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The airborne dispersal of foot-and-mouth disease virus from vaccinated and recovered pigs, cattle and sheep after exposure to infection.

Foot-and-mouth disease virus was detected during two periods in the air of looseboxes which housed susceptible, vaccinated or recovered pigs, cattle or sheep exposed to infection. The first was 30 min to 22 h after exposure and occurred in all animals. The second was two to seven days after exposure and occurred with those susceptible and vaccinated animals which developed clinical lesions, and with vaccinated and recovered pigs and sheep, which did not develop clinical lesions. Vaccination of animals before exposure resulted in less or no virus being detected. The virus during the first period was attributed to virus trapped on the animal during exposure, and the virus during the second period to limited multiplication in the respiratory tract. Control of movement for two weeks after contact with infection is suggested as a means of preventing spread of foot-and-mouth disease in areas that contain vaccinated animals.

Air Microbiology↗

Mouse footpad Langerhans cells as an indicator for safety of foot and mouth disease virus vaccines.

The effect of various vaccines against foot and mouth disease virus (FMDV) was tested on Langerhans cell density in the footpad epidermis of mice. Injection of monovalent, bivalent and trivalent FMDV vaccines caused a reduction in Langerhans cell density in the murine skin, which was more marked at the center of the footpad, the site of injection, than at the periphery. Testing of the various components of the vaccine showed that saponin caused a marked reduction in Langerhans cells while injection of aluminium hydroxide had a lesser effect and the virus alone had no effect on these cells. Thus Langerhans cell density could serve as an efficient marker to test the safety of vaccines to FMDV since the integrity of Langerhans cells, which are the antigen-presenting cells in the skin epidermis, is needed for an effective immune response to the vaccine.

Adenosine Triphosphatases↗

Identification and isolation of foot-and-mouth disease virus from primary suspect cases in Korea in 2000.

The Republic of Korea had been free from foot and mouth disease (FMD) since 1934, until a recent outbreak in 2000. From March to April 2000, a total of 15 FMD outbreaks due to the serotype O virus were recorded. Coincidental outbreaks of FMD in cattle or pigs by the serotype O virus were reported in the region, including Taiwan, China, Japan, Russia and Mongolia. In this report, the results of emergency investigations of FMD cases on a dairy farm located approximately 5-km from the demilitarized zone in Korea are described. The causative agent of the disease was identified as the FMD virus O by reverse transcription-polymerase chain reaction (RT-PCR) assays using primers derived from the 3D polymerase, internal ribosome entry site (IRES), 1D/2B regions, enzyme-linked immunosorbent assay (ELISA) for antigen detection and typing. Sequence data of the partial 1D/2B region obtained from vesicular fluid showed close similarity (98% sequence identity) to the Kinmen isolate of the FMD virus O in Taiwan. The causative virus was isolated using black goat fetal lung cells following propagation in unweaned mice.

Animals↗

Early and cost-effective identification of high risk/priority control areas in foot-and-mouth disease epidemics.

Geo-referenced data from the 2001 Uruguayan foot-and-mouth disease (FMD) epidemic were explored to assess whether spatial analysis could lead to cost-benefit based policies. Four variables were analysed: (i) location and size of 4022 individual rural land parcels, of which 574 were infected over 60 days, (ii) animal density, (iii) percentage of dairy farms per county, and (iv) road density. Each variable was categorized into two to five classes (e.g. small/medium/large) and the proportion of cases per class reported at days 1-3 of the epidemic was compared with that reported at days 4-6. A higher proportion of cases was found at days 4-6 than at days 1-3 in areas with: small and medium size land parcels, high animal density, > 20% farms specialized in dairy production, and high road density (P < 0.03 for each). Each of these classes showed a greater proportion of cases at days 7-60 than the proportion of the total territory covered by each class's area (early case concentration ratios: 1.14-1.37). Land parcel clusters were indicated by Moran's I-test (P < 0.01). A new region was constructed by intersecting the four spatial classes associated with higher proportions of cases at days 4-6. At days 7-60, this region included 50.4% of all cases and represented 30.6% of the territory under study (final case concentration ratio: 1.65). The final area per case in this region was at least 33% lower and covered at least 45% less territory than any of the four single-variable approaches. Bio-statistical, multivariate spatial analysis of early cases may greatly increase the efficiency of epidemiologic policy.

