Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 27, Number 7—July 2021
Research

Plasmodium falciparum kelch 13 Mutations, 9 Countries in Africa, 2014–2018

Sarah E. Schmedes1, Dhruviben Patel1, Simran Dhal, Julia Kelley, Samaly S. Svigel, Pedro Rafael Dimbu, Adicatou-Laï Adeothy, Gauthier Mesia Kahunu, Papy Mandoko Nkoli, Abdoul Habib Beavogui, Simon Kariuki, Don P. Mathanga, Ousmane Koita, Deus Ishengoma, Ally Mohamad, Moonga Hawela, Leah F. Moriarty, Aaron M. Samuels, Julie Gutman, Mateusz M. Plucinski, Venkatachalam Udhayakumar, Zhiyong Zhou, Naomi W. Lucchi, Meera Venkatesan, Eric S. Halsey, and Eldin TalundzicComments to Author 
Author affiliations: Association of Public Health Laboratories, Silver Spring, Maryland, USA (S.E. Schmedes); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (S.E. Schmedes, D. Patel, S.S. Svigel, A.M. Samuels, J. Gutman, M.M. Plucinski, V. Udhayakumar, Z. Zhou, N.W. Lucchi, E. Talundzic); Williams Consulting LLC, Baltimore, Maryland, USA (D. Patel); The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta (S. Dahl); CDC Foundation, Atlanta (J. Kelley); National Malaria Control Program, Ministry of Health, Luanda, Angola (P.R. Dimbu); National Malaria Control Program, Ministry of Health, Porto-Novo, Benin (A.-L. Adeothy); University of Kinshasa, Kinshasa, Democratic Republic of the Congo (G.M. Kahunu); National Institute of Biomedical Research, Kinshasa (P.M. Nkoli); Maferinyah Rural Health Research Center, Mafèrinyah, Guinea (A.H. Beavogui); Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya (S. Kariuki); University of Malawi College of Medicine, Blantyre, Malawi (D.P. Mathanga); University of Sciences, Techniques, and Technologies of Bamako, Bamako, Mali (O. Koita); Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA (D. Ishengoma); National Institute for Medical Research, Tanga Research Centre, Dar es Salaam, Tanzania (D. Ishengoma, A. Mohamad); Monash University Faculty of Pharmaceutical Sciences, Melbourne, Australia (D. Ishengoma); National Malaria Elimination Centre, Lusaka, Zambia (M. Hawela); US President’s Malaria Initiative, Centers for Disease Control and Prevention, Atlanta (L.F. Moriarty, M.M. Plucinski, E.S. Halsey); US President’s Malaria Initiative, US Agency for International Development, Washington, DC, USA (M. Venkatesan)

Main Article

Table 4

Summary of Pfk13 nonsynonymous mutations detected in Plasmodium falciparum pretreatment and DF samples, 9 countries in Africa, 2014–2018*

Mutation Country Codon change No. samples pretreatment (DF) Country or region where previously reported (reference)
I416V Tanzania ATA → GTA 1 (0) Tanzania (14)
P419S Guinea CCA → TCA 1 (0) NA
E433D Tanzania GAA → GAC 1 (0) Tanzania (14)
R471S Tanzania CGT → AGT 1 (0) Tanzania (14)
S477Y DRC TCT → TAT 0 (1) Grande Comore Island (16)
A504V Angola (2017) GCT → GTT 1 (0) Gabon (17)
S522C Kenya AGT → TGT 2 (0) Africa (18)
A569G Benin GCA → GGA 1 (0) Gambia (19) and Niger (20)
A578S Angola (2015) GCT → TCT 4 (0) Africa (19)
A578S DRC GCT → TCT 1 (1) Africa (19)
A578S Mali GCT → TCT 1 (0) Africa (19)
A578S Kenya GCT → TCT 6 (2) Africa (19)
A578S Tanzania GCT → TCT 1 (0) Africa (19)
A578S Zambia GCT → TCT 1 (0) Africa (19)
Q613R Angola (2015) CAA → CGA 1 (0) NA
Q613E
Tanzania
CAA → GAA
2 (0)
Tanzania (14)
Total 25 (4)

*DF, day of failure; DRC, Democratic Republic of the Congo; NA, not available; Pfk13, Plasmodium falciparum kelch 13.

