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PubMed2003

Molecular epidemiology of SAT3-type foot-and-mouth disease.

VP1 gene nucleotide sequences of 51 SAT3-type foot-and-mouth disease (FMD) viruses from seven southern and eastern African countries were used to infer a gene phylogeny. Results obtained by phylogenetic analysis of the homologous 405 nt region corresponding to the C-terminal 128 amino acids of 1D and adjacent 7 amino acids of 2A indicate that there are six distinct virus lineages evolving independently in different geographical localities in accordance with the FMD topotype concept. Topotypes I-IV occur in southern Africa, whilst topotypes V and VI are unique to East Africa. Viruses of different topotypes differ from each other at 20% or more of the nucleotide sites, specified in this study. Despite the limited geographical distribution of this serotype, the level of intratypic variation is intermediate between that of SAT1 and SAT2, both of which are widely distributed in sub-Saharan Africa. Within SAT3, 37.3% and 47.4% of sites were completely conserved on nucleotide and amino acid levels, respectively. The locality-specific grouping of viruses permits accurate determination of the sources of outbreaks, whilst the high levels of variation within the immunodominant 1D protein has implications for the control of the disease through vaccination.

Africa, Eastern↗
PubMed1984

Serological response of cattle to simultaneous vaccinations against foot-and-mouth disease and haemorrhagic septicaemia.

In Malaysia, where vaccination campaigns against foot-and-mouth disease and haemorrhagic septicaemia are routinely carried out, it was desirable to determine whether it was safe and efficacious to administer both vaccines simultaneously. A trial group of 104 cattle was divided into three groups; group 1 animals received both vaccines simultaneously, group 2 animals received only foot-and-mouth disease vaccine and group 3 animals received only haemorrhagic septicaemia vaccine. The serological response to vaccinations was monitored at 0, 21 and 35 days by the virus neutralisation test for foot-and-mouth disease and the mouse-protection and indirect haemagglutination tests for haemorrhagic septicaemia. The simultaneous administration of the two inactivated vaccines produced no adverse effects and the serological response did not differ from the response to either vaccine given separately, thus indicating that cattle may be safely and effectively vaccinated simultaneously in this way.

Animals↗
PubMed2004

The use of vaccines in South American foot-and-mouth disease eradication programmes.

Since the beginning of organized campaigns in the 1960s, vaccination has been a major component of national FMD control and eradication programmes in South America. Aqueous vaccines were used in the 1960s and 1970s, and the introduction of oil vaccines in the mid 1980s helped to decrease endemism. Bi- and trivalent FMD vaccine production increased from 266 thousand doses in 1967 to 580 million doses in 2002. Currently, over 200 million cattle are vaccinated twice yearly throughout the continent. This massive vaccination programme, along with outbreak and animal movement control, helped eradicate FMD in sizeable areas in the 1990s. Outbreaks in the Southern Cone during 2000/2001 were curbed mostly by repeated massive vaccination of cattle. The Hemispheric FMD Eradication Plan, with its end date of 2009, relies on cyclic vaccinations as a major instrument. Vaccination as the major component will continue until when?

Animals↗
PubMed2005

The application of new techniques to the improved detection of persistently infected cattle after vaccination and contact exposure to foot-and-mouth disease.

Detection of antibodies to the non-structural proteins (NSP) of foot-and-mouth disease virus (FMDV) was compared with conventional serological and virological methods and with RT-PCR for the identification of FMDV carrier animals obtained after experimental contact challenge of vaccinated cattle. Transmission from carriers to sentinels was also monitored. Twenty FMDV vaccinated and five unvaccinated cattle were challenged by direct contact with five donor cattle excreting FMDV and monitored until 28 days post challenge-exposure . Twelve vaccinated and three unvaccinated animals were retained up to 24 weeks post exposure to FMDV in order to monitor viral persistence, transmission and antibody responses. In nine vaccinated animals, infection persisted beyond 28 days post exposure, virus being detected more frequently and for longer in oesophagopharyngeal samples from these animals when examined by RT-PCR rather than by virus isolation. Although recovery of FMDV RNA became increasingly sporadic over time, the number of RNA copies detected in positive samples declined only slowly. Two naïve sentinel cattle housed with the persistently infected animals between 93 and 168 days after the latter had been challenge-exposed to FMDV did not become infected. There were differences in the ability of commercially available serological tests to detect antibodies to FMDV non-structural proteins (NSP) in vaccinated and subsequently challenged cattle. Although no single test could identify all of the vaccinated cattle that became persistently infected, the most poorly recognised animals were those with the least evidence of virus replication based on other tests. The potential of the detection of antibodies to the 2B NSP of FMDV for diagnosing persistent FMDV infection was demonstrated.

