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Foot-and-mouth disease eradication efforts in the Republic of Korea.

On March 20, 2000, a suspected vesicular disease in cattle was reported to the National Veterinary Research and Quarantine Service (NVRQS) of the Republic of Korea. This represented the index case of a foot-and-mouth disease (FMD) outbreak, which spread through several provinces. The Republic of Korea had been free of FMD for 66 years prior to the reintroduction of the virus and had recently suspended imports of pork and pork products from neighboring Japan owing to a reported FMD out-break in that country. The Korean outbreak was ultimately controlled through the combination of preemptive slaughter, animal movement restrictions, and a strategy of ring vaccination. The purpose of this paper is to review the current FMD situation in Korea in the aftermath of its 2000 epizootic and how it may affect future efforts to eradicate or reduce risk of reintroduction of the disease into Korea.

Animals↗

Adenovirus type 21-associated acute flaccid paralysis during an outbreak of hand-foot-and-mouth disease in Sarawak, Malaysia.

We report the virological and clinical features of 8 children who presented with adenovirus-associated acute flaccid paralysis (AFP) during an epidemic of enterovirus type 71 (EV71)-associated hand-foot-and-mouth disease (HFMD) in Sarawak, Malaysia, in 1997. Neutralization tests and phylogenetic analysis revealed adenovirus type 21 (Ad21), although DNA restriction digests suggested that this virus was different from the prototype Ad21. Four children had upper-limb monoparesis, 2 had lower-limb monoparesis (one of whom had changes in the anterior spinal cord noted on magnetic resonance imaging), and 2 had flaccid paraparesis. At follow-up, 4 children were noted to have made full recoveries and 3 had residual flaccid weakness and wasting. Neurophysiological investigation revealed a mixture of axonal and demyelinating features in motor and sensory nerves, with denervation. These findings suggest that Ad21 might cause AFP by anterior horn cell damage or neuropathy of the brachial or lumbosacral plexus. The occurrence of these unusual adenovirus infections during an outbreak of EV71-associated HFMD suggests that an interaction between the 2 viruses may have occurred.

Acute Disease↗

Environmental impacts of the foot and mouth disease outbreak in Great Britain in 2001: the use of risk analysis to manage the risks in the countryside.

Restrictions imposed for more than ten months throughout Great Britain in 2001 to control and eradicate foot and mouth disease (FMD) had a damaging effect on tourism and rural businesses. Risk assessment can play a valuable role in ensuring that the action taken is proportionate to the risk, and that countryside activities are allowed to resume when this can be done without compromising the objective of controlling and eradicating the disease. A risk assessment unit was established at the commencement of the epidemic to consider the risks posed by particular activities, to identify ways of managing those risks, and to make recommendations which could be used by policy makers when deciding what action to take. The assessments produced by the unit were published and the scientific rationale which supported policy and procedural changes was thereby exposed to public scrutiny and criticism. The author lists the activities subjected to veterinary risk assessments and describes how the process was used to consider public access to the countryside, leading to policy changes which within nine months resulted in the reopening of more than 96% of footpaths and bridleways without causing new outbreaks of FMD. A completed risk assessment is also included.

Animals↗

Development of DNA vaccines for foot-and-mouth disease, evaluation of vaccines encoding replicating and non-replicating nucleic acids in swine.

We have developed naked DNA vaccine candidates for foot-and-mouth disease (FMD), an important disease of domestic animals. The virus that causes this disease, FMDV, is a member of the picornavirus family, which includes many important human pathogens, such as poliovirus, hepatitis A virus, and rhinovirus. Picornaviruses are characterized by a small (7-9000 nucleotide) RNA genome that encodes capsid proteins, processing proteinases, and enzymes required for RNA replication. We have developed two different types of DNA vaccines for FMD. The first DNA vaccine, pP12X3C, encodes the viral capsid gene (P1) and the processing proteinase (3C). Cells transfected with this DNA produce processed viral antigen, and animals inoculated with this DNA using a gene gun produced detectable antiviral immune responses. Mouse inoculations with this plasmid, and with a derivative containing a mutation in the 3C proteinase, indicated that capsid assembly was essential for induction of neutralizing antibody responses. The second DNA vaccine candidate, pWRMHX, encodes the entire FMDV genome, including the RNA-dependent RNA polymerase, permitting the plasmid-encoded viral genomes to undergo amplification in susceptible cells. pWRMHX encodes a mutation at the cell binding site, preventing the replicated genomes from causing disease. Swine inoculated with this vaccine candidate produce viral particles lacking the cell binding site, and neutralizing antibodies that recognize the virus. Comparison of the immune responses elicited by pP12X3C and pWRMHX in swine indicate that the plasmid encoding the replicating genome stimulated a stronger immune response, and swine inoculated with pWRMHX by the intramuscular, intradermal, or gene gun routes were partially protected from a highly virulent FMD challenge.

