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A farming perspective on the 2001 foot and mouth disease epidemic in the United Kingdom.

The outbreak of foot and mouth disease (FMD) that occurred in the United Kingdom (UK) in 2001 was the single largest epidemic of FMD the world had ever experienced. This outbreak raises important issues about future FMD control strategies, including the use of vaccination. The outbreak has also stimulated a wider debate in the UK on the role and direction of agriculture. The author presents the views of the National Farmers' Union of England and Wales on the handling of the outbreak by the UK Government and summarises some of the key lessons to be learned from a farming perspective.

Agriculture↗

Experimental placental transfer of foot-and-mouth disease virus in mice.

An attenuated type O foot-and-mouth disease (FMD) virus which was virulent for infant, but not for pregnant, mice proved to be superior to a virulent type C FMD virus in the development of a model system for the study of placental transfer of FMD in mice. When mice were inoculated at day 8 or 12 of gestation with type O FMD virus, the virus was detectable in the maternal pancreas for 3 days and in the placenta for 6 days. Viral levels in the fetus and the amniotic fluid were inconsistent and were apparently due to a spillover from the placental infection. The elimination of the virus from the placenta coincided with the expected production of maternal 7S antibody. Mice inoculated from days 0 to 12 of gestation did not have a significant increase in dead young by day 18 (the day of necropsy). Similarly inoculated mice, when permitted to go to term, produced and raised normal-size litters. Inoculation on day 15 of gestation resulted in an increased number of deaths due to morbidity of the dams. It was concluded that the placenta serves as an active site of infection for FMD virus in pregnant mice, but the fetus is relatively resistant to infection.

Animals↗

Experimental transmission of foot-and-mouth disease virus from carrier African buffalo (Syncerus caffer) to cattle in Zimbabwe.

Four female cattle and three male African buffalo (Syncerus caffer) which were free of foot-and-mouth disease (FMD) virus were held together on an island in Lake Kariba, Zimbabwe. The buffalo were experimentally infected with FMD virus type SAT2, developed generalised disease and became virus carriers. While the buffalo were in the acute phase of the disease the susceptible contact cattle did not show lesions, no virus was recovered from them and they did not develop serum antibodies. However, five months later the cattle developed severe foot-and-mouth disease. Direct nucleotide sequencing of the virus used to infect the buffalo and of the virus from the in-contact cattle showed that the two isolates were almost identical. The results suggest that in nature it is possible for the virus to be transmitted from buffalo to cattle under the influence of factors not yet defined, and that there was very little change in the nucleotide sequence of the virus during the carrier period of five months.

Amino Acid Sequence↗

The effects of spraying on the amounts of airborne foot-and-mouth disease virus present in loose-boxes.

The air of loose-boxes which had previously held pigs infected with foot-and-mouth disease was sampled for virus after various procedures. Removal of infected pigs led to a 12- to 16-fold reduction in the amount of virus after 5 min. and a 400-fold reduction after 60 min. After heavy spraying (1.2 mm. of water in 5 min.) the amount of virus was reduced 500-fold compared to 30-fold after light spraying (0.20 mm. of water in 5 min.). The partition of infectivity associated with particle size was measured. The partition found after light spraying was similar to that found 5 min. after the pigs had been removed. Heavy spraying brought about a reduction in the infectivity associated with the large particles (> 6 mum.) but had no effect on particles less than 3 mum. A similar partition was found 60 min. after the pigs had been removed. The findings are discussed in relation to the spread of foot-and-mouth disease by the airborne route.

Air Microbiology↗

Occurrence of cross reactions to foot-and-mouth disease virus in normal swine sera.

Sera from 101 swine never exposed to foot-and-mouth disease virus were tested by the plaque-reduction neutralization (PRN) and radial immunodiffusion techniques for cross-reactions to 5 types of foot-and-mouth disease viruses. Depending on the group of sera and the virus used, the percentage of sera cross-reacting at low levels varied from 0 to 50% with the PRN technique and 0 to 20% with the radial immunodiffusion technique. 5erum-neutralization tests in mice support the finding of neutralizing antibody by the PRN technique. Ultracentrifugation and 2-mercaptoethanol studies indicate that the cross-reactions are the result of immunoglobulin M or similar macroglobulins.

Animals↗

Extending the foot-and-mouth disease module to the control of other diseases.

