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PubMed1973

Observations of cattle, goats and pigs after administration of synthetic interferon inducers and subsequent exposure to foot and mouth disease virus.

Polyriboinosinic-polyribocytidylic acid (poly [rI.rC]) was administered intravenously to 11 cattle and 13 goats in doses of 0.25 to 4.0, and 1.0 to 5.0 mg/kg, respectively. Subsequent exposure of these and untreated control animals to foot and mouth disease virus (FMDV) failed to demonstrate any differences in either the course or severity of the disease. Serum interferon was detected in cattle one hour after the intravenous administration of poly (rI.rC). Six pigs given 4, 20, or 100 mg/kg of itaconic-acrylic acid copolymer (IAA, HMW) intraperitoneally reacted clinically the same as six untreated control pigs after contact exposure to FMDV. Three pigs given 50, 100, or 200 mg/kg of divinyl ether-maleic anhydride copolymer (DVE/MA, pyran) intraperitoneally similarly failed to show any difference in clinical reaction from three untreated control pigs after intranasal instillation of FMDV. Three pigs given 100, 200 or 400 mg/kg of DVE/MA intraperitoneally developed rapid diffuse peritonitis causing the death of one in 48 hours.

Acrylates↗
PubMed1997

[Seroepidemiologic indicators for the evaluation of campaigns for the control of foot-and-mouth disease].

A sero-epidemiological survey was conducted in two districts in Argentina between 1993 and 1995, to provide additional information on the epidemiology of foot and mouth disease (FMD) in Argentina and to assess the level of immunity in cattle populations, and the circulation of FMD virus. As part of the final stage of this survey, a comparison was made of the results obtained by the enzyme-linked immunosorbent assay (ELISA) and agar gel immunodiffusion techniques. Levels of population immunity against the four types of virus included in the vaccine increased progressively during the period of the survey until, in 1995, at the end of the vaccination period, the percentage of animals possessing adequate levels of protection was approximately 77% in yearlings, and more than 94% in cattle over one year old. During the three-year study, there was a clear tendency for viral activity to diminish, until in 1995 when between 3% and 0.6% were positive to the agar gel immunodiffusion test for the antigen associated with viral infection. By contrast, the ELISA detected antibody in about five times as many animals. The authors show how the increase in the level of population immunity was accompanied by a fall in viral activity.

Animals↗
PubMed2006

Comparison of different control strategies for foot-and-mouth disease: a study of the epidemics in Canada in 1951/52, Hampshire in 1967 and Northumberland in 1966.

The measures used to control the epidemics of foot-and-mouth disease in Canada in 1951/52 (29 outbreaks) were compared with those used in the epidemic in Hampshire in 1967 (29 outbreaks). In both epidemics the disease spread more from premises where the disease was reported late and the imposition of quarantine or restrictions on infected premises was delayed. In Hampshire, area restrictions were imposed, susceptible livestock on infected premises and on premises in direct contact were slaughtered, and contacts were traced. In Canada, the initial diagnosis was vesicular stomatitis, no area restrictions were imposed, no tracing was carried out and the animals on infected premises were allowed to recover. However, apart from the disease's spread through infected meat and by unknown or airborne routes, it did not spread from infected premises once quarantine was imposed, partly owing to the low population density of livestock in the area. The effects of the slaughter of infected premises and direct contacts in the Fareham area of Hampshire in 1967 and in the Chathill area of Northumberland in 1966 were compared with what might have happened if, in addition, culling on contiguous premises or culling on premises within 3 km or emergency vaccination had been put into effect. The slaughter of cattle, sheep, goats and pigs on premises within 3 km two days after confirmation of the first outbreak would have resulted in fewer outbreaks and a shorter period to complete slaughter, but more animals would have been slaughtered. In the Chathill area, the slaughter of sheep, goats and pigs only on premises within 3 km two days after confirmation of the first outbreak would not have resulted in fewer outbreaks and more animals would have been slaughtered. Fewer premises and animals would have been slaughtered by a contiguous cull than by a 3 km cull but more than by the slaughter of infected premises and direct contacts. Emergency vaccination within 3 km, providing protection at four days (but not to animals already infected before the development of immunity), would have resulted in the fewest animals being slaughtered and could have reduced the number of outbreaks in the Fareham area by one and in the Chathill area by two or three. All the procedures would have had a greater effect the sooner they were introduced. However, with many foci of infection, priorities for action would have had to have been established. Earlier tracing of the last outbreak in the Fareham area could have shortened the Hampshire epidemic. Surveillance of a farm identified as at risk through animal movements and by the use of an airborne-prediction model could have eliminated the source of further outbreaks in the Chathill area.

