Enterovirulent Escherichia coli. Tom Cheasty Laboratory of Enteric Pathogens

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1 Enterovirulent Escherichia coli Tom Cheasty Laboratory of Enteric Pathogens

2 Classes of Enterovirulent E. coli Urinary Tract Septicaemia / Meningitis Enteropathogenic Enteroinvasive Enterotoxigenic Vero cytotoxigenic Enteroaggregative Diffusely adherrent (EPEC) (EIEC) (ETEC) (VTEC) (EAEC) (DAEC)

3 Enterovirulent E. coli Infections: Symptoms Mild watery diarrhoea Dysentery Severe bloody diarrhoea Persistent diarrhoea Vomiting, abdominal pain, fever Haemolytic uraemic syndrome

4 EVEC and Routine Microbiology Phenotypic EPEC: slide agglutination EIEC: MacConkey ETEC: nothing VTEC: CTSMAC + serology for O157 ELISA VT2 Genotypic PCR Proteomics DNA Arrays EAEC: nothing DAEC: nothing

5 Expertise Provided by the Reference Laboratory All strains: Selected strains: Confirmation of ID O:H serotyping Phage typing Antibiotic resistance Plasmid profiles Gene testing Gene subtyping PFGE Other methods Serodiagnosis: Immunoblot, ELISA

6 Infective doses of enterovirulent E. coli Pathogen Infective dose (cfu) Reference Type of study EPEC High ( ) Ferguson and June 1952 DuPont et al Savarino 1993, Donnenberg et al v ETEC High (10 6 ) Levine et al v EIEC High ( ) DuPont et al v VTEC Low (<100) Griffin & Tauxe 1991, Burnens et al. 1993, Wachsmuth 1994 Willshaw et al (1994) c15 org/gram e e e, also micro EAggEC High (10 10 ) Nataro et al v DAEC High (?) Previously classified as EPEC

7 Pathotype Predominant O Serogroups Enteropathogenic (EPEC) Infantile diarrhea O26, O55, O86, O111, O114, O119, O125ac, O126, O127, O128ab, O142, O158 Enteroinvasive (EIEC) Dysenteric disease in all age groups O28ac, O112ac, O124, O136, O143, O144, O152, O164, O167, O173 Enterotoxigenic (ETEC) Common cause of travellers diarrhea Cause of diarrheal disease in both humans and animals. O6, O8, O15, O20, O25, O27, O63, O78, O128ac, O148, O153, O159, O167 Vero cytotoxigenic (VTEC) or Shiga toxin-producing (STEC) Diarrhea frequently bloody, in all age groups, in young children leading to hemolytic-uremic syndrome (HUS) Enteroaggregative (EAggEC) Associated with persistent diarrhea and travellers diarrhea O5, O26, O91, O103, O111, O113, O128ab, O145, O157 O3, O44, O51, O77, O86, O92, O111ac, O125, O126 Diffusely adherent (DAEC) Diarrhea in children O1, O2, O21, O75

8 Enteropathogenic E. coli -EPEC Watery diarrhoea with vomiting and fever Can cause protracted chronic enteritis Traditionally associated with children <3yrs Large hospital outbreaks with high mortality

9 EPEC Outbreaks England & Wales Incident Cases Serotype Source Type Coach Trip 40 O111ab H9 Restaurant (1995) Wedding Party >30 O? H10 Food Atypical (1997) Conference Teachers 20 O88 H5? Atypical (2000)

10 EPEC Around the World Country Serogroup(s) Comments Reference Australia O126 H12 14/19 children Barlow et al (1999) J Med Microbiol 12: Bangladesh O127, O114, O126, O125, O119, O128, O142 2 surveys, strong association EPEC and diarrhoea Ansaruzzaman M et al (2000) J Med Microbiol 49: Brazil O26, O55, O111, O119 Bovine mastitis Correa MG (2002) EPEC 40% of cattle Vet Microbiol 85: Brazil O55 Pasteurised milk Da Silva ZN (2001) Rev Saude Publica 35:1-8 Finland O55 in 1 case only 3.2% of 603 cases of diarrhoea Keskimaki M et al (2001) Diag Microbiol Infect Dis 40:151 India O55, O125, O126 Children with diarr Prasannan M et al (2001) Ind J Med Res 14:95-8 Japan O55, O114, O119, O127 Travellers diarr, adults 3.6% Ogata K (2002) Jpn J Inf Dis 55: Poland O26, O86, O127 All atypical EPEC Paciorek J (2002) EAF -ve J Med Microbiol 51: Spain O10, O26, O71, O145, O % of healthy cattle Orden JA et al (2002) n = 412 J Appl Microbiol 93:29-35

