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PubMed2006

An antiviral mechanism investigated with ribavirin as an RNA virus mutagen for foot-and-mouth disease virus.

To prove whether error catastrophe/lethal mutagenesis is the primary antiviral mechanism of action of ribavirin against foot-and-mouth disease virus (FMDV). Ribavirin passage experiments were performed and supernatants of Rp1 to Rp5 were harvested. Morphological alterations as well as the levels of viral RNAs, proteins, and infectious particles in the BHK-21 cells infected using the supernatants of Rp1 to Rp5 and control were measured by microscope, real-time RT-PCR, western-blotting and plaque assays, respectively. The mutation frequency was measured by sequencing the complete P1- and 3D-encoding region of FMDV after a single round of virus infection from ribavirin-treated or untreated FMDV-infected cells. Ribavirin treatment for FMDV caused dramatically inhibition of multiplication in cell cultures. The levels of viral RNAs, proteins, and infectious particles in the BHK-21 cells infected were more greatly reduced along with the passage from Rp1 to Rp5, moreover, nucleocapsid protein could not be detected and no recovery of infectious virus in the supernatant or detection of intracellular viral RNA was observed at the Rp5-infected cells. A high mutation rate, giving rise to an 8-and 11-fold increase in mutagenesis and resulting in some amino acid substitutions, was found in viral RNA synthesized at a single round of virus infection in the presence of ribavirin of 1000 microM and caused a 99.7% loss in viral infectivity in contrast with parallel untreated control virus. These results suggest that the antiviral molecular mechanism of ribavirin is based on the lethal mutagenesis/error catastrophe, that is, the ribavirin is not merely an antiviral reagent but also an effective mutagen.

Animals↗

PubMed1992

Proliferative lymphocyte responses to foot-and-mouth disease virus and three FMDV peptides after vaccination or immunization with these peptides in cattle.

We studied proliferative responses of bovine T lymphocytes to foot-and-mouth disease virus (FMDV) serotypes A, O and C as well as to three peptides including the two major B-cell epitopes of FMDV (VP1[141-156] and VP1[200-213]). Peripheral blood mononuclear cells (PBMC) from cattle previously vaccinated with monovalent vaccine responded to both homotypic and heterotypic virus strains. Of 14 FMDV-specific bovine T-cell clones, which were prepared from PBMC of an animal vaccinated with the trivalent vaccine, 11 reacted to each of the three serotypes A, O and C. This indicates that several T-cell epitopes might be conserved among these serotypes. PBMC from one of two cattle immunized with VP1[141-156]KLH, one of two cattle immunized with VP1[200-213]KLH and two of three cattle immunized with CC-VP1[200-213]-PPS-VP1[141-156]-PCG responded to the homotypic virus strain. After immunizations with VP1[200-213]KLH also heterotypic responses were found. Thus, it appears that these two B-cell sites include T-cell determinants that are recognized by some cattle. However, when proliferative responses of PBMC from an animal vaccinated with the trivalent vaccine were tested, no responses were found to VP1[141-156] and VP1[200-213], whereas the response was very poor to CC-VP1[200-213]-PPS-VP1[141-156]-PCG. These results suggest that these sequences do not represent dominant T-cell epitopes and/or that T-cell reactivity towards these synthetic peptides does not completely cover the T-cell reactivity towards the fragments present after processing of the whole virus.

Animals↗

PubMed1986

Destruction and repair of mammary gland parenchyma of cows infected with foot-and-mouth disease.

Bovine mammary gland secretory epithelial cells show signs of infection as early as three days after exposure of lactating host dairy cows to pigs infected with foot-and-mouth disease. Isolated foci of necrotic alveoli, as observed by scanning electron microscopy, increased in area and number with time. Infection of individual milk synthesizing cells progressed to involve the entire secretory epithelium. Alveolar luminal contents, in contrast to those in control preparations, consisted of heavy concentrations of cellular debris and connective tissue fragments; few leukocytes were observed. Involutionary changes occurred 10 days after cow exposure. Significant evidence of repair in necrotic areas was present at 15 days, but limited repair occurred earlier. Characteristics of replacement secretory epithelium made it possible to differentiate it from older mammary gland parenchyma.

Animals↗

PubMed1976

The role of sheep and goats in the epizootiology of foot-and-mouth disease in Kenya.

The pathogenicity of two bovine field strains of virus for indigenous goats was examined in the laboratory. The goats failed to develop clinical disease or become virus carriers although the majority showed a definite immune response. A field survey in a foot-and-mouth disease enzootic area showed that the indigenous sheep and goat populations were frequently exposed to infection as evidenced by a high proportion of sero-positive animals but the incidence of virus carriers was very low in goats and no carriers were detected in sheep.