Animals↗
PubMed1994

Development of an effective vaccine against foot-and-mouth disease with partially purified and concentrated virus antigen.

Foot-and-mouth disease (FMD) virus is poorly immunogenic. There is need to improve the quality of the vaccine by incorporating enhanced quantity of purified virus antigen to prevent sporadic breakdown of immunity in regularly vaccinated organized herds. A technique has been standardized for virus purification and concentration by polyethylene glycol (PEG) treatment for large scale production of concentrated FMD vaccine. The vaccine prepared with tenfold concentrated antigen was given field trial in an organised farm with a reduced dose as compared to the conventional vaccine. High level serum neutralizing antibody in cattle was observed throughout the entire period of study. The concentrated vaccine controlled the spread of the disease when used in face of outbreak in villages adjacent to the organized farm.

Animals↗
PubMed2001

Genetic and antigenic analysis of type A foot-and-mouth disease viruses isolated in India during 1987-1996.

Twenty-three foot-and-mouth disease virus (FMDV) type A field isolates, recovered from different outbreaks during 1987-1996 in India, were subjected to antigenic and genetic analysis. The isolates showed a close antigenic relationship to the current vaccine strain (IND 17/77) in micro-neutralization test conducted using a vaccine strain (IND 17/77) antiserum and a peptide (aa 136-151 of VP1 protein of the A22/Azerbaijan/65 strain) antiserum. However, the isolates revealed minor antigenic differences in their reactivity with three neutralizing monoclonal antibodies (MAbs) recognizing trypsin-sensitive conformation-independent epitopes of the vaccine virus strains. Phylogenetic relationship between the isolates was carried out employing a part of the 1D gene (168 nucleotides at the 3'-end). Additional seven type A Indian field isolates reported earlier were included in the analysis. The percent similarity among the Indian isolates varied from 82.7% to 99.4% at nucleotide level, and from 83.9% to 100% at amino acid level. These observations clearly demonstrate genetic heterogeneity of the field isolates. The current vaccine strain IND 17/77 showed divergence of 9.7% at nucleotide level and 5.6% at amino acid level from the A22 Iraq 24/64 isolate. The field strains were divergent from the vaccine strain IND 17/77 by 5.6%-14.6% and 3.7% 13.7% at nucleotide and amino acid level, respectively. In the phylogenetic tree, the isolates were distributed into 21 genetic groups. The clustering pattern of the isolates in the phylogenetic tree revealed no specific distribution pattern of the foot-and-mouth disease (FMD) outbreaks in relation to their geographical locations, caused by unrestricted animal movement and endemic nature of the disease.

Amino Acid Sequence↗
PubMed1995

Receptor binding site-deleted foot-and-mouth disease (FMD) virus protects cattle from FMD.

Binding of foot-and-mouth disease virus (FMDV) to cells requires an arginine-glycine-aspartic acid (RGD) sequence in the capsid protein VP1. We have genetically engineered an FMDV in which these three amino acids have been deleted, producing a virus particle which is unable to bind to cells. Cattle vaccinated with these receptor binding site-deleted virions were protected from disease when challenged with a virulent virus, demonstrating that these RGD-deleted viruses could serve as the basis for foot-and-mouth disease vaccines safer than those currently in use. This strategy may prove useful in the development of vaccines for other viral diseases.

Amino Acid Sequence↗
PubMed2005

Non-capsid proteins to identify foot-and-mouth disease viral circulation in cattle irrespective of vaccination.

The ability of foot-and-mouth disease virus (FMDV) to establish subclinical and even persistent infection, the so called carrier state, imposes the need to reliably demonstrate absence of viral circulation, to monitor the progress of control measures, either during eradication programs or after reintroduction of virus in free areas. This demonstration becomes critical in immunized populations, because of the concern that silent viral circulation could be hidden by immunization. This concern originates from the fact that vaccination against foot-and-mouth disease (FMD) protects against clinical disease, but not necessarily against subclinical infection or establishment of the carrier state in cattle. A novel approach, developed and validated at PANAFTOSA during the 1990s, based on an immunoenzymatic system for detection of antibodies against non-capsid proteins (NCP) has proven valuable for monitoring viral circulation within and between herds, irrespective of the vaccination status. Antibodies against NCP are induced during infection but, in principle, not upon vaccination. The validation of this system led to its international recognition as the OIE index test. The fitness of this serosurvey tool to assess viral circulation in systematically vaccinated populations was demonstrated through its extensive application in most regions in South America. The experience attained in these regions supported the incorporation of the "free of FMD with vaccination" provisions into the OIE code. Likewise, it opened the way to alternatives to the "stamping out" policy. The results gave input to an old controversy related to the real epidemiological significance, if any, of carrier animals under the vaccination conditions in South America, and supported the development of recommendations and guidelines that are being implemented for serosurveys that go with control measures in vaccinated populations.

