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Non-O157 Verotoxigenic (Shiga Toxin Producing) E. coli

Non-O157 Verotoxigenic (Shiga Toxin Producing) E. coli. Barbara Marshall, MES, CPHI(C) Frank Pollari, Andre Ravel, Katarina Pintar, Angela Cook, Andrea Nesbitt Public Health Agency of Canada. CIPHI National 77th Annual Educational Conference, Halifax, N.S. June 28, 2011. Outline.

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Non-O157 Verotoxigenic (Shiga Toxin Producing) E. coli

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  1. Non-O157 Verotoxigenic(Shiga Toxin Producing) E. coli Barbara Marshall, MES, CPHI(C) Frank Pollari, Andre Ravel, Katarina Pintar, Angela Cook, Andrea Nesbitt Public Health Agency of Canada CIPHI National 77th Annual Educational Conference, Halifax, N.S. June 28, 2011

  2. Outline • C-EnterNet • - Digging Deeper • VTEC • Non O157 • EHEC/HUS-outbreak, Germany, 2011 • Canada • Summary & Final Words M. Gilmour, NML Public Health Agency of Canada | Agence de la santé publique du Canada

  3. C-EnterNet Overview • C-EnterNet is an integrated surveillance program • designed to monitor human enteric illness and to inform • food & water safety policy • Core Objectives: • Detect changes in trends of human enteric disease • incidence and pathogen exposure levels from food, • animal and water sources • Source attribution: determine the proportion of human • cases that are due to water, food & animal contact and • determine statistically significant risk factors for enteric • illness Public Health Agency of Canada | Agence de la santé publique du Canada

  4. C-EnterNet Exposure Assessment • Human case information • and enhanced risk factor information • collected through standardized • questionnaires Enhanced Lab Testing Enhanced Lab Testing • Retail sampling • raw pork chops • ground beef • chicken breasts • bagged lettuce, berries • Animal / Farm sampling • Beef Dairy • Swine Poultry Enhanced Lab Testing • Surface Water testing • 5 sites • Physical parameters • and pathogens Enhanced Lab Testing Public Health Agency of Canada | Agence de la santé publique du Canada

  5. C-EnterNet Pathogens • E. coli O157 • Shigella spp. • Salmonella spp. • Yersinia enterocolitica • Campylobacter • Rotavirus* • Norovirus* • Giardia • Cryptosporidium • Cyclospora • Listeria Enhanced sub-typing is done for all human cases of illness in the community and for the food, water, & on-farm samples being collected = microbial source tracking • Speciation • Sero-typing • Phage-typing • AMR • PFGE • Genotyping *Episodic Public Health Agency of Canada | Agence de la santé publique du Canada

  6. C-EnterNet Framework PHAC C-EnterNet Central Continuous Episodic Sentinel Sites across Canada *similar to but broader than CDC FoodNet Public Health Agency of Canada | Agence de la santé publique du Canada

  7. Sentinel Sites • Site#1 Region of Waterloo, ON & Public Health Ontario - TPHL • Pilot site • Full implementation: Human, Retail, Farm & • Water • Since June 2005 • Site#2 Fraser Health Authority, BC & BCPHL • Partial implementation: Human, Retail, Water • Official launch June 2010 Public Health Agency of Canada | Agence de la santé publique du Canada

  8. Integrated Surveillance • Primary goal is linking source and human illness and ultimately attribution • Integrate laboratory and epi information • Integrate across sources • Incorporate other information sources Water data Retaildata Farm data Human data Public Health Agency of Canada | Agence de la santé publique du Canada

  9. C-EnterNet Outputs & Moving Forward Knowledge Translation : Science to Policy • Reports, Publications & Presentations • Success stories - Rec. Water & Crypto - Travel cases* • Building Capacity: Training Information – Raw Milk • Healthy Control Study • Campy Exposure Study • Non-O157 testing *Ravel A et. al. “Description and burden of travel-related cases caused by enteropathogens reported in a Canadian community”. Journal of Travel Medicine,2011 Public Health Agency of Canada | Agence de la santé publique du Canada

