Assessing the Contribution Made by the Food Chain to the Burden of UK-Acquired Norovirus Infection Investigators
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Assessing the contribution made by the food chain to the burden of UK- acquired norovirus infection FS101040 24 September 2019 Report compiled by S. Williams, S.J. O’Brien FS101040: Assessing the contribution made by the food chain to the burden of UK-acquired norovirus infection Investigators University of Liverpool, Faculty of Health and Life Sciences, L69 3GL Sarah J O’Brien ([email protected]), Miren Iturriza-Gomara ([email protected]) Leatherhead Food Research, Yew Tree Bottom Road, Epsom, KT18 5XT Angus Knight ([email protected]) Centre for Environment, Fisheries and Aquaculture Science (Cefas), The Northe, Barrack Road, Weymouth, Dorset DT4 8UB David Lees ([email protected]), James Lowther ([email protected]) Fera, Sand Hutton, York, YO41 1LZ Nigel Cook ([email protected]), Martin D’Agostino ([email protected]) Public Health England, 61 Colindale Avenue, London NW9 5EQ David James Allen ([email protected]), Nicola Elviss ([email protected]), Andrew Fox ([email protected]) University of East Anglia, School of Medicine, Norwich, NR4 7TJ Paul Hunter ([email protected]), James Maas ([email protected]) Newcastle University, School of Natural and Environmental Sciences, Newcastle, NE1 7RU Stephen Rushton ([email protected]), Roy Sanderson ([email protected]) Acknowledgments We acknowledge the Food Standards Agency (FSA) for the funding received for this research project (Project reference: FS101040). Collaborating partners on the project are Cefas, Fera, Leatherhead Food Research, Liverpool Clinical Laboratories (Royal Liverpool and Broadgreen University Hospital Trust), Public Health England, University of East Anglia and University of Liverpool. 2 Contents Investigators 2 Acknowledgments 2 1. Executive Summary 7 1.1. Summary 7 1.2. Recommendations 11 1.2.1. For research 11 1.2.2. For policy 12 2. Background to the project 13 3. Work Package 1: Foodborne and food-handler-associated norovirus outbreaks: Systematic review. 15 3.1. Summary 15 3.2. Introduction 15 3.3. Methods 17 3.3.1. Literature search 17 3.3.2. Study inclusion criteria 17 3.3.3. Data Collection 17 3.3.4. Analyses 18 3.4. Results 18 3.4.1. Literature Search 18 3.4.2. Norovirus Foodborne outbreaks 20 3.4.3. Norovirus Food handler associated outbreaks 20 3.5. Discussion 21 3.5.1. Main Findings 21 3.5.2. Limitations 22 3.6. Conclusion 23 4. Work Package 2: Determining the origins of human norovirus RT-qPCR signals 47 4.1. Summary 47 4.2. Application of the Capsid Integrity Assay (CIA) to CEN Methods 48 4.2.1. Introduction 48 4.2.2. Methods 50 4.2.3. Results 51 4.2.4. CIA Discussion 74 4.3. Application of VPg Magnetic Immuno0Capture RT-qPCR to CEN Methods 79 4.3.1. Introduction 79 3 4.3.2. Methods 81 4.3.3. Results 83 4.3.4. VPg Discussion 84 5. Work Package 3: Acquisition of data on norovirus contamination levels in oysters at retail 86 5.1. Summary 86 5.2. Introduction 86 5.3. Materials and Methods 87 5.3.1. Sampling Plan 87 5.3.2. Sample Collection 88 5.3.3. Sample Receipt 89 5.3.4. Detection and quantification of norovirus 89 5.3.5. Detection and quantification of Escherichia coli 91 5.3.6. Capsid Integrity Assay 92 5.3.7. Determination of ssRNA virus viability ratios using bacteriophage 92 5.3.8. Next Generation Sequencing (NGS) 93 5.4. Results/Discussion 94 5.4.1. Noroviruses 95 5.4.2. E.coli 107 5.4.3. Capsid Integrity Assay 109 5.4.4. Determination of ssRNA virus viability ratios using bacteriophage 110 5.4.5. More on Next Generation Sequencing (NGS) 111 5.5. Conclusion 114 6. Work Package 4: Prevalence of norovirus in fresh produce sold at retail 116 6.1. Summary 116 6.2. Introduction 116 6.3. How the survey was conducted 117 6.3.1. Survey Design 117 6.3.2. Sampling 118 6.3.3. Sample receipt 118 6.3.4. Sample treatment 118 6.3.5. Detection of Norovirus and mengovirus 119 6.3.6. Interpretation of RT-PCR results 119 6.3.7. Capsid Integrity Assay 119 6.3.8. Detection of Escherichia coli 119 6.4. Results 120 6.5. Discussion 130 4 7. Work Package 5: Prevalence of norovirus in the catering environment in outbreak and non-outbreak premises 133 7.1. Summary 133 7.2. Aims of the Study 133 7.3. Materials and Methods 134 7.3.1. Surveillance sampling 134 7.3.2. Sampling during outbreaks 135 7.3.3. Virology: Norovirus testing 136 7.3.4. Bacteriological testing 138 7.4. Results 139 7.4.1. Premises sampled 139 7.4.2. Virology results 141 7.4.3. Norovirus characterisation 143 7.4.4. Bacteriology results 144 7.5. Discussion 146 8. Work