Molecular analysis of markers associated with chloroquine and sulfadoxine/pyrimethamine resistance in Plasmodium falciparum malaria parasites from southeastern C te-d'Ivoire by the time of Artemisinin-based Combination Therapy adoption in 2005

lecular analysis of markers associated with chloroquine and sulfadoxine/pyrimethamine resistance in Plasmodium falciparum malaria parasites from southeastern C te-d'Ivoire by the time of Artemisinin-based Combination Therapy adoption in 2005 Original Research (1325) Total Article Views Authors: Ako BA, Offianan AT, Johansson M, Penali LK, Nguetta SP, Sibley CH Published Date August 2012 Volume 2012:5 Pages 113 - 120 DOI: http://dx.doi.org/10.2147/IDR.S31409 Received: 03 March 2012 Accepted: 07 May 2012 Published: 01 August 2012 Berenger Aristide Ako,1 André Toure Offianan,1 Marnie Johansson,2 Louis Koné Penali,1 Simon-Pierre Assanvo Nguetta,3 Carol Hopkin Sibley2 1Department of Malariology, Institut Pasteur de C te-d'Ivoire, Abidjan, C te d'Ivoire; 2Department of Genome Sciences, University of Washington, Seattle, WA, USA; 3Laboratoire de Génétique, Université de Cocody, Abidjan, C te d'Ivoire Purpose: Artemisin-based combination therapies became the recommended therapy in C te-d'Ivoire in 2005, but both chloroquine (CQ) and sulfadoxine/pyrimethamine (SP) have been heavily used for many decades. Despite this long history, little is known about the geographical distribution of drug resistance–conferring genotypes outside the capital city of Abidjan. In this work, we compared the prevalence of drug-resistant genotypes in Bonoua, an urban area, and Samo, a rural agricultural area, in southeastern C te-d'Ivoire, about 59 km from Abidjan. Patients and methods: Samples were collected from symptomatic patients in both sites during the rainy season in 2005. Genomic DNA was isolated and codons associated with resistance to CQ and SP were analyzed: pfcrt codons Cys-72-Ser, Val-73-Val, Met-74-Ile, Arg-75-Glu, Lys-76-Thr; pfdhfr codons Ala-16-Val, Arg-51-Ile, Cys-59-Arg, Ser-108-Arg/Thr, and Ile-164-Leu; pfdhps codons Ser-436-Ala, Ala-437-Gly, Lys-540-Glu, Ala-581-Gly, and Ala-613-Thr/Ser. Results: A limited number of genotypes were found in Bonoua compared with Samo. In both sites, the triple-mutant allele CVIET of pfcrt predominated: 100% in Bonoua and 86.2% in Samo. The wild-type allele, NCSI of pfdhfr, was common – 50% in Bonoua and 38.7% in Samo – but the triple-mutant IRNI and double-mutant NRNI were also frequent (IRNI, 32.6% in Bonoua and 19.4% in Samo; NRNI, 15.2% in Bonoua and 9.7% in Samo). In Samo, a wide range of different genotypes of Pfdhps was observed, with alleles carrying the Gly-437 codon fixed in Bonoua and comprising 73% of the isolates in Samo. Conclusion: Although these two sites are only 8 km apart, they belonged to very different ecological environments. The overall prevalence of alleles of single-nucleotide polymorphisms associated with resistance to CQ and SP in both locations was among the highest of the region by 2005, although the more rural site showed a more diverse set of alleles and mixed infections. Continued surveillance of these markers will be a useful tool for drug policy, as both CQ and SP are still frequently used ye