No between-pen transmission of foot-and-mouth disease virus in vaccinated pigs

Many studies have shown transmission of foot-and-mouth disease virus (FMDV) within groups of pigs, even when vaccinated, but only limited information is available on transmission between pens. Three new experiments were carried out in two replicates, which consisted of infectious pigs housed in a central pen surrounded by four separate pens. First, all pigs were non-vaccinated and pens were separated by a walkway of 40–70 cm. Second, all pigs were non-vaccinated again but pens were adjacent. Third, this was repeated with all pigs vaccinated.     

The effect of vaccination on foot and mouth disease virus transmission among dairy cows

The aim of this study was to quantify the effect of a single vaccination of dairy cows on foot and mouth disease virus (FMDV) transmission. To estimate if vaccination could significantly reduce virus transmission, we performed two replicates of a transmission experiment with one group of vaccinated and one group of non-vaccinated dairy cows (ten animals per group). Half of both groups were intranasally inoculated, with FMDV field isolate O/NET2001, and housed with the other half of the group (contact-exposed cows) from the next day onwards. Virus transmission was quantified by estimating the reproduction ratio R, which is the average number of secondary cases caused by one infectious animal. In the non-vaccinated groups all cows became infected and Rnv was significantly above 1. In the vaccinated groups infection was demonstrated in three inoculated cows, and no transmission was observed (Rv was 0, not significantly below 1). Transmission was significantly reduced in the groups of vaccinated cows when compared to the groups of unvaccinated cows. Our findings indicate that after a single vaccination cows are protected against infection of FMD and that most likely no virus transmission will occur within a vaccinated herd.     

Response of sheep vaccinated with large doses of vaccine to challenge by airborne foot and mouth disease virus

Administration of three-fold or six-fold larger doses of conventional monovalent type O foot and mouth disease (FMD) vaccine to sheep prevented viraemic distribution of virus after exposure to airborne virus one week later. However, virus replication in the respiratory tract or excretion in oesophageal-pharyngeal fluids and breath was not prevented. The implication of these findings for the use of vaccine as an adjunct to a 'stamping out' policy for countries which are free from FMD and which do not practice mass annual vaccination are discussed.     

Identification of foot and mouth disease virus carrier and subclinically infected animals and differentiation from vaccinated animals

Countries that are free of foot and mouth disease (FMD) are reluctant to use vaccine in the event of an outbreak because of the difficulties this can cause in re-establishing freedom from FMD status to the satisfaction of trading partners. The problem does not lie in distinguishing between vaccinated and recovered animals as vaccinated animals can be tagged or otherwise marked to show that they have been vaccinated; the difficulty is in identifying vaccinated animals that have had contact with live virus and become carriers. The traditional probang test is not sufficiently sensitive and is labour- and laboratory-intensive, but alternative serological tests such as those for antibodies to non-structural proteins (NSPs), or specific immunoglobulin A (IgA) are also not 100% sensitive. However, these newer tests do provide increased security by reducing the likelihood of trading carrier animals and can be used to help define the limits of an outbreak; the use of vaccine to help control an outbreak of FMD in a previously free country still has significant consequences on trade in FMD susceptible animals and their products.     

Vaccination against foot and mouth disease reduces virus transmission in groups of calves

The aim of vaccination during an epidemic of foot and mouth disease (FMD) is not to induce clinical protection, but to reduce virus transmission. Since no quantitative data were available on the effectiveness of vaccination in cattle, we investigated whether a single vaccination against FMD could reduce virus transmission in groups of calves by estimating the reproduction ratio R, i.e. the average number of secondary cases caused by one infectious animal in a susceptible population. We performed two experiments with six groups of either four vaccinated or four non-vaccinated calves each. Vaccination was carried out with O(1) Manisa vaccine. Two weeks after vaccination, two calves per group were inoculated intra-nasally with FMDV field isolate O/NET 2001. The two other calves were contact-exposed to the inoculated calves. Contact infections were observed by clinical inspection, virus isolation and RT-PCR on heparinised blood, oro-pharyngeal fluid and probang samples and antibody response to non-structural proteins. In all six non-vaccinated groups, transmission to contact-exposed calves was recorded; in the vaccinated groups, virus transmission was observed to one contact-exposed calf. In the non-vaccinated groups R(c) was 2.52 and significantly above 1, whereas in the vaccinated groups R(v)=0.18 and significantly below 1, indicating that vaccination may successfully be applied as additional intervention tool to reduce virus transmission in a future epidemic of FMD.     

