Challenges and opportunities of sharing animal health data for research and disease management: a case study of bovine tuberculosis.

The sharing of animal disease data should be encouraged. The analysis of such data will broaden our knowledge of animal diseases and potentially provide insights into their management. However, the need to conform to data protection rules in the sharing of such data for analysis purposes often poses practical difficulties. This paper sets out the challenges and the methods used for the sharing of animal health data in England, Scotland and Wales - Great Britain - using bovine tuberculosis (bTB) data as a case study. The data sharing described is undertaken by the Animal and Plant Health Agency on behalf of the Department for Environment, Food and Rural Affairs and the Welsh and Scottish Governments. It should be noted that animal health data are held at the level of Great Britain (rather than the United Kingdom - which includes Northern Ireland), as Northern Ireland's Department of Agriculture, Environment and Rural Affairs has its own separate data systems. Bovine tuberculosis is the most significant and costly animal health problem facing cattle farmers in England and Wales. It can be devastating for farmers and farming communities and the control costs for taxpayers in Great Britain are over £150 million a year. The authors describe two methods of data sharing - first, where data are requested by, and delivered to, an academic institution for epidemiological or scientific analysis, and second, where data are proactively published in an accessible and meaningful way. They provide details of an example of the second method, namely, the free-to-access website â€Ëœinformation bovine TB' (https://ibtb.co.uk), which publishes bTB data for the benefit of the farming community and veterinary health professionals.

L'échange et le partage de données sur les maladies animales sont des pratiques à encourager. En effet, l'analyse de ces données permet d'étoffer les connaissances sur les maladies animales et peut aussi apporter un nouvel éclairage sur leur gestion. Néanmoins, la nécessité de se conformer aux règles sur la protection des données pose souvent des difficultés pratiques lors des échanges de ce type de données à des fins d'analyse. Les auteurs expliquent les difficultés rencontrées en matière d'échange de données de santé animale en Angleterre, en écosse et au Pays de Galles (Grande-Bretagne), ainsi que les méthodes utilisées, à partir de l'exemple concret des données relatives à la tuberculose bovine. L'échange et le partage de données sont réalisés par l'Agence britannique de santé animale et végétale, pour le compte du ministère britannique de l'Environnement, de l'Alimentation et des Affaires rurales et des gouvernements gallois et écossais. Il convient de préciser que les données de santé animale dont il s'agit sont celles conservées au niveau de la Grande-Bretagne seulement (et non du Royaume-Uni, qui inclut l'Irlande du Nord), étant donné que le ministère de l'Agriculture, de l'Environnement et des Affaires rurales de l'Irlande du Nord possède ses propres systèmes de données. La tuberculose bovine est le principal problème de santé animale auquel sont confrontés les éleveurs de bovins en Angleterre et au Pays de Galles, et le plus coûteux à traiter. La survenue de la tuberculose bovine est une catastrophe pour les éleveurs affectés et leur communauté. En outre, le coût annuel de son contrôle s'élève à plus de 150 millions de livres pour le contribuable britannique. Les auteurs décrivent deux méthodes d'échange et de partage de données : la première est celle où une institution de recherche demande et obtient l'accès à des données particulières afin de réaliser une étude épidémiologique ou scientifique ; la deuxième consiste à publier les données de manière proactive et constructive, en les rendant facilement accessibles. Un exemple concret de cette deuxième méthode est décrit en détail : il s'agit du site web d'information sur la tuberculose bovine (https://ibtb.co.uk), d'accès libre, qui diffuse des informations sur cette maladie à l'intention des éleveurs et des professionnels de la santé animale.

