A cross-sectional survey to establish Theileria parva prevalence and vector control at the wildlife-livestock interface, Northern Tanzania.

East Coast fever (ECF) in cattle is caused by the protozoan parasite Theileria parva, transmitted by Rhipicephalus appendiculatus ticks. In cattle ECF is often fatal, causing annual losses >$500 million across its range. The African buffalo (Syncerus caffer) is the natural host for T. parva but the transmission dynamics between wild hosts and livestock are poorly understood. This study aimed to determine the prevalence of T. parva in cattle, in a 30 km zone adjacent to the Serengeti National Park, Tanzania where livestock and buffalo co-exist, and to ascertain how livestock keepers controlled ECF and other vector-borne diseases of cattle. A randomised cross-sectional cattle survey and questionnaire of vector control practices were conducted. Blood samples were collected from 770 cattle from 48 herds and analysed by PCR to establish T. parva prevalence. Half body tick counts were recorded on every animal. Farmers were interviewed (n = 120; including the blood sampled herds) using a standardised questionnaire to obtain data on vector control practices. Local workshops were held to discuss findings and validate results. Overall prevalence of T. parva in cattle was 5.07% (CI: 3.70-7.00%), with significantly higher prevalence in older animals. Although all farmers reported seeing ticks on their cattle, tick counts were very low with 78% cattle having none. Questionnaire analysis indicated significant acaricide use with 79% and 41% of farmers reporting spraying or dipping with cypermethrin-based insecticides, respectively. Some farmers reported very frequent spraying, as often as every four days. However, doses per animal were often insufficient. These data indicate high levels of acaricide use, which may be responsible for the low observed tick burdens and low ECF prevalence. This vector control is farmer-led and aimed at both tick- and tsetse-borne diseases of livestock. The levels of acaricide use raise concerns regarding sustainability; resistance development is a risk, particularly in ticks. Integrating vaccination as part of this community-based disease control may alleviate acaricide dependence, but increased understanding of the Theileria strains circulating in wildlife-livestock interface areas is required to establish the potential benefits of vaccination.

Antigenic Diversity in Theileria parva Populations From Sympatric Cattle and African Buffalo Analyzed Using Long Read Sequencing.

East Coast fever (ECF) in cattle is caused by the Apicomplexan protozoan parasite Theileria parva, transmitted by the three-host tick Rhipicephalus appendiculatus. The African buffalo (Syncerus caffer) is the natural host for T. parva but does not suffer disease, whereas ECF is often fatal in cattle. The genetic relationship between T. parva populations circulating in cattle and buffalo is poorly understood, and has not been studied in sympatric buffalo and cattle. This study aimed to determine the genetic diversity of T. parva populations in cattle and buffalo, in an area where livestock co-exist with buffalo adjacent to the Serengeti National Park, Tanzania. Three T. parva antigens (Tp1, Tp4, and Tp16), known to be recognized by CD8+ and CD4+ T cells in immunized cattle, were used to characterize genetic diversity of T. parva in cattle (n = 126) and buffalo samples (n = 22). Long read (PacBio) sequencing was used to generate full or near-full length allelic sequences. Patterns of diversity were similar across all three antigens, with allelic diversity being significantly greater in buffalo-derived parasites compared to cattle-derived (e.g., for Tp1 median cattle allele count was 9, and 81.5 for buffalo), with very few alleles shared between species (8 of 651 alleles were shared for Tp1). Most alleles were unique to buffalo with a smaller proportion unique to cattle (412 buffalo unique vs. 231 cattle-unique for Tp1). There were indications of population substructuring, with one allelic cluster of Tp1 representing alleles found in both cattle and buffalo (including the TpM reference genome allele), and another containing predominantly only alleles deriving from buffalo. These data illustrate the complex interplay between T. parva populations in buffalo and cattle, revealing the significant genetic diversity in the buffalo T. parva population, the limited sharing of parasite genotypes between the host species, and highlight that a subpopulation of T. parva is maintained by transmission within cattle. The data indicate that fuller understanding of buffalo T. parva population dynamics is needed, as only a comprehensive appreciation of the population genetics of T. parva populations will enable assessment of buffalo-derived infection risk in cattle, and how this may impact upon control measures such as vaccination.

Assessing the effect of insecticide-treated cattle on tsetse abundance and trypanosome transmission at the wildlife-livestock interface in Serengeti, Tanzania.