Main Article

References
  1. World Health Organization. World malaria report 2019 [cited 2020 May 15]. https://www.who.int/publications/i/item/9789241565721
  2. World Health Organization. Guidelines for the treatment of malaria. 3rd edition. 2015 [cited 2020 May 15]. https://apps.who.int/iris/handle/10665/162441
  3. World Health Organization. Artemisinin resistance and artemisinin-based combination therapy efficacy: status report. 2018 [cited 2020 May 15]. https://apps.who.int/iris/handle/10665/274362
  4. Cheeseman  IH, Miller  BA, Nair  S, Nkhoma  S, Tan  A, Tan  JC, et al. A major genome region underlying artemisinin resistance in malaria. Science. 2012;336:7982. DOIPubMedGoogle Scholar
  5. Takala-Harrison  S, Clark  TG, Jacob  CG, Cummings  MP, Miotto  O, Dondorp  AM, et al. Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia. Proc Natl Acad Sci U S A. 2013;110:2405. DOIPubMedGoogle Scholar
  6. Ariey  F, Witkowski  B, Amaratunga  C, Beghain  J, Langlois  A-C, Khim  N, et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature. 2014;505:505. DOIPubMedGoogle Scholar
  7. Ashley  EA, Dhorda  M, Fairhurst  RM, Amaratunga  C, Lim  P, Suon  S, et al.; Tracking Resistance to Artemisinin Collaboration (TRAC). Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014;371:41123. DOIPubMedGoogle Scholar
  8. World Health Organization. Methods for surveillance of antimalarial drug efficacy. 2009 [cited 2020 May 15]. https://www.who.int/malaria/publications/atoz/9789241597531/en
  9. Halsey  ES, Venkatesan  M, Plucinski  MM, Talundzic  E, Lucchi  NW, Zhou  Z, et al. Capacity Development through the US President’s Malaria Initiative-Supported Antimalarial Resistance Monitoring in Africa Network. Emerg Infect Dis. 2017;23:S536. DOIPubMedGoogle Scholar
  10. Plucinski  MM, Dimbu  PR, Macaia  AP, Ferreira  CM, Samutondo  C, Quivinja  J, et al. Efficacy of artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum malaria in Angola, 2015. Malar J. 2017;16:62. DOIPubMedGoogle Scholar
  11. Ljolje  D, Dimbu  PR, Kelley  J, Goldman  I, Nace  D, Macaia  A, et al. Prevalence of molecular markers of artemisinin and lumefantrine resistance among patients with uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2015. Malar J. 2018;17:84. DOIPubMedGoogle Scholar
  12. Davlantes  E, Dimbu  PR, Ferreira  CM, Florinda Joao  M, Pode  D, Félix  J, et al. Efficacy and safety of artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in three provinces in Angola, 2017. Malar J. 2018;17:144. DOIPubMedGoogle Scholar
  13. Chebore  W, Zhou  Z, Westercamp  N, Otieno  K, Shi  YP, Sergent  SB, et al. Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya. Malar J. 2020;19:291. DOIPubMedGoogle Scholar
  14. Ishengoma  DS, Mandara  CI, Francis  F, Talundzic  E, Lucchi  NW, Ngasala  B, et al. Efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated malaria and prevalence of Pfk13 and Pfmdr1 polymorphisms after a decade of using artemisinin-based combination therapy in mainland Tanzania. Malar J. 2019;18:88. DOIPubMedGoogle Scholar
