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PubMed2004

Differentiating infection from vaccination in foot-and-mouth-disease: evaluation of an ELISA based on recombinant 3ABC.

Recent devastating outbreaks of foot-and-mouth disease (FMD) in Europe have reopened the discussion about the adequacy of the non-vaccination strategy implemented by the EU in 1991. Here we describe the evaluation of a new commercially available test kit for the discrimination between vaccination and infection. The test is based on the detection of antibodies against the recombinant non-structural (NS) protein 3ABC. In contrast to immunization with vaccines free of 3ABC, these antibodies are elicited as a consequence of infection. Testing more than 3600 negative sera from several countries revealed a specificity of > 99% for bovine, ovine, and porcine samples. Antibodies specific for 3ABC can be detected as soon as 10 days post-infection. As compared with the occurrence of antibodies against structural proteins of FMDV, anti-3ABC antibodies can be detected 5-10 days later, depending on the species. No anti-3ABC antibodies were detected in sera from vaccination experiments or in field sera from vaccinated animals. However, anti-3ABC antibodies can be detected in vaccinated animals upon challenge. These results provide evidence that this test can facilitate the use of vaccines in new strategies against FMD.

Animals↗
PubMed1995

Rapid detection and characterization of foot-and-mouth disease virus by restriction enzyme and nucleotide sequence analysis of PCR products.

Reverse transcription coupled with PCR was used for the detection of foot-and-mouth disease virus serotypes A, C, and O in organ extracts from experimentally infected cattle. Primers were selected from conserved sequences flanking the genome region coding for the major antigenic site of the capsid located in the C-terminal part of viral protein 1 (VP1). Because this region of the capsid is highly variable its coding sequence is considered to be the most appropriate for the characterization of virus isolates and, therefore, for the determination of the epidemiological relationships between viruses of the same serotype. For differentiation between serotypes and for detailed characterization of individual virus isolates restriction enzyme cleavage and nucleotide sequence analysis of the respective PCR products were carried out. In order to minimize the time required for sample preparation from clinical material, viral RNA was released from particles by heating the sample for 5 min at 90 degrees C. Finally, an air thermocycler was used, which allows performance of a PCR of 30 cycles in approximately 20 min. The results show that reverse transcription PCR followed by restriction enzyme analysis and/or nucleotide sequence analysis of the PCR products is useful for the rapid detection and differentiation of foot-and-mouth disease virus.

Animals↗
PubMedDate not supplied

Residual foot-and-mouth disease virus antibodies in French cattle and sheep six years after the vaccination ban.

A serological survey was carried out on French cattle to establish a reference pattern of residual vaccine antibodies and non-specific reactions against the foot-and-mouth disease virus 6 years after the ban on vaccination and in the absence of any foot-and-mouth disease outbreak. Most of the multi-vaccinated cattle still displayed high titres of antibodies and up to 50% of those which had received a single injection still had antibodies. Non-specific reactors were also recorded among animals born during and after 1991. Most of them displayed low titres close to the threshold. Sheep were also tested and, as for cattle, 4.6% of non-specific reactors were recorded, with titres close to the threshold for two-thirds of them. As part of these animals have been resampled and retested, sera revealed negative confirming that these animals are true non-specific reactors. Serological testing as a mean of FMD control should take these facts into account.

Animals↗
PubMed2006

Molecular characterization of foot-and-mouth disease virus in Hong Kong during 2001-2002.

Most of the molecular epidemiological studies of foot-and-mouth disease virus (FMDV) are based on comparison of VP1 gene sequence. In this report, The nucleotide sequences of the VP1 coding region of FMDV type O strains O/HKN/3/01, O/HKN/5/01, O/HKN/12/01, O/HKN/7/02 and O/HKN/10/02, isolated from the disease outbreak that occurred in Hong Kong Special Administrative Region (Hong Kong SAR) of China during 2001-2002, were determined and compared with the sequences of other FMDVs. The results revealed that the VP1 gene of the five isolates had the same nucleotide (nt) sequences (639 nt), coding for 213 amino acids, and no changes were found either at the critical amino acid sites 144 (Val), 148 (Leu), 154 (Lys) and 208 (Pro) within the VP1 protein epitope (amino acids 140-160, 200-213), or in the amino acids 145-147 comprising the arginine-glycine-aspartic acid (RGD) sequence that is involved in the adsorption of virus to host cell. Analysis of the VP1 gene nucleotide sequence revealed that the five isolates examined were most closely related to FMDVs found in Hong Kong from 1991 to 1999 and Taiwan in 1997. Furthermore, although the critical amino acids on the antigen epitope of the prevalent Hong Kong isolates and the serotype O vaccine strain, O1/Manisa/Turkey/69, showed relative conservativeness, they were distantly related genetically, which showed that there existed variation between the prevalent Hong Kong FMDV strains and the vaccine strain.

