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Linear hoof defects in sheep infected with foot-and-mouth disease.

During the epidemic of foot-and-mouth disease (FMD) in The Netherlands in 2001, a sheep farm was identified that had been subclinically infected with the disease. The FMD virus genome was detected in 12 of 16 probang samples collected from the sheep and the virus was isolated from four of these samples. Linear defects were observed, 1 to 3 cm from the coronary band, in the hooves of several of the sheep. The defects were thought to have been caused by the FMD infection. It was thought that the distance of the defects from the coronary band might be an indication of the time since the animals had been infected. To determine the growth rate of the claws of sheep, the growth of the hoof horn of uninfected lambs and ewes was measured; in the lambs the growth rate was 0.44 mm per day and in the ewes it was 0.29 mm per day.

Animals↗

Rapid correlation between field isolates and vaccine strains of foot-and-mouth disease virus.

Antigenic relationships between field isolates of foot-and-mouth disease virus and available vaccine strains can be rapidly determined by ELISA. The most suitable vaccine strain to control an outbreak caused by the field isolate can then be quickly identified. The classical method of subtyping strains of foot-and-mouth disease virus should be replaced with a nomenclature which describes the relationship between a strain and the most antigenically closely related vaccine strain.

Animals↗

Selective lymphocyte depletion during the early stage of the immune response to foot-and-mouth disease virus infection in swine.

Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious vesicular disease of cloven-hoofed animals. In the present study we use FMDV serotype C infection of swine to determine, by analytical techniques, the direct ex vivo visualization of virus-infected immune cells during the first 17 days of infection. We report, for the first time, that FMDV C-S8c1 can infect T and B cells at short periods of time postinoculation, corresponding with the peak of the viremia. There is a significant lymphopenia that involves CD3(+) CD4(-) CD8(+/-), CD3(+) CD4(-) CD8(+)Tc, and CD3(+) CD4(+) CD8(+) memory Th but not CD3(+) CD4(+) CD8(-) naïve Th lymphocytes. In addition, a profound depletion of the vast majority of peripheral T cells in lymph nodes and spleen is observed. This selective depletion of T cells is not due mainly to in situ death via apoptosis as visualized by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique. Thus, early infection of T cells by FMDV may be the main cause of the observed T-cell depletion. Importantly, this lack of T cells is reflected in a reduced response to mitogen activation, which in many cases is totally eliminated. These data suggest a mechanism by which the virus causes a transient immunosuppression, subvert the immune systems, and spreads. These results have important implications for our understanding of early events in the development of a robust immune response against FMDV.

Animals↗

Multiple-infected diagnostic specimens from foot and mouth disease endemic regions.

The current routine diagnostic procedures for foot and mouth disease (FMD) virus antigen detection combine the use of an indirect sandwich enzyme-linked immunosorbent assay (ELISA) with virus isolation and amplification on cell culture. Several field samples recently received by the World Reference Laboratory for Foot and Mouth Disease which were initially diagnosed as containing a single virus type have subsequently been found to contain an additional virus type. Examples are given of the results of ELISAs performed on certain Saudia Arabian samples; these examples illustrate the problem which such multiple-infected samples present for laboratory diagnosis.

Animals↗

[Foot-and-mouth disease: clinical aspects, epizootiology and diagnosis].

A description of the clinical signs, differential diagnosis, epizootiology and laboratory diagnosis of foot-and-mouth disease in ruminants and pigs is given. Clinical signs are most easily recognised in cattle and pigs. Sheep and goats with foot-and-mouth disease do not show distinct clinical signs and can easily be missed. Clinical diagnosis by the veterinary practitioner is very important in case of an outbreak of foot-and-mouth disease.

Animals↗

Sites of release of airborne foot-and-mouth disease virus from infected pigs.

Pigs infected with foot-and-mouth disease virus by different routes of exposure were air-sampled individually, first as 'intact' (I-) pigs and then as 'intubated' (T-) pigs, using an endotracheal tube. Irrespective of the route of infection it was found that during the early stages of disease more virus was recovered from I-pigs than from T-pigs. Most of the virus from I-pigs during incubation and early disease was associated with large and medium sized particles. T-pigs infected by direct or indirect contact excreted a range of particle sizes at this time but T-pigs infected by inoculation only excreted small particles. During advanced disease all sizes of particle were excreted by I- and T-pigs. Greater amount of airborne virus were recovered at this time from I-pigs than T-pigs infected by indirect contact but I-pigs infected by intravenous or intradermal inoculation excreted less infectivity than T-pigs. The results show that the respiratory tract is involved during the early stages of foot-and-mouth disease in pigs infected by either natural or experimental routes of exposure and suggest that upper respiratory infection precedes lower.

