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PubMed2001

Genetic heterogeneity of SAT-1 type foot-and-mouth disease viruses in southern Africa.

Genetic relationships of 50 SAT-1 type foot-and-mouth disease viruses were determined by phylogenetic analysis of an homologous 417 nucleotide region encoding the C-terminal half of the VP1 gene and part of the 2A segment. Viruses obtained from persistently-infected African buffalo populations were selected in order to assess the regional genetic variation within the host species and compared with ten viruses recovered from recent and historical cases of clinical infection. Phylogenetic reconstructions identified three independently evolving buffalo virus lineages within southern Africa, that correspond with the following discrete geographic localities: (1) South Africa and southern Zimbabwe, (2) Namibia, Botswana and western Zimbabwe, and (3) Zambia, Malawi and northern Zimbabwe. This strict geographic grouping of viruses derived from buffalo was shown to be useful for determining the origin of recent SAT-1 epizootics in livestock. The percentage of conserved amino acid sites across the 50 SAT-1 viruses compared in this study was 50%. Most mutations were clustered within three discrete hypervariable regions, which coincide with the immunogenic G-H loop, H-1 loop and C-terminus region of the protein. Despite the high levels of variation within the primary sequence, secondary structural features appear to be conserved.

Africa South of the Sahara↗

PubMed2003

A stochastic-modeling evaluation of the foot-and-mouth-disease survey conducted after the outbreak in Miyazaki, Japan in 2000.

When foot-and-mouth-disease (FMD) was identified in Miyazaki prefecture in March 2000, Japan conducted an intensive serological and clinical survey in the areas surrounding the index herd. As a result of the survey during the 21 days of the movement-restriction period, two infected herds were detected and destroyed; there were no other cases in the months that followed. To evaluate the survey used for screening the disease-control area and surveillance area, we estimated the herd-level sensitivity of the survey (HSe) through a spreadsheet model using Monte-Carlo methods. The Reed-Frost model was incorporated to simulate the spread of FMD within an infected herd. In the simulations, 4, 8 and 12 effective-contact scenarios during the 5-day period were examined. The estimated HSes of serological tests (HSeE) were 71.0, 75.3 and 76.3% under the 4, 8 and 12 contact scenarios, respectively. The sensitivity analysis showed that increasing the number of contacts beyond 12 did not improve HSeE, but increasing the number of sampled animals and delaying the dates of sampling did raise HSeEs. Small herd size in the outbreak area (>80% of herds have <20 animals) seems to have helped in maintaining HSeE relatively high, although the serological inspection was carried out before sero-positive animals had a chance to increase in infected herds. The estimated herd-level specificity of serological tests (HSpE) was 98.6%. This HSpE predicted 224 false-positive herds (5th percentile estimate was 200 and 95th percentile was 249), which proved close to the 232 false-positive herds actually observed. The combined-test herd-level sensitivity (serological and clinical inspections combined; CTHSe), averaged 85.5, 87.6 and 88.1% for the 4, 8 and 12 contact scenarios, respectively. Using these CTHSes, the calculated probability that no infected herd was overlooked by the survey was > or =62.5% under the most-conservative, four-contact scenario. The probability that no more than one infected herd was overlooked was > or =89.7%.

Animals↗

PubMed2003

Results of epidemic simulation modeling to evaluate strategies to control an outbreak of foot-and-mouth disease.

OBJECTIVE: To assess estimated effectiveness of control and eradication procedures for foot-and-mouth disease (FMD) in a region of California. SAMPLE POPULATION: 2,238 herds and 5 sale yards in Fresno, Kings, andTulare counties of California. PROCEDURE: A spatial stochastic model was used to simulate hypothetical epidemics of FMD for specified control scenarios that included a baseline eradication strategy mandated by USDA and supplemental control strategies of slaughter or vaccination of all animals within a specified distance of infected herds, slaughter of only high-risk animals identified by use of a model simulation, and expansion of infected and surveillance zones. RESULTS: Median number of herds affected varied from 1 to 385 (17% of all herds), depending on type of index herd and delay in diagnosis of FMD. Percentage of herds infected decreased from that of the baseline eradication strategy by expanding the designated infected area from 10 to 20 km (48%), vaccinating within a 50-km radius of an infected herd (41%), slaughtering the 10 highest-risk herds for each infected herd (39%), and slaughtering all animals within 5 km of an infected herd (24%). CONCLUSIONS AND CLINICAL RELEVANCE: Results for the model provided a means of assessing the relative merits of potential strategies for control and eradication of FMD should it enter the US livestock population. For the study region, preemptive slaughter of highest-risk herds and vaccination of all animals within a specified distance of an infected herd consistently decreased size and duration of an epidemic, compared with the baseline eradication strategy.

