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Whole Genome Sequencing (WGS) for food safety management-Perspectives from Canada

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http://tiny.cc/faowgsworkshop
Potential usefulness of genome sequencing technology on food safety management - Canada. Presentation from the FAO expert workshop on practical applications of Whole Genome Sequencing (WGS) for food safety management - 7-8 December 2015, Rome, Italy.

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Whole Genome Sequencing (WGS) for food safety management-Perspectives from Canada

  1. 1. Perspectives from Canada Canadian Food Inspection Agency Public Health Agency of Canada Health Canada Sabah Bidawid, PhD Chief, Microbiology Research Division Food Directorate, Bureau of Microbial Hazards Health Canada Celine Nadon, PhD Chief, Enteric Diseases National Microbiology Laboratory Public Health Agency of Canada
  2. 2. 2 FOOD SAFETY IN CANADA
  3. 3. 3 Federal food safety responsibilities are shared PRODUCTION PROCESSING/DISTRIBUTION/RETAIL/FOOD SERVICE CONSUMERS On-farm Food Safety Programs Policy & Standards Monitoring/ Early Warning Education & Outreach Inspection & Enforcement Public Health Surveillance AGRICULTURE & AGRIFOOD CANADA •Contributes to research and development of on- farm food safety programs HEALTH CANADA •Establishes food safety policy and standards •Conducts health risk assessments •Informs Canadians about potential risk to their health •Safety of veterinary drugs and pesticides • Research vis-a-vis policy development CANADIAN FOOD INSPECTION AGENCY •Design and delivery of federal food inspection programs •Monitors industry’s compliance with Acts and regulations •Undertakes enforcement action as necessary PUBLIC HEALTH AGENCY OF CANADA •Public health surveillance •Leads outbreak investigations with P/T public health officials HEALTH CANADA CFIA PHAC AAFC
  4. 4. 4 IMPLEMENTATION OF WGS – REGULATORY/INSPECTION Outbreak investigation Monitoring program Isolated colony WGS Bioinformatics Report of analysis Health Risk Assessment Regulatory Action (e.g., recall) Map reads Assembly Identification Typing/Signature sequences Virulence profile Quality metricsDesired outcomes: • Comprehensive analysis • Definitive identification • Risk profiling • Timely interventions Canadian Food Inspection Agency Approximately 12,500 food samples analyzed annually for compliance and investigation Fresh Produce – 10% Imported and Manufactured Foods – 4% 2014-2015 SAMPLED PRODUCTS
  5. 5. 5 IMPLEMENTATION OF WGS - POLICY NO YES YES STRONG EVIDENCE PFGE ANALYSIS PHAC/ HC/CFIA Link cases to food Section B STRONG EVIDENCE NO NO HRA HC Section E Appendix E NO RISK ASSIGNED TO FOOD HC Section F CHECK GMPs and HACCP CFIA RISK MANAGEMENT ACTION CFIA Section G GMP, HACCP, QA, Investigation Check additional products LEGEND STRONG EVIDENCE NO YES NEXT BACK AND FORTH YES CONTINUE SURVEILLANCE PHAC/CFIA Continue epidemiological investigation NO MORE LEADS CLOSED UNSOLVED TRACEBACK/TRACEFORWARD Products identified in distribution CFIA Section D YES STRONG EVIDENCE EPIDEMIOLOGICAL ANALYSIS PHAC (# cases, demographics, clinical presentation, food history/exposures) Section C YES CONTINUE PHAC SURVEILLANCE NO CASES OF ILLNESS (food, # of cases, history, etc.) PHAC Section C FOOD SAMPLE (in-situ; for pathogen ID) CFIA* Section A ISOLATE MATCH PHAC (link between cases) Section B
  6. 6. 6 IMPLEMENTATION OF WGS - POLICY
  7. 7. 7 IMPLEMENTATION OF WGS - POLICY “While PFGE and MLVA are the gold standard subtyping methods for foodborne bacterial pathogens, newer methods are being developed for genetic profiling, including whole genome sequencing. This research and development is done to ensure that the best technology and most current science are available for foodborne disease investigations and with the application of validated interpretation criteria and assessment of weight of evidence. When new tests are applied during outbreak investigations for this purpose, they are applied in parallel to the primary tests and are carefully interpreted on a case-by-case basis.”