In the absence of national control programmes against Rhodesian human African trypanosomiasis, farmer-led treatment of cattle with pyrethroid-based insecticides may be an effective strategy for foci at the edges of wildlife areas, but there is limited evidence to support this. We combined data on insecticide use by farmers, tsetse abundance and trypanosome prevalence, with mathematical models, to quantify the likely impact of insecticide-treated cattle. Sixteen percent of farmers reported treating cattle with a pyrethroid, and chemical analysis indicated 18% of individual cattle had been treated, in the previous week. Treatment of cattle was estimated to increase daily mortality of tsetse by 5-14%. Trypanosome prevalence in tsetse, predominantly from wildlife areas, was 1.25% for T. brucei s.l. and 0.03% for T. b. rhodesiense. For 750 cattle sampled from 48 herds, 2.3% were PCR positive for T. brucei s.l. and none for T. b. rhodesiense. Using mathematical models, we estimated there was 8-29% increase in mortality of tsetse in farming areas and this increase can explain the relatively low prevalence of T. brucei s.l. in cattle. Farmer-led treatment of cattle with pyrethroids is likely, in part, to be limiting the spill-over of human-infective trypanosomes from wildlife areas.

A Tool for Prioritizing Livestock Disease Threats to Scotland.

There are a number of disease threats to the livestock of Scotland that are not presently believed to be circulating in the UK. Here, we present the development of a tool for prioritizing resources for livestock disease threats to Scotland by combining a semi-quantitative model of the chance of introduction of different diseases with a semi-quantitative model of disease impact. Eighteen key diseases were identified and then input into a model framework to produce a semi-quantitative estimate of disease priorities. We estimate this through a model of the potential impacts of the infectious diseases in Scotland that is interpreted alongside a pre-existing generic risk assessment model of the risks of incursion of the diseases. The impact estimates are based on key metrics which influence the practical impact of disease. Metrics included are the rate of spread, the disease mitigation factors, impacts on animal welfare and production, the human health risks and the impacts on wider society. These quantities were adjusted for the size of the Scottish livestock population and were weighted using published scores. Of the 18 livestock diseases included, the model identifies highly pathogenic avian influenza, foot and mouth disease in cattle and bluetongue virus in sheep as having the greatest priority in terms of the combination of chance of introduction and disease impact. Disregarding the weighting for livestock populations and comparing equally between industry sectors, the results demonstrate that Newcastle disease and highly pathogenic avian influenza generally have the greatest potential impact. This model provides valuable information for the veterinary and livestock industries in prioritizing resources in the face of many disease threats. The system can easily be adjusted as disease situations evolve.

Geostatistical models using remotely-sensed data predict savanna tsetse decline across the interface between protected and unprotected areas in Serengeti, Tanzania.

Monitoring abundance is essential for vector management, but it is often only possible in a fraction of managed areas. For vector control programmes, sampling to estimate abundance is usually carried out at a local-scale (10s km2), while interventions often extend across 100s km2. Geostatistical models have been used to interpolate between points where data are available, but this still requires costly sampling across the entire area of interest. Instead, we used geostatistical models to predict local-scale spatial variation in the abundance of tsetse-vectors of human and animal African trypanosomes-beyond the spatial extent of data to which models were fitted, in Serengeti, Tanzania.We sampled Glossina swynnertoni and Glossina pallidipes >10 km inside the Serengeti National Park (SNP) and along four transects extending into areas where humans and livestock live. We fitted geostatistical models to data >10 km inside the SNP to produce maps of abundance for the entire region, including unprotected areas.Inside the SNP, the mean number of G. pallidipes caught per trap per day in dense woodland was 166 (± 24 SE), compared to 3 (±1) in grassland. Glossina swynnertoni was more homogenous with respective means of 15 (±3) and 15 (±8). In general, models predicted a decline in abundance from protected to unprotected areas, related to anthropogenic changes to vegetation, which was confirmed during field survey. Synthesis and applications. Our approach allows vector control managers to identify sites predicted to have relatively high tsetse abundance, and therefore to design and implement improved surveillance strategies. In East and Southern Africa, trypanosomiasis is associated with wilderness areas. Our study identified pockets of vegetation which could sustain tsetse populations in farming areas outside the Serengeti National Park. Our method will assist countries in identifying, monitoring and, if necessary, controlling tsetse in trypanosomiasis foci. This has specific application to tsetse, but the approach could also be developed for vectors of other pathogens.

Assessing the Economic Impact of Vaccine Availability When Controlling Foot and Mouth Disease Outbreaks.

