Spatial Scales of Plasmodium Falciparum Generations; Implications for Elimination

恶性疟原虫世代的空间尺度；

• 批准号: 9316230
• 负责人: Wendy PrudhommeOMeara
• 金额: $ 18.77万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-15 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9316230
• 关键词: Achievement; Africa South of the Sahara; Antibodies; Area; Back; Blood; Breeding; Civilization; Communities; Culicidae; DNA; Detection; Disease; Enrollment; Environmental Risk Factor; Event; Fever; Flying body movement; Generations; Genes; Genetic; Genetic Drift; Genetic Heterogeneity; Genome; Genotype; Geographic Locations; Geography; Heterogeneity; Home environment; Household; Human; Incidence; Individual; Infection; Intervention; Kenya; Light; Link; Logic; Longitudinal cohort; Malaria; Measures; Molecular; Operations Research; Parasites; Plasmodium falciparum; Population; Prevalence; Probability; Process; Public Health; Reporting; Risk; Risk Factors; Salivary Glands; Sampling; Science; Shapes; Site; Source; Sporozoites; Spottings; Structure; Techniques; Testing; Time; Work; base; deep sequencing; density; design; improved; insight; interest; intervention effect; malaria infection; malaria transmission; member; remediation; scale up; screening; success; theories; therapy design; transmission process; vector; vector mosquito

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.

项目摘要 疟疾是一个主要的公共卫生问题，估计在2013年全球范围内发生了1.98亿个病例。 减少疟疾传播和疾病的有效策略已经非常成功，导致40％ 自2000年以来，撒哈拉以南非洲疟疾病例的减少。已经观察到感染簇 随着传输的下降，地理上和这种聚类变得更加明显。科学 识别感染或传播焦点的“热点”是一个增长的区域，有望帮助目标 干预措施更有效。但是，尚未显示感染的人是否紧密地感染了身体 接近（即在同一家庭中）由于仅生活在一个危险的地方而被共同感染，或者是因为 感染的家庭成员是附近易感人群的危险因素。如果前者，则针对 热点应集中于减少热门人群周围地区的环境风险因素。如果后者，那 识别和治疗“发射器”的干预措施将减少传输并降低新的发生率 案例。因此，我们需要了解疟疾传播的空间尺度，以预测 社区案例检测和热点定位。为了阐明这个重要问题，我们提出了两个 科学目标。首先，我们将衡量同一家庭中感染的遗传相关性 与进一步距离感染的相关性相比。我们将确定这种关系是否 发烧的“热点”（高烧发病率的地理簇）和发烧“冷点”不同。寄生虫DNA来自 从肯尼亚西部一个中等流行研究区收集的干血点（约15 km x 28 包含80多个村庄的KM将在中等多态性基因上进行测序 测序技术。如果附近感染更多，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，在您到达时，感染才开始差异 蚊子飞行范围的距离。我们的第二个目标是捕获疟疾蚊子并识别 感染的蚊子。我们将通过对寄生虫进行测序来确定蚊子感染的来源 蚊子唾液腺，与人类的寄生虫基因型进行比较。通过这样做，我们可以找出 在家庭规模还是传播中，感染在地理上是“充分混合”的 并且仅受蚊子范围的限制。如果成功，这将是链接个人的第一个报告 蚊子的感染对人类来源。追踪从人到蚊子感染的能力和 再次返回将使我们能够以一种没有的方式理解传输的动态和规模 以前是可能的。我们希望在随后的研究中将这种方法扩展到更大的人群。 这些结果将洞悉旨在针对热点的干预措施的预期影响。