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

乌干达抗疟药和杀虫剂耐药性对疟疾传播的影响

• 批准号: 10330552
• 负责人: Melissa D Conrad
• 金额: $ 14.12万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-21 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10330552
• 关键词: Africa South of the Sahara; Anopheles Genus; Anopheles gambiae; Anti-malarial drug resistance; Biological Assay; Biology; Blood; Characteristics; Clinical; Clinical Research; Consumption; Culicidae; Data; Data Analyses; Development; Development Plans; Disease; Drug resistance; Entomology; Female; Genes; Genotype; Goals; Human; Immune response; Infection; Infrastructure; Innate Immune Response; Insecticide Resistance; Insecticides; Intervention; Laboratories; Learning; Malaria; Markov chain Monte Carlo methodology; Measures; Membrane; Mentors; Midgut; Modeling; Molecular; Molecular Epidemiology; Natural Immunity; Oocysts; Parasites; Parasitology; Patients; Pharmaceutical Preparations; Plasmodium falciparum; Policies; Policy Maker; Prevalence; Process; Research; Research Personnel; Research Technics; Resistance; Resistance profile; Resource-limited setting; Sex Ratio; Site; Source; Sporozoites; Techniques; Testing; Training; Uganda; Universities; Vaccination; Variant; Work; career; career development; clinical infrastructure; density; drug sensitivity; experimental study; feeding; improved; malaria infection; malaria transmission; molecular marker; skills; transmission process; vector; vector control; vector mosquito

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.

项目概要 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、控制病媒并减少向蚊子的传播。 然而，我们对控制疟疾传播效率的因素的理解并不完整， 限制了我们准确预测减少传播干预措施影响的能力。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。测试 根据这一假设，我们将利用我们在乌干达托罗罗完善的临床和昆虫学基础设施来 使用来自感染恶性疟原虫的乌干达人的血液感染现场采集的按蚊和群体按蚊 膜喂养测定。然后我们将分析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 调查配子体密度、感染复数和性别比、寄生虫耐药性和 基因型，以及蚊子杀虫剂抗性和基因型。使用贝叶斯马尔可夫链蒙特卡罗 技术，我们将模型拟合我们的数据，允许明确估计与传染性相关的参数 需要重现观察到的数据，使我们能够检验我们关于变化的假设 传染性，测量这些影响的程度，并确定变异的假定来源， 对于促进控制和最终的政策决策至关重要的信息 消除疟疾。具体来说，我们的结果将帮助我们优先考虑针对以下目标的控制措施： 乌干达的寄生虫（毒品）和蚊子（杀虫剂）。 该项目的 PI 将极大地受益于现有的临床和昆虫学研究基础设施 作为加州大学旧金山分校和马凯雷雷多年合作的一部分，她在乌干达的现场建立了 大学。该基础设施包括临床设施、分子和寄生虫学实验室以及 昆虫的。此外，还组建了一支由杰出导师和合作者组成的团队，以提供 她所提议的研究的各个方面的专业知识。该项目将使 PI 将她的研究范围扩大到 研究疟疾传播，是建立独立职业的理想焦点。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、项目管理和 作为独立研究员取得成功职业生涯的其他基本技能。