1

Risk of rabies introduction by non-commercial movement of pets

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”

P. Have, L. Alban, L.T. Berndtsson, F. Cliquet, P. Hostnik, S.C. Rodeia and M. Sanaa

2

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

3

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

4

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

5

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

6

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)

7

Model parameters

• distribution of incubation periods– Dogs: 1 week to several

months– Cats: 9 days to 6

months

• described by a log-normal distribution with mean 38 days

0 50 100 150 200

0.0

00

0.0

05

0.0

10

0.0

15

0.0

20

0.0

25

days

fun

ctio

n(x

) d

lno

rm(x

, me

an

log

= 3

.37

, sd

log

= 0

.75

) (x

)

Incubation period

8

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

9

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

10

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

11

Risk pathways

Pet at timeof vaccination

Currently Notincubating rabies

Currentlyincubating rabies

1 - P

P

Not Protected

1- EV

Tested falsepositive forprotection

Not Tested

Becomesinfected during

waiting time

Becomesinfected during

waiting time

Doesn’t showClinical signs

during WT

Doesn’t showClinical signs

during WT

RIWT

Not Protected

1Doesn’t showClinical signs

during WT

1- fA

1- SP

TYPE B RISK

TYPE A RISK

1- fB

12

Type A risk

Incubation period

VaccinationVaccinationDay ofDay ofinfectioninfection

ClinicalClinicalsignsign

Waiting time

Residual Incubation period

Time

13

Type B risk

Incubation period

VaccinationVaccinationClinicalClinical

signsign

Waiting time

Day ofDay ofinfectioninfection

Time

14

Model descriptionPrevalence A and B

• prevalence Pa of animals already incubating rabies will gradually decrease as a result of developing clinical diseasePa = P * f(t)

• prevalence Pb of animals infected after the time of vaccination will gradually replace PaPb = P * (1- f(t))

0 50 100 150 200

0.0

0.2

0.4

0.6

0.8

1.0

Waiting period

f(t)

PaPb

15

Model descriptionRisk A and B

• Type A risk

• Type B risk with vaccination

• Type B risk with vaccination and serology

• Ra = P * f(t) = Pa

• Rb = (1 - Ev) * Pb

• Rb = (1 – Sp) * (1 - Ev) * Pb

16

Model descriptionTotal 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 orRtot = P * (f(t) + (1 – Sp) * (1 - Ev) * (1- f(t))) or

Rtot = P * (1 – (Ev + Sp - Ev * Sp )*(1- f(t))

17

Model descriptionmodelling 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 iterations0 50 100 150 200

0.0

0.2

0.4

0.6

0.8

1.0

Waiting period

f(t)

PaPb

18

Model descriptionnon-linear least squares estimate of f(t)

• f(t) = exp(-0.0313*t)

Rtot = P * (1 – (Ev + Sp - Ev * Sp )*(1- exp(-0.0313*t))

0 50 100 150 200

0.0

0.2

0.4

0.6

0.8

1.0

waiting period

f(t)

19

Effect of serological testing

0 50 100 150 200

24

68

10

waiting period

ga

in fa

cto

r fo

r se

rolo

gic

al t

est

ing