Control of foot-and-mouth disease.
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Since March 1997 two strains of foot and mouth disease (FMD) virus have found their way into Taiwan, causing severe outbreaks in pigs and in Chinese yellow cattle. Outbreaks occurred in March 1997 were caused by a pig-adapted virus strain (O/Taiwan/97) which did not infect other species of cloven-hoofed animals by natural route. The epidemic spread over the whole region of Taiwan within two months and the aftermath was 6,147 pig farms infected and 3,850,746 pigs destroyed. In June 1999, the second strain of FMD virus (O/Taiwan/99) was isolated from the Chinese yellow cattle in the Kinmen Prefecture and in the western part of Taiwan. By the end of 1999, Chinese yellow cattle were the only species infected and those infected cattle did not develop pathological lesions. Seroconversions of serum neutralization antibody and on non-structural protein (NSP) antibodies were the best indicators for infection in non-vaccinated herds. The infected animals, however, excreted infectious levels of virus to infect new hosts. Based on the detection of the specific antibody to FMD virus, and virus isolation from oesophageal-pharyngeal (OP) fluid samples, ten herds of Chinese yellow cattle located in Kinmen and Taiwan were declared to have been infected. During the period of January to March 2000, however, five outbreaks caused by FMD virus similar to the O/Taiwan/99 virus occurred in four prefectures of Taiwan. The infected species included goats, Chinese yellow cattle and dairy cattle. Those outbreaks have caused high mortality in goat kids under two weeks old and also developed typical clinical signs of infection in dairy cattle.
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Mass annual vaccination against foot-and-mouth disease, previously applied by eight member states in the European Community (EC), was progressively phased out during 1990-91. The other four member states (the United Kingdom, Denmark, the Republic of Ireland and Greece) either never have vaccinated or ceased to do so several years ago. The EC should increase its international competitiveness if it maintains its present foot-and-mouth disease-free, non-vaccinating status. Freedom from disease and a harmonised disease control policy will also permit unrestricted movement of livestock and animal products throughout the EC when the single market is completed in 1992. Vaccination against foot-and-mouth disease on continental Europe has greatly reduced the number of outbreaks during the last 30 years and this reduction has been of indirect benefit to Great Britain. However, the cessation of vaccination will result in a higher proportion of fully susceptible cattle and in the event of outbreaks will increase the likelihood of the rapid dissemination of virus and increase the risk that the infection will enter Great Britain. The main risks of entry are likely to be associated with live animals in which the disease can be mild or inapparent, ie, sheep and goats, and with airborne virus originating from pigs on the nearby continent especially in Brittany and the Benelux countries where they are present in very high densities.
The Foot-and-Mouth Disease virus (FMDV) is not a public health threat, but it is highly contagious to cloven-footed animals. The virus is shed into milk up to 33 h before there are apparent signs of the disease in dairy cows, and, in extreme cases, signs of disease may not appear for up to 14 d. During this time, raw milk can serve as a vector for spread of the disease both at the farm and during transport to the processing plant by milk tanker. Raw milk and milk products fed to animals have the potential to cause infection, but the potential for pasteurized milk products to cause infection is largely unknown. Current minimum pasteurization standards may not be adequate to eliminate FMDV in milk completely. The purpose of this paper is to assess the literature on the thermal resistance of FMDV in milk and milk products, to identify the risks associated with ingestion of pasteurized products by animals, and to lay a strategy to prevent the spread of FMDV from contaminated milk.
An epidemic of foot-and-mouth disease (FMD) causing a total of 23 cases in 1982-1983, primarily on the island of Funen, Denmark, was subjected to molecular epidemiological investigations. In an attempt to exploit the quasi-species nature of foot-and-mouth disease virus strains for molecular high-resolution strain identification in order to analyse the dynamics of this epidemic, full-length VP1 coding regions were sequenced for 17 isolates collected at different farms during the epidemic. The sequence information together with epidemiological information gathered during the epidemic suggests that the epidemic was caused by at least three introductions across Danish borders and one case of airborne transmission between two islands in Denmark over a distance of 70 km. The assortment of nucleotide markers among the three strains is indicative of common recombination events in their evolutionary history, and the prerequisite of co- or superinfection of animals with variant strains in turn implies that they have a common source or epidemiologically related sources originating from an area with endemic FMD.
