Foot-and-mouth disease: the question of implementing vaccinal control during an epidemic.

The question of whether or not to use vaccines during an epidemic of foot-and-mouth disease (FMD) has interested veterinary administrators for many decades. This review assesses the historical uses, successes and failures of vaccinal control, and addresses the questions of where, how, and when to use vaccination against FMD. Approaching the problem in this manner can aid in identifying which tools are likely to be most effective during an epidemic, and how successful a given contingency plan might be. The infection status (endemic, semi-endemic, disease-free) of a region has historically mapped where global vaccination has been implemented according to the generality: endemic>semi-endemic>disease-free. More specifically, biomodels and cost-benefit analyses can indicate when vaccination should be implemented for optimal disease control. Finally, numerous local epidemiological factors will provide useful insights into how vaccinal controls can be used effectively.

Capripoxviruses: an emerging worldwide threat to sheep, goats and cattle.

Capripoxviruses are the cause of sheeppox, goatpox and lumpy skin disease (LSD) of cattle. These diseases are of great economic significance to farmers in regions in which they are endemic and are a major constraint to international trade in livestock and their products. Although the distribution of capripoxviruses is considerably reduced from what it was even 50 years ago, they are now expanding their territory, with recent outbreaks of sheeppox or goatpox in Vietnam, Mongolia and Greece, and outbreaks of LSD in Ethiopia, Egypt and Israel. Increased legal and illegal trade in live animals provides the potential for further spread, with, for instance, the possibility of LSD becoming firmly established in Asia. This review briefly summarizes what is known about capripoxviruses, including their impact on livestock production, their geographic range, host-specificity, clinical disease, transmission and genomics, and considers current developments in diagnostic tests and vaccines. Capripoxviruses have the potential to become emerging disease threats because of global climate change and changes in patterns of trade in animals and animal products. They also could be used as economic bioterrorism agents.

WITHDRAWN: Veterinary vaccines: An unfulfilled promise.

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Geographical and age-stratified distributions of foot-and-mouth disease virus-seropositive and probang-positive cattle herds in the Adamawa province of Cameroon.

Six of the seven known serotypes of foot-and-mouth disease (FMD) virus occur in Africa. This paper describes the results of a population-based cross-sectional study of the seroprevalence of FMD and the persistence of the virus in cattle herds and associated sheep flocks in the Adamawa province of Cameroon. Antibody titres measured by the virus neutralising test indicated that serotypes O, A and SAT2 viruses had been circulating in the province. The estimates of apparent seroprevalence in cattle herds, based on five juvenile animals (eight to 24 months old) per herd, were 74.8 per cent for serotype SAT2, 30.8 per cent for serotype A and 11.2 per cent for serotype O, indicating recent exposure; the estimates based on animals more than 24 months of age were 91.1 per cent for SAT2, 83.6 per cent for A and 34.2 per cent for serotype O. Epithelial and oropharyngeal samples were collected from cattle and small ruminants, cultured and typed by ELISA; serotypes A and SAT2 were isolated from both types of sample. The herd-level estimate of apparent prevalence of probang-positive herds was 19.5 per cent and the animal-level estimate of apparent prevalence was 3.4 per cent. The geographical distribution of the seropositive herds based on juveniles suggested that recent SAT2 exposure was widespread and particularly high in the more northern and western parts of the province, whereas recent exposure to serotype A was patchy and more concentrated in the south and east. This distribution corresponded very closely with the distribution of herds from which virus was recovered by probang, indicating recent exposure or infection. No serotype O viruses were recovered from cattle, and the distribution of seropositive herds suggested very localised recent exposure. The apparent prevalence of probang-positive animals declined with the age of the animal and the period since the last recorded outbreak in the herd.

Use and abuse of mathematical models: an illustration from the 2001 foot and mouth disease epidemic in the United Kingdom.

