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A novel genetic lineage differentiating RT-PCR as a useful tool in molecular epidemiology of foot-and-mouth disease in India.

Comparison of nucleotide sequences at the VP1 coding region of foot-and-mouth disease serotype Asia1 viruses from India has revealed two genetic lineages with emergence of a genetically divergent group in recent years. In this study a simple, fast, relatively costeffective multi-primer RT-PCR assay to differentiate genetic lineages of type Asia1 viruses was developed. Efforts were made in the design of novel lineage-specific primers and in optimization of the multi-primer assay protocol in conjunction with the use of the serotype specific primer for confirmation of serotype Asia1 virus. This assay promises to be an effective tool in molecular epidemiological investigation of FMD in the country.

Capsid Proteins↗

Development of synthetic peptide ELISA based on nonstructural protein 2C of foot and mouth disease virus.

It was reported that the sera of convalescent animals contain antibodies to foot and mouth disease (FMD) virus (FMDV) 2C, highly conserved nonstructural protein (NSP), whereas the sera of vaccinated animals do not. But ELISA methods using this protein were not reported and developed until recently. In this study, NSP 2C peptides were synthesized within the amino acid sequence of the conserved 2C nonstructural region of FMDV according to the sequences from Genbank database and used for identifying antigenic determinants. One of the synthesized thirteen peptides gave strong positive reactivity with most of the sera from 13 FMD infected farms, but not with sera from vaccinated and non-infected animals. Moreover, with the sera collected through serial bleedings from four cattle and five goats infected with FMDV O/SKR/2000 experimentally, positive results were obtained in two species after 10 days post infection (DPI). Therefore, we tried to develop and evaluate this ELISA based on 2C peptides. In comparison with the commercial NSP ELISA, the 2C peptide based ELISA method showed good specificity and sensitivity. These results demonstrate that the synthetic 2C peptide ELISA can be a complementary marker to differentiate FMDV-infected from vaccinated on a herd basis.

Animals↗

Epizootiology of foot and mouth disease in Saudi Arabia: II. Current status on dairy farms and control measures in operation.

Specifically-designed questionnaires were distributed to the managers and/or veterinarians of all dairy farms in Saudi Arabia in order to obtain data on the occurrence of foot and mouth disease (FMD) on these farms from 1971 to 1989, as well as data on current control measures. Of 39 farms, 27 responded to the questionnaire and 15 (56%) reported FMD outbreaks. Notification and collection of samples for diagnosis were not performed consistently. Laboratory tests were undertaken at the World Reference Laboratory for Foot and Mouth Disease, Pirbright, United Kingdom. FMD virus serotypes O, A and C were isolated. Epizootiological factors contributing to the occurrence of FMD in Saudi dairy farms and recommendations for improving control of the disease are discussed in depth.

Animals↗

Genetic relationships between southern African SAT-2 isolates of foot-and-mouth-disease virus.

Sequencing of part of the 1D gene of foot-and-mouth disease virus was used to determine the relationships between SAT-2 viruses isolated from outbreaks which occurred in cattle in Zimbabwe and Namibia and in impala in South Africa between 1979 and 1989. The results demonstrated that the outbreaks in different countries were unrelated. Surprisingly close relationships were shown between all SAT-2 viruses isolated from cattle in Zimbabwe since 1983 but the two major epizootics which occurred in 1989 were caused by viruses which were clearly different. Conversely, two apparently unrelated outbreaks in impala in South Africa were caused by viruses which could not be distinguished.

Africa, Southern↗

Foot-and-mouth disease virus: a long known virus, but a current threat.

Foot-and-mouth disease virus (FMDV) was the first animal virus identified. Since then, FMDV has become a model system in animal virology and a considerable amount of information on its structure, biology and vaccinology has been obtained. However, the disease that this virus produces (FMD) still constitutes one of the main animal health concerns. In this review, we have attempted to summarise the state of the knowledge in different basic and applied areas of FMDV research, with emphasis on those aspects relevant to the control of the disease.