  10. VTECWhat are verotoxigenic E. coli? • A diverse group of E. coli • All produce exotoxins, called verotoxins (VT) or Shiga toxins (STX) • VTEC vary in their ability to cause disease M. Gilmour, NML Public Health Agency of Canada | Agence de la santé publique du Canada

  11. VTEC/STEC What’s in a Name? • Shiga toxin/verotoxin-producing _E. coli • STEC • VTEC • EHEC • - Enterohemorrhagic _E. coli • - Escherichia coli (E.coli) bacteria Scanning Electron Micrograph - ECDC Virulent sub-group of VTEC: Prototype: E. coli O157:H7 Public Health Agency of Canada | Agence de la santé publique du Canada

  12. Evolution of Pathogenic E. coli Salmonella O157:H7 Humans I E.coli STEC EHEC II EPEC O157:H7 Animals EIEC ETEC EAEC Shigella Keith Warriner, 2011 Public Health Agency of Canada | Agence de la santé publique du Canada

  13. Escherichia coli O157:H7 • First described in 1982 • Differ in 1300 genes compared to non-pathogenic E. coli. • High acid tolerance • High virulence (10 -100 cells) • Young, elderly and immuno-compromised K. Warriner,2011 Public Health Agency of Canada | Agence de la santé publique du Canada

  14. Inflamed tissue Hemorrhagic lesions VTEC • E. coli O157:H7 is the STEC most frequently isolated in North America and is the serotype most often associated with bloody diarrhea and HUS • This is changing • Non-O157 STEC causes sporadic illness and outbreaks of bloody diarrhea and HUS - under reporting is an issue Intestinal pathology of virulent VTEC: Colon showing lesions of hemorrhagic colitis (HC) - R. Johnson Public Health Agency of Canada | Agence de la santé publique du Canada

  15. VTEC & HUS • In the US about 6%* (5-10%**) of patients (with a majority being children under five years old and the elderly - the most susceptible) - develop HUS, characterised by acute kidney failure, bleeding and neurological symptoms * NEJM,2011 ** CDC,2011 Public Health Agency of Canada | Agence de la santé publique du Canada

  16. VTEC: Source • The main reservoir: grass-feeding animals (ruminants), cattle in particular • Beef may become contaminated by faecal matter due to poor processing methods during slaughter • Faeces might contaminate other foods (e.g. milk, fresh produce) and water Public Health Agency of Canada | Agence de la santé publique du Canada

  17. Public Health Agency of Canada | Agence de la santé publique du Canada

  18. VTEC Canada 2001- 2010 80 70 60 50 DepVar 40 Cases Pred 30 20 10 0 1 27 53 79 105 131 157 183 209 235 261 287 313 339 365 391 417 443 469 495 521 Weeks 2002 2003 2004 2005 2006 2007 2008 2009 2001 2010 VTEC (O157) in Canada 2001 – 2010 through NESP 1333 1284 1063 1164 808 1113 1018 702 613 484 Counts Pollari,2011 Public Health Agency of Canada | Agence de la santé publique du Canada

  19. Incidence of O157:H7 STEC and non-O157 STEC Infections within US Public Health Agency of Canada | Agence de la santé publique du Canada

  20. Non-O157 VTEC • Non-O157 VTEC not well understood, partly because outbreaks due to them are rarely identified • As a whole, the non-O157 serogroup is less likely to cause severe illness than E. coli O157; however, some non-O157 STEC serogroups can cause the most severe manifestations of STEC illness Public Health Agency of Canada | Agence de la santé publique du Canada

  21. Non-O157 VTEC Subset of Enterohemorrhagic E. coli (EHEC) Produce a vero/shiga-toxin (VT,ST) Most non-O157 associated with self-limiting diarrhea Some non-O157 are highly pathogenic Combinations of factors contribute to pathogenicity – not fully known Have been associated with outbreaks of bloody diarrhea and HUS FoodNet active surveillance found O157 to non-O157 about 1:1 Argentina prospective study found O157 to non-O157 about 1.5:1 20 Public Health Agency of Canada | Agence de la santé publique du Canada