Animals↗
PubMed1999

[Foot-and-mouth disease of cattle is not a zoonosis].

In 1997 there was an outbreak of foot-and-mouth disease (FMD) among cattle in Turkey. People visiting that country were warned against importing animal products into the Netherlands. This had nothing to do with hazards to human health, as FMD virus is not a zoonotic virus, but with the risk of spread of the disease to livestock in the Netherlands, notably to cattle and pigs. A disease with similar clinical symptoms in pigs is swine vesicular disease (SVD), which is not a zoonosis either. FMD virus is an aphtovirus, SVD virus is an enterovirus. Hand-foot-and-mouth disease in humans is caused by other enteroviruses, i.e. Coxsackie virus and enterovirus 71.

Animals↗
PubMed1986

The use of serum neutralizing antibody assay for the determination of the potency of foot and mouth disease (FMD) vaccines in cattle.

The Permanent Commission of O.I.E. on foot and mouth disease has proposed a series of potency standards for foot and mouth disease vaccines. No totally in vitro assay has yet been developed to satisfy these requirements, and most Control Authorities require a potency assay to be carried out in cattle using challenge with virulent virus. There are various reasons why challenge tests should be replaced by serological tests, but a stumbling block to this is the requirement that the 50% protective antibody level (PA50) is valid only for a specific combination of vaccine virus seed lot with cattle virus seed lot in a laboratory. The results of challenge and antibody tests for 38 U.K. Control Authority vaccine batch tests were analysed to examine the correlation between potencies measured by the two methods. The correlation between the methods was high and the proportion of misclassification of batches was low. It is suggested that the results provide a good basis for future use of the serological method, but that it is still sometimes necessary to carry out challenge tests.

Animals↗
PubMed2002

The effects of gamma interferon on replication of foot-and-mouth disease virus in persistently infected bovine cells.

Foot-and-mouth disease virus (FMDV) causes a highly contagious viral disease of cloven-hoofed animals, which has a considerable socio-economic impact on the countries affected. In addition, persistent infection can occur following clinical or sub-clinical disease in either vaccinated or non-vaccinated cattle. The mechanism(s) by which FMDV persistence is established and maintained is not fully understood. To better understand the basic mechanisms controlling the virus infection in cattle, the effects of interferon gamma (IFN-gamma) on the replication of FMDV was evaluated in vitro in persistently infected-epithelial cells isolated from FMDV infected cattle. Initially primary bovine thyroid (BTY) cells were treated with varying doses of bovine recombinant IFN-gamma. The cytokine activity was measured by detection of viral antigen in cell supernatants and viral RNA expression compared with cells without INF-gamma treatment. Pretreatment with IFN-gamma profoundly affected FMDV growth in BTY cells. The replication of FMDV was affected in the presence of more than 2.5 u/ml of IFN-gamma and the effect was both dose-dependent and related to the time of exposure. Analysis of the mechanism of inhibition suggests that IFN-gamma did not inhibit the viral replication through induction of nitric oxide. More interesting is the finding that continuous treatment with IFN-gamma severely restricts FMDV replication or even cures persistently infected bovine epithelial cells, indicating that a cytokine-mediated pathway may be involved in the in vivo clearance of persistent FMDV.

Animals↗
PubMed2003

Antigenic characterization of foot-and-mouth disease virus serotype Asia1 field isolates using polyclonal and monoclonal antibodies.

Foot-and-mouth disease virus (FMDV) serotype Asia1 field isolates (n = 100) were compared using a panel of 11 monoclonal antibodies (Mab) in sandwich ELISA. The majority (over 89%) of the isolates showed either homologous (76% and above reactivity) or reduced affinity (20-75% reactivity) for the Mabs 2A, 13, 40, 34 and 81, suggesting that these Mab binding epitopes are conserved, whereas a more variable reactivity was observed for the Mabs B3, 1A, 24, 72, 82 and 89. Polyclonal relationship ('r' value) of the field isolates in liquid phase blocking (LPB) ELISA was examined, and the mean 'r' value was 0.62 relative to vaccine virus IND 63/72. Some of the field isolates (n = 34) were tested in virus neutralization test (VNT) and showed an 'r' value of >0.40. Although a minor antigenic difference was observed in the Mab profiling study, there has not been large antigenic divergence between reference virus and field viruses, thereby providing evidence of wide antigenic coverage of the vaccine strain.