Convendría alentar la puesta en común de datos zoosanitarios, pues el análisis de estos datos nos ayudará a conocer más y mejor las enfermedades animales y, a la postre, puede darnos pistas sobre la mejor manera de afrontarlas. Ocurre a menudo, sin embargo, que el prescriptivo cumplimiento de las reglas de protección de datos plantee dificultades prácticas para poner estos datos en común con fines de análisis. Los autores, empleando como ejemplo un estudio sobre la tuberculosis bovina, describen esas dificultades y los métodos utilizados para compartir datos zoosanitarios en Inglaterra, Escocia y Gales (Gran Bretaña). En el ejemplo descrito, la Agencia de Sanidad Animal y Vegetal del Reino Unido fue la instancia que impulsó la puesta en común de los datos en nombre del Departamento de Medio Ambiente, Alimentación y Asuntos Rurales del Reino Unido y de los gobiernos galés y escocés. Conviene puntualizar que los datos zoosanitarios cubren el territorio de Gran Bretaña (y no de todo el Reino Unido, que incluye Irlanda del Norte), ya que el Departamento de Medio Ambiente, Alimentación y Asuntos Rurales norirlandés dispone de su propio sistema de datos independiente. La tuberculosis bovina es el problema zoosanitario más importante y oneroso al que hacen frente las explotaciones de vacuno en Inglaterra y Gales. Esta enfermedad no solo puede ser devastadora para los productores y profesionales del sector, sino que la lucha contra ella cuesta al contribuyente británico más de 150 millones de libras al año. Los autores describen dos métodos para compartir de datos: en el primero de ellos, un establecimiento universitario solicita y recibe los datos con fines de análisis científico o epidemiológico; en el segundo, una entidad toma la iniciativa de hacer públicos los datos de forma accesible y coherente. Los autores exponen en detalle un ejemplo del segundo procedimiento, a saber, el sitio web de información sobre la tuberculosis bovina (https://ibtb.co.uk) en libre acceso, en el cual se publican datos sobre la enfermedad dirigidos a los profesionales del sector pecuario y la sanidad animal.

Diabetes With Multiple Autoimmune and Inflammatory Conditions Linked to an Activating SKAP2 Mutation.

OBJECTIVE: Multiple genome-wide association studies have identified a strong genetic linkage between the SKAP2 locus and type 1 diabetes (T1D), but how this leads to disease remains obscure. Here, we characterized the functional consequence of a novel SKAP2 coding mutation in a patient with T1D to gain further insight into how this impacts immune tolerance. RESEARCH DESIGN AND METHODS: We identified a 24-year-old individual with T1D and other autoimmune and inflammatory conditions. The proband and first-degree relatives were recruited for whole-exome sequencing. Functional studies of the protein variant were performed using a cell line and primary myeloid immune cells collected from family members. RESULTS: Sequencing identified a de novo SKAP2 variant (c.457G>A, p.Gly153Arg) in the proband. Assays using monocyte-derived macrophages from the individual revealed enhanced activity of integrin pathways and a migratory phenotype in the absence of chemokine stimulation, consistent with SKAP2 p.Gly153Arg being constitutively active. The p.Gly153Arg variant, located in the well-conserved lipid-binding loop, induced similar phenotypes when expressed in a human macrophage cell line. SKAP2 p.Gly153Arg is a gain-of-function, pathogenic mutation that disrupts myeloid immune cell function, likely resulting in a break in immune tolerance and T1D. CONCLUSIONS: SKAP2 plays a key role in myeloid cell activation and migration. This particular mutation in a patient with T1D and multiple autoimmune conditions implicates a role for activating SKAP2 variants in autoimmune T1D.

Strategy and Efficacy of Generic and Pan-genotypic Sofosbuvir/Velpatasvir in Chronic Hepatitis C Virus: A Myanmar Experience.

BACKGROUND: In resource-constrained areas, generic direct-acting antivirals (DAAs) have considerably reduced the cost of hepatitis C virus (HCV) therapy while there remain significant costs related to the baseline and follow-up virologic assays. AIM: The aim was to assess the efficacy and safety of HCV therapy in Myanmar with pan-genotypic generic DAA sofosbuvir/velpatasvir (SOF/VEL) and with and without the baseline genotype testing, while the duration of treatment and use of ribavirin (RBV) was dictated by cirrhosis and prior treatment failure. METHODS: Between September 2016 and June 2017, data from the 359 participants who completed treatment with SOF/VEL (± RBV) for 12-24 weeks were analyzed. Two hundred one patients did not have the baseline HCV genotype tested. RESULTS: Regimens included SOF/VEL for 12 weeks (n = 43), SOF/VEL/RBV for 12 weeks (n = 275), or SOF/VEL/RBV for 24 weeks (n = 41). The mean age was 52 years, 44% were men (n = 159), 41 (11.4%) had a history of previous DAA therapy, 7 (1.9%) had a history of hepatocellular carcinoma, and 55 (15.3%) had cirrhosis. Overall, the sustained viral response (SVR)12 rate was 98.6% (354/359) and with a good adverse event profile. SVR rates were similar to those with and without baseline genotype testing and also across all genotypes in those who had genotype tested. CONCLUSIONS: In Myanmar, generic and pan-genotypic SOF/VEL ± RBV is a highly effective and safe treatment for HCV, regardless of the HCV genotype, and therefore, the requirement for the baseline genotype can be eliminated. Future strategies should include elimination of treatment and end of treatment HCV RNA testing to enhance treatment uptake and further reduce cost.

