Comparison of two malaria multiplex immunoassays that enable quantification of malaria antigens

Abstract Background Immunoassay platforms that simultaneously detect malaria antigens including histidine-rich protein 2 (HRP2)/HRP3 and Plasmodium lactate dehydrogenase (pLDH), are useful epidemiological tools for rapid diagnostic test evaluation. This study presents the comparative evaluation of t...

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Main Authors: Ihn Kyung Jang, Alfons Jiménez, Andrew Rashid, Rebecca Barney, Allison Golden, Xavier C. Ding, Gonzalo J. Domingo, Alfredo Mayor
Format: Article
Language:English
Published: BMC 2022-06-01
Series:Malaria Journal
Subjects:
Online Access:https://doi.org/10.1186/s12936-022-04203-9
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author Ihn Kyung Jang
Alfons Jiménez
Andrew Rashid
Rebecca Barney
Allison Golden
Xavier C. Ding
Gonzalo J. Domingo
Alfredo Mayor
author_facet Ihn Kyung Jang
Alfons Jiménez
Andrew Rashid
Rebecca Barney
Allison Golden
Xavier C. Ding
Gonzalo J. Domingo
Alfredo Mayor
author_sort Ihn Kyung Jang
collection DOAJ
description Abstract Background Immunoassay platforms that simultaneously detect malaria antigens including histidine-rich protein 2 (HRP2)/HRP3 and Plasmodium lactate dehydrogenase (pLDH), are useful epidemiological tools for rapid diagnostic test evaluation. This study presents the comparative evaluation of two multiplex platforms in identifying Plasmodium falciparum with presence or absence of HRP2/HRP3 expression as being indicative of hrp2/hrp3 deletions and other Plasmodium species. Moreover, correlation between the malaria antigen measurements performed at these platforms is assessed after calibrating with either assay standards or international standards and the cross-reactivity among Plasmodium species is examined. Methods A 77-member panel of specimens composed of the World Health Organization (WHO) international Plasmodium antigen standards, cultured parasites for P. falciparum and Plasmodium knowlesi, and clinical specimens with mono-infections for P. falciparum, Plasmodium vivax, and Plasmodium malariae was generated as both whole blood and dried blood spot (DBS) specimens. Assays for HRP2, P. falciparum–specific pLDH (PfLDH), P. vivax–specific pLDH (PvLDH), and all human Plasmodium species Pan malaria pLDH (PanLDH) on the Human Malaria Array Q-Plex and the xMAP platforms were evaluated with these panels. Results The xMAP showed a higher percent positive agreement for identification of hrp2-deleted P. falciparum and Plasmodium species in whole blood and DBS than the Q-Plex. For whole blood samples, there was a highly positive correlation between the two platforms for PfLDH (Pearson r = 0.9926) and PvLDH (r = 0. 9792), moderate positive correlation for HRP2 (r = 0.7432), and poor correlation for PanLDH (r = 0.6139). In Pearson correlation analysis between the two platforms on the DBS, the same assays were r = 0.9828, r = 0.7679, r = 0.6432, and r = 0.8957, respectively. The xMAP HRP2 assay appeared to cross-react with HRP3, while the Q-Plex did not. The Q-Plex PfLDH assay cross-reacted with P. malariae, while the xMAP did not. For both platforms, P. knowlesi was detected on the PvLDH assay. The WHO international standards allowed normalization across both platforms on their HRP2, PfLDH, and PvLDH assays in whole blood and DBS. Conclusions Q-Plex and xMAP show good agreement for identification of P. falciparum mutants with hrp2/hrp3 deletions, and other Plasmodium species. Quantitative results from both platforms, normalized into international units for HRP2, PfLDH, and PvLDH, showed good agreement and should allow comparison and analysis of results generated by either platform.