Animal Husbandry↗

Foot-and-mouth disease in the Americas: epidemiology and ecologic changes affecting distribution.

Foot-and-mouth disease(FMD) was first recorded in South America (SA) circa 1870, in Buenos Aires, Argentina, in Uruguay, and in southern Brazil as a result of the introduction of cattle from Europe during the early days of colonization. Livestock production to trade with neighboring countries was established in the La Plata Region, and the trade of livestock and products with Chile, northeastern and central western states of Brazil, to Peru, Bolivia, and Paraguay spread FMD, which reached Venezuela and Colombia in the 1950s and finally Ecuador in 1961. The traditional forms of livestock husbandry influence the diffusion and maintenance of the FMD virus (FMDV) in different areas. Cattle production in SA depends mainly on a strong relation between cattle-calf operations and fattening operations in a complementary cycle, revealing the vulnerability and susceptibility of these areas to FMDV. Understanding the relationship between time-space behavior of the disease and the forms of production defines the FMD ecosystems, a key concept to elaborating the control/eradication strategies of national FMD eradication programs, which must be modified when trade opportunities between zones of differing sanitary status change. The role of other susceptible species besides bovines, including wildlife, in maintaining and spreading FMDV has been the subject of several studies, but in SA, bovines are so far considered to determine disease presentation. Buffalo (Bubalus bubalis) have been implicated in the spread of the disease between farms in at least one case in Brazil. Sheep are almost on a par with bovine in terms of number, especially in the Southern Cone, but their role in the maintenance of infection is not considered important, possibly owing to rearing practices. Camelid populations in the Andean region do not play an important role in the maintenance of FMD, because of short persistence of infection and low population densities in these species. The importance of wildlife is not clear, but it is accepted that animals are mostly affected as a spinoff during outbreaks in domestic species. Experimentally infected capybaras (Hydrochoerus hydrochoeris hydrochoeris) showed clinical signs and infected other susceptible species, but their role in the maintenance of infection in nature is so far not clear.

Animals↗

The 3A non-structural-protein coding region of the southern African SAT type isolates differs from that of other foot-and-mouth disease viruses.

The 3A non-structural protein of foot-and-mouth disease viruses is a relatively conserved protein comprising 153 amino acids. Recent studies have demonstrated correlation between mutations in the 3A non-structural-protein-coding region, including a 10-amino acid deletion, and attenuation of the viruses in cattle. Although the 3A coding region of several type A, O and C isolates has previously been described, nucleotide sequence data of the 3A coding region of the South African Types (SAT) 1, 2 and 3 viruses are limited. Therefore, the 3A non-structural-coding region of different SAT serotypes was determined, analysed and compared to that of European, South American and Asian isolates. The 3A regions of the SAT isolates investigated differed markedly from that of types A, O, C and Asia-1, but were similar within the group.

Africa South of the Sahara↗

The role of small ruminants in the epidemiology and transmission of foot-and-mouth disease.

Despite representing the largest part of the world's foot-and-mouth disease (FMD)-susceptible domestic livestock, sheep and goats have generally been neglected with regard to their epidemiological role. This is partly due to the often inapparent nature of the disease in these hosts. Nevertheless, their ability to become carriers represents a reservoir for further infection and spread of disease, and so trade of live sheep and goats present a major risk of entry of FMD to disease-free countries. Research and epidemiological studies continue to be necessary in order both to prevent the entry of the virus and to assist in control should the disease reoccur. This review concentrates primarily on more recent studies relating to sheep and goats and, in particular, considers the importance of these hosts in the overall epidemiology of FMD.

