Direct estimation of sensitivity of Plasmodium falciparum rapid diagnostic test for active case detection in a high-transmission community setting

Abstract

Community-based active case detection of malaria parasites with conventional rapid diagnostic tests (cRDTs)is a strategy used most commonly in low-transmission settings. We estimated the sensitivity of this approach in a high-transmission setting in Western Kenya. We tested 3,547 members of 912 households identified in 2013–2014 by index children with (case) and without (control) cRDT-positive malaria. All were tested for Plasmodium falciparum withbothacRDTtargeting histidine-rich protein 2 and with an ultrasensitive real-time polymerase chain reaction (PCR). We computed cRDT sensitivity against PCR as the referent, compared prevalence between participant types, and estimated cRDT detect ability as a function of PCR-estimated parasite density. Parasite prevalence was 22.9% by cRDTs and 61.5% by PCR. Compared with children aged < 5 years or adults aged > 15 years, geometric mean parasite densities (95% CI) were highest in school-age children aged5–15 years(8.4p/uL;6.6–10.6). The overall sensitivity of cRDT was36%; among asymptomatic household members, cRDT sensitivity was 25.5% and lowest in adults aged > 15 years (15.8%).When modeled as a function of parasitedensity, relative to school-age children, the probability of cRDT positivity was reduced in both children aged < 5 years (odds ratio [OR] 0.48; 95% CI: 0.34–0.69) and in adults aged > 15 years (OR: 0.35; 95% CI: 0.27–0.47). An HRP2-detecting cRDT had poor sensitivity for active P.falciparum case detection in asymptomatic community members,and sensitivity was lowest in highly prevalent low-density infections and in adults. Future studies can model the incremental effects of high-sensitivity rapid diagnostic tests and the impacts on transmission