RESUMO
INTRODUCTION: Parasite clearance is useful to detect artemisinin resistance. The aim of this study was to investigate parasite clearance in patients treated with artesunate + amodiaquine (AS + AQ) and artemether + lumefantrine (AL): the two artemisinin-based combination therapies (ACTs) recommended in the first-line treatment of uncomplicated malaria in Côte d'Ivoire. METHODS: This study was conducted in Bouaké, Côte d'Ivoire, from April to June 2016. Patients aged at least 6 months with uncomplicated malaria and treated with AS + AQ or AL were hospitalized for 3 days, and follow-up assessments were performed on days 3, 7, 14, 21, 28, 35, and 42. Blood smears were collected at the time of screening, pre-dose, and 6-hour intervals following the first dose of administration until two consecutive negative smears were recorded, thereafter at day 3 and follow-up visits. Parasite clearance was determined using the Worldwide Antimalarial Resistance Network's parasite clearance estimator. The primary end points were parasite clearance rate and time. RESULTS: A total of 120 patients (57 in the AS + AQ group and 63 in the AL group) were randomized among 298 patients screened. The median parasite clearance time was 30 hours (IQR, 24-36 hours), for each ACT. The median parasite clearance rate had a slope half-life of 2.36 hours (IQR, 1.85-2.88 hours) and 2.23 hours (IQR, 1.74-2.63 hours) for AS + AQ and AL, respectively. The polymerase chain reaction-corrected adequate clinical and parasitological response was 100% and 98.07% at day 42 for AS + AQ and AL, respectively. CONCLUSION: Patients treated with AS + AQ and AL had cleared parasites rapidly. ACTs are still efficacious in Bouaké, Côte d'Ivoire, but continued efficacy monitoring of ACTs is needed.
RESUMO
PURPOSE: Artemisin-based combination therapies became the recommended therapy in Côte-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 Côte-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 years after withdrawal, and SP is recommended by the World Health Organization for intermittent preventive therapy for pregnant women and infants. Data analyzed herein are among the first to be generated during the year of artemisin-based combination-therapy introduction in Côte-d'Ivoire and could be of some interest for malaria policy-makers.