Animals↗

PubMed1988

Serological and biochemical analysis of foot-and-mouth disease virus (serotype C3) isolated in Argentina between 1981 and 1986.

The evolution in the field is described for foot-and-mouth disease viruses belonging to serotype C3 in Argentina between 1981 and 1986. During 1981 and 1982 only three isolations of this serotype took place, which showed minor serological and biochemical variations from the prototype strain C3 Resende-Brasil/55. At the beginning of 1983 an outbreak was detected in a restricted geographical region caused by strains which had important serological and biochemical differences from the prototype strain. However, revaccination of the animals with the available commercial vaccine was sufficient to control the disease. During 1984 and up to 1986, a new outbreak of the same serotype took place in an extended geographical region of Argentina. During this outbreak, two field strains were isolated, studied and later included in the vaccine. One of them, strain C84, was a serological variant of the prototype strain and its inclusion in the vaccine had only a limited effect in controlling the disease. Inclusion of the other representative strain, C85, together with virus C84 finally reduced the number of outbreaks to the usual number reported.

Animals↗

PubMed2001

Immune responses and protection against foot-and-mouth disease virus (FMDV) challenge in swine vaccinated with adenovirus-FMDV constructs.

A replication-defective adenovirus 5 encoding foot-and-mouth disease virus (FMDV) capsid and 3C proteinase coding regions (Ad5-FMDV3CWT) was used to vaccinate swine. A single inoculation utilizing 1 x 10(8) plaque forming units (pfu) or an inoculation of 1 x 10(8) followed by a boost of 5 x 10(8) pfu Ad5-FMDV3CWT were tested, along with an inoculation and boost using an adenovirus encoding the FMDV capsid coding region and an inactive form of the 3C proteinase (Ad5-FMDV3CMUT). Sera collected from these animals were examined for the presence of FMDV-specific antibodies using immunoprecipitation, neutralization, and ELISA assays specific for IgM, IgG1 and IgG2. Efficacy studies were performed by placing the vaccinated swine in contact with an FMDV-infected swine and monitoring for signs of disease and changes in serum antibody levels. Ad5-FMDV3CMUT, which is unable to produce FMDV capsid structures, did not elicit FMDV-neutralizing antibodies or protect against FMD. Single inoculation with Ad5-FMDV3CWT generated FMDV-specific neutralizing antibodies, and reduced clinical signs in challenged swine, but failed to completely protect the majority of swine from FMD. Swine which received a primary vaccination with Ad5-FMDV3CWT followed by the boost at 4 weeks generated high levels of FMDV-neutralizing antibodies resulting in complete protection of five of the six swine and limited disease in the remaining animal. Increased efficacy of the two-dose regimen was associated with heightened levels of FMDV-specific IgG1 and IgG2 antibodies.

Adenoviruses, Human↗

PubMed2001

Sequence analysis of recent Indian isolates of foot-and-mouth disease virus serotypes O, A and Asia 1 from clinical materials.

Partial nucleotide sequences of 1D gene of 38 isolates of foot-and-mouth disease virus (FMDV) of serotypes O, A and Asia 1 originating from various parts of India were determined. Field materials were subjected straight to RNA extraction, reverse transcription - PCR (RT-PCR) and sequencing. Also 3 FMDV vaccine strains, IND R2/75 (serotype O), IND 63/72 (serotype Asia 1) and IND 17/77 (serotype A) were included in the analysis. The seqences were compared mutually as well as with available corresponding sequences of other FMDV isolates, and their phylogenetic relationships were calculated. The deduced amino acid sequences showed that the serotype O isolates were relatively conserved as compared to serotype Asia 1 or A isolates from India. In phylogenetic analysis, the serotype O viruses clustered in two genotypes, one including the European vaccine strain (O1/K) and the other represented by the isolates from Bangladesh, India, Nepal and Turkey. The serotype Asia 1 viruses clustered in two groups of single genotype where the prototype strain from Pakistan (PAK 1/54) formed one group and the other was formed by the isolates from Bangladesh, Bhutan, India, Israel and Nepal. In serotype A viruses three well-differentiated genotypes were observed. The isolates from Azerbaijan, Bangladesh, Malaysia and India formed the first genotype. The second genotype was formed by isolates from Iran, Saudi Arabia and Turkey, while two recent Iranian isolates represented the third genotype. In India, the prevalence of at least one genotype could be identified in each serotype. This evolutionary clustering of isolates from the neighbor countries is not surprising, since these countries share border with India. The genetic relatedness between sequences of isolates from India and those from distant places is indicative of spread of the virus between the countries. Of importance is the fact that clinical materials proved useful for rapid generation of sequences and subsequent studying of molecular epidemiology of the disease.