Package 6: Estimating the disease burden from foodborne norovirus in the UK, a microsimulation based quantitative microbial risk assessment 150 8.1. Summary 150 8.2. Introduction 152 8.3. Systematic Review 154 8.3.1. Methods 154 8.3.2. Results 154 8.3.3. Conclusions 155 8.4. Methods and Justification 157 8.4.1. Model Overview 157 8.4.2. Estimating dose per meal for oysters 167 8.4.3. Estimating dose per meal for lettuce and raspberries 169 8.4.4. Estimating dose per catered meals 170 8.4.5. Dose response model 173 8.4.6. Calculating risk per meal, per day and annually 174 8.4.7. Adjusting for acquired immunity from prior infection 176 8.4.8. Reporting uncertainty 178 8.5. Results 179 8.5.1. Virus exposure per meal 179 8.5.2. Risk results 180 8.5.3. Epidemic model – accounting for multiple prior infections 186 8.5.4. Sensitivity analyses 187 8.5.5. Synthesis 194 5 8.5.6. Validation 195 8.6. Discussion 196 8.7. Conclusions 199 9. Individual-based model to investigate the dynamics of norovirus infections in communities 200 9.1. Introduction 200 9.2. Methods 200 9.2.1. The individual-based model 200 9.2.2. Extending the individual-based model to include data on oysters, berry fruits and lettuce collected in the NoVAS project 204 9.2.3. Interpreting VIP scores 207 9.3. Results 207 9.3.1. Exposure risk and exposure levels to norovirus 207 9.3.2. Sensitivity analysis of exposure and transmission parameters on community burden of disease in norovirus naïve and norovirus non-naïve communities 208 9.4. Discussion 212 10. The models in context 215 10.1. Introduction 215 10.2. Re-cap of major outcomes from each model 215 10.3. Strengths 228 10.4. Limitations 229 10.5. Sources of Uncertainty 230 10.6. Conclusions 230 11. Recommendations 231 11.1. For research 231 11.2. For policy 232 12. List of abbreviations and acronyms used 233 13. Authors’ Information 236 14. Acknowledgments 237 15. References for Chapter 3 (Work Package 1) 238 16. References for Chapter 4 (Work Package 2) 248 17. References for Chapter 5 (Work Package 3) 250 18. References for Chapter 6 (Work Package 4) 253 19. References for Chapter 7 (Work Package 5) 255 20. References for Chapter 8 (Work Package 6) 257 21. References for Chapter 9 262 22. References for Chapter 10 263 6 1 Executive Summary 1.1 Summary Noroviruses (NoVs) are the most commonly identified cause of infectious diarrhoea and vomiting in the community, often causing outbreaks, especially in closed or semi closed communities. Like other organisms that affect the gut norovirus can be passed from person to person, or be picked up from a contaminated environment or through eating food contaminated at source or by infected food handlers. What is not reliably known is exactly what proportion of norovirus infection is food-related as opposed to transmitted by other means. Estimates from international research groups of the proportion of norovirus that is transmitted through contaminated food vary quite widely. Through a series of linked studies we sought to answer the following major research questions:- a) How much norovirus is transmitted through contaminated food? b) What is the role of infected food handlers in transmission? c) Is it possible to differentiate between infectious and non-infectious virus in a variety of food matrices? Specifically the objectives of this project were to:- 1. Review existing evidence for foodborne transmission of norovirus and undertake feasibility studies of new data collection. A systematic review of outbreaks attributed to norovirus between January 2003 and July 2017 was conducted to assess the contribution of food handlers to the burden of norovirus, and to identify any foods commonly associated with norovirus outbreaks. Three thousand and eighty seven articles were retrieved, of which 27 met the definition of confirmed foodborne outbreaks and 47 met the criteria for definite food handler-associated norovirus outbreaks. Of all food types, shellfish were implicated in the greatest number of definite foodborne outbreaks. Food handlers contributed to definite food handler outbreaks involving a diverse range of foodstuffs and in a wide variety of settings, including weddings and military establishments. More genotypes of norovirus were found in people that were ill than in samples from food and food handlers. The potential for both food products and food handlers to contribute to the burden of norovirus infection was demonstrated conclusively. 2. Investigate the application of a capsid integrity assay to the CEN detection methods and so develop improved methods for the detection of infectious virus particles.