Animals↗

PubMed2002

Further studies on the early protective responses of pigs following immunisation with high potency foot and mouth disease vaccine.

The ability of an emergency oil adjuvanted foot-and-mouth disease (FMD) vaccine to elicit early protective immunity in pigs against direct contact homologous challenge was examined. All vaccinates showed reduced viraemia and shedding of FMDV, and certain animals were protected, showing no clinical signs. IL-6, IL-8 and IL-12 were consistently detected in challenged animals that had been vaccinated. Other cytokines--IL-1, IL-2, TNF, TGF and interferons--were not detected. This demonstrates that the vaccine did not induce a systemic inflammatory response, nor a systemic elevation of T lymphocyte activity. Although the IL-6 and IL-8 did not relate to protection, IL-12 production was highest in the protected vaccinated pigs. Thus, the induction of monocytic cell activity, demonstrable by the production of IL-6, IL-8 and IL-12, appears to play a critical role in FMDV emergency vaccine induction of the innate immune defences which relate to early protection against FMD. The possible modes of defence in which such cytokine activity would be involved are discussed.

Animals↗

PubMed2006

Application of non-structural protein antibody tests in substantiating freedom from foot-and-mouth disease virus infection after emergency vaccination of cattle.

There has been much debate about the use of the so-called "vaccinate-to-live" policy for the control of foot-and-mouth disease (FMD) in Europe, according to which, spread of the FMD virus (FMDV) from future outbreaks could be controlled by a short period of "emergency" vaccination of surrounding herds, reducing the need for large-scale preemptive culling of at-risk animals. Since vaccinated animals may become subclinically infected with FMDV following challenge exposure, it is necessary to either remove all vaccinates (vaccinate-to-kill) or to detect and remove vaccinates in which virus is circulating or has established persistent infections (vaccinate-to-live), in order to rapidly regain the most favoured trading status of FMD-free without vaccination. The latter approach can be supported by testing vaccinated animals for the presence of antibodies to certain non-structural proteins (NSP) of FMDV, which are induced by infection with the virus, but not by vaccination with purified FMD vaccines. Using test sensitivity and specificity data established at a recent workshop on NSP assays [Brocchi E, Bergmann I, Dekker A, Paton DJ, Sammin DJ, Greiner M, et al. Comparative performance of six ELISAs for antibodies to the non-structural proteins of foot-and-mouth disease. Vaccine, in press], this paper examines the ways in which serological testing with NSP ELISAs can be used and interpreted and the effect that this will have on the confidence with which freedom from infection can be demonstrated within guidelines specified by the World Animal Health Organisation and the European Commission.

Animals↗

PubMed1993

Detection of foot-and-mouth disease virus RNA in clinical samples and cell culture isolates by amplification of the capsid coding region.