Predictive models have been used extensively to assess the likely effectiveness of vaccination policies as part of control measures in the event of a foot and mouth disease (FMD) outbreak. However, the availability of vaccine stocks and the impact of vaccine availability on disease control strategies represent a key uncertainty when assessing potential control strategies. Using an epidemiological, spatially explicit, simulation model in combination with a direct cost calculator, we assessed how vaccine availability constraints may affect the economic benefit of a "vaccination-to-live" strategy during a FMD outbreak in Scotland, when implemented alongside culling of infected premises and dangerous contacts. We investigated the impact of vaccine stock size and restocking delays on epidemiological and economic outcomes. We also assessed delays in the initial decision to vaccinate, maximum daily vaccination capacity, and vaccine efficacy. For scenarios with conditions conducive to large outbreaks, all vaccination strategies perform better than the strategy where only culling is implemented. A stock of 200,000 doses, enough to vaccinate 12% of the Scottish cattle population, would be sufficient to maximize the relative benefits of vaccination, both epidemiologically and economically. However, this generates a wider variation in economic cost than if vaccination is not implemented, making outcomes harder to predict. The probability of direct costs exceeding £500 million is reduced when vaccination is used and is steadily reduced further as the size of initial vaccine stock increases. If only a suboptimal quantity of vaccine doses is initially available (100,000 doses), restocking delays of more than 2 weeks rapidly increase the cost of controlling outbreaks. Impacts of low vaccine availability or restocking delays are particularly aggravated by delays in the initial decision to vaccinate, or low vaccine efficacy. Our findings confirm that implementing an emergency vaccination-to-live strategy in addition to the conventional stamping out strategy is economically beneficial in scenarios with conditions conducive to large FMD outbreaks in Scotland. However, the size of the initial vaccine stock available at the start of the outbreak and the interplay with other factors, such as vaccine efficacy and delays in restocking or implementing vaccination, should be considered in making decisions about optimal control strategies for FMD outbreaks.

Exploring the role of small-scale livestock keepers for national biosecurity-The pig case.

Small-scale keepers are less likely to engage with production organisations and may therefore be less aware of legislation, rules and biosecurity practices which are implemented in the livestock sector. Their role in the transmission of endemic and exotic diseases is not well studied, but is believed to be important. The authors use small-scale pig keepers in Scotland as an example of how important small-scale livestock keepers might be for national biosecurity. In Scotland more than two thirds of pig producers report that they keep less than 10 pigs, meaning that biosecurity practices and pig health status on a substantial number of holdings are largely unknown; it is considered important to fill this knowledge gap. A questionnaire was designed and implemented in order to gather some of this information. The questionnaire comprised a total of 37 questions divided into seven sections (location of the enterprise, interest in pigs, details about the pig enterprise, marketing of pigs, transport of pigs, pig husbandry, and pig health/biosecurity). Over 610 questionnaires were sent through the post and the questionnaire was also available online. The questionnaire was implemented from June to October 2013 and 135 questionnaires were returned by target respondents. The responses for each question are discussed in detail in this paper. Overall, our results suggest that the level of disease identified by small-scale pig keepers is low but the majority of the small-scale pig keepers are mixed farms, with associated increased risk for disease transmission between species. Almost all respondents implemented at least one biosecurity measure, although the measures taken were not comprehensive in the majority of cases. Overall as interaction between small-scale keepers and commercial producers exists in Scotland the former can pose a risk for commercial production. This investigation fills gaps in knowledge which will allow industry stakeholders and policy makers to adapt their current disease programmes and contingency plans to the reality of small-scale pig-keeping enterprises' health and biosecurity status. We predict that some conclusions from this work will be relevant to countries with similar pig production systems and importantly some of these findings will relate to small-scale producers in other livestock sectors.

Vulnerability of the British swine industry to classical swine fever.

Classical swine fever (CSF) is a notifiable, highly contagious viral disease of swine which results in severe welfare and economic consequences in affected countries. To improve preparedness, it is critical to have some understanding of how CSF would spread should it be introduced. Based on the data recorded during the 2000 epidemic of CSF in Great Britain (GB), a spatially explicit, premises-based model was developed to explore the risk of CSF spread in GB. We found that large outbreaks of CSF would be rare and generated from a limited number of areas in GB. Despite the consistently low vulnerability of the British swine industry to large CSF outbreaks, we identified concerns with respect to the role played by the non-commercial sector of the industry. The model further revealed how various epidemiological features may influence the spread of CSF in GB, highlighting the importance of between-farm biosecurity in preventing widespread dissemination of the virus. Knowledge of factors affecting the risk of spread are key components for surveillance planning and resource allocation, and this work provides a valuable stepping stone in guiding policy on CSF surveillance and control in GB.