Animals↗
PubMed1975

Management of deer for experimental studies with foor-and-mouth disease virus.

Red, sika, fallow, roe and muntjac deer adapted to captivity in experimental units designed for working with foot-and-mouth disease. The red, sika and fallow deer readily accepted rolled oats and hay as their staple diet. This diet was replaced for the roe and muntjac deer with flaked maize, calf starter pellets and green browse. Etorphine/acepromazine ans xylazine were found to be suitable sedatives for detailed examination of the tongue and oral cavity of the various species of deer and gave adequate analgesia for the inoculation and collection of virus samples.

Abortion, Veterinary↗
PubMed1985

Dose-response evaluation of a genetically engineered foot-and-mouth disease virus polypeptide immunogen in cattle.

Four groups of 9 cattle each were vaccinated with 10, 50, 250, or 1,250 micrograms of foot-and-mouth disease (FMD) virus A12 VP1 fusion protein that was produced in Escherichia coli and emulsified in an oil adjuvant. The groups given the 10 and 50 micrograms of antigen were revaccinated at 15 weeks and were challenge exposed at 30 weeks; 5 of 9 and 7 of 9 cattle, respectively, were protected from FMD virus infection. The remaining 2 groups, vaccinated with 250 or 1,250 micrograms of antigen, were revaccinated at 32 weeks and were challenge exposed at 45 weeks; 8 of 9 and 9 of 9 cattle, respectively, were protected. The results indicated that the biosynthetic polypeptide FMD vaccine was effective using vaccination intervals frequently followed with conventional whole-virus vaccines.

Animals↗
PubMed1978

Neurovirulence in cynomolgus monkeys of enterovirus 71 isolated from a patient with hand, foot and mouth disease.

Six cynomolgus monkeys were inoculated subcutaneously with enteroviurs 71 (E71), isolated from the stools of a patient with hand, foot and mouth disease (HFMD). Clinical symptoms were observed in three of the six monkeys. One monkey showed complete paralysis of the lower extremities and two animals showed weakness in the hind limbs 4 to 7 days after inoculation. Lesions were found in the central nervous system (CNS) of all monkeys. Mild to moderate vascular lesions, perivascular cuffings, degeneration and disappearance of the neurons and meningial lymphocytic infiltration were observed in the grey and/or white matter of the spinal cord, medulla oblongata, cerebral cortex and brain stem. No virus was recovered from the CNS or liver of any of the six monkeys. However, serum neutralizing antibody titers had risen in monkeys inoculated with E71.

Animals↗
PubMed1976

Growth of foot-and-mouth disease virus in the upper respiratory tract of non-immunized, vaccinated, and recovered cattle after intranasal inoculation.

Non-immunized, vaccinated, and recovered cattle were inoculated intranasally with various doses of foot-and-mouth disease virus. Samples of oesophageal-pharyngeal (OP) fluid were taken periodically for up to 7 days after inoculation and virus titres of these samples were plotted as pharyngeal virus growth curves. In non-immunized cattle, the length of the lag period and of the growth period were inversely proportional to the dose of virus given. Maximum titres were observed when clinical signs were first detected. Three of the 10 cattle studied had virus growth rates that were lower than rates of others given the same dose of virus, and clinical signs appeared later than expected in these three cattle. Cattle vaccinated with an inactivated virus oil-adjuvant vaccine had pharyngeal virus growth curves that were similar to those obtained from non-immunized cattle for 30 h. after inoculation. Titres of virus in OP fluid samples taken 2-7 days after inoculation were substantially lower in cattle with a high pre-exposure serum mouse protection index than titres from partly-immunized or non-immunized cattle. Nine of 14 cattle had detectable but reduced virus growth after intranasal inoculation with homologous virus. Five recovered cattle inoculated with heterologous virus reacted similarly to non-immunized animals.

