Shayan Ahmed, Jamia Millia Islamia, New Delhi
Pediatric Severe Malaria:
Malaria continues to be a major source of illness and mortality in children, with an estimated 272,000 deaths in children under the age of five worldwide in 2018. Cerebral Malaria (CM) and Severe Malarial Anaemia (SMA) are two frequent symptoms of pediatric Severe Malaria (SM) in Ugandan children. CM is linked to a high rate of mortality (18-21%), as well as neurologic sequelae and difficulties with cognition, attention, memory, and behavior in children. When compared to community children, children with SMA have a higher risk of post-discharge morbidities, such as recurrent hospitalizations, poorer cognitive functioning, and more behavioral difficulties.
After clinical trials showed that artesunate was superior to quinine in terms of parasite clearance and mortality, the World Health Organization recommended intravenous artesunate as the first-line treatment for SM in 2011. However, the focus of this research was on inpatient outcomes. Post-discharge evidence comparing long-term clinical, cognitive, and behavioral outcomes after therapy with artesunate or quinine is sparse.
Artesunate versus Quinine:
A prospective cohort study of children with Pediatric Severe Malaria (SM) was recently undertaken to examine mortality and long-term outcomes following treatment with quinine or artemisinin derivatives. In Uganda, artesunate was introduced as the first-line treatment for SM at the same time. The influence of artemisinin derivatives on long-term clinical, cognitive, and behavioral outcomes in children with severe malaria is assessed in this post hoc analysis. This current investigation indicates that artesunate is more effective than quinine in treating severe malaria.
According to researchers, in comparison to quinine, artemisinin derivatives were linked to less acute neurologic impairments in children with cerebral malaria and improved long-term behavioral and executive function outcomes in preschool children with severe malaria. Artemisinin derivatives were linked to less neurologic impairments upon discharge in children with CM than quinine, as well as improved internalizing and externalizing behaviors and executive function over two years in children with CM or SMA. Anti-malarial therapy did not affect general cognition, attention, or associative memory. After accounting for demographic, socioeconomic risk factors, illness severity, and other variables that may influence these outcomes, the disparities in behavior and executive function remained substantial.
Artesunate Downregulates Inflammation:
Treatment of CM with artesunate reduced pro-inflammatory cytokine production in the hippocampus reduced astrocyte and microglia activation, and down-regulated several inflammasome pathways in mice. In a model of traumatic brain injury, it also altered neurotropic factors that impact neuronal survival, including brain-derived neurotropic factor, which has been linked to the severity of CM. During key times of brain development and maturation, systemic and persistent inflammatory responses can impair development, particularly in myelinated pathways in the frontal lobe. Furthermore, systemic inflammation can redirect nutrients required for brain growth (e.g., iron and amino acids). The frontal lobe regulates executive function and behavior, whereas association regions of the brain such as the temporal, parietal, and occipital lobes govern cognition. Through one or more of these mechanisms, artesunate may be able to protect executive function and enhance behavioral outcomes. Future research should look at the mechanisms through which artesunate impacts behavior and executive function.
Significance of Study:
The study demonstrates that children treated with artemisinin derivatives for severe malaria had a lower death rate than children treated with quinine. Researchers discovered that survivors treated with artesunate had superior neurobehavioral and executive function than those treated with quinine. The data show that artesunate when compared to quinine therapy, not only decreases mortality in children with severe malaria but also may give a long-term advantage in behavioral and executive function in survivors.
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Reference:
- Conroy, A. L., Opoka, R. O., Bangirana, P., Namazzi, R., Okullo, A. E., Georgieff, M. K., Cusick, S., Idro, R., Ssenkusu, J. M., & John, C. C. (2021). Parenteral artemisinins are associated with reduced mortality and neurologic deficits and improved long-term behavioral outcomes in children with severe malaria. BMC medicine, 19(1), 168. https://doi.org/10.1186/s12916-021-02033-1
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Author info:
Shayan Ahmed is currently pursuing a Master of Science degree in Microbiology from the Department of Biosciences, Jamia Millia Islamia, New Delhi. His area of research interest lies in antibiotic resistance and associated molecular mechanisms. His recent work was focused on understanding colistin resistance patterns in the environment, particularly in water bodies.
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