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Participatory diagnosis of a heat-intolerance syndrome in cattle in Tanzania and association with foot-and-mouth disease.

A heat-intolerance (HI) syndrome in cattle in Tanzania was suspected to be associated with previous, clinical foot-and-mouth disease (FMD). A participatory appraisal (PA) method called "matrix scoring" was used to explore livestock-keeper perceptions of association between HI and cattle diseases. A PA method called 'proportional piling' was used to estimate herd incidence of FMD and other diseases, herd incidence of HI, and association between HI and other cattle diseases. Use of matrix scoring and proportional piling with pastoral Maasai informants demonstrated association between FMD and HI. With agropastoral Sukuma informants, the matrix-scoring method did not indicate an association between FMD and HI, whereas the proportional piling method indicated a weak association. Results were supported by calculation of positive predictive values for herder diagnosis of HI and FMD. Clinical examination of cattle by veterinarians was used to confirm HI cases and detection of antibody to non-structural proteins of FMD virus was used to confirm previous clinical FMD.

Animals↗

A clustering outbreak of hand, foot, and mouth disease caused by Coxsackie virus A10.

A clustering outbreak of hand, foot, and mouth disease (HFMD) occurred from July, 1981 to January, 1982 in Matsue City and Gotsu City, Shimane Prefecture. Thirty-seven patients with clinical HFMD were virologically and serologically examined, and Coxsackie virus A10 (CA10) was isolated in 18 patients from vesicles (7/16), throat-swabs (9/31) and feces (6/7). During the period, no CA16 or enterovirus 71 were isolated from HFMD patients or from other diseases such as pharyngitis, febrile diseases, and aseptic meningitis. Serological diagnosis was performed employing an African green monkey kidney cell (AG-1)-adapted CA10 which demonstrated cytopathogenic effects on the cells. Paired sera from seven patients including three cases in which isolation failed showed a significant increase of neutralizing antibody titer against CA10. Finally, an etiological diagnosis was made in 21 out of 37 patients with clinical HFMD. This is the first report of a clustering outbreak of HFMD caused by CA10 in Japan.

Antibodies, Viral↗

Reactivity with monoclonal antibodies of viruses from an episode of foot-and-mouth disease.

A panel of 12 monoclonal antibodies (MAbs) raised against foot-and-mouth disease virus (FMDV) of serotype C1 (FMDV C-S8c1) and 11 MAbs raised against other FMDVs have been used to evaluate the reactivity of 14 isolates of FMDV of serotype C1 (series FMDV C-S), 12 of them from one disease episode (Spain 1979-1982). The assays used were immunoelectrotransfer blot, immunodot and neutralization of infectivity. None of the isolates could be clearly distinguished by its reactivity with 6 non-neutralizing and 2 neutralizing MAbs raised against FMDV C-S8c1. In contrast, the isolates were distinguished in two groups by a 10(2)-fold difference in their reactivity with 6 neutralizing MAbs. The reactivity of MAbs with synthetic peptides indicated that conserved and non-conserved epitopes recognised respectively by neutralizing MAbs 4G3 and SD6 are localized in the immunogenic region (amino acids 138-156) of VP1. Thus, epidemiologically related FMDVs differ in at least one epitope critical for virus neutralization.

Amino Acid Sequence↗

Spatial statistical modeling of disease outbreaks with particular reference to the UK foot and mouth disease (FMD) epidemic of 2001.

In this paper we examine issues relating to the analysis of spatially-referenced disease data. Initially, we discuss the use of exploratory statistical tools such as density estimation and nonparametric regression. We then consider the need for descriptive epidemic models in space, time, and space-time models for epidemic dynamics. Implicitly space-time must be considered in any analysis of the spatial structure of epidemics. The use of Bayesian models for disease spread is discussed and applied to the recent foot and mouth outbreak in the UK.

Animals↗

Quantitative analysis of foot-and-mouth disease virus RNA loads in bovine tissues: implications for the site of viral persistence.

