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[Bacterial synthesis of immunogenic epitopes of foot-and-mouth disease virus fused either to human necrosis factor or to hepatitis B core antigen].

Using recombinant DNA technology, construction and bacterial expression of genes was carried out which code for hybrid proteins, human tumor necrosis factor and hepatitis B core protein fused to immunogenic epitopes of foot-and-mouth disease virus, strains A22 and O1-194. Hybrids of tumor necrosis factor with foot-and-mouth disease antigenic determinants protected laboratory animals against the experimental challenge with a homologous strain of foot-and-mouth disease virus. Hybrid protein that contained immunogenic regions of two strains, A22 and O1-194, protected animals against infection with both A and O serotypes. Hybrid proteins based on hepatitis B virus core antigen retained the ability to assemble into core-like particles.

Animals↗

T-lymphocyte responses in guinea pigs vaccinated with foot-and-mouth disease virus.

The guinea pig provides an alternative experimental model for analysis of the immune response against foot-and-mouth disease virus (FMDV). The cellular immune response against FMDV in this experimental animal is unknown and was analyzed by in vivo and in vitro studies. In guinea pigs immunized with an FMDV A5 vaccine, a marked change in T-lymphocyte count appeared. For analyzing which functional T-cell compartment was affected, immunofluorescence studies, using monoclonal antibodies directed against differentiation antigens on guinea pig lymphoid cells, were performed. The proliferating T-cells were predominantly CD4-positive and, therefore, helper cells. T-cells from these animals were re-stimulated in vitro with homologous inactivated virus. The antigen-specific proliferative response of the T-cells in vitro was measured using the thymidine incorporation assay. A proliferative response to FMDV was observed that depended on the dose of the antigen. High concentration of virus had an inhibitory effect on T-cell proliferation. These data indicate that the guinea pig is a useful model for analysis of T-cell mediated mechanisms in the pathogenesis and immunity of foot-and-mouth disease.

Animals↗

Use of inactivated foot-and-mouth disease virus antigen in liquid-phase blocking ELISA.

A liquid-phase blocking ELISA is used by the World Reference Laboratory for Foot-and-Mouth Disease for the quantification of antibodies to foot-and-mouth disease virus. The potential for using inactivated FMDV antigens in the assay has been assessed by titrating bovine convalescent sera to all seven serotypes and comparing the titres obtained with live or inactivated antigens. The titres were similar indicating that either live or inactivated antigens can be used in the liquid-phase blocking ELISA. Removing the need to use live antigens in tests for FMD antibody would reduce disease security risk and widen the acceptability of kits for FMD antibody detection and assay.

Animals↗

Foot and mouth disease in Brazil and its control--an overview of its history, present situation and perspectives for eradication.

The objective of eliminating foot and mouth disease (FMD) in Brazil has been mainly motivated by the constant preoccupation of Brazilian authorities, livestock breeders and the meat industry with avoiding economic losses due to export restrictions. In 1934, the first national sanitary legislation was enacted, and the Pan-American Foot and Mouth Disease Center in Rio de Janeiro was inaugurated in 1951, with international participation. An overview is given of the past campaigns against FMD, the legislation, policies and field activities. The reasons for the failure of the past campaigns are discussed. The structure of the existing campaign and the present epidemiological situation are explained, and the further possibilities of being recognized as an FMD-free country are discussed.

Animals↗

Review of the status of foot and mouth disease in countries of South America and approaches to control and eradication.

Since the signing in 1987 of the Hemispheric Plan for the Eradication of Foot-and-Mouth Disease (PHEFA) by the countries of South America, clinical cases of foot and mouth disease (FMD) have decreased significantly throughout the continent. During the early 1990s, national laboratories diagnosed an average of 766 cases per year in South America. By the late 1990s, this continent-wide average had fallen to 130. By the end of the 1990s, the international community recognised Argentina, Chile, Guyana and Uruguay as free of FMD without vaccination. In 1999, clinical signs of FMD were absent in 60% of all cattle of the continent. These cattle represented 41% of all herds in South America and extended over 60% of the geographical area of the continent. However, in the spring of 2001, FMD re-appeared in certain countries of the Southern Cone. This widespread re-occurrence of the disease in Argentina, Uruguay and the State of Rio Grande do Sul in Brazil called into question the basic premise of the PHEFA--that countries in South America can achieve and maintain FMD-free status, with or without vaccination. The authors suggest that these countries can regain their FMD-free status by supporting the PHEFA. A successful disease eradication strategy relies on high levels of vaccination, effectiveness of outbreak responses, and control of animal movement. This strategy must have a regional, not national, focus and must be based on risk analysis methodology. The multilateral administration of vaccination campaigns and field activities to ensure wide and simultaneous vaccine application, along with primary prevention and joint border activities, is the key to eradicating FMD and maintaining areas free of the disease.