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Pigs were vaccinated with the emergency inactivated foot-and-mouth disease virus (FMDV) vaccine--water-in-oil-in-water emulsion with Montanide ISA206--known to protect after 3-5 days. Peripheral blood leukocyte (PBL) sub-populations did not differ between vaccinates and controls post-vaccination. There was neither lymphopenia nor inflammatory reaction. FMDV-specific antibody and T lymphocyte activity developed in the vaccinates. Virus-induced Th1-like cytokine protein and mRNA (IFNgamma and IL-2) were identified, particularly IFNgamma. Th2-like cytokine protein and mRNA (IL-4 and IL-6) were also induced in an FMDV-specific manner. IL-10 was induced by both virus and mock antigen. The current emergency FMDV vaccine induces a diverse immune defence network--innate, and both Th1-like and Th2-like responses--without adverse reactions such as lymphopenia or inflammatory responses.
Foot-and-mouth disease virus (FMDV) variants adapted to BHK-21 cells showed an expanded host-cell tropism that extended to primate and human cell lines. Virus replication in human HeLa and Jurkat cells has been documented by titration of virus infectivity, quantification of virus RNA, expression of a virus-specific non-structural antigen, and serial passage of virus in the cells. Parallel serial infections of human Jurkat cells with the same variant FMDVs indicates a strong stochastic component in the progression of infection. Chimeric viruses identified the capsid as a genomic region involved in tropism expansion. These results indicate that, contrary to theoretical predictions, replication of an RNA virus in a constant cellular environment may lead to expansion of cellular tropism, rather than to a more specialized infection of the cellular type to which the virus has been adapted.
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Serological evaluations of foot-and-mouth disease type SAT 2 viruses isolated in Kenya between 1979 and 1982 were performed using the two-dimensional microneutralization test. Nine field isolates of epizootiological significance were compared with four vaccine viruses. The results obtained identified Tan 5/68 as the most appropriate reference vaccine virus strain since it had the broadest serological spectrum. Potent Tan 5/68 vaccines would be expected to provide adequate protection against the contemporary SAT 2 field viruses. In the case of K183/74, which also was shown to have a broad spectrum with viruses isolated in Kenya, the results show that the 1982 isolate from central Kenya was significantly divergent (r less than 1.00 at P = 0.01) and warranted tactical revaccination for its control. The study highlighted the fact that strain R1215 which had been isolated from the oesophageal-pharyngeal swabs of asymptomatic carrier cattle had a narrow serological spectrum suggesting that such viruses could be unsuitable as vaccine for the national campaign.
BACKGROUND: Foot-and-Mouth Disease (FMD) causes significant economic losses in Turkish livestock. We have analysed the genetic diversity of the 1D sequences, encoding the hypervariable surface protein VP1, of Turkish isolates of serotype A and O collected from 1998 to 2004 in order to obtain epidemiological and immunological information. RESULTS: The 1D coding region of 33 serotype O and 20 serotype A isolates, obtained from outbreaks of FMD between 1998 and 2004, was sequenced. For serotype A, we confirmed the occurrence of the two subtypes IRN99 and IRN96. These subtypes are most divergent within the region encoding the immuno-dominant GH-loop. Also a close relationship to Foot-and-Mouth Disease virus (FMDV) serotype A isolates obtained from outbreaks in Iraq and Iran were detected and a clustering of isolates collected during the same period of time were found. The analysis of the deduced amino-acid sequences of these subtypes revealed evidence of positive selection in one site and one deletion, both within the GH-loop region. By inferring the ancestral history of the positively selected codon, two potential precursors were found. Furthermore, the structural alignment of IRN99 and IRN96 revealed differences between the tertiary structures of these subtypes. The similarity plot of the serotype O isolates suggested a more homogeneous group than the serotype A isolates. However, phylogenetic analysis revealed two major groups, each further divided in subgroups, of which some only consisted of Turkish isolates. Positively selected sites and structural differences of the Turkish isolates analysed, were not found. CONCLUSION: The sequence and structural analysis of the IRN99 strains is indicative of positive selection suggesting an immunological advantage compared to IRN96. However, results of antigenic comparison reported elsewhere do not substantiate such a conclusion. There is evidence that IRN99 was introduced to Turkey, in all probability from Iran. Since, a member of the IRN96 lineage was included as a component of the FMDV vaccine produced since 2000, the outbreaks caused by IRN96 strains in 2004 could be due to incomplete vaccine coverage. The Turkish type O strains, all with a VP1 structure similar to the O1/Manisa/69 vaccine, appear in several sublineages. Whether these sublineages reflect multiple samplings from a limited number of outbreaks, or if they reflect cross-boundary introductions is not clear.
