WHO , 2020. World Malaria Report, 20 Years of Global Progress and Challenges. Geneva, Switzerland: World Health Organization. Available at: https://reliefweb.int/report/world/world-malaria-report-2020. Accessed February 6, 2021.
Trape JF, 2001. The public health impact of chloroquine resistance in Africa. Am J Trop Med Hyg 64: 12–17.
Payne D, 1987. Spread of chloroquine resistance in Plasmodium falciparum. Parasitol Today 3: 241–246.
Trape JF, Pison G, Preziosi MP, Enel C, Desgrées du Loû A, Delaunay V, Samb B, Lagarde E, Molez JF, Simondon F, 1998. Impact of chloroquine resistance on malaria mortality. C R Acad Sci III 321: 689–697.
Kitua AY, 1999. Antimalarial drug policy: Making systematic change. Lancet 354 (Suppl ):SIV32.
Gatton ML, Martin LB, Cheng Q, 2004. Evolution of resistance to sulfadoxine-pyrimethamine in Plasmodium falciparum. Antimicrob Agents Chemother 48: 2116–2123.
Roper C, Pearce R, Nair S, Sharp B, Nosten F, Anderson T, 2004. Intercontinental spread of pyrimethamine-resistant malaria. Science 305: 1124.
Wootton JC, Feng X, Ferdig MT, Cooper RA, Mu J, Baruch DI, Magill AJ, Su X-Z, 2002. Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum. Nature 418: 320–323.
WHO , 2001. Antimalarial Drug Combination Therapy - Report of a WHO Technical Consultation. Geneva, Switzerland: World Health Organization. Available at: https://apps.who.int/iris/bitstream/handle/10665/66952/WHO_CDS_RBM_2001.35.pdf?sequence=1. Accessed June 5, 2020.
WHO , 2019. World Malaria Report. Geneva, Switzerland: World Health Organization. Available at: https://www.who.int/publications-detail/world-malaria-report-2019. Accessed January 29, 2021.
Huang F, Yan H, Xue JB, Cui YW, Zhou SS, Xia ZG, Abeyasinghe R, Ringwald P, Zhou XN, 2021. Molecular surveillance of pfcrt, pfmdr1 and pfk13-propeller mutations in Plasmodium falciparum isolates imported from Africa to China. Malar J 0: 73.
Lu F et al., 2017. Emergence of indigenous artemisinin-resistant Plasmodium falciparum in Africa. N Engl J Med 376: 991–993.
Bergmann C et al., 2021. Increase in kelch 13 polymorphisms in Plasmodium falciparum, southern Rwanda. Emerg Infect Dis 27: 294–296.
Bwire GM, Ngasala B, Mikomangwa WP, Kilonzi M, Kamuhabwa AAR, 2020. Detection of mutations associated with artemisinin resistance at k13-propeller gene and a near complete return of chloroquine susceptible falciparum malaria in southeast of Tanzania. Sci Rep 10: 3500.
Tacoli C, Gai PP, Bayingana C, Sifft K, Geus D, Ndoli J, Sendegeya A, Gahutu JB, Mockenhaupt FP, 2016. Artemisinin resistance-associated k13 polymorphisms of Plasmodium falciparum in southern Rwanda, 2010–2015. Am J Trop Med Hyg 95: 1090–1093.
Uwimana A et al., 2020. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 r561h mutant parasites in Rwanda. Nat Med 26: 1602–1608.
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.
Asua V et al., 2021. Changing prevalence of potential mediators of aminoquinoline, antifolate, and artemisinin resistance across Uganda. J Infect Dis 223: 985–994.
Ariey F et al., 2014. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505: 50–55.
Zaw MT, Emran NA, Lin Z, 2018. Updates on k13 mutant alleles for artemisinin resistance in Plasmodium falciparum. J Microbiol Immunol Infect 51: 159–165.
Nag S, Dalgaard MD, Kofoed PE, Ursing J, Crespo M, Andersen LO, Aarestrup FM, Lund O, Alifrangis M, 2017. High throughput resistance profiling of Plasmodium falciparum infections based on custom dual indexing and Illumina next generation sequencing-technology. Sci Rep 7: 2398.
Ménard D et al., 2016. A worldwide map of Plasmodium falciparum k13-propeller polymorphisms. N Engl J Med 374: 2453–2464.
Taylor SM et al., 2015. Absence of putative artemisinin resistance mutations among Plasmodium falciparum in sub-Saharan Africa: a molecular epidemiologic study. J Infect Dis 211: 680–688.
Preston MD et al., 2014. A barcode of organellar genome polymorphisms identifies the geographic origin of Plasmodium falciparum strains. Nat Commun 5: 4052.
Das MK et al., 2017. Malaria epidemiology in an area of stable transmission in tribal population of Jharkhand, India. Malar J 16: 181.
Mkumbaye SI et al., 2017. The severity of Plasmodium falciparum infection is associated with transcript levels of var genes encoding endothelial protein c receptor-binding P. falciparum erythrocyte membrane protein 1. Infect Immun 85: e00841–16.
