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<jats:title>ABSTRACT</jats:title> <jats:p>Malaria rapid diagnostic tests (RDTs) primarily detect <jats:named-content content-type="genus-species">Plasmodium falciparum</jats:named-content> antigen histidine-rich protein 2 (HRP2) and the malaria-conserved antigen lactate dehydrogenase (LDH) for <jats:named-content content-type="genus-species">P. vivax</jats:named-content> and other malaria species. The performance of RDTs and their utility is dependent on circulating antigen concentration distributions in infected individuals in a population in which malaria is endemic and on the limit of detection of the RDT for the antigens. A multiplexed immunoassay for the quantification of HRP2, <jats:named-content content-type="genus-species">P. vivax</jats:named-content> LDH, and all-malaria LDH (pan LDH) was developed to accurately measure circulating antigen concentration and antigen distribution in a population with endemic malaria. The assay also measures C-reactive protein (CRP) levels as an indicator of inflammation. Validation was conducted with clinical specimens from 397 asymptomatic donors from Myanmar and Uganda, confirmed by PCR for infection, and from participants in induced blood-stage malaria challenge studies. The assay lower limits of detection for HRP2, pan LDH, <jats:named-content content-type="genus-species">P. vivax</jats:named-content> LDH, and CRP were 0.2 pg/ml, 9.3 pg/ml, 1.5 pg/ml, and 26.6 ng/ml, respectively. At thresholds for HRP2, pan LDH, and <jats:named-content content-type="genus-species">P. vivax</jats:named-content> LDH of 2.3 pg/ml, 47.8 pg/ml, and 75.1 pg/ml, respectively, and a specificity ≥98.5%, the sensitivities for ultrasensitive PCR-confirmed infections were 93.4%, 84.9%, and 48.9%, respectively. <jats:named-content content-type="genus-species">Plasmodium</jats:named-content> LDH (pLDH) concentration, in contrast to that of HRP2, correlated closely with parasite density. CRP levels were moderately higher in <jats:named-content content-type="genus-species">P. falciparum</jats:named-content> infections with confirmed antigenemia versus those in clinical specimens with no antigen. The 4-plex array is a sensitive tool for quantifying diagnostic antigens in malaria infections and supporting the evaluation of new ultrasensitive RDTs.</jats:p>

Original publication

DOI

10.1128/jcm.00948-18

Type

Journal article

Journal

Journal of Clinical Microbiology

Publisher

American Society for Microbiology

Publication Date

07/11/2018

Volume

57