Rapid Diagnostic Tests for Malaria at Sites of Varying Transmission Intensity in Uganda

Abstract

Based on the high PPV and NPV, HRP2-based RDTs are likely to be the best diagnostic choice for areas with medium-to-high malaria transmission rates in Africa.

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.…”

Accuracy of Two Malaria Rapid Diagnostic Tests (RDTS) for Initial Diagnosis and Treatment Monitoring in a High Transmission Setting in Uganda

“…10,11 Another factor that contributes to false-positive HRP2 results is sub-patent parasitemia, i.e., presence of parasite density levels below the detection threshold for expert microscopy of 10-50 parasites/ μL. 8,19 A study done at sites of varying malaria transmission intensity in Uganda found up to 45% of samples that were negative for malaria by microscopy to be positive by PCR at the site with the highest transmission rate. 8 The high sensitivity and NPV of the HRP2-based RDT implies that true malaria cases would rarely be missed making it an appropriate test for initial diagnosis of malaria.…”

“…8,19 A study done at sites of varying malaria transmission intensity in Uganda found up to 45% of samples that were negative for malaria by microscopy to be positive by PCR at the site with the highest transmission rate. 8 The high sensitivity and NPV of the HRP2-based RDT implies that true malaria cases would rarely be missed making it an appropriate test for initial diagnosis of malaria. However, the high number of false-positive HRP2 results and low specificity could lead to over-diagnosis of malaria in patients presenting with alternative causes of fever.…”

“…The HRP2-based RDTs have been recommended for Uganda by the Ministry of Health on the basis of accuracy and ease of use. 7,8 Currently, HRP2 assays appear to be somewhat more sensitive than pLDH-based tests. 8,9 However, HRP2 antigen remains in the bloodstream for several weeks after parasite clearance, thus contributing to false-positive results and limiting specificity.…”

“…7,8 Currently, HRP2 assays appear to be somewhat more sensitive than pLDH-based tests. 8,9 However, HRP2 antigen remains in the bloodstream for several weeks after parasite clearance, thus contributing to false-positive results and limiting specificity. [10][11][12][13][14] The pLDH-based assays may be more useful for monitoring patients' recovery after treatment and avoiding unnecessary retreatment of malaria because they turn negative soon after parasite clearance from the blood.…”