Animals↗

Molecular characterization of foot-and-mouth disease virus O/SKR/2000.

Molecular cloning and sequencing of the genome of foot-and-mouth disease virus (FMDV) O/SKR/2000, one of PanAsia strain, were performed from FMDV infected cattle. From the poly (C) tract of the 5' nontranslated region (NTR) to the 3' NTR including 14 base pairs (bp) of poly (A) tail, 7813 bp sequences comprising approximately 95% of the whole genome were obtained by reverse transcription polymerase reaction (RT-PCR). The deduced amino acid sequences of the structural and nonstructural proteins (NSP) of the O/SKR/2000 virus were analyzed for the sequence similarity among type O strains. Comparison between FMDV O/SKR/2000 and other strains indicates that overall the number of amino acids appears to be conserved without any deletion in either NSP or capsid proteins, thus, suggesting that O/SKR/2000 evolved with minor difference from preexisting strains.

Amino Acid Sequence↗

Quantitative estimates of the risk of new outbreaks of foot-and-mouth disease as a result of burning pyres.

The risk of dispersing foot-and-mouth disease virus into the atmosphere, and spreading it to susceptible holdings as a result of burning large numbers of carcases together on open pyres, has been estimated for six selected pyres burned during the 2001 outbreak in the UK. The probability of an animal or holding becoming infected was dependent on the estimated level of exposure to the virus predicted from the concentrations of virus calculated by the Met Office, Bracknell. In general, the probability of infection per animal and per holding decreased as their distance from the pyre increased. In the case of two of the pyres, a holding under the pyre plumes became infected on a date consistent with when the pyre was lit. However, by calculating their estimated probability of infection from the pyres it was concluded that it was unlikely that in either case the pyre was the source of infection.

Animals↗

Serological and molecular analysis of serotype O foot-and-mouth disease virus isolated from disease outbreaks in India during 1987-91.

Foot-and-mouth disease virus (FMDV) type O outbreaks have been reported frequently in vaccinated cattle in India. Twenty-five field isolates, recovered from outbreaks in vaccinated and unvaccinated cattle between 1987 and 1991, were analyzed in relation to the vaccine strain (R2/75) by complement fixation, serum neutralization and partial nucleotide sequencing of the VP1 gene. These sequences were compared with the viral sequences in GenEMBL database. Although the Indian type O viruses were close to the European type O1 viruses, they constituted a separate group of type O FMDVs. One of the field viruses, isolated from an outbreak in vaccinated cattle and designated as BAK/90, showed significant serological and nucleotide sequence variations from the vaccine strain. Phylogenetic analysis showed that the BAK/90 and R2/75 viruses belong to separate subgroups. The other isolates were found to be serologically related to both the BAK/90 and the vaccine strain. The BAK/90 strain gave broader antigenic coverage, showed better immunogenicity, and yielded larger amounts of 146S particles in suspension cultures as compared with R2/75. Taken together, these results favour inclusion of the BAK/90 strain in the vaccine to provide adequate protection against the field variants of type O FMDV currently circulating in India.

Amino Acid Sequence↗

An extended state-transition model for foot-and-mouth disease epidemics in France.

The dynamics of foot-and-mouth disease epidemics in France was examined through simulations based on an extended state-transition model. Contagion modelling depended on specific parameters: the so-called dissemination rates. Estimation of these parameters relied on a specific discrete-event simulation model. We were able to address the problem of the hidden spread of the epidemic, before the first outbreak is diagnosed. Furthermore, we took into account the silent development of the disease in affected herds before the diagnosis. The effect of control measures such as the active search for secondary outbreaks could thus be studied. We used the model to compare the development of FMD epidemics in two very different French regions and for different control strategies implemented by the animal-health authorities. These strategies gave similar results in a low herd density area, whereas in a high herd density area, the slaughter of contact herds greatly improved the stamping-out strategy. Finally, key parameters of the model were detected through a sensitivity analysis.