During the recent devastating epidemics of foot-and-mouth disease (FMD), bluetongue (BT), the highly pathogenic avian influenza (HPAI) and New Castle disease, more than 115 million animals were culled. The mass slaughter of animals raised serious ethical questions. These epidemics showed that the use of emergency vaccination is an essential element in disease control. During the last decade the FMD antigen banks have proved to be effective and this module should be extended. An international vaccine stock should be considered for classical swine fever and HPAI. Agreements with vaccine producers should be made easily available, with instant access to a vaccine reserve for rinderpest, peste des petits ruminants, BT, African horse sickness and Rift valley fever. These vaccines should meet international standards and should allow distinction between vaccinated and infected animals. Information should be gathered proactively on the use of vaccines for lumpy skin disease, sheep and goat pox and contagious bovine pleuropneumonia.

Animals↗

Molecular epidemiology of serotype O foot-and-mouth disease virus with emphasis on West and South Africa.

Genetic relationships of serotype O foot-and-mouth disease (FMD) viruses recovered from outbreaks of the disease in the West African countries of Niger, Burkina Faso and, Ghana (1988-1993) and those from South Africa (2000) were determined by partial VP1 gene characterization. A 581-bp fragment, corresponding to the C-terminus half of the ID (VP1 gene) region was amplified and sequenced. An homologous region of 495 nucleotides was ultimately used to determine genetic relationships of serotype O viruses from the Middle East, Europe, South America, North Africa, East Africa, southern Africa and Asia. Seven distinct type O genotypes were identified by phylogenetic reconstruction, consisting of viruses from the following geographical regions: Genotype A: Asia, the Middle East, and South Africa, Genotype B: East Africa, Genotype C: West and North Africa, Genotype D: Taiwan and Russia, Genotype E: Angola and Venezuela, Genotype F: Western Europe, and Genotype G: Europe and South America. The genotypes constitute three different evolutionary lineages (I-III), which correspond to three discrete continental regions, some of which display inter-continental distributions due to introductions. Results further indicate that the outbreaks in Burkina Faso (1992) and Ghana (1993) are part of the same epizootic and that the strain involved in a recent outbreak of the disease in South Africa is most closely related (97% sequence identity) to a 1997 Bangladesh strain.

Africa, Western↗

Foot-and-mouth disease in tropical wildlife.

This review of foot-and-mouth disease in cloven-hoofed, free-living animals, describes the disease, the wide range of the hosts, the carrier state, and the interrelationship between disease in domestic livestock and wildlife. This information becomes even more crucial to the development of control strategies when linked to the process of pathogenesis and the epidemiology of the disease.

Animals↗

A quantitative assessment of the risk of transmission of foot-and-mouth disease, bluetongue and vesicular stomatitis by embryo transfer in cattle.

This paper addresses the risks involved when bovine embryos are moved internationally and, specifically, the possibilities of transmitting foot-and-mouth disease, bluetongue and vesicular stomatitis by embryos originating from an area in South America. The risk scenario pathway was divided into three phases for analysis. The first phase dealt with the potential for embryo contamination which depends on the disease situation in the exporting country and/or region, the health status of the herds and the donor cows from which the embryos are collected, and the pathogenetic characteristics of the specified disease agent. The second phase covers risk mitigation by use of internationally accepted standards for processing of embryos, and the third phase encompassed the risk reductions resulting from post-collection surveillance of the donors and donor herds, and also from testing of embryo-collection (flushing) fluids for the disease agent. Quantitative risk analysis showed that under the circumstances specified in the paper, the risk of transmission of foot-and-mouth disease and vesicular stomatitis by embryos would be likely to be less than 1 in 100 billion (10(-11.0)) and 1 in 100 million (10(-8.0)), respectively. The values for bluetongue were 1 in 30,000 (10(-4.2)) when embryos were collected in the vector season and 1 in 1 million (10(-6.0)) in the season with low vector activity. These risk values were influenced by the incidence of each disease in the area of origin and the ease with which clinical signs can be recognised. Competent embryo processing according to procedures recommended by the International Embryo Transfer Society were also of great importance. The analysis showed that the reasons for the low levels of risk of transmission differed for each of the three diseases. In the case of bluetongue, vector ecology was of major importance.

Animals↗

A large-scale evaluation of peptide vaccines against foot-and-mouth disease: lack of solid protection in cattle and isolation of escape mutants.

A large-scale vaccination experiment involving a total of 138 cattle was carried out to evaluate the potential of synthetic peptides as vaccines against foot-and-mouth disease. Four types of peptides representing sequences of foot-and-mouth disease virus (FMDV) C3 Argentina 85 were tested: A, which includes the G-H loop of capsid protein VP1 (site A); AT, in which a T-cell epitope has been added to site A; AC, composed of site A and the carboxy-terminal region of VP1 (site C); and ACT, in which the three previous capsid motifs are colinearly represented. Induction of neutralizing antibodies, lymphoproliferation in response to viral antigens, and protection against challenge with homologous infectious virus were examined. None of the tested peptides, at several doses and vaccination schedules, afforded protection above 40%. Protection showed limited correlation with serum neutralization activity and lymphoproliferation in response to whole virus. In 12 of 29 lesions from vaccinated cattle that were challenged with homologous virus, mutant FMDVs with amino acid substitutions at antigenic site A were identified. This finding suggests the rapid generation and selection of FMDV antigenic variants in vivo. In contrast with previous studies, this large-scale vaccination experiment with an important FMDV host reveals considerable difficulties for vaccines based on synthetic peptides to achieve the required levels of efficacy. Possible modifications of the vaccine formulations to increase protective activity are discussed.