Foot-and-mouth disease is one of the most economically important virus diseases of livestock. Two important requirements for the control of this disease are rapid laboratory diagnosis and epidemiological investigation. The use of the polymerase chain reaction method (PCR) to amplify specific nucleic acid regions offers the unique possibility of combining swift viral detection with the production of genetic material suitable for sequencing and other methods of molecular epidemiological analysis. The sequencing of the region of foot-and-mouth disease virus (FMDV) genome encoding the capsid proteins of the virus (approximately 2260 bps), provides valuable information that adds to the molecular characterisation of an isolate. This paper describes the use of the PCR for the amplification of this region of the FMDV genome from bovine clinical samples and cell culture isolates. Suitable pairs of oligonucleotide primers were selected from the published sequence of FMDV type O1, Kaufbeuren. One primer set amplified 2091 bps of the capsid coding region of all seven serotypes of FMDV. The other primer set amplified 216 bp from this region of FMDV type O1, BFS 1860, in nucleic acid extracts from several clinical samples. Nucleic acid extracts from the picornaviruses, bovine enterovirus and swine vesicular disease virus, which affect the same animals, were not amplified. Direct sequencing was carried out on the amplified fragments and showed that the PCR products were > 98% homologous to published FMDV sequences.

Animals↗

PubMed1965

RELATIONSHIP OF DONOR AGE TO IN VITRO PRODUCTION OF FOOT-AND-MOUTH DISEASE VIRUS BY MOUSE KIDNEY CELLS.

Multiplication of foot-and-mouth disease virus (FMDV) was compared in kidney cells from 7- to 35-day-old mice representing various degrees of age resistance to this virus. Three types of cell preparations were used: primary monolayer cultures, suspensions of dispersed cells, and suspensions of minced tissue. Virus multiplication in the two types of cell suspensions was related to the age of the donors both in regard to time when multiplication first became evident and to the amount of virus produced. While adsorption rates were similar in the cells from all age groups, virus multiplication began earlier in cells from younger mice and more virus was produced by these cells than by cells from older animals. There was no significant difference in the virus growth rates in the primary monolayer cultures of cells. The results indicate that kidney cells from mice 7 to 35 days old vary in their ability to produce virus in relation to the degree of susceptibility of the cell donors. After propagation of the cells in primary monolayer cultures, however, this difference no longer exists probably because of cell selection under the cultural conditions.

Aging↗

PubMed2004

Isolation of foot-and-mouth disease virus specific bovine antibody fragments from phage display libraries.

Foot-and-mouth disease virus (FMDV) is an important veterinary pathogen which can cause widespread epidemics. Due to the high antigenic variability of FMDV, it is important to undertake mutation analysis under immunological pressure. To study the bovine antibody response at a molecular level, phage display technology was used to produce bovine anti-FMDV Fabs. CH1-VH chains with FMDV specific binding could be isolated after selection from a library made from vaccinated cattle. Though their involvement in the bovine immune response remains to be ascertained, it is planned to express the five different selected VH domains in bacterial or insect systems as sequence homologies with integrin beta6 chain could shed light on the basis of FMDV type receptor specificities.

Amino Acid Sequence↗

PubMed1970

Studies on the 1967-8 foot-and-mouth disease epidemic. The relation of weather to the spread of disease.

An analysis of the 1967-8 foot-and-mouth disease epidemic with reference to the initial spread, the origin of outbreaks more than 60 km. from the main epidemic area, the series of outbreaks near Worcester, a specific case history and the daily rate of spread of the epidemic, strongly suggests that the weather played a major part in the spread of disease. The two main factors involved in this type of spread are wind and precipitation. It is noted that after the epidemic had been checked, following anticyclonic weather, the association between the weather and the spread of disease was less apparent.

Air Microbiology↗

PubMed1998

Antigenic structure of foot and mouth disease virus type A22 (Indian isolates).

Variations in foot and mouth disease virus are due to amino acid substitutions in the VP1, which is a major immunogen. Analysis of this hypervariable region is essential to know the antigenic structure of the serotype and is necessary to select a suitable vaccine strain. FMDV type A22 is one of the four prevailing virus types for which the vaccine is used regularly. To understand the antigenic structure of this type, carboxy- terminal region of VP1 from two field isolates and vaccine virus were sequenced and analysed. The results indicate that, Indian A22 has distinct antigenic structure.

Amino Acid Sequence↗

PubMed2004

Reintroduction of foot-and-mouth disease in Argentina: characterisation of the isolates and development of tools for the control and eradication of the disease.