Animals↗

Symposium: international challenges and perspectives: internationalism and survival of foot-and-mouth disease virus in cattle and food products.

Foot-and-mouth disease is a serious world-wide economic disease of livestock and diverse animal species. The closing of borders to infected countries is a frequent aftermath of disease outbreaks. Historically, animals and animal products have been implicated as vehicles for transmission of the disease. Control programs encompass stringent importation policies, vaccination, quarantine, and slaughter. Joint efforts have been instituted successfully in previous control campaigns and would be the logical approach to large-scale eradication schemas.

Animals↗

Role of the international organisation for animal health (Office International des Epizooties: OIE) in the control of foot and mouth disease.

The author describes activities conducted by the International Organisation for Animal Health (OIE: Office International des Epizooties) to control foot and mouth disease (FMD) world-wide. These activities fall within the framework of the principal missions of the OIE. The first of these missions is the collection and dissemination of epidemiological information and of scientific knowledge on animal diseases, the socio-economic or disease implications of which can be particularly serious. The implementation of the measures required to control the disease and to protect countries threatened by FMD depends on the quality and rapidity of the transmission of this information. The co-ordination of studies, research and control programmes against FMD is equally important for the OIE. This work is based, in particular, on work conducted by the OlE foot and mouth disease and other epizootics Commission. OIE Member Countries not only have access to the most recent data on the diagnosis, surveillance and control of FMD but also have recourse to the official recognition procedure for disease-free status provided by this Commission. Finally, through the standardisation of health recommendations, diagnostic tests, manufacture protocols and the control of biological products, made available by the OIE International Animal Health Code Commission in regard to the former and by the OIE Standards Commission in regard to the latter, the OIE provides the reference for international trade in animals and animal products, and is recognised in this role by the World Trade Organization.

Animal Welfare↗

A generic spreadsheet model of a disease epidemic with application to the first 100 days of the 2001 outbreak of foot-and-mouth disease in the UK.

A generic, stochastic spreadsheet model was developed to calculate the number of cases within the first 100 days of a propagating epidemic and with the ability to incorporate generic control measures. Foot-and-mouth disease (FMD) epidemics were simulated with a range of assumptions about the number of cases incubating the disease on day 1 and the efficiency of control measures. Particularly severe epidemics resulted from scenarios with low efficiency of control measures and high numbers incubating. Control measures that prevented 0.8 of cases from resulting in new cases were able to reduce substantially the cumulative number of cases. The results of various scenarios using the model were compared to the number of cases of FMD in the first 100 days of the 2001 outbreak in the UK, with specific reference to cases in Cumbria and Anglesey. Potential practical and educational applications of the model are discussed.

Animals↗

Foot-and-mouth disease. A review for the practitioner.

Foot-and-mouth disease (FMD) is perhaps the most infectious disease known to human and veterinary medicine. This article is written with the practitioner in mind, concentrating on early recognition, epidemiology, occurrence around the world, and sampling and diagnostic methods. The article stresses that there are numerous FMD viruses, and not all behave in a similar fashion. The practitioner must be acute in his or her herd inspection of animals in which vesicular disease is suspected and knowledgeable as to differential diagnosis.

Animals↗

Densitygradient centrifugation with infectious ribonucleic acid of foot-and-mouth disease virus.

The sedimentation constant of an infectious component in ribonucleic acid preparations from foot-and-mouth disease virus has been determined by density-gradient centrifugation. A sedimentation constant of 37 Svedberg units (S(t)) was obtained. On the assumption that the relation between the molecular weight and the sedimentation constant found by Gierer is applicable to our system as well, a value of 3.1 x 10(6) was calculated for the molecular weight of the infectious component.

Animals↗

Demonstration of bovine CD8+ T-cell responses to foot-and-mouth disease virus.

The aim of this study was to investigate the importance of cellular immunity in foot-and-mouth disease in cattle, in particular to determine whether a CD8+ T-cell response could be detected, as these cells may play a role in both immunity and virus persistence. As attempts to characterize classical cytotoxic T cells had yielded non-reproducible results, largely due to high backgrounds in control cultures, a proliferation assay was developed that was demonstrated to detect antigen-specific, MHC class I-restricted bovine CD8+ cells responding to foot-and-mouth disease virus (FMDV). Proliferative CD8+ T-cell responses were detected consistently from 10 to 14 days following infection with FMDV and typically lasted 3-4 weeks. The role of CD8+ T cells in control of the disease, in particular their relevance for the establishment of persistence, may now be investigated.

