Serological evidence of vaccination and perceptions concerning Foot-and-Mouth Disease control in cattle at the wildlife-livestock interface of the Kruger National Park, South Africa.

Communal livestock farming areas adjoining the Greater Kruger National Park Area within South Africa are part of the Foot-and-mouth disease (FMD) Protection Zone with Vaccination due to the proximity to wildlife reservoirs. FMD and its control affect the productivity of resource-poor farmers who often depend on livestock for their livelihoods. A cross-sectional study was performed with the objectives to evaluate the perceptions of farmers concerning FMD control, estimate the proportion of cattle with presumed protective antibody titres against FMD, as well as the proportion of herds with adequate herd immunity at the wildlife-livestock interface within Mpumalanga Province. One hundred and four farmers were interviewed with 73% (76/104) being cattle owners and the remainder hired cattle herders. The majority of respondents (79%, 82/104) reported a high level of satisfaction with the current animal health programmes in general. The educational level of the respondents varied by satisfaction level: the median (interquartile range; IQR) education level was standard 9 (2-12) for non-satisfied respondents, standard 3 (0-6) for little satisfied and standard 7 (2-11) for very satisfied respondents (P=0.036). Animals are not always treated at FMD inspections points, but satisfied respondents were more likely to seek veterinary assistance (P=0.001). The majority of respondents (92%, 96/104) identified the African buffalo (Syncerus caffer) as a risk factor for FMD outbreaks. Liquid-phase blocking ELISA antibody titres ≥1.6log10 were used to indicate positive serology secondary to FMD vaccination. At the time of sampling and relative to this threshold, 23% (95% confidence interval (CI): 12%-34%) of the sampled cattle had positive serology to SAT-1, 41% (95%CI: 33%-48%) to SAT-2 and 29% (95%CI: 19%-39%) to SAT-3. The median (IQR) time between the previous vaccination and sampling was 189 (168-241) days. The sampled cattle had a longer inter-vaccination interval as scheduled by state veterinary services and antibody levels were low at the time of the study. The majority of respondents expressed high satisfaction with the currently applied FMD vaccination programme, which provides an opportunity for progressive adaption of animal health programmes within the study area.

Eradication of Transboundary Animal Diseases: Can the Rinderpest Success Story be Repeated?

A matrix system was developed to aid in the evaluation of the technical amenability to eradication, through mass vaccination, of transboundary animal diseases (TADs). The system involved evaluation of three basic criteria - disease management efficiency, surveillance and epidemiological factors - each in turn comprised of a number of elements (17 in all). On that basis, 25 TADs that have occurred or do occur in southern Africa and for which vaccines are available, in addition to rinderpest (incorporated as a yardstick because it has been eradicated worldwide), were ranked. Cluster analysis was also applied using the same criteria to the 26 diseases, creating division into three groups. One cluster contained only diseases transmitted by arthropods (e.g. African horse sickness and Rift Valley fever) and considered difficult to eradicate because technologies for managing parasitic arthropods on a large scale are unavailable, while a second cluster contained diseases that have been widely considered to be eradicable [rinderpest, canine rabies, the Eurasian serotypes of foot and mouth disease virus (O, A, C & Asia 1) and peste des petits ruminants] as well classical swine fever, Newcastle disease and lumpy skin disease. The third cluster contained all the other TADs evaluated with the implication that these constitute TADs that would be more difficult to eradicate. However, it is acknowledged that the scores assigned in the course of this study may be biased. The point is that the system proposed offers an objective method for assessment of the technical eradicability of TADs; the rankings and groupings derived during this study are less important than the provision of a systematic approach for further development and evaluation.

International trade standards for commodities and products derived from animals: the need for a system that integrates food safety and animal disease risk management.

