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PubMed1973

Transmission of the virus of foot and mouth disease between animals and man.

The virus of foot and mouth disease causes severe epizootics in animals and infrequently evokes painful, but transient, clinical signs in man. Adults in certain occupational groups and young children are particularly exposed to risk. Infected persons may disseminate virus for up to about 14 days. The virus can be transmitted from animals to animals, from animals to man, from man to animals and, probably, from man to man. Evidence for transfer of the disease between human and animal populations is reviewed in detail and modern methods of diagnosis are described. Predisposing factors play an important role in the development of overt foot and mouth disease in man. Subclinical infection occurs. The possibility of aerial transfer of the virus between man and domestic livestock constitutes a hazard, especially to the latter. Attention is directed to the need for sophisticated diagnostic techniques, to requirements for adequate precautions in the handling and disposal of affected animals, and to hygienic measures for disease control.

Animals↗

PubMed1982

Immunosuppression in bovine trypanosomiasis: response of cattle infected with Trypanosoma congolense to foot-and-mouth disease vaccination and subsequent live virus challenge.

The primary and secondary antibody responses to foot-and-mouth disease virus vaccine were examined in cattle infected with Trypanosoma congolense and the response of some of these animals to live foot-and-mouth disease virus challenge was assessed. Infected groups of cattle had rather lower antibody responses than uninfected control cattle after primary vaccination but the antibody titres were not significantly depressed until after secondary vaccination. These levels remained depressed for the duration of the experiment, ie, 183 days. Trypanocidal therapy with diminazene aceturate of infected cattle at the time of vaccination did not significantly improve the antibody response to primary vaccination. Their subsequent response to live virus challenge was somewhat equivocal in that the number of animals protected was not significantly different in comparison to the untreated infected and uninfected controls. It was concluded that trypanosome-infected cattle do not produce optimal responses to foot-and-mouth disease vaccination. Nevertheless, the antibody titres are generally above those considered adequate to confer 95 per cent protection against needle challenge.

Animals↗

PubMed2003

Rapid serological profiling by enzyme-linked immunosorbent assay and its use as an epidemiological indicator of foot-and-mouth disease viral activity.

Frequency distribution of reactivity levels of foot-and-mouth disease infection-specific antibodies in livestock populations was analysed. Specific antibody responses against non-capsid polyprotein 3ABC were assessed through a highly sensitive indirect enzyme-linked immonosorbent assay (I-ELISA 3ABC). A graphic display of data was designed based on three negative and three positive categories to illustrate reactivity patterns. The resulting patterns were correlated to the epidemiological status. On this basis, results of over 100,000 sera derived from cattle populations in regions with various well-documented epidemiological situations were compiled and are exemplified in this paper.Distinct distributions of antibody reactivity patterns reflecting the various epidemiological situations were attained. Whereas non-affected areas presented a rather homogenous negative pattern with very limited test-positive reactions, affected regions revealed quite heterogeneous profiles, including positive and negative categories, with distributions that varied according to the region. The use of graphic prints encompassing I-ELISA 3ABC antibody profile responses constituted an adequate epidemiological indicator of the risk of foot-and-mouth disease viral activity, providing immediate visualization for a rapid inference of the epidemiological situation of a region. Moreover, such profiles allowed for convenient follow-up of infection after a focus as a function of time and geographical spread.

Animals↗

PubMed2005

Comparative studies of the capsid precursor polypeptide P1 and the capsid protein VP1 cDNA vectors for DNA vaccination against foot-and-mouth disease virus.