  22. Sources of non-O157 VTEC Little reason to expect these to differ from sources of VTEC O157. 21 • Ruminants are main animal reservoirs • Transmission via • Foods • Meat • Produce • Water • Animal contact • Person to person - Beutin et al 1993 Public Health Agency of Canada | Agence de la santé publique du Canada

  23. Sources of non-O157 VTEC • Sheep (high diversity O145 host specificity) • Wild animals (deer and elk) • Human carriage: Unknown • Pigs and rodents: Not significant sources K.Warriner,2011 Public Health Agency of Canada | Agence de la santé publique du Canada

  24. Non-O157 VTEC Over 100 serotypes have been identified from cases Over 20 outbreaks in U.S. 1990-2007 Foodborne, person-to-person, water, animal contact Salads, berries, cider, meat, dairy products and punch 75% of cases from six serotypes : O26, O111, O103, O121, O45,and O145 CDC Public Health Agency of Canada | Agence de la santé publique du Canada

  25. Seasonality from Minnesota 2000 - 2006 24 CID 2009:49 Hedican et al Public Health Agency of Canada | Agence de la santé publique du Canada

  26. Comparisonfrom CDC FoodNet 25 Preliminary data 2000-2008; CDC, Luna et al, 2010 Public Health Agency of Canada | Agence de la santé publique du Canada

  27. Non-O157 VTEC Infections:True incidence is underestimated • Stool testing normally only sought with bloody diarrhea, persistent watery diarrhea or HUS • i. e. underreporting is significant • Only 1 in 4-8 cases are identified (Michel, 1998) • True prevalence is best estimated by: • Enhanced surveillance and prospective studies • Lab testing for O157 and non-O157 VTEC • Epi investigations Public Health Agency of Canada | Agence de la santé publique du Canada

  28. CDC RecommendationsOctober 2009, MMWR Routine screening of stools submitted from patients with community acquired diarrhea at the clinical laboratory for O157 STEC and Shiga toxins These guidelines should result in improving detection of outbreaks of non-O157 STEC infection State public health laboratories should adopt STEC guidelines for public health laboratory testing when they are released State and local health departments should investigate and report all clusters of non-O157 STEC infection 27 Public Health Agency of Canada | Agence de la santé publique du Canada

  29. VTEC Outbreaks Japan,1996 - world's largest reported outbreak of E. coli O157:H7 infections - White (daikon) radish sprouts shipped on July 7-9 from one particular farm epidemiologically linked to approximately 6,000 of the nearly 10,000 cases reported - Emerg Infect Dis. 1999 Sep-Oct; 5(5) Japan, April, 2011- E. coli O111 outbreak with 4 deaths and 100 cases linked to Korean raw beef dish - yukhoe Public Health Agency of Canada | Agence de la santé publique du Canada

  30. Some Non-O157 Outbreaks K.Warriner,2011 Public Health Agency of Canada | Agence de la santé publique du Canada

  31. CDC: Non O157 Outbreaks • There were at least 27 outbreaks associated with the 6 lesser-known strains of E. coli between 1990 and 2008, with 1,225 cases and 123 hospitalizations • 12 of the outbreaks occurred in locations where children frequent – daycare facilities and camps - at least 5 outbreaks were transmitted via person-to-person contact • Most of the outbreaks occurred during the traditional high season for E. coli O157:H7, between May and September. CDC, Internal Document, 2011 Public Health Agency of Canada | Agence de la santé publique du Canada

  32. Shiga-Toxin–Producing Escherichia coli O104:H4 Outbreak in Germany • May 19, 2011 – Robert Koch Institute, Germany’s national level public health authority informed of cluster of 3 cases HUS in children admitted to a university hospital in Hamburg • one of the largest ever reported outbreaks of haemolytic uremic syndrome (HUS) and bloody diarrhoea caused by Shiga toxin-producing Escherichia coli (STEC) Public Health Agency of Canada | Agence de la santé publique du Canada