Amino Acid Sequence↗
PubMed2005

Vaccination against foot and mouth disease reduces virus transmission in groups of calves.

The aim of vaccination during an epidemic of foot and mouth disease (FMD) is not to induce clinical protection, but to reduce virus transmission. Since no quantitative data were available on the effectiveness of vaccination in cattle, we investigated whether a single vaccination against FMD could reduce virus transmission in groups of calves by estimating the reproduction ratio R, i.e. the average number of secondary cases caused by one infectious animal in a susceptible population. We performed two experiments with six groups of either four vaccinated or four non-vaccinated calves each. Vaccination was carried out with O(1) Manisa vaccine. Two weeks after vaccination, two calves per group were inoculated intra-nasally with FMDV field isolate O/NET 2001. The two other calves were contact-exposed to the inoculated calves. Contact infections were observed by clinical inspection, virus isolation and RT-PCR on heparinised blood, oro-pharyngeal fluid and probang samples and antibody response to non-structural proteins. In all six non-vaccinated groups, transmission to contact-exposed calves was recorded; in the vaccinated groups, virus transmission was observed to one contact-exposed calf. In the non-vaccinated groups R(c) was 2.52 and significantly above 1, whereas in the vaccinated groups R(v)=0.18 and significantly below 1, indicating that vaccination may successfully be applied as additional intervention tool to reduce virus transmission in a future epidemic of FMD.

Animals↗
PubMed2003

Detection of carrier cattle and sheep persistently infected with foot-and-mouth disease virus by a rapid real-time RT-PCR assay.

The detection of foot-and-mouth disease virus (FMDV) in persistently infected carriers among exposed ruminants is of great importance in disease control. For this purpose, a real time, fluorogenic reverse transcription polymerase chain reaction (real-time RT-PCR) assay was evaluated for the identification of FMDV carrier animals. The results indicate that this real time RT-PCR assay may be suitable for detection of FMDV carrier animals.

Animals↗
PubMed2003

Comparisons of the complete genomes of Asian, African and European isolates of a recent foot-and-mouth disease virus type O pandemic strain (PanAsia).

During the last 12 years, a strain of foot-and-mouth disease (FMD) virus serotype O, named PanAsia, has spread from India throughout Southern Asia and the Middle East. During 2000, this strain caused outbreaks in the Republic of Korea, Japan, Russia (Primorsky Territory), Mongolia and South Africa (KwaZulu-Natal Province), areas which last experienced FMD outbreaks in 1934, 1908, 1964, 1974 and 1957, respectively. In February 2001, the PanAsia strain spread to the United Kingdom where, in just over 7 months, it caused outbreaks on 2030 farms. From the UK, it quickly spread to the Republic of Ireland, France and the Netherlands. Previous studies that utilized RT-PCR to sequence the VP1-coding region of the RNA genomes of approximately 30 PanAsia isolates demonstrated that the UK virus was most closely related to the virus from South Africa (99.7 % nucleotide identity). To determine if there was an obvious genetic reason for the apparently high level of fitness of this new strain, and to further analyse the relationships between the PanAsia viruses and other FMDVs, complete genomes were amplified using long-range PCR techniques and the PCR products were sequenced, revealing the sequences for the entire genomes of five PanAsia isolates as well as an animal-passaged derivative of one of them. These genomes were compared to two other PanAsia genomes. These analyses revealed that all portions of the genomes of these isolates are highly conserved and provided confirmation of the close relationship between the viruses responsible for the South Africa and UK outbreaks, but failed to identify any genetic characteristic that could account for the unprecedented spread of this strain.

3' Untranslated Regions↗
PubMed2002

A review of the status of foot and mouth disease in South-East Asia and approaches to control and eradication.

