Antipyretic therapy effectively lowers temperature and seizure risk in children with CNS malaria: JAMA

A recent study published in the Journal of American Medical Association highlighted an innovative treatment approach revealed promising outcomes in children with malaria and neurological involvement. The randomized clinical trial compared aggressive antipyretic therapy using both acetaminophen and ibuprofen against the standard care (acetaminophen alone) in children with central nervous system (CNS) malaria.

Malaria remains a critical health challenge in many parts of the world and its neurological complications lead to severe sequelae in children. Identifying effective treatments to reduce these outcomes is crucial. Thereby, this study analyzed whether aggressive antipyretic therapy could reduce the risk factors associated with neurological sequelae like high maximum temperature (Tmax) and seizures.

The trial was conducted across two hospitals in Zambia and one in Malawi by targeting children aged 2 to 11 years diagnosed with CNS malaria. Children with creatinine levels above 1.2 mg/dL were excluded from this study. The study enrolled a total of 256 participants from 2019 to 2022 with data analysis between December 2022 and April 2023.

The participants in the aggressive antipyretic group received a combination of acetaminophen and ibuprofen every six hours for 72 hours, irrespective of their temperature. However, the standard care group was administered acetaminophen only when their temperature reached 38.5°C or higher. The maximum temperature (Tmax) over the 72-hour period was the primary outcome measured. The aggressive antipyretic group demonstrated a significantly lower Tmax which averaged to 38.6°C when compared to 39.2°C in the usual care group. This reduction in Tmax aligned with temperatures observed in children without neurological impairments in previous studies.

The aggressive antipyretic therapy significantly reduced the odds of facing multiple or prolonged seizures. Only 8% of children in the aggressive therapy group had such seizures when compared to 27% in the usual care group. Also, no significant difference was observed between the two groups in terms of parasite clearance time. However, the incidence of severe adverse events was reduced in the aggressive antipyretic group (12%) when compared to the usual care group (20%). The aggressive antipyretic group also faced fewer deaths (3 against 10) which indicated a potentially safer profile for this treatment approach.

The outcomes suggests that aggressive antipyretic therapy can effectively lower Tmax and reduce the incidence of seizures in children with CNS malaria without increasing the parasitemia duration. Further research and potential changes in treatment protocols for pediatric malaria are imperative for aggressively managing fever and seizures to improve long-term health outcomes.

Reference:

Birbeck, G. L., Seydel, K. B., Mwanza, S., Tembo, D., Chilombe, M., Watts, A., Ume-Ezeoke, I., Mathews, M., Patel, A. A., Mwenechanya, M., Pensulo, P., & McDermott, M. P. (2024). Acetaminophen and Ibuprofen in Pediatric Central Nervous System Malaria. In JAMA Neurology. American Medical Association (AMA). https://doi.org/10.1001/jamaneurol.2024.1677