Animals↗

Molecular epidemiology of foot-and-mouth disease (FMD) in Israel in 1994 and in other Middle-Eastern countries in the years 1992-1994.

The reverse transcriptase-polymerase chain reaction (RT-PCR) and direct sequencing were employed in the diagnosis and typing of foot-and-mouth disease virus (FMDV) in samples taken during the 1994 disease outbreak in Israel. Using PCR, virus isolation and serological methods it was shown that the 1994 disease outbreak in Israel and other Middle-Eastern countries was caused by O1 type virus. Direct PCR sequencing of VP1 genes and homology analysis of the virus isolates revealed that there were two distinct outbreaks in Israel. The first originated in Jordan, moved to the West Bank territory and then to the Lower Galilee. The second outbreak, caused by another virus, was responsible for disease outbreaks in South Lebanon, Upper Galilee and the Golan Heights. When viral sequences of isolates from the 1993 outbreaks in Egypt and Lebanon were included in the analysis, they showed a high degree of VP1 sequence homology between themselves, suggesting a common origin.

Animals↗

[Production, control and use in swine of anti-foot-and-mouth disease vaccine in oil adjuvant].

A certain number of parameters involved in the manufacture, control and use of an efficacious vaccine against foot-and-mouth disease have been studied. This report considers the problems raised by the standardization of the raw material constituent to the vaccine as well as the different types of innocuity and activity testing carried out on sows, young pigs and bacon pigs. Special attention is given to virulence testing methods, to the criteria allowing evaluation of the quality of the vaccines and to the transmission of maternal immunity of the sows to their piglets and its incidence on the vaccination schedule.

Adjuvants, Immunologic↗

Quality assurance/quality control of foot and mouth disease solid phase competition enzyme-linked immunosorbent assay--Part II. Quality control: comparison of two charting methods to monitor assay performance.

Diagnostic laboratories are increasingly required to meet stringent quality standards, and validated assays are needed to achieve formal accreditation. Validation of test methods is often considered to be finalised when the assay parameters and characteristics have been established. However, like any process, diagnostic assays are subject to random variation resulting in shifts in the mean test values. Continuous monitoring of assays using control charts will alert the interpreter of changes in performance. For this purpose, several charting methods have been developed and implemented. This paper compares the Shewhart and the exponentially weighted moving average (EWMA) control charts with respect to the day to day monitoring of internal quality control samples for the foot and mouth disease solid phase competition enzyme-linked immunosorbent assay. Both chart types are equally sensitive to shifts, but the EWMA method seems to provide the best balance between false rejection and false acceptance.

Animals↗

Direct and indirect contact rates among beef, dairy, goat, sheep, and swine herds in three California counties, with reference to control of potential foot-and-mouth disease transmission.

OBJECTIVE: To estimate direct and indirect contact rates on livestock facilities and distance traveled between herd contacts. SAMPLE POPULATION: 320 beef, dairy, goat, sheep, and swine herds, 7 artificial insemination technicians, 6 hoof trimmers, 15 veterinarians, 4 sales yard owners, and 7 managers of livestock-related companies within a 3-county region of California. PROCEDURE: A questionnaire was mailed to livestock producers, and personal and telephone interviews were conducted with individuals. RESULTS: Mean monthly direct contact rates were 2.6, 1.6, and 2.0 for dairies with < 1,000, 1,000 to 1,999, and > or = 2,000 cattle, respectively. Mean indirect contact rates on dairies ranged from 234 to 743 contacts/mo and increased by 1 contact/mo as herd size increased by 4.3. Mean direct monthly contact rate for beef herds was 0.4. Distance traveled by personnel and vehicles during a 3-day period ranged from 58.4 to 210.4 km. Of livestock arriving at sales yards, 7% (500/7,072) came from > or = 60 km away, and of those sold, 32% (1,180/3,721) were destined for a location > or = 60 km away. Fifty-five percent (16/29) of owners of large beef herds observed deer or elk within 150 m of livestock at least once per month. CONCLUSIONS AND CLINICAL RELEVANCE: Direct and indirect contacts occur on livestock facilities located over a wide geographic area and at a higher frequency on larger facilities. Knowledge of contact rates may be useful for planning biosecurity programs at the herd, state, and national levels and for modeling transmission potential for foot-and-mouth disease virus.

Agriculture↗

Cleavage of translation initiation factor 4AI (eIF4AI) but not eIF4AII by foot-and-mouth disease virus 3C protease: identification of the eIF4AI cleavage site.