This paper describes the antigenic and molecular characterisation of foot-and-mouth disease virus (FMDV) strains isolated during the 2000-2002 epidemic in Argentina, and the strategy implemented for disease control. Two different FMDV serotypes, O and A, were involved. Of the various field isolates studied, two distinct O1 lineages (strains Corrientes/00 and Misiones/00) and two serotype A lineages (A/Argentina/00 and A/Argentina/01 prototypes) were identified. The genome sequences of these strains were compared with sequences of previous regional isolates and sequences of vaccine strains. O1 strains were found to be related to regional strains while serotype A strains were found to be more distanced from them. The updating of the antigenic composition of the vaccines used in the emergency was a key issue, since the outbreaks stopped shortly after the implementation of the vaccination programs. The O1 strains quickly disappeared from the field following strict control measures and the use of vaccines containing O1/Campos strain. However, in the case of the A serotype strains, the situation was different, since the use of a vaccine containing strain A24/Cruzeiro yielded acceptable levels of protection only after re-vaccination. Therefore, the new field strains A/Argentina/00 and A/Argentina/01 were incorporated into the vaccine, leading to an effective control of the disease. Viral circulation greatly diminished, as indicated by the significant reduction in the number of outbreaks and in the number of animals with antibodies against non-structural proteins. Satisfactory levels of protective antibodies were subsequently detected in the cattle population (above 75% protection). The absence of outbreaks after January 2002 indicated that the epidemic was controlled.

Animals↗

PubMed1994

Development of an effective vaccine against foot-and-mouth disease with partially purified and concentrated virus antigen.

Foot-and-mouth disease (FMD) virus is poorly immunogenic. There is need to improve the quality of the vaccine by incorporating enhanced quantity of purified virus antigen to prevent sporadic breakdown of immunity in regularly vaccinated organized herds. A technique has been standardized for virus purification and concentration by polyethylene glycol (PEG) treatment for large scale production of concentrated FMD vaccine. The vaccine prepared with tenfold concentrated antigen was given field trial in an organised farm with a reduced dose as compared to the conventional vaccine. High level serum neutralizing antibody in cattle was observed throughout the entire period of study. The concentrated vaccine controlled the spread of the disease when used in face of outbreak in villages adjacent to the organized farm.

Animals↗

PubMed2003

Antigenic characterization of foot-and-mouth disease virus serotype Asia1 field isolates using polyclonal and monoclonal antibodies.

Foot-and-mouth disease virus (FMDV) serotype Asia1 field isolates (n = 100) were compared using a panel of 11 monoclonal antibodies (Mab) in sandwich ELISA. The majority (over 89%) of the isolates showed either homologous (76% and above reactivity) or reduced affinity (20-75% reactivity) for the Mabs 2A, 13, 40, 34 and 81, suggesting that these Mab binding epitopes are conserved, whereas a more variable reactivity was observed for the Mabs B3, 1A, 24, 72, 82 and 89. Polyclonal relationship ('r' value) of the field isolates in liquid phase blocking (LPB) ELISA was examined, and the mean 'r' value was 0.62 relative to vaccine virus IND 63/72. Some of the field isolates (n = 34) were tested in virus neutralization test (VNT) and showed an 'r' value of >0.40. Although a minor antigenic difference was observed in the Mab profiling study, there has not been large antigenic divergence between reference virus and field viruses, thereby providing evidence of wide antigenic coverage of the vaccine strain.

Animals↗

PubMed2002

The fencing issue relative to the control of foot-and-mouth disease.

Certain livestock diseases in sub-Saharan Africa, such as foot-and-mouth disease are difficult to control because of the large numbers of infected wildlife hosts. These wildlife disease reservoirs form a continuous hazard of transmittal of the diseases to domestic livestock, which limits the access of livestock products from southern Africa to international markets. The disease reservoirs are often found in border areas between countries with susceptible species and infected reservoir animals continuously crossing the border. A regional approach to disease control is probably the only way to achieve any real progress. Here we review the positive and negative attributes of fencing as a control mechanism for disease transmission.

Animal Husbandry↗

PubMed2002

Natural aerosol transmission of foot-and-mouth disease virus to pigs: minimal infectious dose for strain O1 Lausanne.