A case is made for greater emphasis to be placed on value chain management as an alternative to geographically based disease risk mitigation for trade in commodities and products derived from animals. The geographic approach is dependent upon achievement of freedom in countries or zones from infectious agents that cause so-called transboundary animal diseases, while value chain-based risk management depends upon mitigation of animal disease hazards potentially associated with specific commodities or products irrespective of the locality of production. This commodity-specific approach is founded on the same principles upon which international food safety standards are based, viz. hazard analysis critical control points (HACCP). Broader acceptance of a value chain approach enables animal disease risk management to be combined with food safety management by the integration of commodity-based trade and HACCP methodologies and thereby facilitates 'farm to fork' quality assurance. The latter is increasingly recognized as indispensable to food safety assurance and is therefore a pre-condition to safe trade. The biological principles upon which HACCP and commodity-based trade are based are essentially identical, potentially simplifying sanitary control in contrast to current separate international sanitary standards for food safety and animal disease risks that are difficult to reconcile. A value chain approach would not only enable more effective integration of food safety and animal disease risk management of foodstuffs derived from animals but would also ameliorate adverse environmental and associated socio-economic consequences of current sanitary standards based on the geographic distribution of animal infections. This is especially the case where vast veterinary cordon fencing systems are relied upon to separate livestock and wildlife as is the case in much of southern Africa. A value chain approach would thus be particularly beneficial to under-developed regions of the world such as southern Africa specifically and sub-Saharan Africa more generally where it would reduce incompatibility between attempts to expand and commercialize livestock production and the need to conserve the subcontinent's unparalleled wildlife and wilderness resources.

Balancing livestock production and wildlife conservation in and around southern Africa's transfrontier conservation areas.

Biodiversity conservation, of which the transfrontier conservation area movement is an integral part, and more effective livestock production/trade are pivotal to future rural development in southern Africa. For that reason, it is imperative to effectively ameliorate the obstacles that have impeded progress towards the coexistence of these two sectors for more than half a century. Transboundary animal diseases, foot and mouth disease in particular, have been and continue to be the most important of these obstacles. Fortunately, new developments in international sanitary standards applicable to trade in commodities and products derived from animals are beginning to make a solution possible. However, while progress in principle has been achieved, practical implementation remains problematic for technical reasons, exacerbated by inconsistent attitudes towards acceptance of non-traditional international trade standards. This paper describes the background to this situation, progress that has been achieved in the recent past and remaining difficulties that need to be overcome to advance towards achievement of balanced rural development in southern Africa.

Currently important animal disease management issues in sub-Saharan Africa.

The present international approach to management of transboundary animal diseases (TADs) is based on the assumption that most can be eradicated; consequently, that is the usual objective adopted by international organizations concerned with animal health. However, for sub-Saharan Africa and southern Africa more particularly, eradication of most TADs is impossible for the foreseeable future for a variety of technical, financial and logistical reasons. Compounding this, the present basis for access to international markets for products derived from animals requires that the area of origin (country or zone) is free from trade-influencing TADs. The ongoing development of transfrontier conservation areas (TFCAs), extending across huge areas of southern Africa, therefore presents a development conundrum because it makes creation of geographic areas free from TADs more difficult and brings development based on wildlife conservation on the one hand and that based on livestock production on the other into sharp conflict. Sub-Saharan Africa is consequently confronted by a complex problem that contributes significantly to retarded rural development which, in turn, impedes poverty alleviation. In southern Africa specifically, foot-and-mouth disease (FMD) presents the greatest problem in relation to access to international markets for animal products. However, it is argued that this problem could be overcome by a combination between (1) implementation of a commodity-based approach to trade in products derived from animals and (2) amendment of the international standards for FMD specifically (i.e. the FMD chapter in the Terrestrial Animal Health Code of the World Organisation for Animal Health [OIE]) so that occurrence of SAT serotype viruses in free-living African buffalo need not necessarily mean exclusion of areas where buffalo occur from international markets for animal products. This would overcome a presently intractable constraint to market access for southern African countries and enable conservation and livestock production to be more effectively integrated, to the benefit of both.