  8. 8. 8 IMPLEMENTATION OF WGS POLICY:  Foodborne Pathogens • Canada is in the process of incorporating information from WGS into Health Risk Assessments and Epidemiological Surveillance – WGS is being performed on, Bacteria, Viruses, and Parasites from Clinical, Environmental, and Food Sources – WGS data: currently used to monitor trends in emerging pathogens, AMR, to identify novel virulence factors, and as an parallel/alternative to traditional analyses like MLST and serotyping – HC is also working on Quality Assurance and Best Practices Standards Guidelines for sequence analysis (Pightling et al., 2015; 2014). – Working toward using WGS to support the development of policy/ standards/compliance.
  9. 9. 9 IMPLEMENTATION OF WGS: SURVEILLANCE & OUTBREAKS PulseNet Canada Genomic Epidemiology Roadmap Aleisha Reimer with contributions from Drs Celine Nadon, Morag Graham, and PulseNet Canada members October 16, 2013 Based on existing PulseNet Canada model De-centralized sequencing and analysis Parallel, centralized storage & analysis of national data sets Continued NML support in reference testing, training, certification & proficiency Continued method development, refinement, and KT
  10. 10. 10 IMPLEMENTATION OF WGS: SURVEILLANCE & OUTBREAKS WGS initiated by NML or member and permission granted by member laboratory Sequencing performed by NML Sequencing performed by member laboratory, but part of a multijurisdictional cluster/outbreak Member uploads raw sequence to NML database Multi-jurisdictional bioinformatics analysis performed by NML Member can download raw sequences Results & interpretations are verified with the submitting laboratories for consensus NML provides results interpretations to PHAC managers & epidemiologists, OICC, and international partners (as determined in previous step). Information Flow: Whole Genome Sequencing Challenges: - Comfort level among partners on appropriate use of data - IP and isolate ownership: national agreements to enable meta-data sharing - Paradigm shift about what should be publicly available Mitigations: - Transparency - Rigorous communications protocols - Trust building - MOU
  11. 11. 11 BIOINFORMATICS AND IT INFRASTRUCTURE NML IRIDA BioNumerics HPC AB BC SK MB ON QC NL NB NS PEI NU NT Hub and Spoke Model - High speed connections from FPT partners to NML - IRIDA and BioNumerics used for data storage, management, surveillance, analysis - Centralised IT and bioinformatics experts - Intent – common platform for federal partners
  12. 12. 12 CFIA BIOINFORMATICS HUB NML BIOINFORMATICS HUB Public Health Lab WGS Capacity Food Lab WGS Capacity
  13. 13. 13 STANDARDS AND HARMONIZATION International standards for Bioinformatics and Genomics for public health and regulatory activities - currently under way. Government of Canada active in: • Global Coalition for Regulatory Science Research Working Group on Bioinformatics - developing Best Practices for bioinformatics for food regulatory application • Global Microbial Identifier international consortium developing standards for genomic epidemiology • PulseNet International harmonization and standards for surveillance and outbreak response • International Standards Organization Technical Committee (ISO/TC 34/SC 9/WG25) – QA standards for genomics in food testing • IRIDA platform incorporates ontologies, public APIs, data provenance, and a flexible QA/QC system for WGS-based analyses Approach: Harmonized, non-prescriptive standards and best practices
  14. 14. 14 EDUCATION NEED GOAL APPROACH TO DATE… Lab capacity – data analysis specialists to perform genomic analyses and interpretation “frontline” Knowledge of how to interpret genomic information by partner laboratories Hub and Spoke: Expert computational resources that cascade skills to wider users (hub); lab staff receive training appropriate to their role (spokes) Technical bioinformatics workshops; genomics wet lab training; practice (repeated outbreak analyses) Stakeholders with comfort &understanding of the added value & benefits offered by WGS Stakeholder fluency in genomics-based evidence HUB & SPOKE model; different audience than for operational training Educational webinars, multi-jurisdictional task groups, annual meetings, briefing notes, white papers Knowledge translation activities critically important, tailored for audience
  15. 15. 15 CASE STUDIES Organism Case or Outbreak Details (putative/confirmed vehicle) L. monocytogenes Collaboration with USA (lettuce product) L. monocytogenes Collaboration with USA (RTE meat product) Salmonella Thompson National laboratory investigation to support outbreak response in a single province (suspected chicken products) E. coli O157:H7 Large outbreak in a single province (pork products) L. monocytogenes Ongoing cluster of common PFGE pattern L. monocytogenes Collaboration with USA (caramel apples) S. Enteritidis Collaboration with USA (bean sprouts) Selected Investigations Supported Prospectively by WGS, PulseNet Canada, 2014 Usefulness of WGS application to outbreaks in 2014: - Increased resolution; ability to rule in/out matching PFGE patterns - Provided confirmation of PFGE/MLVA findings - Grouped unrelated PFGE patterns – large clusters that otherwise may have been missed - Facilitated development of data sharing protocols for use in real time as well as knowledge translation to lab and epi partners