Foot and mouth disease (FMD) is a major threat, not only to countries whose economies rely on agricultural exports, but also to industrialised countries that maintain a healthy domestic livestock industry by eliminating major infectious diseases from their livestock populations. Traditional methods of controlling diseases such as FMD require the rapid detection and slaughter of infected animals, and any susceptible animals with which they may have been in contact, either directly or indirectly. During the 2001 epidemic of FMD in the United Kingdom (UK), this approach was supplemented by a culling policy driven by unvalidated predictive models. The epidemic and its control resulted in the death of approximately ten million animals, public disgust with the magnitude of the slaughter, and political resolve to adopt alternative options, notably including vaccination, to control any future epidemics. The UK experience provides a salutary warning of how models can be abused in the interests of scientific opportunism.

Predictions for the timing and use of culling or vaccination during a foot-and-mouth disease epidemic.

First-fortnight incidence (FFI) is a modelling parameter that can be used to predict both the prevalence and duration of a foot-and-mouth disease (FMD) epidemic at regional and national levels. With an indication of how long an epidemic may last by the end of week two, it becomes possible to estimate whether vaccination would be economically viable from the start of an epidemic. Where FFI indicates that an epidemic is unlikely to last for as long as an export ban on agricultural produce, it may be inappropriate to implement a policy of 'vaccination to live'. Alternatively where FFI indicates that an epidemic will equal or exceed the ban length, then the benefits of vaccination should be considered at an early stage, during or after the first fortnight. Since blanket vaccination of the national or regional herds and flocks would be both costly and heighten the risk of producing carrier animals, targetting vaccination through risk assessment becomes useful.

A review of foot-and-mouth disease with special consideration for the clinical and epidemiological factors relevant to predictive modelling of the disease.

Modelling the epidemiology of foot-and-mouth disease (FMD) has been undertaken since the early 1970s. We review here clinical factors and modelling procedures that have been used in the past, differentiating between those that have proved to be more relevant in controlling FMD epidemics, and those that have showed less significance. During the 2001 UK FMD epidemic, many previously developed FMD models were available for consideration and use. Accurate epidemiological models can become useful tools for determining relevant control policies for different scenarios and, conversely, inaccurate models may become an abuse for disease control. Inaccuracy presents two opposing difficulties. Firstly, too much control (in terms of animal slaughter for 2001) would negatively impact the farming community for many subsequent years, whilst too little control would permit an epidemic to persist. Accuracy however, presents the optimal permutation of control measures that could be implemented for a given set of conditions, and is a prerequisite to boosting public confidence in the use of epidemiological models for future epidemics.

Risk factors for herdsman-reported foot-and-mouth disease in the Adamawa Province of Cameroon.

We analysed responses from 147 Fulani herdsmen to a questionnaire about cattle herd-level risk factors for foot-and-mouth disease (FMD) in the previous year. The study used a cross-sectional design with a stratified, two-stage random sample of cattle herds in the Adamawa Province of Cameroon. The questionnaire was pre-tested at a local cattle market before a final version was translated into Foulfoulde (the local Fulani dialect). Variables were screened using a univariable analysis and logistic multiple-regression models were developed in a forward-selection process. Fifty-eight percent (50-65; 90% CIs) of herdsmen reported FMD in their herd in the previous 12 months. Important risk factors for FMD in the previous 12 months included going on transhumance (OR=2.6), buying cattle from markets (OR=2.2), mixing of herds at watering points (OR=2.4), feeding cotton-seed cake (OR=3.3), buffalo near the herd (OR=2.2) and administrative division. For the subset of herds that went on transhumance, coming in contact with an FMDV-diseased herd while on transhumance was the strongest factor (OR=16).

Comparison of two 3ABC enzyme-linked immunosorbent assays for diagnosis of multiple-serotype foot-and-mouth disease in a cattle population in an area of endemicity.