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.     

Foot and mouth disease: the experience of South Africa

Foot and mouth disease (FMD) is endemic in African buffalo (Syncerus caffer) in the Kruger National Park (KNP) and surrounding game parks in South Africa. The last outbreak of the disease in domestic stock outside the FMD control zone occurred in 1957. Due to the success in containing the disease, the country was accorded zone freedom from FMD without vaccination by the Office International des Epizooties (OIE: World organisation for animal health) in 1995. This status was lost in September 2000 when the first-ever recorded case of serotype O in South Africa was diagnosed in a piggery in KwaZulu-Natal after the illegal feeding of untreated swill. In November 2000, an outbreak of FMD caused by serotype South African Territories (SAT) 1 was diagnosed in a feedlot within the free zone of Mpumalanga Province. The SAT 1 outbreak was traced to cattle in the FMD control zone south of the KNP after the game-proof fence surrounding the KNP was severely damaged by floods. This enabled buffalo to come into direct contact with cattle outside the KNP. A further outbreak caused by SAT 2 was diagnosed within the FMD control zone in February 2001, also as a result of buffalo having escaped from the KNP. All these outbreaks were successfully contained, with the re-instatement of zone freedom from FMD without vaccination by the OIE in May 2002. These outbreaks made it necessary to re-examine the methods of control and containment of FMD that have been practised for many years and which are in line with accepted international practices. The authors describe the rationale for the different control strategies that were followed, the need for a multidisciplinary approach to disease control, the interface between control and technological and diagnostic support and the lessons learned. Some suggestions for future control strategies are also offered.     

Foot and mouth disease: lessons to be learned from the experience of France

The appearance of foot and mouth disease (FMD) in the United Kingdom in late February 2001 took European veterinary services by surprise. Differences in the types of measures taken by European countries, and in the speed with which they were implemented, partly explain the different animal health situations observed. France, as a major importer of British sheep, is an interesting country to study. The measures taken there are described in detail, as is the history of the two cases registered on 13 and 23 March 2001. The crisis management procedure is also detailed. The majority of the decisions taken and protocols followed are part of the national intervention plan for FMD. However, experience has shown that it is also important to remain pragmatic and to be able to adapt to new developments during the implementation of the plan. While pre-emptive killing may indeed have reduced the number of outbreaks in France, the social impact of such measures also needs to be taken into account in the development of animal health policy.     

Foot and mouth disease: the perspective of farmers in Ireland

The first outbreak of foot and mouth disease (FMD) recorded in Ireland since 1941 was successfully eliminated due to four main factors, as follows: --the willingness of the farmers in Cooley to sacrifice themselves in the national interest --decisive action was taken rapidly once the first outbreak was declared --geographical location of the Meigh and Proleek outbreaks which enabled the authorities to effectively seal off and regionalise the area, thus protecting exports from the rest of the country --national awareness and willingness at all levels, from Government to the general public, to take whatever action was necessary to keep FMD out of Ireland. The author recounts the story, from the perspective of a farmer, of the outbreak of FMD that occurred in Ireland in 2001, from the first confirmed case in Meigh, County Armagh, through Proleek and the cull, into dealing with the aftermath in terms of compensation payments, premia payments, the evolving human tragedy and lessons learned. Major policy issues must be addressed at both a national and European Union level to prevent outbreaks of FMD in Europe in the future. At a national level, the dual animal health status between Northern Ireland and Great Britain and between Northern Ireland and the Republic of Ireland must not be allowed to re-emerge. Some regulation loopholes allowed FMD to enter Ireland. The Government of Ireland handled the initial FMD crisis very well, with the co-operation of farmers and the public in general.     

Clinical variation in foot and mouth disease: pigs

In intensively reared pigs, the introduction of foot and mouth disease (FMD) results in severe clinical disease and vesicular lesions in adult and fattening animals, and high mortality in piglets. Vaccination of uninfected herds can assist FMD control and eradication programmes by reducing susceptibility of pigs older than 12 to 14 weeks and providing early protection to piglets through maternal antibody, but once FMD is established on a farm, vaccination alone will not prevent recurrent outbreaks of clinical disease.     