  33. E. coli O104:H4 Outbreak in Germany • 3,879 cases including 870 HUS cases (~22%) and 45 deaths have occurred since May 8, 2011 • an unusually large proportion of HUS cases as compared with diarrhoea cases • HUS adult cases (previously rare) • great majority of cases in this outbreak are adults and two thirds are women WHO, 2011 ECDC, June 24, 2011 Euro Surveill. 2011;16(21) Public Health Agency of Canada | Agence de la santé publique du Canada

  34. E. coli O104:H4 Outbreak in Germany • Incubation period is 8 days (data from 43 patients) (compared to 3 to 4 days for E coli O157:H7) • Pathogen is a hybrid – EHEC & enteroaggregative • Extended-spectrum betalactamase – resistant to some antibiotics • There is no reason to think that this strain was modified intentionally • > 95% of STEC cases reported from Germany - vast majority of cases reside in or history of recent travel to northern Germany • Additional cases reported from Europe, US and Canada • number of new infections has declined significantly over the past two weeks CDC,2011 The Lancet, June 23,2011 WHO EHEC outbreak: Jun 2011 Public Health Agency of Canada | Agence de la santé publique du Canada

  35. NEJM,June 23,2011 Public Health Agency of Canada | Agence de la santé publique du Canada

  36. NEJM, 2011 Public Health Agency of Canada | Agence de la santé publique du Canada

  37. Search for the Source… • Initial epi findings : raw vegetables and salads consumed in Northern Germany indentified as vehicle: cucumbers, tomatoes and lettuce • Recommendations made to abstain from these products of infections: • May 26 - cucumbers from Spain • May 30 - Russia bans imports • May 31 – doubts – strain different • Countries demand compensation from EU • Epidemiological investigations implicated an organic sprout farm in Lower Saxony near Hamburg as the potential source of the outbreak WHO,2011 Public Health Agency of Canada | Agence de la santé publique du Canada

  38. Search for the Source • Trace back information led to the same farm • German public health authorities are still working to identify the STEC O104:H4 organism in seeds, sprouts, and in environmental samples • They have not yet found it on the farm • Organism found in an opened product sample from the home of an infected person • On 10 Jun 2011, German public health and food safety authorities issued a joint statement recommending people to abstain from consuming sprouts • A decrease in the number of new cases was seen after 6 Jun 2011 ProMed Public Health Agency of Canada | Agence de la santé publique du Canada

  39. E. coli O104:H4 Cluster in France • June 24, France reported a cluster of 8 patients with bloody diarrhoea, attended event in Bègles, Bordeaux – June 8 • 7 developed HUS, 6 are women between 31-78 years of age, and 2 are men, aged 34 and 41 years. • Date of onset of disease between June 15-21 • 3 patients - infection with E. coli O104:H4 confirmed • 6 cases reported having eaten sprouts at the event • Suspected sprouts were locally produced, and were not imported from the farm implicated in the outbreak in Germany. • Investigations being carried out to determine suspected vehicle of infection in the French cluster, and whether there is any link between that cluster and the large outbreak reported from Germany • European Food Safety Authority, has set up a task force to coordinate investigations to track down the source of any contaminated sprouted seeds in the European Union Public Health Agency of Canada | Agence de la santé publique du Canada ECDC

  40. Source • Where the sprouting seeds in both the French and German outbreaks contaminated at the same place -- either where the seeds were grown or very soon afterwards? • UK Food Standards Agency is revising its guidance on the consumption of sprouted seeds such as alfalfa, mung beans (usually known as beansprouts) and fenugreek: “Sprouted seeds should only be eaten if they have been cooked thoroughly until steaming hot throughout; they should not be eaten raw” http://www.food.gov.uk/ Public Health Agency of Canada | Agence de la santé publique du Canada

