Comparative performance of aldolase and lactate dehydrogenase rapid diagnostic tests in Plasmodium vivax detection.

Emmanuel E Dzakah,Keren Kang,Jufang Wang,Jihua Wang,Chao Ni,Shixing Tang

doi:10.1186/1475-2875-13-272

Emmanuel E Dzakah, Keren Kang + Show 4 more

Open Access

https://doi.org/10.1186/1475-2875-13-272

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Abstract

BackgroundMisdiagnosis of malaria by commercial rapid diagnostic tests (RDTs) is a major cause of concern in the diagnosis of malaria. This retrospective study was aimed at assessing the relative performance of four RDTs with emphasis on the detection of two Plasmodium vivax antigens: aldolase and lactate dehydrogenase (LDH).MethodsThree commercially available Plasmodium LDH or aldolase antigen detection kits (One Step Malaria P.f/P.v, ParaHit Total ver. 1.0, SD Bioline Malaria) and an anti-P. vivax aldolase-specific monoclonal antibody (mAb) pair 1C3-12 F10 were evaluated with P. vivax positive as well as non-P. vivax samples and healthy samples using blood smear examination as standard. Each test was read according to the manufacturer’s instructions.ResultsMAb 1C3-12 F10 pair targeting P. vivax-specific aldolase exhibited very good specificity and sensitivity of 100 and 97.4%, respectively. Positive predictive value (PPV) and negative predictive value (NPV) of 100 and 99.5%, respectively, were also observed. The anti-P. vivax LDH in the One-Step Malaria P.f/P.v test showed sensitivity, specificity, PPV and NPV of 93.5, 98.0, 88.9 and 98.8%, respectively. ParaHit Total ver. 1.0 targeting the pan-aldolase antigen showed sensitivity, specificity of 97.4 and 99.6%, respectively. PPV and NPV were both 99.5%. SD Bioline had sensitivity, specificity, PPV and NPV of 93.5, 100, 100 and 98.8%, respectively. The overall sensitivity and specificity of all four RDTs were acceptable, especially for the aldolase detection tests. Five (6.5%) of the P. vivax-positive samples (n = 77) that were confirmed by microscopic examination as well as the two aldolase detection RDTs (mAb 1C3-12 F10 and ParaHit Total ver.1.0) were undetected by the two LDH detection RDTs (One Step Malaria P.f/P.v and SD Bioline). Similarly, two positive samples (2.6%) that were positively confirmed by the LDH detection RDTs were also undetected by the aldolase detection test kits.ConclusionAldolase and LDH antigens perform differently in different P. vivax samples; hence there is a high risk of misdiagnosis when monoclonal antibodies are used against only one particular antigen in the test. A combination of both aldolase and LDH in RDTs for the rapid diagnosis of P. vivax will enhance the sensitivity of the assay and reduce misdiagnosis.

Highlights

Misdiagnosis of malaria by commercial rapid diagnostic tests (RDTs) is a major cause of concern in the diagnosis of malaria
The various RDTs were retrospectively studied for their ability to detect either the aldolase or lactate dehydrogenase (LDH) antigen in clinical samples
All five P. vivax-positive samples which showed false negative results in the two LDH-detecting categories were detected with very strong bands in the aldolasedetecting category

Summary

Introduction

Misdiagnosis of malaria by commercial rapid diagnostic tests (RDTs) is a major cause of concern in the diagnosis of malaria. This retrospective study was aimed at assessing the relative performance of four RDTs with emphasis on the detection of two Plasmodium vivax antigens: aldolase and lactate dehydrogenase (LDH). The standard method of malaria diagnosis is by the routine microscopic examination of Giemsa-stained blood smears [5]. Rapid diagnostic tests (RDTs) that detect malaria parasite proteins by immunochromatography have been used as complementary detection method for malaria diagnosis [8,9]. The PfHRP2based test is a reliable complimentary test to routine microscopy for the diagnosis of P. falciparum malaria [12], the relative sensitivity and specificity of RDTs to non-P. falciparum species is low [11,12,13]

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