The NSP immune response of vaccinated animals after in-field exposure to FMDV

The aim was to examine the immune response (IR) to non-structural proteins (NSPs), in order to assess the validity of the detection of antibodies to NSPs as a means of diagnosing foot and mouth disease (FMD infection) infection when vaccinated populations are in close contact with clinically sick animals. The study was performed during FMD outbreaks in Israel in January 2004; the IR was examined in vaccinated dairy and feedlot cattle herds under natural field exposure to FMDV, and in vaccinated and unvaccinated sheep flocks. During the 2004 outbreaks, clinical signs were age-related and were noted only among imported calves, although they had been vaccinated; such signs were not found among the local dairy cattle populations. The NSP IR among the feedlot cattle that had been vaccinated more than 4 months prior to the in-field exposure was 86%, compared with only 30% among those feedlot cattle that had received one dose of vaccine less than 4 months before the field exposure. The prevalence of NSP IR indicates that animals vaccinated once, less than 4 months prior to exposure, were clinically resistant to FMDV infection, although possibly still susceptible to subclinical infections, whereas those vaccinated more than 4 months prior to the in-field exposure presented clinical manifestations. This situation is unlikely to occur among repeatedly vaccinated livestock; these remained refractory to FMD exposure, as reflected in the absence of clinical manifestations and a relatively low prevalence of NSP IR compared with that in imported calves.     

Immune response in guinea pigs vaccinated with DNA vaccine of foot-and-mouth disease virus O/China99

In order to obtain the gene P12X3C of foot-and-mouth disease virus (FMDV O/China99) that includes full length P1, 2A, 3C and part of 2B and 3B, the site mutation strategy was used. The recombinant plasmid pcDNA3.1/P12X3C was transfected into BHK-21 cells. The capsid proteins of FMDV expressed in BHK-21 cells were confirmed by sandwich-ELISA and indirect immunofluorescence test. Then the plasmid pcDNA3.1/P12X3C was administered to guinea pigs intramuscularly, and purified FMDV O/China993D protein expressed in yeast cells was injected together with pcDNA3.1/P12X3C. Anti-FMDV antibodies were detected by indirect ELISA, the T-lymphocyte proliferation response was tested by MTT assay, and neutralizating antibodies titers were analyzed by micro-neutralization assay. The result showed that the plasmid pcDNA3.1/P12X3C was able to express immunocompetent proteins of FMDV in BHK-21 cells. Furthermore, anti-FMDV antibodies were elicited and increased by plasmid pcDNA3.1/P12X3C in the second week after vaccination. Neutralizating antibodies were induced and the T-lymphocyte proliferation response was enhanced after vaccination. In the challenge test, all of guinea pigs vaccinated with pcDNA3.1/P12X3C were fully protected from FMDV challenge. However, the result obtained from animals that were injected with protein 3D together with plasmid pcDNA3.1/P12X3C was not satisfied. In conclusion, the results encouraged further work towards the development of a DNA vaccine against FMDV and provided the basis of research for DNA vaccine.     

Foot and mouth disease revisited: re-analysis using Bayesian spatial susceptible-infectious-removed models

The foot and mouth disease (FMD) outbreak in the United Kingdom in 2001 was modeled via the use of Bayesian spatial susceptible-infected-removed (SIR) models. In these models the underlying mean of the incident cases was modeled spatially and in time. Dependence structures at the parish level between previous and current cases were modeled either with individual dependence or with neighborhood dependencies. Additional confounding was modeled via random effects that can have either uncorrelated or spatially correlated prior distributions. The best models found relied on lagged population and infection count within the same parish but neighborhood lagged dependencies overall did not provide a good fit. Models with only a space-time interaction effect were preferred over more complex models. The estimation of 'decline' markers for different areas was considered via difference operators as posterior functionals. These proved to be useful in giving an early indication of the waning phase of the epidemic locally.     

Foot and mouth disease (FMD) virus: quantification of whole virus particles during the vaccine manufacturing process by size exclusion chromatography

Foot and mouth disease (FMD) is a highly infectious viral disease that affects cattle, sheep, goats and swine causing severe economic losses worldwide. The efficacy of inactivated vaccines is critically dependent on the integrity of foot and mouth disease virus (FMDV) particles. The recommended method to quantify the active ingredient of vaccines is the 140S quantitative sucrose density gradient analysis. This method has been an immensely valuable tool over the past three decades but it is highly operator dependent and difficult to automate. We developed a method to quantify FMDV particles during the vaccine manufacturing process that is based on separation of components by size-exclusion chromatography and measurement of virus by absorption at 254 nm. The method is linear in the 5-70 μg/mL range, it is applicable to different FMDV strains, and has a good correlation with the 140S test. The proposed method uses standard chromatographic media and it is amenable to automation. The method has potential as a process analytical technology and for control of final product by manufacturers, international vaccine banks and regulatory agencies.