Animals↗
PubMed1995

Protective effect of lidocaine in the experimental foot-and-mouth disease pancreatitis.

Experimental infection of mice with foot-and-mouth disease virus (FMDV) induces a necrotizing pancreatitis of the exocrinar portion of the organ. The lesions are characterized by vascular congestion, edema and interstitial polymorphonuclear leukocyte (PMN) infiltrates. When infected mice were treated with different amounts of lidocaine (a local anesthetic, chemically defined as a tertiary amide compound), reduction in intensity of the pancreatic necrosis and in the number of PMN were observed. Even though lidocaine could interfere with FMDV post-replicative cytolytic mechanisms, it appears that protection against pancreatic necrosis is by attenuation of PMN presentation in the infected tissue.

Animals↗
PubMed1999

Vital elements for the successful control of foot-and-mouth disease by vaccination.

The efficient control of foot-and-mouth disease (FMD) by immunisation depends not only on the appropriate choice of vaccine in terms of innocuity, potency and strain composition, but also on a series of inter-related zoo-sanitary factors which are equally important. These include: national, centralised planning (including contingency planning) and control; vaccination and revaccination policy; the availability of epizootiological intelligence based on adequate diagnostic capability and ongoing immunological surveillance; the logistics of supply with its components of storage, transport and distribution; proper vaccine application; cleaning and disinfection of premises, vehicles and personnel; identification of individual animals; control of animal movement; recording; ongoing economic outcome and benefit analyses: training and retraining of professional and technical staff; public relations and especially the commitment of the agricultural community. These elements are reviewed in this paper.

Animals↗
PubMed1982

Ultrastructural changes and antigen localization in tissues from foot-and-mouth disease virus-infected guinea-pigs.

Foot-and-mouth disease virus (FMDV)-induced ultrastructural changes in guinea-pig tongue, heelpad, mammary and liver tissues were examined using scanning and transmission electron microscopy. FMDV infection caused cell rounding and the release of virus in membrane limited vesicles in the animal tissues similar to that seen in other work in cell cultures. Microfilaments were present which may be responsible for cell rounding. Immunoperoxidase labeling revealed the attachment of the virus-infection associated (VIA) antigen to the smooth vacuoles of mammary and liver tissues, and to milk fat globules. The electron microscope immunoperoxidase procedure increased the sensitivity of detection sufficiently to allow the visualization of VIA antigen in tissues not previously shown to have the antigen. It is postulated that the release of the smooth vacuoles from the liver cells stimulates the animal's immune response to the VIA antigen.

Adipose Tissue↗
PubMed2002

Integrin alphavbeta1 is a receptor for foot-and-mouth disease virus.

Infection by field strains of Foot-and-mouth disease virus (FMDV) is initiated by binding to certain species of arginine-glycine-aspartic acid (RGD)-dependent integrin including alphavbeta3 and the epithelial integrin alphavbeta6. In this report we show that the integrin alphavbeta1, when expressed as a human/hamster heterodimer on transfected CHOB2 cells, is a receptor for FMDV. Virus binding and infection mediated by alphavbeta1 was inefficient in the presence of physiological concentrations of calcium and magnesium but were significantly enhanced by reagents that activate the integrin and promote ligand binding. The ability of chimeric alpha5/alphav integrin subunits, in association with the beta1 chain, to bind FMDV and mediate infection matched the ligand binding specificity of alphavbeta1, not alpha5beta1, thus providing further evidence for the receptor role of alphavbeta1. In addition, data are presented suggesting that amino acid residues near the RGD motif may be important for differentiating between the binding specificities of alphavbeta1 and alphavbeta6.

Animals↗
PubMed2002

Natural aerosol transmission of foot-and-mouth disease virus to pigs: minimal infectious dose for strain O1 Lausanne.

Foot-and-mouth disease virus (FMDV) can spread by a variety of mechanisms, including, under certain circumstances, by the wind. Simulation models have been developed to predict the risk of airborne spread of FMDV and have played an important part in decision making during emergencies. The minimal infectious dose of FMDV for different species by inhalation is an important determinant of airborne spread. Whereas the doses for cattle and sheep have been quantified, those for pigs are not known. The objective of the study was to obtain that data in order to enhance the capability of simulation models. Under experimental conditions, forty pigs were exposed individually to naturally generated aerosols of FMDV, strain O1 Lausanne. The results indicated that doses under 100 TCID50 failed to infect pigs but doses of approximately 300 TCID50 caused short-term sub-clinical infection. The calculations suggested that a dose of more than 800 TCID50 is required to cause infection and typical disease.

Aerosols↗