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spelling doaj.art-3557b8769d134ec9b494dc9b6e873f472022-12-22T00:18:43ZengBMCMalaria Journal1475-28752022-06-0121111310.1186/s12936-022-04203-9Comparison of two malaria multiplex immunoassays that enable quantification of malaria antigensIhn Kyung Jang0Alfons Jiménez1Andrew Rashid2Rebecca Barney3Allison Golden4Xavier C. Ding5Gonzalo J. Domingo6Alfredo Mayor7Diagnostic Group, PATHISGlobal, Barcelona Institute for Global Health, Hospital Clínic—Universitat de BarcelonaDiagnostic Group, PATHDiagnostic Group, PATHDiagnostic Group, PATHThe Foundation for Innovative New DiagnosticsDiagnostic Group, PATHISGlobal, Barcelona Institute for Global Health, Hospital Clínic—Universitat de BarcelonaAbstract Background Immunoassay platforms that simultaneously detect malaria antigens including histidine-rich protein 2 (HRP2)/HRP3 and Plasmodium lactate dehydrogenase (pLDH), are useful epidemiological tools for rapid diagnostic test evaluation. This study presents the comparative evaluation of two multiplex platforms in identifying Plasmodium falciparum with presence or absence of HRP2/HRP3 expression as being indicative of hrp2/hrp3 deletions and other Plasmodium species. Moreover, correlation between the malaria antigen measurements performed at these platforms is assessed after calibrating with either assay standards or international standards and the cross-reactivity among Plasmodium species is examined. Methods A 77-member panel of specimens composed of the World Health Organization (WHO) international Plasmodium antigen standards, cultured parasites for P. falciparum and Plasmodium knowlesi, and clinical specimens with mono-infections for P. falciparum, Plasmodium vivax, and Plasmodium malariae was generated as both whole blood and dried blood spot (DBS) specimens. Assays for HRP2, P. falciparum–specific pLDH (PfLDH), P. vivax–specific pLDH (PvLDH), and all human Plasmodium species Pan malaria pLDH (PanLDH) on the Human Malaria Array Q-Plex and the xMAP platforms were evaluated with these panels. Results The xMAP showed a higher percent positive agreement for identification of hrp2-deleted P. falciparum and Plasmodium species in whole blood and DBS than the Q-Plex. For whole blood samples, there was a highly positive correlation between the two platforms for PfLDH (Pearson r = 0.9926) and PvLDH (r = 0. 9792), moderate positive correlation for HRP2 (r = 0.7432), and poor correlation for PanLDH (r = 0.6139). In Pearson correlation analysis between the two platforms on the DBS, the same assays were r = 0.9828, r = 0.7679, r = 0.6432, and r = 0.8957, respectively. The xMAP HRP2 assay appeared to cross-react with HRP3, while the Q-Plex did not. The Q-Plex PfLDH assay cross-reacted with P. malariae, while the xMAP did not. For both platforms, P. knowlesi was detected on the PvLDH assay. The WHO international standards allowed normalization across both platforms on their HRP2, PfLDH, and PvLDH assays in whole blood and DBS. Conclusions Q-Plex and xMAP show good agreement for identification of P. falciparum mutants with hrp2/hrp3 deletions, and other Plasmodium species. Quantitative results from both platforms, normalized into international units for HRP2, PfLDH, and PvLDH, showed good agreement and should allow comparison and analysis of results generated by either platform.https://doi.org/10.1186/s12936-022-04203-9MalariaImmunoassayMultiplexHRP2pLDHP. falciparum
spellingShingle Ihn Kyung Jang
Alfons Jiménez
Andrew Rashid
Rebecca Barney
Allison Golden
Xavier C. Ding
Gonzalo J. Domingo
Alfredo Mayor
Comparison of two malaria multiplex immunoassays that enable quantification of malaria antigens
Malaria Journal
Malaria
Immunoassay
Multiplex
HRP2
pLDH
P. falciparum
title Comparison of two malaria multiplex immunoassays that enable quantification of malaria antigens
title_full Comparison of two malaria multiplex immunoassays that enable quantification of malaria antigens
title_fullStr Comparison of two malaria multiplex immunoassays that enable quantification of malaria antigens
title_full_unstemmed Comparison of two malaria multiplex immunoassays that enable quantification of malaria antigens
title_short Comparison of two malaria multiplex immunoassays that enable quantification of malaria antigens
title_sort comparison of two malaria multiplex immunoassays that enable quantification of malaria antigens
topic Malaria
Immunoassay
Multiplex
HRP2
pLDH
P. falciparum
url https://doi.org/10.1186/s12936-022-04203-9
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