Molecular tools for diagnosis of visceral leishmaniasis: systematic review and meta-analysis of diagnostic test accuracy.
Molecular methods have been proposed as highly sensitive tools for the detection of Leishmania parasites in visceral leishmaniasis (VL) patients. Here, we evaluate the diagnostic accuracy of these tools in a meta-analysis of the published literature. The selection criteria were original studies that evaluate the sensitivities and specificities of molecular tests for diagnosis of VL, adequate classification of study participants, and the absolute numbers of true positives and negatives derivable from the data presented. Forty studies met the selection criteria, including PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA), and loop-mediated isothermal amplification (LAMP). The sensitivities of the individual studies ranged from 29 to 100%, and the specificities ranged from 25 to 100%. The pooled sensitivity of PCR in whole blood was 93.1% (95% confidence interval [CI], 90.0 to 95.2), and the specificity was 95.6% (95% CI, 87.0 to 98.6). The specificity was significantly lower in consecutive studies, at 63.3% (95% CI, 53.9 to 71.8), due either to true-positive patients not being identified by parasitological methods or to the number of asymptomatic carriers in areas of endemicity. PCR for patients with HIV-VL coinfection showed high diagnostic accuracy in buffy coat and bone marrow, ranging from 93.1 to 96.9%. Molecular tools are highly sensitive assays for Leishmania detection and may contribute as an additional test in the algorithm, together with a clear clinical case definition. We observed wide variety in reference standards and study designs and now recommend consecutively designed studies.
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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de Ruiter
Koninklijk Instituut voor de Tropen (KIT), Biomedical Research, Amsterdam, The Netherlands.
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van der Veer
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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Leeflang
Biomedical Sciences Department, Institute of Tropical Medicine, Antwerp, Belgium.
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Deborggraeve
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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Lucas
Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom Warwick Medical School, Warwick University, Coventry, United Kingdom Emily.adams@lstmed.ac.uk.
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Adams
D058621:Blood Buffy Coat / Q000469:parasitology; D001853:Bone Marrow / Q000469:parasitology; D006801:Humans; D007891:Leishmania / Q000302:isolation & purification; D007898:Leishmaniasis, Visceral / Q000175:diagnosis*; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D012680:Sensitivity and Specificity