Cattle, sheep and pigs vaccinated against foot and mouth disease: does trade in these animals and their products present a risk of transmitting the disease?

The foot and mouth disease (FMD) status of a country or region has a profound bearing on access to export markets for live animals and animal products. In countries without FMD-free status, and in accordance with the international standards of the World Organisation for Animal Health (OIE), restrictions may be applied to trade in both vaccinated and unvaccinated animals and their products. Available information suggests that, provided there is compliance with essential criteria concerning vaccines, vaccination and other zoosanitary measures (especially quarantine and ante- and post-mortem inspection), the risk of spreading FMD through the importation of vaccinated cattle, sheep and pigs is extremely small. The risk from products derived from vaccinated animals is even smaller, provided that appropriate risk mitigation measures are applied. Knowledge of the zoosanitary status of the exporting country is critical for risk assessment, but can be difficult to verify. Although empirical evidence and practical experience strongly indicate low risk, it is not possible to assert that the risk is zero for vaccinated animals or their products. In the absence of key factual data, risk analysis is only practicable on a qualitative or semi-quantitative basis. However, a very low level of risk is both unavoidable and acceptable if such trade is to be conducted.

Aspects of emergency vaccination against foot-and-mouth disease.

Emergency vaccination is one of several measures which may be deployed to control outbreaks of foot-and-mouth disease. It can be a valuable adjunct to the application of the essential zoosanitary controls which must include rapid diagnosis, tracing, movement control and disinfection and which may also include slaughter of infected and in-contact animals and their safe disposal. Criteria which determine the successful application of emergency vaccination include access to vaccine(s) that (i) contain virus strain(s) of sufficient antigenic relatedness to the outbreak strain(s) (ii) are of the required type of vaccine formulation (iii) have acceptable innocuity and potency (iv) have appropriate availability, including quantity and immediacy of supply and (v) meet considerations of cost. Contingency planning should include provision for emergency vaccination and must address the complex decisions of not only when, where, and how to apply vaccine but also its economic consequences. Computer modelling may be a useful aid to cost benefit and decision support systems in this context. Planning must be detailed and regularly reviewed and should ensure, (i) that the legal and financial aspects are catered for (ii) that any contractual supply agreements are in place (iii) that information is collected and its currency maintained on the species, numbers and whereabouts of susceptible livestock (iv) that vaccination teams are formed and trained (v) that the vaccine cold chain is established and maintained (vi) that supplies of vaccination equipment are held in readiness and (vii) that briefing materials are available to inform the various stakeholders on relevant aspects of emergency vaccination. Knowledge concerning the characteristics and performance of emergency vaccines is summarised and areas identified for further research.

The pathogenesis and diagnosis of foot-and-mouth disease.

The pathogenesis of foot-and-mouth disease (FMD) is reviewed, taking account of knowledge gained from field and experimental studies and embracing investigations at the level of the virus, the cell, the organ, the whole animal and the herd or flock. The review also addresses the immune response and the carrier state in FMD. Progress made in understanding the pathogenesis of the disease is highlighted in relation to developments in diagnosis and methods of control.

Foot and mouth disease: the future of vaccine banks.

The authors briefly review the history of vaccine banks for foot and mouth disease, their current location and their constituent serotypes and strains, together with the occasions on which they have been activated. Experimental studies on emergency vaccines are summarised and areas identified for further investigation. The future of such banks is considered, including the principal strengths and weaknesses of existing banks, and suggestions are made for potential improvements. The fact that the banks have been activated on relatively few occasions over the 25 years of their existence testifies in part to the relatively rare calls which have been made upon them, but also reflects the difficulty in deciding when and how to utilise emergency vaccination. Nevertheless, in an era of increasing global risks of the spread of foot and mouth disease, banks will most certainly continue to have strategic and tactical importance in the control of this most readily communicable of animal diseases.

Investigation of the possible spread of foot-and-mouth disease virus by the burning of animal carcases on open pyres.

An atmospheric dispersion model was used to predict the airborne spread and concentrations of foot-and-mouth disease virus within the plumes generated by 11 pyres built to burn infected carcases during the epidemic of 2001 in the UK. On the basis of assumptions about the quantity of virus emitted during the three hours after the pyres were built and the threshold concentration of virus required to cause an infection in cattle, it was concluded that none of the disease breakdowns which occurred under the plumes was due to the spread of virus from the pyres.

Vital elements for the successful control of foot-and-mouth disease by vaccination.