Amino Acid Sequence↗

PubMed2000

Genetic analysis of foot-and-mouth disease virus type O isolates responsible for field outbreaks in India between 1993 and 1999.

Partial nucleotide sequence at the 3' end of ID (VP1-encoding) gene of 90 foot-and-mouth disease virus type O isolates recovered from field outbreaks in India between 1993-9 were determined. The sequences were compared with each other and reference viruses. The published sequences of 15 type O isolates recovered from different parts of Asia and one isolate (O1BFS) from Europe and one from Egypt (O1/Sharquia/Egypt/72) were also included in the analysis for comparison. On the basis of phylogenetic analysis the viruses could be grouped into four distinct genotypes (genotypes I-IV). All 90 isolates from India were genotype-I, as were the reference isolates from Bangladesh, China, Egypt, Iran, Saudi Arabia, Syria and Turkey. Genotype-I isolates were further subdivided into 16 sub-genotypes. The Indian isolates were found to be extremely heterogeneous in nature and clustered into 12 different genetic groups. In genotype-I, the nucleotide sequence difference seen between the isolates was 0-11.6%, while among the Indian isolates it is 0-8.8%. Viruses of similar genetic groups are circulating in India, Bangladesh and countries of the Middle East. Genotype-II and -III are represented by isolates from Lebanon (O1/South Lebanon) and Europe (O1-BFS), respectively. Genotype-IV is formed by isolates from China, Hong Kong and Taiwan. The present study reveals the occurrence of viruses belonging to multiple genetic groups over a short period of time and persistence of single genetic group in the same geographical area over several years. This is consistent with the endemic nature of the disease in the country.

Animals↗

PubMed1993

Risk assessment on the importation of milk and milk products (excluding cheese) from countries not free from foot and mouth disease.

The authors discuss the risk assessment conducted by the Australian Quarantine and Inspection Service (AQIS) on the importation of milk and milk products (excluding cheese) from countries not free from foot and mouth disease (FMD). This assessment was undertaken in response to requests from countries wishing to export dairy products for sale on the Australian market. AQIS conducted a public consultation on the proposal, in line with Australian Government policy on transparency and accountability in the quarantine decision-making process. The authors examine the procedures involved in the investigation of the likely presence of FMD virus in milk of vaccinated and non-vaccinated cows, and of the heat treatment parameters effective in the inactivation of the virus. The data provide a useful aid in the assessment of the risk factors associated with the importation of milk and milk products, and in the development of quarantine conditions for importation.

Animals↗

PubMed2002

The dynamics and impact of foot and mouth disease in smallholder farming systems in South-East Asia: a case study in Laos.

There is a general lack of data on the different patterns of dynamics and impact of foot and mouth disease (FMD) in South-East Asia and the impact the disease has on different sectors, in particular the smallholder sector in which livestock play such an important role. A pilot study was conducted of a recent outbreak of FMD that swept across the southern part of Laos during the second half of 1999. The main objectives of the study were to investigate the possible routes of transmission of the disease and the impact of FMD on the predominantly smallholder rice/livestock production system of Savannakhet Province. The study was performed by group interviews of farmers in ten villages, located in five districts across the width of the Province, and of district and provincial veterinary officials. Results suggested that the infection had probably been introduced from the eastern border and had spread rapidly west, along a principal trading route of pigs, cattle and buffalo. In the process, many villages adjacent to this trading route became infected and the disease spread rapidly within infected villages. The disease had a significant impact on the agricultural system, but the impact would have been much greater had the epidemic occurred during the season of paddy field preparation. Mortality was observed in young buffalo, cattle and pigs, and long periods of morbidity were observed in buffalo, often requiring extended treatment. The sale of livestock for cash was severely restricted, creating additional repercussions on that sector. It was concluded that the most appropriate approach to FMD control would be to prevent infected animals from entering the principal trading routes for pigs, cattle and buffalo. This will require the involvement of all the stakeholders of the livestock industry, including traders and veterinary authorities. A further tactic to be considered would be to protect livestock systems adjacent to these trading routes by vaccination. An economic study of the market incentives of both traders and smallholders is recommended and this approach is advocated in other parts of South-East Asia where livestock trading routes present the major risk of FMD outbreaks.

Animal Husbandry↗

PubMed1997

A risk-assessment model for foot and mouth disease (FMD) virus introduction through deboned beef importation.

