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[The effectiveness of foot-and-mouth disease vaccines in Switzerland. II. Stability problems].

One of the vaccines that were used in 1988 to immunize the Swiss national cattle population against foot-and mouth disease (FMD) was apparently not stable. Data, provided by the manufacturer, indicated a high initial antigenic content for serotype O. Protection experiments at the end of the vaccination campaign, however, indicated a substantial loss of serotype O antigen in the vaccine. Serological data, obtained during the campaign indicated that only 12% of the primovaccinated animals and 63% of previously vaccinated animals received an amount of FMD viral antigen sufficient to induce protective immunity. The primovaccinated animals were revaccinated in fall 1988 with a new batch provided by the same manufacturer. The new vaccine induced high titers of neutralizing antibodies in primo- and an anamnestic response in revaccinated cattle.

Animals↗

The minor role of pigs in outbreaks of foot-and-mouth disease of northern Thailand.

A study was undertaken in northern Thailand to examine the involvement of pigs in outbreaks of foot-and-mouth disease (FMD). Data were collected by surveying selected villages, by serological monitoring of pigs and by investigating outbreaks. Fifty-three of 58 villages (91%) surveyed reported that pigs did not develop FMD during the most recent outbreak. The source of 49/60 (82%) outbreaks was attributed to either recent purchases of infected cattle and buffalo or commingling of cattle and buffalo with stock from an infected neighbouring village. One of 60 villages (1.7%) reported that the source was introduced infected pigs. There was no association between the various hypothesised risk factors relating to the management of pigs and the frequency of FMD outbreaks in the survey. The percentage of seropositive pigs during 3 rounds of serological monitoring conducted at 6-monthly intervals in selected villages was 3.5%, 2.6% and 0%, respectively. No clinically affected pigs were observed in 11 outbreak investigations. It was concluded that pigs did not commonly become infected when there were outbreaks of FMD in village cattle and buffalo in northern Thailand. This was probably due to the pig feeding and housing practices employed by villagers that protected pigs from exposure to virus from infected cattle or buffalo, or their products.

Animals↗

Risk of foot-and-mouth disease associated with proximity in space and time to infected premises and the implications for control policy during the 2001 epidemic in Cumbria.

An analysis was made that calculated the risk of disease for premises in the most heavily affected parts of the county of Cumbria during the foot-and-mouth disease epidemic in the UK in 2001. In over half the cases the occurrence of the disease was not directly attributable to a recently infected premises being located within 1.5 km. Premises more than 1.5 km from recently infected premises faced sufficiently high infection risks that culling within a 1.5 km radius of the infected premises alone could not have prevented the progress of the epidemic. A comparison of the final outcome in two areas of the county, south Penrith and north Cumbria, indicated that focusing on controlling the potential spread of the disease over short distances by culling premises contiguous to infected premises, while the disease continued to spread over longer distances, may have resulted in excessive numbers of premises being culled. Even though the contiguous cull in south Penrith appeared to have resulted in a smaller proportion of premises becoming infected, the overall proportion of premises culled was considerably greater than in north Cumbria, where, because of staff and resource limitations, a smaller proportion of premises contiguous to infected premises was culled.

Animals↗

Quality assurance/quality control of foot and mouth disease solid phase competition enzyme-linked immunosorbent assay--Part I. Quality assurance: development of secondary and working standards.

International movement in animals and animal products has urged organisations like the World Organisation for Animal Health (OIE) to draw up guidelines to regulate and facilitate trade between Member Countries. However, as the global market continues to grow, further standardisation and harmonisation of antibody detection assays for infectious diseases are needed, especially regarding the development and use of reference materials. For OIE notifiable diseases for which primary or international reference standards are available or under development, National or Regional Reference Laboratories are encouraged to establish their own secondary and/or working standards. This paper describes the development of standards for the foot and mouth disease (FMD) solid phase competition enzyme-linked immunosorbent assay using positive serum obtained from calves vaccinated against the FMD virus. The procedure outlined in this manuscript can easily be extrapolated to similar serological assays and should lead to further international harmonisation of assays and test results.