  41. Non-O157 VTEC in Canada True level of infection is unknown No province routinely tests for the non-O157 bacteria in clinical stool samples About 60 cases/year reported to NESP last 3 years Almost all reported from 2 provinces The top 4 serotypes last 3 years are O111, O26, O127 and O55 40 Public Health Agency of Canada | Agence de la santé publique du Canada

  42. Non-O157 VTEC in Alberta Alberta studies found 1.7% of stools positive for shiga-toxigenic E. coli using real-time PCR Collected mostly in summer months: 2001-2002 and 2006-2010 O157:H7 most common (39%) Ratio of O157 to non-O157 0.6:1 The top non-O157’s were O26 (16), O121 (8), O111 (4), O103 (3), 0145 (3) – 72% 41 Dr. Linda Chui Alberta Prov. Lab Public Health Agency of Canada | Agence de la santé publique du Canada

  43. Non-O157 VTEC in B.C. BC verocell assay results yielded 53 to 135 positives per year over last 9 years Ratio of O157 to non-O157 varied by year from 3:1 to less than 1:1 Over 38 serotypes were identified The majority (64%) were O157 (349) The top non-O157’s were O26 (65), O111 (31), O121 (24), O103 (21) and O145 (10) BC PHL 42 Public Health Agency of Canada | Agence de la santé publique du Canada

  44. Canada: Surveillance and Outbreak Challenges Detection No plan for routine testing No selective media Toxin or toxin gene detection Does not identify serotype Immunologic based detection Need specific antibodies for strains Difficult to identify colonies for culture Varying sensitivity and specificity affect trends Case definition Case definition if STEC positive but not cultured Affect of lab changes on OB detection, trends and analyses 43 Pollari, 2011 Public Health Agency of Canada | Agence de la santé publique du Canada

  45. Canada: Surveillance and Outbreak Challenges HUS Surveillance in Canada • Most provinces HUS is reportable - 6 provinces • Hospital syndromic surveillance How strong is physician reporting in your area? Public Health Agency of Canada | Agence de la santé publique du Canada

  46. Canada – Are we prepared? • Improvements in enteric surveillance at the local, prov/territorial and federal levels in the last decade • Efforts towards enhanced communication, relationship-building, epi tools and lab methods • Have growing Lab expertise – Prov Labs, LFZ and NML • FIORP & Weight of Evidence • IMS/EOC Public Health Agency of Canada | Agence de la santé publique du Canada

  47. Issues • Laboratory • Capacity, Methods • Epidemiology • A new game! • Identifying the source a big problem • Weight of scientific evidence – source/recall-balance • International collaboration • Speed of communication: EU and international public health and food safety laboratory alert networks, informal - twitter, blogs) and publications (NEJM, Lancet) • Fresh, local, organic produce Sprouts! Public Health Agency of Canada | Agence de la santé publique du Canada

  48. Non-O157 What we know What we need to know • What are the important sources? • Significance of person-to-person transfer • Dissemination in the environment • How to detect and differentiate • Are the interventions for O157 adequate for non-O157? • Non-O157 STEC high prevalence • High diversity • Host specific • Increasing virulence • Alternative virulence factors K.Warriner,2011 Public Health Agency of Canada | Agence de la santé publique du Canada

  49. Final Words… The diversity and complexity of the VTEC family requires that laboratories and public health surveillance systems have the ability to detect and monitor all serotypes of VTEC - Johnson, R. et. al. JFP Volume 59, Number 10, October 1996 These efforts require increased clinical suspicion, improved clinical laboratory isolation, and continued serotyping of isolates in public health laboratories - J. Brooks et. al, JID Public Health Agency of Canada | Agence de la santé publique du Canada

  50. Final Words Public health efforts: • continuous public health surveillance to detect disease outbreaks • rapid response by local public health/hospitals • rapid epidemiological investigation of outbreaks • public health reference laboratories that can examine and identify uncommon organisms that sometimes cause disease  • food safety authorities that take appropriate measures to control the source of the infection and prevent similar events from happening in the future. CDC,2011 Public Health Agency of Canada | Agence de la santé publique du Canada

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