BACKGROUND: Foot-and-mouth disease virus (FMDV) causes a severe livestock disease, and the virus is an interesting target for virology and vaccine studies. MATERIALS AND METHODS: Here we evaluated comparatively three different viral antigen-encoding DNA sequences, delivered via two physical means (i.e., gene gun delivery into skin and electroporation delivery into muscle), for naked DNA-mediated vaccination in a mouse system. RESULTS: Both methods gave similar results, demonstrating commonality of the observed DNA vaccine effects. Immunization with a cDNA vector expressing the major viral antigen (VP1) alone routinely failed to induce the production of anti-VP1 or neutralizing antibodies in test mice. As a second approach, the plasmid L-VP1 that produces a transgenic membrane-anchored VP1 protein elicited a strong antibody response, but all test mice failed in the FMDV challenge experiment. In contrast, for mice immunized with the viral capsid precursor protein (P1) cDNA expression vector, both neutralizing antibodies and 80-100% protection in test mice were detected. CONCLUSIONS: This strategy of using the whole capsid precursor protein P1 cDNA for vaccination, intentionally without the use of virus-specific protease or other encoding genes for safety reasons, may thus be employed as a relevant experimental system for induction or upgrading of effective neutralizing antibody response, and as a convenient surrogate test system for DNA vaccination studies of FMDV and presumably other viral diseases.

Animals↗

PubMed2002

Vaccination against foot-and-mouth disease: the implications for Canada.

Vaccination of susceptible animals against foot-and-mouth disease (FMD) is a well established strategy for helping to combat the disease. Traditionally, FMD vaccine has been used to control a disease incursion in countries where the disease has been endemic rather than in countries considered free of the disease. In 2001, the use of vaccine was considered but not implemented in the United Kingdom (1), whereas vaccine was used to help to control FMD in The Netherlands (2,3). Canadian contingency plans provide for the use of vaccine; Canada is a member of the North American Foot-and-Mouth Disease Vaccine Bank, which could supply vaccine if needed. This article explains why Canada might use FMD vaccine to combat an outbreak and the factors that are relevant to the disposal of vaccinated animals and their products. It concludes that vaccination is an important mechanism in Canada's preparedness for an outbreak of FMD and that products from vaccinated animals are safe for human consumption.

Animals↗

PubMedDate not supplied

Utility of automated real-time RT-PCR for the detection of foot-and-mouth disease virus excreted in milk.

Foot-and-mouth disease virus (FMDV) can be excreted in milk and thereby spread infection to susceptible animals in other holdings. The feasibility of using real-time reverse transcription polymerase chain reaction (rRT-PCR) as a diagnostic tool for detection of FMDV in milk was assessed by studying the excretion of virus from experimentally-infected cattle. Fore- and machine milk samples were collected over a 4-week period from two dairy cows infected with FMDV and from two in-contact cows held in the same pen. The whole, skim, cream and cellular debris components of the milks were tested by automated rRT-PCR and results compared to virus isolation (VI) in cell culture. The onset of clinical signs of FMD in all four cows correlated with viraemia, and the presence of FMDV in other clinical samples. rRT-PCR results matched closely with VI in detecting FMDV in all milk components and generally coincided with, but did not consistently precede, the onset of clinical signs. rRT-PCR detected FMDV in milk up to 23 days post inoculation which was longer than VI. Furthermore, the detection limit of FMDV in milk was greater by rRT-PCR than VI and, in contrast to VI, rRT-PCR detected virus genome following heat treatment that simulated pasteurisation. rRT-PCR was also able to detect FMDV in preservative-treated milk. In conclusion, this study showed that automated rRT-PCR is quicker and more sensitive than VI and can be used to detect FMDV in whole milk as well as milk fractions from infected animals.

Animals↗

PubMed2006

Production and characterization of two serotype independent monoclonal antibodies against foot-and-mouth disease virus.

