Prolonged macrophage activation and persistent anaemia in children with complicated malaria

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 2.0 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.