The development of a serological test for foot-and-mouth disease virus (FMDV) which is quick and easy to use, which can identify all seven serotypes, and which can differentiate vaccinated from convalescing or potential virus carriers would be a major advance in the epidemiological toolkit for FMDV. The nonstructural polyprotein 3ABC has recently been proposed as such an antigen, and a number of diagnostic tests are being developed. This paper evaluates the performance of two FMDV tests for antibodies to nonstructural proteins in an unvaccinated cattle population from a region of Cameroon with endemic multiple-serotype FMD. The CHEKIT-FMD-3ABC bo-ov (CHEKIT) enzyme-linked immunosorbent assay (ELISA) (Bommeli Diagnostics/Intervet) is a commercially available test that was compared with a competitive 3ABC ELISA (C-ELISA) developed in Denmark. The tests were compared with the virus neutralization test as the "gold standard." Diagnostic sensitivity and specificity were examined over a range of test cutoffs by using receiver operating characteristic curves, which allowed comparison of the overall performance of each test. The results indicated that the CHEKIT ELISA kit was 23% sensitive and 98% specific and the Danish C-ELISA was 71% sensitive and 90% specific at the recommended cutoff. These results have important implications if the tests are to be used to screen herds or individual cattle in surveillance programs, at border crossings for import-export clearance, or following emergency vaccination in an outbreak situation.

Molecular epidemiology of foot-and-mouth disease viruses in the Adamawa province of Cameroon.

Foot-and-mouth disease virus (FMDV) causes a highly contagious viral disease of even-toed ungulates and is one of the most important economic diseases of livestock. Most studies of FMDV are done in countries where control measures are being implemented. In contrast, in areas such as sub-Saharan Africa, where FMDV is endemic and new strains are likely to emerge, there are only sporadic submissions to the World Reference Laboratory, Pirbright, United Kingdom. This paper describes the molecular epidemiology of FMDV in the Adamawa province of Cameroon based on a population sample of cattle herds. Serotypes SAT2 and A were isolated in the cross-sectional study. SAT2 isolates were all similar, with phylogenetic distances of <6%, and were most closely related to published sequences of isolates from Eritrea and Saudi Arabia. Serotype A isolates were more variable, with phylogenetic distances of 0 to 11%, and were most closely related to historic isolates from Cameroon. Use of a population-based sample gives a representative sample of virus diversity and will improve our understanding of the evolution of FMDV and its epidemiology. A supplementary study of pigs passing through the railhead collection yard at Ngaoundere detected a serotype O virus. A third pilot longitudinal study monitored viral persistence in three cattle herds over 12 months, and serotype O and A viruses were recovered from a herd 12 months after it was first recorded as being infected with SAT2 virus. The pig type O isolate was not closely related to that recovered from the cattle, suggesting that the pigs had not introduced the O virus into the cattle herds.

Foot and mouth disease and livestock husbandry practices in the Adamawa Province of Cameroon.

Foot and mouth disease (FMD) is a highly contagious viral disease of even-toed ungulates and is endemic in most of the tropics. A cross-sectional study using a stratified, two-stage random sample design was undertaken in the Adamawa Province of Cameroon. The objectives were to measure the reported herd-level prevalence of FMD and a range of husbandry practices important for its transmission. The owner-reported prevalence for the previous 12 months was 57.9% (50.4-65.4%), although there was a significant variation across the Province. During the previous dry season, 46.5% (38.6-54.4%) of herds had gone on transhumance. Herds had high numbers of contacts with other herds while on transhumance (98.6%), at pasture (95.8%) and at night (74.4%), with medians of 7-10, 4-6 and 1-3 daily contacts, respectively. The high level of endemic FMD and potential for disease spread presents a significant challenge for control and eradication. Locally sustainable methods need to be developed upon which larger regional control programmes could be built in the future.

Vaccines for lumpy skin disease, sheep pox and goat pox.

Sheep pox, goat pox and lumpy skin disease (Neethling) are diseases of sheep, goats and cattle respectively, caused by strains of poxvirus, within the genus Capripoxvirus. Strains affecting sheep and goats are not totally host-specific; some cause disease in both sheep and goats while others may cause disease in only one species. Those causing disease in cattle appear to be specific for cattle, and this is reflected in the different geographical distribution of lumpy skin disease (LSD) and sheep pox and goat pox (sheep and goat pox); LSD is confined to Africa, while sheep and goat pox are present in Africa north of the equator, and throughout West Asia and India, as far East as China and Bangladesh. Occasionally sheep and goat pox spreads from Turkey into Greece. All strains of capripoxvirus so far examined are antigenically indistinguishable, and recovery from infection with one strain provides immunity against all other strains. Because of this antigenic homology among all strains, there is the potential to use a single vaccine strain to protect cattle, sheep and goats.