Thymic tuft cells promote an IL-4-enriched medulla and shape thymocyte development.

The thymus is responsible for generating a diverse yet self-tolerant pool of T cells1. Although the thymic medulla consists mostly of developing and mature AIRE+ epithelial cells, recent evidence has suggested that there is far greater heterogeneity among medullary thymic epithelial cells than was previously thought2. Here we describe in detail an epithelial subset that is remarkably similar to peripheral tuft cells that are found at mucosal barriers3. Similar to the periphery, thymic tuft cells express the canonical taste transduction pathway and IL-25. However, they are unique in their spatial association with cornified aggregates, ability to present antigens and expression of a broad diversity of taste receptors. Some thymic tuft cells pass through an Aire-expressing stage and depend on a known AIRE-binding partner, HIPK2, for their development. Notably, the taste chemosensory protein TRPM5 is required for their thymic function through which they support the development and polarization of thymic invariant natural killer T cells and act to establish a medullary microenvironment that is enriched in the type 2 cytokine, IL-4. These findings indicate that there is a compartmentalized medullary environment in which differentiation of a minor and highly specialized epithelial subset has a non-redundant role in shaping thymic function.

Farm characteristics and farmer perceptions associated with bovine tuberculosis incidents in areas of emerging endemic spread.

While much is known about the risk factors for bovine tuberculosis (bTB) in herds located in high incidence areas, the drivers of bTB spread in areas of emerging endemicity are less well established. Epidemiological analysis and intensive social research identified natural and social risk factors that may prevent or encourage the spread of disease. These were investigated using a case-control study design to survey farmers in areas defined as recently having become endemic for bTB (from or after 2006). Telephone surveys were conducted for 113 farms with a recent history of a bTB incident where their officially tuberculosis free status had been withdrawn (OTFW) (cases) and 224 controls with no history of a bTB incident, matched on location, production type and the rate of endemic bTB spread. Farmers were questioned about a range of farm management strategies, farm characteristics, herd health, wildlife and biosecurity measures with a focus on farmer attitudes and behaviours such as farmers' perception of endemicity and feelings of control, openness and social cohesion. Data generated in the telephone surveys was supplemented with existing herd-level data and analysed using conditional logistic regression. Overall, herd size (OR 1.07), purchasing an animal at a cattle market compared to purchasing outside of markets (OR 2.6), the number of contiguous bTB incidents (2.30) and the number of inconclusive reactors detected in the 2 years prior to the case incident (OR 1.95) significantly increased the odds of a bTB incident. Beef herds using a field parcel more than 3.2km away from the main farm and dairy herds reporting Johne's disease in the previous 12 months were 3.0 and 4.7 times more likely to have a recent history of a bTB incident, respectively. Beef herds reporting maize growing near, but not on, their farm were less likely to be case herds. Operating a closed farm in the two years prior to the case breakdown did not reduce the odds of a bTB incident. Farmers that had recently experienced a bTB incident were more likely to have implemented badger biosecurity in the previous year, but no more likely than control farms to have implemented cattle biosecurity. Case farmers felt significantly less likely to be influenced by government, vets or other farmers compared to those with no history of bTB. This suggests that alternative methods of engaging with farmers who have recently had a breakdown may need to be developed.

Farming on the edge: farmer attitudes to bovine tuberculosis in newly endemic areas.

Defra's recent strategy to eradicate bovine tuberculosis (bTB) establishes three spatial zones: high-risk areas (HRAs) and low-risk areas, and an area referred to as 'the edge', which marks the areas where infection is spreading outwards from the HRA. Little is known about farmers in the edge area, their attitudes towards bTB and their farming practices. This paper examines farmers' practices and attitudes towards bTB in standardised epidemiologically defined areas. A survey was developed to collect data on farmer attitudes, behaviours, practices and environmental conditions as part of an interdisciplinary analysis of bTB risk factors. Survey items were developed from a literature review and focus groups with vets and farmers in different locations within the edge area. A case-control sampling framework was adopted with farms sampled from areas identified as recently endemic for bTB. 347 farmers participated in the survey including 117 with bTB, representing a 70per cent response rate. Results show that farmers believe they are unable to do anything about bTB but are keen for the government intervention to help control the spread of bTB.

