Citation
Murungi, Moses; Fulton, Travis; Reyes, Raquel; Matte, Michael; Ntaro, Moses; Mulogo, Edgar M.; Nyehangane, Dan; Juliano, Jonathan J.; Siedner, Mark J.; & Boum, Yap, 2nd, et al. (2017). Improving the Specificity of Plasmodium Falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm. Journal of Clinical Microbiology, 55(5), 1540-1549. PMCID: PMC5405272Abstract
Poor specificity may negatively impact rapid diagnostic test (RDT)-based diagnostic strategies for malaria. We performed real-time PCR on a subset of subjects who had undergone diagnostic testing with a multiple-antigen (histidine-rich protein 2 and pan-lactate dehydrogenase pLDH [HRP2/pLDH]) RDT and microscopy. We determined the sensitivity and specificity of the RDT in comparison to results of PCR for the detection of Plasmodium falciparum malaria. We developed and evaluated a two-step algorithm utilizing the multiple-antigen RDT to screen patients, followed by confirmatory microscopy for those individuals with HRP2-positive (HRP2(+))/pLDH-negative (pLDH(-)) results. In total, dried blood spots (DBS) were collected from 276 individuals. There were 124 (44.9%) individuals with an HRP2(+)/pLDH(+) result, 94 (34.1%) with an HRP2(+)/pLDH(-) result, and 58 (21%) with a negative RDT result. The sensitivity and specificity of the RDT compared to results with real-time PCR were 99.4% (95% confidence interval [CI], 95.9 to 100.0%) and 46.7% (95% CI, 37.7 to 55.9%), respectively. Of the 94 HRP2(+)/pLDH(-) results, only 32 (34.0%) and 35 (37.2%) were positive by microscopy and PCR, respectively. The sensitivity and specificity of the two-step algorithm compared to results with real-time PCR were 95.5% (95% CI, 90.5 to 98.0%) and 91.0% (95% CI, 84.1 to 95.2), respectively. HRP2 antigen bands demonstrated poor specificity for the diagnosis of malaria compared to that of real-time PCR in a high-transmission setting. The most likely explanation for this finding is the persistence of HRP2 antigenemia following treatment of an acute infection. The two-step diagnostic algorithm utilizing microscopy as a confirmatory test for indeterminate HRP2(+)/pLDH(-) results showed significantly improved specificity with little loss of sensitivity in a high-transmission setting.URL
http://dx.doi.org/10.1128/jcm.00130-17Reference Type
Journal ArticleYear Published
2017Journal Title
Journal of Clinical MicrobiologyAuthor(s)
Murungi, MosesFulton, Travis
Reyes, Raquel
Matte, Michael
Ntaro, Moses
Mulogo, Edgar M.
Nyehangane, Dan
Juliano, Jonathan J.
Siedner, Mark J.
Boum, Yap, 2nd
Boyce, Ross M.