A comparison of risk factor investigation and experts' opinion elicitation analysis for identifying foot-and-mouth disease (FMD) high-risk areas within the FMD protection zone of South Africa (2007-2016).

Foot-and-mouth disease is a controlled disease in accordance with the South African Animal Diseases Act (Act 35 of 1984). The country was classified by the World Organisation for Animal Health (WOAH) as having a FMD free zone without vaccination in 1996. However, this status was suspended in 2019 due to a FMD outbreak outside the controlled zones. FMD control in South Africa includes animal movement restrictions placed on cloven-hoofed species and products, prophylactic vaccination of cattle, clinical surveillance of susceptible species, and disease control fencing to separate livestock from wildlife reservoirs. The objectives of this study were to evaluate differences in identifying high-risk areas for FMD using risk factor and expert opinion elicitation analysis. Differences in risk between FMD introduction and FMD spread within the FMD protection zone with vaccination (PZV) of South Africa (2007-2016) were also investigated. The study was conducted in the communal farming area of the FMD PZV, which is adjacent to wildlife reserves and characterised by individual faming units. Eleven risk factors that were considered important for FMD occurrence and spread were used to build a weighted linear combination (WLC) score based on risk factor data and expert opinion elicitation. A multivariable conditional logistic regression model was also used to calculate predicted probabilities of a FMD outbreak for all dip-tanks within the study area. Smoothed Bayesian kriged maps were generated for 11 individual risk factors, overall WLC scores for FMD occurrence and spread and for predicted probabilities of a FMD outbreak based on the conditional logistic regression model. Descriptively, vaccine matching was believed to have a great influence on both FMD occurrence and spread. Expert opinion suggested that FMD occurrence was influenced predominantly by proximity to game reserves and cattle density. Cattle populations and vaccination practices were considered most important for FMD spread. Highly effective cattle inspections were observed within areas that previously reported FMD outbreaks, indicating the importance of cattle inspection (surveillance) as a necessary element of FMD outbreak detection. The multivariable conditional logistic regression analysis, which was consistent with expert opinion elicitation; identified three factors including cattle population density (OR 3.87, 95% CI 1.47-10.21) and proximities to game reserve fences (OR 0.82, 95% CI 0.73-0.92) and rivers (OR 1.04, 95% CI 1.01-1.07) as significant factors for reported FMD outbreaks. Regaining and maintaining an FMD-free status without vaccination requires frequent monitoring of high-risk areas and designing targeted surveillance.

Efficacy of a foot-and-mouth disease vaccine against a heterologous SAT1 virus challenge in goats.

Goats are susceptible to infection with foot-and-mouth disease virus (FMDV), but their role in the epidemiology of the disease and response to vaccination is poorly understood. In southern Africa, FMDV serotypes Southern African Territories (SAT) 1, 2 and 3 are known to be endemic. In this study, we evaluated the efficacy of a pentavalent FMD vaccine in goats against heterologous challenge with a pool of field SAT1 FMDV. Forty FMD sero-negative goats (6-12 months of age) of mixed sexes were randomly allocated to one of five treatment groups: full cattle dose (2 ml), 1/3rd (0.67 ml), 1/6th (0.33 ml), 1/12th (0.16 ml) or unvaccinated placebo control. Goats were vaccinated with an inactivated pentavalent FMD vaccine containing serotypes SAT1, SAT2 and SAT3 on day 0 and revaccinated at day 20 post vaccination. Thereafter, thirty-four goats were challenged by tongue inoculation at day 41 post-vaccination using 104.57 50% tissue culture infective dose (TCID50) FMDV SAT1 pool. Animals were examined daily and clinical signs were scored. Rectal temperatures were measured daily, with temperatures ≥40 °C defined as fever. Clinical specimens (nasal, oral and rectal swabs) were collected on days 0, 2, 4 and 6 post challenge. Viral shedding was determined using reverse-transcriptase real-time PCR. None of the goats vaccinated with the full cattle dose developed secondary lesions. All vaccinated groups had lower temperatures compared to the unvaccinated controls (P < 0.001). Based on RT-PCR results, goats in the unvaccinated control group shed more virus compared to all groups except for 1/12th (P < 0.05), while goats in the full dose group shed less virus than goats in the 1/12th and the unvaccinated control group (P < 0.05). The results suggest that the 1/3rd (0.67 ml) dose of the vaccine is sufficient to reduce viral shedding after heterologous challenge with a FMDV SAT1 pool.