A novel approach to mapping and calculating the rate of spread of endemic bovine tuberculosis in England and Wales.

A mathematical method for estimating the endemic status of bovine tuberculosis (bTB) in cattle in England and Wales has been developed. 6.25km(2) hexagonal cells were used as the base resolution. Maps were produced for overlapping two-year periods spanning 2001/03 to 2009/11. Distance from a farm to the ten nearest 'Officially Tuberculosis Free status - Withdrawn' incidents within the same time period was measured. Endemic areas were defined as those hexagons containing farms where the 3rd nearest incident occurred within 7km. Temporal spread of endemic bTB was estimated by creating a contour map displaying the spread of endemic bTB over the two-year periods, and using boundary displacement to calculate the rate of spread across each hexagon. A rate was obtained for ∼2300 cells and varied between 0.04km and 15.9km per year (median=3.3km per year). This work will enable further analysis of the factors associated with this expansion.

Incidence and distribution of foot-and-mouth disease in Asia, Africa and South America; combining expert opinion, official disease information and livestock populations to assist risk assessment.

Risk assessment procedures frequently require quantitative data on the prevalence of the disease in question. Although most countries are members of the World Organization for Animal Health (OIE), the importance attached to foot-and-mouth disease (FMD) reporting or surveillance for infection varies enormously between infected countries. There is a general consensus that FMD outbreaks in endemic countries are greatly under-reported, to a degree related either to the economic or the political development level of the country. This exploratory study was first undertaken by FAO, but thereafter extended and reviewed by the working group on FMD risk co-ordinated by the European Food Safety Authority (EFSA). The paper attempts to overcome the lack of reporting through using expert opinion to extrapolate incidence indices from countries considered to have 'representative' levels of FMD. These were combined with livestock density distributions to provide maps of prevalence indices, which were found to be highest in China (pigs), India (cattle), the Near East (small ruminants) and the Sahel (small ruminants and cattle). Similar patterns were found when weighted expert rankings of a range of additional ranked disease parameters were also produced, and then combined with susceptible animal densities to produce a weighted multi-species density. Results suggest that the methods can provide useful information at both national and sub-national resolution, even for countries for which quantitative FMD data is currently unavailable: two of the regions identified provide little or no data on a regular basis to the OIE and therefore may be overlooked if the level of officially reported FMD is only used. As the estimated prevalences are based on recent disease history and expert opinion, they are most likely to be inaccurate where FMD incursions are infrequent as a result of the preventive measures and geographical and trade isolation. This study, therefore, highlights the need for specific detailed country risk assessments where livestock trade is under consideration. Validating the approach including ground truthing, will require collaboration between a number of agencies and institutions, in critical countries, particularly those with high disease burdens that share borders or trade livestock with currently FMD-free nations.

Cattle movements and bovine tuberculosis in Great Britain.

For 20 years, bovine tuberculosis (BTB) has been spreading in Great Britain (England, Wales and Scotland) and is now endemic in the southwest and parts of central England and in southwest Wales, and occurs sporadically elsewhere. Although its transmission pathways remain poorly understood, the disease's distribution was previously modelled statistically by using environmental variables and measures of their seasonality. Movements of infected animals have long been considered a critical factor in the spread of livestock diseases, as reflected in strict import/export regulations, the extensive movement restrictions imposed during the 2001 foot-and-mouth disease outbreak, the tracing procedures after a new case of BTB has been confirmed and the Government's recently published strategic framework for the sustainable control on BTB. Since January 2001 it has been mandatory for stock-keepers in Great Britain to notify the British Cattle Movement Service of all cattle births, movements and deaths. Here we show that movements as recorded in the Cattle Tracing System data archive, and particularly those from areas where BTB is reported, consistently outperform environmental, topographic and other anthropogenic variables as the main predictor of disease occurrence. Simulation distribution models for 2002 and 2003, incorporating all predictor categories, are presented and used to project distributions for 2004 and 2005.

Ecological sources of zoonotic diseases.

