Detection of Artemisinin Resistance Marker Kelch-13 469Y in Plasmodium falciparum, South Kivu, Democratic Republic of the Congo, 2022

Welmoed van Loon Institute of International Health, Center for Global Health, Charité—Universitätsmedizin Berlin, Berlin, Germany;

Search for other papers by Welmoed van Loon in
Current site
Google Scholar
PubMed
Close
,
Bertin C. Bisimwa Center for Tropical Diseases & Global Health, Université Catholique de Bukavu, Bukavu, Democratic Republic of the Congo;
Institut Supérieur des Techniques Médicales de Bukavu, Bukavu, Democratic Republic of the Congo;

Search for other papers by Bertin C. Bisimwa in
Current site
Google Scholar
PubMed
Close
,
Valéry Byela Institut Supérieur des Techniques Médicales de Bukavu, Bukavu, Democratic Republic of the Congo;

Search for other papers by Valéry Byela in
Current site
Google Scholar
PubMed
Close
,
Rebecca Kirby University of California, San Diego School of Medicine, San Diego, California;

Search for other papers by Rebecca Kirby in
Current site
Google Scholar
PubMed
Close
,
Patrick M. Bugeme Center for Tropical Diseases & Global Health, Université Catholique de Bukavu, Bukavu, Democratic Republic of the Congo;
Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland;

Search for other papers by Patrick M. Bugeme in
Current site
Google Scholar
PubMed
Close
,
Aimé Balagizi Hôpital Général de Référence de Nyantende, Nyantende, Democratic Republic of the Congo;

Search for other papers by Aimé Balagizi in
Current site
Google Scholar
PubMed
Close
,
David Lupande Center for Tropical Diseases & Global Health, Université Catholique de Bukavu, Bukavu, Democratic Republic of the Congo;
Hôpital Provincial Général de Référence de Bukavu, Bukavu, Democratic Republic of the Congo;

Search for other papers by David Lupande in
Current site
Google Scholar
PubMed
Close
,
Espoir B. Malembaka Center for Tropical Diseases & Global Health, Université Catholique de Bukavu, Bukavu, Democratic Republic of the Congo;
Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland;

Search for other papers by Espoir B. Malembaka in
Current site
Google Scholar
PubMed
Close
,
Frank P. Mockenhaupt Institute of International Health, Center for Global Health, Charité—Universitätsmedizin Berlin, Berlin, Germany;

Search for other papers by Frank P. Mockenhaupt in
Current site
Google Scholar
PubMed
Close
, and
Esto Bahizire Center for Tropical Diseases & Global Health, Université Catholique de Bukavu, Bukavu, Democratic Republic of the Congo;
Centre de Recherche en Sciences Naturelles de Lwiro, Bukavu, Democratic Republic of the Congo;
Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya

Search for other papers by Esto Bahizire in
Current site
Google Scholar
PubMed
Close
Restricted access

ABSTRACT.

Partial artemisinin resistance has emerged in East Africa, posing a threat to malaria control across the continent. The Democratic Republic of the Congo carries one of the heaviest malaria burdens globally, and the South Kivu province directly borders current artemisinin resistance hot spots, but indications of such resistance have not been observed so far. We assessed molecular markers of antimalarial drug resistance in 256 Plasmodium falciparum isolates collected in 2022 in South Kivu, Democratic Republic of the Congo. One isolate carried the P. falciparum Kelch-13 469Y variant, a marker associated with partial artemisinin resistance and decreased lumefantrine susceptibility in Uganda. In addition, the multidrug resistance-1 mutation pattern suggested increased lumefantrine tolerance.

Author Notes

Financial support: This work was supported by a mobility grant from the Berlin Center for Global Engagement of the Berlin University Alliance to E. B. and by a grant from the German Research Foundation (grant number DFG MO 852/12-1).

Disclosures: Ethical approval was obtained from the Institutional Ethics Committee of the Université Catholique de Bukavu (UCB/CIES/NC/012/2022). Informed consent from study participants was waived because no additional sample material was collected other than for diagnostic purposes, and the respective samples were collected retrospectively from health facilities in a completely anonymous way.

