Plasmodium falciparum Parasitemia and Band Sensitivity of the SD Bioline Malaria Ag P.f/Pan Rapid Diagnostic Test in Madagascar

Abstract

Current malaria rapid diagnostic tests (RDTs) contain antibodies against <i>Plasmodium falciparum</i>-specific histidine-rich protein 2 (PfHRP2), <i>Plasmodium</i> lactate dehydrogenase (pLDH), and aldolase in various combinations. Low or high parasite densities/target antigen concentrations may influence the accuracy and sensitivity of PfHRP2-detecting RDTs. We analyzed the SD Bioline Malaria Ag P.f/Pan RDT performance in relation to <i>P. falciparum</i> parasitemia in Madagascar, where clinical <i>Plasmodium vivax</i> malaria exists alongside <i>P. falciparum</i>. Nine hundred sixty-three samples from patients seeking care for suspected malaria infection were analyzed by RDT, microscopy, and <i>Plasmodium</i> species-specific, ligase detection reaction-fluorescent microsphere assay (LDR-FMA). <i>Plasmodium</i> infection positivity by these diagnostics was 47.9%, 46.9%, and 58%, respectively. <i>Plasmodium falciparum</i>-only infections were predominant (microscopy, 45.7%; LDR-FMA, 52.3%). In all, 16.3% of <i>P. falciparum</i>, 70% of <i>P. vivax</i>, and all of <i>Plasmodium malariae</i>, <i>Plasmodium ovale</i>, and mixed-species infections were submicroscopic. In 423 <i>P. falciparum</i> mono-infections, confirmed by microscopy and LDR-FMA, the parasitemia in those who were positive for both the PfHRP2 and pan-pLDH test bands was significantly higher than that in those who were positive only for the PfHRP2 band (<i>P</i> < 0.0001). <i>Plasmodium falciparum</i> parasitemia in those that were detected as <i>P. falciparum</i>-only infections by microscopy but <i>P. falciparum</i> mixed infections by LDR-FMA also showed similar outcome by the RDT band positivity. In addition, we used varying parasitemia (3-0.0001%) of the laboratory-maintained 3D7 strain to validate this observation. A positive pLDH band in high <i>P. falciparum</i>-parasitemic individuals may complicate diagnosis and treatment, particularly when the microscopy is inconclusive for <i>P. vivax</i>, and the two infections require different treatments.