Transcript Document

Risk of rabies introduction by non-commercial
movement of pets
P. Have, L. Alban, L.T. Berndtsson, F. Cliquet, P.
Hostnik, S.C. Rodeia and M. Sanaa
The EFSA Journal (2006) 436 1-54, ”Assessment of the risk of rabies
introduction into the UK, Ireland, Sweden, Malta, as a consequence of
abandoning the serological test measuring protective antibodies to rabies”
1
Current legislation
• Regulation (EC) No 998/2003
– valid anti-rabies vaccination
– waiting time of at least 21 days (COM 2005/91/EC)
– derogations for UK, Ireland, Sweden and Malta to
maintain serological test
– review of derogations at the end of transitory period of
5 years following receipt of a scientific opinion of
EFSA
2
EFSA mandate
• Commission requested EFSA to issue a
scientific opinion on the risk assessment of
rabies introduction into Ireland, the UK, Sweden
and Malta, as a consequence of abandoning the
serological test for antibody titration for rabies
3
Mandate cont’
• To what extent the abandoning of the individual
serological test for neutralising rabies-antibodies
titration could be envisaged without increasing
the risk
• If the need to maintain the serological test is
scientifically justified, what is the regime to be
considered as giving equivalent assurance
4
Approach
• Quantitative risk assessment based on
– prevalence of rabies in the country of origin in pets
– distribution of incubation periods of rabies
– efficiency of establishing protective immunity by
vaccination
– specificity of the neutralization test for rabies (RFFIT
or FAVN)
– length of the waiting period
5
Model parameters
Prevalence (P)
– estimated from annual incidence data by assuming a
mean incubation time of 38 days
– pet population size estimated from 1.0 dog and 1.1
cats per 10 people
P = incidence*38/(population at risk*365)
6
Model parameters
• described by a log-normal
distribution with mean 38
days
0.025
0.020
0.015
0.010
0.005
– Dogs: 1 week to several
months
– Cats: 9 days to 6 months
0.000
• distribution of incubation
periods
function(x) dlnorm(x, meanlog = 3.37, sdlog = 0.75) (x)
Incubation period
0
50
100
150
200
days
7
Model parameters
Efficiency of vaccination (Ev)
– assessed indirectly by measuring the antibody
response
– measured after first, single vaccination
– absence of antibodies not always associated with loss
of protection
– interval between vaccination and testing major
determinant
– Ev of 98% used tentatively in this study
8
Model parameters
Test specificity (Sp)
– determines whether truly antibody-negative
individuals are correctly assigned as such or whether
some individuals are classified as false positive
– FAVN test more specific than RFFIT
– a tentative value of 99% is used here
9
Model parameters
• Length of waiting period (t)
– Measured from time of vaccination
– t will determine the residual prevalence Pa of animals
incubating rabies due to pre-vaccination exposure
10
Risk pathways
1- SP
Tested false
positive for
protection
Becomes
infected during
waiting time
1- EV
1- fB
RIWT
Currently Not
incubating rabies
Not Protected
Not Tested
1-P
Becomes
infected during
waiting time
Doesn’t show
Clinical signs
during WT
TYPE B RISK
Doesn’t show
Clinical signs
during WT
Pet at time
of vaccination
1- fA
P
1
Currently
incubating rabies
Not Protected
Doesn’t show
Clinical signs
during WT
TYPE A RISK
11
Type A risk
Waiting time
Time
Day of
infection
Vaccination
Clinical
sign
Residual Incubation period
Incubation period
12
Type B risk
Waiting time
Time
Vaccination
Day of
infection
Clinical
sign
Incubation period
13
Model description
Pb = P * (1- f(t))
0.2
0.0
• prevalence Pb of animals
infected after the time of
vaccination will gradually
replace Pa
0.4
f(t)
0.6
Pa = P * f(t)
Pa
Pb
0.8
• prevalence Pa of animals
already incubating rabies
will gradually decrease as
a result of developing
clinical disease
1.0
Prevalence A and B
0
50
100
150
200
Waiting period
14
Model description
Risk A and B
• Type A risk
• Ra = P * f(t) = Pa
• Type B risk with
vaccination
• Rb = (1 - Ev) * Pb
• Type B risk with
• Rb = (1 – Sp) * (1 - Ev) * Pb
vaccination and serology
15
Model description
Total risk
• Total risk Rtot that an animal incubates rabies at
time t after vaccination and serological testing is
given by the sum of Ra and Rb:
Rtot = P * f(t) + (1 – Sp) * (1 - Ev) * Pb
Rtot = P * (f(t) + (1 – Sp) * (1 - Ev) * (1- f(t)))
or
or
Rtot = P * (1 – (Ev + Sp - Ev * Sp )*(1- f(t))
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Model description
0.6
0.8
Pa
Pb
0.0
0.2
0.4
f(t)
• Sample an incubation period
(ip) from the lognormal
distribution
• Sample an interval between
infection time and vaccination
(int) from a uniform distribution
between 0 and 365 days prior
to vaccination
• F(t) calculated from positive
values of ip-int
• 100.000 iterations
1.0
modelling f(t)
0
50
100
150
200
Waiting period
17
Model description
0.4
0.0
0.2
• f(t) = exp(-0.0313*t)
f(t)
0.6
0.8
1.0
non-linear least squares estimate of f(t)
0
50
100
150
200
waiting period
Rtot = P * (1 – (Ev + Sp - Ev * Sp )*(1- exp(-0.0313*t))
18
8
6
4
2
gain factor for serological testing
10
Effect of serological testing
0
50
100
150
200
waiting period
19