Foot-and-mouth disease virus (FMDV) can spread by a variety of mechanisms, including, under certain circumstances, by the wind. Simulation models have been developed to predict the risk of airborne spread of FMDV and have played an important part in decision making during emergencies. The minimal infectious dose of FMDV for different species by inhalation is an important determinant of airborne spread. Whereas the doses for cattle and sheep have been quantified, those for pigs are not known. The objective of the study was to obtain that data in order to enhance the capability of simulation models. Under experimental conditions, forty pigs were exposed individually to naturally generated aerosols of FMDV, strain O1 Lausanne. The results indicated that doses under 100 TCID50 failed to infect pigs but doses of approximately 300 TCID50 caused short-term sub-clinical infection. The calculations suggested that a dose of more than 800 TCID50 is required to cause infection and typical disease.

Aerosols↗

PubMed1991

Developments in foot-and-mouth disease vaccines.

The current status of foot-and-mouth disease (FMD) vaccine production is reviewed. The production of antigen in bovine tongue epithelium (Frenkel culture) is described and improvements in monolayer and suspension cultures of cell lines are outlined. Inactivation of viral antigen and safety tests are discussed. A 'minimum safety level' is recommended: at the end of the inactivation process, antigen batches of any size should contain less than one virus particle. After inactivation the antigen can be formulated into a vaccine or purified and concentrated for storage at ultra-low temperatures in a vaccine bank. Vaccines prepared with the adjuvants Al(OH)3 and saponin are compared with (double) oil emulsion vaccines. Because oil vaccines can protect both cattle and pigs and induce long-term protection, they are most suitable for use in ring vaccinations. A new generation of vaccines, based on constructed modified-live viruses or (bio-) synthetic peptides, is briefly reviewed.

Animals↗

PubMed2003

Innate immune responses following emergency vaccination against foot-and-mouth disease virus in pigs.

Inactivated "emergency" foot-and-mouth disease virus (FMDV) vaccine of high potency will induce early protection against the disease, implying a critical role for innate immune defences. At 3 and 6 days post-vaccination (dpv), there was no evidence of vaccine-induced specific anti-FMDV antibodies (Abs), nor enhanced uptake and destruction of opsonised virus by macrophages. Sera from vaccinates and control animals showed similar capacity to neutralise the virus, and were not different from the pre-vaccination sera. There were also no distinguishable changes in the distribution of the different peripheral blood leucocyte (PBL) subpopulations. Nor was any vaccine-induced increase in production of acute phase proteins noted. In contrast, chemotaxis assays identified an increase in PBL migratory activity which was vaccine-related. Furthermore, sera from 3 days post-vaccination contained elevated chemotactic potential. These results demonstrate that enhanced chemotaxis of cells of the innate immune defences, could play an important role during the early protection induced by emergency FMDV vaccines.

Acute-Phase Proteins↗

PubMed2003

Molecular epidemiology of SAT3-type foot-and-mouth disease.

VP1 gene nucleotide sequences of 51 SAT3-type foot-and-mouth disease (FMD) viruses from seven southern and eastern African countries were used to infer a gene phylogeny. Results obtained by phylogenetic analysis of the homologous 405 nt region corresponding to the C-terminal 128 amino acids of 1D and adjacent 7 amino acids of 2A indicate that there are six distinct virus lineages evolving independently in different geographical localities in accordance with the FMD topotype concept. Topotypes I-IV occur in southern Africa, whilst topotypes V and VI are unique to East Africa. Viruses of different topotypes differ from each other at 20% or more of the nucleotide sites, specified in this study. Despite the limited geographical distribution of this serotype, the level of intratypic variation is intermediate between that of SAT1 and SAT2, both of which are widely distributed in sub-Saharan Africa. Within SAT3, 37.3% and 47.4% of sites were completely conserved on nucleotide and amino acid levels, respectively. The locality-specific grouping of viruses permits accurate determination of the sources of outbreaks, whilst the high levels of variation within the immunodominant 1D protein has implications for the control of the disease through vaccination.

Africa, Eastern↗