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

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，这使得 采取更加积极的控制措施。其中包括活动病例检测(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，这是 哪些被动发现的病例触发了诊断检测的“环形筛查”，以便识别二次 案子。世界卫生组织的《消除疟疾框架》将RACD描述为 淘汰赛策略。由于缺乏空间，RACD在许多非洲环境中被认为是不可行的 病例聚集、业务能力限制以及无法检测到低密度感染(&lt；100 寄生虫/L[p/L])疟疾快速诊断试验(RDT)。重要的是，下一代RDT正在实现 检测到极低密度的寄生虫(~1 p/µL)，这表明，再加上传播的下降， 在许多非洲环境中，带有RDT的RACD可能成为一种有效的病例检测战略。我们要做的是 不知道针对RACD的下一代RDT对以下两方面的增量收益的预测影响 二次病例检测以及与标准ACD相比的病例发现率。在本R03中 项目中，我们将使用2014年在肯尼亚Webuye进行的一项研究中收集的样本，该研究 有季节性、常年传播的恶性疟原虫；这项研究招募了有临床症状和无临床症状的儿童 疟疾(由标准RDT评估)作为索引病例，然后对其所有家庭成员进行抽样调查 干血斑点。在4,000个样本中，我们将使用实时聚合酶链式反应检测恶性疟原虫 以多拷贝基因靶点为靶点，可以检测到寄生虫低至0.1p/µL，并定量低至1p/µL。 目标1，我们将使用分子寄生虫密度测量来估计被检测到的 由RACD程序使用RDT的寄生虫，其检测极限从200到1p/µL。在目标2， 我们将比较ACD和RACD之间的增量二次病例发现率 被新一代RDT检测到，检测极限为1 p/µL。我们的数据将使Rational 设计实施研究，以测试下一代区域发展技术作为非洲区域发展的工具的使用情况。这些 研究最终将为更广泛地将RACD作为公共卫生部署提供证据基础 在非洲国家继续推动消灭疟疾的同时，这一活动也取得了进展。

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.