Animals↗

Response of sheep vaccinated with large doses of vaccine to challenge by airborne foot and mouth disease virus.

Administration of three-fold or six-fold larger doses of conventional monovalent type O foot and mouth disease (FMD) vaccine to sheep prevented viraemic distribution of virus after exposure to airborne virus one week later. However, virus replication in the respiratory tract or excretion in oesophageal-pharyngeal fluids and breath was not prevented. The implication of these findings for the use of vaccine as an adjunct to a 'stamping out' policy for countries which are free from FMD and which do not practice mass annual vaccination are discussed.

Animals↗

Enhancement, by two carboxylic acid interferon inducers of resistance stimulated in mice by foot-and-mouth disease vaccine.

Simultaneous injection of divinyl ether-maleic amhydride (DVE/MA) or itaconic-acrylic acid and foot-and-mouth disease virus vaccine enhanced the survival of infant mice to subsequent injections of virus. This enhanced resistance was obtained even with doses of interferon inducers which, when administered alone, failed to protect the mice. There was some increase in serum-neutralizing antibody in mice 7 days after injection of DVE/MA and vaccine, as compared with mice given vaccine alone, but there was no clear connection between antibody level and amount of DVE/MA administered.

Animals↗

[I&R (identification and registration) system cattle: an analysis of its use during a foot-and-mouth-disease outbreak in The Netherlands].

The performance of the Dutch cattle I&R system was analysed, with emphasis on the potential use of the system for the control of an outbreak of foot and mouth disease (FMD). The analysis showed that not all mutations were centrally registered within the three working days that are allowed to pass between the actual change and the obligatory report. In particular, young calves and cattle heading for slaughter were reported too late. During an outbreak of FMD, the best strategy to trace animals off a farm seems to be first to identify all animals on the farm, using a preprocessed list of the animals that should be present on the farm according to the I&R system. Then all the animals that have left the farm during the last month can be traced in the central I&R computer or by asking the person to whom the farmer sold the cattle (the next owner). In the present study, 54% of the animals were localized within one day, and 94% within one week. Finally, some suggestions for improvement for the system are given.

Animal Husbandry↗

Immune responses to foot-and-mouth disease DNA vaccines can be enhanced by coinjection with the Isatis indigotica extract.

The Isatis indigotica extract is widely used in clinical practice for the treatment of influenza, epidemic hepatitis, epidemic encephalitis B etc. The goal of this study was to investigate whether coinjection of the Isatis indigotica extract with foot-and-mouth disease virus (FMDV) DNA vaccine could increase the protective immune response. Mice were vaccinated twice with either FMDV DNA vaccine plus the Isatis indigotica extract or DNA vaccine alone. Compared with the group of DNA vaccine alone, in the group that received DNA vaccine plus the Isatis indigotica extract was observed a significant increase in not only FMDV-specific antibody response but also T cell proliferation assay. All swine immunized with either FMDV DNA vaccine plus the Isatis indigotica extract or DNA vaccine alone were partially protected from FMDV challenge, but the signs of DNA vaccine plus the Isatis indigotica extract group were less severe than that of DNA vaccine alone. Coinjection of the Isatis indigotica extract with DNA vaccine has adjuvant effect on the immune response against viral pathogens and its application provides an effective strategy to improve the efficacy of DNA vaccines.

Adjuvants, Immunologic↗

Experiments on an early protection against foot-and-mouth disease virus.

The influence of the peptide diacetylsplenopentin (SP5) on an early protection of guinea pigs against foot-and-mouth disease (FMD) was investigated. 80% protection was achieved if SP5 was applied in a dose of 2 mg one day before challenge with FMD virus (FMDV) type O1 Lausanne strain. In comparison with this a conventional commercial adsorbate vaccine protected guinea pigs about 7 days after vaccination. An earlier protection can be obtained in general by vaccination with a higher content of the immunogen. A tenfold increase of the 146 S particle dose in a conventional oil adjuvanted FMDV vaccine protected pigs about 2 days earlier as observed after inoculating a "normal" vaccine (about 11 days).

