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Source attribution in Campylobacter jejuni. Daniel Wilson Nuffield Department of Clinical Medicine www.danielwilson.me.uk JR Microbiology Seminar 16 th November 2010. Sam Sheppard University of Oxford. Andrew Fox Health Protection Agency. Martin Maiden University of Oxford.
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Source attribution in Campylobacter jejuni Daniel Wilson Nuffield Department of Clinical Medicine www.danielwilson.me.uk JR Microbiology Seminar 16th November 2010
Sam Sheppard University of Oxford Andrew FoxHealth Protection Agency Martin MaidenUniversity of Oxford Paul Fearnhead Lancaster University Edith Gabriel Universite d’Avignon Peter Diggle Lancaster University Petra Mullner Massey University Funded by HEFCE, DEFRA, EPSRC Wellcome Trust Food Standards Agency Scotland New Zealand Food Safety Authority Nigel French Massey University
Resistance genes Vaccination Hostsusceptibility Diagnosis Adaptation Emergence Relatedness Evolution Epidemiology Control + prevention Transmission Contact tracing R0 Source attribution Population dynamics Population structure Evolutionary genetics as a framework for understanding genetic diversity Genetics
Inferring host-host transmission: zoonotic transmission of Campylobacter jejuni
Foodborne illness in the UKFood Standards Agency figures for 2000 $8bn Annual cost to US economy Buzby et al. JID (1997)
Cases and controls Risk Significance Poisson point process
25.4% reduction year-on-year Seasonal patterns Harmonic regression
21 257 48 104 45 53 50 19 61 574 Multi-locus sequence typing (MLST)
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
Haplotype structure in sequences of known originfrom pubMLST origin PIG SHEEP ENVIRONMENT BIRD CHICKEN CATTLE
Haplotype structure in human isolates key NOVEL PIG SHEEP ENVIRONMENT BIRD CHICKEN CATTLE
Haplotype structure in human isolates key NOVEL PIG SHEEP ENVIRONMENT BIRD CHICKEN CATTLE
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
BIRD SHEEP CATTLE CHICKEN ENVIRONMENT PIG
BIRD SHEEP CATTLE CHICKEN ENVIRONT PIG HUMAN
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
Simulation and empirical cross-validationResults: Linked model
Case-by-casesourceprobability PIG ENVIRONMENT WILD BIRD CATTLE CHICKEN SHEEP
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.
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.
daniel.wilson@ndm.ox.ac.uk www.danielwilson.me.uk