1. Source attribution in Campylobacter jejuni Daniel Wilson Nuffield Department of Clinical Medicine www.danielwilson.me.uk JR Microbiology Seminar 16 th November 2010

2. Paul Fearnhead Lancaster University Andrew Fox Health Protection Agency Edith Gabriel Universite d’Avignon Peter Diggle Lancaster University Petra Mullner Massey University Nigel French Massey University Martin Maiden University of Oxford Sam Sheppard University of Oxford Funded by HEFCE, DEFRA, EPSRC Wellcome Trust Food Standards Agency Scotland New Zealand Food Safety Authority

3. Evolutionary genetics as a framework for understanding genetic diversity Genetics Relatedness Contact tracing Population structure Transmission Source attribution Epidemiology Population dynamics R0R0 Resistance genes Host susceptibility Vaccination Diagnosis Evolution Adaptation Emergence Control + prevention

4. Inferring host-host transmission: zoonotic transmission of Campylobacter jejuni

5. Foodborne illness in the UK Food Standards Agency figures for 2000 $8bn Annual cost to US economy Buzby et al. JID (1997)

7. Cases and controlsRiskSignificance Poisson point process

9. Seasonal patterns Harmonic regression 25.4% reduction year-on-year

10. Multi-locus sequence typing (MLST)

11. 21 257 48 104 45 53 50 19 61 574 Multi-locus sequence typing (MLST)

12. ST 21: 2 1 1 3 2 1 5 ST 104: 2 1 1 3 7 1 5 ST 50: 2 1 12 3 2 1 5 ST 21: 2 1 1 3 2 1 5

15. BIRD CATTLE CHICKEN ENVIRONMENT PIG SHEEP Haplotype structure in sequences of known origin from pubMLST origin

16. BIRD CATTLE CHICKEN ENVIRONMENT PIG SHEEP Haplotype structure in human isolates key NOVEL

17. BIRD CATTLE CHICKEN ENVIRONMENT PIG SHEEP Haplotype structure in human isolates key NOVEL

18. Attributing novel genotypes ST 574: 7 53 2 10 11 3 3 Human-specific, but similar to... ST 305: 9 53 2 10 11 3 3 ST 713: 12 53 2 10 11 3 3 ST 728: 4 53 2 10 10 3 3 ST 2585: 7 2 3 10 11 3 3 All these found in chicken, so the likely source is chicken

19. Zoonotic transmission in Campylobacter jejuni

22. CATTLE SHEEP CHICKEN PIG BIRD ENVIRONMENT

23. CATTLE SHEEP CHICKEN PIG BIRD ENVIRONT HUMAN

24. Does it work? Empirical cross-validation Split sequences of known origin into two groups. Treat one group as having unknown origin (pseudo- human cases) Infer the proportion of pseudo-human cases drawn from each source population Repeat 100 times to study the performance of the method

25. Simulation and empirical cross-validation Results: Linked model

26. Gene flow between source populations

27. Case-by-case source probability CATTLE SHEEP CHICKEN PIGWILD BIRDENVIRONMENT

30. The evidence provided by our approach has supported national policy making by providing an important contribution to the New Zealand Food Safety Authority (NZFSA) Campylobacter Risk Management Strategy (2007), which has subsequently included mandatory targets for limiting contamination with Campylobacter spp. of chilled poultry carcasses. The introduction of these interventions has coincided with a dramatic decrease in human campylobacteriosis notifications to a 16-year low. In 2008 some 6689 human cases were reported in New Zealand compared to 15,873 cases in 2006; the year before the announcement and implementation of control measures.

32. Conclusions Incidence is spatially heterogeneous at broad scales and clustered at fine scales. Urban areas suffer greater incidence of campylobacteriosis in general, and poultry-associated infections in particular. Incidence is periodic, peaking in summer. The primary source of Campylobacter jejuni infectious to humans is meat, in particular poultry. The further observation that environmental sources appear unimportant strongly suggests a food-borne transmission route. These patterns are consistent in England, Scotland and New Zealand. Measures to limit Campylobacter infection in poultry appear to have reduced human disease in New Zealand.

33. daniel.wilson@ndm.ox.ac.uk www.danielwilson.me.uk