Spatial Scales of Plasmodium Falciparum Generations; Implications for Elimination

项目摘要 疟疾是一个主要的公共卫生问题，据估计，2013年全世界有1.98亿例疟疾病例。 减少疟疾传播和疾病的有效战略非常成功，导致40% 自2000年以来撒哈拉以南非洲疟疾病例的减少。已经观察到感染聚集性 在地理上，随着传播的下降，这种聚集变得更加明显。这门学问 识别感染热点或传播源是一个不断增长的领域，有望帮助 更有效的干预措施。然而，目前还没有显示出感染者是否处于密切的身体状况 就近(即在同一个家庭中)由于仅仅生活在危险的地方，或者因为 受感染的家庭成员是附近易感人群的危险因素。如果是前者，那么就瞄准 热点地区应把重点放在减少热点地区的环境风险因素上。如果是后者，那么 识别和治疗“传播者”的干预措施将减少传播和减少新的 案子。因此，我们需要了解疟疾传播的空间规模，以预测 社区病例检测和热点定位。为了阐明这一重要问题，我们提出了两个 科学目标。首先，我们将测量同一家庭内感染的遗传相关性 与更远距离感染的关联性相比。我们将确定这一关系是否 在发烧“热点”(高热发病率的地理聚集地)和发烧“冷点”方面有所不同。寄生虫DNA来自 从肯尼亚西部中度地方病研究区(约15公里乘28公里)收集的干血点 KM覆盖80多个村庄)将在一个中等多态的基因上使用DEPER进行测序 测序技术。如果附近的感染更多，这将为局部、局部传播提供证据 密切相关或将指向混合传播，感染只有在你到达 蚊子飞行的距离。我们的第二个目标是诱捕疟疾蚊子媒介并确定 被感染的蚊子。我们将通过对蚊子体内的寄生虫进行测序来确定蚊子的感染源 蚊子唾液腺，并与人类寄生虫基因型别进行比较。通过这样做，我们可以找出 感染是在家庭范围内传播，还是在地理上“混合良好”传播 而且只受到蚊子活动范围的限制。如果成功，这将是第一个链接个人的报告 蚊子对人类来源的感染。能够跟踪从人到蚊子的感染，以及 这将使我们能够以一种前所未有的方式了解传播的动力学和规模 以前是有可能的。我们希望在随后的研究中将这种方法扩大到更大的人群。 这些结果将为针对热点的干预措施的预期影响提供洞察。

Project Summary Malaria is a major public health problem, with an estimated 198 million cases occurring world-wide in 2013. Effective strategies to reduce malaria transmission and disease have been highly successful leading to a 40% reduction in malaria cases in sub-Saharan Africa since 2000. It has been observed that infections cluster geographically and such clustering becomes more pronounced as transmission declines. The science of identifying `hotspots' of infection or foci of transmission is a growing area that promises to help target interventions more effectively. However, it has not been shown whether infected individuals in close physical proximity (i.e. in the same household) are jointly infected due to simply living in a risky place, or because an infected household member is a risk factor for nearby susceptible individuals. If the former, then targeting hotspots should focus on reducing environmental risk factors in the area around a hotpsot. If the latter, then interventions to identify and treat `transmitters' will reduce transmission and reduce the incidence of new cases. Therefore, we need to understand the spatial scale of malaria transmission to predict the impact of community case detection and hotspot targeting. To shed light on this important issue, we propose two scientific objectives. First, we will measure the genetic relatedness of infections within the same household compared to the relatedness of infections at further distances. We will determine whether this relationship differs in fever `hotspots' (geographic clusters of high fever incidence) and fever `coldspots'. Parasite DNA from dried blood spots collected from a moderate endemic study area in western Kenya (approximately 15 km by 28 km encompassing more than 80 villages) will be sequenced at a moderately polymorphic gene using deep sequencing techniques. This will provide evidence for local, focal transmission if nearby infections are more closely related or will point to mixed transmission whereby infections only begin to differ as you reach the distance of mosquito flying ranges. Our second objective is to trap malaria mosquito vectors and identify infected mosquitoes. We will determine the source of the mosquito's infection by sequencing parasites in the mosquito salivary glands and comparing to parasite genotypes in humans. By doing so, we can find out whether infections are being transmitted at a household scale or transmission is `well mixed' geographically and only limited by the range of the mosquito. If successful, this will be the first report of linking individual infections in mosquitoes to their human source. The ability to track infections from human to mosquito and back again would allow us to understand the dynamics and scale of transmission in a way that has not previously been possible. We expect to scale up this approach to larger populations in subsequent studies. These results will provide insight into the expected impact of interventions designed to target hotspots.