False-Positive Results of a Plasmodium Falciparum Histidine-Rich Protein 2–detecting Malaria Rapid Diagnostic Test Due to High Sensitivity in a Community With Fluctuating Low Parasite Density

The persistence of parasite histidine-rich protein 2 (HRP2) in the circulation after parasite clearance has been considered a drawback for rapid diagnostic tests (RDTs) targeting HRP2 and a major cause of false-positive results. This paper reports results of a study into whether a proportion of RDT HRP2 false-positive cases carried parasites using polymerase chain reaction analysis as the gold standard rather than microscopy. The high rate of RDT false-positive parasitemia results in comparison with microscopy was shown to predominantly represent cases that had a parasite density below the threshold for detection by microscopy. Despite the generally low disease-endemic prevalence of malaria in the area, there was a high prevalence of chronic infections with low, fluctuating, parasite densities that were better detected by RDT. Our results suggest that in areas known to have low-density parasitemias, RDTs targeting HRP2 may increase diagnostic sensitivity in comparison with microscopy. While microscopy remains the standard for comparison of malaria diagnostic accuracy, the limitations of microscopy, and the possibility that RDTs may have superior accuracy in some circumstances, should be taken into account when interpreting results of diagnostic trials.