Attempted mechanical transmission of lumpy skin disease virus by biting insects.

The mosquitoes Anopheles stephensi Liston and Culex quinquefasciatus Say (Diptera: Culicidae), the stable fly Stomoxys calcitrans Linnaeus (Diptera: Muscidae) and the biting midge Culicoides nubeculosus Meigen (Diptera: Ceratopogonidae) were allowed to feed on either lumpy skin disease (LSD) infected animals or through a membrane on a bloodmeal containing lumpy skin disease virus (LSDV). These arthropods were then allowed to refeed on susceptible cattle at various intervals after the infective feed. Virus was detected in the insects by polymerase chain reaction immediately after feeding and at sufficiently high titre to enable transmission to occur. However, no transmission of virus from infected to susceptible animals by An. stephensi, S. calcitrans, C. nubeculosus and Cx. quinquefasciatus was observed.

Clinical and laboratory investigations of five outbreaks of foot-and-mouth disease during the 2001 epidemic in the United Kingdom.

Clinical and laboratory investigations of five outbreaks of foot-and-mouth disease (FMD) were made during the early stages of the 2001 epidemic in the UK. The first outbreak, confirmed on February 20, was at an abattoir in Essex which specialised in the processing of culled sows and boars. On February 23, the disease was confirmed at a pig farm in Northumberland which held cull sows and boars fed on waste food; the findings indicated that it was the first of the five premises to be infected. The disease had probably been present since early February, and it was the most likely origin of the epidemic. The other premises investigated were a waste food-fed cull sow/boar pig unit in Essex, approximately 30 km from the abattoir, which was probably infected at the same time or before the abattoir, a sheep and cattle farm approximately 6 km from the Northumberland pig farm, which was probably infected by airborne virus from it in the period immediately before February 13, and a sheep and cattle farm in Devon which had clinical disease from February 20 and was probably infected by sheep transported from Northumberland on February 13 which arrived on February 15.

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.

Dose-dependent responses of sheep inoculated intranasally with a type O foot-and-mouth disease virus.

Unlike foot-and-mouth disease (FMD) in cattle and pigs, which spreads rapidly, resulting in easily detectable foci of clinical infection, the disease in sheep is characterized by restricted transmission, low morbidity and sporadic clinical cases. The study described was designed to investigate whether the ability of sheep to transmit and maintain FMD virus was dose-related. The viral isolate used was known to be associated epidemiologically with rapid fade-out of transmission within sheep flocks. Five separate transmission experiments were performed, with different doses of FMD virus, each experiment containing five intranasally inoculated donor sheep and 10 in-contact recipient sheep. The lowest dose required to cause clinical infection by inoculation (10(4) 50% tissue culture infectious doses; 10(4) TCID50) was also the optimum dose for producing in-contact transmission. Inoculation of donor sheep with higher doses (10(5) and 10(6) TCID50) resulted in reduced transmission, characterized by reduced duration and degree of viraemia and an early humoral and cell-mediated immune response. Principal component analysis was used to interpret the complex interactions of the dose-related responses to infection.

Experimental studies with foot-and-mouth disease virus, strain O, responsible for the 2001 epidemic in the United Kingdom.

In 2001, the United Kingdom experienced its worst epidemic of foot-and-mouth disease (FMD). To date approximately 3.9 million animals have been culled and direct and indirect revenue losses are probably in excess of pound 12 billion. This study was carried out to investigate the biological characteristics of the FMD virus strain O/UKG/2001 responsible for the epidemic. Animal transmission experiments indicated that this strain is not host restricted and will infect the three main susceptible livestock species (cattle, sheep and pigs). Immunisation with high potency emergency vaccine derived from O(1) Manisa strain of FMD virus protected all three species against clinical disease when challenged with FMD virus strain O/UKG/2001.