Longitudinal study to investigate the role of impala (Aepyceros melampus) in foot-and-mouth disease maintenance in the Kruger National Park, South Africa.

A longitudinal study was performed in the Kruger National Park, South Africa to investigate the role of impala (Aepyceros melampus) in maintaining SAT serotypes of foot-and-mouth disease (FMD) virus. Three sampling sites with different histories of FMD outbreaks in impala and also of varying ecology were chosen. At three monthly intervals approximately 40 impala were bled and examined for clinical FMD at each of these sites for a period of 6 years, followed by 4 years of less frequent sampling. During the 10 years of the study, clinical disease was only observed once at a single sampling site, while at two of the three locations, serological evidence of infection was detected; in one locality this was a frequent occurrence. The discrepancy between clinically evident disease and serological evidence of infection indicated that sub-clinical infection with these viruses may be more regular than previously suspected. Furthermore, there was evidence that either SAT-serotype infection is maintained within local impala populations for prolonged periods or that re-infection of impala by buffalo occurs repetitively, sometimes at frequent intervals. A mixed-effects logistic regression model showed that females and older animals had a higher risk of seropositivity, while summer and autumn also represent periods when there is a heightened risk of seropositivity (as opposed to winter and spring which previous studies had shown to be associated with clinical disease). Comparison of impala and buffalo ratios in the three sampling regions indicated that the higher the impala density, the more likely disease transmission is from buffalo to impala, and that this is independent of buffalo numbers (presumably above an undetermined threshold). This study confirmed the potential role of impala for propagating FMD in southern Africa and this factor should therefore be considered when designing control strategies where wildlife and domestic animals interact.

De-boned beef - an example of a commodity for which specific standards could be developed to ensure an appropriate level of protection for international trade.

De-boned beef from which lymph nodes and risk material associated with bovine spongiform encephalopathy have been removed, is a product which can be produced for safe international trade irrespective of whether the locality of production is recognized as free from so-called transboundary diseases or not. Further processing of such beef provides an additional safety factor. However, this approach requires specific control measures being in place, supported by appropriate auditing and certification procedures. This document presents the arguments supporting this concept and details how safety in respect of both animal diseases and human food safety can be achieved using an integrated hazard analysis and critical control points approach.

A qualitative risk assessment of factors contributing to foot and mouth disease outbreaks in cattle along the western boundary of the Kruger National Park.

Between November 2000 and the end of 2007, five outbreaks of foot and mouth disease (FMD) occurred in cattle in the area adjacentto the Kruger National Park (KNP) in the north-eastern corner of South Africa. To help understand the factors behind these outbreaks a qualitative risk assessment based on the World Organisation for Animal Health (OIE) assessment framework was adopted, using available data from published sources and various unpublished South African sources. Risk was assessed on the basis of the following factors: data on South African Territories (SAT) type infections of buffalo and impala in the KNP, permeability of the fence along the western boundary of the KNP, the potential for contact between livestock and wildlife susceptible to FMD in areas adjacent to the KNP, and the level of herd immunity in cattle generated by prophylactic vaccination. Scenario pathways for FMD occurrence outside the KNP are presented as a conceptual framework to qualitatively assess the risk of FMD outbreaks. Factors that are likely to have most influence on the risk were identified: fence permeability, vaccination coverage, or the efficiency of animal movement control measures. The method and results are provided as an approach that may be used as a basis to evaluate the risk of FMD outbreaks occurring in other wildlife/livestock interface areas of southern Africa.

Certification for regional and international trade in livestock commodities: the need to balance credibility and enterprise.

The current system for the certification of internationally traded animal commodities can act as a barrier to developing countries accessing high-value international markets. In this Viewpoint article, Gavin Thomson and colleagues discuss the situation as it stands and identify inconsistencies with respect to the certification process. They suggest ways to address the lack of capacity for credible certification in some developing countries that will encourage market access for livestock commodities. They emphasise the role of mechanisms other than demonstrating that an area of production is free from a range of animal diseases, arguing that this could be of significant benefit to developing regions and countries, but that a reliable and independent system of certification based on international standards is essential.