To understand better the pathogenesis of foot-and-mouth disease (FMD), the levels of viral RNA in various bovine tissues during the acute and persistent stages of FMD virus (FMDV) infection were investigated by using quantitative RT-PCR. The viral RNA levels in the tissues examined had peaked by day 1 post-infection (p.i.) and were markedly different among the tissues examined. The epithelium collected from sites of lesion development, i.e. the interdigital area and coronary band on the feet, and the tongue, contained the highest level of viral RNA, indicating the predominant tissue sites of viral infection and amplification during the acute stage of infection. Clearance of viral RNA from most of the tissues occurred relatively rapidly and the rate of clearance was largely independent of the level of viral RNA. The viral RNA load in most of the tissues declined slower than in serum, in which viral clearance is rapid. Beyond 28 days p.i., a proportion of pharyngeal region tissues (soft palate, pharynx, tonsil and mandibular lymph node) from infected animals still contained a detectable level of viral RNA, while viral RNA in non-pharyngeal region tissues was generally only detectable for variable periods ranging from 4 to 14 days p.i. The presence of viral RNA in dorsal soft palate tissue had a good correlation with the presence of infectious virus in oesophageal-pharyngeal fluid (OP-fluid) samples, a finding indicative of the specific tissue sites of FMDV persistence.

Acute Disease↗

Cloned viral protein vaccine for foot-and-mouth disease: responses in cattle and swine.

A DNA sequence coding for the immunogenic capsid protein VP3 of foot-and-mouth disease virus A12, prepared from the virion RNA, was ligated to a plasmid designed to express a chimeric protein from the Escherichia coli tryptophan promoter-operator system. When Escherichia coli transformed with this plasmid was grown in tryptophan-depleted media, approximately 17 percent of the total cellular protein was found to be an insoluble and stable chimeric protein. The purified chimeric protein competed equally on a molar basis with VP3 for specific antibodies to foot-and-mouth disease virus. When inoculated into six cattle and two swine, this protein elicited high levels of neutralizing antibody and protection against challenge with foot-and-mouth disease virus.

Amino Acid Sequence↗

Studies of genetically defined chimeras of a European type A virus and a South African Territories type 2 virus reveal growth determinants for foot-and-mouth disease virus.

The three South African Territories (SAT) types of foot-and-mouth disease virus (FMDV) display great genetic and antigenic diversity, resulting from the independent evolution of these viruses in different geographical localities. For effective control of the disease in such areas, the use of custom-made vaccines is required. To circumvent the tedious process of vaccine strain selection, an alternative in the control process is being investigated. Specifically, it is proposed to replace the antigenic determinants of an infectious genome-length cDNA copy of a good SAT vaccine strain with those of appropriate field strains, producing custom-made FMDV chimeras for use in vaccine production. Here the construction of an infectious genome-length cDNA copy of the SAT2 vaccine strain, ZIM/7/83, is described, created utilizing an exchange-cassette strategy with an existing A(12) genome-length cDNA clone. The virus derived from this cDNA (designated vSAT2) displayed excellent growth properties in cell culture, indicating its potential usefulness in the production of custom-made vaccine strains. Evaluation of the growth of various SAT2/A12 chimeras created during the derivation of SAT2 infectious cDNA suggested incompatibilities between the non-structural proteins of ZIM/7/83 and the 5' UTR of A(12).

Animals↗

Change of major genotype of enterovirus 71 in outbreaks of hand-foot-and-mouth disease in Taiwan between 1998 and 2000.

Two outbreaks of hand-foot-and-mouth disease (HFMD) occurred in Taiwan between 1998 and 2000. Enteroviruses were isolated from a total of 1,892 patients in this laboratory during this period. Of the virus isolates, enterovirus 71 (EV71) was diagnosed in 44.4% of the patients (132 of 297) in 1998, 2% (13 of 646) in 1999, and 20.5% (195 of 949) in 2000. Genetic analyses of the 5'-untranslated and VP1 regions of EV71 isolates by reverse transcription-PCR and sequencing were performed to understand the diversity of EV71 in these outbreaks of HFMD. Most EV71 isolates from the 1998 epidemic belonged to genotype C, while only one-tenth of the isolates were genotype B. Interestingly, all EV71 isolates tested from 1999 to 2000 belonged to genotype B. This study indicated that two genogroups of EV71 capable of inducing severe clinical illness have been circulating in Taiwan. Furthermore, the predominant EV71 genotypes responsible for each of the two major HFMD outbreaks within the 3-year period in Taiwan were different.

5' Untranslated Regions↗

Improved detection of persistent foot-and-mouth disease infection in cattle by the polymerase chain reaction.

Persistent foot-and-mouth disease (FMD) infection of cattle was established by exposure to infected pigs. Oesophageal-pharyngeal fluid samples collected ante-mortem and tissue samples obtained post-mortem were tested for virus by conventional means and for viral RNA by the polymerase chain reaction (PCR). The results showed that the PCR was superior for detecting the carrier state in tissue samples. A high neutralising activity in tissues probably influenced the yields of virus obtained by infectivity assay.

