Background: Routine antipyretic therapy in children with infectious diseases has long been the source of controversy. Each year, in addition to antimalarial medication, millions of children with Plasmodium falciparum malaria receive paracetamol to reduce fever. However, the usefulness of this practice has not been proven.
Methods: In a randomised trial in Lambaréné, Gabon, 50 children with P falciparum malaria were treated with intravenous quinine, and received either mechanical antipyresis alone, or in combination with paracetamol. Rectal body temperature and parasitaemia were recorded every 6 h for 4 days. Plasma concentrations and inducible concentrations of tumour necrosis factor (TNF) and interleukin-6 were measured every 24 h. In addition, production of oxygen radicals was measured in both groups.
Findings: The mean fever clearance time was 32 h for children treated with paracetamol and 43 h for those who received mechanical antipyresis alone; however, this 11 h difference was not significant (95% CI -2 to 24 h; p = 0.176). Parasite clearance time was significantly prolonged in patients who received paracetamol with a difference of 16 h (8-24 h; p = 0.004). Plasma concentrations of TNF and interleukin-6 were similar in both groups during the study. However, the induced concentrations of TNF, and the production of oxygen radicals, were significantly lower in children treated with paracetamol than those who received mechanical antipyresis alone.
Interpretation: These data suggest that paracetamol has no antipyretic benefits over mechanical antipyresis alone in P falciparum malaria. Moreover, paracetamol prolongs parasite clearance time, possibly by decreased production of TNF and oxygen radicals.
PIP: Although paracetamol is routinely used to control fever in African children with Plasmodium falciparum, the usefulness of this treatment has not been established. In a randomized clinical trial, 50 children 2-7 years of age from Lambarene, Gabon, with P. falciparum malaria were treated with intravenous quinine and received either mechanical antipyresis alone (electric fanning, tepid sponging, and cool blankets) or in combination with paracetamol. The mean fever clearance time was 32 hours for children treated with paracetamol and 43 hours for those who received antipyresis alone--a nonsignificant difference. Parasite clearance time was significantly prolonged (by an average of 16 hours) in children who received paracetamol. Although plasma concentrations of tumor necrosis factor and interleukin-6 were similar in both groups, induced concentrations of tumor necrosis factor and the production of oxygen radicals were significantly lower in paracetamol-treated children. Overall, these findings indicate that paracetamol confers no benefits over mechanical antipyresis alone and actually prolongs parasite clearance time. Further studies are required, however, before recommendations for ancillary treatment can be changed.