A Preliminary Randomized Double Blind Placebo-Controlled Trial of Intravenous Immunoglobulin for Japanese Encephalitis in Nepal
A Preliminary Randomized Double Blind Placebo-Controlled Trial of Intravenous Immunoglobulin for Japanese Encephalitis in Nepal
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DOI：
10.1371/journal.pone.0122608
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发表时间：
2015-04-17
期刊：
影响因子：
3.7
通讯作者：
Solomon, Tom
中科院分区：
文献类型：
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作者：
Rayamajhi, Ajit;Nightingale, Sam;Solomon, Tom
背景日本脑炎（JE）病毒（JEV）是一种在亚洲发现的蚊媒黄病毒，与西尼罗河病毒密切相关。目前还没有针对任何黄病毒的已知抗病毒治疗方法。体外研究和动物模型的结果表明，含有病毒特异性中和抗体的静脉注射免疫球蛋白（IVIG）可能有效改善病毒性脑炎的预后。 IVIG 的抗炎特性也可能是有益的。 方法/主要发现 我们在尼泊尔的两个地点对疑似乙型脑炎的儿童进行了一项可行性随机双盲安慰剂对照试验，试验中含有抗 JEV 中和抗体（ImmunoRel，400mg/kg/天，持续 5 天）；我们还检查了对血清中和抗体滴度和细胞因子谱的影响。招募了 22 名儿童，其中 13 名确诊乙脑； 11 人接受 IVIG 治疗，11 人接受安慰剂，没有违反方案。一名儿童（IVIG 组）在治疗期间死亡，两名儿童（安慰剂组）在出院后死亡。总体而言，出院或随访时治疗组之间的结果没有差异。乙型脑炎病毒阴性儿童中观察到抗乙型脑炎病毒抗体的被动转移。使用 IVIG 治疗的 JEV 阳性儿童的 JEV 特异性中和抗体滴度比使用安慰剂治疗的儿童高约 16 倍 (p=0.2)，这超出了仅用被动转移所能解释的程度。 IVIG 组中 IL-4 和 IL-6 较高。 结论/意义 在尼泊尔进行 IVIG 治疗乙脑试验是可行的。 IVIG 可能会增强 JEV 阳性患者中和抗体的产生。 IVIG 似乎是乙脑治疗的一个有吸引力的选择，值得进一步研究。
BackgroundJapanese encephalitis (JE) virus (JEV) is a mosquito-borne flavivirus found across Asia that is closely related to West Nile virus. There is no known antiviral treatment for any flavivirus. Results from in vitro studies and animal models suggest intravenous immunoglobulin (IVIG) containing virus-specific neutralizing antibody may be effective in improving outcome in viral encephalitis. IVIG's anti-inflammatory properties may also be beneficial.Methodology/PrincipalFindings We performed a pilot feasibility randomized double-blind placebo-controlled trial of IVIG containing anti-JEV neutralizing antibody (ImmunoRel, 400mg/kg/day for 5 days) in children with suspected JE at two sites in Nepal; we also examined the effect on serum neutralizing antibody titre and cytokine profiles. 22 children were recruited, 13 of whom had confirmed JE; 11 received IVIG and 11 placebo, with no protocol violations. One child (IVIG group) died during treatment and two (placebo) subsequently following hospital discharge. Overall, there was no difference in outcome between treatment groups at discharge or follow up. Passive transfer of anti-JEV antibody was seen in JEV negative children. JEV positive children treated with IVIG had JEV-specific neutralizing antibody titres approximately 16 times higher than those treated with placebo (p=0.2), which was more than could be explained by passive transfer alone. IL-4 and IL-6 were higher in the IVIG group.Conclusions/SignificanceA trial of IVIG for JE in Nepal is feasible. IVIG may augment the development of neutralizing antibodies in JEV positive patients. IVIG appears an appealing option for JE treatment that warrants further study.