Impact of malaria control interventions on the infectious reservoir, host immunity, and drug resistance in Uganda

项目总结/摘要 该合同将使Joaniter Nankabirwa博士能够调查室内滞留喷洒对环境的影响， 杀虫剂（IRS）单独或与大量药物给药（MDA，全剂量给药 所有人，不论感染状况如何，都能得到抗疟治疗） 宿主免疫和耐药性。调查将利用来自一个国家的数据和样本， 正在乌干达东北部进行的一项研究，比较疟疾干预措施对社区的影响 发病率、死亡率和传播。这项工作将在一个有经验的小组的指导下进行 在流行病学、免疫学、分子微生物学和设计方面具有很强专业知识的导师， 临床研究的实施和分析。Nankabirwa博士将通过以下方式促进其职业发展：1） 进行实验室分析，2）参加临床研究，免疫学，分子生物学课程 微生物学和数据分析，以及3）参加并出席国际研究会议。这 该计划将是至关重要的，使Nankabirwa博士建立一个职业生涯作为一个独立的疟疾 乌干达的研究员。在乌干达，疟疾防治进展缓慢，防治成果一直没有取得。 脆弱，在停止执行《消除对妇女一切形式歧视公约》后， 有效的控制措施。为了改善控制和最终消除，干预措施应 旨在消除疟疾寄生虫的宿主，包括微观和亚微观感染， 同时使宿主免疫力的丧失和抗性的发展最小化。该项目提议 本文将着重介绍IRS和MDA对亚显微感染、宿主免疫和发育的影响 以及撤销对这些标志物的干预的反弹效应。 了解这些干预措施的影响将有助于确定最佳干预措施， 在乌干达消灭疟疾。我们假设实施IRS将导致 寄生虫感染，并增加MDA将与进一步减少和持续减少， 普遍存在，但与单独使用IRS相比，宿主免疫力有所丧失，耐药性有所增加。 这项研究的结果将指导如何最好地实施干预措施，以控制和 在乌干达消灭疟疾。

PROJECT SUMMARY/ABSTRACT This award will enable Dr. Joaniter Nankabirwa to investigate the impact of indoor residual spraying of insecticides (IRS) alone or in combination with mass drug administration (MDA, administration of a full doses of antimalarial treatment to an entire population irrespective of infection status) on the malaria infectious reservoir, host immunity, and drug resistance. The investigations will leverage data and samples from an on- going study in north-eastern Uganda comparing the community impacts of the interventions on malaria morbidity, mortality and transmission. This work will be undertaken with the guidance of an experienced team of mentors with strong expertise in epidemiology, immunology, molecular microbiology, and the design, implementation and analysis of clinical studies. Dr. Nankabirwa will further her career development by; 1) conducting the laboratory assays, 2) attending courses in clinical research, immunology, molecular microbiology, and data analysis, and 3) attending and presenting at international research conferences. This program will be critical in enabling Dr. Nankabirwa to establish a career as an independent malaria researcher in Uganda. In Uganda, malaria control progress has been slow and control gains have been fragile, with increases in parasite prevalence being observed following cessation of implementation of effective control interventions. For improved control and ultimately elimination, interventions should be designed to eliminate reservoirs of malaria parasites, including microscopic and sub-microscopic infections, and yet minimize both the loss of host immunity, and the development of resistance. The project proposed here will focus on the effects of IRS and MDA on sub-microscopic infections, host immunity and development of resistance, as well as the rebound effects of withdrawing the interventions on these markers. Understanding the impacts of these interventions will help to identify the optimal interventions to control and eliminate malaria in Uganda. We hypothesise that implementing IRS will lead to decreased prevalence of parasite infection, and adding MDA will be associated with a further decrease and sustained reduction in the prevalence, but with some loss of host immunity and increase in drug resistance compared to IRS alone. Findings from this study will guide decision making on how best to implement interventions to control and eliminate malaria in Uganda.