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Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria
C H Brandts1, M Ndjavé, W Graninger
1Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon.
Insights
Paracetamol offers no fever reduction benefit for children with malaria and may prolong parasite clearance. This study suggests avoiding routine paracetamol use in pediatric malaria cases.
Area of Science:
- Pediatric Infectious Diseases
- Malariology
- Pharmacology
Background:
- Routine fever management in children with infectious diseases, including malaria, is controversial.
- Millions of children with Plasmodium falciparum malaria receive paracetamol alongside antimalarial drugs, despite unproven benefits.
Purpose of the Study:
- To evaluate the efficacy of paracetamol as an adjunct to mechanical antipyresis in children with Plasmodium falciparum malaria.
- To investigate the impact of paracetamol on fever clearance, parasite clearance, and inflammatory markers.
Main Methods:
- A randomized trial involving 50 children with P. falciparum malaria in Gabon.
- Comparison of mechanical antipyresis alone versus mechanical antipyresis with paracetamol.
- Monitoring of rectal temperature, parasitaemia, plasma cytokine concentrations (TNF, IL-6), and oxygen radical production.
Main Results:
- No significant difference in fever clearance time between groups (32h vs 43h).
- Paracetamol significantly prolonged parasite clearance time by 16 hours (p=0.004).
- Lower induced tumor necrosis factor (TNF) and reduced oxygen radical production observed in the paracetamol group.
Conclusions:
- Paracetamol provides no additional antipyretic benefit over mechanical methods for P. falciparum malaria.
- Paracetamol may negatively impact malaria parasite clearance, potentially due to reduced TNF and oxygen radical production.
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.