We present a risk-assessment model to assess the risk of introduction of foot and mouth disease (FMD) virus associated with deboned beef importation. The model was developed in accordance with the risk-reduction procedures proposed by the European Community for meat importation. The risk reduction procedures include farm-level inspection, ante-mortem inspection, post-mortem inspection, chilling and deboning. The risk assessment was based on the prevalence of FMD-infected cattle in herds as well as the prevalence of infected herds in the exporting country. Computer simulations were carried out to evaluate the probability of FMD virus introduction by importing 100 tons of deboned beef in relation to FMD prevalence, number of cattle selected from each herd, and sample sizes in ante-mortem and post-mortem inspections. The effects of the risk-reduction procedures on the probability of FMD virus introduction were examined.

Animals↗

PubMed1998

The possible use of native foot-and-mouth disease non-structural protein 3A in a serological screening test.

ELISA's for antibodies to non-structural proteins of foot-and-mouth disease developed to date use recombinant proteins as antigens. To compare the antibody response to recombinant antigen and native antigen we developed an antigen capture ELISA for foot-and-mouth protein 3A. The concentration of 3A protein in virus cultures was significantly higher in the cell debris than in the supernatant, which made it possible to use proteins directly eluted from cells separated from virus culture using Filteraid. The antigen was trapped between one monoclonal antibody coated to the plate, and a second monoclonal antibody conjugated with horseradish peroxidase. The reaction of the second (conjugated) monoclonal antibody could be blocked by several post-infection sera. Further research has to be performed to determine whether or not this method can result in a reproducible serological test.

Animals↗

PubMed2005

[Detection of enterovirus 71 and coxsackievirus A16 from children with hand, foot and mouth disease in Shanghai, 2002].

OBJECTIVE: It was noticed that coxsackievirus A16 (CA16) and enterovirus 71 (EV71) were two major etiological agents of hand, foot and mouth disease (HFMD) in children. Recently there were several large outbreaks of HFMD in the Asia-Pacific region, and there was a propensity to cause severe complications or death in children under 5 years of age. The severe forms were associated with EV71 infection. Although epidemics of HFMD have been reported in the mainland of China, few reports about EV71 as the pathogen of HFMD epidemics are available. The present study was conducted to investigate the causal agent of an HFMD epidemic in children in Shanghai from April to June of 2002. METHODS: Totally 102 specimens (including vesicle fluid, stool and throat swabs) were collected from 72 patients with HFMD. The specimens were inoculated into Vero and/or RD cells. At first all the isolates were respectively neutralized by the RIVM pools of enterovirus antiserum, the type-specific antisera to EV71 or to CA16. Secondly all untyped isolates were tested by RT-PCR assay with two specific primer pairs for VP1 genes of EV71 and CA16 respectively. The EV71 and CA16 were identified depending on the size of PCR products. Sequence analyses of VP1 genes of 9 virus strains were performed by the laboratory of China CDC. RESULTS: Viruses were isolated from 91 specimens from 67 patients. Serotyping by neutralization failed for all the isolates. But the RT-PCR results indicated that the viruses isolated from 78 specimens from 58 patients were identified as positive for CA16 and the isolates from 13 specimens from 9 patients were identified as positive for EV71, the ratio between CA16 and EV71 was 6.4:1. The results of sequence analyses were consistent with those of PCR assay. Two EV71 strains isolated in this study belonged to a new lineage (C4) within genogroup C. One patient with EV71-associated HFMD had a complication of encephalitis with convulsion, shock, coma and dyspnea. CONCLUSION: CA16 and EV71 were the primary causes of HFMD during the epidemic. It was the first report of EV71-associated severe encephalitis occurred in patients with HFMD in Shanghai.

Animals↗

PubMed1975

The evaluation of hypersensitivity tests in cattle after foot-and-mouth disease vaccination.

The response to passive cutaneous anaphylaxis, dermal hypersensitivity and intravenous provocation tests has been compared in 30, 40, 31 and 24 cattle injected with foot-and-mouth disease vaccine 0, 1, 2 and 3 times respectively, using vaccine components and other substances as test materials. Reaginic antibodies demonstrated by passive cutaneous anaphylaxis in goats, were directed against BHK 21 cell extracts (20), hydroxypropylmethylcellulose (3) and an unidentified vaccine component (3), and distributed in 0, 5, 19 and 75 per cent of the cattle vaccinated 0, 1, 2 and 3 times. None of the animals showed clinical signs of allergy after vaccination. When BHK 21 cell extract was injected intradermally a significant correlation was noted between the development of large weals and the presence of reagins although the size of the weals was not correlated with the reagin titres. In the case of hydroxypropylmethylcellulose a similar trend was evident. The majority of cattle with large dermal weals possessed reagins but the number of reactions was too small for statistical evaluation. Dermal reactions to sodium penicillin, sodium carboxymethylcellulose, saponin and whole vaccine occurred in both unvaccinated and vaccinated cattle but BHK 21 cell lysate and normal bovine serum provoked weals which increased in frequency according to the number of vaccinations experienced. Intravenous hydroxypropylmethylcellulose elicited a response in all the animals previously injected with certain batches of vaccine but cell extract intravenously produced a clinical response in half the tested animals which was uncorrelated with the results of the passive cutaneous anaphylaxis or dermal hypersensitivity tests.