Ndiaye M, Sow D, Nag S, Sylla K, Tine RC, Ndiaye JL, Lo AC, Gaye O, Faye B, Alifrangis M, 2017. Country-wide surveillance of molecular markers of antimalarial drug resistance in Senegal by use of positive malaria rapid diagnostic tests. Am J Trop Med Hyg 97: 1593–1596.
WWARN , 2013. PCR and Sequencing for Genotyping of Candidate Plasmodium falciparum Artemisinin Resistance SNPs in the Kelch 13 Gene. Available at: https://www.wwarn.org/tools-resources/procedures/pcr-and-sequencing-genotyping-candidate-plasmodium-falciparum-artemisinin. Accessed May 11, 2021.
Tyagi S, Das A, 2015. Mitochondrial population genomic analyses reveal population structure and demography of Indian Plasmodium falciparum. Mitochondrion 24: 9–21.
Tyagi S, Pande V, Das A, 2014. New insights into the evolutionary history of Plasmodium falciparum from mitochondrial genome sequence analyses of Indian isolates. Mol Ecol 23: 2975–2987.
Tyagi S, Pande V, Das A, 2014. Mitochondrial genome sequence diversity of Indian Plasmodium falciparum isolates. Mem Inst Oswaldo Cruz 109: 494–498.
Schoone GJ, Oskam L, Kroon NC, Schallig HD, Omar SA, 2000. Detection and quantification of Plasmodium falciparum in blood samples using quantitative nucleic acid sequence-based amplification. J Clin Microbiol 38: 4072–4075.
Conway DJ et al., 2000. Origin of Plasmodium falciparum malaria is traced by mitochondrial DNA. Mol Biochem Parasitol 111: 163–171.
Hughes AL, Verra F, 2001. Very large long-term effective population size in the virulent human malaria parasite Plasmodium falciparum. Proc Biol Sci 268: 1855–1860.
Tanabe K et al., 2010. Plasmodium falciparum accompanied the human expansion out of Africa. Curr Biol 20: 1283–1289.
Escalante AA, Barrio E, Ayala FJ, 1995. Evolutionary origin of human and primate malarias: evidence from the circumsporozoite protein gene. Mol Biol Evol 12: 616–626.
Joy DA et al., 2003. Early origin and recent expansion of Plasmodium falciparum. Science 300: 318–321.
Talundzic E, Chenet SM, Goldman IF, Patel DS, Nelson JA, Plucinski MM, Barnwell JW, Udhayakumar V, 2015. Genetic analysis and species specific amplification of the artemisinin resistance-associated kelch propeller domain in P. falciparum and P. vivax. PLoS One 10: e0136099.
Ocholla H et al., 2014. Whole-genome scans provide evidence of adaptive evolution in Malawian Plasmodium falciparum isolates. J Infect Dis 210: 1991–2000.
Amambua-Ngwa A et al., 2019. Major subpopulations of Plasmodium falciparum in sub-Saharan Africa. Science 365: 813–816.
Mishra N, Bharti RS, Mallick P, Singh OP, Srivastava B, Rana R, Phookan S, Gupta HP, Ringwald P, Valecha N, 2016. Emerging polymorphisms in falciparum kelch 13 gene in northeastern region of India. Malar J 15: 583.
Rana R, Ranjit M, Bal M, Khuntia HK, Pati S, Krishna S, Das A, 2020. Sequence analysis of the k13-propeller gene in artemisinin challenging Plasmodium falciparum isolates from malaria endemic areas of Odisha, India: a molecular surveillance study. BioMed Res Int 2020: 8475246.
Chhibber-Goel J, Sharma A, 2019. Profiles of kelch mutations in Plasmodium falciparum across south Asia and their implications for tracking drug resistance. Int J Parasitol Drug Resist 11: 49–58.
Torrentino-Madamet M et al., 2014. Limited polymorphisms in k13 gene in Plasmodium falciparum isolates from Dakar, Senegal in 2012–2013. Malar J 13: 472.
Madamet M et al., 2017. Absence of association between polymorphisms in the k13 gene and the presence of Plasmodium falciparum parasites at day 3 after treatment with artemisinin derivatives in Senegal. Int J Antimicrob Agents 49: 754–756.
Conrad MD, Bigira V, Kapisi J, Muhindo M, Kamya MR, Havlir DV, Dorsey G, Rosenthal PJ, 2014. Polymorphisms in k13 and falcipain-2 associated with artemisinin resistance are not prevalent in Plasmodium falciparum isolated from Ugandan children. PLoS One 9: e105690.
Wang Z, Shrestha S, Li X, Miao J, Yuan L, Cabrera M, Grube C, Yang Z, Cui L, 2015. Prevalence of k13-propeller polymorphisms in Plasmodium falciparum from China-Myanmar border in 2007–2012. Malar J 14: 168.
Takala-Harrison S et al., 2015. Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast Asia. J Infect Dis 211: 670–679.
Doolan DL, Dobaño C, Baird JK, 2009. Acquired immunity to malaria. Clin Microbiol Rev 22: 13–36.
