Abstract
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.
Highlights
Hemoglobinopathies are inherited globin disorders [24] that affect 7% of the world population. 300,000 to 400,000 children are born each year with a severe form of the disease [28]
Another study showed that artesunate and chloroquine had less activity against Plasmodium falciparum growing in alpha-thalassemia and/or HbCS (Hb Constant Spring) erythrocytes than in normal erythrocytes, while the activity of pyrimethamine was the same for all erythrocytes
This study focuses on parasite clearance in patients with hemoglobin disorders
Summary
Hemoglobinopathies are inherited globin disorders [24] that affect 7% of the world population. 300,000 to 400,000 children are born each year with a severe form of the disease [28]. Another study showed that artesunate and chloroquine had less activity against Plasmodium falciparum growing in alpha-thalassemia and/or HbCS (Hb Constant Spring) erythrocytes than in normal erythrocytes, while the activity of pyrimethamine was the same for all erythrocytes This could be due to an increased amount of antioxidant enzymes naturally found in abnormal erythrocytes, which could counterbalance the oxidative activity of artesunate [9, 32]. This suggests that patients with hemoglobinopathies may be at increased risk of inadequate response to artemisinin combination therapies (ACTs), especially in areas where parasite resistance or tolerance to artemisinin derivatives have emerged [18]. The usual time to denote artemisinin resistance is 5 h [8]
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