source attribution in campylobacter jejuni

Source attribution in Campylobacter jejuni

Daniel Wilson

Nuffield Department of Clinical Medicine

www.danielwilson.me.uk

JR Microbiology Seminar 16th November 2010

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Paul FearnheadLancaster University

Andrew FoxHealth Protection Agency

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Edith GabrielUniversite d’Avignon



Peter DiggleLancaster University






Petra MullnerMassey University

Nigel FrenchMassey University


are needed to see this picture.Martin MaidenUniversity of Oxford

Sam SheppardUniversity of Oxford

Funded byHEFCE, DEFRA, EPSRCWellcome TrustFood Standards Agency ScotlandNew Zealand Food Safety Authority

Evolutionary genetics as a framework for understanding genetic diversity

GeneticsRelatedness

Contact tracing

Population structure

Transmission

Source attribution

Epidemiology

Population dynamics

R0

Resistance genesHost

susceptibilityVaccination

Diagnosis

Evolution

Adaptation

Emergence

Control + prevention

Inferring host-host transmission: zoonotic transmission of Campylobacter jejuni







Foodborne illness in the UKFood Standards Agency figures for 2000

Salmonella 16,987 20.9%

Campylobacter 62,867 77.3%

E.coli O157 1,147 1.4%

Clostridium perf. 166 0.2%

Listeria 113 0.1%

Total 81,280

$8bnAnnual cost to US economy

Buzby et al. JID (1997)

Cases and controls RiskSignificance

Poisson point process



Seasonal patterns

Harmonic regression

25.4% reduction year-on-year

Multi-locus sequence typing (MLST)

tkt 459bp

glyA 507bp489bp uncA

498bp pgm

402bp gltA

477bp glnA

477bp aspA

1.6 million bp genome

MLST: 3300 bp in total(0.2%)



0

20

40

60

80

100

120

140

21 257 48 104 45 53 50 19 61 574

Sequence Type

Abundance

21

257

48104

4553

50

1961

574

Multi-locus sequence typing (MLST)

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

CATTLE cattle 212beef offal or meat 47calf 12cows milk 11calf faeces 1cattle faeces 1 284

CHICKEN chicken 222chicken offal or meat 153chick 17 392

BIRD wild bird 172starling 71goose faeces 25turkey 22goose 12duck 7starling faeces 4 313

ENVIRONMENT sand (bathing beach) 52environmental waters 28soil 3potable/drinking water 2 85

SHEEP sheep 84lamb offal or meat 74lamb 10sheep faeces 2 170

PIG pig 35pork offal or meat 10piglet 1 46

broiler environment 17cat 3dog 5farm slurry 10gazelle 1giraffe 1goat 5horse 1human blood culture 57human stool 1684human unspecified 102marmoset 2ostrich 1other animal 25rabbit 3unspecified 144

BIRD

CATTLE

CHICKEN

ENVIRONMENT

PIG

SHEEP

Haplotype structure in sequences of known originfrom pubMLST

origin

BIRD

CATTLE

CHICKEN

ENVIRONMENT

PIG

SHEEP

Haplotype structure in human isolates

key

NOVEL

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



Zoonotic transmission in Campylobacter jejuni

CATTLE

SHEEP

CHICKEN

PIG

BIRD

ENVIRONMENT

CATTLE

SHEEP

CHICKEN

PIG

BIRD

ENVIRONT

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

Unlinked model Linked modelPredicted Correct 0.86 0.66Actual Correct 0.56 0.58Coverage CATTLE 22 100

CHICKEN 85 82BIRD 81 100

ENVIRONMENT 63 99SHEEP 16 98

PIG 89 94Combined 18 95

Bias CATTLE -0.13 0.00CHICKEN -0.01 -0.05

BIRD -0.02 -0.02ENVIRONMENT -0.01 0.00

SHEEP 0.16 0.06PIG 0.01 0.00

RMSE CATTLE 0.14 0.08CHICKEN 0.03 0.05

BIRD 0.03 0.04ENVIRONMENT 0.03 0.04

SHEEP 0.17 0.09PIG 0.01 0.01

Gene flow between source populations

Case-by-casesourceprobability

CATTLE

SHEEP

CHICKEN

PIG WILD BIRDENVIRONMENT







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.

[email protected]

www.danielwilson.me.uk

source attribution in campylobacter jejuni

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