Aerosols↗

Carcass disposal: lessons from Great Britain following the foot and mouth disease outbreaks of 2001.

The foot and mouth disease (FMD) outbreak that occurred in the United Kingdom in 2001 was of an unprecedented scale and severity and presented a massive logistical challenge to Government. Over 6.5 million animals were slaughtered and disposed of, over 4 million as a direct result of disease and a further 2.5 million on welfare grounds. On-farm burial and on-farm burning were the principal routes for disposal at the commencement of the outbreak. On-farm burial was limited by legislation to protect groundwater supplies and pyre burning came increasingly under attack from local communities concerned about health risks from smoke and emissions. Burning also painted a vivid but distressing picture of the war against disease. Increasingly, rendering capacity made an important contribution to disposal. The peak of the outbreak could only be managed by the development of a new disposal route--mass burial in engineered sites and by using licensed landfill where available. During the course of the outbreak, a disposal hierarchy was developed to reflect environmental and public health concerns, namely: rendering and incineration ranked first, licensed landfill next, followed by burning with mass burial or on-farm burial as the least preferred options. However, the campaign against the disease could not have been won without the tactical use of mass burial in addition to all the other available disposal routes. The authors describe the development and deployment of the disposal routes used in the 2001 outbreak.

Air Pollution↗

Pre-lytic release of foot-and-mouth disease virus in cytoplasmic blebs.

The pre-lytic release mechanism of foot-and-mouth disease virus was investigated by immunofluorescence, acridine orange staining, and electron microscopy in infected bovine and porcine kidney coverslip cultures. Cells with cytoplasmic fluorescence and which were positive for single stranded RNA with acridine orange staining were observed at 2 h after infection. Scanning electron microscopy showed cytoplasmic blebs in all cultures examined 2 h after infection. Rounded cells with virus inclusions began to appear 3 h after infection. Rounded cells and cytoplasmic blebs were shown to have single stranded RNA by acridine orange staining. Immunofluorescence and transmission electron microscopy with immunoferritin tagging demonstrated foot-and-mouth disease virus in cytoplasmic blebs. This study presents evidence for a pre-lytic release of foot-and-mouth disease virus through virus-containing cytoplasmic blebs emerging from infected cells.

Aphthovirus↗

[Specific immunoprophylaxis trials with calves against foot-and-mouth disease].

Studies were conducted on vaccination of different age groups of calves with monovalent and biovalent vaccine against foot-and-mouth disease using various immunization patterns. The studies showed that passive immunity of calves impedes the building up of solid immunity. It is recommended on the basis of comparative studies of different immunization schemes to vaccinate calves under 6 months of age with double vaccine dose and to revaccinate them 1--2 months later. It was shown that calves aged 6 to 12 months react to vaccine against foot-and-mouth disease as adult animals but revaccination is also recommended to build up solid immunity. The influence is discussed of various factors hindering the building up of solid post vaccination immunity in young animals following vaccination with vaccine against foot-and-mouth disease.

Animals↗

[Effect of hormones on the susceptibility of the swine cell line IB-RS-2 to foot-and-mouth disease virus].

The actions of hydrocortisone and insulin on the multiplication of foot-and-mouth disease virus were studied. The data obtained showed that the infectivity and the synthesis of the virus nucleic acid as evaluated through the plaque assay method and the kinetics of Uridine-3H incorporation were increased or decreased by hydrocortisone (2 x 10(-6) M). The induction of both effects seems to be related to the carbohydrate metabolism: when the maintenance medium contained glucose or glucose plus calf serum there was an inhibition on virus multiplication and no effect was observed in the absence of both serum and glucose. This was found both when the hormone was added to the cell culture 24 hours before infection as well as when it was added immediately or thirty minutes after virus adsorption. The possibility that these effects could be related to the synthesis of viral RNA-polimerase is discussed. Insulin (50 ng/ml) did not induce any effect on foot-and-mouth disease virus multiplication. However this hormone antagonized the action of hydrocortisone on the infectivity and on the synthesis of foot-and-mouth disease virus nucleic acid.