Animals↗
PubMed1984

Genetic and phenotypic characteristics of enterovirus 71 isolates from patients with encephalitis and with hand, foot and mouth disease.

Biological and biochemical characters of seven enterovirus 71 (E71) isolates were compared. Four isolates (two from patients with hand, foot and mouth disease [HFMD] and two from patients with encephalitis) grew in cynomolgus monkey kidney cells both at 39.5 and 35 degrees C. However, the remaining three strains (from patients with HFMD) grew at 35 degrees C, but not at 39.5 degrees C. Three temperature-resistant and two temperature-sensitive strains were tested for neurovirulence in monkeys. Temperature-resistant strains were shown to be neurovirulent, whereas temperature-sensitive strains were less neurovirulent. The results suggest correlation between temperature-sensitive growth and neurovirulence in monkeys of E71. Variation in the electrophoretic mobility of the viral polypeptides was detected in three out of seven strains. The fingerprinting of oligonucleotides generated from the viral genome showed similar patterns in two isolates from patients with HFMD and one from patient with encephalitis and variable patterns in each genomic map of remaining four strains. These variations of polypeptide patterns and of oligonucleotide maps could not be correlated with pathogenicity (encephalitis or HFMD), temperature-sensitive growth and neurovirulence in monkeys.

Animals↗
PubMed2005

Structure of Foot-and-mouth disease virus serotype A10 61 alone and complexed with oligosaccharide receptor: receptor conservation in the face of antigenic variation.

Foot-and-mouth disease viruses (FMDVs) target epithelial cells via integrin receptors, but can acquire the capacity to bind cell-surface heparan sulphate (or alternative receptors) on passage in cell culture. Vaccine viruses must be propagated in cell culture and, hence, some rationale for the selection of variants in this process is important. Crystal structures are available for type O, A and C viruses and also for a complex of type O strain O(1)BFS with heparin. The structure of FMDV A10(61) (a cell culture-adapted strain) complexed with heparin has now been determined. This virus has an RGSD motif in place of the otherwise conserved RGD integrin-binding motif and the potential to bind heparan sulphate (suggested by sequence analyses). FMDV A10(61) was closely similar in structure to other serotypes, deviating most in antigenic sites. The VP1 GH loop comprising the integrin-binding motif was disordered. Heparin bound at a similar site and in a similar conformation to that seen in the analogous complex with O(1)BFS, although the binding had a lower affinity and was more ionic.

Amino Acid Sequence↗
PubMed2004

[Phylogenetic analysis of enterovirus 71 isolated from patients with hand, foot and mouth disease in Guangdong and Fujian provinces, 2000-2001].

OBJECTIVE: To identify enterovirus 71 (EV71) strains isolated from patients with hand, foot and mouth disease (HFMD) in Guangdong and Fujian provinces from 2000 to 2001 by using phylogenetic analysis. METHODS: All 25 samples were first tested for enteric viruses by RT-PCR using enterovirus specific primers EV-1 and EV-2, and then were identified for EV71 by RT-PCR using EV71 specific primers 159S and 162A. The amplicons of 485bp segment (part of the VP1 gene) were cloned into pGEM-T and sequenced. A phylogenetic tree was constructed by comparison of the sequences with other 12 EV71 strains isolated from China, Japan, Hungary, and the United States including the prototype BrCr. RESULTS: The positive rate of EV71 was about 20%. The sequence analysis showed that the new isolate (GZH2000) shared 94%-96% nucleotide identity with three strains isolated in 1998 and 2000, and 91% with a strain isolated in 1987 from Chinese mainland, but shared only 82%-84% homology with EV71 isolates studied abroad. CONCLUSIONS: EV71 is one of the important pathogens of HFMD in south China. The strains isolated from mainland were closely related with most isolates from Taiwan, but different from most EV71 strains reported abroad. The symptoms of EV71 infection in mainland were not as intensive as those described in Taiwan's outbreak.