Selection of foot and mouth disease vaccine strains--a review.

The choice of the most appropriate strains of foot and mouth disease (FMD) virus vaccines to use in FMD control programmes and to store in vaccine antigen reserves is based on the matching of representative field isolates from outbreaks around the world to available vaccine strains. However, those involved in FMD control at a national level do not always give this work a high priority, while in countries without effective control of FMD there is little incentive to collect samples or to overcome the constraints on submission to international reference laboratories. In the short term, specific initiatives for targeted collection can provide samples on a periodic basis, but a long-term solution requires the development of FMD control measures. This must be underpinned by the strengthening of local Veterinary Services and laboratories, and by demand-driven provision of sufficient amounts of high-quality vaccine. Difficulties may be increased by commercial constraints on disclosure of the strains used for vaccine production and on the supply of reagents needed for matching tests. Vaccine matching tests are mainly based on in vitro methods - such as virus neutralisation, enzyme-linked immunosorbent assay with polyclonal antibodies and complement fixation - and are performed in a relatively small number of laboratories around the world. In addition to the difficulties of gathering representative field and vaccine strains, neither the reagents nor the methods used for vaccine matching are fully harmonised. Consequently, there is no strict equivalence in the results obtained. Alternative approaches using monoclonal antibody panels and/or viral capsid gene sequencing are being developed and could complement the currently employed serological tests. However, there is limited in vivo cross-protection information, more of which is essential for future validation of the vaccine matching methods. In response to the funding and leadership deficit for vaccine strain selection, a network of World Organisation for Animal Health (OIE) and Food and Agriculture Organization FMD reference laboratories has been established; this gives these laboratories the potential to strengthen the coordination of their work and reporting and thereby improve recommendations on vaccine strain selection.

International trade in livestock and livestock products: the need for a commodity-based approach.

International animal health standards designed to facilitate safe trade in livestock and livestock products are set by the Office International des Epizooties (OIE) under the Sanitary and Phytosanitary Agreement of the World Trade Organization (WTO) and documented in the OIE's Terrestrial Animal Health Code. A core principle of the Code is the need for countries to eradicate important transboundary animal diseases (TADs) to reduce the risk of exporting disease to trading partners. International food safety standards are set by the Codex Alimentarius Commission, administered jointly by the World Health Organization and the Food and Agriculture Organization of the United Nations. The goal of global eradication of most TADs is unachievable for the foreseeable future, other than in the case of rinderpest, and this prevents many countries, especially developing nations, from engaging in international trade under WTO rules. This paper proposes an alternative, commodity-based approach to the formulation of international animal health and food safety standards, based on the fact that different commodities pose very different risks when it comes to the spread of human and animal pathogens. Therefore, the risk mitigation strategies required are equally commodity-dependent. The authors conclude that more focused commodity standards would improve access to international markets for all countries, especially those in the developing world. For this objective to be realised, credible and independent certification is required.

Co-circulation of two genetically distinct viruses in an outbreak of African swine fever in Mozambique: no evidence for individual co-infection.

In 1998, domestic pigs originating from villages within a 40 km radius of Ulongwe in the northern Tete Province of Mozambique were held in a quarantine facility for a 3-month period prior to their importation into South Africa. Eight of a total of 25 pigs died within the first 3 weeks of quarantine of what appeared clinically and on post mortem examination to be African swine fever (ASF). Organs were collected and preserved in formol-glycerosaline and the presence of ASF virus in these specimens was confirmed by three independent polymerase chain reaction (PCR) tests. Two gene regions were characterised, namely the C-terminus end of the major immunodominant protein VP72 and the central variable region (CVR) of the 9RL open reading frame (ORF). Results confirmed the presence of two genetically distinct viruses circulating simultaneously within a single outbreak focus. However, despite the pigs being housed within the same facility, no evidence of co-infection was observed within individual animals. Comparison of the two 1998 virus variants with viruses causing historical outbreaks of the disease in Mozambique revealed that these viruses belong to two distinct genotypes which are unrelated to viruses causing outbreaks between 1960 and 1994. In addition, the CVR and p72 gene regions of one of the 1998 Mozambique virus variants (variant-40) was shown to be identical to the virus recovered from an ASF outbreak in Madagascar in the same year, whilst the other (variant-92) was identical to a 1988 pig isolate from Zambia.

