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 39

40 Prevention Clean water Esp dysentery and cholera Breast feeding Measles vaccination Vitamin A?hygeine-??no impact on rotavirus vaccines 40

41 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 41

42 Rotavirus protection and vaccine 1 st infection homotypic (same G type) 2 nd infection heterotypic infection RRV-TV G1-4 Withdrawn 1998 Intussusception Peak d3-7 post dose 1?no community increase Increased risk if older with 1 st dose RRV3 HU1 HU2 RRV1 RRV2 RRV3 HU4 RRV4 42

43 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? 43

44 Rotavirus Vaccines: NEJM 5 Jan 06 Rotarix (GSK) Human monovalent G1 P[8] Safe, effective, 2 doses % 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 44