Takala-Harrison S, Laufer MK, 2015. Antimalarial drug resistance in Africa: key lessons for the future. Ann N Y Acad Sci 1342: 62–67.
Mukherjee A et al., 2017. Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia. Malar J 16: 195.
Sutherland CJ et al., 2017. Pfk13-independent treatment failure in four imported cases of Plasmodium falciparum malaria treated with artemether-lumefantrine in the United Kingdom. Antimicrob Agents Chemother 61: e02382–e02316.
Adams T, Ennuson NAA, Quashie NB, Futagbi G, Matrevi S, Hagan OCK, Abuaku B, Koram KA, Duah NO, 2018. Prevalence of Plasmodium falciparum delayed clearance associated polymorphisms in adaptor protein complex 2 mu subunit (pfap2mu) and ubiquitin specific protease 1 (pfubp1) genes in Ghanaian isolates. Parasit Vectors 11: 175.
Ofori MF, Kploanyi EE, Dickson EK, Kyei-Baafour E, Mensah BA, Koram KA, Abuaku BK, Gyabaa S, Tetteh M, Ghansah A, 2021. Ex vivo sensitivity profile of Plasmodium falciparum clinical isolates to a panel of antimalarial drugs in Ghana 13 years after national policy change. Infect Drug Resist 14: 267–276.
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The emergence of artemisinin-resistant Plasmodium falciparum parasites in Southeast Asia threatens malaria control and elimination. The interconnectedness of parasite populations may be essential to monitor the spread of resistance. Combining a published barcoding system of geographically restricted single-nucleotide polymorphisms (SNPs), mainly mitochondria of P. falciparum with SNPs in the K13 artemisinin resistance marker, could elucidate the parasite population structure and provide insight regarding the spread of drug resistance. We explored the diversity of mitochondrial SNPs (bp position 611-2825) and identified K13 SNPs from malaria patients in the districts of India (Ranchi), Tanzania (Korogwe), and Senegal (Podor, Richard Toll, Kaolack, and Ndoffane). DNA was amplified using a nested PCR and Sanger-sequenced. Overall, 199 K13 sequences (India: N = 92; Tanzania: N = 48; Senegal: N = 59) and 237 mitochondrial sequences (India: N = 93; Tanzania: N = 48; Senegal: N = 96) were generated. SNPs were identified by comparisons with reference genomes. We detected previously reported geographically restricted mitochondrial SNPs (T2175C and G1367A) as markers for parasites originating from the Indian subcontinent and several geographically unrestricted mitochondrial SNPs. Combining haplotypes with published P. falciparum mitochondrial genome data suggested possible regional differences within India. All three countries had G1692A, but Tanzanian and Senegalese SNPs were well-differentiated. Some mitochondrial SNPs are reported here for the first time. Four nonsynonymous K13 SNPs were detected: K189T (India, Tanzania, Senegal); A175T (Tanzania); and A174V and R255K (Senegal). This study supports the use of mitochondrial SNPs to determine the origin of the parasite and suggests that the P. falciparum populations studied were susceptible to artemisinin during sampling because all K13 SNPs observed were outside the propeller domain for artemisinin resistance.
These authors contributed equally to this work.
Financial support: This work was supported by Building Stronger Universities Phase 3 (BSU3) programme (at University of Ghana and Kilimanjaro Christian Medical College) and by the DANIDA Fellowship Centre at the Danish Foreign Ministry. The work was also financially supported by the Wedell-Wedellsborgs Fond (Denmark) and the Aase og Ejnar Danielsens Fond (Denmark).
Authors’ addresses: Tine Kliim Nydahl, Helle Hansson, Marina Crespo Bravo, Christian William Wang, Michael Theisen, Susheel Kumar Singh, and Michael Alifrangis, Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Denmark, E-mails: email@example.com, firstname.lastname@example.org, email@example.com, firstname.lastname@example.org, email@example.com, firstname.lastname@example.org, and email@example.com. Samuel Yao Ahorhorlu, Centre for Tropical Clinical Pharmacology and Therapeutics, University of Ghana Medical School, University of Ghana, Ghana, E-mail: firstname.lastname@example.org. Magatte Ndiaye, Service de Parasitologie–Mycologie, Faculté de Médecine, Université Cheikh Anta DIOP, Dakar, Senegal, E-mail: email@example.com. John Lusingu, National Institute for Medical Research, Tanga Centre, Tanzania, E-mail: firstname.lastname@example.org. Manoj Kumar Das, Field Unit, National Institute of Malaria Research, Ranchi, Jharkhand, India, E-mail: email@example.com. Subhash Singh, Indian Institute of Integrative Medicine, Jammu, India, E-mail: firstname.lastname@example.org. Susana Campino and Cally Roper, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom, E-mail: email@example.com and firstname.lastname@example.org. Ole Lund, Genomic Epidemiology, Department of Bio and Health Informatics, Technical University of Denmark, Copenhagen, Denmark, E-mail: email@example.com.