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

Abstract

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.

• Authors: Hamma Maiga, 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, Abdoulaye A Djimde
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 11 (Jun 03 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34205228 (Publication Type: Journal Article)

Chemical References

• Artemether, Lumefantrine Drug Combination
• Artemisinins
• Mdr1 protein, Plasmodium falciparum
• Membrane Transport Proteins
• Multidrug Resistance-Associated Proteins
• PfCRT protein, Plasmodium falciparum
• Protozoan Proteins
• Chloroquine
• artemisinin

Topics

• Alleles
• Artemether, Lumefantrine Drug Combination (administration & dosage, adverse effects)
• Artemisinins (administration & dosage, adverse effects)
• Child
• Child, Preschool
• Chloroquine (administration & dosage, adverse effects)
• Drug Resistance (genetics)
• Female
• Humans
• Malaria, Falciparum (drug therapy, genetics, parasitology, pathology)
• Male
• Membrane Transport Proteins (genetics)
• Multidrug Resistance-Associated Proteins (genetics)
• Plasmodium falciparum (drug effects, pathogenicity)
• Protozoan Proteins (genetics)