Animals↗

Serological comparison of type Asia 1 foot and mouth disease virus isolates from Thailand.

Antigenic variation of type Asia 1 foot and mouth disease (FMD) virus in Thailand was examined using a total of 50 field viruses isolated between 1986 and 1992. A two-dimensional serum neutralisation test was used to calculate r values for comparison of these isolates with a reference vaccine strain, Asia 1 Bangkok 1960 (BKK/60). Viruses were also compared to two field isolates, Asia 1 36-2/88 and Asia 1 45/88, and some were compared to another vaccine strain, Asia 1 Nakhon Pathom 1984 (NPT/84). In 80% of cases, field isolates were deemed to be significantly different from the vaccine virus Asia 1 BKK/60, and the distribution of r values indicated that there would be some advantage in selecting a new vaccine strain more closely related to contemporary field strains.

Animals↗

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.

Agriculture↗

Endurance of immunity against foot-and-mouth disease in cattle after three consecutive annual vaccinations.

Protection against foot-and-mouth disease (FMD) and ability to transmit FMD virus to susceptible contact animals were studied in cattle vaccinated three times in annual field campaigns with the Dutch trivalent vaccine. Eighty vaccinated cattle and 16 susceptible controls were intranasally exposed to an aerosol containing a homologous FMD challenge virus (O1 BFS, A10 Holland or C1 Detmold) or a heterologous virus (A5 Modena or C1 Modena). The day after exposure, vaccinated cattle were stabled individually with an FMD-susceptible contact. All cattle challenged with an homologous virus strain at one year (20 head), at two years (10 head) and at three years (30 head) after the last vaccination were protected against the development of clinical signs of disease; one, zero and five cattle of these groups, respectively, transmitted virus to their contacts. In each group, approximately two out of three exposed cattle had virus-positive oropharyngeal fluid samples and seroconverted. The amount of virus recovered from probang samples increased with the time since the last vaccination. Mean antibody titres of cattle that had not been vaccinated for three consecutive years did not change significantly over the last two-year period. All 10 cattle challenged with the vaccine strain-related C1 Modena virus were protected against clinical disease, whereas three out of 10 challenged with the heterologous A5 Modena strain virus one year after the last vaccination contracted FMD and transmitted the virus. Five others (four in the C1 group and one in the A5 group) spread the virus to their contacts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Genetic diversity in the VP1 gene of foot-and-mouth disease virus serotype Asia 1.

Complete nucleotide sequence of the 1D (VP1-encoding) gene of 61 foot-and-mouth disease (FMD) serotype Asia I virus isolates recovered from different outbreaks in India between 1985 and 1999 including two vaccine strains currently used were determined. The sequences were compared with each other and those from other Asian countries. On the basis of phylogenetic analysis the viruses could be grouped into four genotypes (genotypes I-IV). All the 61 isolates from India belong to a single genotype (genotype-II) which is further subdivided into three lineages (B1, B2 and B3) under the same genotype. The viruses of the lineage B1 and B3 were found to be more prevalent before 1996 while the viruses of lineage B2 appeared to be new variants responsible for most of the recent outbreaks. Most of the isolates of lineage B1 lack one amino acid in the VP1 protein (position 44) whereas most of the isolates of lineage B2 and B3 contain it which indicates the possibility of these lineages having evolved independently. The rate of evolution of FMDV Asia 1 virus was also estimated and found to be 2.7 x 10(-2) synonymous substitutions per nucleotide per year.

Amino Acid Sequence↗

The implications of virus diversity within the SAT 2 serotype for control of foot-and-mouth disease in sub-Saharan Africa.

