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Pfhrp2-deleted Plasmodium falciparum parasites in the Democratic Republic of the Congo: a national cross-sectional survey

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Title: Pfhrp2-deleted Plasmodium falciparum parasites in the Democratic Republic of the Congo: a national cross-sectional survey
Authors: Parr, JB
Verity, R
Doctor, SM
Janko, M
Carey-Ewend, K
Turman, BJ
Keeler, C
Slater, HC
Whitesell, AN
Mwandagalirwa, K
Ghani, AC
Likwela, JL
Tshefu, AK
Emch, M
Juliano, JJ
Meshnick, SR
Item Type: Journal Article
Abstract: Background. Rapid diagnostic tests (RDTs) account for more than two-thirds of malaria diagnoses in Africa. Deletions of the Plasmodium falciparum hrp2 (pfhrp2) gene cause false-negative RDT results and have never been investigated on a national level. Spread of pfhrp2-deleted P. falciparum mutants, resistant to detection by HRP2-based RDTs, would represent a serious threat to malaria elimination efforts. Methods. Using a nationally representative cross-sectional study of 7,137 children under five years of age from the Democratic Republic of Congo (DRC), we tested 783 subjects with RDT-/PCR+ results using PCR assays to detect and confirm deletions of the pfhrp2 gene. Spatial and population genetic analyses were employed to examine the distribution and evolution of these parasites. Results. We identified 149 pfhrp2-deleted parasites, representing 6.4% of all P. falciparum infections country-wide (95% confidence interval 5.1–8.0%). Bayesian spatial analyses identified statistically significant clustering of pfhrp2 deletions near Kinshasa and Kivu. Population genetic analysis revealed significant genetic differentiation between wild-type and pfhrp2-deleted parasite populations (GST = .046, p ≤ .00001). Conclusions. Pfhrp2-deleted P. falciparum is a common cause of RDT-/PCR+ malaria among asymptomatic children in the DRC and appears to be clustered within select communities. Surveillance for these deletions is needed, and alternatives to HRP2-specific RDTs may be necessary.
Issue Date: 14-Nov-2016
Date of Acceptance: 2-Nov-2016
URI: http://hdl.handle.net/10044/1/50661
DOI: https://dx.doi.org/10.1093/infdis/jiw538
ISSN: 0022-1899
Publisher: Oxford University Press (OUP)
Start Page: 36
End Page: 44
Journal / Book Title: Journal of Infectious Diseases
Volume: 216
Issue: 1
Copyright Statement: © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
Sponsor/Funder: Bill & Melinda Gates Foundation
Medical Research Council (MRC)
Funder's Grant Number: OPP1068440
MR/N01507X/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
Microbiology
rapid diagnostic tests
false-negative
diagnostic resistance
histidine-rich protein 2
pfhrp3
hrp2
hrp3
RDT
deletion
malaria
HISTIDINE-RICH PROTEIN-2
RAPID DIAGNOSTIC-TESTS
POPULATION-STRUCTURE
GENETIC DIVERSITY
MALARIA
DELETION
PFHRP2
PERU
PCR
SURVEILLANCE
Antigens, Protozoan
Bayes Theorem
Child, Preschool
Cross-Sectional Studies
DNA, Protozoan
Democratic Republic of the Congo
Diagnostic Tests, Routine
Gene Deletion
Humans
Malaria, Falciparum
Microsatellite Repeats
Plasmodium falciparum
Prevalence
Protozoan Proteins
11 Medical And Health Sciences
06 Biological Sciences
Publication Status: Published
Appears in Collections:Centre for Environmental Policy
Faculty of Natural Sciences
Epidemiology, Public Health and Primary Care



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