An investigation into the source and spread of foot and mouth disease virus from a wildlife conservancy in Zimbabwe.

African buffalo were introduced into a wildlife conservancy in the southeast of Zimbabwe in an effortto increase the conservancy's economic viability, which is primarily based on eco-tourism. The buffalo were infected with SAT serotypes (SAT-1, SAT-2 and SAT-3) of foot and mouth disease (FMD) virus, and in order to isolate the conservancy and prevent the transmission of FMD to adjacent populations of domestic livestock, the conservancy was surrounded by a double-fence system, 1.8 m in height. The intention was to prevent the movement of both wildlife and domestic animals across the perimeter. However, two years after the buffalo were introduced, FMD occurred in cattle farmed just outside of the conservancy. Using serological and molecular diagnostic tests, epidemiological investigations showed that it was most likely that antelope (impala or kudu), infected through contact with the buffalo herd within the conservancy, had jumped over the fence and transmitted the virus to the cattle.

An investigation into natural resistance to African swine fever in domestic pigs from an endemic area in southern Africa.

A population of domestic pigs in northern Mozambique with increased resistance to the pathogenic effects of African swine fever (ASF) virus was identified by the high prevalence of circulating antibodies to ASF virus. An attempt was made to establish whether the resistance in this population was heritable. Some of these pigs were acquired and transported to a quarantine facility and allowed to breed naturally. Offspring of the resistant pigs were transferred to a high security facility where they were challenged with two ASF viruses, one of which was isolated from one of the Mozambican pigs and the other a genetically closely-related virus from Madagascar. All but one of the 105 offspring challenged developed acute ASF and died. It therefore appears that the resistance demonstrated by these pigs is not inherited by their offspring, or could not be expressed under the conditions of the experiment. The question remains therefore as to the mechanism whereby pigs in the population from which the experimental pigs were derived co-existed with virulent ASF viruses.

The implications of virus diversity within the SAT 2 serotype for control of foot-and-mouth disease in sub-Saharan Africa.

SAT 2 is the serotype most often associated with outbreaks of foot-and-mouth disease (FMD) in livestock in southern and western Africa and is the only SAT type to have been recorded outside the African continent in the last decade. Its epidemiology is complicated by the presence of African buffalo (Syncerus caffer), which play an important role in virus maintenance and transmission. To assess the level of genetic complexity of this serotype among viruses associated with both domestic livestock and wildlife, complete VP1 gene sequences of 53 viruses from 17 countries and three different host species were analysed. Phylogenetic analysis revealed eleven virus lineages, differing from each other by at least 20 % in pairwise nucleotide comparisons, four of which fall within the southern African region, two in West Africa and the remaining five in central and East Africa. No evidence of recombination between these lineages was detected, and thus we conclude that these are independently evolving virus lineages which occur primarily in discrete geographical localities in accordance with the FMD virus topotype concept. Applied to the whole phylogeny, rates of nucleotide substitution are significantly different between topotypes, but most individual topotypes evolve in accordance with a molecular clock at an average rate of approximately 0.002 substitutions per site per year. This study provides an indication of the intratypic complexity of the SAT 2 serotype at the continental level and emphasizes the value of molecular characterization of diverse FMD field strains for tracing the origin of outbreaks.