11 Enteroinvasive E. coli (EIEC) Symptoms Profuse diarrhoea or dysentery-like illness Chills, fever, cramps. 1-7 days incubation Sites Developing countries, endemic 1-5% of diarrhoea; travellers diarrhoea Occasional outbreaks in developed countries Sources Man, Transmission Foodborne (mainly epidemiological) person-person

12 EIEC Outbreak caused by soft cheese USA 1971 Cases: 387 ill; diarrhoea, bloody diarrhoea, fever, nausea. 14 states involved Organism: Enteroinvasive E. coli O124 Source: Mould-ripened imported soft cheese 25 cheese samples +ve for E. coli O124 cfu /g Ref: Marier et al (1973) Lancet ii: 1376

13 Outbreak associated with Enteroinvasive E. coli October 2003 Site: Indian restaurant Leeds Organism: E. coli O124 (ASSuTm) Cases: 24 (age range 13yrs 51yrs) Symptoms: diarrhoea, abdp, fever Laboratory findings: 2 no symptoms (restaurant staff) All 24 isolates had same MDR pattern, were PCR + for ipah and had identical PFGE profiles

14 Enterotoxigenic E. coli ETEC Cause of cholera-like diarrhoea Common cause of diarrhoea in children in developing countries Leading cause of traveller s diarrhoea

15 Enteroaggregative E. coli -EAEC Watery diarrhoea (sometimes bloody) with vomiting Persistent diarrhoea lasting >14days Developing countries

16 Verocytotoxigenic E. coli: Symptoms Diarrhoea (no blood) Diarrhoea with blood (haemorrhagic colitis) Haemolytic uraemic syndrome (HUS) Thrombotic thrombocytopaenic purpura (TTP) Asymptomatic carriage

17 O157 VTEC Human Isolates Annual Figures England and Wales * *

18 O157 VTEC: Sources linked to human infection United Kingdom beef burgers, butcher s meat, sausages, cooked meat, gravy, Dairy produce Person to Person Open Farms Untreated water

19 175 General Outbreaks The number of animal-related general outbreaks range from 1-6 per year (17%) 57 (33%) 9/12 waterborne outbreaks source most likely animal faeces (no direct microbiology) 25 (14%) 52 (30%) Foodborne Person to Person Animal contact Waterborne Unknown

20 South Wales E. coli O157 Outbreak summary Number of cases 158 Deaths 1 Hospital Admissions Children 28 Adults 5 Children tertiary care 9 Number of Scools 42 Stool samples investigated 2100 Environmental samples 400

21 O157 PT8 Incident November 2005 O157 PT8 VT1+2 Increase in isolates late October - November Distribution initially throughout England Total of 80 isolates to end December 2005

22 Sorbitol fermenting O157 VTEC Appeared in the late 80 s, Outbreak of HUS in Germany Europe outbreaks and sporadic cases, HUS (Austria, Czech Republic, Denmark, Finland) Australia England 1 isolate (2004) Scotland 2 isolates, 1 HUS (2002, 2003) SF

23 Outbreak of Sorbitol positive VTEC O157 England April-May 2006 Yorkshire & Humberside Health Region: 3 cases with HUS (1 fatal) 1 family contact Total: 4 cases O157:H- PT RDNC VT2 Epidemiology inconclusive

24 Non-O157 VTEC Outbreaks Country Year O Group Vehicle Site Japan 1984 O145? Nursery Italy 1992 O111? Community USA 1994 O104 Raw milk Community Germany 1994 C. freundii Australia 1995 O111 Metwurst Community USA 1999 O111? Campers Ireland 1999 O26? Community Ireland 2000 O26 P to P Nursery Germany 2000 O26 Seemrolle Multistate

25 Stay Healthy Thank you for Listening

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