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

一旦被咬：对人类和蚊子之间成功的疟疾寄生虫传播事件的纵向观察研究

• 批准号: 9978708
• 负责人: Wendy PrudhommeOMeara
• 金额: $ 60.07万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-16 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978708
• 关键词: Africa; Africa South of the Sahara; Anopheles Genus; Anopheles gambiae; Behavioral; Bioinformatics; Biometry; Blood; Cessation of life; Characteristics; Clinical; Clinical Management; Couples; Culicidae; Data; Detection; Diagnostic; Enrollment; Entomology; Epidemiology; Event; Falciparum Malaria; Frequencies; Generations; Genetic; Genotype; Goals; Household; Human; Individual; Infection; Ingestion; Interruption; Intervention; Ivermectin; Kenya; Longitudinal Studies; Longitudinal observational study; Malaria; Mass Screening; Measurement; Measures; Medical Entomology; Midgut; Molecular Profiling; Oocysts; Parasites; Participant; Persons; Plasmodium falciparum; Population; Research; Rest; Risk Factors; Sampling; Source; Testing; Time; Translating; Translations; clinical epidemiology; cohort; design; epidemiology study; feeding; human DNA; insight; malaria mosquito; malaria transmission; member; models and simulation; modifiable risk; population based; programs; public health relevance; tool; transmission process; transmission-blocking vaccine; vector; vector competence; vector control; vector mosquito

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.

项目摘要 在撒哈拉以南非洲，疟疾病例和死亡人数大幅下降， 部署病媒控制和临床管理工具。这些工具正在由一个新的 生成旨在减少并可能中断传输的可用策略。这些 减少传播的干预措施包括阻断传播的疫苗、大规模接种 杀内外寄生虫剂（如伊维菌素）破坏载体能力，在感染者中连续使用杀配子剂 个人和大规模屏幕和治疗程序使用敏感的诊断。这些战略将是最 有效地利用它们的目标人群，最有可能有助于向前发展， 疟疾传播。这些“高发射器”的存在是由以下事实表明的，在许多情况下， 只有20%的个体遭受80%的感染，这表明在异质人群中， 有些人不成比例地参与了疟疾传播的持续循环。这群 传播者也被称为疟疾“传染源”，并通过确定稳定或可改变的风险因素， 对于这一储备库的成员，我们可以更有效地进行干预，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直接测量自然条件下的 条件，其中感染的人传播疟疾寄生虫自然喂养的蚊子， 人被疟疾蚊子媒介叮咬。我们将在一个观察性的实验中直接检验我们的中心假设。 对肯尼亚西韦布耶75户家庭进行的流行病学研究，那里的疟疾传播是季节性的， 是一种由冈比亚按蚊（Anopheles gambiae s.）L. (88%）和一个。funestus（12%）。在这些 我们将在人类参与者中建立主动和被动的疟疾病例检测， 对他们家中的休眠蚊子进行采样。在目标1中，我们将直接记录成功的前进 通过收集活的、吸血的蚊子， 参与者家庭，将其饲养7天以使寄生虫卵囊发育，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， 活动在目标2中，我们将量化人类传染性水库如何通过媒介叮咬偏倚形成，这是 通常非随机和高度过度分散在人群中，使用人类的分子指纹， DNA直接匹配个别家庭成员的人类血液餐，已被摄入的 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， 增强寄生虫的传播，并将使我们能够更精确地定义人类宿主。与此 了解，我们将能够更好地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。