SAT 2 is the serotype most often associated with outbreaks of foot-and-mouth disease (FMD) in livestock in southern and western Africa and is the only SAT type to have been recorded outside the African continent in the last decade. Its epidemiology is complicated by the presence of African buffalo (Syncerus caffer), which play an important role in virus maintenance and transmission. To assess the level of genetic complexity of this serotype among viruses associated with both domestic livestock and wildlife, complete VP1 gene sequences of 53 viruses from 17 countries and three different host species were analysed. Phylogenetic analysis revealed eleven virus lineages, differing from each other by at least 20 % in pairwise nucleotide comparisons, four of which fall within the southern African region, two in West Africa and the remaining five in central and East Africa. No evidence of recombination between these lineages was detected, and thus we conclude that these are independently evolving virus lineages which occur primarily in discrete geographical localities in accordance with the FMD virus topotype concept. Applied to the whole phylogeny, rates of nucleotide substitution are significantly different between topotypes, but most individual topotypes evolve in accordance with a molecular clock at an average rate of approximately 0.002 substitutions per site per year. This study provides an indication of the intratypic complexity of the SAT 2 serotype at the continental level and emphasizes the value of molecular characterization of diverse FMD field strains for tracing the origin of outbreaks.

Africa South of the Sahara↗

The nucleotide sequence of foot-and-mouth disease virus O/FRA/1/2001 and comparison with its British parental strain O/UKG/35/2001.

The complete nucleotide sequence of foot-and-mouth disease virus (FMDV) O/FRA/1/2001 (bovine isolate) was determined from five cDNA clones covering most of the genome and compared with the British porcine isolate (O/UKG/35/2001) it originated from. Seven substitutions, out of which three resulted in amino acid changes (in the leader protease, 3A protein and 3D RNA-dependent RNA polymerase sequences) were identified and confirmed by direct sequencing of RT-PCR products obtained from in vitro infected cells and skin vesicles of an infected cow. RACE amplification allowed determination of the exact 3' end of the genome. These changes and possibly the unusual 3A substitution between the British and its French derivate may account for the consecutive species shifts.

Amino Acid Sequence↗

[Risk of transmission of foot and mouth disease by milk and its products: perspectives in South America].

The authors highlight the importance of trade in dairy products in South America and throughout the world, and discuss the problem of restrictions engendered by foot and mouth disease (FMD) on exports to countries free from the disease. The epidemiological features of the disease and properties of the causal agent are described in relation to the dairy industry, with special reference to survival of the virus. Discussion then focuses on the risk of foot and mouth disease in relation to the effects the disease has on animal production before and after milking and the industrial processing of dairy products. Finally, the authors review progress achieved in FMD control and eradication programmes in Latin America, particularly in the southern sector where countries such as Chile and Uruguay are free from the disease, while in other countries (such as Argentina, Paraguay and parts of southern Brazil) no case has been reported for more than two years. It is concluded that dairy products can be exported from the region without creating a risk to animal health, provided that there has been proper risk analysis, according to the clearly defined regionalization criteria.

Animals↗

Regional status and approaches to control and eradication of foot and mouth disease in the Middle East and North Africa.

The Middle East is regarded as the region of the world most heavily affected by foot and mouth disease (FMD). The situation in the Middle East and North Africa constitutes a threat to other regions of the world, especially Europe. Risk management differs between North Africa and the Middle East due to different epidemiological situations. In the Middle East, the national cattle population is the principal target of preventive vaccination. Vaccination is used as a tool for preventing economic losses due to the disease, rather than as a means to prevent the spread of the infection. In North Africa, as FMD occurs almost cyclically, management is more focused on emergency preparedness and limitation of the spread of the disease upon diagnosis, as well as on effective control measures based on quarantine and mass vaccination. To reduce future outbreaks of FMD in the countries of the two regions, a common strategic programme should be adopted, based on effective regional co-operation at many levels. This should be complemented by efforts to restructure and consolidate the national Veterinary Services.

Africa, Northern↗

Application of monoclonal antibodies to quality control of foot-and-mouth disease vaccines.

Panels of monoclonal antibodies (mAbs) produced against foot-and-mouth disease (FMD) virus types O, A and C were selected for cell culture neutralization titre (NT), mouse protection index (MPI), trypsin sensitivity (TS) and avidity to different epitopes. The selected sets were used to assay the antigen concentration and the fit between FMDV vaccine and challenge strains. It was observed that FMD vaccines protect more than 75% of vaccinated cattle when manufactured with antigens characterized by (1) a high degree of fit with the potency control virus, and (2) mean ELISA 50% titres (T50) > 28 for O, > 18 for A and > 75 for C types, respectively, using the corresponding mAb set.

