Prolonged macrophage activation and persistent anaemia in children with complicated malaria

Trop Med Int Health. 1998 Jan;3(1):60-5. doi: 10.1046/j.1365-3156.1998.00168.x.


Objective: To determine if prolonged immune activation may be associated with the persistence of anaemia after treatment for severe malaria, we measured serum concentrations of neopterin and interleukin-4 during one week of antimalarial therapy and determined haemoglobin levels one month later. Neopterin is a clinically valuable marker for monitoring activation of macrophages by gamma-interferon and thus reflects the TH-1 immune response. Interleukin-4 is a major cytokine that tends to be inhibited by TH-1 activity.

Method: The study population consisted of 26 Zambian children < 6 years of age who presented with cerebral malaria to a rural hospital in 1994 and who were treated with quinine for seven days. Six children (23%) were anaemic (haemoglobin < 11 g/dl) one month after completing antimalarial therapy.

Results: On admission, concentrations of neopterin were markedly elevated in all patients. During the seven days of anti-malarial therapy, neopterin levels remained elevated in the 6 children who proved to have persistent anaemia one month after finishing treatment but declined significantly (P = 0.008) in the 20 children who corrected their haemoglobin levels by that time. Conversely, interleukin-4 levels declined in the children with persistent anaemia (P = 0.043) but not in the other children.

Conclusion: Persistence of the TH-1 mediated immune response and associated activation of macrophages may be involved in the pathogenesis of lingering anaemia after treatment of malaria.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Anemia / complications
  • Anemia / immunology*
  • Antimalarials / therapeutic use
  • Child, Preschool
  • Deferoxamine / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Hemoglobins / analysis
  • Humans
  • Infant
  • Interleukin-10 / blood
  • Interleukin-4 / blood
  • Interleukin-6 / blood
  • Macrophage Activation*
  • Malaria, Cerebral / complications*
  • Malaria, Cerebral / drug therapy
  • Malaria, Cerebral / immunology
  • Male
  • Neopterin / blood
  • Pyrimethamine / therapeutic use
  • Quinine / therapeutic use
  • Retrospective Studies
  • Sulfadoxine / therapeutic use


  • Antimalarials
  • Hemoglobins
  • Interleukin-6
  • Interleukin-10
  • Interleukin-4
  • Neopterin
  • Sulfadoxine
  • Quinine
  • Deferoxamine
  • Pyrimethamine