  16. 16. 16 CASE STUDIES In Canada, WGS is routinely applied during cluster investigation or outbreak response in parallel to PFGE/MLVA. General findings: WGS CONFIRMS MOLECULAR RESULTS WGS PROVIDES ADDITIONAL INFORMATION Example: beef-associated E. coli O157:H7 outbreak (2012) PFGE & MLVA used for case definition; WGS in parallel gave same results Example: Canadian cases - US outbreak of listeriosis associated with caramel apples Canada had 2 PFGE matches One case reported apple exposure, one did not WGS confirmed that the case with no exposure was not outbreak-related, despite the PFGE match Only molecular results “officially” used
  17. 17. 17 CASE STUDIES WGS CONFIRMS MOLECULAR RESULTS Example: beef-associated E. coli O157:H7 outbreak (2012) Example: Canadian cases - US outbreak of listeriosis associated with caramel apples WGS used in parallel with established molecular tests enables database building & increases knowledge transfer activities while providing the “comfort” of the gold standard Independent analyses using two pipelines (US and Canada) were in agreement, thus increased confidence in WGS results of a higher resolution than PFGE In Canada, WGS is routinely applied during cluster investigation or outbreak response in parallel to PFGE/MLVA. General findings: WGS PROVIDES ADDITIONAL INFORMATION
  18. 18. 18 SUMMARY Status: government-wide tiered approach; mostly in parallel with traditional tests so far Implementation challenges: what happens when funding is insufficient? When volumes are low? How long until traditional tests are phased out? What will new interpretation criteria look like? Primary issues present in Canada: standardization/harmonization, IT and bioinformatics infrastructure, data integration, sharing, and KT
  19. 19. 19 Co-Authors Canadian Food Inspection Agency (CFIA) - Burton Blais Health Canada (HC) - Sabah Bidawid - Franco Pagotto - Nicholas Petronella - Jennifer Ronholm - Jennifer Holtzman Public Health Agency of Canada (PHAC) - Celine Nadon - Morag Graham - John Nash - Aleisha Reimer - Gary Van Domselaar
  20. 20. 20 Additional Materials - Discussion points on FAO questions - GMO perspective on use of genomics
  21. 21. 21 INSIGHTS Is WGS considered beneficial for food safety management in Canada? What could be the drawbacks? • Benefits – Harmonize methodology (decrease lab to lab variability) – one test fits all approach – Highly informative tests results (identification, characterization, risk assessment) – Third party evaluation of results – Cost effective and timely • Drawbacks – Still need an isolate – Possible decline of culture collections – Comparison to legacy data What are the necessary conditions /infrastructure to employ WGS technology for food safety management in Canada? • Sequencing capacity • High Capacity Storage and Data analysis • Bioinformatics support in the form of tools, expertise, & databases • Interpretation criteria/policy for data use • Governance for sharing If in the future this will be used for food safety management, what are the key prerequisite activities? • Database construction • Validation experiments
  22. 22. 22 INSIGHTS What agencies are/should be involved to make good results? How they are (can be) working together on this topic? Are there any important stakeholders (industry/company or academia/research) who should be involved? • Health Canada (HC); Public Health Agency of Canada (PHAC); Canadian Food Inspection Agency (CFIA). • Provincial and territorial public health • Food Industry What could be the real challenges (overall and specific) in when actually using WGS for food safety management? • Sharing (databases, sequencing data, tools, results of validation experiments etc.) • Food Industry outpacing regulatory and compliance agencies (CIFA, PHAC, HC) • Predictive accuracy (e.g. predicting phenotype) What roles do you expect/wish that international organisations would play on this topic? • Standardization/harmonization (not prescriptive though) • Database
  23. 23. 23 Capacity building for pre-market assessment of genetically modified organisms • Mandated activity (Division 28 of the Food and Drug Regulations) – molecular characterization, nutritional composition, chemical safety number of DNA insertion sites in the genome, presence of complete or partial copies, intact insert, absence of plasmid backbone • Companies typically provide data generated by classical molecular biology methods (Southern blot, PCR, Sanger sequencing), however there is interest from industry to provide regulators with molecular characterization data generated using WGS • Approach – Consultation with experts and stakeholders (CFIA lead, March 2015) – Draft internal guidance by GoC expert working group (Health Canada lead, Nov. 2015) – External guidance will be developed by GoC working group (2016)

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