Novel molecular approaches for understanding the epidemiology of endemic anthrax

该项目将研究炭疽病，这是一种人和动物的细菌性疾病，在疾病广泛传播的发展中国家环境中。虽然炭疽通常被称为生物恐怖主义的一种制剂，但事实上，它仍然是许多贫穷农村地区，特别是撒哈拉以南非洲地区的一种常见疾病。它主要影响反刍家畜和野生动物，其中疾病表现为突然死亡。引起炭疽热的细菌孢子也可以继发性感染人类。炭疽病在人体内有三种形式之一，这取决于传播途径：一种不太严重，导致皮肤病变，两种更严重的形式影响消化和呼吸系统。如果不治疗，这三种形式都是致命的。畜牧业社区受到这种疾病的影响最大，动物损失对生计和粮食安全造成重大损失，并导致人类接触的风险。这个地区-有着丰富的各种野生动物-是马赛牧民的家园，他们几乎完全依靠牲畜来获得食物和收入。炭疽是该地区动物和人类健康的主要问题。牲畜损失时有发生，近四分之一的家庭在过去两年中报告了其畜群中的疑似病例。此外，仅在2016年下半年，该地区医院就发现了40多例人类炭疽病例，其中包括5例死亡病例。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的主要感染源，以及这些病例之间的联系。这项研究的主要目标是确定导致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的传播频率，并确定牲畜和人类的主要风险来源。我将培训一个由当地人类和动物卫生专业人员组成的小组，进行深入的病例调查。该小组将在爆发期间收集详细的数据和样本。这一培训不仅有助于该项目，而且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、卫生工作者以及地方和国家决策者参与研究的各个阶段，我将邀请这些群体的代表参加我将主持的年度研讨会。这将通过提高疾病意识，改善社区和政府关键人员之间的联系，并确保项目结果能够直接用于政策制定，最大限度地发挥我的研究成果。在该项目期间从不同宿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。将对这些不同来源（例如牲畜、野生动物和人）的DNA进行全面分析，以获得每种细菌的基因组。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，确定特定菌株与不同宿主物种之间的关联，并了解单个病例是否可能是多源感染的结果。我将利用我的研究产生的新信息为农村畜牧社区的炭疽提供管理和控制建议，从而提高动物和人类健康，并通过减少生产损失改善粮食安全和减贫。

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.