Authors’ addresses: Welmoed van Loon and Frank P. Mockenhaupt, Institute of International Health, Center for Global Health, Charité—Universitätsmedizin Berlin, Berlin, Germany, E-mails: welmoed.van-loon@charite.de and frank.mockenhaupt@charite.de. Bertin C. Bisimwa, Center for Tropical Diseases & Global Health, Université Catholique de Bukavu, Bukavu, Democratic Republic of the Congo, and Institut Supérieur des Techniques Médicales de Bukavu, Bukavu, Democratic Republic of the Congo, E-mail: bcasinga@gmail.com. Valéry Byela, Institut Supérieur des Techniques Médicales de Bukavu, Bukavu, Democratic Republic of the Congo, E-mail: valerybyela@gmail.com. Rebecca Kirby, University of California, San Diego School of Medicine, San Diego, CA, E-mail: rekirby@health.ucsd.edu. Patrick M. Bugeme and Espoir B Malembaka, Center for Tropical Diseases & Global Health, Université Catholique de Bukavu, Bukavu, Democratic Republic of the Congo, and Department of Epidemiology, Johns Hopkins University, Baltimore, MD, E-mails: pbugeme1@jhmi.edu and bwenge.malembaka@ucbukavu.ac.cd. Aimé Balagizi, Hôpital Général de Référence de Nyantende, Nyantende, Democratic Republic of the Congo, E-mail: balagiziaime@yahoo.fr. David Lupande, Center for Tropical Diseases & Global Health, Université Catholique de Bukavu, Bukavu, Democratic Republic of the Congo, and Hôpital Provincial Général de Référence de Bukavu, Bukavu, Democratic Republic of the Congo, E-mail: lupande2000@gmail.com. Esto Bahizire, Center for Tropical Diseases & Global Health, Université Catholique de Bukavu, Bukavu, Democratic Republic of the Congo, Centre de Recherche en Sciences Naturelles de Lwiro, Bukavu, Democratic Republic of the Congo, and Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya, E-mail: esto.bahizire@ucbukavu.ac.cd.

Address correspondence to Welmoed van Loon, Institute of International Health, Center for Global Health, Charité—Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail: welmoed.van-loon@charite.de
  • 1.

    World Health Organization , 2022. World Malaria Report 2022. Geneva, Switzerland: WHO.

  • 2.

    World Health Organization , 2022. Strategy To Respond to Antimalarial Drug Resistance in Africa. Geneva, Switzerland: WHO.

  • 3.

    van der Pluijm RW et al., 2019. Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study. Lancet Infect Dis 19: 952961.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Bergmann C et al., 2021. Increase in Kelch 13 polymorphisms in Plasmodium falciparum, Southern Rwanda. Emerg Infect Dis 27: 294296.

  • 5.

    Uwimana A et al., 2021. Association of Plasmodium falciparum kelch13 R561H genotypes with delayed parasite clearance in Rwanda: an open-label, single-arm, multicentre, therapeutic efficacy study. Lancet Infect Dis 21: 11201128.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Straimer J , Gandhi P , Renner KC , Schmitt EK , 2022. High prevalence of Plasmodium falciparum K13 mutations in Rwanda is associated with slow parasite clearance after treatment with artemether-lumefantrine. J Infect Dis 225: 14111414.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Tumwebaze PK et al., 2022. Decreased susceptibility of Plasmodium falciparum to both dihydroartemisinin and lumefantrine in northern Uganda. Nat Commun 13: 6353.

  • 8.

    Conrad MD et al., 2023. Evolution of partial resistance to artemisinins in malaria parasites in Uganda. N Engl J Med 389: 722732.

  • 9.

    Fola AA et al., 2023. Plasmodium falciparum resistant to artemisinin and diagnostics have emerged in Ethiopia. Nat Microbiol 8: 19111919.

  • 10.

    Veiga MI , Dhingra SK , Henrich PP , Straimer J , Gnädig N , Uhlemann AC , Martin RE , Lehane AM , Fidock DA , 2016. Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies. Nat Commun 7: 11553.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Venkatesan M et al., 2014. Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine. Am J Trop Med Hyg 91: 833843.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Okell LC et al., 2018. Emerging implications of policies on malaria treatment: genetic changes in the Pfmdr-1 gene affecting susceptibility to artemether-lumefantrine and artesunate-amodiaquine in Africa. BMJ Glob Health 3: e000999.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Verity R et al., 2020. The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC. Nat Commun 11: 2107.

  • 14.

    Ntamabyaliro NY et al., 2022. Determinants of patients’ adherence to malaria treatment in the Democratic Republic of the Congo. Trop Med Infect Dis 7: 138.

  • 15.

    Ariey F et al., 2014. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505: 5055.

  • 16.

    Li J et al., 2014. High prevalence of pfmdr1 N86Y and Y184F mutations in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea. Pathog Glob Health 108: 339343.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Mesia Kahunu G et al., 2023. Identification of the PfK13 mutations R561H and P441L in the Democratic Republic of Congo. Int J Infect Dis 139: 4149.

  • 18.

    Kayiba NK et al., 2021. Spatial and molecular mapping of Pfkelch13 gene polymorphism in Africa in the era of emerging Plasmodium falciparum resistance to artemisinin: a systematic review. Lancet Infect Dis 21: e82e92.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Yobi DM et al., 2021. Assessment of Plasmodium falciparum anti-malarial drug resistance markers in pfk13-propeller, pfcrt and pfmdr1 genes in isolates from treatment failure patients in Democratic Republic of Congo, 2018–2019. Malar J 20: 144.

    • PubMed
    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 1074 1074 128
Full Text Views 72 72 18
PDF Downloads 87 87 21
 
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save