Animals↗

Isolation of mononuclear cytotoxic cells from cattle vaccinated against foot-and-mouth disease.

Mononuclear cells from peripheral blood leucocytes of foot-and-mouth disease (FMD) vaccinated cattle underwent blast transformation after in vitro culture with purified, inactivated, 146 S FMD virus antigen. From the prolonged culture of blast cells in medium with Interleukin-2 (5-10 U/ml), CD 45-positive effector cells were derived, which showed a potent, non MHC-restricted activity against virus-infected cells, the extent of which was inversely correlated with multiplicity of infection (MOI). Extensive characterization of effector cells by means of monoclonal antibodies (MAbs) in flow cytometry, lysis of various cell populations with MAbs and complement, Fc receptor analysis and 51Cr release assays indicated that the isolated cells share some phenotypic and functional features of the human and murine Large Granular Lymphocyte/Natural Killer (N.K.) lineage.

Animals↗

Foot-and-mouth disease typing and serology in Zimbabwe.

A small foot-and-mouth disease diagnostic unit was established in Zimbabwe. Twenty-six out of 27 field specimens were successfully typed using the complement fixation technique. The antibody response in cattle to the SAT II vaccine was determined using a microtitre neutralisation method. Techniques are described which should be within the capacity of laboratories in developing countries.

Animals↗

Analysis of the B and T cell response in guinea pigs induced with recombinant vaccinia expressing foot-and-mouth disease virus structural proteins.

Recombinant vaccinia viruses expressing foot-and-mouth disease virus (FMDV) P1 and VP1 genes have been used to study the immune response induced by these viral polypeptides in guinea pigs. Anti-FMDV antibodies, but not neutralizing activity, were detected in the sera from immunized animals. The results indicate that both CD4+ and CD8+ FMDV-specific T cells were induced by the vaccinia recombinants. Consistently with the activation of CD4+ T cells, lymphocytes from immunized animals specifically proliferated in vitro in response to whole virus. The induction of virus-specific CD8+ T cells was determined by CTL assay of immune splenocytes restimulated in vitro with FMDV infected cells. Altogether, the results obtained indicate that both B and T cell immune responses to FMDV are elicited upon immunization of guinea pigs with vaccinia recombinants expressing FMDV structural polypeptides.

Animals↗

Identification of virus neutralizing epitopes on naturally occurring variants of type A12 foot-and-mouth disease virus.

Four naturally occurring antigenic variants of foot-and-mouth disease virus type A12 were examined for their capacity to be neutralized by a number of monoclonal antibodies (MAb) which recognize different sites on the virus surface. The VP1 coding region of the RNA genome was sequenced and amino acid changes were determined for the variants. One of the neutralizing sites accounted for the differing antigenic properties of the variants and the epitope was mapped to amino acid residues 150-156 of VP1. Another epitope originally thought to occupy a single site in the area of amino acids 168-179 of VP1 was found on all of the variants. Competitive binding assays did not identify the exact binding site for this monoclonal antibody and the results suggest that the epitope may represent a site more complex than a sequential epitope. A polyclonal antiserum to a 13 kDa fragment of VP1 (residues 55-179) was found to have all the virus reactivity associated with sites located between residues 133-164 of VP1. In contrast, an antiserum to VP1 was found to have additional virus binding sites outside of the 133-164 region of VP1.

Antibodies, Monoclonal↗

Nucleotide sequence heterogeneity of the RNA from a natural population of foot-and-mouth-disease virus.

The genomic RNA from isolates of foot-and-mouth-disease virus (FMDV) of serological types O or C obtained during epizootic outbreaks have been analysed by two-dimensional gel electrophoresis of the T1 RNase-generated oligonucleotides (T1 fingerprinting). Among virus isolates that are closely related serologically, 4-12 oligonucleotide changes were detected constitute the genome, the variations affect 0.7%-2.2% positions in FMDV RNA. Higher nucleotide-sequence divergence exists between the genomic RNAs from serologically unrelated viruses, while a 100-fold lower RNA sequence heterogeneity has been detected by analysis of individual clones derived from one viral isolate. Oligonucleotide mapping indicates that the variant oligonucleotides are scattered throughout the FMDV genome. We suggest that extensive genetic variability at many RNA sites is the basis for the antigenic diversity of FMDV.