The efficient control of foot-and-mouth disease (FMD) by immunisation depends not only on the appropriate choice of vaccine in terms of innocuity, potency and strain composition, but also on a series of inter-related zoo-sanitary factors which are equally important. These include: national, centralised planning (including contingency planning) and control; vaccination and revaccination policy; the availability of epizootiological intelligence based on adequate diagnostic capability and ongoing immunological surveillance; the logistics of supply with its components of storage, transport and distribution; proper vaccine application; cleaning and disinfection of premises, vehicles and personnel; identification of individual animals; control of animal movement; recording; ongoing economic outcome and benefit analyses: training and retraining of professional and technical staff; public relations and especially the commitment of the agricultural community. These elements are reviewed in this paper.

Immune response to virus-infection-associated (VIA) antigen in cattle repeatedly vaccinated with foot-and-mouth disease virus inactivated by formalin or acetylethyleneimine.

The results of experiments to investigate antibody to 'virus infection associated' (VIA) antigen in cattle repeatedly vaccinated with formalin- or acetylethyleneimine- (AEI) inactivated foot-and-mouth disease (FMD) vaccines under laboratory conditions are reported. Results are also presented from some vaccinated animals subsequently exposed to FMD infection. Antibody against VIA was not detected before and after the first vaccination with formalin or AEI-inactivated vaccine but did develop in all animals after the second formalin vaccination and persisted throughout the experiment. After the second AEI vaccination, 4 of 12 animals developed antibody which persisted for at least 37 days. This transient response in some cattle was repeated after successive vaccinations but, in general, more animals responded as the number of vaccinations increased. After exposure to infection a transient VIA antibody response was occasionally observed in immune AEI-vaccinated animals. Some immune repeatedly AEI-vaccinated cattle did not develop detectable VIA antibody after challenge despite the persistence of virus in oesophageal-pharyngeal (O/P) fluid. The presence of antibody to VIA antigen is not conclusive proof that vaccinated animals have been exposed to infection and field data must be interpreted with caution.

In vivo and in vitro studies on temperature-sensitive mutants of swine vesicular disease virus.

Two temperature-sensitive mutants of the Ukg 27/72 strain of swine vesicular disease virus were isolated in tissue culture and a third was derived following adaptation in mice. All three were found to have similar growth restrictive temperatures, but varied considerably in their virulence when administered to pigs. The route of inoculation appeared to exert a considerable influence on the apparent degree of attenuation, the antibody titre engendered and the transmission of disease to pigs held in contact with inoculated animals. One strain appeared almost totally attenuated when inoculated animals. One strain appeared almost totally attenuated when inoculated into pigs but spread to animals in contact causing severe disease. Virus re-isolated from one such animal was found to have retained its temperature sensitive phenotype, suggesting that virulence in this case was not directly related to temperature sensitivity. Pigs with high antibody titres were found to be susceptible when placed in contact with challenge animals, although the lesions which developed were mild.

An evalutation of some methods of assay of foot-and-mouth disease antigen for vaccines.

The relative merits of various in vitro assay systems for the measurement of the quality and quantity of foot-and-mouth disease virus vaccine antigen will be discussed. The assay systems include : viral infectivity, complement fixing activity, particle counts, radial diffusion titre and single radial haemolysis titre. The predictive value of the tests for the immunogenicity of the final vaccine product will be evaluated against the results of 50% Protective Dose titres determined in guinea pigs and cattle by antibody assay and by challenge.

The use of BHK suspension cells for the commercial production of foot and mouth disease vaccines over a twenty year period.

The Wellcome Foundation Ltd first used BHK suspension cells for the commercial production of foot and mouth disease vaccine in 1964. Since that time both the scale of operation and the volume of production has increased dramatically and in 1983 the Wellcome Group produced almost 350 million monovalent equivalent doses of vaccine from just over 2 million litres of antigen. Experience gained during this period has shown that with careful attention to plant design and operation this large industrial scale tissue culture process can be managed reliably and efficiently. Data will be presented to show the level of production and success rate achieved in our Foot and Mouth Vaccine production units together with an analysis of antigen yields and the comparatively few failures experienced.

A blastogenic test for foot-and-mouth disease.

A blastogenic test to detect peripheral blood leukocytes specifically sensitized to foot-and-mouth disease virus antigen is described. The test is carried out in microtitre plates and optimum conditions were found by titration. These employed 7.5 x 10(5) cells/well and 20 complement fixing units of antigen. Peak [3H]thymidine incorporation was found to take place at 2-3 days.