title: Plasmodium falciparum clearance is rapid and pitting independent in immune Malian children treated with artesunate for malaria.
abstract: BACKGROUND
  In Plasmodium falciparum-infected patients treated with artemisinins, parasitemia declines through so-called pitting, an innate splenic process that transforms infected red blood cells (iRBCs) into once-infected RBCs (O-iRBCs).
  
  
  METHODS
  We measured pitting in 83 French travelers and 42 Malian children treated for malaria with artesunate.
  
  
  RESULTS
  In travelers, O-iRBCs peaked at 107.7% initial parasitemia. In Malian children aged 1.5-4 years, O-iRBCs peaked at higher concentrations than in children aged 9-13 years (91.60% vs 31.95%; P = .0097). The parasite clearance time in older children was shorter than in younger children (P = .0001), and the decline in parasitemia in children aged 1.5-4 years often started 6 hours after treatment initiation, a lag phase generally absent in infants and older children. A 6-hour lag phase in artificial pitting of artesunate-exposed iRBCs was also observed in vitro. The proportion of iRBCs recognized by autologous immunoglobulin G (IgG) correlated with the parasite clearance time (r = -0.501; P = .0006) and peak O-iRBC concentration (r = -0.420; P = .0033).
  
  
  CONCLUSIONS
  Antimalarial immunity correlates with fast artemisinin-induced parasite clearance and low pitting rates. In nonimmune populations, artemisinin-induced P. falciparum clearance is related to pitting and starts after a 6-hour lag phase. In immune populations, passively and naturally acquired immune mechanisms operating faster than pitting may exist. This mechanism may mitigate the emergence of artemisinin-resistant P. falciparum in Africa.
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, INSERM U1135, UPMC CR7, CNRS ERL 8255 Centre National de Référence du Paludisme site Pitié-Salpêtrière Laboratory of Excellence GR-Ex.
authors.forename: Papa Alioune
authors.initials: PA
authors.lastname: Ndour
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Lopera-Mesa
authors.affiliation: Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Odonto-stomatology, University of Bamako, Mali.
authors.forename: Seidina A S
authors.initials: SA
authors.lastname: Diakité
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Serena
authors.initials: S
authors.lastname: Chiang
authors.affiliation: AP-HP, Hôpital Pitié-Salpêtrière, Service de Parasitologie-Mycologie et Service des Maladies Infectieuses et Tropicales, Paris, France.
authors.forename: Oussama
authors.initials: O
authors.lastname: Mouri
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, INSERM U1135, UPMC CR7, CNRS ERL 8255.
authors.forename: Camille
authors.initials: C
authors.lastname: Roussel
authors.affiliation: Centre National de Référence du Paludisme site Pitié-Salpêtrière AP-HP, Hôpital Pitié-Salpêtrière, Service de Parasitologie-Mycologie et Service des Maladies Infectieuses et Tropicales, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jauréguiberry
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, INSERM U1135, UPMC CR7, CNRS ERL 8255 Centre National de Référence du Paludisme site Pitié-Salpêtrière.
authors.forename: Sylvestre
authors.initials: S
authors.lastname: Biligui
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, INSERM U1135, UPMC CR7, CNRS ERL 8255 Centre National de Référence du Paludisme site Pitié-Salpêtrière.
authors.forename: Eric
authors.initials: E
authors.lastname: Kendjo
authors.affiliation: Centre for Immunity, Infection and Evolution, University of Edinburgh, United Kingdom.
authors.forename: Antoine
authors.initials: A
authors.lastname: Claessens
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, INSERM U1135, UPMC CR7, CNRS ERL 8255 Centre National de Référence du Paludisme site Pitié-Salpêtrière.
authors.forename: Liliane
authors.initials: L
authors.lastname: Ciceron
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, INSERM U1135, UPMC CR7, CNRS ERL 8255 Centre National de Référence du Paludisme site Pitié-Salpêtrière AP-HP, Hôpital Pitié-Salpêtrière, Service de Parasitologie-Mycologie et Service des Maladies Infectieuses et Tropicales, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, INSERM U1135, UPMC CR7, CNRS ERL 8255 Centre National de Référence du Paludisme site Pitié-Salpêtrière AP-HP, Hôpital Pitié-Salpêtrière, Service de Parasitologie-Mycologie et Service des Maladies Infectieuses et Tropicales, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Thellier
authors.affiliation: Malaria Research and Training Center, Faculty of Medicine, Pharmacy and Odonto-stomatology, University of Bamako, Mali.
authors.forename: Mahamadou
authors.initials: M
authors.lastname: Diakité
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Fairhurst
authors.affiliation: Centre d'Immunologie et des Maladies Infectieuses de Paris, INSERM U1135, UPMC CR7, CNRS ERL 8255 Centre National de Référence du Paludisme site Pitié-Salpêtrière Laboratory of Excellence GR-Ex AP-HP, Hôpital Pitié-Salpêtrière, Service de Parasitologie-Mycologie et Service des Maladies Infectieuses et Tropicales, Paris, France.
authors.forename: Pierre A
authors.initials: PA
authors.lastname: Buffet
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D008302:Mali; D059208:Parasite Load; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate
keywords: Plasmodium falciparum; acquired immunity; artemisinin; malaria; parasite clearance; pitting; spleen