Assessing the potential for Bluetongue virus 8 to spread and vaccination strategies in Scotland.

Europe has seen frequent outbreaks of Bluetongue (BT) disease since 2006, including an outbreak of BT virus serotype 8 in central France during 2015 that has continued to spread in Europe during 2016. Thus, assessing the potential for BTv-8 spread and determining the optimal deployment of vaccination is critical for contingency planning. We developed a spatially explicit mathematical model of BTv-8 spread in Scotland and explored the sensitivity of transmission to key disease spread parameters for which detailed empirical data is lacking. With parameters at mean values, there is little spread of BTv-8 in Scotland. However, under a "worst case" but still feasible scenario with parameters at the limits of their ranges and temperatures 1 °C warmer than the mean, we find extensive spread with 203,000 sheep infected given virus introduction to the south of Scotland between mid-May and mid-June. Strategically targeted vaccine interventions can greatly reduce BT spread. Specifically, despite BT having most clinical impact in sheep, we show that vaccination can have the greatest impact on reducing BTv infections in sheep when administered to cattle, which has implications for disease control policy.

Using national movement databases to help inform responses to swine disease outbreaks in Scotland: the impact of uncertainty around incursion time.

Modelling is an important component of contingency planning and control of disease outbreaks. Dynamic network models are considered more useful than static models because they capture important dynamic patterns of farm behaviour as evidenced through animal movements. This study evaluates the usefulness of a dynamic network model of swine fever to predict pre-detection spread via movements of pigs, when there may be considerable uncertainty surrounding the time of incursion of infection. It explores the utility and limitations of animal movement data to inform such models and as such, provides some insight into the impact of improving traceability through real-time animal movement reporting and the use of electronic animal movement databases. The study concludes that the type of premises and uncertainty of the time of disease incursion will affect model accuracy and highlights the need for improvements in these areas.

Impact of temperature, feeding preference and vaccination on Schmallenberg virus transmission in Scotland.

First identified in 2011, Schmallenberg virus (SBV) is principally transmitted by Culicoides midges and affects ruminants. Clinical presentation is typified by foetal abnormalities, but despite very high infection rates, relatively few animals present with clinical signs. In this paper we further develop a previously published stochastic mathematical model of SBV spread to investigate the optimal deployment of a vaccine for SBV in Scotland, a country that has experienced only sporadic and isolated cases of SBV. We consider the use of the vaccine under different temperatures and explore the effects of a vector preference for feeding on cattle. We demonstrate that vaccine impact is optimised by targeting it at the high risk areas in the south of Scotland, or vaccinating only cattle. At higher than average temperatures, and hence increased transmission potential, the relative impact of vaccination is considerably enhanced. Vaccine impact is also enhanced if vectors feed preferentially on cattle. These findings are of considerable importance when planning control strategies for SBV and also have important implications for management of other arboviruses such as Bluetongue virus. Environmental determinants and feeding preferences should be researched further to inform development of effective control strategies.

How commercial and non-commercial swine producers move pigs in Scotland: a detailed descriptive analysis.

BACKGROUND: The impact of non-commercial producers on disease spread via livestock movement is related to their level of interaction with other commercial actors within the industry. Although understanding these relationships is crucial in order to identify likely routes of disease incursion and transmission prior to disease detection, there has been little research in this area due to the difficulties of capturing movements of small producers with sufficient resolution. Here, we used the Scottish Livestock Electronic Identification and Traceability (ScotEID) database to describe the movement patterns of different pig production systems which may affect the risk of disease spread within the swine industry. In particular, we focused on the role of small pig producers. RESULTS: Between January 2012 and May 2013, 23,169 batches of pigs were recorded moving animals between 2382 known unique premises. Although the majority of movements (61%) were to a slaughterhouse, the non-commercial and the commercial sectors of the Scottish swine industry coexist, with on- and off-movement of animals occurring relatively frequently. For instance, 13% and 4% of non-slaughter movements from professional producers were sent to a non-assured commercial producer or to a small producer, respectively; whereas 43% and 22% of movements from non-assured commercial farms were sent to a professional or a small producer, respectively. We further identified differences between producer types in several animal movement characteristics which are known to increase the risk of disease spread. Particularly, the distance travelled and the use of haulage were found to be significantly different between producers. CONCLUSIONS: These results showed that commercial producers are not isolated from the non-commercial sector of the Scottish swine industry and may frequently interact, either directly or indirectly. The observed patterns in the frequency of movements, the type of producers involved, the distance travelled and the use of haulage companies provide insights into the structure of the Scottish swine industry, but also highlight different features that may increase the risk of infectious diseases spread in both Scotland and the UK. Such knowledge is critical for developing more robust biosecurity and surveillance plans and better preparing Scotland against incursions of emerging swine diseases.

