{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T07:47:05Z","timestamp":1790408825807,"version":"4.1.0"},"reference-count":64,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T00:00:00Z","timestamp":1622678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Malaria Research and Training Center","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"name":"Standards Diagnosis (SD)","award":["NA"],"award-info":[{"award-number":["NA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Artemether-lumefantrine is a highly effective artemisinin-based combination therapy that was adopted in Mali as first-line treatment for uncomplicated Plasmodium falciparum malaria. This study was designed to measure the efficacy of artemether-lumefantrine and to assess the selection of the P. falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multi-drug resistance 1 (pfmdr1) genotypes that have been associated with drug resistance. Methods: A 28-day follow-up efficacy trial of artemether-lumefantrine was conducted in patients aged 6 months and older suffering from uncomplicated falciparum malaria in four different Malian areas during the 2009 malaria transmission season. The polymorphic genetic markers MSP2, MSP1, and Ca1 were used to distinguish between recrudescence and reinfection. Reinfection and recrudescence were then grouped as recurrent infections and analyzed together by PCR-restriction fragment length polymorphism (RFLP) to identify candidate markers for artemether-lumefantrine tolerance in the P. falciparum chloroquine resistance transporter (pfcrt) gene and the P. falciparum multi-drug resistance 1 (pfmdr1) gene. Results: Clinical outcomes in 326 patients (96.7%) were analyzed and the 28-day uncorrected adequate clinical and parasitological response (ACPR) rate was 73.9%. The total PCR-corrected 28-day ACPR was 97.2%. The pfcrt 76T and pfmdr1 86Y population prevalence decreased from 49.3% and 11.0% at baseline (n = 337) to 38.8% and 0% in patients with recurrent infection (n = 85); p = 0.001), respectively. Conclusion: Parasite populations exposed to artemether-lumefantrine in this study were selected toward chloroquine-sensitivity and showed a promising trend that may warrant future targeted reintroduction of chloroquine or\/and amodiaquine.<\/jats:p>","DOI":"10.3390\/ijms22116057","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T21:03:32Z","timestamp":1622754212000},"page":"6057","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Selection of pfcrt K76 and pfmdr1 N86 Coding Alleles after Uncomplicated Malaria Treatment by Artemether-Lumefantrine in Mali"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5849-0562","authenticated-orcid":false,"given":"Hamma","family":"Maiga","sequence":"first","affiliation":[{"name":"Institut National de Sante Publique, INSP, Bamako P.O. Box 1771, Mali"},{"name":"Malaria Research & Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako, Bamako P.O. Box 1805, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2227-6978","authenticated-orcid":false,"given":"Anastasia","family":"Grivoyannis","sequence":"additional","affiliation":[{"name":"Weill Cornell Medical College, Weill Cornell Medicine, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issaka","family":"Sagara","sequence":"additional","affiliation":[{"name":"Malaria Research & Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako, Bamako P.O. Box 1805, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Traore","sequence":"additional","affiliation":[{"name":"Malaria Research & Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako, Bamako P.O. Box 1805, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oumar B.","family":"Traore","sequence":"additional","affiliation":[{"name":"Malaria Research & Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako, Bamako P.O. Box 1805, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youssouf","family":"Tolo","sequence":"additional","affiliation":[{"name":"Malaria Research & Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako, Bamako P.O. Box 1805, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliou","family":"Traore","sequence":"additional","affiliation":[{"name":"Malaria Research & Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako, Bamako P.O. Box 1805, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amadou","family":"Bamadio","sequence":"additional","affiliation":[{"name":"Malaria Research & Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako, Bamako P.O. Box 1805, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8858-5557","authenticated-orcid":false,"given":"Zoumana I.","family":"Traore","sequence":"additional","affiliation":[{"name":"Malaria Research & Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako, Bamako P.O. Box 1805, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kassim","family":"Sanogo","sequence":"additional","affiliation":[{"name":"Malaria Research & Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako, Bamako P.O. Box 1805, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ogobara K.","family":"Doumbo","sequence":"additional","affiliation":[{"name":"Malaria Research & Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako, Bamako P.O. Box 1805, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher V.","family":"Plowe","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Maryland, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0062-2283","authenticated-orcid":false,"given":"Abdoulaye A.","family":"Djimde","sequence":"additional","affiliation":[{"name":"Malaria Research & Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Pharmacy, Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako, Bamako P.O. Box 1805, Mali"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/med.10016","article-title":"Chloroquine resistance in the malarial parasite, Plasmodium falciparum","volume":"22","author":"Ursos","year":"2002","journal-title":"Med. Res. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S1473-3099(02)00239-6","article-title":"Epidemiology of drug-resistant malaria","volume":"2","author":"Wongsrichanalai","year":"2002","journal-title":"Lancet Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1136\/bmj.1.4646.147","article-title":"Proguanil-resistant falciparum malaria in Malaya","volume":"1","author":"Edeson","year":"1950","journal-title":"Br. Med. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1172\/JCI21682","article-title":"Antimalarial drug resistance","volume":"113","author":"White","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1128\/AAC.41.7.1413","article-title":"Assessment of the pharmacodynamic properties of antimalarial drugs in vivo","volume":"41","author":"White","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_6","unstructured":"WHO (2010). Guidelines for the Treatment of Malaria, World Health Organization. [2nd ed.]."},{"key":"ref_7","unstructured":"WHO (2015). Global Technical Strategy for Malaria Control 2016\u20132030, World Health Organization."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"630","DOI":"10.4269\/ajtmh.2006.75.630","article-title":"A randomized trial of artesunate-sulfamethoxypyrazine-pyrimethamine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali","volume":"75","author":"Sagara","year":"2006","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"655","DOI":"10.4269\/ajtmh.2008.79.655","article-title":"A randomized trial of artesunate-mefloquine versus artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Mali","volume":"79","author":"Sagara","year":"2008","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Diarra, M., Coulibaly, D., Tapily, A., Guindo, B., Sanogo, K., Kone, D., Kone, Y., Kone, K., Bathily, A., and Yattara, O. (2021). Monitoring of the Sensitivity In Vivo of Plasmodium falciparum to Artemether-Lumefantrine in Mali. Trop. Med. Infect. Dis., 6.","DOI":"10.3390\/tropicalmed6010013"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"105","DOI":"10.2165\/00003088-199937020-00002","article-title":"Clinical pharmacokinetics and pharmacodynamics and pharmacodynamics of artemether-lumefantrine","volume":"37","author":"White","year":"1999","journal-title":"Clin. Pharmacokinet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"455","DOI":"10.4269\/ajtmh.2008.78.455","article-title":"Efficacy, safety, and selection of molecular markers of drug resistance by two ACTs in Mali","volume":"78","author":"Djimde","year":"2008","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1056\/NEJM200101253440403","article-title":"A molecular marker for chloroquine-resistant falciparum malaria","volume":"344","author":"Djimde","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1086\/315787","article-title":"Rapid selection of Plasmodium falciparum dihydrofolate reductase mutants by pyrimethamine prophylaxis","volume":"182","author":"Doumbo","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"475","DOI":"10.4269\/ajtmh.1999.60.475","article-title":"Pyrimethamine-sulfadoxine efficacy and selection for mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase in Mali","volume":"60","author":"Diourte","year":"1999","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0166-6851(95)02492-1","article-title":"Analysis of pfmdr1 and drug susceptibility in fresh isolates of Plasmodium falciparum from subsaharan Africa","volume":"74","author":"Basco","year":"1995","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1128\/AAC.47.8.2418-2423.2003","article-title":"Resistance to antimalarials in Southeast Asia and genetic polymorphisms in pfmdr1","volume":"47","author":"Pickard","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1111\/j.1365-2958.2005.04729.x","article-title":"pfmdr1 mutations contribute to quinine resistance and enhance mefloquine and artemisinin sensitivity in Plasmodium falciparum","volume":"57","author":"Sidhu","year":"2005","journal-title":"Mol. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/j.1365-2958.2005.04556.x","article-title":"Defining the role of PfCRT in Plasmodium falciparum chloroquine resistance","volume":"56","author":"Bray","year":"2005","journal-title":"Mol. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1086\/427997","article-title":"In vivo selection of Plasmodium falciparum pfmdr1 86N coding alleles by artemether-lumefantrine (Coartem)","volume":"191","author":"Sisowath","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1111\/j.1365-3156.2007.01843.x","article-title":"The role of pfmdr1 in Plasmodium falciparum tolerance to artemether-lumefantrine in Africa","volume":"12","author":"Sisowath","year":"2007","journal-title":"Trop. Med. Int. Health"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1086\/596738","article-title":"In vivo selection of Plasmodium falciparum parasites carrying the chloroquine-susceptible pfcrt K76 allele after treatment with artemether-lumefantrine in Africa","volume":"199","author":"Sisowath","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1186\/s12936-016-1503-3","article-title":"Selection of Plasmodium falciparum pfcrt and pfmdr1 polymorphisms after treatment with artesunate-amodiaquine fixed dose combination or artemether-lumefantrine in Liberia","volume":"15","author":"Otienoburu","year":"2016","journal-title":"Malar. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11553","DOI":"10.1038\/ncomms11553","article-title":"Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies","volume":"7","author":"Veiga","year":"2016","journal-title":"Nat. Commun"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1086\/432554","article-title":"Coartem (artemether-lumefantrine) in Africa: The beginning of the end?","volume":"192","author":"Hastings","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1128\/AAC.00875-06","article-title":"Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria","volume":"51","author":"Humphreys","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1016\/S0140-6736(12)60484-X","article-title":"Emergence of artemisinin-resistant malaria on the western border of Thailand: A longitudinal study","volume":"379","author":"Phyo","year":"2012","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5408","DOI":"10.1128\/AAC.05102-11","article-title":"Increased pfmdr1 copy number and sequence polymorphisms in Plasmodium falciparum isolates from Sudanese malaria patients treated with artemether-lumefantrine","volume":"55","author":"Gadalla","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1093\/cid\/cir066","article-title":"Efficacy and effectiveness of artemether-lumefantrine after initial and repeated treatment in children <5 years of age with acute uncomplicated Plasmodium falciparum malaria in rural Tanzania: A randomized trial","volume":"52","author":"Ngasala","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/1475-2875-10-64","article-title":"Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania: An open label prospective study","volume":"10","author":"Ngasala","year":"2011","journal-title":"Malar. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/1475-2875-11-58","article-title":"Efficacy of artemether-lumefantrine in treatment of malaria among under-fives and prevalence of drug resistance markers in Igombe-Mwanza, north-western Tanzania","volume":"11","author":"Kamugisha","year":"2012","journal-title":"Malar. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/infdis\/jiq001","article-title":"Similar efficacy and tolerability of double-dose chloroquine and artemether-lumefantrine for treatment of Plasmodium falciparum infection in Guinea-Bissau: A randomized trial","volume":"203","author":"Ursing","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_33","first-page":"234683","article-title":"Amodiaquine-Artesunate versus Artemether-Lumefantrine against Uncomplicated Malaria in Children Less Than 14 Years in Ngaoundere, North Cameroon: Efficacy, Safety, and Baseline Drug Resistant Mutations in pfcrt, pfmdr1, and pfdhfr Genes","volume":"2013","author":"Ali","year":"2013","journal-title":"Malar. Res. Treat."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1128\/AAC.01413-09","article-title":"Selection of known Plasmodium falciparum resistance-mediating polymorphisms by artemether-lumefantrine and amodiaquine-sulfadoxine-pyrimethamine but not dihydroartemisinin-piperaquine in Burkina Faso","volume":"54","author":"Some","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.meegid.2011.01.003","article-title":"Increased prevalence of the Plasmodium falciparum Pfmdr1 86N genotype among field isolates from Franceville, Gabon after replacement of chloroquine by artemether-lumefantrine and artesunate-mefloquine","volume":"11","author":"Zatra","year":"2011","journal-title":"Infect. Genet. Evol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1186\/1475-2875-13-300","article-title":"Prevalence of pfmdr1 alleles associated with artemether-lumefantrine tolerance\/resistance in Maputo before and after the implementation of artemisinin-based combination therapy","volume":"13","author":"Lobo","year":"2014","journal-title":"Malar. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.4269\/ajtmh.2010.10-0339","article-title":"Association between the pfmdr1 gene and in vitro artemether and lumefantrine sensitivity in Thai isolates of Plasmodium falciparum","volume":"83","author":"Mungthin","year":"2010","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1186\/1475-2875-12-377","article-title":"Increased pfmdr1 gene copy number and the decline in pfcrt and pfmdr1 resistance alleles in Ghanaian Plasmodium falciparum isolates after the change of anti-malarial drug treatment policy","volume":"12","author":"Duah","year":"2013","journal-title":"Malar. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.actatropica.2009.01.011","article-title":"Parasites bearing a single copy of the multi-drug resistance gene (pfmdr-1) with wild-type SNPs predominate amongst Plasmodium falciparum isolates from Malawi","volume":"111","author":"Nkhoma","year":"2009","journal-title":"Acta Trop."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1128\/AAC.00968-08","article-title":"Selection of Plasmodium falciparum multidrug resistance gene 1 alleles in asexual stages and gametocytes by artemether-lumefantrine in Nigerian children with uncomplicated falciparum malaria","volume":"53","author":"Happi","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/1475-2875-13-264","article-title":"Surveillance of artemether-lumefantrine associated Plasmodium falciparum multidrug resistance protein-1 gene polymorphisms in Tanzania","volume":"13","author":"Kavishe","year":"2014","journal-title":"Malar. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1093\/infdis\/jir486","article-title":"Prolonged selection of pfmdr1 polymorphisms after treatment of falciparum malaria with artemether-lumefantrine in Uganda","volume":"204","author":"Baliraine","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1086\/606009","article-title":"Plasmodium falciparum multidrug resistance protein 1 and artemisinin-based combination therapy in Africa","volume":"200","author":"Dahlstrom","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"833","DOI":"10.4269\/ajtmh.14-0031","article-title":"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","volume":"91","author":"Venkatesan","year":"2014","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nature12876","article-title":"A molecular marker of artemisinin-resistant Plasmodium falciparum malaria","volume":"505","author":"Ariey","year":"2014","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1093\/jac\/dku125","article-title":"Plasmodium falciparum multidrug resistance protein 1 (pfmrp1) gene and its association with in vitro drug susceptibility of parasite isolates from north-east Myanmar","volume":"69","author":"Gupta","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1586\/14787210.2015.1052793","article-title":"The emerging threat of artemisinin resistance in malaria: Focus on artemether-lumefantrine","volume":"13","author":"Djimde","year":"2015","journal-title":"Expert Rev. Anti. Infect. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12936-017-1700-8","article-title":"Reduced ex vivo susceptibility of Plasmodium falciparum after oral artemether-lumefantrine treatment in Mali","volume":"16","author":"Dama","year":"2017","journal-title":"Malar. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1128\/AAC.50.5.1893-1895.2006","article-title":"Selection of Plasmodium falciparum pfmdr1 alleles following therapy with artemether-lumefantrine in an area of Uganda where malaria is highly endemic","volume":"50","author":"Dokomajilar","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1046\/j.1365-2125.2002.01696.x","article-title":"Pharmacokinetics and electrocardiographic pharmacodynamics of artemether-lumefantrine (Riamet) with concomitant administration of ketoconazole in healthy subjects","volume":"54","author":"Lefevre","year":"2002","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5069","DOI":"10.1128\/AAC.00638-09","article-title":"In vitro activities of piperaquine, lumefantrine, and dihydroartemisinin in Kenyan Plasmodium falciparum isolates and polymorphisms in pfcrt and pfmdr1","volume":"53","author":"Mwai","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1093\/infdis\/jis747","article-title":"Plasmodium falciparum drug resistance phenotype as assessed by patient antimalarial drug levels and its association with pfmdr1 polymorphisms","volume":"207","author":"Malmberg","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.actatropica.2011.09.009","article-title":"Molecular markers of Plasmodium falciparum drug resistance in southern highland Rwanda","volume":"121","author":"Zeile","year":"2012","journal-title":"Acta Trop."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"184","DOI":"10.4269\/ajtmh.2003.69.184","article-title":"Short report: Association between chloroquine and amodiaquine resistance and allelic variation in the Plasmodium falciparum multiple drug resistance 1 gene and the chloroquine resistance transporter gene in isolates from the upper Nile in southern Sudan","volume":"69","author":"Ochong","year":"2003","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/j.1365-3156.2007.01995.x","article-title":"Chloroquine-resistance molecular markers (Pfcrt T76 and Pfmdr-1 Y86) and amodiaquine resistance in Burkina Faso","volume":"13","author":"Tinto","year":"2008","journal-title":"Trop. Med. Int. Health"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"467","DOI":"10.4269\/ajtmh.1996.55.467","article-title":"Community pyrimethamine-sulfadoxine use and prevalence of resistant Plasmodium falciparum genotypes in Mali: A model for deterring resistance","volume":"55","author":"Plowe","year":"1996","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/j.1574-695X.2009.00641.x","article-title":"A molecular map of chloroquine resistance in Mali","volume":"58","author":"Djimde","year":"2010","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"558","DOI":"10.4269\/ajtmh.2003.69.558","article-title":"Clearance of drug-resistant parasites as a model for protective immunity in Plasmodium falciparum malaria","volume":"69","author":"Djimde","year":"2003","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_59","unstructured":"PNLP: PNDLclP (2009). Manuel du Participant. BG VF: Formation Pour la Prise en Charge du Paludisme Dans les Structures Sanitaires, PNLP."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"565","DOI":"10.4269\/ajtmh.1995.52.565","article-title":"Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: Polymerase chain reaction methods for surveillance in Africa","volume":"52","author":"Plowe","year":"1995","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0035-9203(99)90120-7","article-title":"Biased distribution of msp1 and msp2 allelic variants in Plasmodium falciparum populations in Thailand","volume":"93","author":"Snounou","year":"1999","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S0035-9203(97)90539-3","article-title":"Molecular analysis of recrudescent parasites in a Plasmodium falciparum drug efficacy trial in Gabon","volume":"91","author":"Taylor","year":"1997","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1126\/science.286.5443.1351","article-title":"A genetic map and recombination parameters of the human malaria parasite Plasmodium falciparum","volume":"286","author":"Su","year":"1999","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0166-6851(00)00201-2","article-title":"The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin","volume":"108","author":"Duraisingh","year":"2000","journal-title":"Mol. Biochem. Parasitol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/6057\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:10:42Z","timestamp":1760163042000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/6057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,3]]},"references-count":64,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22116057"],"URL":"https:\/\/doi.org\/10.3390\/ijms22116057","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,3]]}}}