Review of the status and control of foot and mouth disease in sub-Saharan Africa.

Six of the seven serotypes of foot and mouth disease (FMD) virus (i.e. all but Asia 1) are prevalent in Africa although there are marked regional differences in distribution. Three of these serotypes are unique to Africa, namely the three South African Territories (SAT) serotypes. Serotype C may also now be confined to Africa because it has not been reported elsewhere recently. In southern Africa at least, the SAT serotypes have an intimate and probably ancient association with African buffalo (Syncerus caffer) that is instrumental in their maintenance. Within each of the six prevalent serotypes, with the possible exception of C, there are a number of different lineages with more or less defined distributions (i.e. topotypes) that in some cases are sufficiently immunologically different from one another to require specific vaccines to ensure efficient control. This immunological diversity in prevalent serotypes and topotypes, in addition to uncontrolled animal movement in most parts of the continent, render FMD difficult to control in present circumstances. This fact, together with poorly developed intercontinental trade in animals and animal products has resulted in the control of FMD being afforded a low priority in most parts of the continent, although the northern and southern regions of the continent are an exception. As a consequence, eradication of FMD from Africa as a whole is not a prospect within the foreseeable future. In southern Africa, the use of fencing and other means to strictly control the movement of wildlife and livestock as well as judicious application of vaccine has resulted in countries of the region being able to access beef and other livestock markets in Europe and elsewhere in the developed world. Significant marketing of livestock and livestock products from Africa outside the continent is unlikely to be achieved unless similar approaches can be developed for other regions of Africa. This will result in continuing under-exploitation of a valuable resource in the arid and semi-arid regions of Africa, with increasing marginalisation of human populations living there.

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.

Tracing movement of African buffalo in southern Africa.

Genetic characterisation of two pathogens, namely foot and mouth disease (FMD) virus and Mycobacterium bovis, isolated from African buffalo (Syncerus caffer) in southern Africa was used to determine the origin of buffalo in situations where the source of infection was obscure. By determining the phylogenetic relatedness of various FMD virus isolates using partial sequencing of the main antigenic determinant, VP1, the origin of buffalo moved illegally to the non-endemic region of South Africa was traced to the Kruger National Park (KNP) where FMD is endemic in the buffalo population. Comparative analysis of the 'genetic fingerprints' of bovine tuberculosis isolates from buffalo and cattle has aided in tracing the original source of infection of buffalo populations in the KNP. Furthermore, these analyses have assisted in tracing the origin of infected animals that have been moved to other parts of South Africa.

Molecular epidemiology of serotype O foot-and-mouth disease virus with emphasis on West and South Africa.

Genetic relationships of serotype O foot-and-mouth disease (FMD) viruses recovered from outbreaks of the disease in the West African countries of Niger, Burkina Faso and, Ghana (1988-1993) and those from South Africa (2000) were determined by partial VP1 gene characterization. A 581-bp fragment, corresponding to the C-terminus half of the ID (VP1 gene) region was amplified and sequenced. An homologous region of 495 nucleotides was ultimately used to determine genetic relationships of serotype O viruses from the Middle East, Europe, South America, North Africa, East Africa, southern Africa and Asia. Seven distinct type O genotypes were identified by phylogenetic reconstruction, consisting of viruses from the following geographical regions: Genotype A: Asia, the Middle East, and South Africa, Genotype B: East Africa, Genotype C: West and North Africa, Genotype D: Taiwan and Russia, Genotype E: Angola and Venezuela, Genotype F: Western Europe, and Genotype G: Europe and South America. The genotypes constitute three different evolutionary lineages (I-III), which correspond to three discrete continental regions, some of which display inter-continental distributions due to introductions. Results further indicate that the outbreaks in Burkina Faso (1992) and Ghana (1993) are part of the same epizootic and that the strain involved in a recent outbreak of the disease in South Africa is most closely related (97% sequence identity) to a 1997 Bangladesh strain.