Protocol for a Magnetic Resonance Imaging (MRI) Study of Participants in the Fever Randomized Controlled Trial: Does fever control prevent brain injury in malaria?

Protocol for a Magnetic Resonance Imaging (MRI) Study of Participants in the Fever Randomized Controlled Trial: Does fever control prevent brain injury in malaria?
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发烧随机对照试验参与者的磁共振成像 (MRI) 研究方案:发烧控制是否可以预防疟疾引起的脑损伤?

DOI:
10.1101/2023.11.10.23298374
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发表时间:
2023
期刊:
medRxiv : the preprint server for health sciences
影响因子:
--
通讯作者:
Birbeck,GretchenL
Birbeck,GretchenL
中科院分区:
--
文献类型:
--
作者:
Chilombe,MosesB;Seydel,KarlB;Hammond,Colleen;Mwanza,Suzanna;Patel,ArchanaA;Lungu,Frank;Somwe,SomweWa;Kampondeni,Sam;Potchen,MichaelJ;McDermott,MichaelP;Birbeck,GretchenL

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尽管努力根除疟疾,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。较新的抗疟疾药物可迅速清除外周寄生虫血症并提高生存率,但死亡率仍然很高,疟疾后神经损伤并没有相应下降。2019年,在马拉维和赞比亚进行了一项随机对照试验,用对乙酰氨基酚和布洛芬积极退热治疗疟疾(Fever RCT)。我们建议在随机对照试验的背景下使用神经影像学来进一步评估积极退热治疗的神经保护作用。方法:这项观察性磁共振成像(MRI)辅助研究将获得先前参加Fever RCT的儿童在出院后1个月和12个月的神经影像学、神经发育和行为结果。分析将比较积极退热治疗组和常规护理组之间基于MRI结构异常的任何脑损伤的几率。对于没有深度镇静就无法进行影像学检查的儿童,将使用神经发育和行为结果来识别脑损伤。神经影像学是儿科中枢神经系统疟疾脑损伤后神经系统预后的一种成熟、有效的替代方法。这项MRI辅助研究将通过确定积极退热治疗是否对中枢神经系统疟疾具有神经保护作用,为Fever RCT增加价值。这也可能有助于阐明神经保护的潜在机制,并扩展FEVER RCT安全性评估。
Background 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. Methods 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. Discussion 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.
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