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Modelling vaccination strategies against foot-and-mouth disease.

Vaccination has proved a powerful defence against a range of infectious diseases of humans and animals. However, its potential to control major epidemics of foot-and-mouth disease (FMD) in livestock is contentious. Using an individual farm-based model, we consider either national prophylactic vaccination campaigns in advance of an outbreak, or combinations of reactive vaccination and culling strategies during an epidemic. Consistent with standard epidemiological theory, mass prophylactic vaccination could reduce greatly the potential for a major epidemic, while the targeting of high-risk farms increases efficiency. Given sufficient resources and preparation, a combination of reactive vaccination and culling might control ongoing epidemics. We also explore a reactive strategy, 'predictive' vaccination, which targets key spatial transmission loci and can reduce markedly the long tail that characterizes many FMD epidemics. These analyses have broader implications for the control of human and livestock infectious diseases in heterogeneous spatial landscapes.

Animals↗

Differentiation of type A, Asia1 and O foot-and-mouth disease virus variants, amplified by the same system, by sequencing of the capsid protein genes.

A reverse transcription-dependent polymerase chain reaction (RT-PCR) is described that amplifies the genes encoding the capsid proteins VP1-3 of at least three evolutionary lineages each of the foot-and-mouth disease (FMD) virus types A, Asia1 and O. Most of these lineages are circulating at present in Asia and Africa. The method is not only suitable to confirm suspected outbreaks of FMD, but also describes the modulation of major and minor antigenic sites in the course of an epizootic by nucleotide sequence determination of the obtained RT-PCR products. Such knowledge helps to choose suitable vaccines for disease control.

Animals↗

Clinical and laboratory investigations of five outbreaks of foot-and-mouth disease during the 2001 epidemic in the United Kingdom.

Clinical and laboratory investigations of five outbreaks of foot-and-mouth disease (FMD) were made during the early stages of the 2001 epidemic in the UK. The first outbreak, confirmed on February 20, was at an abattoir in Essex which specialised in the processing of culled sows and boars. On February 23, the disease was confirmed at a pig farm in Northumberland which held cull sows and boars fed on waste food; the findings indicated that it was the first of the five premises to be infected. The disease had probably been present since early February, and it was the most likely origin of the epidemic. The other premises investigated were a waste food-fed cull sow/boar pig unit in Essex, approximately 30 km from the abattoir, which was probably infected at the same time or before the abattoir, a sheep and cattle farm approximately 6 km from the Northumberland pig farm, which was probably infected by airborne virus from it in the period immediately before February 13, and a sheep and cattle farm in Devon which had clinical disease from February 20 and was probably infected by sheep transported from Northumberland on February 13 which arrived on February 15.

Abattoirs↗

Control of foot and mouth disease: lessons from the experience of Ireland.

The authors outline the measures applied in Ireland to prevent the introduction of foot and mouth disease (FMD) from the United Kingdom, France and The Netherlands, to stamp out the disease in Ireland following confirmation of an outbreak on 22 March 2001 and to conduct serological surveillance in order to prove freedom from the disease. Successful control was the result of prompt action and extensive culling in the area around the infected premises. This was achieved by the State Veterinary Service operating with the assistance of the personnel and equipment resources of many Government departments, private industry and private veterinary practitioners, with the co-operation of the farming community and general public. In order to ensure effective use of these resources, good systems of communication and information technology are vital, as are the existence of detailed contingency plans and trained staff.

Animals↗

Epidemic of hand, foot and mouth disease in Gifu Prefecture in 1978.

During the period from May to August, 1978, an epidemic of hand, foot and mouth disease (HFMD) occurred in Gifu prefecture. Epidemiological, virological and serological investigations were performed. Cases involved ranged from 0 to 31 years of age, and 80.2% of them were under 5 years of age. The incidence of HFMD with neurological complication (3.7%) was lower than that in 1973. Enterovirus 71 (EV71) was isolated from 83 of 108 cases (75.9%) and a significant rise in the neutralization antibody titer against the isolate was found in 14 of 25 cases (56%). Thus, it was confirmed that the causative agent of the epidemic of HFMD in Gifu prefecture in 1978 was enterovirus 71.