Antigens, Viral↗

Purification and immunogenicity of fusion VP1 protein of foot and mouth disease virus.

A procedure has been developed to purify foot and mouth disease virus (FMDV) VP1 surface antigens from recombinant Escherichia coli. The VP1 antigens are expressed as fusion proteins derived from the E. coli Trp operon and VP1 surface protein of FMDV. The procedure is capable of recovering greater than 96% of the desired product at a purity of greater than 96%. The resulting antigens induce significant levels of virus-neutralizing antibody in guinea pigs and cattle as determined by a mouse protection assay [Skinner, H.H. (1952) Proc. Int. Vet. Congr., 15th 1, 195]. E. coli contaminants have a deleterious effect on ion-exchange chromatography as well as immunogenicity of the expressed fusion VP1 antigens. The method presented removes significant E. coli contaminants, yielding fusion VP1 proteins which are immunogenically potent. In particular, virus neutralization titers at 100-micrograms dosage of the fusion VP1 proteins of the O1 and A24 serotypes are similar to that induced by the natural VP1 proteins isolated from FMD virions.

Antigens, Viral↗

Biochemical aspects of variation in foot-and-mouth disease virus.

The biochemical basis for variation in foot-and-mouth disease virus (FMDV) has been explored by analysis of the virus RNA and the virus-induced and structural proteins of three isolates of the virus. Two of the isolates were from serotype A and the third was from serotype O. Hybridization studies of the RNAs showed greater than 80% homology between the two type A viruses and about 65% homology between the two type A viruses and the virus of type O. The ribonuclease T1 maps of the three viruses gave distinct patterns typical of FMDV, but did not show that any two of the three viruses were more closely related. The virus-induced primary translation products, P88, P52 and P100 isolated from infected cells, were compared by tryptic peptide analysis. Combinations of 3H- and 14C-leucine-labelled polypeptides were hydrolysed with trypsin and resolved on an ion-exchange column. Much greater differences were found in P88 than in P52 or P100, indicating that the major variation occurs in the region of the genome coding for the structural proteins. Similar analysis of combinations of the structural proteins of the three viruses showed that there were differences in VP1, VP2 and VP3 and these results were supported by those obtained by PAGE analysis of the Staphylococcus aureus V8 protease cleavage products.

Aphthovirus↗

Comparison of the immune response elicited by infectious and inactivated foot-and-mouth disease virus in mice.

The immune response to foot-and-mouth disease virus (FMDV) elicited by infection or immunization with inactivated virus in adult mice was examined. A model of adoptive transfer of immunocompetent cells was used for this purpose. The results presented here indicate that both short- and long-term secondary immune responses elicited by high doses of inactivated virus are indistinguishable, at the humoral or cellular level, from that observed after infection. The responses to inactivated or infectious virus were both efficiently mediated by B cells. However, immunization with low doses of inactivated virus induced a response which, although effective in aborting infection, was fully dependent on FMDV-specific T cell cooperation. These findings suggest that the different immune responses observed after infection and immunization are mainly the result of the different viral mass presented to the immune system in each case.

Animals↗

Evidence for a mouse pathogenicity locus in certain temperature-sensitive mutants of foot-and-mouth disease virus.

Serial tissue culture passaging of three foot-and-mouth disease temperature-sensitive mutants demonstrated the stability of their temperature sensitivity and mouse avirulence characteristics. Recovery of mouse-virulent temperature-sensitive viruses after passage of the mutants in mice suggested that these were not covariant expressions of the same locus, but were under the control of different genes.

Animals↗