Plasmodium falciparum clearance rates in response to artesunate in Malian children with malaria: effect of acquired immunity
Tatiana M Lopera-Mesa, Saibou Doumbia, Serena Chiang, Amir E Zeituni, Drissa S Konate, Mory Doumbouya, Abdoul S Keita, Kasia Stepniewska, Karim Traore, Seidina A S Diakite, Daouda Ndiaye, Juliana M Sa, Jennifer M Anderson, Michael P Fay, Carole A Long, Mahamadou Diakite, Rick M Fairhurst, Tatiana M Lopera-Mesa, Saibou Doumbia, Serena Chiang, Amir E Zeituni, Drissa S Konate, Mory Doumbouya, Abdoul S Keita, Kasia Stepniewska, Karim Traore, Seidina A S Diakite, Daouda Ndiaye, Juliana M Sa, Jennifer M Anderson, Michael P Fay, Carole A Long, Mahamadou Diakite, Rick M Fairhurst
Abstract
Background: Artemisinin resistance, a long parasite clearance half-life in response to artemisinin, has been described in patients with Plasmodium falciparum malaria in southeast Asia. Few baseline half-lives have been reported from Africa, where artemisinins were recently introduced.
Methods: We treated P. falciparum malaria in 215 Malian children aged 0.5-15 years with artesunate (0, 24, 48 hours) and amodiaquine (72, 96, 120 hours). We estimated half-life by measuring parasite density every 6 hours until undetectable and evaluated the effects of age, sex, ethnicity, and red blood cell (RBC) polymorphisms on half-life. We quantified the proportion of parasitized RBCs recognized by autologous immunoglobulin G (IgG).
Results: The geometric mean half-life was 1.9 hours (95% confidence interval, 1.8-2.0) and did not correlate with parasite ex vivo susceptibility to artemisinins. In a linear model accounting for host factors, half-life decreased by 4.1 minutes for every 1-year increase in age. The proportion of parasitized RBCs recognized by IgG correlated inversely with half-life (r = -0.475; P = .0006).
Conclusions: Parasite clearance in response to artesunate is faster in Mali than in southeast Asia. IgG responses to parasitized RBCs shorten half-life and may influence this parameter in areas where age is not an adequate surrogate of immunity and correlates of parasite-clearing immunity have not been identified.
Clinical trials registration: NCT00669084.
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Source: PubMed