Adolescent↗

Detection of foot-and-mouth disease viral sequences in various fluids and tissues during persistence of the virus in cattle.

OBJECTIVE: To assess whether foot-and-mouth disease virus (FMDV)-specific sequences could be identified in tissues from persistently virus-infected animals. DESIGN: Cattle with experimentally induced persistent FMDV infections were slaughtered at 750 days after viral exposure. Experimentally infected pigs were slaughtered at 28 days after FMDV inoculation. Postmortem specimens were asceptically removed. ANIMALS: Three bovids and 3 pigs were studied, as well as 1 control animal for each species. PROCEDURE: Various tissues were examined for the presence of FMDV-specific sequences by dot-blot hybridization assay, using a molecularly cloned FMDV cDNA corresponding to the polymerase coding region. RESULTS: The FMDV-specific genomic sequences were only detected in RNA from spleen, lung, larynx, tonsils, pancreas, liver, esophagus, and WBC of bovids. CONCLUSIONS: It was established that, at late stages of the persistent infection, when virus isolation was not possible, cattle may carry FMDV-specific sequences in different tissues. Retention of viral sequences could not be demonstrated in specimens from experimentally infected swine, 28 days after viral inoculation.

Animals↗

Application of universal primers for identification of Foot-and-mouth disease virus and Swine vesicular disease virus by PCR and PCR-ELISA.

Two approaches for simultaneous identification of both Foot-and-mouth disease virus (FMDV) and Swine vesicular disease virus (SVDV) are described: (1) a single-step reverse transcription-PCR with three primers and (2) a PCR-ELISA assay with two universal primers for genome amplification and two virus-specific probes for identification. These methods are based on the use of 3D gene universal PCR primers, the structure of which was optimized and refined due to the close relationship between the two viruses belonging to different genera of the Picornaviridae family. In procedure (1), a three-primer PCR containing one universal antisense primer and two virus-specific primers was shown to differentiate between FMDV and SVDV in one reaction, due to the different length of the amplified DNA fragments (600 and 340 base pairs, respectively). In procedure (2), the two viruses were identified by PCR-ELISA, i.e. PCR for the 3D gene followed by two parallel hybridizations with FMDV and SVDV-specific probes in microplate wells and ELISA detection. The application of universal primers could halve the number of PCR experiments in both cases, as compared to the usual virus-specific PCR procedures. Also, we investigated the 3D gene structure of several SVDV strains isolated at different times. No essential changes were detected in the regions coding for conserved motifs of the RNA-dependent RNA polymerase recognized by our universal primers. The multi-primer PCR was successfully tested on 38 FMDV and 15 SVDV strains, and the PCR-ELISA on 32 FMDV and 16 SVDV strains including clinical material from disease cases.

Amino Acid Motifs↗

[Testing the effectiveness of foot-and-mouth disease vaccines: the relationship between test infection results and corresponding neutralization titers of vaccinated cattle].

In the course of vaccine controls, the potency of 25 foot-and-mouth disease (FMD) vaccines was tested quantitatively in parallel in cattle using the intradermal infection and the determination of the SN titres. More than 95% of the vaccinated cattle with SN titres of greater than 1:20 were protected from generalized FMD, regardless of the virus type tested. 61.5% of the vaccinated cattle with SN titres less than or equal to 1:20 were not protected and developed generalized FMD. Comparison of the PD50 values calculated from the results of the intradermal infection and the corresponding SN titres (minimum protection titre greater than 1:20) showed that the results were in complete agreement in 56% of the tested vaccines. In a further 32% of vaccines, the PD50 calculated from the SN titre was slightly below that for the intradermal infection, in the remaining 12% it was somewhat above. The possibility of using the minimum titre determination for testing a vaccine and the significance of this titre as an expression of protection by vaccination are discussed.

Animals↗

Infection of cattle by airborne foot-and-mouth disease virus: minimal doses with O1 and SAT 2 strains.

