Plasmodium falciparum clearance is rapid and pitting independent in immune Malian children treated with artesunate for malaria

J Infect Dis. 2015 Jan 15;211(2):290-7. doi: 10.1093/infdis/jiu427. Epub 2014 Sep 2.


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.

Keywords: Plasmodium falciparum; acquired immunity; artemisinin; malaria; parasite clearance; pitting; spleen.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antimalarials / therapeutic use*
  • Artemisinins / therapeutic use*
  • Artesunate
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Humans
  • Infant
  • Malaria, Falciparum / drug therapy*
  • Malaria, Falciparum / immunology*
  • Male
  • Mali
  • Parasite Load
  • Parasitemia / drug therapy
  • Parasitemia / parasitology
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / isolation & purification
  • Retrospective Studies
  • Treatment Outcome


  • Antimalarials
  • Artemisinins
  • Artesunate