Download Quantification of foot and mouth disease virus excretion and transmission within groups of sheep with and without vaccination

Appendix 39
Quantification of foot and mouth disease virus excretion and transmission within groups
of sheep with and without vaccination
Orsel, K1,*, Dekker, A.2 , Bouma, A1., Stegeman, J.A1., De Jong, M.C.M3,
1: University of Utrecht, Veterinary Faculty, Department of Farm Animal Health,
Utrecht, The Netherlands.
2: Central Institute for Animal Disease Control, CIDC-Lelystad (Wageningen-UR), Lelystad, The
Netherlands
3: Animal Sciences Group, Wageningen University and Research Centre, Wageningen, The
Netherlands
* P.O. box 80.151,3508 TD Utrecht, The Netherlands. Tel.: +31 30 2537551, Fax: +31 30
2521887 Email address: [email protected]
Abstract:
The aim of this study is to quantify FMDV O/NET2001 virus excretion and transmission in groups of
sheep with and without vaccination.
Material and Methods: Transmission of FMDV was studied in experiments with 6 groups of 4 nonvaccinated, and in 6 groups of 4 single-vaccinated lambs. Two lambs per group were inoculated
with FMDV and the other two were exposed by direct contact to the inoculated sheep. We
estimated the transmission rate β using a generalized linear mixed effect model, the reproduction
ratio R using the final size method, and the duration of the infectious period using parametric
(exponential) survival analysis.
Results: Clinical signs were mild and rare. Virus was excreted in oropharyngeal fluid before and
after clinical signs were observed and also in subclinically infected sheep. In the non-vaccinated
groups, the transmission rate β was 0.105 (0.044;0.253) per day, and the reproduction ratio Rnv
1.14 (0.3;3.3). The duration of the infectious period was estimated to be 21.11 (10.6;42.1) days.
In the vaccinated group, β and duration could not be determined due to limited observations of
virus excretion in oro-pharyngeal fluid. The reproduction ratio Rv was 0.22 (0.01;1.78). The nonvaccinated lambs had a significantly higher mean daily virus excretion and number of days virus
was excreted compared to the vaccinated groups.
Conclusion: Virus transmission did not differ significantly between vaccinated and unvaccinated
groups, although the Rv tends to be lower than Rnv. Since in this experiment within-pen
transmission was studied, it seems reasonable to assume that the between-herd transmission will
be lower because of the lower contact rate between farms. Vaccination has a significant effect on
mean daily virus excretion and number of days virus is excreted. Therefore vaccination of sheep
should be considered in FMD contingency plans, especially since clinical diagnosis in sheep is
difficult.
Introduction:
An outbreak of foot-and-mouth disease occurred in The Netherlands in 2001(Bouma et al., 2003).
The capacity for pre-emptive culling and destruction appeared to be insufficient and therefore
emergency vaccination was applied. In cattle it is known that vaccination prevents clinical signs of
FMD, and single vaccination reduces virus transmission (Donaldson & Kitching, 1989, Orsel et al.,
2005, Orsel et al., 2006). Experiments with pigs showed that emergency vaccination reduces
transmission of FMD virus (Eble et al., 2004, Salt et al., 1998). Extrapolation of results from pigs
and cattle to sheep may not be valid, because difference in susceptibility, infectivity and clinical
appearance are known (Kitching, 2002, Kitching & Alexandersen, 2002, Kitching & Hughes, 2002).
Therefore the important question remains whether FMDV can sustain in a susceptible sheep
population and, if so, whether single vaccination can reduce FMDV transmission sufficiently to stop
an epidemic (R < 1). The objective of the study was to quantify virus transmission within groups of
lambs and in addition to determine the effect of vaccination thereon.