Two foot-and-mouth disease virus (FMDV) monoclonal antibodies (mAbs) were produced from mice immunized with either FMDV serotype A, subunit (12S) or FMDV serotype O, whole virus (140S). Both mAbs (F1412SA and F21140SO) recognized all seven serotypes of FMDV in a double antibody sandwich (DAS) ELISA, suggesting that the binding epitopes of the two mAbs are conserved between serotypes. These mAbs are IgG1 isotype and contain kappa light chains. In order to define the mAb binding epitopes, the reactivity of these mAbs against trypsin-treated and denatured FMDV were examined using an indirect ELISA. The binding site of the mAb, F1412SA is trypsin sensitive and the epitope is linear. Both ELISA and Western blot results suggested that the polypeptide VP2 contributed to the immunodominant site. This mAb showed reactivity to VP2 peptide (DKKTEETTILEDRIL). The mAb, F21140SO, recognized an epitope which is trypsin resistant and discontinuous. This mAb binding to FMDV is dependent on conformational structures of intact viral (140S) or subunit (12S) particle, since it failed to recognize any viral protein in Western blot. This conformational and highly conserved epitope is the first identified epitope among all seven FMDV serotypes. Because the use of mAbs increases the specificity, accuracy and efficiency of diagnostic tests compared to polyclonal antisera, these two mAbs with different specificities are suitable for type-independent diagnosis of FMDV, such as DAS ELISA, or could be adapted to immuno-chromatographic or flow-through rapid test.

Amino Acid Sequence↗

PubMed1999

Clinical features and risk factors of pulmonary oedema after enterovirus-71-related hand, foot, and mouth disease.

BACKGROUND: In Taiwan, from April to July, 1998, an epidemic of hand, foot, and mouth disease associated with enterovirus 71 (EV71) occurred with fatal complications. We did a clinical study of EV71-related diseases in Taiwan. METHODS: We studied 154 children with virus-culture confirmed EV71 infection. Children were divided into three groups: 11 patients with pulmonary oedema; 38 patients with central nervous system (CNS) involvement and no pulmonary oedema; and 105 children without complications. We compared the clinical features, laboratory findings, risk factors, and outcome among these three groups. FINDINGS: Nine children with pulmonary oedema had hand, foot, and mouth disease, one had herpangina, and one had febrile illness with eight children with limb weakness and one with limb hypesthesia. All children had had sudden onset of tachycardia, tachypnoea, and cyanosis 1-3 days after onset of the disease. Nine of 11 children died within 12 h of intubation; one child was braindead within 15 h and died 17 days after intubation; one child was in deep coma and died 3 months later. In children with CNS complication and no pulmonary oedema, one child died of pneumonia after 4 months of ventilator support and four children had sequelae. All 105 children without complications recovered. There was a significant association between CNS involvement and pulmonary oedema (odds ratio 12.4 [95% CI 2.6-60.1], p=0.001). Risk factors for pulmonary oedema after CNS involvement were hyperglycaemia, leucocytosis, and limb weakness. Hyperglycaemia was the most significant prognostic factor for pulmonary oedema (odds ratio 21.5 [3-159], p=0.003). INTERPRETATION: EV71 can cause hand, foot, and mouth disease, CNS involvement with severe sequelae, and fatal pulmonary oedema. Hyperglycaemia is the most important prognostic factor.

Adolescent↗

PubMed2000

[Familial variability in the clinical expression of hand-foot-mouth disease].

Aim of the paper is to describe the variability of clinical symptoms in hand, foot and mouth disease, especially among patients belonging to the same family. In spring 1999, during an epidemic of hand, foot and mouth disease, nineteen cases were observed by the authors. In eight cases also some members of the family were affected. A great variability in the clinical expression of the disease, above all among the members of the same family were observed. No cases in children below twelve months or in elderly members of the family were found. Children below three years had more stressed general symptoms, but in no case hospitalization was necessary. Hand, foot and mouth disease does not always show vesicles and aphthae in the affected areas. Clinical expression can also be lacking, but in this case diagnosis can be made easy by the presence of an epidemic or of other cases in the same family.

Child, Preschool↗

PubMed2005

Evaluation of in vitro inhibitory potential of small interfering RNAs directed against various regions of foot-and-mouth disease virus genome.

