Treatment of Fever Due to Malaria With Ibuprofen

Randomised, Double-Blind, Placebo Controlled Study of the Antipyretic Effect of Ibuprofen in Children With Uncomplicated Malaria

Drugs to treat fever are widely used in children with fever. But there is a controversy about the benefit of reducing fever in children with malaria. Ibuprofen is often used to treat malarial fever. This study evaluates the capacity of ibuprofen to reduce fever in malaria. The effect of ibuprofen on fever compared to only mechanical measures is investigated in children with malaria.

Fever is the most apparent clinical manifestation of Plasmodium falciparum infection during the acute phase. The role of fever in defence against malaria or in other infectious diseases remains unclear. However, it has been shown that febrile temperatures inhibit the growth of P. falciparum in vitro. Antipyretic drugs are commonly and widely used to treat malarial fever in endemic areas. There is however a controversy about the benefit of reducing fever in children with malaria. Data from Gabon have revealed that neither paracetamol, nor naproxen or metamizol - antipyretics often used in this area - had an effect on fever clearance time. Worryingly, paracetamol increased parasite-clearance times (i.e. inhibited clearance of parasites) and decreased significantly the production of oxygen radicals and tumour necrosis factor (TNF), mechanisms of the innate immune response, pivotal to combat infections. Another antipyretic drug often used to treat malarial fever in endemic areas is ibuprofen. However, the rationale of its use and its capacity of reducing fever due to P. falciparum infections has never been proven in this area. Comparison: The effect of ibuprofen plus mechanical fever "treatment" (continuous fanning, tepid sponging, and cooling blankets) is compared to mechanical treatment alone to treat fever in children with malaria.

Inclusion Criteria: Uncomplicated falciparum malaria Asexual parasitaemia between 20,000 and 200,000/µL Fever with temperature above 38 °C or history of fever during the preceding 24 hours Informed consent Exclusion Criteria: Effective anti-malarial treatment for the present attack Antipyretic use within 6 hours of presentation Contraindications to the use of ibuprofen (history of asthma, dyspeptic symptoms, gastro-intestinal bleeding, or allergy to ibuprofen) Mixed plasmodial infection Haemoglobin < 7 g/dL Packed-cell volume < 20% White cell count > 16,000/L Platelet count < 40,000/µL Schizontaemia > 50/µL Impaired consciousness Convulsions or history of convulsions Concomitant diseases masking assessment of response

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