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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↗

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↗

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↗

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↗

Use of molecular assay in diagnosis of hand, foot and mouth disease caused by enterovirus 71 or coxsackievirus A 16.

Hand, foot and mouth disease is a common illness in children and is usually caused by coxsackievirus A 16 and enterovirus 71. It has been noted that enterovirus 71 infection is more severe with significantly greater frequency of serious complications and fatality than coxsackievirus A 16. Therefore, it is important to develop a rapid and specific assay for discriminating coxsackievirus A 16 and enterovirus 71 in hand, foot and mouth disease outbreaks. In this study we designed two sets of RT-PCR primers specific for coxsackievirus A 16 and enterovirus 71. One hundred and eighty-nine viruses were evaluated for this molecular diagnosis assay. Among 110 enterovirus 71 strains, the enterovirus 71 specific primers gave clear signal for 107 clinical enterovirus 71 isolates and three reference enterovirus 71 strains. None of coxsackievirus A 16, other enteroviruses or non-enteroviruses show signal for enterovirus 71-specific primers. On the other hand, among 28 coxsackievirus A 16 strains, the coxsackievirus A 16-specific primers detect 27 clinical isolates and one reference strain but show no cross-reaction with other viruses. The molecular assay developed in this study provides a sensitive and specific way to distinguish coxsackievirus A 16 and enterovirus 71 induced hand, foot and mouth disease, which will be a useful rapid diagnostic method in future outbreaks.

Enterovirus↗

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↗

Sequencing and analysis for the full-length genome RNA of foot-and-mouth disease virus China/99.

The complete nucleotide sequence of genomic RNA of foot and mouth disease virus (FMDV) strain China/99 from infected bovine tongue epithelium is presented. The nucleotide sequence extending from the 5' end of the genomic RNA to the 5' end of poly (A) tail contains 8173 nucleotides (nt). Its open reading frame, which encodes a single polypeptide of 2332 amino acids, encompasses 6999 nt starting from the initiation codon AUG and terminating at the UAA codon 93 bases upstream from the 5' end of poly (A) tract. The 5' untranslated region (UTR) is composed of 1081 nt. The consensus of the 1d gene of FMDV strain China/99 compared with that of UKG/6/2001, UKG/12/2001, China/99HN4 and China/3/Tibet is over 97%. The result showed the stains belong to the members of the Pan-Asia family. There is a remarkable differentiation in the function-unknown (FUR), p2 and p3 regions between FMDV isolates from infected cattle and swine, especially in 3a gene. No deletion was found in genes I, 1a, 1b, 2a, 2c, 3b, and 3d. These genes might be indispensable to the surviving of FMDV. The secondary structures of small (S) fragments, FUR and an internal ribosome entry site can be classified into three types, and the S fragment and 3' UTR of the positive-sense RNA fold into stem-loop structures similar to the shape of clover.

Animals↗

Extending the foot-and-mouth disease module to the control of other diseases.

During the recent devastating epidemics of foot-and-mouth disease (FMD), bluetongue (BT), the highly pathogenic avian influenza (HPAI) and New Castle disease, more than 115 million animals were culled. The mass slaughter of animals raised serious ethical questions. These epidemics showed that the use of emergency vaccination is an essential element in disease control. During the last decade the FMD antigen banks have proved to be effective and this module should be extended. An international vaccine stock should be considered for classical swine fever and HPAI. Agreements with vaccine producers should be made easily available, with instant access to a vaccine reserve for rinderpest, peste des petits ruminants, BT, African horse sickness and Rift valley fever. These vaccines should meet international standards and should allow distinction between vaccinated and infected animals. Information should be gathered proactively on the use of vaccines for lumpy skin disease, sheep and goat pox and contagious bovine pleuropneumonia.

Animals↗

Genetic variation of foot-and-mouth disease virus during persistent infection in cattle.

Genetic variation of foot-and-mouth disease virus O1 Campos has been analyzed in consecutive isolates recovered over a one- or two-year period from four cattle with experimental persistent infection. Comparisons of RNase T1 two-dimensional maps and nucleotide sequences of the VP1-coding region revealed a continual, although irregular, increase in the fixation of mutations as the infection progressed. Most changes were not conserved in consecutive isolates. These results, together with the substantial rates of genomic variation observed between some pairs of strains recovered at close time periods, suggested the coexistence of heterogeneous populations in which variants evolve independently from each other, and predominate at irregular time intervals. Furthermore, non-related patterns of variation were observed in the four animals. Similarly, genetic diversity of representative strains from major serotype O outbreaks in endemic disease regions of southeastern Brazil and central eastern Argentina which occurred between 1958 and 1983, suggested that outbreak strains are also likely to represent fluctuations of heterogeneous populations which evolve independently from each other. The possible role of persistent infections in the introduction of variant populations in the field is discussed.