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Materials and Methods:
We used 12 groups of 4 lambs each; lambs in 6 groups were vaccinated 14 days prior to
inoculation with a DOE O-Manisa vaccine. In each group of 4 lambs, 2 lambs were intranasally
inoculated with approximately 1500 CID50 (cow infectious dose 50%) of the first cattle passage of
the FMD field isolate O/NET2001. This dose is equal to 104.6 plague forming units on secondary
lamb kidney cells. Transmission of FMDV to contact exposed lambs was observed by recording the
clinical signs and by virus titration and RT-PCR on OPF (oro pharyngeal fluid from swabs) and
plasma (from heparinised blood samples) (Terpstra et al., 1990). Antibody response to the FMDV
infection was detected by a virus neutralization assay (Dekker & Terpstra, 1996) and NS ELISA on
serum samples. At the end of the experiment (Day 29-30-31), probang sputum samples were
collected for virus isolation.
The mean daily virus excretion (MDV) was calculated per lamb for each day that virus was detected
in the oro-pharyngeal fluid (OPF) samples to compare the virus excretion in the different groups.
The transmission rate parameter β in the non-vaccinated groups of lambs was calculated using a
generalised linear model (GLM) described by Klinkenberg et al (Klinkenberg et al., 2002). The
estimation of β was based on the numbers of newly infected (C), susceptible (S) and infectious (I)
lambs per day. The duration of the infectious period, T, was based on the presence of virus in the
OPF samples. T was estimated with a parametric survival analysis with an exponential distribution
(S-PLUS 7.0). Finally we quantified the virus transmission with a S-I-R model in which the lambs
were classified as S (=susceptible), I (= infectious) and R (= recovered) at the beginning and the
end of the experiment. Lambs were classified as infectious when they showed clinical signs or when
one of the laboratory tests gave a positive result. Transmission was quantified with the maximum
likelihood estimator (MLE) for the reproduction ratio (R) in the S-I-R model.
Results:
Clinical signs were mild and rare. Virus was excreted in oropharyngeal fluid before and after clinical
signs were observed. Virus was also isolated from sheep without clinical signs. The MDV excretion
between vaccinated and non-vaccinated lambs differed significantly (p=0.001). Within the
vaccinated or the non-vaccinated groups no difference was observed between the inoculated and
contact-exposed lambs, which is an indication for the validity of our inoculation method with
respect to the excretion of infectious virus of lambs. In the non-vaccinated groups, the
transmission rate β was 0.105 (0.044;0.253) per day, and the reproduction ratio Rnv 1.14 (0.3;3.3).
The duration of the infectious period was estimated to be 21.11 (10.6;42.1) days. In the
vaccinated group, β and duration could not be determined due to limited observations of virus
excretion in oro-pharyngeal fluid. The reproduction ratio Rv was 0.22 (0.01;1.78). When testing the
hypothesis as to whether transmission in groups with and without vaccination is the same, no
significant difference was found (p=0.11). Final size of infection is shown in figure 1.
Discussion:
Transmission expressed as reproduction ratio R did not differ significantly between vaccinated and
unvaccinated groups, although the Rv tends to be lower than Rnv. However, this experiment studied
within-pen transmission, and it seems reasonable to assume that the between-herd transmission
will be lower because of the lower contact rate between farms. Vaccination has a significant effect
on mean daily virus excretion and number of days virus is excreted. Therefore vaccination of sheep
should be considered in FMD contingency plans, especially since clinical diagnosis in sheep is
difficult, and virus is excreted before, after and without clinical signs.
Acknowledgements:
•Financial support from the ministry of agriculture in the Netherlands (BOP 7-428)
•Financial support from the European Union (EU SSPE-CT-2003-503603)
•Technicians from the FMD-laboratory and animal technicians in Lelystad
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Figure 1
Final size of infection in twelve groups of four lambs
Non-vaccinated groups
1
begin
2
3
4
5
6
←Inoculated
←Contact
end
Vaccinated groups
7
begin
end
←Inoculated
←Contact
8
9
10
11
12
←Inoculated
← Contact
←Inoculated
←Contact
Infectious lamb
Susceptible lamb
270