Equipment has been constructed and methods developed for exposing individual cattle to two strains of foot-and-mouth disease (FMD) virus in aerosols to determine the minimal infective dose by the respiratory route. The aerosols used were produced either artificially by a spinning-top aerosol generator, in which case they were of homogeneous small particle size (less than 3 micron in diameter) or else they were derived naturally from infected pigs, in which case the particles were heterogeneous in size. Two strains of FMD virus were used: an O1 strain of UK origin and a SAT 2 strain from South Africa. The lowest doses which initiated infection were 12.5 TCID50 of O1 BFS virus and 25 TCID50 of SAT 2 virus, infectivity having been assayed in primary bovine thyroid cell cultures. Following exposure to low doses of virus (range 12 to 316 TCID50) 33 per cent of the cattle exposed to O1 BFS virus and 27 per cent exposed to SAT 2 virus were infected but did not develop detectable vesicular lesions.

Aerosols↗

Factors associated with the clinical diagnosis of foot and mouth disease during the 2001 epidemic in the UK.

The purpose of this investigation was to identify factors associated with the clinical diagnosis of foot and mouth disease during the 2001 epidemic in the United Kingdom. Using logistic regression, we compared: (1) reports of suspect disease that resulted in the declaration of FMD to reports that did not, and (2) laboratory-positive cases to laboratory-negative cases. From 6,801 reports of suspect disease, 2,026 cases of FMD were identified. Suspect cases were more likely to become clinical cases if: (1) the report originated from the disease control authorities ('active surveillance') rather than the public, usually farmers ('passive surveillance'); (2) cattle were the species suspected of disease, as opposed to sheep; (3) the report was filed during the peak of the epidemic; (4) the reporting premises was within 3 km of an FMD case detected within the previous 2 weeks; or (5) the report originated from certain local disease control centres. There were significant two-way interactions between: type of surveillance and species suspected of disease, type of surveillance and proximity of other infected premises, species suspected and time in the epidemic, and time in the epidemic and proximity of other infected premises. Clinical cases were more likely to be laboratory positive if: (1) they were found by passive versus active surveillance, (2) cattle were suspected of disease (versus sheep), (3) oldest lesions were less than 3 days, (4) the report was filed at any time other than the peak of the epidemic, or (5) the report originated from certain local disease control centres. Significant two-way interactions were found between: type of surveillance and species suspected of disease, and type of surveillance and time in the epidemic.

Analysis of Variance↗

The 1993 Italian foot-and-mouth disease epidemic: epidemiological features of the four outbreaks identified in Verona province (Veneto region).

Imported cattle gave rise to an epidemic of foot-and-mouth disease (FMD) in Italy during 1993. Four outbreaks occurred in large housed beef herds in Verona province. Investigations revealed that there were no movements of livestock out of the infected premises and meteorological analyses suggested that the airborne spread of infectious particles had been limited by the anticyclonic conditions. Surveillance was therefore concentrated on the areas immediately surrounding the outbreaks and the infection was prevented from spreading.

Animals↗

Epidemiological investigations of the 2001 foot-and-mouth disease outbreak in Argentina.

A total of 2126 herds, an attack rate of 0.82 per cent, were affected during an epidemic of foot-and-mouth disease in Argentina in 2001. The spatial and temporal distribution of the epidemic was investigated using nearest-neighbour and spatial scan tests and by estimating the frequency distributions of the times to intervention, and distances and times between outbreaks. The outbreaks were clustered and associated significantly (P<0.01) with herd density; 94 per cent were located in the Pampeana region, where the cattle population is concentrated, which had an attack rate of 1.4 per cent. The clustering results suggested that the virus had spread locally between outbreaks. Most of the outbreaks were separated by one day and the maximum distance between outbreaks was almost 2000 km, indicating that the infection spread rapidly over large distances. The index outbreak was detected more than 15 days after the primary outbreak, and restrictions on the movement of cattle were probably not enforced until about one month after infection occurred. As in other major epidemics, the period between the first outbreaks and the effective application of control strategies was probably crucial in determining the progress of the epidemic.

Animals↗

Foot and mouth disease in Mali: the current situation and proposed control strategies.