Adolescent↗
PubMed2001

Development of a novel real-time RT-PCR assay for quantitation of foot-and-mouth disease virus in diverse porcine tissues.

Pigs are more difficult to immunise and more variable in their response to foot-and-mouth disease (FMD) than other livestock species. This has important consequences for FMD control during both prophylactic vaccination programmes in endemic situations and when emergency vaccination may be used as an adjunct to stamping out during outbreaks in countries normally free from the disease. The rapid and effective control of FMD in pigs is especially important in regions of high pig density since infected pigs have the potential to generate plumes of airborne virus and spread infection beyond the immediate control area. Increased knowledge of the kinetics of FMDV replication in pigs, especially in their respiratory tracts, could create opportunities for strategies to improve FMD vaccines for pigs. A fluorogenic TaqMan RT-PCR assay specific for the IRES (internal ribosome entry site) sequence of the O(1) Kaufbeuren/Lausanne strain of FMDV has been developed for this purpose. The assay had a sensitivity of 0.1 TCID(50)/ml, and a dynamic range of at least eight orders of magnitude. It was found that an established method of quantitation, relative to a housekeeping gene, exhibited two significant shortcomings when applied to a set of 16 anatomically highly diverse solid tissues: (i) tissue differences in housekeeping gene expression caused errors of up to 60-fold in estimated FMDV concentrations; and (ii) variability in total RNA yields caused unpredictable saturation of RT reactions, which in turn caused errors of up to 250-fold in the estimated FMDV concentration. A novel quantitation strategy, designated the C(t)(min) method, was developed to overcome these problems. The C(t)(min) method was based on the the RT-PCR examination of a dilution series of spectrophotometrically quantitated total RNA, spanning the optimum for the RT-PCR system used. The new method was influenced minimally by any tissue-specific RT-PCR inhibitors and was used to determine FMDV concentrations in tissues from four experimentally infected pigs. The results suggest that the lungs play a less important role in the replication of FMDV in pigs than was thought previously.

Animals↗
PubMed2000

Improvement of a serodiagnostic strategy for foot-and-mouth disease virus surveillance in cattle under systematic vaccination: a combined system of an indirect ELISA-3ABC with an enzyme-linked immunoelectrotransfer blot assay.

Foot-and-mouth disease (FMD) recombinant non-capsideal viral antigens 3A, 3B, 2C, 3D and 3ABC were assessed individually in an indirect enzyme-linked immunosorbent assay (I-ELISA) for their ability to screen for persistent infection-specific antibodies in cattle, regardless of vaccination condition. Results of sequential serum samples from non-vaccinated animals with experimentally induced persistent infection, and their correlation with virus isolation, indicated that the polypeptides 3A, 3B and 3ABC showed the most adequate characteristics for further field studies. Reliable performance of the I-ELISA with the selected antigen 3ABC was indicated by the distinct patterns observed for the frequency distribution values of naive and true positive samples. For regularly vaccinated livestock, a clear negative profile was proved in samples from regions without recent history of FMD. In contrast, at 90 and 900 days post-outbreak, coexistence of a positive and a negative population was established. These findings indicated that, irrespective of vaccination, the test allowed a classification of the herd-disease status. A high degree of agreement was observed between I-ELISA-3ABC and EITB results for clearly reactive and non-reactive sera. For samples with reactivity values close to that of the cut-off, the EITB profiles upheld the definition of the infection condition. On this basis, screening by I-ELISA-3ABC, together with confirmation of suspect or positive samples by EITB is proposed as an adequate and accurate approach for large-scale epidemiological surveillance.

Animals↗
PubMed2003

Recovery of infectious foot-and-mouth disease virus from suckling mice after direct inoculation with in vitro-transcribed RNA.

We assayed the infectivity of naked foot-and-mouth disease virus (FMDV) RNA by direct inoculation of suckling mice. Our results demonstrate that transcripts generated from full-length cDNA clones were infectious, as was virion-extracted RNA. Interestingly, infectious virus could be recovered from a mutant transcript encoding amino acid substitution L-147-->P in capsid protein VP1, known to be noninfectious for BHK-21 cells. The model described here provides a useful tool for virulence studies in vivo, bypassing possible selection of variants during viral replication in cell culture.