Animals↗

Synthetic peptides as potential vaccines against foot-and-mouth disease.

Advances made in our knowledge of the structure of foot-and-mouth disease virus have enabled us to identify a fragment, consisting of 20 amino acids, of one of the four proteins of the particle, which elicits neutralizing antibodies in experimental animals and in cattle and pigs. The fragment has been synthesised chemically by Merrifield's solid phase method and biochemically as part of different fusion proteins. The level of the immune response to the peptide, which depends critically on the way it is presented, affords protection against experimental challenge and holds out promise for its future as a vaccine.

Amino Acid Sequence↗

A study on the immune response of sheep to foot and mouth disease virus vaccine type 'O' prepared with different inactivants and adjuvants.

Foot and mouth disease virus (FMDV) type 'O' was inactivated either with formaldehyde or binaryethyleneimine (BEI). Vaccines were prepared with inactivated virus incorporating aluminum hydroxide gel or mineral oil as an adjuvant. The antibody response in sheep was monitored by serum neutralization and ELISA test for a period of six months. Significant difference in antibody response was not observed between vaccines inactivated with formaldehyde or BEI. On the other hand significant difference in the antibody response was noticed between alhydrogel and oil vaccines. The high titer of antibodies stimulated by oil adjuvant vaccines persisted longer than those of alhydrogel vaccines within the period of study.

Adjuvants, Immunologic↗

Morphogenesis of vesiculation in foot-and-mouth disease.

The morphogenesis of vesiculation in cattle inoculated (aerosol expsoure) with foot-and-mouth disease virus was investigated by examining alternate, frozen sections of selected tissues stained by fluorescent antibody technique and with hematoxylin and eosin. Viremia preceded the development of lesions, and virus appeared to be transported to the epithelium via papillae. Lesions were initiated usually by the infection of single cells in the stratum spinosum adjacent to the papillae. Three types of lesions were observed. A vesicle developed mainly from the lysis of swollen, spherical cells and the release of intracellular fluid. The 2nd type of lesion was formed mainly by the accumulation of intercellular edema. The 3rd type was characterized by the absence of a vesicle due to seepage and loss of edema fluid and desiccation of the lesion.

Animals↗

Infectivity assays of foot-and-mouth disease virus: contact transmission between cattle and buffalo (Bubalus bubalis) in the early stages of infection.

No differences were observed between cattle and Indian buffalo (Bubalus bubalis) in terms of temperature, viraemia or virus replication in the pharyngeal area, during the acute phase of foot-and-mouth disease. Like cattle, the Indian buffalo became infected and excreted virus before any clinical signs of foot-and-mouth disease developed. The disease was transmitted from cattle to buffalo and vice versa, during the acute stage of infection, as if the animals had been of the same species, presumably because of their close phylogenetic relationship. There were more tongue lesions in the cattle than in the buffalo. Foot lesions in the buffalo at first had a scaley appearance, but later became vesicular. Anti-virus infection associated antigen and neutralising antibodies were synthesised at the same time in both species and reached similar titres in the same period. Persistent infection in the buffalo during the first 35 days after infection was similar to that in the cattle.

Animals↗

Sequence and secondary structure requirements in a highly conserved element for foot-and-mouth disease virus internal ribosome entry site activity and eIF4G binding.

Foot-and-mouth disease virus (FMDV) and other picornaviruses initiate translation of their positive-strand RNA genomes at the highly structured internal ribosome entry site (IRES), which mediates ribosome recruitment to an internal site of the virus RNA. This process is facilitated by eukaryotic translation initiation factors (eIFs), such as eIF4G and eIF4B. In the eIF4G-binding site, a characteristic, discontinuous sequence element is highly conserved within the cardio- and aphthovirus subgroup (including FMDV) of the picornaviruses. This conserved element was mutated in order to investigate its primary sequence and secondary structure requirements for IRES function. Both binding of eIF4G to the IRES and IRES-directed translation are seriously impaired by mutations in two unpaired dinucleotide stretches that are exposed from the double-stranded (ds)RNA. In the base-paired regions of the conserved element, maintenance of the double-stranded secondary structure is essential, whilst in some cases, the primary sequence within the dsRNA regions is also important for IRES function. Extra eIF4F added to the translation reaction does not restore full IRES activity or eIF4G binding, indicating that disturbances in the structure of this conserved element cannot be overcome by increased initiation factor concentrations.

Animals↗