India is endemic for foot-and-mouth disease and it continues to be a major threat to the livestock industry despite vaccination programmes. In the present study, the ability of specific small interfering (si)RNAs directed against different genomic regions of foot-and-mouth disease virus (FMDV) to inhibit virus replication in BHK-21 cells was examined. For preliminary evaluation of possible siRNA-mediated FMDV inhibition, a cocktail of several unique populations of 12-30bp siRNAs were successfully produced corresponding to three target regions located at structural (VP3-VP1), non-structural (2A-2C), and non-structural-untranslated (3D-3'UTR) region of serotype Asia1. Once the populations of siRNAs generated were found to reduce the virus titre significantly, two highly conserved 21bp siRNA duplexes were designed by analysing all FMDV sequence entries available in public-domain databases. In virus titration assay, more than 99% inhibition of virus yield for all the four serotypes (type Asia1, O, A, and C) could be demonstrated in cells transfected with each of the FMDV-specific siRNAs at 24h post-infection, compared to control cells transfected with scrambled siRNA. This was well supported by reduction in OD values in FMDV-specific sandwich ELISA. Although 100-fold reduction in virus titre with siRNA1 is substantial considering the transfection efficiency and fixed level of input siRNA, siRNA2 emerged to be a better choice as target where more than 300-fold reduction was observed and its inhibitory effect extended up to 48 h post-infection against all the serotypes. Interestingly, in the present study type A virus (IND 17/77) had a single mismatch at position 2 in the siRNA2 target region but it did not abrogate the inhibitory effect.

Animals↗

PubMed2004

Strategy for the control of foot-and-mouth disease in Southeast Asia (SEAFMD).

The OIE Southeast Asia Foot-and-Mouth Disease Campaign (SEAFMD) involves the coordinated control of foot-and-mouth disease by eight of the ASEAN countries. A long term vision for SEAFMD has been developed and the core element is a progressive zoning approach to the control and eradication of FMD in the region. This paper describes the current status of FMD in Southeast Asia and progress towards achievement of OIE free zone status for FMD in parts of the Philippines and Malaysia and the initiation of the Malaysia-Thailand-Myanmar (MTM) Peninsular Campaign for FMD Freedom. In mainland Southeast Asia, the progressive zoning approach involves several sub-regional groups working in parallel to oversee the epidemiological and economic studies required to determine the feasibility of the approach. Areas involved include the Lower Mekong Basin, Upper Mekong Basin, parts of Myanmar and the Red River Delta of Vietnam. The paper describes the current usage of vaccines for FMD in Southeast Asia and provides recommendations for their supply and use in the new regional initiatives.

Animals↗

PubMed1983

Identification of an exposed region of the immunogenic capsid polypeptide VP1 on foot-and-mouth disease virus.

Iodination of intact foot-and-mouth disease virus results in the selective labeling of VP1, substantiating its exposed location on the virion. A comparison of tryptic peptides revealed that a single tyrosine-containing peptide was labeled with iodine on intact or protease-cleaved virus. The labeled peptide from intact and protease-cleaved virus was characterized by molecular weight sizing and sequence analysis. Carboxypeptidase digestion of intact VP1, limited trypsin-cleaved VP1, and VP1 purified from bacterially contaminated tissue cultures yielded carboxyterminal residues of leucine, valine-arginine, and serine-alanine, respectively. The correlation of these findings with previous data on the amino acid sequence derived from nucleotide sequencing of serotypes A12 and O1 of foot-and-mouth disease virus VP1 places the probable exposed antigenic region of VP1 in a serotype-variable region including residues 136 through 144.

Amino Acid Sequence↗

PubMed1978

In vitro comparison of foot-and-mouth disease virus subtype variants causing disease in vaccinated cattle.

Foot-and-mouth disease virus isolates of types O, A and SAT 2, from diseased animals in herds routinely vaccinated twice a year were compared antigenically with the vaccine strains in the complement-fixation, neutralization and radial immunodiffusion tests. It was found that strains which had readily infected vaccinated cattle had R values against the vaccine strain in the complementfixation and radial immunodiffusion tests of 30 or less, while strains causing primary outbreaks with little spread had R values of 30-40. Threefold differences in humoral neutralizing antibody concentration between the field variant and the vaccine strain in sera from vaccinated animals were likely to be significant in terms of protection.

Animals↗

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↗

PubMed1986

Nosocomial outbreak of hand-foot-and-mouth disease among operating suite personnel.

