Background Decreased efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria 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 dihydro-artemisinin (DHA) to provide a hypothesis to explain this treatment failure. Methods Isolates were collected from patients attending health centres in Abidjan with uncomplicated P . falciparum malaria. The haemoglobin 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 obtained. Parasitaemia and haemoglobin levels at inclusion were lower in patients with haemoglobin HbSS and HbSC than in patients with normal HbAA. After ex vivo RSA and drug inhibition assays, the lowest rate of parasitic growth was found with isolates from HbAS red cells. Conversely, a significantly higher survival rate of parasites ranging from 15 to 34% were observed in isolates from HbSS. Isolates with in vitro reduced DHA sensitivity correlate with lower RBC count and haematocrit and higher parasitaemia at inclusion compared to those with isolates with normal DHA sensitivity. However, this decrease of in vitro sensitivity to DHA was not associated with Kelch 13-Propeller gene polymorphism. Conclusion This study highlights an in vitro decreased sensitivity to DHA, for isolates collected from HbSS patients, not related to the Pfkelch13 gene mutations. These results are in line with recent studies pointing out the role of the redox context in the efficacy of the drug. Indeed, SCD red cells harbour a highly different ionic and redox context in comparison with normal red cells. This study offers new insights into the understanding of artemisinin selective pressure on the malaria parasite in the context of haemoglobinopathies in Africa.

Background Partial 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.Results A 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.Conclusion This 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.

Background: Artemisinin-based treatment in malaria patients with abnormal hemoglobin may be ineffective because of their genetic particularity, which could lead to resistance. The main purpose of this study was to assess the effect of artemisinin derivatives on in vivo parasite clearance according to erythrocyte variants. In vivo response was investigated through retrospective data obtained over a 42-day artemether-lumefantrine/artesunate amodiaquine efficacy protocol conducted from 2012 to 2016. Results: A total of 770 patients in Côte d’Ivoire attending the hospitals of Anonkoua-koute (Abidjan), Petit Paris (Korhogo), Libreville (Man), Dar es salam (Bouaké), Ayamé and Yamoussoukro with acute uncomplicated falciparum malaria were selected for successful hemoglobin typing. HbAS, HbSS, HbAC, and HbSC genotypes were found. Parasite clearance time was obtained for 414 patients. In the population with abnormal hemoglobin, parasite densities on admission and parasite clearance rates were significantly lower in the HbSC group compared to HbAA (p = 0.02 and p = 0.007, respectively). After PCR correction on day 42, the acute treatment rate was 100% for each group. Parasite half-life and time for initial parasitaemia to decline by 50 and 99% were longer for the HbSC group (p < 0.05). The study also investigated the prevalence of K13-propeller polymorphisms across different hemoglobin genotype groups. A total of 185 and 63 samples were sequenced in the HbAA group and patients with abnormal Hb, respectively. Only two nonsynonymous mutations D559N and V510M were found in the HbAA group. Conclusion: Although this study proved good efficacy of artemether-lumefantrine and artesunate amodiaquine in the treatment of uncomplicated Plasmodium falciparum malaria in patients with abnormal hemoglobin, the increased delay of parasite clearance may represent a threat to health in these patients in relation with sickle cell crisis, which could support selection of parasites resistant to artemisinin.

Background: Artemisinin combination therapies have been wildly used in the treatment of uncomplicated falciparum malaria in most endemic countries. This strategy has been implemented in Cote d’Ivoire since 2005 with Artesunate + Amodiaquine (AS + AQ) and Artemether + lumefantrine (AL). The goal of this study was to assess efficacy and safety of these two drugs in two sentinel’s sites, Man and Abidjan in Cote d’Ivoire. Methods: An open label, randomized, clinical trial was conducted in Man in the west and Abidjan in the south of Cote d’Ivoire. Patients older than 6 months with uncomplicated falciparum malaria after consent were randomized in AS+AQ and AL group and were followed up for 42 days. The first endpoint was Adequate Clinical and Parasitological Response adjusted by PCR at day 42. The second endpoints were fever and parasite clearance time, crude cure rate at day 42 and safety of the two ACTs. Results: A total of 241 patients were randomized in AS+AQ (120) and AL (121) group. The crude cure rate at day 42 in PP analysis was 95.8% and 87.9% in AS+AQ and AL respectively. After correction by PCR ACPR at day 42 was 99.2% in AS+AQ group and 97.4% in AL group. The two ACTs were well tolerated. Conclusion: AS+AQ and AL remains efficacious in the uncomplicated malaria treatment in the two areas but continue monitoring is needed particularly for AL.