Chilombe Moses B, Seydel Karl B, Hammond Colleen, Mwanza Suzanna, Patel Archana A, Lungu Frank, Somwe Somwe Wa, Kampondeni Sam, Potchen Michael J, McDermott Michael P, Birbeck Gretchen L
Blantyre Malaria Project, Kamuzu University of Health Sciences, Blantyre, Malawi.
Department of Osteopathic Medical Specialties, Michigan State University, East Lansing, Michigan, USA.
medRxiv. 2023 Nov 10:2023.11.10.23298374. doi: 10.1101/2023.11.10.23298374.
Despite eradication efforts, ~135,000 African children sustained brain injuries as a result of central nervous system (CNS) malaria in 2021. Newer antimalarial medications rapidly clear peripheral parasitemia and improve survival, but mortality remains high with no associated decline in post-malaria neurologic injury. A randomized controlled trial of aggressive antipyretic therapy with acetaminophen and ibuprofen (Fever RCT) for malarial fevers being conducted in Malawi and Zambia began enrollment in 2019. We propose to use neuroimaging in the context of the RCT to further evaluate neuroprotective effects of aggressive antipyretic therapy.
This observational magnetic resonance imaging (MRI) ancillary study will obtain neuroimaging and neurodevelopmental and behavioral outcomes in children previously enrolled in the Fever RCT at 1- and 12-months post discharge. Analysis will compare the odds of any brain injury between the aggressive antipyretic therapy and usual care groups based upon MRI structural abnormalities. For children unable to undergo imaging without deep sedation, neurodevelopmental and behavioral outcomes will be used to identify brain injury.
Neuroimaging is a well-established, valid proxy for neurological outcomes after brain injury in pediatric CNS malaria. This MRI ancillary study will add value to the Fever RCT by determining if treatment with aggressive antipyretic therapy is neuroprotective in CNS malaria. It may also help elucidate the underlying mechanism(s) of neuroprotection and expand upon FEVER RCT safety assessments.
尽管开展了根除工作，但2021年仍有约13.5万名非洲儿童因中枢神经系统（CNS）疟疾而遭受脑损伤。新型抗疟药物能迅速清除外周血寄生虫血症并提高生存率，但死亡率仍然很高，且疟疾后神经损伤并未随之下降。一项在马拉维和赞比亚针对疟疾发热进行的对乙酰氨基酚和布洛芬积极退热治疗随机对照试验（发热随机对照试验）于2019年开始招募患者。我们建议在该随机对照试验的背景下使用神经影像学，以进一步评估积极退热治疗的神经保护作用。
这项观察性磁共振成像（MRI）辅助研究将在先前参与发热随机对照试验的儿童出院后1个月和12个月时获取神经影像学以及神经发育和行为结果。分析将基于MRI结构异常情况比较积极退热治疗组和常规治疗组发生任何脑损伤的几率。对于在未深度镇静的情况下无法接受成像检查的儿童，将使用神经发育和行为结果来确定脑损伤情况。
神经影像学是小儿中枢神经系统疟疾脑损伤后神经学结果的一种成熟且有效的替代指标。这项MRI辅助研究将通过确定积极退热治疗在中枢神经系统疟疾中是否具有神经保护作用，为发热随机对照试验增添价值。它还可能有助于阐明神经保护的潜在机制，并扩展发热随机对照试验的安全性评估。
