title: Plasmodium falciparum clearance rates in response to artesunate in Malian children with malaria: effect of acquired immunity.
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.
  
  
  BACKGROUND
  NCT00669084.
authors: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors: Tatiana M
authors: TM
authors: Lopera-Mesa
authors: Saibou
authors: S
authors: Doumbia
authors: Serena
authors: S
authors: Chiang
authors: Amir E
authors: AE
authors: Zeituni
authors: Drissa S
authors: DS
authors: Konate
authors: Mory
authors: M
authors: Doumbouya
authors: Abdoul S
authors: AS
authors: Keita
authors: Kasia
authors: K
authors: Stepniewska
authors: Karim
authors: K
authors: Traore
authors: Seidina A S
authors: SA
authors: Diakite
authors: Daouda
authors: D
authors: Ndiaye
authors: Juliana M
authors: JM
authors: Sa
authors: Jennifer M
authors: JM
authors: Anderson
authors: Michael P
authors: MP
authors: Fay
authors: Carole A
authors: CA
authors: Long
authors: Mahamadou
authors: M
authors: Diakite
authors: Rick M
authors: RM
authors: Fairhurst
mesh_terms: D056704:Adaptive Immunity; D000293:Adolescent; D000655:Amodiaquine / Q000008:administration & dosage; D000913:Antibodies, Protozoan / Q000097:blood; D000962:Antimalarials / Q000008:administration & dosage*; D037621:Artemisinins / Q000008:administration & dosage*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D008302:Mali; D059208:Parasite Load; D018512:Parasitemia / Q000188:drug therapy / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000913:Antibodies, Protozoan; D000962:Antimalarials; D037621:Artemisinins; D007074:Immunoglobulin G; D000655:Amodiaquine; D000077332:Artesunate