1-Propanol↗

PubMed2002

Economic costs of the foot and mouth disease outbreak in the United Kingdom in 2001.

The authors present estimates of the economic costs to agriculture and industries affected by tourism of the outbreak of foot and mouth disease (FMD) in the United Kingdom (UK) in 2001. The losses to agriculture and the food chain amount to about Pound Sterling3.1 billion. The majority of the costs to agriculture have been met by the Government through compensation for slaughter and disposal as well as clean-up costs. Nonetheless, agricultural producers will have suffered losses, estimated at Pound Sterling355 million, which represents about 20% of the estimated total income from farming in 2001. Based on data from surveys of tourism, businesses directly affected by tourist expenditure are estimated to have lost a similar total amount (between Pound Sterling2.7 and Pound Sterling3.2 billion) as a result of reduced numbers of people visiting the countryside. The industries which supply agriculture, the food industries and tourist-related businesses will also have suffered losses. However, the overall costs to the UK economy are substantially less than the sum of these components, as much of the expenditure by tourists was not lost, but merely displaced to other sectors of the economy. Overall, the net effect of FMD is estimated to have reduced the gross domestic product in the UK by less than 0.2% in 2001.

Agriculture↗

PubMed1998

Deaths among children during an outbreak of hand, foot, and mouth disease--Taiwan, Republic of China, April-July 1998.

During April-July 1998, the Ministry of Health in Taiwan received approximately 90,000 reports of hand, foot, and mouth disease (HFMD) among young children based on passive surveillance from sentinel physicians. Approximately 320 children have been hospitalized with HFMD associated with suspected meningitis, encephalitis, or acute flaccid paralysis (AFP), and at least 55 have died. This report describes the clinical course of two fatal cases and presents summary findings from an ongoing clinical, epidemiologic, and laboratory investigation of the 55 deaths.

Child↗

PubMed2006

A serological survey for antibodies to foot-and-mouth disease virus in indigenous Tswana goats and sheep in Kasane, Maun and Shakawe districts in northwestern Botswana.

A serological survey was conducted in apparently healthy, unvaccinated indigenous Tswana goats and sheep in Kasane, Maun and Shakawe districts in northwestern Botswana in order to determine in these animals, the levels of exposure to the South African Territories (SAT) serotypes: SAT 1, SAT 2 and SAT 3 of foot-and-mouth disease virus (FMDV). A total of 250, 142 and 134 goat sera originating respectively from Kasane, Maun and Shakawe districts were tested for FMDV antibodies against the three SAT serotypes by the liquid phase blocking enzyme-linked immunosorbent assay and 26 of 250 (10.4%), 5 of 142 (3.5%) and 18 of 134 (13.4%) were positive either to SAT 1 or SAT 3, or to both serotypes. None of the goats' sera was positive to SAT 2 serotype. All sheep sera (n = 9) tested negative against all three serotypes of the virus. The findings are discussed in relation to results of other serological surveys carried out elsewhere.

Animals↗

PubMed2000

Antigenic variation among foot-and-mouth disease virus type A field isolates of 1997-1999 from Iran.

The sequences of the antigenically relevant capsid proteins VP1-3 of 10 isolates obtained during an epizootic of serotype A foot-and-mouth disease virus in Iran, and collected within two and a half years, were found to be highly similar. However, each isolate differed by at least one amino acid from all others. This prompted us to analyze the immunological reactivity of the isolates. To this end, monoclonal antibodies (mAbs) against one isolate were generated and characterized with regard to neutralizing activity and reactivity with trypsinized virus. These mAbs as well as others raised against A22 virus were used for antigen profiling. This distinguished four antigenic conditions among the isolates and 16 reactivities among the mAbs. These findings, together with the observed sequence differences indicated the location of several epitopes. Many mAbs recognized the minor antigenic sites on VP2 and 3 and some the major site, the GH-loop of VP1. One epitope was composed of residues of the capsid proteins VP1 and 2.

Amino Acid Sequence↗