In the fall of 1983 an outbreak of hand-foot-and-mouth disease occurred in a large urban hospital. The outbreak began among surgical nurses confined to one area of the operating suite and appeared to spread by direct contact to personnel working in the other areas. No cases were diagnosed among hospital patients. There was no evidence to support an ongoing community epidemic as only three of 98 physicians surveyed had seen hand-foot-and-mouth disease in their practices, and none occurred among family members of 94 unaffected employees. The outbreak resulted in 82 lost workdays at an estimated cost to the hospital of $5,676. Existing infection control guidelines do not address the issue of transmission of hand-foot-and-mouth disease from hospital personnel to patients; our experience suggests that the risk of transmission, at least in the operating suite environment, may be greater for other personnel than for patients.

Adult↗

PubMed1994

Foot-and-mouth disease in Ethiopia from 1988 to 1991.

During the period 1988 to 1991 samples from 16 foot-and-mouth disease outbreaks in Ethiopia were examined at the National Veterinary Institute, Ethiopia, and at the FAO World Reference Laboratory for Foot-and-Mouth Disease, UK. Typing of the virus responsible was possible in 13 of these outbreaks representing 10 separate disease events; 8 of these were caused by serotype O and 2 by serotype SAT2. This is the first record of the presence of serotype SAT2 foot-and-mouth disease virus in Ethiopia. In contrast to earlier studies serotypes A and C were not detected.

Animals↗

PubMed2005

[Foot-and-mouth disease:: an old disease--new solutions].

The recent outbreak of foot-and-mouth disease in United Kingdom provoked a crisis in the European Union with deleterious consequences not only for livestock industry. Public opinion is more and more concerned about stamping out measures used to control the disease even with previously vaccinated animals. Presently the trend is to "vaccinate for life". This policy change requires to improve vaccines and diagnostic tools. It is not foreseen nevertheless to come back to a generalized vaccination of cattle as it was the case previously in continental Europe, despite its efficacy. According to the new policy, it will only be emergency vaccination to control outbreaks; it will compulsorily use inactivated vaccines. The vaccines will have to confer quickly a strong (sterile) protection against several serotypes during the same outbreak. Several serotypes could be involved in case of agroterrorism. Another feature of foot-and-mouth virus infection is the generation of asymptomatic carriers of wild virus after infection even in previously vaccinated animals. In order to get round this problem, so-called "marker vaccines" associated with a companion diagnostic test are developed: it aims to be able to differentiate simply vaccinated animals from infected ones, whether they were previously vaccinated or not. These vaccines are presently highly purified inactivated vaccines and the companion diagnostic test is based upon the detection of specific antibodies directed against virus-induced non-structural proteins. These antibodies should not be detected in simply vaccinated animals. This technology takes into account the fact that foot-and-mouth disease virus multiplication implies the synthesis of a polyprotein subsequently cleaved. It allows to certify the absence of infection at a herd level not yet at an individual level. Another research trend is to identify virus receptors in animals in order to better understand the pathogenesis of the infection and the reasons why some animals become asymptomatic carriers of wild virus after infection.

Animals↗

PubMed1996

Antigenically profound amino acid substitutions occur during large population passages of foot-and-mouth disease virus.

Foot-and-mouth disease virus (FMDV) with amino acid substitutions next to the highly conserved R-G-D motif were isolated following large population passages of the virus (N. Sevilla and E. Domingo, 1996, J. Virol., in press). Reactivity with a panel of monoclonal antibodies which recognize different epitopes within site A was abolished or highly diminished in the mutants. This provides direct evidence of a drastic antigenic change occurring in the absence of selection by antibodies. Molecular modeling studies predict only minor alterations in the conformation of the G-H loop of VP1 and the R-G-D motif in these mutants. None of these variants became dominant in many serial infections involving smaller FMDV population numbers. In addition to documenting profound antigenic variation without immune selection, the results suggest that the repertoire of antigenic variants evolving in viral quasispecies may be greatly influenced by the population size of the virus.

Amino Acids↗