The construction and analysis of epidemic trees with reference to the 2001 UK FMDV outbreak
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The construction and analysis of epidemic trees with reference to the 2001 UK FMDV outbreak Dan Haydon, Dept Zoology, University of Guelph, On. Ca.
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The construction and analysis of epidemic trees with reference to the 2001 UK FMDV outbreak Dan Haydon, Dept Zoology, University of Guelph, On. Ca. Provide case reproduction ratios from outbreak data as it arises Explore the consequences of applying stricter control measures - PowerPoint PPT Presentation
Transcript of The construction and analysis of epidemic trees with reference to the 2001 UK FMDV outbreak
The construction and analysis of epidemic trees with reference to the 2001 UK FMDV outbreak
Dan Haydon,Dept Zoology,University of Guelph, On. Ca.
• Provide case reproduction ratios from outbreak data as it arises
• Explore the consequences of applying stricter control measures
Woolhouse, MEJ., Topping, M.C., Haydon, D.T. and 8 others. 2001. Foot-and-mouth disease under control in the UK.Nature 411, 258-259.
Haydon, D.T., Topping, M.C., Shaw, D.J., Matthews, L., Friar, J.K., Wilesmith, J., and Woolhouse, M.E.J.
2003. The construction and analysis of epidemic trees with reference to the 2001 UK foot-and-mouth outbreak. Proceedings: Biological Sciences (The Royal Society, UK) 270, 121-127.
Date
10-Feb
17-Feb
24-Feb
03-Mar
10-Mar
17-Mar
24-Mar
31-Mar
07-Apr
14-Apr
21-Apr
28-Apr
05-May
12-May
19-May
26-May
02-Jun
09-Jun
16-Jun
23-Jun
30-Jun
07-Jul
14-Jul
21-Jul
28-Jul
04-Aug
11-Aug
18-Aug
25-Aug
01-Sep
08-Sep
15-Sep
Num
bers
0
100
200
300
400
500a)
Num
ber
of in
fect
ed p
rem
ises
∞
skiing Move to Guelph
d)
Transmission distance (km's)
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Furth
er
Fre
quen
cy
0.0
0.1
0.2
0.3
0.4
0.5
0.6Pre NMB contact tracingPost NMB contact tracing
Post NMB inferred
time
5 km
3 km
3 km
13 km
0.5 km
1.5 km
Reportingdate
Cullingdate
Infection date
d)
Transmission distance (km's)
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50
Furth
er
Fre
quen
cy
0.0
0.1
0.2
0.3
0.4
0.5
0.6Pre NMB contact tracingPost NMB contact tracing
Post NMB inferred
Always pick the closestPick candidates with equal probabilityPick candidates with probabiltiy weighted by distance
time
1
7
0
0
0
0
0
1
4
1
0
1
0
0
0
0
0
0 5 10 15 20 25 30
Infection week
Rt
0
1
2
3
4
5a)
47
101316
Infection week
Ca
se R
ep
rod
uct
ion
Ra
tio
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
Cumbria Devon Dumfries & Galloway Settle0
12
30
12
30
12
30
12
3b)
timeParent
reportingdate
Estimatedparent
infectiondate
Daughter reporting
date
Parent Infected – daughter reporting interval
c)
Parent infection to daughter reporting (IDR) interval
0 5 10 15 20 25 30
Fre
quen
cy
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
93%60%
Rt
0 2 4 6 8 10 12 14 16 18
Fre
quen
cy
0.0
0.1
0.2
0.3
0.4
0.5
Post NMB Pre NMB
20th Feb. Time
20th Feb. 23rd Feb. Time
NMB
20th Feb. 23rd Feb.
X
X
Time
NMB
20th Feb. 23rd Feb. Time
NMB
Imposing the NMB on Feb. 20th, or 21st
Epidemic size
600 800 1000 1200 1400 1600 1800 2000
Pro
ba
bili
ty
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
0.16
0.18
0.20
Imposing 24 hr reporting to cull interval from Feb. 24th
Epidemic size600 800 1000 1200 1400 1600 1800 2000
Pro
babi
lity
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
a)
b)
Between 20th – evening of 23rd of February:
• 17 IPs infected at distance greater than 20km
• 16 of these IPs have positive contact tracing
• 13 were infected by animal movements from markets
time
time
time
Imposing the NMB on Feb. 20th, or 21st
Epidemic size
600 800 1000 1200 1400 1600 1800 2000
Pro
babi
lity
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
0.16
0.18
0.20
Imposing 24 hr reporting to cull interval from Feb. 24th
Epidemic size600 800 1000 1200 1400 1600 1800 2000
Pro
babi
lity
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
a)
b)
20th Feb. 23rd Feb. Time
NMB
20th Feb. 23rd Feb. Time
NMB
X
X
20th Feb. 23rd Feb. Time
NMB
20th Feb. Time
Distance of IP from infection source (km's)
0.01 0.1 1 10 100 1000
Tot
al n
umbe
r of
des
cend
ents
left
res
ultin
gfr
om t
rans
mis
sion
link
s <
20
km d
ista
nt
0.1
1
10
100
1000IPs infected post-NMBIPs infected pre-NMB
a)
0
0
50
100
150
200
250
300
1 3 5 7 9
11 13
15
17
19
21
23
25
27
29
31
Week
Num
ber
of n
ew in
fect
ions
The government, however, dismisses Woolhouse's figures as an overestimate. It also argues that it could not have acted any faster than it did. "A national ban was imposed as soon as it became clear that there was a national problem," a spokesman for the Department for Environment Food and Rural Affairs told New Scientist. But he did add that such a ban would be imposed immediately if any future outbreak occurred.
