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Selection of pfcrt K76 and pfmdr1 N86 Coding Alleles after Uncomplicated Malaria Treatment by Artemether-Lumefantrine in Mali

1
Institut National de Sante Publique, INSP, Bamako P.O. Box 1771, Mali
2
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
3
Weill Cornell Medical College, Weill Cornell Medicine, New York, NY 10021, USA
4
School of Medicine, University of Maryland, Baltimore, MD 21201, USA
*
Author to whom correspondence should be addressed.
Deceased.
Academic Editor: Davide Gentilini
Int. J. Mol. Sci. 2021, 22(11), 6057; https://doi.org/10.3390/ijms22116057
Received: 4 February 2021 / Revised: 18 March 2021 / Accepted: 19 March 2021 / Published: 3 June 2021
(This article belongs to the Section Molecular Genetics and Genomics)
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. View Full-Text
Keywords: Plasmodium falciparum; Pfcrt; Pfmdr1; Artemether-lumefantrine; Mali Plasmodium falciparum; Pfcrt; Pfmdr1; Artemether-lumefantrine; Mali
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MDPI and ACS Style

Maiga, H.; Grivoyannis, A.; Sagara, I.; Traore, K.; Traore, O.B.; Tolo, Y.; Traore, A.; Bamadio, A.; Traore, Z.I.; Sanogo, K.; Doumbo, O.K.; Plowe, C.V.; Djimde, A.A. Selection of pfcrt K76 and pfmdr1 N86 Coding Alleles after Uncomplicated Malaria Treatment by Artemether-Lumefantrine in Mali. Int. J. Mol. Sci. 2021, 22, 6057. https://doi.org/10.3390/ijms22116057

AMA Style

Maiga H, Grivoyannis A, Sagara I, Traore K, Traore OB, Tolo Y, Traore A, Bamadio A, Traore ZI, Sanogo K, Doumbo OK, Plowe CV, Djimde AA. Selection of pfcrt K76 and pfmdr1 N86 Coding Alleles after Uncomplicated Malaria Treatment by Artemether-Lumefantrine in Mali. International Journal of Molecular Sciences. 2021; 22(11):6057. https://doi.org/10.3390/ijms22116057

Chicago/Turabian Style

Maiga, Hamma, Anastasia Grivoyannis, Issaka Sagara, Karim Traore, Oumar B. Traore, Youssouf Tolo, Aliou Traore, Amadou Bamadio, Zoumana I. Traore, Kassim Sanogo, Ogobara K. Doumbo, Christopher V. Plowe, and Abdoulaye A. Djimde. 2021. "Selection of pfcrt K76 and pfmdr1 N86 Coding Alleles after Uncomplicated Malaria Treatment by Artemether-Lumefantrine in Mali" International Journal of Molecular Sciences 22, no. 11: 6057. https://doi.org/10.3390/ijms22116057

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