The translation initiation factor eIF4A is cleaved within mammalian cells infected by foot-and-mouth disease virus (FMDV). The FMDV 3C protease cleaves eIF4AI (between residues E143 and V144), but not the closely related eIF4AII. Modification of eIF4AI, to produce a sequence identical to eIF4AII around the cleavage site, blocked proteolysis. Alignment of mammalian eIF4AI onto the three-dimensional structure of yeast eIF4A located the scissile bond within an exposed, flexible portion of the molecule. The N- and C-terminal cleavage products of eIF4AI generated by FMDV 3C dissociate. Cleavage of eIF4AI by FMDV 3C is thus expected to inactivate it.

3C Viral Proteases↗

Induction of neutralizing antibodies and immunity in vaccinated guinea pigs by cyanogen bromide-peptides of VP3 of foot-and-mouth disease virus.

The specificity of guinea pig antisera against large cyanogen bromide-cleaved peptides of the virus capsid protein VP3 of foot-and-mouth disease virus type O1, strain Kaufbeuren has been characterized by double immunodiffusion, virus neutralization and protection tests. Antibodies to purified 146S particles and the cleavage peptides of VP3 showed an incomplete cross-section against VP3 peptide antigen when reacted in immunodiffusion tests, indicating that new antigenic determinants are exhibited by the peptides which are not recognized by the antiserum against the native virus proteins. The immune response against the reduced, unfolded chain constituents of VP3 was lower in comparison to that of native virus particles but still some immunological determinants remained actively capable of inducing virus-neutralizing antibodies in immunized guinea pigs.

Animals↗

[The use of synthetic peptides for detection of antibodies against foot-and-mouth disease virus in the blood from convalescent animals].

Peptides were synthesized, which, according to theoretical analysis of the antigenic structure of protein VP1 of foot-and-mouth disease (FMD) virus types A, 0, and Asia 1, corresponded to potential immunodominant protein sites. Activities of the peptides were studied by solid-phase indirect radioimmunoassay on polyethylene film with purified immunoglobulins against intact FMD virus. Virtually no cross reactions were observed. Blood sera of cattle convalescent after FMD were tested with the FMD virus and peptides containing VP1 fragments 141-160 (A22 No. 550), 140-160 (O1 No. 194), and 140-153 (Asia 1 No. 48). The specificity of interactions between the sera and peptides and the virus was uniform, this permitting the identification of the virus type which caused the disease.

Amino Acid Sequence↗

Protection of swine against foot-and-mouth disease with viral capsid proteins expressed in heterologous systems.

Three groups of swine were each inoculated with a different antigen preparation of foot-and-mouth disease virus (FMDV) capsid proteins and challenged by contact exposure to animals infected with FMDV. One group of four animals was inoculated with an extract from cells infected with a recombinant baculovirus containing the FMDV P1-2A structural protein precursor gene and a portion of the P2 gene. Two out of four animals were protected from clinical disease, but not from virus replication. A second group of animals was inoculated with an extract from Escherichia coli that expressed FMDV proteins from a construct containing the P1-2A gene, a portion of the P2 gene and the 3C protease gene. Three out of four animals in this group did not develop clinical signs of FMD upon challenge and two of four were protected against virus replication. In contrast, inoculation of a third group of swine with an extract from E. coli expressing the same FMDV construct as present in the recombinant baculovirus failed to protect any of the four animals from generalized FMD.

Animals↗

Foot-and-mouth disease: changes in serum-neutralizing activity of immunized cattle shortly after virus exposure.

After infection of the upper respiratory tract with foot-and-mouth disease (FMD) virus in immunized cattle, a drop in specific serum-neutralizing antibody activity was observed. Vaccinated cattle with high preexposure serum antibody titers had a precipitous drop for the first 4 days after virus exposure, followed by a rise in titer. This drop was also seen in passively immunized cattle with high preexposure titers; however, their antibody titers decreased for 5 to 7 days after exposure to virus. Some vaccinated and passively immunized cattle with low preexposure antibody titers showed fluctuations in their titers shortly after exposure. These data suggest that the course of infection with FMD virus in immunized cattle depends on the rapidity of new antibody formation as well as on the level of neutralizing antibody titer at the time of exposure.

Animals↗

The suitability of the 'emergency' foot-and-mouth disease antigens held by the International Vaccine Bank within a global context.