Amino Acid Sequence↗
PubMed1991

High-affinity antibody induced by immunization with a synthetic peptide is associated with protection of cattle against foot-and-mouth disease.

Previous work has shown that the synthetic peptide C-C-(200-213)-P-P-S-(141-158)-P-C-G, in which residues 200-213 and 141-158 correspond to immunogenic regions of the VP1 protein of foot-and-mouth disease virus (FMDV), is capable of inducing high levels of neutralizing antibody but only inconsistent protection of cattle against virulent FMDV challenge. The possibility exists that differences in affinity may well underlie the observed variations in biological effectiveness of the anti-peptide antibodies in immunized animals. This has been investigated by assessing the affinity for peptide and whole virus of the anti-peptide antibodies in sera from protected and non-protected cattle using both fluid-phase and solid-phase assays. The results obtained show that the affinities of serum antibodies for peptide and virus in protected cattle were significantly higher than those in non-protected animals. Thus in order to assess vaccine efficacy, particularly in the case where synthetic immunogens are employed, consideration should be given to the determination of antibody affinity in addition to other parameters of the antibody response.

Animals↗
PubMed1988

Detection of foot-and-mouth disease antigen in bovine epithelial samples: comparison of sites of sample collection by an enzyme linked immunosorbent assay (ELISA) and complement fixation test.

Serially collected epithelial samples from lesions in the mouth and on the feet of calves experimentally infected with foot-and-mouth disease (FMD) type O1 BFS 1860 were assayed for the presence of FMD viral antigen using a double antibody sandwich enzyme-linked immunosorbent assay (ELISA) and a complement fixation (CF) test. The amount of infectious virus in each sample was also determined. FMD viral antigen was detected by ELISA in 70 per cent of the mouth samples and 92 per cent of samples from the feet. The CF test was less sensitive; it detected antigen in 44 per cent of mouth and 85 per cent of foot samples. In mouth samples the amount of antigen decreased rapidly becoming undetectable by the fourth day of sampling whereas in foot samples the quantity of antigen declined more slowly, and could be detected until the seventh day of sampling. Therefore it was concluded that the age of lesion and the site from which epithelial samples are collected are both important determinants in the laboratory diagnosis of FMD. In cattle, foot lesions are more likely than mouth lesions to yield antigen and to remain positive for a longer period.

Animals↗
PubMed2003

Hand, foot and mouth disease in Singapore: a comparison of fatal and non-fatal cases.

AIM: An epidemic of hand, foot and mouth disease (HFMD) occurred in Singapore between September and November 2000. During the epidemic, there were four HFMD-related deaths and after the epidemic, another three HFMD-related deaths. This study sought to determine the risk factors predictive of death from HFMD disease. METHODS: The risk factors for fatal HFMD were determined by comparing clinical and laboratory findings between fatal cases (n = 7) and non-fatal controls (n = 131) admitted between September 2000 and April 2001. Enterovirus 71 positive fatal cases (n = 4) and non-fatal controls (n = 63) were also compared. RESULTS: In total, 138 HFMD cases with a mean age of 32 mo were studied. The majority of fatal cases died from interstitial pneumonitis, of whom three also had brainstem encephalitis. Of the 131 non-fatal cases, 3 had concomitant infections (respiratory syncytial virus bronchiolitis, right-sided pneumonia, Haemophilus influenzae type b meningitis), 2 had aseptic meningitis, and 1 each had transient drowsiness, intravenous immunoglobulin-related complications and transverse myelitis. By multivariate logistic regression analysis, atypical physical findings (p = 0.0006), raised total white cell count (p = 0.0128), vomiting (p = 0.0116) and absence of mouth ulcers (p = 0.043) were predictive of a fatal course. Although previous epidemics have described neurogenic pulmonary oedema as the main cause of death, the fatal cases in this study died mainly from interstitial pneumonitis alone or with myocarditis or encephalitis. CONCLUSION: Although HFMD is generally a benign disease, risk factors such as vomiting, absence of mouth ulcers, atypical presentation and raised total white cell count should alert the physician of a fatal course of illness.

