Identification of the PfK13 mutations R561H and P441L in Democratic Republic of Congo (DRC).

Democratic Republic of Congo PfK13 antimalarial drugs artemisinin drug resistance

Journal

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
ISSN: 1878-3511
Titre abrégé: Int J Infect Dis
Pays: Canada
ID NLM: 9610933

Informations de publication

Date de publication:
26 Nov 2023
Historique:
received: 19 09 2023
revised: 10 11 2023
accepted: 20 11 2023
medline: 29 11 2023
pubmed: 29 11 2023
entrez: 28 11 2023
Statut: aheadofprint

Résumé

Partial artemisinin resistance, mediated by P. falciparum K13 (PfK13) mutations, has been confirmed in certain areas of East Africa which are historically associated with high-level antimalarial resistance. DRC borders these areas in the East. To determine the prevalence of resistance markers in six national malaria control programme (NMCP) surveillance sites; Boende, Kabondo, Kapolowe, Kimpese, Mikalayi and Rutshuru. The SNPs in P. falciparum genes PfK13, Pfdhfr, Pfdhps, Pfmdr1 and Pfcrt were assessed using targeted NGS of isolates collected at enrolment in therapeutic efficacy studies. 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 SP chemoprevention efficacy, ranged from 0.8% in Mikalayi (central DRC) to 42.2% in Rutshuru (East DRC). R561H and P441L observed in eastern DRC are a concern, as they are associated with delayed ACT-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.

Sections du résumé

BACKGROUND BACKGROUND
Partial artemisinin resistance, mediated by P. falciparum K13 (PfK13) mutations, has been confirmed in certain areas of East Africa which are historically associated with high-level antimalarial resistance. DRC borders these areas in the East.
OBJECTIVES OBJECTIVE
To determine the prevalence of resistance markers in six national malaria control programme (NMCP) surveillance sites; Boende, Kabondo, Kapolowe, Kimpese, Mikalayi and Rutshuru.
METHODS METHODS
The SNPs in P. falciparum genes PfK13, Pfdhfr, Pfdhps, Pfmdr1 and Pfcrt were assessed using targeted NGS of isolates collected at enrolment in therapeutic efficacy studies.
RESULTS 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 SP chemoprevention efficacy, ranged from 0.8% in Mikalayi (central DRC) to 42.2% in Rutshuru (East DRC).
CONCLUSIONS CONCLUSIONS
R561H and P441L observed in eastern DRC are a concern, as they are associated with delayed ACT-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.

Identifiants

pubmed: 38016502
pii: S1201-9712(23)00787-7
doi: 10.1016/j.ijid.2023.11.026
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Gauthier Mesia Kahunu (G)

Department of Pharmacology and Therapeutics, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.

Sarah Wellmann Thomsen (S)

Center for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.

Louise Wellmann Thomsen (L)

Center for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.

Hypolite Muhindo Mavoko (H)

Department of Tropical Medicine, University of Kinshasa, Democratic Republic of Congo.

Patrick Mitashi Mulopo (P)

Department of Tropical Medicine, University of Kinshasa, Democratic Republic of Congo.

Emma Filtenborg Hocke (E)

Center for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.

Papy Mandoko Nkoli (P)

National Institute of Biomedical Research, Kinshasa, Democratic Republic of the Congo.

Vito Baraka (V)

National Institute for Medical Research, Tanga Centre, Tanga, Tanzania.

Daniel T R Minja (DTR)

National Institute for Medical Research, Tanga Centre, Tanga, Tanzania.

Andria Mousa (A)

Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.

Cally Roper (C)

Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.

Destin Mbongi Moke (D)

Centre Hospitalier Monkole, Kinshasa, Democratic Republic of the Congo.

Dieudonné Mumba Ngoyi (D)

Department of Tropical Medicine, University of Kinshasa, Democratic Republic of Congo; National Institute of Biomedical Research, Kinshasa, Democratic Republic of the Congo.

Eric Mukomena Sompwe (E)

Faculty of Medicine, University of Lubumbashi, Democratic Republic of the Congo; National Malaria Control Program, Ministry of Health, Kinshasa, Democratic Republic of the Congo.

Jean Jacques Muyembe Tanfum (JJ)

Department of Tropical Medicine, University of Kinshasa, Democratic Republic of Congo; National Institute of Biomedical Research, Kinshasa, Democratic Republic of the Congo.

Helle Hansson (H)

Center for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.

Michael Alifrangis (M)

Center for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: Micali@sund.ku.dk.

Classifications MeSH