Evaluation of artemether-lumefantrine efficacy in the treatment of uncomplicated malaria and its association with pfmdr1, pfatpase6 and K13-propeller polymorphisms in Luanda, Angola. (December 2015)

• Record Type: Journal Article
• Authors: Kiaco, Kinanga; Teixeira, Joana; Machado, Marta; Rosário, Virgílio; Lopes, Dinora
• Is Part Of: Malaria journal. Volume 14:Number 1(2015)
• Page Start: 1
• Page End: 10
• Publication Date: 2015-12
• Subjects: Plasmodium falciparum -- Artemether-lumefantrine -- Therapeutic efficacy -- Polymorphisms -- pfmdr1 -- pfatp6 -- pfK13 -- Angola; Malaria -- Periodicals; 616.9362
• DOI: 10.1186/s12936-015-1018-3
• Languages: English
• ISSNs: 1475-2875

Abstract

Abstract Background Drug resistance inPlasmodium falciparum has posed an obstacle to effective treatment and challenges many malaria control programmes in endemic areas. In Angola, until 2003, chloroquine (CQ) was used as first-line therapy for uncomplicated malaria. It was replaced initially by amodiaquine and, in 2006, by artemisinin-based combination therapy (ACT) with artemether-lumefantrine (AL, Coartem® ). Efficacy study of ACT, conducted in Angola between 2004 and 2005, showed a baseline efficacy of ≈99 %. Methods 103 malaria patients were enrolled according to WHO proceedings. Patients were followed up with clinical and parasitological evaluations for 28 days, parasite density and identification was evaluated by microscopy, thepfmsp2 were genotyped by nested-PCR, to distinguish parasite recrudescence from new infections; the polymorphisms at codons 86 and 1246 ofpfmdr1 gene, and 769 ofpfatp6 gene were assessed by PCR–RFLP and sequencing forpfk13 -propeller genotype. Results The cure rate was 91.3 %. The obtained results showed that from 103 patients, 12.6 % (n = 13) still had parasitaemia 1 day after the treatment was finished. On day 0, of the 94 evaluated samples, wild-type alleles were identified in 73.4 % (n = 69) forpfmdr1 N86Y position and only one sample carried the mutant allele (Y) forpfmdr1 1246; 14 % of these samples showed increasedpfmdr1 copy number; 100 % (n = 21) had wild-type allele ofk13 gene in all the studied positions. Discussion These results showed changes in parasite profile susceptibility to AL in comparison to the baseline data from 2002 to 2004 and on the genotyping characteristics; the clinical outcome after treatment with AL did not link a particular genotype with treatment failure; observed changes do not provide sufficient evidence for a treatment policy change, but they suggest that a carefully monitoring is needed in this area.