The author presents reports of foot and mouth disease (FMD) submitted between 1996 and 2001 to the Office International des Epizooties (OIE: World organisation for animal health) Sub-Commission for FMD in South-East Asia. Of the ten countries in South-East Asia, FMD is endemic in seven (Cambodia, Laos, Malaysia, Myanmar, the Philippines, Thailand and Vietnam) and three are free of the disease (Brunei, Indonesia and Singapore). Part of the Philippines is also recognised internationally as being free of FMD. From 1996 to 2001, serotype O viruses caused outbreaks in all seven of the endemically infected countries. On the mainland, three different type O lineages have been recorded, namely: the South-East Asian (SEA) topotype, the pig-adapted or Cathay topotype and the pan-Asian topotype. Prior to 1999, one group of SEA topotype viruses occurred in the eastern part of the region and another group in the western part. However, in 1999, the pan-Asian lineage was introduced to the region and has become widespread. The Cathay topotype was reported from Vietnam in 1997 and is the only FMD virus currently endemic in the Philippines. Type Asia 1 has never been reported from the Philippines but was reported from all countries on the mainland except Vietnam between 1996 and 2001. Type A virus has not been reported from east of the Mekong River in the past six years and seems to be mainly confined to Thailand with occasional spillover into Malaysia. The distribution and movement of FMD viruses in the region is a reflection of the trade-driven movement of livestock. There is great disparity across the region in the strength and resources of the animal health services and this has a direct impact on FMD control. Regulatory environments are not well developed and enforcement of regulations can be ineffectual. The management of animal movement is quite variable across the region and much market-driven transboundary movement of livestock is unregulated. Formal quarantine approaches are generally not supported by traders or are not available. Vaccination is not used widely as a control tool because of the expense. However, it is applied by the Veterinary Services in Malaysia to control incursions of the disease and there is a mass vaccination programme for large ruminants in Thailand where the Government produces and distributes vaccine. Vaccination is also used by the commercial pig sector, particularly in the Philippines and Thailand.

Animals↗
PubMed2004

No foot-and-mouth disease virus transmission between individually housed calves.

The foot-and-mouth disease outbreak in The Netherlands in 2001 most likely started on a mixed veal-calf/dairy-goat farm. The outbreak among the 74 calves on this farm appeared to be limited to four animals, and no clinical signs of FMD were reported. Also on a second veal-calf farm minor clinical signs and limited virus transmission were observed. Since FMD is known to be a very contagious disease, and can cause severe lesions, these observations were disputed. Therefore, we carried out two experiments to determine whether the Dutch FMD virus isolate from 2001 does spread among individually housed calves with limited contacts, either indirect (experiment 1) or direct (experiment 2). In experiment 1, four pairs of calves were housed in an individual box at 1m distance from each other. In experiment 2, two groups of three calves were housed in individual boxes, directly bordering each other. We infected one animal per pair in experiment 1, and the calf in the middle in experiment 2. We recorded clinical signs, virus shedding in saliva and the development of antibodies. In addition, we determined whether the virus was transmitted from the inoculated calves to the neighbour(s). All inoculated calves showed mild signs of FMD--fever, and some vesicles on hooves and/or in the mouth--but only one calf showed signs that were visible without physical examination. All inoculated calves shed virus in the saliva and developed neutralising antibodies. None of the contact animals seroconverted, indicating that virus transmission did not occur. These experiments showed that no virus transmission among individual housed calves can occur. This finding supports the hypothesis of the route of virus introduction to The Netherlands in 2001 and show that the observations on the two veal-calf farms were not impossible.

Animals↗
PubMed2002

Antigenic sites of foot-and-mouth disease virus (FMDV): an analysis of the specificities of anti-FMDV antibodies after vaccination of naturally susceptible host species.

Of the known neutralizing antigenic sites of foot-and-mouth disease virus (FMDV), site 1 or A, formed in part by the G-H loop of VP1, has historically been considered immunodominant because of evidence implicating its importance in the induction of a protective immune response. However, no systematic study has been done to determine the relative importance of the various specificities of antibodies against the known neutralizing antigenic sites of FMDV in the polyclonal immune response of a natural host after vaccination. In this report, we have adopted a monoclonal antibody-based competition ELISA and used antibodies specific to sites 1, 2 and 3 to provide some insight into this issue. Following vaccination of the three main target species, cattle, pigs and sheep, with an O1 serotype strain, results indicate that none of these three antigenic sites can be considered immunodominant in a polyclonal serum. Interestingly, pigs did not respond to epitopes on the carboxy terminus end of VP1 as efficiently as the ruminant species. In addition to the known sites, other as yet undefined sites might also be important in the induction of a protective immune response. Possible implications for the design of new vaccine strategies for foot-and-mouth disease are discussed.

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↗
PubMed2000

Characteristics of foot and mouth disease virus in Taiwan.