New Scientist vol. 176 issue 2372 (07 December 2002)
What the foot and mouth virus looks like (not actual size)
1.5% yr-1
1.0% yr-1 1.4% yr-1
1.0% yr-1
1.1% yr-1
0.4% yr-1
Wildtype virus
Mutant virus
Assume:
Simple exponential population growth
Simple Poisson mutation process (no back mutation)
Mutants are either tolerated and equally fit as wildtypeor not tolerated at all
WITHIN HOST POPULATION DYNAMICS
Haydon, D.T., Samuel, A.R., and Knowles, N.J. (2001). The generation and persistence of genetic variation in foot-and-mouth disease virus. Preventative Veterinary Medicine 51, 111-124.
Poliovirus (from Smith and Inglis, 1987)
Monoclonal Target Freq. Resistant #mutations Log freq. each Antibody Antigen Variants (log10) conferring mutation
resistance 27-4-4 VP1 -3.9 7 -4.7 25-5-5 VP1 -3.1 3 -3.6 25-4-12 VP1 -3.2 4 -3.8 I32 VP1 -3.1 1 -3.1 I34 VP1 -3.9 3 -4.4 ICJ31-10 VP1 -5.2 1 -5.2 D3 VP2 -4.6 3 -5.1 IBM55-6 VP2 -5.1 1 -5.1 ICJ27 VP3 -3.0 1 -3.0 ICJ12-9 VP3 -5.3 1 -5.3 IH8-4 VP3 -2.7 1 -2.7 IH8-25 VP3 -3.0 1 -3.0 IBA12 VP3 -2.9 1 -2.9 ICJ12 VP3 -3.6 2 -3.6
Average mutation rate at least 0.0001 per site per replication cycle i.e. at least 1 mutation per genome duplication
0 10 20 30 40 50
10-3
10-4
10-5
10-6
Viral Generations (t)
Error Rate(per base
per replicationcycle)
The fraction of mutant capsid genes in an infected animal?
• observed rates of change in the field are 0.5 - 1.5 % yr-1
• corresponding to 10 - 30 nucleotide changes in capsids genes yr-1
• plausible that the bulk of virus excreted by infected animals differs by at least one point mutation to capsid genes from that which ‘went in’
• therefore sequential chains of infection of 10 - 30 animals yr-1 could give rise to observed rates of change
Uncertainty surrounds many of the critical parameters governing the generation of genetic variation during a single infection
In particular:
• the mutation rate• the number of viral generations• the viability of variants
However, if variation is generated at the rate anticipated, then transmission networks may be traced at a much finer resolution than practiced to date
Group 1 Group 2 Group 3 Group 4
Introduceinfection
Hughes, G.J., Mioulet, V., Haydon, D.T., Kitching, P.R., Donaldson , A.I., and Woolhouse, M.E.J. (2002). Serial passage of foot-and-mouth disease virus in sheep reveals declining levels of viraemia through time. Journal of General Virology 83, 1907-1914.
07
98
83
06
97
90 82
05
96
89 81
04
95
88 80
03
94
87 79
02 86 78
85 77
Inoculum Group 1 Group 2 Group 3 Group 4
01 93
84 76 00 92
99 91
NOT DONE
NOT DONE
NOT DONE
NOT DONE
NOT DONE
NOT DONE
NOT DONE
NOT DONE
Inoculum a
Inoculum b
Ø
487
23487
231,2
487
23487577
23487
23487577
23487
23487577
231,2
487
23487577
23487577
23487577
23
231,2
4875771,2
487
487
NOT INFECTED
NOT INFECTED
NOT INFECTED
NOT INFECTED
NOT INFECTED NOT INFECTED
NOT INFECTED
NOT INFECTED
NOT INFECTED