Two main reasons prompted the authors to write this paper. First, outbreaks of foot and mouth disease (FMD) have occurred repeatedly in Mali and neighbouring countries during the last decade. Secondly, there is a pressing need for control strategies, since the first molecular epidemiological studies of FMD virus in West Africa have demonstrated that FMD transmission across national boundaries is common in this region. The authors discuss the FMD outbreaks that occurred during the period of 1980 to 1996, which were reported to the Central Livestock Office in Mali by field veterinarians. The outbreaks in 1980 and 1982 were confined to the regions of Kayes and Gao, respectively. Between 1991 and 1992, outbreaks occurred in Segou, Sikasso and Bamako. In 1996, FMD outbreaks were reported in cattle populations throughout Mali, except in Kidal in the Sahara desert, where temperatures reach 45 degrees C. High mortality was reported in young animals, while morbidity approached 100% in adult cattle.

Animals↗

Rapid and sensitive detection of foot-and-mouth disease virus in tissues by enzymatic RNA amplification of the polymerase gene.

Direct detection of foot-and-mouth disease (FMD) virus from infected bovine and porcine tissue was investigated using a modified polymerase chain reaction (PCR) technique. A high degree of conservation was found in the genomic region coding for the viral RNA polymerase among the seven FMD viral (FMDV) serotypes. An oligomeric primer pair and probe were constructed from consensus sequence data within this area. First strand cDNA was synthesized using random hexamers and Moloney MuLV reverse transcriptase. The oligomeric primers used for PCR of the random primed cDNA yielded a 454-base-pair target amplification product. The PCR product was sized by agarose gel electrophoresis and hybridized strongly with the consensus sequence oligomeric probe. The PCR product was further examined by digestion with NcoI, confirming the predicted internal restriction enzyme site. All seven serotypes of FMDV RNA were amplified in a few hours and the PCR product tested positive. The sensitivity of the enzymatic amplification for detection of FMDV was 10 TCID50 by gel electrophoresis and less than 1 TCID50 when combined with hybridization to a labeled probe. The technique was specific, as determined by examination of at least 12 other viruses, including enteroviruses and other agents of vesicular disease. In vitro enzymatic amplification of cDNA from FMDV RNA using the modified PCR technique is highly specific, rapid and at least as sensitive as presently used procedures for FMDV laboratory diagnosis.

Animals↗

Single dilution ELISA for detection of serum antibody to foot-and-mouth disease virus in cattle.

A single dilution blocking ELISA was developed and evaluated for measuring serum antibody to foot-and-mouth disease virus (FMDV). Basic parameters of the assay were established and a positive-negative threshold determined from testing 176 specific antibody negative sera from Australian cattle. Sera collected from immunised animals in Thailand were tested by ELISA and virus-neutralisation (VN) tests and the results compared. A positive correlation between ELISA and VN titres was recorded for each of the 3 FMDV serotypes endemic in Thailand, with the overall correlation coefficient being r = 0.8990. A positive correlation for each of the serotypes was also found between ELISA titre and the degree of blocking (percentage inhibition) of each test serum at a dilution of 1:16, with the overall correlation being r = 0.8704. This simplified ELISA was sensitive, specific and gave reproducible results, and had the potential to test quickly and efficiently a considerable number of sera.

Animals↗

Foot-and-mouth disease in the UK: what should we do next time?

Mathematical models were used to guide the UK foot-and-mouth disease (FMD) control policy during the 2001 epidemic. Based on data collected during the epidemic, prospective modelling using a variety of approaches gave the same conclusions: (i) that the epidemic had not been brought under control by 'traditional' methods, and (ii) that neighbourhood control measures (the contiguous cull) could bring the epidemic under control and result in a net saving of livestock. Retrospective analyses suggest that the subsequent course of the epidemic was consistent with a beneficial impact of the contiguous cull and that it would have been difficult to achieve a better outcome using reactive vaccination, which would have required very large-scale vaccination programmes to have been implemented quickly. Perhaps the most important lesson to be learned is the vital importance of rapid and decisive intervention in response to an outbreak, including the earliest possible implementation of a national ban on the movement of livestock once the presence of disease is confirmed.

Animals↗

Application of the enzyme linked immunosorbent assay to the detection and identification of foot-and-mouth disease viruses.

An indirect enzyme linked immunosorbent assay (ELISA) was applied to the detection and identification of foot-and-mouth disease (FMD) virus types. The test proved successful for the specific detection of virus from infected tissue culture, and from epithelial tissues from bovines suspected of having FMD. The ELISA compared favourably with the complement fixation (CF) test, being more sensitive and unaffected by anticomplementary factors.

Animals↗