Animals↗

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↗

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↗

Cloned viral protein vaccine for foot-and-mouth disease: responses in cattle and swine.

A DNA sequence coding for the immunogenic capsid protein VP3 of foot-and-mouth disease virus A12, prepared from the virion RNA, was ligated to a plasmid designed to express a chimeric protein from the Escherichia coli tryptophan promoter-operator system. When Escherichia coli transformed with this plasmid was grown in tryptophan-depleted media, approximately 17 percent of the total cellular protein was found to be an insoluble and stable chimeric protein. The purified chimeric protein competed equally on a molar basis with VP3 for specific antibodies to foot-and-mouth disease virus. When inoculated into six cattle and two swine, this protein elicited high levels of neutralizing antibody and protection against challenge with foot-and-mouth disease virus.

Amino Acid Sequence↗

Histological and histochemical characterisation of mammary gland tissue of cows infected with foot-and-mouth disease by contact exposure.

Foot-and-mouth disease virus was observed to replicate in secretory epithelial cells of bovine mammary gland alveoli as a result of systemic infection initiated by exposure to infected animals. Viral antigens were demonstrated using fluorescent antibody and immunoperoxidase labelling techniques before the development of signs of clinical disease. In addition, labelled antigens were observed associated with cytoplasmic-like fragments in luminal membrane limited structures. Histologically, lesions of the alveolar secretory epithelium consisted of focal necrosis of these cells which eventually sloughed into the lumen.

Animals↗

[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↗

Airborne spread of foot-and-mouth disease in Saskatchewan, Canada, 1951-1952.

Farms affected with foot-and-mouth disease during the epidemic in Saskatchewan, in 1951-1952, for which the origin of virus was not known or uncertain, were studied to determine if infection could have been introduced by the airborne route. A short-range Gaussian plume dispersion model was used to estimate the concentration of virus downwind and the dose available for individual animals. The investigation suggested that a large virus source due to infected pigs in a feedlot in January 1952 could have been responsible for airborne dispersion northwestwards downwind to farms up to 20 km distant. Subsequent spread from these farms was to neighboring farms and was influenced by the local topography of a creek. The dispersion model could be used for predicting airborne spread if foot-and-mouth disease should occur.

Air Microbiology↗

Early antibody responses of cattle for foot-and-mouth disease quadrivalent double oil emulsion vaccine.

Foot-and-mouth disease (FMD) is an economically important disease of cloven-hoofed animals. The multiplicity of FMDV serotypes in animals poses a central problem in the policy of vaccination and is of much concern to health authorities. Hence it is the practice of vaccination with polyvalent vaccine for prophylactic measure. In the present report, we analysed the early antibody responses elicited by FMDV quadrivalent (FMDV O, A, C and Asia 1 serotypes) double emulsion (Montanide ISA 206) vaccines in cattle. We observed variations between various viral serotypes in eliciting early antibody response although neutralizing antibody response against all the four serotypes were detected as early as fourth day following vaccination. The duration of immunity also appeared to maintain for long period. The neutralizing antibody titres were maintained well above 2log(10) even after 6 months of vaccination irrespective of serotypes. Thus, allows the possibilities of two vaccinations per year for the maintenance of herd immunity.

Adjuvants, Immunologic↗

The role of the World Reference Laboratories for Foot-and-Mouth Disease and for Rinderpest.

The World Reference Laboratories for Foot-and-Mouth Disease and for Rinderpest provide a worldwide diagnostic and surveillance service for these disease for FAO and OIE. Both laboratories are housed within the high security facility of the Institute for Animal Health, Pirbright, UK. Foot-and-mouth disease (FMD) and rinderpest (RP) are OIE List A diseases and historically have caused huge losses to agricultural economies around the world, prompting the establishment of veterinary colleges in Europe and environmentally controversial control programs in Africa. FMD and RP have now been geographically restricted, but the large legal and illegal world trade in live animals and animal products constantly threatens to allow them to spread back into disease-free areas. The Reference Laboratories provide a center of excellence for the development of improved diagnostic techniques and a repository of isolates collected over many years. These libraries provide material for investigations of the molecular epidemiology and evolution of the viruses and a data base against which new isolates can be compared. Thus it is possible to individually characterize new outbreak strains, identify their likely origin and provide the most up-to-date support for their control.

Africa↗