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Campylobacter jejuni Epidemiology and Evolution

Campylobacter jejuni Epidemiology and Evolution. Veterinary Training Research Initiative Food-borne zoonotic pathogens: Transmission, pathogen evolution and control. Lancaster University Paul Fearnhead, Edith Gabriel, Peter Diggle University of Liverpool

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Campylobacter jejuni Epidemiology and Evolution

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  1. Campylobacter jejuniEpidemiology and Evolution

  2. Veterinary Training Research InitiativeFood-borne zoonotic pathogens:Transmission, pathogen evolution and control • Lancaster University • Paul Fearnhead, Edith Gabriel, Peter Diggle • University of Liverpool • Howard Leatherbarrow, Tony Hart, Malcolm Bennett • Health Protection Agency • Andrew Fox, Steve Gee, Sam James • John Cheesbrough, Eric Bolton • Funding: DEFRA • (Department for Environment, Food and Rural Affairs, UK Government)

  3. Characterisation ofC. jejuni infection • Epidemiology • Evolutionary history • Population genetics • Source of human cases

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

  5. Cases and controls Risk Significance Poisson point process

  6. 25.4% reduction year-on-year Seasonal patterns Harmonic regression

  7. MLST: Multi-locus sequence typing 477bp aspA 477bp glnA 1.6 million bp genome MLST: 3300 bp in total(0.2%) 402bp gltA 498bp pgm tkt 459bp 489bp uncA glyA 507bp Multi-locus sequence typing (MLST)

  8. 21 257 48 104 45 53 50 19 61 574 Multi-locus sequence typing (MLST)

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

  10. Genetic inhomogeneity in Campylobacter jejuni

  11. gene flow Common ancestor Campylobacterjejuni Campylobactercoli

  12. Putatative Campylobacter jejuni isolates Putatative Campylobacter coli isolates Population Structure: identifying hybrids

  13. C. jejuni – C. coli hybrids3 sequence types, 20/881 isolates (2.2%) Population Structure: identifying hybrids

  14. Common ancestor Campylobacterjejuni Campylobactercoli gene flow aspA-33pgm-93uncA-17

  15. Coalescent modelling with ABC

  16. uncA-17 pgm-93 aspA-33 MRCA 1592(1772 -1305) 1966 1998 2000 2002 Campylobacterjejuni Campylobactercoli

  17. 4 500 BC(1 500 -10 000 BC) Domestic pig domestication in the Paris Basin, circa 4000 BCLarson et al. PNAS (2007) gene flow Common ancestor aspA-33pgm-93uncA-17 present Campylobacter jejuni Campylobacter coli

  18. 9.9 m 24 m 6.6 m 32 m 9.8 m 51 m 7.5 m years

  19. BIRD SHEEP CATTLE CHICKEN ENVIRONMENT PIG

  20. BIRD SHEEP CATTLE CHICKEN ENVIRONT PIG HUMAN

  21. Haplotype structure in sequences of known originfrom pubMLST origin PIG SHEEP ENVIRONMENT BIRD CHICKEN CATTLE

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

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

  24. 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

  25. BIRD SHEEP CATTLE CHICKEN ENVIRONMENT PIG

  26. BIRD SHEEP CATTLE CHICKEN ENVIRONT PIG HUMAN

  27. Model C: unlinked

  28. 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

  29. Simulation and empirical cross-validationResults: Linked model

  30. Case-by-case: probability of source PIG ENVIRONMENT WILD BIRD CATTLE CHICKEN SHEEP

  31. Gene flow between source populations

  32. Tracing the source of infection: results

  33. Tracing the host species of humanfood-borne infections • Infected meat principal source (97%) • No evidence for environment or wild birds as a major transmission route • Prevention strategies: • Enhanced on-farm biosecurity • Interrupting transmission chain

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