Once bitten: A longitudinal, observational study of successful malaria parasite transmission events between humans and mosquitos

项目总结 撒哈拉以南非洲的疟疾病例和死亡人数显著下降，原因是广泛的 部署病媒控制和临床管理工具。这些工具得到了一个新的补充 生成旨在减少甚至可能中断传输的可用策略。这些 减少传播的干预措施包括传播阻断疫苗、大规模接种 杀菌剂(如伊维菌素)，以破坏媒介能力，在感染的患者中辅助使用配子杀菌剂 个人，以及使用敏感诊断的大规模筛选和治疗程序。这些策略将是最 通过将它们定位于最有可能对未来做出贡献的人类群体来有效利用 疟疾传播。事实表明，在许多情况下， 低至20%的个体遭受80%的感染，这表明在不同的人类群体中， 有些人不成比例地参与了疟疾传播的持续循环。这群人 传播者也被称为疟疾“感染源”，通过确定稳定或可改变的危险因素。 对于这个储备库的成员，我们可以更有效地针对干预措施，以最大限度地发挥其影响 减少疟疾传播。该项目的具体目标是在自然条件下直接测量 被感染的人将疟疾寄生虫传播给自然喂养的蚊子的条件，以及 人类被疟疾蚊子媒介叮咬。我们将在观测中直接测试我们的中心假设 肯尼亚韦布耶西部75户家庭的流行病学研究，那里的疟疾传播是季节性的和 多年生，由冈比亚按蚊S、L(88%)和按蚊传播。Funestus(12%)。在这些区域内 家庭，我们将建立主动和被动检测疟疾病例的人类参与者和每周 在他们的家庭中采集休息的蚊子样本。在目标1中，我们将直接记录成功继续 从感染者到按蚊的传播事件通过收集活的血液喂养的蚊子 参与者家庭，饲养7天以允许寄生虫卵囊发育，并对寄生虫进行基因分型 为了离散地匹配寄生虫，从而确定成功传播的人类来源 事件。在目标2中，我们将量化人类感染性宿主是如何由媒介叮咬偏见形成的，这是 典型的非随机和高度过度分散的人类种群，使用人类的分子指纹 DNA将单个家庭成员与被人类摄入的血粉直接匹配 蚊子。这些分析的结果将为蚊子与人类的相互作用提供新的见解 加强寄生虫传播，将使我们能够更准确地确定人类宿主。有了这个 理解，我们将实现更好的基于人口的传播潜力估计，并提供经验 支持合理确定疟疾控制干预措施的目标。

PROJECT SUMMARY Malaria cases and deaths have declined significantly in sub-Saharan Africa as a result of the broad deployment of vector control and clinical management tools. These tools are being supplemented by a new generation of available strategies that are designed to reduce and possibly interrupt transmission. These transmission-reducing interventions include transmission-blocking vaccines, mass administration of endectocides (e.g. ivermectin) to undermine vector competence, adjunctive use of gametocytocides in infected individuals, and mass screen and treat programs using sensitive diagnostics. These strategies will be most efficiently employed by targeting them to human populations that are most likely to contribute to onward malaria transmission. The existence of these “high transmitters” is suggested by the fact that, in many settings, as few as 20% of individuals suffer 80% of infections, indicating that within heterogeneous human populations, some people participate disproportionately in the continual cycle of malaria transmission. This group of transmitters is also called the malaria `infectious reservoir', and by identifying stable or modifiable risk factors for membership in this reservoir we can more efficiently target interventions to maximize their impact on reducing malaria transmission. The specific objective of this project is to directly measure, under natural conditions, which infected humans transmit malaria parasites to naturally-feeding mosquitoes and also which humans are bitten by malaria mosquito vectors. We will directly test our central hypothesis in an observational epidemiologic study of 75 households in in Webuye West, Kenya, where malaria transmission is seasonal and perennial and is transmitted by Anopheles gambiae s. l. (88%) and An. funestus (12%). Within these households, we will establish active and passive detection of malaria cases in human participants and weekly sampling of resting mosquitos in their households. In Aim 1, we will directly record successful onward transmission events from infected people to Anopheline mosquitos by collecting live, blood-fed mosquitos in participant households, raising them for 7 days to allow parasite oocysts to develop, and genotyping parasites in order to discretely match parasites and therefore ascertain the human source of the successful transmission event. In Aim 2, we will quantify how the human infectious reservoir is shaped by vector biting bias, which is typically non-random and highly overdispersed in human populations, using molecular fingerprinting of human DNA to directly match individual household members to human blood meals that have been ingested by mosquitoes. The results of these analyses will provide new insight into mosquito-human interactions that enhance parasite transmission and will enable us to more precisely define the human reservoir. With this understanding, we will enable better population-based estimates of transmission potential and furnish empiric support for the rational targeting of malaria control interventions.