Novel molecular approaches for understanding the epidemiology of endemic anthrax

该项目将在炭疽病流行的发展中国家环境中研究炭疽病，这是一种人和动物的细菌性疾病。虽然炭疽病通常被认为是生物恐怖主义的一种媒介，但在许多贫穷的农村地区，尤其是在撒哈拉以南的非洲地区，炭疽病实际上仍然是一种常见病。它主要影响反胃家畜和野生动物，表现为猝死。引起炭疽病的细菌孢子也可以二次感染人类。根据传播途径的不同，炭疽病在人体内可能有三种形式之一：一种不太严重，会导致皮肤损伤；另两种更严重的形式会影响消化系统和呼吸系统。如果不治疗，这三种形式都可能是致命的。牲畜饲养社区感受到了这种疾病的最大影响，在那里，动物损失意味着生计和粮食安全的巨大代价，并导致人类暴露的风险。该项目将设在东非坦桑尼亚的恩戈罗保护区。这一地区拥有丰富的野生动物，是马赛牧民的家园，他们的食物和收入几乎完全依赖牲畜。炭疽病是这一地区动物和人类健康的主要问题。牲畜损失经常发生，在过去两年中，大约四分之一的家庭报告了他们的牛群中的疑似病例。此外，仅在2016年下半年，该地区医院就发现了40多例人类炭疽热病例--包括5例死亡。在这个独特的研究系统中，我将应用新技术来研究从受影响的动物和人身上获得的细菌的遗传特征。这些分析将使我能够确定动物和人类的主要感染源，以及这些病例是如何联系在一起的。这项研究的主要目标是确定引起炭疽的细菌是如何传播和传播的，特别是在疫情爆发期间。这包括评估不同宿主物种之间传播的频率，并确定牲畜和人的主要风险来源。我将培训一支由当地人类和动物卫生专业人员组成的团队，进行深入的案件调查。该小组将在疫情爆发期间收集详细的数据和样本。这项培训不仅将有助于该项目，还将加强当地处理这一疾病和其他动物疾病的能力。为了确保受影响的社区成员、卫生从业者以及地方和国家政策制定者参与研究的所有阶段，我将邀请这些群体的代表参加我将主持的年度研讨会。这些将最大限度地提高我的研究的好处，提高对疾病的认识，改善社区和政府关键个人之间的联系，并确保项目成果能够直接纳入政策。在这个项目期间从不同寄主物种收集的样本将作为细菌DNA的来源，可用于跟踪传播，类似于法医调查中的DNA指纹。来自这些不同来源(例如牲畜、野生动物和人)的DNA将被全面分析，以获得每一种细菌的基因组。这些数据将提供令人难以置信的高分辨率信息，使我能够重建受影响物种之间的传播链，确定特定菌株和不同宿主物种之间的关联，并了解个别病例是否可能是来自多种来源的感染的结果。我将使用我的研究产生的新信息，为农村畜牧业社区的炭疽病提供管理和控制建议，从而提高动物和人类的健康，并通过减少生产损失来改善食品安全和扶贫。

This project will study anthrax, a bacterial disease of people and animals, in developing-country settings where the disease is widespread. While anthrax is most commonly known as an agent of bio-terrorism, it in fact remains a common disease in many poor rural areas, particularly in sub-Saharan Africa. It primarily affects ruminant livestock and wildlife, wherein the disease manifests as sudden deaths. The bacterial spores that cause anthrax can also secondarily infect humans. Anthrax can take one of three forms in people, depending on the route of transmission: a less serious from causing skin lesions, and two more severe forms affecting the digestive and respiratory systems. All three forms can be fatal if left untreated. The greatest impacts of this disease are felt by livestock-keeping communities, where animal losses represent significant costs for livelihoods and food security, and result in risk of human exposure.This project will be based in the Ngorongoro Conservation Area in Tanzania, East Africa. This area - rich in a variety of wildlife - is home to Maasai pastoralists who depend almost entirely on livestock for food and income. Anthrax is a major issue for both animal and human health in this area. Livestock losses occur regularly, with approximately a quarter of households reporting suspected cases in their herds over the past two years. Additionally, more than 40 cases of human anthrax - including five deaths - were seen at the regional hospital in the second half of 2016 alone. In this unique study system, I will apply novel techniques to study the genetic characteristics of bacteria obtained from affected animals and people. These analyses will allow me to determine the main sources of infection for animals and people, and how these cases are linked.The main objective of this study is to determine how the bacterium that causes anthrax is spread and transmitted, particularly during outbreaks. This includes assessing how often transmission occurs between different host species, and identifying the main sources of risk for livestock and people. I will train a team of local human and animal health professionals to conduct in-depth case investigations. The team will collect detailed data and samples during outbreaks. This training will contribute not only to the project, but will strengthen local capacity to handle this and other animal diseases. To ensure that affected community members, health practitioners, and local and national policy makers are involved at all stages of the research, I will invite representatives from these groups to attend annual workshops that I will host. These will maximise the benefits of my research by increasing disease awareness, improving connectivity among key individuals in the community and government, and ensuring that project results are able to feed directly into policy.The samples collected from the different host species during this project will serve as a source of bacterial DNA that can be used to track transmission, similarly to DNA fingerprinting in forensics investigations. The DNA from these various sources (e.g. livestock, wildlife and people) will be fully analysed to obtain the genome of each individual bacterium. These data will provide incredibly high-resolution information that will allow me to reconstruct chains of transmission amongst affected species, determine associations between particular strains and different host species, and understand whether individual cases may be the result of infection from multiple sources.I will use the novel information generated by my study to provide management and control recommendations for anthrax in rural livestock-keeping communities, leading to enhanced animal and human health, and improved food security and poverty alleviation through reduced production losses.