Identification of the PfK13 mutations R561H and P441L in the Democratic Republic of Congo
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Identification of the PfK13 mutations R561H and P441L in the Democratic Republic of Congo. / Mesia Kahunu, Gauthier; Wellmann Thomsen, Sarah; Wellmann Thomsen, Louise; Muhindo Mavoko, Hypolite; Mitashi Mulopo, Patrick; Filtenborg Hocke, Emma; Mandoko Nkoli, Papy; Baraka, Vito; Minja, Daniel T.R.; Mousa, Andria; Roper, Cally; Mbongi Moke, Destin; Mumba Ngoyi, Dieudonné; Mukomena Sompwe, Eric; Muyembe Tanfum, Jean Jacques; Hansson, Helle; Alifrangis, Michael.
I: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, Bind 139, 2024, s. 41-49.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Identification of the PfK13 mutations R561H and P441L in the Democratic Republic of Congo
AU - Mesia Kahunu, Gauthier
AU - Wellmann Thomsen, Sarah
AU - Wellmann Thomsen, Louise
AU - Muhindo Mavoko, Hypolite
AU - Mitashi Mulopo, Patrick
AU - Filtenborg Hocke, Emma
AU - Mandoko Nkoli, Papy
AU - Baraka, Vito
AU - Minja, Daniel T.R.
AU - Mousa, Andria
AU - Roper, Cally
AU - Mbongi Moke, Destin
AU - Mumba Ngoyi, Dieudonné
AU - Mukomena Sompwe, Eric
AU - Muyembe Tanfum, Jean Jacques
AU - Hansson, Helle
AU - Alifrangis, Michael
N1 - Publisher Copyright: Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
PY - 2024
Y1 - 2024
N2 - OBJECTIVES: Partial artemisinin resistance, mediated by Plasmodium falciparum K13 (PfK13) mutations, has been confirmed in certain areas of East Africa that are historically associated with high-level antimalarial resistance. The Democratic Republic of Congo (DRC) borders these areas in the East. This study aimed to determine the prevalence of resistance markers in six National Malaria Control Program surveillance sites; Boende, Kabondo, Kapolowe, Kimpese, Mikalayi, and Rutshuru. METHODS: The single nucleotide polymorphisms (SNPs) in P. falciparum genes PfK13, Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt were assessed using targeted next-generation sequencing of isolates collected at enrollment in therapeutic efficacy studies. RESULTS: PfK13 SNPs were detected in two samples: in Kabondo (R561H) and in Rutshuru (P441L), both areas near Uganda and Rwanda. The Pfdhps ISGEGA haplotype, associated with reduced sulfadoxine-pyrimethamine chemoprevention efficacy, ranged from 0.8% in Mikalayi (central DRC) to 42.2% in Rutshuru (East DRC). CONCLUSIONS: R561H and P441L observed in eastern DRC are a concern, as they are associated with delayed artemisinin-based combination therapies-clearance and candidate marker of resistance, respectively. This is consistent with previous observations of shared drug resistance profiles in parasites of that region with bordering areas of Rwanda and Uganda. The likely circulation of parasites has important implications for the ongoing surveillance of partial artemisinin-resistant P. falciparum and for future efforts to mitigate its dispersal.
AB - OBJECTIVES: Partial artemisinin resistance, mediated by Plasmodium falciparum K13 (PfK13) mutations, has been confirmed in certain areas of East Africa that are historically associated with high-level antimalarial resistance. The Democratic Republic of Congo (DRC) borders these areas in the East. This study aimed to determine the prevalence of resistance markers in six National Malaria Control Program surveillance sites; Boende, Kabondo, Kapolowe, Kimpese, Mikalayi, and Rutshuru. METHODS: The single nucleotide polymorphisms (SNPs) in P. falciparum genes PfK13, Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt were assessed using targeted next-generation sequencing of isolates collected at enrollment in therapeutic efficacy studies. RESULTS: PfK13 SNPs were detected in two samples: in Kabondo (R561H) and in Rutshuru (P441L), both areas near Uganda and Rwanda. The Pfdhps ISGEGA haplotype, associated with reduced sulfadoxine-pyrimethamine chemoprevention efficacy, ranged from 0.8% in Mikalayi (central DRC) to 42.2% in Rutshuru (East DRC). CONCLUSIONS: R561H and P441L observed in eastern DRC are a concern, as they are associated with delayed artemisinin-based combination therapies-clearance and candidate marker of resistance, respectively. This is consistent with previous observations of shared drug resistance profiles in parasites of that region with bordering areas of Rwanda and Uganda. The likely circulation of parasites has important implications for the ongoing surveillance of partial artemisinin-resistant P. falciparum and for future efforts to mitigate its dispersal.
KW - Antimalarial drugs
KW - Artemisinin, PfK13
KW - Democratic Republic of Congo
KW - Drug resistance
U2 - 10.1016/j.ijid.2023.11.026
DO - 10.1016/j.ijid.2023.11.026
M3 - Journal article
C2 - 38016502
AN - SCOPUS:85182501181
VL - 139
SP - 41
EP - 49
JO - International Journal of Infectious Diseases
JF - International Journal of Infectious Diseases
SN - 1201-9712
ER -
ID: 380698072