Although of zoonotic origin, pathogens or infections posing a global threat to human health such as human immunodeficiency virus, severe acute respiratory syndrome or emerging influenza type A viruses may actually have little in common with known, established zoonotic agents, as these new agents merely underwent a transient zoonotic stage before adapting to humans. Evolution towards person-to-person transmission depends on the biological features of the pathogen, but may well be triggered or facilitated by external factors such as changes in human exposure. Disease emergence may thus be depicted as an evolutionary response to changes in the environment, including anthropogenic factors such as new agricultural practices, urbanisation, or globalisation, as well as climate change. Here the authors argue that in the case of zoonotic diseases emerging in livestock, change in agricultural practices has become the dominant factor determining the conditions in which zoonotic pathogens evolve, spread, and eventually enter the human population. Livestock pathogens are subjected to pressures resulting from the production, processing and retail environment which together alter host contact rate, population size and/or microbial traffic flows in the food chain. This process is illustrated by two study cases: a) livestock development in the 'Eurasian ruminant street' (the area extending from central Asia to the eastern Mediterranean basin) and the adjacent Arabian peninsula b) poultry production in Southeast Asia. In both scenarios, environmental factors relating to demography, land pressure and imbalances in production intensification have led to an unstable epidemiological situation, as evidenced by the highly pathogenic avian influenza upsurge early in 2004, when the main outbreaks were located in areas which had both large scale, peri-urban commercial holdings and a high density of smallholder poultry units.

Predicting the distribution of urinary schistosomiasis in Tanzania using satellite sensor data.

In this paper, remotely sensed (RS) satellite sensor environmental data, using logistic regression, are used to develop prediction maps of the probability of having infection prevalence exceeding 50%, and warranting mass treatment according to World Health Organization (WHO) guidelines. The model was developed using data from one area of coastal Tanzania and validated with independent data from different areas of the country. Receiver operating characteristic (ROC) analysis was used to evaluate the model's predictive performance. The model allows reasonable discrimination between high and low prevalence schools, at least within those geographical areas in which they were originally developed, and performs reasonably well in other coastal areas, but performs poorly by comparison in the Great Lakes area of Tanzania. These results may be explained by reference to an ecological zone map based on RS-derived environmental data. This map suggests that areas where the model reliably predicts a high prevalence of schistosomiasis fall within the same ecological zone, which has common intermediate-host snail species responsible for transmission. By contrast, the model's performance is poor near Lake Victoria, which is in a different ecological zone with different snail species. The ecological map can potentially define a template for those areas where existing models can be applied, and highlight areas where further data and models are required. The developed model was then used to provide estimates of the number of schoolchildren at risk of high prevalence and associated programme costs.

Agro-climatic classification systems for estimating the global distribution of livestock numbers and commodities.

Investment in agricultural research in developing countries is being increasingly targeted at those agro-climatic zones and issues where the economic and environmental benefits may be expected to be greatest. This first requires that the zones themselves be defined, along with information on domestic livestock numbers and commodity output within agro-climatic zones in different countries. Different methods for classifying agro-climatic zones were compared. These included methods based on estimated length of growing period (LGP) using rainfall and temperature data, the ratio of precipitation to potential evapotranspiration (PET), and on more detailed agronomic models, remote sensing data and land use information. Zonation based on LGP has already been linked to existing national livestock data. By defining agro-climatic zones and relating concentrations of livestock populations to those of humans, it is possible to make realistic estimates of livestock populations and the production of livestock commodities for most developing countries. Detailed agro-climatic analyses of Mainland East Asia and Sri Lanka have recently been undertaken using the GROWEST agronomic model. Using this model as the basis of agro-climatic classification appears to be significantly superior, particularly in temperate environments, to approaches based solely on LGP. Different ways of subdividing countries and continents into agro-climatic or agro-ecological zones (AEZs) are reviewed in this paper. In addition, we show how the numbers of production and commodities from domestic livestock can be allocated to such zones. We also indicate how some of this information can be applied.

Spatial trypanosomosis management: from data-layers to decision making.

The use of geographical information systems (GIS) in the management of African animal trypanosomosis in sub-Saharan Africa offers potential in assisting decisions on allocation of resources, prioritization of control areas, and planning and management of field operations. Here, Guy Hendrickx and colleagues review approaches being used to develop reliable data-layers and to incorporate these data into GIS models. They argue that techniques should be further refined to produce more-detailed data layers and to include a dynamic element, a problem rarely addressed until now.