Estimating the incremental benefits on active malaria case detection of high-sensitivity rapid diagnostic tests

估计高灵敏度快速诊断测试对活动性疟疾病例检测的增量效益

• 批准号: 9805378
• 负责人: Steve Myer Taylor
• 金额: $ 8.05万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-08 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9805378
• 关键词: Africa; Africa South of the Sahara; African; Biological Assay; Blood; Child; Childhood; Clinical; Communities; Country; Coupled; Data; Detection; Diagnostic; Diagnostic tests; Enrollment; Epidemiology; Gene Targeting; Goals; Health Benefit; Household; Individual; Infection; Kenya; Malaria; Measurement; Measures; Molecular; Parasites; Plasmodium falciparum; Public Health; Research; Residual state; Sampling; Seasons; Site; Source; Specimen; Spottings; Testing; Time; base; density; design; evidence base; field study; indexing; member; next generation; programs; screening; tool; transmission process; treatment program

Project Abstract Malaria control is reducing parasite transmission in many parts of sub-Saharan Africa, which enables the application of more aggressive control measures. Among these are active case detection (ACD), in which community members are screened with diagnostic tests, and reactive case detection (RACD), a strategy in which passively-detected cases trigger “ring screening” with diagnostic testing in order to identify secondary cases. RACD is described by WHO’s Framework for Malaria Elimination as “an important component of an elimination strategy.” RACD has been considered infeasible in many African settings owing to a lack of spatial case aggregation, limits in operational capacity, and the inability to detect low-density infections (< 100 parasites/µL [p/µL]) with malaria rapid diagnostic tests (RDTs). Importantly, next-generation RDTs are enabling detection of parasites to very low densities (~ 1 p/µL), suggesting that, coupled with declines in transmission, RACD with RDTs may become an efficient strategy for case detection in many African settings. What we do not know are the predicted impacts of a next-generation RDT for RACD on both the incremental gains in secondary case detection as well as on the case detection rate compared with standard ACD. In this R03 project, we will use previously-collected specimens from a study conducted in 2014 in Webuye, Kenya, which has seasonal, perennial transmission of P falciparum; the study enrolled children both with and without clinical malaria (assessed by standard RDT) as index cases and then sampled all members of their households for a dried blood spot. In > 4,000 individuals sampled, we will detect P. falciparum using a real-time PCR assay targeting a multi-copy gene target that can detect parasites down to 0.1 p/µL and quantify down to 1 p/µL. In Aim 1, we will use molecular parasite density measurements to estimate the marginal yield of detected parasites by RACD programs employing RDTs with limits of detection that vary from 200 to 1 p/µL. In Aim 2, we will compare between ACD and RACD the incremental secondary case detection rate that would have been detected by a next-generation RDT with a limit of detection of 1 p/µL. Our data will enable the rational design of implementation studies that test the use of next-generation RDTs as tools for RACD in Africa. These studies will ultimately furnish an evidence base for the deployment of RACD more widely as a public health activity as African countries continue to push towards malaria elimination.

项目摘要 疟疾控制正在减少撒哈拉以南非洲许多地区的寄生虫传播， 采取更积极的控制措施。其中包括主动病例检测（ACD），其中 社区成员通过诊断测试和反应性病例检测（RACD）进行筛查， 哪些被动检测到的病例会触发诊断测试的“环形筛查”， 例世卫组织的《消除疟疾框架》将RACD描述为“一项 淘汰战略”。由于缺乏空间，区域艾滋病方案在许多非洲环境中被认为是不可行的。 病例聚集、业务能力有限以及无法检测低密度感染（< 100 寄生虫/微升[p/微升]）与疟疾快速诊断试验（RDTs）。重要的是，下一代RDT使 检测到的寄生虫密度非常低（~ 1 p/µL），这表明，加上传播下降， RACD与RDT可能成为一个有效的战略，在许多非洲的情况下，案件检测。我们做什么 不知道下一代RACD RDT的预测影响， 二次病例检测以及与标准ACD相比的病例检测率。在此R 03 我们将使用2014年在肯尼亚Webuye进行的一项研究中收集的标本， 有恶性疟原虫的季节性、常年性传播;该研究招募了有和没有临床症状的儿童， 疟疾（通过标准RDT评估）作为指标病例，然后对其所有家庭成员进行抽样调查， 干涸的血迹在> 4，000个样本中，我们将使用实时PCR检测法检测恶性疟原虫 靶向多拷贝基因靶标，可检测低至0.1 p/µL的寄生虫，并定量低至1 p/µL。在 目的1，我们将使用分子寄生虫密度测量来估计检测的边际产量， 采用RDT的RACD程序检测寄生虫，检测限从200到1 p/µL不等。在目标2中， 我们将比较ACD和RACD之间的增量继发病例检出率， 下一代RDT检测限为1 p/µL。我们的数据将使理性的 设计执行研究，测试下一代区域主任小组作为非洲区域艾滋病防治工具的使用情况。这些 这些研究最终将为RACD作为一种公共卫生手段更广泛地部署提供证据基础 在非洲国家继续努力消除疟疾的过程中，