  15. Talundzic  E, Chenet  SM, Goldman  IF, Patel  DS, Nelson  JA, Plucinski  MM, et al. Genetic analysis and species specific amplification of the artemisinin resistance-associated kelch propeller domain in P. falciparum and P. vivax. PLoS One. 2015;10:e0136099. DOIPubMedGoogle Scholar
  16. Huang  B, Deng  C, Yang  T, Xue  L, Wang  Q, Huang  S, et al. Polymorphisms of the artemisinin resistant marker (K13) in Plasmodium falciparum parasite populations of Grande Comore Island 10 years after artemisinin combination therapy. Parasit Vectors. 2015;8:634. DOIPubMedGoogle Scholar
  17. Voumbo-Matoumona  DF, Kouna  LC, Madamet  M, Maghendji-Nzondo  S, Pradines  B, Lekana-Douki  JB. Prevalence of Plasmodium falciparum antimalarial drug resistance genes in Southeastern Gabon from 2011 to 2014. Infect Drug Resist. 2018;11:132938. DOIPubMedGoogle Scholar
  18. WWARN K13 Genotype-Phenotype Study Group. Association of mutations in the Plasmodium falciparum Kelch13 gene (Pf3D7_1343700) with parasite clearance rates after artemisinin-based treatments-a WWARN individual patient data meta-analysis. BMC Med. 2019;17:1. DOIPubMedGoogle Scholar
  19. Ménard  D, Khim  N, Beghain  J, Adegnika  AA, Shafiul-Alam  M, Amodu  O, et al.; KARMA Consortium. KARMA Consortium. A worldwide map of Plasmodium falciparum K13-propeller polymorphisms. N Engl J Med. 2016;374:245364. DOIPubMedGoogle Scholar
  20. Laminou  I, Lamine  M, Arzika  I, Mahamadou  B, Gora  D, Dieye  A. Detection of Plasmodium falciparum K13 propeller A569G mutation after artesunate-amodiaquine treatment failure in Niger. J Adv Biol Biotechnol. 2018;18:18. DOIGoogle Scholar
  21. Malaria  GEN. Plasmodium falciparum Community Project. Genomic epidemiology of artemisinin resistant malaria. eLife. 2016;5:e08714. DOIGoogle Scholar
  22. Ocan  M, Akena  D, Nsobya  S, Kamya  MR, Senono  R, Kinengyere  AA, et al. K13-propeller gene polymorphisms in Plasmodium falciparum parasite population in malaria affected countries: a systematic review of prevalence and risk factors. Malar J. 2019;18:60. DOIPubMedGoogle Scholar
  23. Conrad  MD, Rosenthal  PJ. Antimalarial drug resistance in Africa: the calm before the storm? Lancet Infect Dis. 2019;19:e33851. DOIPubMedGoogle Scholar
  24. World Health Organization. Artemisinin and artemisinin-based combination therapy resistance: status report. 2017 [cited 2020 May 15]. https://apps.who.int/iris/handle/10665/255213
  25. Mohon  AN, Alam  MS, Bayih  AG, Folefoc  A, Shahinas  D, Haque  R, et al. Mutations in Plasmodium falciparum K13 propeller gene from Bangladesh (2009-2013). Malar J. 2014;13:431. DOIPubMedGoogle Scholar
  26. Uwimana  A, Legrand  E, Stokes  BH, Ndikumana  JM, Warsame  M, Umulisa  N, et al. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med. 2020;26:16028. DOIPubMedGoogle Scholar
  27. Talundzic  E, Ravishankar  S, Kelley  J, Patel  D, Plucinski  M, Schmedes  S, et al. Next-generation sequencing and bioinformatics protocol for malaria drug resistance marker surveillance. Antimicrob Agents Chemother. 2018;62:e0247417. DOIPubMedGoogle Scholar

Main Article

1These authors contributed equally to this article.

Page created: April 28, 2021
Page updated: June 16, 2021
Page reviewed: June 16, 2021
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external