Child↗
PubMed1995

Selection of vaccine strains of foot and mouth disease virus for use in southern Africa.

In the countries of Southern Africa, types SAT 1, SAT 2 and SAT 3 (SAT: Southern African Territories) of foot and mouth disease (FMD) virus are the most widely represented, especially the SAT 2 virus. Since 1982, examinations have been conducted on 139 isolates of these virus types. Other viruses, types O and A, have been detected in the north of this area. The typing and sub-typing of viruses with the complement fixation (CF) test can be improved by using panels of monoclonal antibodies (MAbs), which provide an accurate antigenic profile of a new strain. A total of 33 SAT 2 strains have been investigated using MAbs, and the results enable the classification of viruses into groups presenting the same profile. The author presents comparisons of isolates and vaccine viruses using conventional methods of serotyping--CF and virus neutralisation (VN) tests--as well as profiling the isolates using MAbs. Both manners of analysis provide information on the relationships between the viruses. The CF and VN tests give details on how animals responded against a particular isolate and how this antibody response would recognise another isolate; from this, the serological relationships can be proposed with respect to how different isolates might induce a humoral immune response. With MAb profiling, details of antigenic relationships between the isolates are obtained, enabling the identification of individual epitopic variations. These analyses can provide the potential to place different isolates into 'antigenic' groups. When compared with vaccine viruses, one can attempt to identify the vaccine virus with the closest profile to the isolate group. Immunological analysis (e.g. using the CF tests employed in this paper) can provide further information on the relationship between a particular vaccine and an antigenic group identified by MAb profiling. Of course, this MAb profiling can provide essential information in a very short time, which is of particular benefit in an emergency situation. Confirmation of the conclusions from the profiling would then be forthcoming through the serological analyses. Such combined analyses offer a more extensive identification of antigenic and immunogenic relationships between FMD virus isolates, as well as between isolates and vaccine viruses.

Africa, Southern↗
PubMed1985

Foot-and-mouth disease and its antigens.

Many factors combine to make foot-and-mouth disease (FMD) one of the most damaging and intractable disease of animals. These include its extreme contagion, wide geographic distribution, great multiplicity of both susceptible animal hosts and viral serotypes, a relatively short duration of immunity to a given serotype and a post-recovery carrier state of the virus in many animal species (e.g., cattle, sheep and goats). Nevertheless, import restrictions and other actions of the U.S. Government have kept the United States free of FMD since 1929, even during outbreaks of the disease in Mexico and Canada in the early 1950's. Beginning in the late 1940's, the systematic vaccination of cattle has been practiced in several areas of the world with varying degrees of success. While this procedure has succeeded in Western Europe in greatly reducing the incidence of FMD, the presence of live virus in some batches of vaccine and the escape of virus from vaccine from manufacturing facilities are now responsible for a large proportion of the outbreaks that still occur there. A vaccine is needed that has no possibility of producing the disease. During the last few years, it has been demonstrated that capsid protein VP1, isolated from type A and C virions or biosynthesized in E. coli transformed with the gene for VP1, can be used to immunize livestock against FMD. Immunization of livestock has also been achieved with a 13 kd fragment (amino acid residues 55 through 179) cleaved with CNBr from the 213 amino acid long VP1 chain of type A virions. Immunogenic sites on intact virions, 12 S subunit particles and isolated VP1 chains have been studied by a combination of methods, including: assessment of the immunogenicity of VP1-specific fragments and synthetic peptides and mapping monoclonal antibodies (Mabs) generated with virus, VP1 and the 13 kd fragment to virus, 12 S subunits, VP1, VP1-specific fragments and a biosynthetic 32mer. Correlation of these results with sites having variant and serotype sequence variability indicates that the 136-179 region of type A12 VP1 possesses four putative neutralization-specific epitopes (ca. 137-143, 146-151, 152-157 and 170-175). Of three neutralization-specific epitopes on type A12 virus, two are also present on 12 S subunits and isolated VP1 chains. Mabs to the three epitopes appear to neutralize virus by different mechanisms: by viral aggregation, by blocking the site on viral VP1 that binds to cell receptors or by interfering with a postreceptor attachment step, possibly penetration or uncoating.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