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Monitoring the threatened utility of malaria rapid diagnostic tests by novel high-throughput detection of Plasmodium falciparum hrp2 and hrp3 deletions: A cross-sectional, diagnostic accuracy study.
Monitoring the threatened utility of malaria rapid diagnostic tests by novel high-throughput detection of Plasmodium falciparum hrp2 and hrp3 deletions: A cross-sectional, diagnostic accuracy study.
- Source :
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EBioMedicine [EBioMedicine] 2019 Dec; Vol. 50, pp. 14-22. Date of Electronic Publication: 2019 Nov 21. - Publication Year :
- 2019
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Abstract
- Background: Plasmodium falciparum deficient for hrp2 and hrp3 genes are a threat to malaria management and elimination, since they escape widely used HRP2-based rapid diagnostic tests and treatment. Hrp2/hrp3 deletions are increasingly reported from all malaria endemic regions but are currently only identified by laborious methodologies.<br />Methods: We developed a novel hydrolysis probe-based, quantitative, real-time PCR (4plex qPCR) for detection and discrimination of P. falciparum infection (cytb) and hrp2 and hrp3 gene status, and to control assay validity (btub). A cross-sectional, diagnostic accuracy study was performed in Gabon for assay validation and deletion screening.<br />Findings: In parallel to identification of P. falciparum infection in samples down to 0.05 parasites/µl, the 4plex qPCR enabled specific and valid interrogation of the parasites´s hrp2 and hrp3 genes in one go - even in low parasitemic samples. The assay was precise and robust also when performed in a routine healthcare setting in Gabon. The risk of falsely identifying hrp2 or hrp3 deletion was reduced by 100-fold compared to conventional PCR. Evaluation against microscopy was performed on 200 blood samples collected in Gabon: sensitivity and specificity of 4plex qPCR (cytb) were 100% and 80%, respectively. Stringent testing revealed hrp2 deletion in 2 of 95 P. falciparum positive and validated samples.<br />Interpretation: The novel 4plex qPCR is sensitive, accurate and allows resource-efficient rapid screening. Monitoring and mapping of hrp2/hrp3 deletions is required to identify areas where control strategies may need to be adapted to ensure appropriate patient care and ultimately achieve malaria elimination.<br />Funding: BMBF (03VP00402).<br /> (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Cross-Sectional Studies
Electrophoresis, Capillary
High-Throughput Screening Assays standards
Humans
Malaria, Falciparum parasitology
Real-Time Polymerase Chain Reaction
Reproducibility of Results
Sensitivity and Specificity
Antigens, Protozoan genetics
High-Throughput Screening Assays methods
Malaria, Falciparum diagnosis
Malaria, Falciparum epidemiology
Plasmodium falciparum genetics
Protozoan Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2352-3964
- Volume :
- 50
- Database :
- MEDLINE
- Journal :
- EBioMedicine
- Publication Type :
- Academic Journal
- Accession number :
- 31761619
- Full Text :
- https://doi.org/10.1016/j.ebiom.2019.10.048