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

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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.