Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo

Abstract The majority of Plasmodium falciparum malaria diagnoses in Africa are made using rapid diagnostic tests (RDTs) that detect histidine-rich protein 2. Increasing reports of false-negative RDT results due to parasites with deletions of the pfhrp2 and/or pfhrp3 genes (pfhrp2/3) raise concern ab...

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Autores principales:	Jonathan B. Parr, Eddy Kieto, Fernandine Phanzu, Paul Mansiangi, Kashamuka Mwandagalirwa, Nono Mvuama, Ange Landela, Joseph Atibu, Solange Umesumbu Efundu, Jean W. Olenga, Kyaw Lay Thwai, Camille E. Morgan, Madeline Denton, Alison Poffley, Jonathan J. Juliano, Pomie Mungala, Joris L. Likwela, Eric M. Sompwe, Eric Rogier, Antoinette K. Tshefu, Adrien N’Siala, Albert Kalonji
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/69b1915c79934da1b83f83083b3f0a84
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spelling	oai:doaj.org-article:69b1915c79934da1b83f83083b3f0a842021-12-02T17:04:35ZAnalysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo10.1038/s41598-021-85913-z2045-2322https://doaj.org/article/69b1915c79934da1b83f83083b3f0a842021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85913-zhttps://doaj.org/toc/2045-2322Abstract The majority of Plasmodium falciparum malaria diagnoses in Africa are made using rapid diagnostic tests (RDTs) that detect histidine-rich protein 2. Increasing reports of false-negative RDT results due to parasites with deletions of the pfhrp2 and/or pfhrp3 genes (pfhrp2/3) raise concern about existing malaria diagnostic strategies. We previously identified pfhrp2-negative parasites among asymptomatic children in the Democratic Republic of the Congo (DRC), but their impact on diagnosis of symptomatic malaria is unknown. We performed a cross-sectional study of false-negative RDTs in symptomatic subjects in 2017. Parasites were characterized by microscopy; RDT; pfhrp2/3 genotyping and species-specific PCR assays; a bead-based immunoassay for Plasmodium antigens; and/or whole-genome sequencing. Among 3627 symptomatic subjects, 427 (11.8%) had RDT-/microscopy + results. Parasites from eight (0.2%) samples were initially classified as putative pfhrp2/3 deletions by PCR, but antigen testing and whole-genome sequencing confirmed the presence of intact genes. 56.8% of subjects had PCR-confirmed malaria. Non-falciparum co-infection with P. falciparum was common (13.2%). Agreement between PCR and HRP2-based RDTs was satisfactory (Cohen’s kappa = 0.66) and superior to microscopy (0.33). Symptomatic malaria due to pfhrp2/3-deleted P. falciparum was not observed. Ongoing HRP2-based RDT use is appropriate for the detection of falciparum malaria in the DRC.Jonathan B. ParrEddy KietoFernandine PhanzuPaul MansiangiKashamuka MwandagalirwaNono MvuamaAnge LandelaJoseph AtibuSolange Umesumbu EfunduJean W. OlengaKyaw Lay ThwaiCamille E. MorganMadeline DentonAlison PoffleyJonathan J. JulianoPomie MungalaJoris L. LikwelaEric M. SompweEric RogierAntoinette K. TshefuAdrien N’SialaAlbert KalonjiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jonathan B. Parr Eddy Kieto Fernandine Phanzu Paul Mansiangi Kashamuka Mwandagalirwa Nono Mvuama Ange Landela Joseph Atibu Solange Umesumbu Efundu Jean W. Olenga Kyaw Lay Thwai Camille E. Morgan Madeline Denton Alison Poffley Jonathan J. Juliano Pomie Mungala Joris L. Likwela Eric M. Sompwe Eric Rogier Antoinette K. Tshefu Adrien N’Siala Albert Kalonji Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo
description	Abstract The majority of Plasmodium falciparum malaria diagnoses in Africa are made using rapid diagnostic tests (RDTs) that detect histidine-rich protein 2. Increasing reports of false-negative RDT results due to parasites with deletions of the pfhrp2 and/or pfhrp3 genes (pfhrp2/3) raise concern about existing malaria diagnostic strategies. We previously identified pfhrp2-negative parasites among asymptomatic children in the Democratic Republic of the Congo (DRC), but their impact on diagnosis of symptomatic malaria is unknown. We performed a cross-sectional study of false-negative RDTs in symptomatic subjects in 2017. Parasites were characterized by microscopy; RDT; pfhrp2/3 genotyping and species-specific PCR assays; a bead-based immunoassay for Plasmodium antigens; and/or whole-genome sequencing. Among 3627 symptomatic subjects, 427 (11.8%) had RDT-/microscopy + results. Parasites from eight (0.2%) samples were initially classified as putative pfhrp2/3 deletions by PCR, but antigen testing and whole-genome sequencing confirmed the presence of intact genes. 56.8% of subjects had PCR-confirmed malaria. Non-falciparum co-infection with P. falciparum was common (13.2%). Agreement between PCR and HRP2-based RDTs was satisfactory (Cohen’s kappa = 0.66) and superior to microscopy (0.33). Symptomatic malaria due to pfhrp2/3-deleted P. falciparum was not observed. Ongoing HRP2-based RDT use is appropriate for the detection of falciparum malaria in the DRC.
format	article
author	Jonathan B. Parr Eddy Kieto Fernandine Phanzu Paul Mansiangi Kashamuka Mwandagalirwa Nono Mvuama Ange Landela Joseph Atibu Solange Umesumbu Efundu Jean W. Olenga Kyaw Lay Thwai Camille E. Morgan Madeline Denton Alison Poffley Jonathan J. Juliano Pomie Mungala Joris L. Likwela Eric M. Sompwe Eric Rogier Antoinette K. Tshefu Adrien N’Siala Albert Kalonji
author_facet	Jonathan B. Parr Eddy Kieto Fernandine Phanzu Paul Mansiangi Kashamuka Mwandagalirwa Nono Mvuama Ange Landela Joseph Atibu Solange Umesumbu Efundu Jean W. Olenga Kyaw Lay Thwai Camille E. Morgan Madeline Denton Alison Poffley Jonathan J. Juliano Pomie Mungala Joris L. Likwela Eric M. Sompwe Eric Rogier Antoinette K. Tshefu Adrien N’Siala Albert Kalonji
author_sort	Jonathan B. Parr
title	Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo
title_short	Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo
title_full	Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo
title_fullStr	Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo
title_full_unstemmed	Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo
title_sort	analysis of false-negative rapid diagnostic tests for symptomatic malaria in the democratic republic of the congo
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/69b1915c79934da1b83f83083b3f0a84
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Analysis of false-negative rapid diagnostic tests for symptomatic malaria in the Democratic Republic of the Congo

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