Strategic reserves of foot-and-mouth disease (FMD) antigen have become an integral part of FMD control policy for many countries. They are based on two principles, ready formulated vaccine stored at +4 degrees C, or concentrated antigen preparations held at ultra-low temperature for later formulation. However, the latter is more economical, since ready formulated vaccine, based on oil or aluminium hydroxide/saponin adjuvants, requires regular replacement. This is primarily the result of the vaccine's limited shelf-life, nominally 18 months at +4 degrees C. Unfortunately, lowering the temperature of storage, in a bid to extend its shelf-life, has a detrimental effect on the vaccine's potency. Montanide ISA 206 and 25, two 'ready-to-formulate' oil adjuvants which can be used in all target species, are ideal for emergency vaccination. Their potential is enhanced by the ease in which they are formulated into oil emulsion vaccines. Here we describe a novel approach of layering the individual components of FMD vaccine in the same primary container and then storing the product at ultra-low temperature. This avoids the detrimental effect on potency, normally observed with frozen formulated FMD vaccine, and could substantially extend the products shelf-life. The implications of this approach for emergency vaccination strategy are discussed.
Sera from cattle vaccinated against either foot-and-mouth disease virus (FMDV) strains A10 Holland, O1 BFS, or C1 Detmold were tested in a serum neutralization test (SNT) and a liquid-phase blocking sandwich ELISA (LBE), and the titers were compared with the results of intradermolingual challenge tests. The LBE test results were significantly more reproducible (P less than 0.005) than the SNT results. The correlation coefficients between SNT and LBE were 0.91 for FMDV strains A10 Holland and O1 BFS, and 0.82 for FMDV strain C1 Detmold (P less than 0.0005). The regression coefficient for strain A10 Holland was 0.80, for strain O1 BFS the value was 0.87, and for strain C1 Detmold it was 0.64. In probit analysis, titers at which 95% of the cattle were protected against challenge with the homologous strain were determined for the SNT and the LBE. In the SNT the 95% protection levels for strains A10 Holland were greater than or equal to 0.84, for O1 BFS greater than or equal to 1.59, and for C1 Detmold greater than or equal to 0.83. In the LBE they were greater than or equal to 1.28, greater than or equal to 1.71, and greater than or equal to 1.74, respectively. Because the SNT and the LBE are highly significantly correlated, and the LBE is more reproducible, the LBE is likely to predict protection more reliably than the SNT.
Thorne, H. V. (Research Institute, Animal Virus Diseases, Pirbright, England). Kinetics of cell infection and penetration by the virus of foot-and-mouth disease. J. Bacteriol. 84:929-942. 1962.-The kinetics of cell infection by the virus of foot-and-mouth disease were determined, using acidification to pH 5.7 to eliminate virus from the system and to stop the reaction at required times. The infection curve was sigmoidal in form with an initial lag stage followed by a linear region of slope, at moderate concentrations, proportional to the virus and cell concentrations. The infection rate was very small below 15 C but increased rapidly with increasing temperature. Cell infection was 90% complete in about 3 min at 37 C and about 20 min at 25 C. By comparison with kinetic equations derived for a simple model of the infection process, adsorption and penetration rate constants were calculated. The adsorption rate constants were of the same order as those obtained from direct measurements of virus adsorption. The half-time for the penetration reaction was about 30 sec at 37 C and 6 min at 20 C; the rate decreased to near zero values below 15 C. The energy of activation for penetration was 24,000 cal/mole.
Experiments were carried out to cultivate the foot-and-mouth disease virus under laboratory conditions in a suspension of the BHK-21 cell line. Results showed that the number of cells cultivated in a susfor 48 to 72 hours of incubation reaches up to 2.2 X 10(6). It was also found that certain conditions should be observed for the successful cultivation of the cells in suspension, such as aeration, pH, and respective temperature. It was demonstrated that foot-and-mouth diseases viruses obtained from BHK cells propagating in suspension possess good antigenic and immunogenic properties.