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

疟疾控制干预措施对乌干达传染源、宿主免疫和耐药性的影响

• 批准号: 9888457
• 负责人: Joaniter Immaculate Nankabirwa
• 金额: $ 10.29万
• 依托单位: INFECTIOUS DISEASES RES COLLABORATION
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-22 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9888457
• 关键词: Affect; Africa; Anti-malarial drug resistance; Antimalarials; Area; Artemisinins; Asia; Award; Beds; Biological Assay; Blood; Case Management; Chemoprevention; Childhood; Clinical Research; Combined Modality Therapy; Communities; Complement; Culicidae; Data; Data Analyses; Decision Making; Disease; Dose; Drug resistance; Drug usage; Epidemiology; Exposure to; Failure; Genotype; Goals; Human; Immunity; Immunoglobulin G; Immunology; Incidence; Individual; Infection; Insecticides; International; Intervention; Investigation; Laboratories; Logistics; Low Prevalence; Malaria; Measures; Mediator of activation protein; Mentors; Methods; Microbiology; Microscopic; Microscopy; Molecular; Morbidity - disease rate; Mutation; Outcome; Outcome Study; Parasitemia; Parasites; Parasitic infection; Parents; Patients; Pharmaceutical Preparations; Plasmodium falciparum; Population; Predisposition; Prevalence; Preventive treatment; Regimen; Research; Research Personnel; Residual state; Resistance; Resistance development; Risk; Sampling; Serological; Testing; Time; Uganda; Withdrawal; Work; base; career; career development; comparative; cost; density; design; drug development; effective therapy; experience; high risk population; improved; intervention effect; malaria infection; mortality; pressure; prevent; programs; response; scale up; symposium; transmission process

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.

项目概要/摘要 该奖项将使 Joaniter Nankabirwa 博士能够研究室内滞留喷洒的影响 单独使用杀虫剂 (IRS) 或与大规模药物施用 (MDA，施用全剂量 对整个人群进行抗疟治疗，无论其感染状况如何） 储存库、宿主免疫和耐药性。调查将利用来自现场的数据和样本 在乌干达东北部进行的一项研究比较了疟疾干预措施对社区的影响 发病率、死亡率和传播。这项工作将在经验丰富的团队的指导下进行 拥有流行病学、免疫学、分子微生物学和设计方面丰富专业知识的导师， 临床研究的实施和分析。 Nankabirwa 博士将通过以下方式进一步发展她的职业发展： 1） 进行实验室检测，2) 参加临床研究、免疫学、分子学课程 微生物学和数据分析，3) 参加国际研究会议并在会上发表演讲。这 该计划对于使 Nankabirwa 博士能够独立从事疟疾治疗工作至关重要 乌干达研究员。在乌干达，疟疾控制进展缓慢，控制成果有限 脆弱，在停止实施后观察到寄生虫流行率增加 有效的控制干预措施。为了改善控制并最终消除，应采取干预措施 旨在消除疟疾寄生虫的储存库，包括微观和亚微观感染， 并最大限度地减少宿主免疫力的丧失和耐药性的产生。拟建项目 这里将重点讨论IRS和MDA对亚显微感染、宿主免疫和发育的影响 抵抗力，以及撤回对这些标记的干预措施的反弹效应。 了解这些干预措施的影响将有助于确定控制和控制的最佳干预措施 消除乌干达的疟疾。我们假设实施 IRS 将导致患病率下降 寄生虫感染，添加MDA将与进一步减少和持续减少相关 流行，但与单独的 IRS 相比，宿主免疫力有所丧失，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来控制和 消除乌干达的疟疾。