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: 10197792
• 负责人: Wendy PrudhommeOMeara
• 金额: $ 55.73万
• 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/10197792
• 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 由于广泛的原因，撒哈拉以南非洲的疟疾病例和死亡人数大大下降 部署向量控制和临床管理工具。这些工具正在补充新的 生成旨在减少和可能中断传输的可用策略。这些 减少传输干预措施包括传输封锁疫苗，大规模给药 端肽（例如IVRMECTIN）破坏载体能力，辅助使用配子细胞在感染中 使用敏感诊断方法，个人以及大众筛选和治疗程序。这些策略最多是 通过将其定位到最有可能进来的人口的人口来有效地使用 疟疾传播。这些“高发射机”的存在是由以下事实提出的：在许多情况下， 只有20％的人遭受80％的感染，表明在异质人群中， 有些人参加疟疾传播的连续周期不成比例。这组 发射器也称为疟疾“传染储水库”，并通过识别稳定或可修改的危险因素 对于在此储层中的会员资格，我们可以更有效地针对干预措施，以最大程度地影响其对 减少疟疾传播。该项目的具体目标是在自然下直接测量 感染人类的​​疾病将疟疾传播到自然喂养的蚊子，也将其传播 人类被疟疾蚊子咬伤。我们将在考试中直接检验我们的中心假设 肯尼亚Webuye West的75个家庭的流行病学研究，疟疾传播是季节性和 多年生植物，由Anopheles gambiae s传播。 l。 （88％）和Funestus（12％）。其中 家庭，我们将在人类参与者和每周的参与者中建立对疟疾病例的积极和被动检测 在他们的家庭中抽样休息的蚊子。在AIM 1中，我们将直接记录成功 通过收集活的，血液喂养的蚊子从感染者到蚊子的传播事件 参与家庭，将其饲养7天，以允许寄生虫卵囊发展和基因分型寄生虫 为了离散匹配寄生虫，因此确定成功传播的人类来源 事件。在AIM 2中，我们将量化人类感染性水库是如何通过向量叮咬偏见来塑造的， 通常，使用人类的分子指纹识别人类种群中的非随机性和高度分散 DNA直接将单个家庭成员与已摄入的人类血液粉相匹配 蚊子。这些分析的结果将为蚊子人类相互作用提供新的见解 增强寄生虫的传播，并使我们能够更精确地定义人类储层。与此 理解，我们将实现更好的基于人群的传播潜力估计并提供经验性 支持疟疾控制干预措施的合理靶向。