Amino Acid Sequence↗

The structure of foot-and-mouth disease virus: implications for its physical and biological properties.

The structure of foot-and-mouth disease virus has been solved at a resolution of 2.9 A by X-ray diffraction techniques. The overall structural organisation of the particle is similar to that seen in other picornaviruses but there are several unique features. Many of these help to explain its characteristic physical and biological properties. In particular the canyon or pit found at the surface of other picornaviruses is lacking, which has important implications for cell attachment and the process of infection. Also there are 60 large disordered protrusions at the surface corresponding to the major antigenic site. This disorder is of particular interest in relation to the striking ability of linear synthetic peptides to induce protective immunity against foot-and-mouth disease.

Animals↗

Comparisons of original laboratory results and retrospective analysis by real-time reverse transcriptase-PCR of virological samples collected from confirmed cases of foot-and-mouth disease in the UK in 2001.

There were 2030 designated cases of foot-and-mouth disease (FMD) during the course of the epidemic in the UK in 2001 (including four from Northern Ireland). Samples from 1720 of the infected premises (IPs) were received in the laboratory and examined for either the presence of FMD virus (virological samples from 1421 IPs) or both FMD virus and antibody (virological and serological samples from 255 IPs) or antibody alone (from 44 IPs). The time taken to issue final diagnostic results ranged from a few hours in cases in which positive results were obtained by ELISA on epithelia containing sufficient virus to be detected, to several days for samples containing small amounts of virus requiring amplification through cell culture, negative samples or samples tested for antibody. Two subsets of samples were analysed retrospectively by real-time reverse transcriptase-PCR (RT-PCR); first, epithelia that were negative by both ELISA and virus isolation (VI) in cell culture, and secondly, samples that were negative by ELISA on epithelial suspension but positive by VI. There was broad agreement between the RT-PCR and VI/ELISA combined, except that the RT-PCR procedure did not detect a group of related virus isolates from Wales. These viruses had evidently evolved during the epidemic and had a nucleotide substitution in the RT-PCR probe site, which prevented them from being detected by the routine diagnostic probe. No evidence of FMD virus, antibody or nucleic acid was found in approximately 23 per cent (390 of 1730) of IPs from which samples were received, suggesting that the incidence of FMD during the outbreak may have been over-reported.

Animals↗

Antigenic variation in Foot and Mouth Disease Virus type Asia 1 isolates circulated during 1993-95 in India.

The antigenic variation in Foot and Mouth Disease Virus (FMDV) is very high. The effective strategy to control the Foot and Mouth Disease (FMD) in India which is a habitat of four serotypes O, A, C and Asia 1, is by regular vaccination, using the vaccine strain most suitable for the local situation. India is an endemic country with the disease being widely distributed. Selection of vaccine strain should therefore need the information on the circulating viruses. Asia 1 causes the second largest number of disease outbreaks in India. As there is no information available with respect to the extent of antigenic variation in FMDV type Asia 1, we have studied FMDV isolates from vaccinated and unvaccinated animals from different parts of the country and compared their relationship with Asia 1 vaccine virus. The immunogenic, hypervariable region of viral protein 1 (VP1) gene was amplified by RT-PCR and sequenced. Analysis of sequence data showed that the viruses from two field outbreaks of Southern India were closely related to each other when compared to the isolate from the North and all the three isolates are away from the vaccine virus.

Animals↗

Epitopes on foot-and-mouth disease virus outer capsid protein VP1 involved in neutralization and cell attachment.

Foot-and-mouth disease virus structural protein VP1 elicits neutralizing and protective antibody and is probably the viral attachment protein which interacts with cellular receptor sites on cultured cells. To study the relationships between epitopes on the molecule related to neutralization and cell attachment, we tested monoclonal antibodies prepared against type A12 virus, isolated A12 VP1, and a CNBr-generated A12 VP1 fragment for neutralization and effect on viral absorption. The antibodies selected for analysis neutralized viral infectivity with varying efficiencies. One group of antibodies caused a high degree of viral aggregation and inhibited the adsorption of virus to cells by 50 to 70%. A second group of antibodies caused little or no viral aggregation but inhibited the adsorption of virus to cells by 80 to 90%. One antibody, which is specific for the intact virion, caused little viral aggregation and had no effect on the binding of virus to specific cellular receptor sites. Thus, at least three antigenic areas on the surface of foot-and-mouth disease virus which were involved in neutralization were demonstrated. One of the antigenic sites appears to have been responsible for interaction with the cellular receptor sites on the surface of susceptible cells.

