COMPARISON OF HRP2- AND pLDH-BASED RAPID DIAGNOSTIC TESTS FOR MALARIA WITH LONGITUDINAL FOLLOW-UP IN KAMPALA, UGANDA

Abstract

Abstract. Presumptive treatment of malaria results in significant overuse of antimalarials. Malaria rapid diagnostic tests (RDTs) may offer a reliable alternative for case management, but the optimal RDT strategy is uncertain. We compared the diagnostic accuracy of histidine-rich protein 2 (HRP2)-and plasmodium lactate dehydrogenase (pLDH)-based RDTs, using expert microscopy as the gold standard, in a longitudinal study of 918 fever episodes over an 8-month period in a cohort of children in Kampala, Uganda. Sensitivity was 92% for HRP2 and 85% for pLDH, with differences primarily due to better detection with HRP2 at low parasite densities. Specificity was 93% for HRP2 and 100% for pLDH, with differences primarily due to rapid clearance of pLDH antigenemia after treatment of a previous malaria episode. RDTs may provide an effective strategy for improving rational delivery of antimalarial therapy; in Kampala, either test could dramatically decrease inappropriate presumptive treatments.

Five Years of Large-Scale dhfr and dhps Mutation Surveillance Following the Phased Implementation of Artesunate Plus Sulfadoxine-Pyrimethamine in Maputo Province, Southern Mozambique

“…This discrepancy could partially be explained by the rapid test detection of the histidine-rich protein 2 malaria antigens in children in whom all parasites had been cleared 2 to 4 weeks previously. 26 Mean asexual parasite prevalence, based on PCR results, decreased from 44.2% in 2004 to 3.8% in 2008 (rate ratio [RR] 0.09; 95% CI: 0.07-0.11; P < 0.0001, Table 1 ). Mixed genotypes were detected in 1030 (51%) samples.…”

False-Negative Rapid Diagnostic Tests for Malaria and Deletion of the Histidine-Rich Repeat Region of the hrp2 Gene

“…These results suggest that the majority of persons with P. falciparum infection are positive using HRP2-based RDTs (454/480 ¼ 95%) and thus, that HRP2-based RDTs are likely to be valuable, especially in regions where skilled microscopists are rare. However, the false-negative HRP2-based RDTs obtained for a minority (5%) of smear-positive specimens indicate that a negative test result with an RDT based on HRP2 (e.g., 3,[20][21][22][23][24][25][26] does not exclude active bloodstream infection with asexual P. falciparum parasites. In addition, the association between false-negative RDTs and a low MOI suggests that this discrepancy may become increasingly important as malaria control becomes more effective.…”

The silent threat: asymptomatic parasitemia and malaria transmission

“…The detection limits of microscopy are typically estimated at 4-20 p/µl in a reference laboratory, but are more realistically 50-100 p/µl under field conditions [43]. A few rapid diagnostic tests (RDTs) have been shown to have greater than 90% sensitivity and specificity for P. falciparum at parasite densities ≥200 p/µl [43][44][45] but may often fail to detect lower density infections. PCR is considered to be the gold standard for detection of parasitemia with a limit of detection of 0.02 p/µl for the most sensitive procedures [46].…”