Animals↗

Novel reverse transcription loop-mediated isothermal amplification for rapid detection of foot-and-mouth disease virus.

Speed is paramount in the diagnosis of foot-and-mouth disease (FMD) and simplicity is required if a test is to be deployed in the field. The development of a one-step, reverse transcription loop-mediated amplification (RT-LAMP) assay enables FMD virus (FMDV) to be detected in under an hour in a single tube without thermal cycling. A fragment of the 3D RNA polymerase gene of the virus is amplified at 65 degrees C in the presence of a primer mixture and both reverse transcriptase and Bst DNA polymerase. Compared with real-time RT-PCR, RT-LAMP was consistently faster, and ten copies of FMDV transcript were detected in twenty-two minutes. Amplification products were detected by visual inspection, agarose gel electrophoresis, or in real-time by the addition of a fluorescent dye. The specificity of the reaction was demonstrated by the absence of amplification of RNA from other viruses that cause vesicular diseases and from that of genetically related picornaviruses. Diagnostic sensitivity was validated by the amplification of reference FMDV strains and archival material from field cases of FMD. In comparison with the performance of the established diagnostic TaqMan assay, RT-LAMP appears to be sensitive, rapid, specific, and cost-effective, with the potential for field deployment and use by developing countries for FMDV surveillance.

Animals↗

Spatio-temporal epidemiology of foot-and-mouth disease in two counties of Great Britain in 2001.

The spatial, temporal, and spatio-temporal features of the 2001 British foot-and-mouth disease epidemic in selected areas within the counties of Cumbria and Devon, which experienced the greatest incidence of disease, are described using hazard functions, extraction mapping and the space-time K-function. In Cumbria, the hazard of foot-and-mouth disease infection peaked at 2.8% in the week commencing 8 March 2001 and farm holdings in this area continued to be identified with disease to 12 September 2001. In contrast, peak infection hazard in Devon was 0.7% in the week commencing 15 March 2001 and eradication of the disease was achieved in this area by 31 May 2001. Persistence of the disease in Cumbria was consistent with: (1) many cattle holdings infected early in the epidemic (creating a high environmental viral load), and (2) a relatively large amount of medium-to-long-distance spread of the virus associated with seasonal farming activities-compounded to some extent by the movement of people and vehicles between disaggregated farm land parcels. The interaction of disease risk in Cumbria showed that premises remained infectious for longer throughout May, June and July, consistent with delays in disease detection during this period.

Animals↗

Adenovirus-mediated RNA interference against foot-and-mouth disease virus infection both in vitro and in vivo.

Foot-and-mouth disease virus (FMDV) infection is responsible for the heavy economic losses in stockbreeding each year. Because of the limited effectiveness of existing vaccines and antiviral drugs, the development of new strategies is needed. RNA interference (RNAi) is an effective means of suppressing virus replication in vitro. Here we demonstrate that treatment with recombinant, replication-defective human adenovirus type 5 (Ad5) expressing short-hairpin RNAs (shRNAs) directed against either structural protein 1D (Ad5-NT21) or polymerase 3D (Ad5-POL) of FMDV totally protects swine IBRS-2 cells from homologous FMDV infection, whereas only Ad5-POL inhibits heterologous FMDV replication. Moreover, delivery of these shRNAs significantly reduces the susceptibility of guinea pigs and swine to FMDV infection. Three of five guinea pigs inoculated with 10(6) PFU of Ad5-POL and challenged 24 h later with 50 50% infectious doses (ID50) of homologous virus were protected from the major clinical manifestation of disease: the appearance of vesicles on the feet. Two of three swine inoculated with an Ad5-NT21-Ad5-POL mixture containing 2 x 10(9) PFU each and challenged 24 h later with 100 ID50 of homologous virus were protected from the major clinical disease, but treatment with a higher dose of adenovirus mixture cannot promote protection of animals. The inhibition was rapid and specific because treatment with a control adenovirus construct (Ad5-LacZ) expressing Escherichia coli galactosidase-specific shRNA showed no marked antiviral activity. Our data highlight the in vivo potential of RNAi technology in the case of FMD.

Adenoviridae↗