title: Artesunate-Amodiaquine and Artemether-Lumefantrine Therapies and Selection of Pfcrt and Pfmdr1 Alleles in Nanoro, Burkina Faso.
abstract: The adoption of Artemisinin based combination therapies (ACT) constitutes a basic strategy for malaria control in sub-Saharan Africa. Moreover, since cases of ACT resistance have been reported in South-East Asia, the need to understand P. falciparum resistance mechanism to ACT has become a global research goal. The selective pressure of ACT and the possibility that some specific Pfcrt and Pfmdr1 alleles are associated with treatment failures was assessed in a clinical trial comparing ASAQ to AL in Nanoro. Dried blood spots collected on Day 0 and on the day of recurrent parasitaemia during the 28-day follow-up were analyzed using the restriction fragments length polymorphism (PCR-RFLP) method to detect single nucleotide polymorphisms (SNPs) in Pfcrt (codon76) and Pfmdr1 (codons 86, 184, 1034, 1042, and 1246) genes. Multivariate analysis of the relationship between the presence of Pfcrt and Pfmdr1 alleles and treatment outcome was performed. AL and ASAQ exerted opposite trends in selecting Pfcrt K76T and Pfmdr1-N86Y alleles, raising the potential beneficial effect of using diverse ACT at the same time as first line treatments to reduce the selective pressure by each treatment regimen. No clear association between the presence of Pfcrt and Pfmdr1 alleles carried at baseline and treatment failure was observed.
authors.affiliation: IRSS / Clinical Research Unit of Nanoro (CRUN), Nanoro, Burkina Faso.
authors.forename: Paul
authors.initials: P
authors.lastname: Sondo
authors.affiliation: IRSS / Clinical Research Unit of Nanoro (CRUN), Nanoro, Burkina Faso.
authors.forename: Karim
authors.initials: K
authors.lastname: Derra
authors.affiliation: IRSS / Clinical Research Unit of Nanoro (CRUN), Nanoro, Burkina Faso.|Centre Muraz of Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso.
authors.forename: Seydou
authors.initials: S
authors.lastname: Diallo Nakanabo
authors.affiliation: IRSS / Clinical Research Unit of Nanoro (CRUN), Nanoro, Burkina Faso.
authors.forename: Zekiba
authors.initials: Z
authors.lastname: Tarnagda
authors.affiliation: IRSS / Clinical Research Unit of Nanoro (CRUN), Nanoro, Burkina Faso.
authors.forename: Adama
authors.initials: A
authors.lastname: Kazienga
authors.affiliation: Centre Muraz of Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso.
authors.forename: Odile
authors.initials: O
authors.lastname: Zampa
authors.affiliation: IRSS / Clinical Research Unit of Nanoro (CRUN), Nanoro, Burkina Faso.|Centre Muraz of Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso.
authors.forename: Innocent
authors.initials: I
authors.lastname: Valéa
authors.affiliation: IRSS / Clinical Research Unit of Nanoro (CRUN), Nanoro, Burkina Faso.
authors.forename: Hermann
authors.initials: H
authors.lastname: Sorgho
authors.affiliation: Kumasi Center for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.
authors.forename: Ellis
authors.initials: E
authors.lastname: Owusu-Dabo
authors.affiliation: IRSS / Clinical Research Unit of Nanoro (CRUN), Nanoro, Burkina Faso.
authors.forename: Jean-Bosco
authors.initials: JB
authors.lastname: Ouédraogo
authors.affiliation: Centre Muraz of Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso.
authors.forename: Tinga Robert
authors.initials: TR
authors.lastname: Guiguemdé
authors.affiliation: IRSS / Clinical Research Unit of Nanoro (CRUN), Nanoro, Burkina Faso.|Centre Muraz of Bobo-Dioulasso, Bobo-Dioulasso, Burkina Faso.
authors.forename: Halidou
authors.initials: H
authors.lastname: Tinto
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000655:Amodiaquine / Q000627:therapeutic use*; D000962:Antimalarials / Q000627:therapeutic use; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use*; D002050:Burkina Faso; D002648:Child; D004338:Drug Combinations; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D005787:Gene Frequency; D005838:Genotype; D006790:Host-Parasite Interactions; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D015999:Multivariate Analysis; D018512:Parasitemia / Q000097:blood / Q000188:drug therapy / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000655:Amodiaquine; D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D015800:Protozoan Proteins; C513498:Mdr1 protein, Plasmodium falciparum; C416369:PfCRT protein, Plasmodium falciparum; C515299:amodiaquine, artesunate drug combination