Animals↗

Identification of foot-and-mouth disease virus-specific linear B-cell epitopes to differentiate between infected and vaccinated cattle.

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals. For several years, vaccination of animals, which had proven to be successful for the eradication of the disease, has been forbidden in the United States and the European Community because of the difficulty of differentiating between vaccinated and infected animals. In this study, detailed investigations of the bovine humoral immune response against FMD virus (FMDV) were performed with the aim of identifying viral epitopes recognized specifically by sera derived from FMDV-infected animals. The use of overlapping 15-mer synthetic peptides, covering the whole open reading frame of FMDV strain O(1)K in a peptide enzyme-linked immunosorbent assay, allowed the identification of 12 FMDV strain O(1)K-specific linear B-cell epitopes. Six of these linear B-cell epitopes, located in the nonstructural proteins, were used in further assays to compare the reactivities of sera from vaccinated and infected cattle. Antibodies recognizing these peptides could be detected only in sera derived from infected cattle. In further experiments, the reactivity of the six peptides with sera from animals infected with different strains of FMDV was tested, and strain-independent infection-specific epitopes were identified. Thus, these results clearly demonstrate the ability of a simple peptide-based assay to discriminate between infected and conventionally FMD-vaccinated animals.

Amino Acid Sequence↗

Functional analysis of the internal translation initiation site of foot-and-mouth disease virus.

Mutagenesis of the large untranslated sequence at the 5' end of the genome of foot-and-mouth disease virus revealed that a region of approximately 450 nucleotides preceding the open reading frame of the viral polyprotein is involved in the regulation of translation initiation at two internal start sites. Variations in two domains of this region reduced the translation efficiency up to 10-fold, whereas an intermediate segment seemed to be less essential. A pyrimidine-rich sequence preceding the start codon was most sensitive in that conversion of single pyrimidine residues to purines decreased the translation efficiency strongly. The data are in agreement with a recently proposed general structural model for the internal ribosome entry site of the cardiovirusaphthovirus subgroup of picornaviruses (E. V. Pilipenko, V. M. Blinov, B. K. Chernov, T. M. Dmitrieva, and V. I. Agol, Nucleic Acids Res. 17:5701-5711, 1989). They suggest, however, that this model represents only a core structure for the internal entry of ribosomes and that foot-and-mouth disease virus and other members of the picornaviruses need additional regulatory RNA elements for efficient translation initiation.

Animals↗

[Hand-foot-mouth disease: its course in the city of Milan (1980-86). Epidemiologic study gathered from the records of the community and scholastic ambulatory services of the Istituto di Clinica Dermatologic I and Dermatologia Pediatrica of the University].

Hand-foot-mouth disease: the Authors describe the epidemiological observations in a period of seven years made in a big urban area of Milan. They point out the periodic course of hand-foot and mouth disease, which is present in particular during May and November and particularly in children under six years. The Authors point out the difference between males and females and they try to correlate their dates with those gathered from the study of the literature.

Adolescent↗

Amitraz effects on foot-and-mouth disease virus in mammalian cells in vitro.

The toxicity of the acaricide amitraz and its effect on foot-and-mouth disease virus multiplication were evaluated in IB-RS-2 cells in vitro. A reduction of cell growth rate that was dependent on the dose and the length of treatment was observed in cells exposed to amitraz concentrations ranging from 20 to 50 micrograms/ml. Foot-and-mouth disease virus infectivity remained essentially unchanged in cells exposed to amitraz (20 micrograms/ml) 24 hr prior to virus infection or after the adsorption period. Viral RNA synthesis evaluated through [3H]uridine incorporation in cells treated for 24 hr prior to infection was not affected by amitraz.

Animals↗