Prolonged macrophage activation and persistent anaemia in children with complicated malaria

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.

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.

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.

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.