Zoonotic tick-borne pathogens contribute to acute febrile illness in rural South Africa

项目总结/摘要部分 超过60%的人类传染病是由动物传播的，通常是通过节肢动物传播的。近几 近年来，许多地区出现或重新出现了病媒传播的病毒、细菌和寄生虫病， 全球健康和经济问题。这些疾病的生态学和流行病学受到 病原体、宿主和环境之间的相互关系。通过病媒传播的感染 因此，家畜或人类的野生动物宿主物种是主要关注的问题。Mnisi One Health 建立了一个平台，以促进人类/牲畜/野生动物界面尖端的研究。关于Mnisi 该社区是位于南非姆普马兰加省的一个农村贫困地区。的 社区与野生动物保护区共享75%的边界，包括克鲁格国家公园，并提供 人类与家养动物和野生动物之间相互作用的环境。汉斯·霍海森 野生动物研究站是一个设备齐全的现场实验室，使研究人员能够在现场处理样本。 社区支持研究活动和干预措施，以换取一系列与健康有关的援助。 地区利用这一丰富的基础设施，我们计划检验一个假设，即相当大比例的非疟疾 Mnisi社区的急性发热性疾病（AFI）可归因于蜱传的人畜共患病。将一些早期的 研究结果表明，人畜共患病，特别是蜱叮咬热，Q热和人粒细胞无形体病， 在Mnisi的发热患者的调查中考虑。为了解决这个问题， 我们计划在野生动物-牲畜-人类界面研究蜱传病原体， 这个社区的发热性疾病的病原体。我们的第一个目标是测试人类患者的样本 在Mnisi社区的卫生诊所因人畜共患病而出现非疟疾AFI的人 使用宏基因组方法研究病原体。接下来我们将分析蜱虫的微生物组，以确定哪种蜱虫- 携带的病原体在社区中传播。我们认为蜱虫是病原体的集中体 在社区中传播，因此将提供蜱传病原体的代表性采样。 在两个样本集中检出的未知微生物将被鉴定为推定病原体。然后我们计划 为了检测一系列样本中斑点热群立克次体的存在，C. burnetii，A. 嗜吞噬细胞菌、巴尔通体属和鉴定的任何其他重要推定病原体。的遗传多样性 将对鉴定出的微生物进行分析。还将确定推定的蜱虫载体和储库宿主。 在此基础上，可以在农村社区进行诊断检测，确保采取适当的干预措施， 有益于人类健康和福祉。该提案侧重于南非的人畜共患蜱传疾病; 我们对影响南非人类健康的人畜共患蜱传病原体的知识基础将得到扩展 并加深我们对生活在交界地带的乡郊社区所面对的挑战的了解。这 不仅对南非，而且对其他非洲国家都有价值。

PROJECT SUMMARY/ABSTRACT SECTION More than 60% of infectious diseases in humans are spread from animals, often by an arthropod vector. In recent years, vector-borne viral, bacterial and parasitic diseases have emerged or re-emerged in many regions causing global health and economic concerns. The ecology and epidemiology of these diseases are affected by the interrelations between the pathogen, the host and the environment. Vector-borne infections transmitted from wildlife reservoir species to domestic animals or humans are thus of major concern. The Mnisi One Health Platform was established to facilitate research at the cusp of human/livestock/wildlife interface. The Mnisi community is a rural, impoverished area that is situated in the Mpumalanga Province, South Africa. The community shares 75% of its boundary with wildlife reserves, including the Kruger National Park, and provides an environment where there is interaction between humans and domestic and wild animals. The Hans Hoheisen Wildlife Research Station is a well-equipped laboratory on site enabling researchers to process samples on site. The community supports research activities and interventions in return for assistance in an array of health related areas. Using this rich infrastructure, we plan to test the hypothesis that a significant proportion of non-malarial acute febrile illness (AFI) in the Mnisi community can be attributed to tick-borne zoonoses. Some of our early findings suggest that zoonoses, particularly tick bite fever, Q fever and human granulocytic anaplasmosis need to be considered in the investigation of febrile patients presenting for care in Mnisi. In an effort to address this, we plan to study tick-borne pathogens at the wildlife-livestock-human interface, and to identify potential aetiological agents of febrile illnesses in this community. Our first goal is to test samples from human patients who present with non-malarial AFI at the health clinics in the Mnisi community for the presence of zoonotic pathogens using a metagenomic approach. Next we will analyze the microbiome of ticks to determine which tick- borne pathogens are circulating in the community. We believe that ticks act as a focal concentrator of pathogens circulating in the community, and therefore will provide a representative sampling of tick-borne pathogens. Unknown organisms that are detected in both sample sets will be identified as putative pathogens. We then plan to examine a range of samples for the presence of the spotted-fever group rickettsiae, C. burnetii, A. phagocytophilum, Bartonella spp and any other significant putative pathogens identified. The genetic diversity of the organisms identified will be analyzed. The putative tick vector(s) and reservoir hosts will also be identified. Based on this, diagnostic tests can be implemented in rural communities ensuring appropriate interventions and benefiting human health and well-being. This proposal focuses on zoonotic tick-borne diseases in South Africa; our knowledge base of zoonotic tick-borne pathogens impacting human health in South Africa will be expanded and our understanding of the challenges faced by rural communities living at the interface will be enhanced. This will be of value not only for South Africa, but also for other African countries.