Amino Acid Sequence↗

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↗

Foot-and-mouth disease in tropical wildlife.

This review of foot-and-mouth disease in cloven-hoofed, free-living animals, describes the disease, the wide range of the hosts, the carrier state, and the interrelationship between disease in domestic livestock and wildlife. This information becomes even more crucial to the development of control strategies when linked to the process of pathogenesis and the epidemiology of the disease.

Animals↗

The fencing issue relative to the control of foot-and-mouth disease.

Certain livestock diseases in sub-Saharan Africa, such as foot-and-mouth disease are difficult to control because of the large numbers of infected wildlife hosts. These wildlife disease reservoirs form a continuous hazard of transmittal of the diseases to domestic livestock, which limits the access of livestock products from southern Africa to international markets. The disease reservoirs are often found in border areas between countries with susceptible species and infected reservoir animals continuously crossing the border. A regional approach to disease control is probably the only way to achieve any real progress. Here we review the positive and negative attributes of fencing as a control mechanism for disease transmission.

Animal Husbandry↗

The use of cyclophosphamide as an enhancer of the vaccine against foot-and-mouth disease.

The immunization of biungulate animals with killed foot-and-mouth disease virus (FMDV) requires periodic vaccinations due to a low vaccine immunogenicity. Therefore, FMDV antigens need to be combined with adjuvants such as aluminium hydroxide, saponin or oil emulsions. Animal handling for periodic inoculations, and the repeated doses of vaccines that have to be administered increase the commercialization costs. Moreover, the use of adjuvants may induce adverse effects. In the present work we show that it is possible to increase the life span of neutralizing antibodies in serum when a single dose of cyclophosphamide (Cy) is administered four days before vaccination with aluminium hydroxidesaponin FMDV vaccine.

Animals↗

Genetic variation of foot-and-mouth disease virus from field outbreaks to laboratory isolation.

Foot-and-mouth disease virus (FMDV), by nature of its RNA genome, possesses a high rate of mutation during replication. This results in extensive genetic polymorphism of virus populations in nature. The emergence of FMDV variants during replication has been reported. Genetic changes in the viral capsid protein (VP1) gene can result in amino acid changes affecting the immunodominant epitopes of FMDV. The genetic heterogeneity of FMDV in the field and the antigenic variants observed after cell culture isolation has been investigated by PCR sequencing and reactivity with monoclonal antibodies. These methods were applied to viruses causing two different outbreaks of FMD before and after replication in cell culture and in the animal host. The VP1 region of the genome was amplified by PCR and sequenced to reveal variant sequences identified after passage and to determine their presence in the original field tissue. In one case, reactivity with monoclonal antibodies was lost after passage as a result of an amino acid change in the subpopulation. These findings suggest that host cells can select specific virus genetic and antigenic subpopulations during virus isolation and propagation.

Amino Acid Sequence↗

Relationship of speed of slaughter on infected premises and intensity of culling of other premises to the rate of spread of the foot-and-mouth disease epidemic in Great Britain, 2001.

During the foot-and-mouth disease epidemic in the UK in 2001, two major control policies were the rapid identification of cases and the culling of animals on infected premises and on dangerous contact premises. Dangerous contact premises were divided into two groups, premises contiguous to an infected premises and non-contiguous premises. In England, the largest numbers of geographically clustered infected premises were in Cumbria, the South West (Somerset, Devon and Cornwall) and the Settle/Clitheroe area straddling the Yorkshire-Lancashire border. In each of these clusters, the rate of spread of the disease, the average time from the first lesion to slaughter on infected premises, and the intensity of culling of contiguous premises and non-contiguous premises were calculated for seven-day periods. Linear regression analysis was used to look for relationships between these factors and the rate of spread of the disease. The average time from the first lesion to slaughter had a statistically significant relationship in two of the three clusters and the intensity of culling of non-contiguous premises had a significant relationship in one. The intensity of culling of contiguous premises had no significant relationship in any of the three clusters.

Abattoirs↗

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↗