Since March 1997 two strains of foot and mouth disease (FMD) virus have found their way into Taiwan, causing severe outbreaks in pigs and in Chinese yellow cattle. Outbreaks occurred in March 1997 were caused by a pig-adapted virus strain (O/Taiwan/97) which did not infect other species of cloven-hoofed animals by natural route. The epidemic spread over the whole region of Taiwan within two months and the aftermath was 6,147 pig farms infected and 3,850,746 pigs destroyed. In June 1999, the second strain of FMD virus (O/Taiwan/99) was isolated from the Chinese yellow cattle in the Kinmen Prefecture and in the western part of Taiwan. By the end of 1999, Chinese yellow cattle were the only species infected and those infected cattle did not develop pathological lesions. Seroconversions of serum neutralization antibody and on non-structural protein (NSP) antibodies were the best indicators for infection in non-vaccinated herds. The infected animals, however, excreted infectious levels of virus to infect new hosts. Based on the detection of the specific antibody to FMD virus, and virus isolation from oesophageal-pharyngeal (OP) fluid samples, ten herds of Chinese yellow cattle located in Kinmen and Taiwan were declared to have been infected. During the period of January to March 2000, however, five outbreaks caused by FMD virus similar to the O/Taiwan/99 virus occurred in four prefectures of Taiwan. The infected species included goats, Chinese yellow cattle and dairy cattle. Those outbreaks have caused high mortality in goat kids under two weeks old and also developed typical clinical signs of infection in dairy cattle.

Animals↗
PubMed1990

Protection of cattle and swine against foot-and-mouth disease, using biosynthetic peptide vaccines.

A single dose of foot-and-mouth disease (FMD) virus protein 1 (VP1) peptide, expressed in Escherichia coli as a fusion protein with 190 amino acids (AA) of the LE' protein of the tryptophan operon of E coli, elicited an immune response in steers sufficient to withstand the challenge of exposure to animals with acute FMD. The 58-micrograms dose of viral peptide, composed of a segment of the VP1 from the A12 strain (A12) of FMD virus (FMDV; A12-32dimer) in a tandem repeat configuration of AA137 through 168 and emulsified with oil adjuvant, elicited a serologic response in cattle equivalent to that obtained using conventional whole virus vaccines. Two groups of swine were vaccinated, 1 with the A12-32dimer as used in cattle and 1 with AA131 through 157 from VP1 of the A24 strain (A24) of FMDV (A24-peptide), expressed in the same system as A12-32dimer, but as a single copy per molecule. In swine, the 58-micrograms dose of the A12-32dimer repeated at 28 days was an effective immunogen; all swine were protected against A12 and, in addition, the vaccine protected 50% of the swine against A24. The 29-micrograms dose of A24-peptide, administered according to the same schedule, elicited protection against A24 in 50% of the vaccinates and, in addition, protected 25% of those vaccinates against A12. The serologic response elicited by A12-32dimer against A24 virus was considerably greater than the response elicited by A24-peptide against A12 virus. The evidence of multiple immunogenic epitopes between AA131 and AA168 was evaluated.

Amino Acid Sequence↗
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↗
PubMed2005

Simulating the spatial dynamics of foot and mouth disease outbreaks in feral pigs and livestock in Queensland, Australia, using a susceptible-infected-recovered cellular automata model.

We describe an approach to modelling the spatio-temporal spread of foot and mouth disease through feral animal and unfenced livestock populations. We used a susceptible-infected-recovered model, implemented in a cellular automata framework, to assess the spread of FMD across two regions of Queensland, Australia. Following a sensitivity analysis on the infectious states, scenario analyses were conducted using feral pigs only as the susceptible population, and then with the addition of livestock, and initiated in the wet season and in the dry season. The results indicate that, depending on the season the outbreak is initiated, and without the implementation of control measures, an outbreak of Foot and Mouth Disease around Winton could continue unchecked, while an outbreak around Cape York may die out naturally. The approach explicitly incorporates the spatial relationships between the populations through which the disease spreads and provides a framework by which the spread of disease outbreaks can be explored through varying the model parameters. It highlights the emergence and importance of spatio-temporal patterns, something that previous modelling of FMD in feral animal and unfenced livestock populations has lacked.

Animals↗
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↗
PubMed2004

Vaccination: foot-and-mouth disease experience in South America.

Vaccination against foot-and-mouth disease (FMD) constitutes an important component of the policy for its control and eradication in South America. Considering that immunization may not impair subclinical infection, it became advisable to ally to vaccination campaigns a surveillance instrument to monitor silent viral circulation. Novel approaches for the evaluation of antibodies to FMD non-capsid proteins (NCPs), developed and validated at PANAFTOSA proved valuable for assessing viral circulation in immunized populations. The extensive and coordinated application in South America of vaccination together with this serosurvey tool indicated the effectiveness of systematic vaccination to prevent FMD spread and to restrain silent viral circulation intra- and inter- herds, and gave input to an old controversy related to the real epidemiological significance, if any, of carrier animals under the vaccination conditions in South America. The fitness of NCP tests to assess viral circulation in a population supported the incorporation into the OIE code of the "free of FMD with vaccination" category as a step prior to the recognition of the "free of FMD without vaccination" category. Likewise it released the path to allow animals, vaccinated for protective purposes during emergencies, to live for the term of their productive lives.

Animals↗