期刊
MALARIA JOURNAL
卷 19, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12936-020-03389-0
关键词
Malaria; Ultra-sensitive RDT; Antigenemia; HRP2; pLDH
资金
- Bill & Melinda Gates Foundation [OPP1053616]
- Siemens Foundation-PATH Fellowship [OPP-00006234]
- National Institutes of Health Intramural Research Program
- Bill and Melinda Gates Foundation [OPP1053616] Funding Source: Bill and Melinda Gates Foundation
BackgroundThe recent expansion of tools designed to accurately quantify malaria parasite-produced antigens has enabled us to evaluate the performance of rapid diagnostic tests (RDTs) as a function of the antigens they detect-typically histidine rich protein 2 (HRP2) or lactate dehydrogenase (LDH).MethodsFor this analysis, whole blood specimens from a longitudinal study in Bancoumana, Mali were used to evaluate the performance of the ultra-sensitive HRP2-based Alere (TM) Malaria Ag P.f RDT (uRDT). The samples were collected as part of a transmission-blocking vaccine trial in a high transmission region for Plasmodium falciparum malaria. Furthermore, antigen dynamics after successful anti-malarial drug treatment were evaluated in these samples using the Q-Plex Human Malaria Array (4-Plex) to quantify antigen concentrations.ResultsThe uRDT had a 50% probability of a positive result at 207 pg/mL HRP2 [95% credible interval (CrI) 160-268]. Individuals with symptomatic infection remained positive by uRDT for a median of 33 days [95% confidence interval (CI) 28-47] post anti-malarial drug treatment. Biphasic exponential decay models accurately captured the population level post-treatment dynamics of both HRP2 and Plasmodium LDH (pLDH), with the latter decaying more rapidly. Motivated by these differences in rates of decay, a novel algorithm that used HRP2:pLDH ratios to predict if an individual had active versus recently cleared P. falciparum infection was developed. The algorithm had 77.5% accuracy in correctly classifying antigen-positive individuals as those with and without active infection.ConclusionsThese results characterize the performance of the ultra-sensitive RDT and demonstrate the potential for emerging antigen-quantifying technologies in the field of malaria diagnostics to be helpful tools in distinguishing between active versus recently cleared malaria infections.
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