Serological responses of cattle inoculated with inactivated trivalent foot-and-mouth disease vaccine at the wildlife-livestock interface of the Kruger National Park, South Africa.

Foot-and-mouth disease (FMD) virus is economically one of the world's most important animal pathogens, which can be responsible for losses in livestock trade, as well as frequent and highly disruptive large-scale epidemics. The control of FMD in southern Africa typically includes vaccination of cattle with a trivalent or bivalent vaccine preparation. The objective of this study was to determine the level and duration of the antibody responses conferred by the current FMD vaccination programme in cattle at the western boundary of the Kruger National Park (KNP) in South Africa. Two hundred and eighty-three cattle from four communal dip tanks were longitudinally sampled after vaccination using an inactivated trivalent FMD vaccine (South African Territories (SAT) 1, SAT 2 and SAT 3). Blood samples were collected fortnightly over four months and antibodies were measured using a liquid-phase blocking ELISA. Only 5%, 43%, and 16% of enrolled cattle had evidence of pre-existing antibody responses to the three SAT viruses at the beginning of the study (≥1.6 log10 titre for SAT 1-3 respectively), which was 7-12 months after the last vaccination campaign. However, 14 days after vaccination this proportion increased to between 66% and 93%, with SAT 2 having the highest proportion. Young animals (<1 year old) tended to have higher predicted baseline antibody levels that peaked by 14 days. Positive serological responses were transient and by 56 days post-vaccination antibody levels begun to decline below the threshold of 1.6 log10 titre. Predicted peak antibody levels only consistently reached 2.0 log10 for SAT 2. Serological responses for SAT 2 tended to be longer, but in most cases the duration of antibody levels was short-lived. More research is necessary to determine the reasons for the limited duration of antibody responses, especially among younger cattle, in order to achieve more effective prophylactic vaccination.

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.

Predicting antigenic sites on the foot-and-mouth disease virus capsid of the South African Territories types using virus neutralization data.

Foot-and-mouth disease virus (FMDV) outer capsid proteins 1B, 1C and 1D contribute to the virus serotype distribution and antigenic variants that exist within each of the seven serotypes. This study presents phylogenetic, genetic and antigenic analyses of South African Territories (SAT) serotypes prevalent in sub-Saharan Africa. Here, we show that the high levels of genetic diversity in the P1-coding region within the SAT serotypes are reflected in the antigenic properties of these viruses and therefore have implications for the selection of vaccine strains that would provide the best vaccine match against emerging viruses. Interestingly, although SAT1 and SAT2 viruses displayed similar genetic variation within each serotype (32 % variable amino acids), antigenic disparity, as measured by r(1)-values, was less pronounced for SAT1 viruses compared with SAT2 viruses within our dataset, emphasizing the high antigenic variation within the SAT2 serotype. Furthermore, we combined amino acid variation and the r(1)-values with crystallographic structural data and were able to predict areas on the surface of the FMD virion as antigenically relevant. These sites were mostly consistent with antigenic sites previously determined for types A, O and C using mAbs and escape mutant studies. Our methodology offers a quick alternative to determine antigenic relevant sites for FMDV field strains.

Mosaic structure of foot-and-mouth disease virus genomes.

The results of a simple pairwise-scanning analysis designed to identify inter-serotype recombination fragments, applied to genome data from 156 isolates of Foot-and-mouth disease virus (FMDV) representing all seven serotypes, are reported. Large numbers of candidate recombinant fragments were identified from all parts of the FMDV genome, with the exception of the capsid genes, within which such fragments are infrequent. As expected, intertypic fragment exchange is most common between geographically sympatric FMDV serotypes. After accounting for the likelihood of intertypic convergence in highly conserved parts of the FMDV genome, it is concluded that intertypic recombination is probably widespread throughout the non-structural genes, but that recombination over the 2B/C and 3B/C gene boundaries appears to be less frequent than expected, given the large numbers of recombinant gene fragments arising in these genes.