Vaccination against foot-and-mouth disease: do initial conditions affect its benefit?

When facing incursion of a major livestock infectious disease, the decision to implement a vaccination programme is made at the national level. To make this decision, governments must consider whether the benefits of vaccination are sufficient to outweigh potential additional costs, including further trade restrictions that may be imposed due to the implementation of vaccination. However, little consensus exists on the factors triggering its implementation on the field. This work explores the effect of several triggers in the implementation of a reactive vaccination-to-live policy when facing epidemics of foot-and-mouth disease. In particular, we tested whether changes in the location of the incursion and the delay of implementation would affect the epidemiological benefit of such a policy in the context of Scotland. To reach this goal, we used a spatial, premises-based model that has been extensively used to investigate the effectiveness of mitigation procedures in Great Britain. The results show that the decision to vaccinate, or not, is not straightforward and strongly depends on the underlying local structure of the population-at-risk. With regards to disease incursion preparedness, simply identifying areas of highest population density may not capture all complexities that may influence the spread of disease as well as the benefit of implementing vaccination. However, if a decision to vaccinate is made, we show that delaying its implementation in the field may markedly reduce its benefit. This work provides guidelines to support policy makers in their decision to implement, or not, a vaccination-to-live policy when facing epidemics of infectious livestock disease.

Epidemic potential of an emerging vector borne disease in a marginal environment: Schmallenberg in Scotland.

During 2011 Schmallenberg virus (SBV) presented as a novel disease of cattle and sheep that had apparently spread through northern Europe over a relatively short period of time, but has yet to infect Scotland. This paper describes the development of a model of SBV spread applied to Scotland in the event of an incursion. This model shows that SBV spread is very sensitive to the temperature, with relatively little spread and few reproductive losses predicted in years with average temperatures but extensive spread (>1 million animals infected) and substantial reproductive losses in the hottest years. These results indicate that it is possible for SBV to spread in Scotland, however spread is limited by climatic conditions and the timing of introduction. Further results show that the transmission kernel shape and extrinsic incubation period parameter have a non-linear effect on disease transmission, so a greater understanding of the SBV transmission parameters is required.

Using molecular data for epidemiological inference: assessing the prevalence of Trypanosoma brucei rhodesiense in tsetse in Serengeti, Tanzania.

BACKGROUND: Measuring the prevalence of transmissible Trypanosoma brucei rhodesiense in tsetse populations is essential for understanding transmission dynamics, assessing human disease risk and monitoring spatio-temporal trends and the impact of control interventions. Although an important epidemiological variable, identifying flies which carry transmissible infections is difficult, with challenges including low prevalence, presence of other trypanosome species in the same fly, and concurrent detection of immature non-transmissible infections. Diagnostic tests to measure the prevalence of T. b. rhodesiense in tsetse are applied and interpreted inconsistently, and discrepancies between studies suggest this value is not consistently estimated even to within an order of magnitude. METHODOLOGY/PRINCIPAL FINDINGS: Three approaches were used to estimate the prevalence of transmissible Trypanosoma brucei s.l. and T. b. rhodesiense in Glossina swynnertoni and G. pallidipes in Serengeti National Park, Tanzania: (i) dissection/microscopy; (ii) PCR on infected tsetse midguts; and (iii) inference from a mathematical model. Using dissection/microscopy the prevalence of transmissible T. brucei s.l. was 0% (95% CI 0-0.085) for G. swynnertoni and 0% (0-0.18) G. pallidipes; using PCR the prevalence of transmissible T. b. rhodesiense was 0.010% (0-0.054) and 0.0089% (0-0.059) respectively, and by model inference 0.0064% and 0.00085% respectively. CONCLUSIONS/SIGNIFICANCE: The zero prevalence result by dissection/microscopy (likely really greater than zero given the results of other approaches) is not unusual by this technique, often ascribed to poor sensitivity. The application of additional techniques confirmed the very low prevalence of T. brucei suggesting the zero prevalence result was attributable to insufficient sample size (despite examination of 6000 tsetse). Given the prohibitively high sample sizes required to obtain meaningful results by dissection/microscopy, PCR-based approaches offer the current best option for assessing trypanosome prevalence in tsetse but inconsistencies in relating PCR results to transmissibility highlight the need for a consensus approach to generate meaningful and comparable data.