The International Vaccine Bank (IVB) based at the Institute of Animal Health (IAH) in Pirbright, United Kingdom (UK), routinely monitors the suitability of the currently held strains of foot-and-mouth disease (FMD) vaccine virus, in anticipation that vaccine may be required to control FMD outbreaks that pose a threat to member countries. Using primarily the two-dimensional micro-neutralisation test (VNT), bovine polyclonal sera raised against each of the seven current 'emergency' antigens were utilised to measure the relationship of IVB stocks to selected field isolates. The 'O' serotypes, Manisa and Lausanne, exhibited adequate levels of cross-protection against most of the type 'O' field isolates examined. A(22) Iraq 24/64 showed the broadest spectrum of reactivity against the type 'A' field isolates examined and was supplemented by A(15) Thailand 1/60. Some type 'Asia1' field isolates, particularly those from South East Asia, showed antigenic difference to the Asia1 India 8/79 vaccine strain by VNT, but in-vivo testing in the guinea pig model indicated this to be insignificant. The only 'C' serotype representative, C(1) Oberbayern, may be one of the least antigenically diverse of the current portfolio of bank antigens. Comparison of the serological and sequence data shows that despite significant genetic variation between the field isolates examined the antigens held by the IVB should still prove efficacious in the field.

Animals↗

Inhibition of L-deleted foot-and-mouth disease virus replication by alpha/beta interferon involves double-stranded RNA-dependent protein kinase.

We previously demonstrated that the ability of foot-and-mouth disease virus (FMDV) to form plaques in cell culture is associated with the suppression of alpha/beta interferon (IFN-alpha/beta). In the present study, we used Escherichia coli-expressed porcine and bovine IFN-alpha or -beta individually to demonstrate that each was equally effective in inhibiting FMDV replication. The block in FMDV replication appeared to be at the level of protein translation, suggesting a role for double-stranded RNA-dependent protein kinase (PKR). In support of these findings, treatment of porcine and bovine cells with 2-aminopurine, an inhibitor of PKR, increased the yield of virus 8.8- and 11.2-fold, respectively, compared to that in untreated infected cells. In addition, results of FMDV infection in mouse embryonic fibroblast cells derived from gene knockout mice lacking the gene for RNase L(-/-) or PKR(-/-) or both indicated an important role for PKR in the inhibition of FMDV replication.

Animals↗

The non-structural polyprotein 3ABC of foot-and-mouth disease virus as a diagnostic antigen in ELISA to differentiate infected from vaccinated cattle.

A diagnostic assay to differentiate antibodies induced by foot-and-mouth disease virus (FMDV) infection from those induced by vaccination was developed. The test is an indirect-trapping ELISA which uses a monoclonal antibody to trap the non-structural 3ABC-FMDV polypeptide expressed in E. coli. Experimental and field sera from naive, vaccinated and infected cattle were examined. Using the established threshold of 0.20 optical density units, the sensitivity of the assay was 100%, as all the experimental post-infection sera (n degree = 137) gave values greater than this threshold, irrespective of the FMDV serotype used for the infection. In contrast, more than 99% of sera from vaccinated animals were negative (225 out of 228 primo-vaccinates and 159 out of 159 multi-vaccinates). A high degree of specificity was also confirmed by the finding that 99.5% (442 out of 444) of sera from naive animals gave negative results. Serum conversion against 3ABC was first detected 8 days post-infection and demonstrable levels of 3ABC specific antibodies were detectable at least 1 year post-infection. The described 3ABC-ELISA is safe, cheap and also easy to perform in large scale serological surveys. The high specificity and sensitivity makes this test an ideal tool for FMD eradication campaigns and control programs.

Animals↗

E. coli expressed proteins as diagnostic reagents for typing of foot-and-mouth disease virus.

Truncated proteins corresponding to the C-terminal half of VP1 of four vaccine strains and two field variants of foot-and-mouth disease virus (FMDV) were expressed in E. coli. The expressed proteins were affinity purified and their type specific reactivity was confirmed by immunoprecipitation with anti-virus antibodies. Antibodies were raised against the purified proteins in guinea pigs and the type specificity of the anti peptide antibodies was confirmed by antigen capture reverse transcription polymerase chain reaction (Ag-RT/PCR) where the sera against a particular type captured the homologous virus. Antibodies were purified by immuno-affinity chromatography and tested for specificity by various serological tests. Using the purified proteins and the antibodies raised against them, tests like ELISA, Ag-RT/PCR, and latex agglutination test (LAT) were standardized. Application of the reagents in various tests was studied by screening a few field samples and by nucleotide sequencing. Specific reactivity of antibodies raised against expressed protein was seen with both vaccine virus and field samples. Thus E. coli expressed proteins and antibodies to them may form an alternative and cheap source of diagnostic reagents. The studies showed that antibodies against peptides were mono-specific and therefore may be used in LAT for rapid typing of FMDV and Ag-RT/PCR for typing ELISA negative field samples.

Animals↗