Improving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm

Hdl Handle:
http://hdl.handle.net/10144/619054
Title:
Improving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm
Authors:
Murungi, M; Fulton, T; Reyes, R; Matte, M; Ntaro, M; Mulogo, E; Nyehangane, D; Juliano, J; Siedner, M; Boum, Y; Boyce, R
Journal:
Journal of Clinical Microbiology
Abstract:
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.
Publisher:
American Society for Microbiology
Issue Date:
May-2017
URI:
http://hdl.handle.net/10144/619054
DOI:
10.1128/JCM.00130-17
PubMed ID:
28275077
Submitted date:
2017-12-13
Language:
en
ISSN:
1098-660X
Appears in Collections:
Malaria

Full metadata record

DC FieldValue Language
dc.contributor.authorMurungi, Men
dc.contributor.authorFulton, Ten
dc.contributor.authorReyes, Ren
dc.contributor.authorMatte, Men
dc.contributor.authorNtaro, Men
dc.contributor.authorMulogo, Een
dc.contributor.authorNyehangane, Den
dc.contributor.authorJuliano, Jen
dc.contributor.authorSiedner, Men
dc.contributor.authorBoum, Yen
dc.contributor.authorBoyce, Ren
dc.date.accessioned2017-12-21T00:00:57Z-
dc.date.available2017-12-21T00:00:57Z-
dc.date.issued2017-05-
dc.date.submitted2017-12-13-
dc.identifier.citationImproving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm. 2017, 55 (5):1540-1549 J. Clin. Microbiol.en
dc.identifier.issn1098-660X-
dc.identifier.pmid28275077-
dc.identifier.doi10.1128/JCM.00130-17-
dc.identifier.urihttp://hdl.handle.net/10144/619054-
dc.description.abstractPoor 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.en
dc.language.isoenen
dc.publisherAmerican Society for Microbiologyen
dc.rightsPublished by the American Society for Microbiology - Archived on this site with kind permission from the American Society for Microbiologyen
dc.subject.meshAdolescenten
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshAlgorithmsen
dc.subject.meshAntigens, Protozoanen
dc.subject.meshAntimalarialsen
dc.subject.meshArtemisininsen
dc.subject.meshChilden
dc.subject.meshDiagnostic Tests, Routineen
dc.subject.meshFemaleen
dc.subject.meshHumansen
dc.subject.meshMalaria, Falciparumen
dc.subject.meshMaleen
dc.subject.meshMicroscopyen
dc.subject.meshPlasmodium falciparumen
dc.subject.meshProspective Studiesen
dc.subject.meshProteinsen
dc.subject.meshProtozoan Proteinsen
dc.subject.meshRNA, Ribosomal, 18Sen
dc.subject.meshReal-Time Polymerase Chain Reactionen
dc.subject.meshSensitivity and Specificityen
dc.subject.meshUgandaen
dc.subject.meshYoung Adulten
dc.titleImproving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithmen
dc.identifier.journalJournal of Clinical Microbiologyen
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