Adjuvants, Immunologic↗

Immunogenicity of foot-and-mouth disease virus type O1 replicated in either monolayer or suspended BHK cell system.

The efficacy of vaccines formulated from the 10th passage of foot-and-mouth disease virus (FMDV) type O1 in monolayer baby hamster kidney (BHK) cells and the 8th passage in suspension BHK cells was compared in steers. The vaccines were inactivated with ethylenimine, contained an equal amount of antigen and were emulsified in oil-adjuvant. Six animals were vaccinated with each vaccine. During the challenge of immunity (91 days post-vaccination, DPV), one out of the six steers from the monolayer vaccine group became infected with the challenge virus while none of the six steers from the suspension vaccine group contracted the disease during the test period. The neutralizing antibody titers (means) of the serum samples taken at different DPV also did not suggest significant variation between these vaccines. In addition exposure to FMDV infected animals demonstrated that both vaccines elicited an immune state in the vaccinates.

Animals↗

Foot-and-mouth disease virus leader proteinase: a papain-like enzyme requiring an acidic environment in the active site.

Foot-and-mouth disease virus leader proteinase (L(pro)), a papain-like cysteine proteinase, has six acidic amino acids between 4 A and 11 A of the catalytic dyad of Cys51 and His148. In contrast, in papain and related enzymes, only one acidic residue lies within this distance. We have examined by site-directed mutagenesis the importance of each of these residues for L(pro) self-processing and cleavage of its cellular substrate, eukaryotic initiation factor 4GI. Only substitution of the electrostatic charge of aspartate 164 affected enzyme activity. Thus, in contrast to the prototype papain, L(pro) activity requires a negative charge 4.5 A from the catalytic dyad.

Amino Acids, Dicarboxylic↗

Inactivation of foot and mouth disease virus in skimmed milk with propionic acid, citric acid and hydrogen peroxide.

In order to protect farm animals from infections such as foot and mouth disease (FMD) and tuberculosis, the pasteurisation of milk and milk products designated for the feeding of animals is compulsory in Switzerland. Nowadays, milk products are often treated chemically with acids or with hydrogen peroxide in order to keep bacterial contamination low. The capacity of these chemical treatments to inactivate FMD virus in skimmed milk within 6 h at 5 degrees C was tested in this study. The results indicated that the addition of 0.1%-0.3% of consumable acids, such as citric acid or propionic acid, could not guarantee the complete inactivation of FMD virus in skimmed milk. Similar results were obtained both with FMD virus deliberately added to skimmed milk and with skimmed milk obtained from naturally infected cows. Hydrogen peroxide in concentrations of 0.1%-0.3% was also an ineffective means of controlling the risk of FMD virus transmission from contaminated milk.

Animals↗

Foot-and-mouth disease virus: a first inter-laboratory comparison trial to evaluate virus isolation and RT-PCR detection methods.

Five European reference laboratories participated in an exercise to evaluate the sensitivity and specificity of their routinely employed RT-PCR tests and cell cultures for the detection and isolation of foot-and-mouth disease (FMD) virus. Five identical sets of 20 coded samples were prepared from 10 vesicular epithelia, which were derived from submissions from suspect cases of FMD or swine vesicular disease (SVD). Sixteen samples were derived from six FMD virus positive epithelia representing four different serotypes (two each of types O and A and one each of types Asia 1 and SAT 2), two from samples which had been found to be negative by antigen ELISA and virus isolation (VI) in cell culture and two from SVD virus positive epithelia. Some of the FMD virus positive samples were prepared from 10-fold serial dilutions of three of the initial suspensions. Each laboratory tested the samples by one or more of its available RT-PCR procedures and inoculated cell cultures that it routinely uses for FMD diagnosis in attempts to isolate virus, the specificity of which was confirmed by antigen ELISA. The best of the RT-PCR assays used in each laboratory gave comparable results while the sensitivity of cell cultures was variable from high in one laboratory, moderate in two and low in two others. This prototype panel of samples would appear suitable for external quality assurance of these tests but would benefit from the inclusion of more negative samples and an extension in the serial dilution range of one or more of the FMD positive sample titration series.