Animals↗

Estimation of 140S particles in foot-and-mouth disease virus (FMDV) vaccine by using the computer analyzing system.

The quantity of 140S particles in inactivated foot-and-mouth disease virus (FMDV) vaccine samples produced in Foot-and-Mouth Disease Vaccine Production Center (FMD Vaccine Production Center) in Thailand was estimated by the sucrose gradient ultracentrifugation and optical density analysis by using the computer applying system. The soft ware; Chromato Data System (CDS) (Nihon Chromato Works Co., Ltd. Japan) which is prepared for the analysis of chromatography, was applied for the estimation of 140S particles in FMDV vaccine. The quantity of 140S particles in each vaccine sample measured by CDS was mostly ranged from 2-4 micrograms/ml and this quantity was consistent with the results of the other reports. This method is considered to be the available method for estimation of 140S particles in FMDV vaccine as routine assay.

Aphthovirus↗

Use of a portable real-time reverse transcriptase-polymerase chain reaction assay for rapid detection of foot-and-mouth disease virus.

OBJECTIVE: To evaluate a portable real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay designed to detect all 7 viral serotypes of foot-and-mouth disease virus (FMDV). DESIGN: Laboratory and animal studies. STUDY POPULATION: Viruses grown in tissue culture and animals experimentally infected with FMDV. PROCEDURE: 1 steer, pig, and sheep were infected with serotype O FMDV. Twenty-four hours later, animals were placed in separate rooms that contained 4 FMDV-free, healthy animals of the same species. Oral and nasal swab specimens, oropharyngeal specimens obtained with a probang, and blood samples were obtained at frequent intervals, and animals were observed for fever and clinical signs of foot-and-mouth disease (FMD). Samples from animals and tissue cultures were assayed for infectious virus and viral RNA. RESULTS: The assay detected viral RNA representing all 7 FMDV serotypes grown in tissue culture but did not amplify a panel of selected viruses that included those that cause vesicular diseases similar to FMD; thus, the assay had a specificity of 100%, depending on the panel selected. The assay also met or exceeded sensitivity of viral culture on samples from experimentally infected animals. In many instances, the assay detected viral RNA in the mouth and nose 24 to 96 hours before the onset of clinical disease. CONCLUSIONS AND CLINICAL RELEVANCE: The assay reagents are produced in a vitrified form, which permits storage and transportation at ambient temperatures. The test can be performed in 2 hours or less on a portable instrument, thus providing a rapid, portable, sensitive, and specific method for detection of FMDV.

Animals↗

The use of cyclophosphamide as an enhancer of the vaccine against foot-and-mouth disease.

The immunization of biungulate animals with killed foot-and-mouth disease virus (FMDV) requires periodic vaccinations due to a low vaccine immunogenicity. Therefore, FMDV antigens need to be combined with adjuvants such as aluminium hydroxide, saponin or oil emulsions. Animal handling for periodic inoculations, and the repeated doses of vaccines that have to be administered increase the commercialization costs. Moreover, the use of adjuvants may induce adverse effects. In the present work we show that it is possible to increase the life span of neutralizing antibodies in serum when a single dose of cyclophosphamide (Cy) is administered four days before vaccination with aluminium hydroxidesaponin FMDV vaccine.

Animals↗

Genetic variation of foot-and-mouth disease virus from field outbreaks to laboratory isolation.

Foot-and-mouth disease virus (FMDV), by nature of its RNA genome, possesses a high rate of mutation during replication. This results in extensive genetic polymorphism of virus populations in nature. The emergence of FMDV variants during replication has been reported. Genetic changes in the viral capsid protein (VP1) gene can result in amino acid changes affecting the immunodominant epitopes of FMDV. The genetic heterogeneity of FMDV in the field and the antigenic variants observed after cell culture isolation has been investigated by PCR sequencing and reactivity with monoclonal antibodies. These methods were applied to viruses causing two different outbreaks of FMD before and after replication in cell culture and in the animal host. The VP1 region of the genome was amplified by PCR and sequenced to reveal variant sequences identified after passage and to determine their presence in the original field tissue. In one case, reactivity with monoclonal antibodies was lost after passage as a result of an amino acid change in the subpopulation. These findings suggest that host cells can select specific virus genetic and antigenic subpopulations during virus isolation and propagation.

Amino Acid Sequence↗