Search

Background Decreased efficacy of artemisinin-based combination therapies (ACTs) during Plasmodium falciparum malaria attack has been previously reported in patients with sickle cell disease (SCD). The main purpose of this study was to investigate the in vitro susceptibility of isolates to DHA to find out hypothesis backing up the reason of this treatment failure.Method Isolates from patients attending health centers in Abidjan with uncomplicated P.falciparum malaria were collected. Hemoglobin type has been identified and in vitro drug sensitivity tests were conducted with the Ring Stage Assay and maturation inhibition assay.Results 134 isolates were selected. Parasitemia and hemoglobin level at inclusion were lower in patients with hemoglobin HbSS and HbSC than in patients with normal HbAA.

BackgroundPartial ACTs treatment failure in Plasmodium falciparum malaria has been previously reported in sickle cell patients. The main purpose of this study was to investigate the in vitro susceptibility of clinical isolates to DHA to find out hypothesis backing up the reason of this poor therapeutic response.ResultsA total of 134 clinical isolates from patients attending health centers in Abidjan with uncomplicated Plasmodium falciparum malaria were selected. Hemoglobin HbAS, HbSS, HbAC, HbSC and HbAA were identified. Parasitemia and hemoglobin level at inclusion were lower in sickle cell patients with major forms than in patients with normal phenotype. A significant number of parasites with survival rates ranging from 14.68 to 33.75% were observed in clinical isolates from the SS phenotype. At inclusion, these resistant clinical isolates showed lower parasite densities, and patients had lower red blood cell count and hematocrit levels compared to those with susceptible clinical isolates. A low rate of parasitic growth has more often occurred with AS sickle cell phenotype. However, the decrease in in vitro sensitivity to DHA was not associated with Kelch 13-Propeller gene polymorphism.ConclusionThis study highlights an in vitro decreased sensitivity to DHA, for clinical isolates collected from sickle cell SS patients living in Abidjan (Côte d’Ivoire), which is not related to the Pfkelch13 gene mutations. These clinical isolates may represent a health threat for sickle cell disease patients especially during crisis. Moreover, these results could suggest additional mechanisms of artemisinin resistance that need to be explored.

Correspondence: Andre T Offianan Malariology Department, Institut Pasteur de Cote d’Ivoire, PO Box 490, Abidjan 01, Cote d’Ivoire Tel +225 22 44 84 25 Fax +225 22 48 53 05 Email andre_offianan@yahoo.fr Background: The emergence of artemisinin resistance has raised concerns that the most potent antimalarial drug may be under threat. Artesunate + amodiaquine (ASAQ) and artemetherlumefantrine (AL) are respectively the firstand second-line treatments for uncomplicated falciparum malaria in Cote d’Ivoire. A comparison of the efficacy and safety of these two drug combinations was necessary to make evidence-based drug treatment policies. Methods: In an open-label, non inferiority, randomized, controlled clinical trial, children aged 6–59 months were randomized to receive ASAQ or AL. Both drug regimens were given for 3 days, and follow-up was for 28 days. The primary endpoint was the 28-day cure rates and was defined as proportion of patients with polymerase chain reaction (PCR)-corrected cure rate after 28 days of follow-up. Findings: A total of 251 patients who were attending the Ayame and Dabakala hospitals and presenting with symptomatic acute uncomplicated falciparum malaria were randomized to receive ASAQ (128) and AL (123). The intention-to-treat analysis showed effectiveness rates of 94.5% and 93.5% for ASAQ and AL, respectively on day 28. After adjustment for PCR results, these rates were 96.1% and 96.8%, respectively. On day 28, the per-protocol analysis showed effectiveness rates of 98.4% and 96.6% for ASAQ and AL, respectively. After adjustment by PCR for reinfection, these rates were 100% for each drug, and both regimens were well tolerated. Conclusion: ASAQ and AL remain efficacious treatments of uncomplicated falciparum malaria in Ivorian children 5 years after adoption. The efficacy of ASAQ and AL in Cote d’Ivoire requires, therefore, continuous monitoring and evaluation.