Animals↗

Neutralization kinetics studies with type SAT 2 foot-and-mouth disease virus strains.

A comparison of homologous and heterologous rates of neutralization demonstrated that antigenic relationships of foot-and-mouth disease virus strains could be differentiated quantitatively by the kinetics of neutralization method described previously (Rwysed this way gave R values which were similar to those obtained with other neutralization test methods but which were generally smaller than those obtained with complement fixation test results. It was demonstrated that there were wide differences between the vaccine strains tested as demonstrated by R value relationships. An examination of r values, however, demonstrated that antisera to the Moz 1/70 strain were highly reactive with most of the virus strains from Central and Southern Africa. The selection of FMD virus strains with a wide serological range for vaccine production is discussed.

Animals↗

Human-mediated foot-and-mouth disease epidemic dispersal: disease and vector clusters.

Disease clusters were retrospectively explored at national level using a geo-referenced dataset from the 2001 Uruguayan Foot-and-Mouth Disease (FMD) epidemic. Disease location and time (first 11 epidemic weeks) were analysed across 250 counties (of which 160 were infected), without and with control for human mobility related factors (human population and road densities). The null hypothesis of random disease distribution over space and/or time was assessed with: (i) purely temporal; (ii) purely spatial; and (iii) space/time tests. At least within epidemic weeks 2 and 6, a principal disease cluster was observed in 33 contiguous counties (P < 0.01). Two secondary clusters, located at >100 km from each other, were also observed (P < 0.01). The purely spatial test that controlled for human population density identified two non-contiguous clusters (P < 0.01). Space and time analysis also revealed the same 33 counties as members of the principal cluster, of which 31 were also clustered when human population was controlled (P < 0.01). No clusters were reported by the spatial test when road density was assessed. The hypothesis that human mobility related factors autocorrelate with disease was empirically supported by two pieces of information: (i) removal of human population/road densities eliminated >93.9% of the counties included in the principal disease cluster; and (ii) statistically significant correlations (P < 0.05) were observed in the first three epidemic weeks between road density and the number of cases. Clusters where human population density was associated with 47% greater number of cases/sq. km than that of the principal cluster indicated possible roles as disease vectors (vector clusters). Selective control policy in vector clusters is recommended. Periodic (i.e. weekly) cluster and correlation analyses of both disease and other covariates may facilitate disease surveillance and help design space-specific control policy.

Animal Husbandry↗

Economic aspects of foot and mouth disease: perspectives of a free country, Australia.

Australia is a significant livestock producer and a major exporter of livestock, livestock products and livestock genetic material. An outbreak of foot and mouth disease (FMD) would have severe economic consequences on the economy. A recent study found that in an outbreak lasting six months, real gross domestic product in Australia would fall by an estimated 0.6% (AUS$3.5 billion), employment by 0.8%, and a depreciation of 3% would be recorded in the exchange rate in the first year. Much of this impact would be due to the loss of export markets. Given the significant consequences of an outbreak of FMD, Australia invests considerable resources in prevention and planning. These measures can be viewed at three levels, namely: pre-border, border and post-border. Australia recently further enhanced quarantine at the border to minimise the risk of entry of FMD. However, no matter how much is invested, there is no guarantee that FMD will not enter the country. Accordingly, it is important to ensure that comprehensive contingency plans are also in place. Recent outbreaks in previously free countries have shown that a large outbreak of FMD poses major problems for the animal health services of a country and a combined government and industry response is required.

Animal Husbandry↗