Campylobacter jejuni Epidemiology and Evolution

1
Campylobacter jejuni Epidemiology and Evolution
2
Veterinary Training Research InitiativeFood-borne
zoonotic pathogensTransmission, 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
(No Transcript)
7
Seasonal patterns
Harmonic regression
8
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)
9
Multi-locus sequence typing (MLST)
10
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
11
Genetic inhomogeneity in Campylobacter jejuni
12
Common ancestor
Campylobacterjejuni
Campylobactercoli
13
Putatative Campylobacter jejuni isolates
Putatative Campylobacter coli isolates
Population Structure identifying hybrids
14
C. jejuni C. coli hybrids3 sequence types,
20/881 isolates (2.2)
Population Structure identifying hybrids
15
Common ancestor
Campylobacterjejuni
Campylobactercoli
gene flow
aspA-33pgm-93uncA-17
16
Coalescent modelling with ABC
17
(No Transcript)
18
MRCA
1592(1772 -1305)
1966
1998
2000
2002
Campylobacterjejuni
Campylobactercoli
19
Common ancestor
aspA-33pgm-93uncA-17
present
Campylobacter jejuni
Campylobacter coli
20
7.5 m years
21
BIRD
SHEEP
CATTLE
CHICKEN
ENVIRONMENT
PIG
22
HUMAN
23
(No Transcript)
24
(No Transcript)
25
(No Transcript)
26
Haplotype structure in sequences of known
originfrom pubMLST
origin
PIG
SHEEP
ENVIRONMENT
BIRD
CHICKEN
CATTLE
27
Haplotype structure in human isolates
key
NOVEL
PIG
SHEEP
ENVIRONMENT
BIRD
CHICKEN
CATTLE
28
Haplotype structure in human isolates
key
NOVEL
PIG
SHEEP
ENVIRONMENT
BIRD
CHICKEN
CATTLE
29
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

30
BIRD
SHEEP
CATTLE
CHICKEN
ENVIRONMENT
PIG
31
HUMAN
32
Model C unlinked
33
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

34
Simulation and empirical cross-validationResults
Linked model
35
Case-by-case probability of source
PIG
WILD BIRD
ENVIRONMENT
CATTLE
CHICKEN
SHEEP
36
Gene flow between source populations
37
Tracing the source of infection results
38
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