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

项目摘要/摘要 该奖项将使Joaniter Nankabirwa博士能够调查室内残留喷洒 杀虫剂(IRS)单独或与大规模给药(MDA，全量给药)联合使用 向整个人群提供抗疟疾治疗，而不考虑感染状况) 宿主免疫和抗药性。调查将利用来自以下方面的数据和样本- 乌干达东北部正在进行的一项研究，比较疟疾干预措施的社区影响 发病率、死亡率和传播。这项工作将在经验丰富的团队的指导下进行 在流行病学、免疫学、分子微生物学和设计方面拥有强大专业知识的导师， 临床研究的实施和分析。南卡比尔瓦博士将通过以下方式促进她的职业发展：1) 进行实验室化验，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)出席和在国际研究会议上发表演讲。这 计划将是使南卡比尔瓦博士能够作为独立的疟疾患者建立职业生涯的关键 乌干达的一名研究员。在乌干达，疟疾控制进展缓慢，控制进展缓慢。 脆弱，在停止执行后观察到寄生虫流行率上升 有效的控制干预措施。为了改善控制并最终消除，干预措施应该是 旨在消除疟疾寄生虫的宿主，包括微观和亚微观感染， 同时最大限度地减少宿主免疫力的丧失和抗药性的发展。建议的项目 这里将集中讨论IRS和MDA对亚微观感染、宿主免疫和发育的影响 耐药性，以及撤销对这些标记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需要控制和控制的最佳干预措施 在乌干达消灭疟疾。我们假设，实施美国国税局将导致减少 寄生虫感染和添加丙二醛将与进一步减少和持续减少 流行，但与单独使用IRS相比，宿主免疫力有所下降，耐药性增加。 这项研究的结果将指导决策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.