The impact of antimalarials and insecticide resistance on malaria transmission in Uganda

项目总结 在无症状感染盛行的高传播环境中消除疟疾将 需要改进干预措施来治疗疟疾，控制病媒，并减少对蚊子的传播。 然而，我们对控制疟疾传播效率的因素的理解是不完整的， 限制我们准确预测减少传播干预措施的影响的能力。我们假设 寄生虫和蚊子因素与疟疾传播给蚊子的可能性有关。为了测试 这一假设，我们将利用我们在乌干达托罗罗建立的完善的临床和昆虫学基础设施来 用感染恶性疟原虫的乌干达人的血液感染现场采集和群体按蚊 膜摄取试验。然后我们将分析#年疟疾感染的流行率和强度 蚊子与测量的寄生虫和媒介特征的关系。在这些特征中，我们将 调查的是配子体密度、感染的多样性和性别比、寄生虫耐药性和 基因分型，蚊虫抗药性和基因分型。贝叶斯马尔可夫链蒙特卡罗方法 技术，我们将根据我们的数据拟合模型，允许显式估计与传染性相关的参数 需要重现观察到的数据，使我们能够测试我们关于 传染性，测量这些影响的大小，并确定可能的变异来源， 对于为政策决策提供信息至关重要的信息，这些决策将有助于控制和最终 消灭疟疾。具体地说，我们的结果将帮助我们确定控制措施的优先顺序 乌干达的寄生虫(毒品)和蚊子(杀虫剂)。 这个项目的PI将极大地受益于临床和昆虫学研究的基础设施 作为加州大学旧金山分校和Makerere多年来合作工作的一部分，在她在乌干达的外地地点建立了 大学。这一基础设施包括临床设施、分子和寄生虫学实验室以及 杀虫剂。此外，还组建了一支由杰出的导师和合作者组成的团队，以提供 在她提议的研究的所有方面都有专业知识。这个项目将允许私家侦探将她的研究扩大到 研究疟疾传播，是建立独立职业的理想着眼点。作为她的一部分 全面的职业发展计划，她将学习新的研究技术，项目管理，以及 作为一名独立研究人员取得成功的其他基本技能。

PROJECT SUMMARY Eliminating malaria in high transmission settings where asymptomatic infections are prevalent will require improved interventions to treat malaria, control vectors, and also decrease transmission to mosquitoes. However, our understanding of what factors govern the efficiency of malaria transmission is incomplete, limiting our ability to accurately predict the impacts of transmission-reducing interventions. We hypothesize that parasite and mosquito factors are associated with the likelihood of malaria transmission to mosquitoes. To test this hypothesis, we will utilize our well-established clinical and entomology infrastructure in Tororo, Uganda to infect field-collected and colony anopheline mosquitoes with blood from P. falciparum-infected Ugandans using membrane feeding assays. We will then analyze the prevalence and intensity of malaria infection in mosquitoes in relation to measured parasite and vector characteristics. Among the characteristics we will investigate are gametocyte density, multiplicity of infection and sex ratio, parasite drug resistance and genotypes, and mosquito insecticide resistance and genotypes. Using Bayesian Markov Chain Monte Carlo techniques, we will fit models to our data, allowing explicit estimation of parameters related to infectiousness needed to reproduce the observed data, allowing us to test our hypotheses regarding variation in infectiousness, measure the magnitude of these effects, and identify putative sources of the variation, information that will be essential to inform policy decisions that will facilitate the control and eventual elimination of malaria. Specifically, our results will help us to prioritize control measures directed toward parasites (drugs) and mosquitoes (insecticides) in Uganda. The PI of this project will greatly benefit from the infrastructure for clinical and entomology research already established in her field sites in Uganda as part of years of collaborative work between UCSF and Makerere University. This infrastructure includes clinical facilities, molecular and parasitology laboratories, and an insectary. In addition, a team of exceptional mentors and collaborators has been assembled to provide expertise in all aspects of her proposed research. This project will allow the PI to broaden her research to the study of malaria transmission, an ideal focus for the establishment of an independent career. As part of her comprehensive career development plan, she will learn new research techniques, project management, and other essential skills for a successful career as an independent researcher.