恢复期血浆
2006年6月,一名感染了HPAI H5N1病毒的31岁男性患者,注射了来自今年早些时候康复患者的恢复期血浆。3剂恢复期血浆治疗后,呼吸道样本的病毒载量下降,32小时内低于检测水平。[127]Zhou B, Zhong N, Guan Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N Engl J Med. 2007;357:1450-1451.http://www.nejm.org/doi/full/10.1056/NEJMc070359http://www.ncbi.nlm.nih.gov/pubmed/17914053?tool=bestpractice.com还有两例接受血浆治疗的 HPAI H5N1 患者,一例血浆来自感染康复者,一例来自疫苗接种者。[128]Yu H, Gao Z, Feng Z, et al. Clinical characteristics of 26 human cases of highly pathogenic avian influenza A (H5N1) virus infection in China. PLoS One. 2008;3:e2985.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0002985http://www.ncbi.nlm.nih.gov/pubmed/18716658?tool=bestpractice.com一份系统评价评估了恢复期血浆和高度免疫性免疫球蛋白对病毒性病因引起的重度急性呼吸道感染的效果,结果表明这种治疗安全,并且可能会降低死亡率。[129]Mair-Jenkins J, Saavedra-Campos M, Baillie JK, et al. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J infect Dis. 2015;211:80-90.https://academic.oup.com/jid/article/211/1/80/799341/The-Effectiveness-of-Convalescent-Plasma-andhttp://www.ncbi.nlm.nih.gov/pubmed/25030060?tool=bestpractice.com而恢复期血浆治疗处于实验阶段,尚未批准用于临床。
静脉注射神经氨酸酶抑制剂
神经氨酸酶抑制剂的胃肠外制剂已经研发成功,包括静脉注射帕拉米韦、奥司他韦和扎那米韦的针剂,但在大多数国家没有经过注册而不能使用。目前美国已经批准将静脉使用帕拉米韦用于 18 岁及以上的非复杂性流行性感冒患者的早期治疗。静脉扎那米韦目前可作为慈善用药,通过在研新药(IND)申请使用。世卫组织建议,静脉注射神经氨酸酶抑制剂治疗应按照相关应急使用的规定使用。静脉神经氨酸酶抑制剂不建议临床试验之外使用。[109]World Health Organization. WHO guidelines for pharmacological management of pandemic (H1N1) 2009 influenza and other influenza viruses. February 2010. http://www.who.int/ (last accessed 4 May 2017).http://www.who.int/csr/resources/publications/swineflu/h1n1_use_antivirals_20090820/en/
拉尼米韦
在日本,一种全新的、用于对抗人类流感的神经氨酸酶抑制剂长效吸入剂获得批准。它在化学结构上类似于扎那米韦,在肺中转换成活性形式,并维持在较高浓度,一次性给药就可用于季节性流感的治疗。拉尼米韦对HPAI H5N1的临床疗效所知甚少,目前不推荐用于HPAI H5N1的治疗。[130]Ikematsu H, Kawai N. Laninamivir octanoate: a new long-acting neuraminidase inhibitor for the treatment of influenza. Expert Rev Anti Infect Ther. 2011;9:851-857.http://www.ncbi.nlm.nih.gov/pubmed/21973296?tool=bestpractice.com
利巴韦林
虽然在大多数国家未授权用于流感的治疗,但是在小鼠模型上已经证实它可以增加奥司他韦抗HPAI H5N1病毒的疗效。[131]Ilyushina NA, Hay A, Yilmaz N, et al. Oseltamivir-ribavirin combination therapy for highly pathogenic H5N1 influenza virus infection in mice. Antimicrob Agents Chemother. 2008;52:3889-3897.http://aac.asm.org/content/52/11/3889.fullhttp://www.ncbi.nlm.nih.gov/pubmed/18725448?tool=bestpractice.com然而,利巴韦林治疗SARS患者的研究发现,大剂量利巴韦林和进行性溶血性贫血之间存在较强关联。[132]Muller MP, Dresser L, Raboud J, et al. Adverse events associated with high-dose ribavirin: evidence from the Toronto outbreak of severe acute respiratory syndrome. Pharmacotherapy. 2007;27:494-503.http://www.ncbi.nlm.nih.gov/pubmed/17381375?tool=bestpractice.comWHO小组的结论是,其疗效或安全性的数据不足以推荐其用于治疗流感。[109]World Health Organization. WHO guidelines for pharmacological management of pandemic (H1N1) 2009 influenza and other influenza viruses. February 2010. http://www.who.int/ (last accessed 4 May 2017).http://www.who.int/csr/resources/publications/swineflu/h1n1_use_antivirals_20090820/en/
糖皮质激素
世界卫生组织 (WHO) 不推荐在 HPAI H5N1 病毒人类感染病例的治疗中使用皮质类固醇。季节性流感病毒感染的研究表明,使用糖皮质激素与症状出现后7天后仍有持续性病毒复制相关联。[133]Lee N, Chan PK, Hui DS, et al. Viral loads and duration of viral shedding in adult patients hospitalized with influenza. J Infect Dis. 2009;200:492-500.http://www.ncbi.nlm.nih.gov/pubmed/19591575?tool=bestpractice.com一项研究报告说,2009年H1N1病毒感染期间,早期使用糖皮质激素是病情危重甚至死亡的危险因素。[134]Han K, Ma H, An X, et al. Early use of glucocorticoids was a risk factor for critical disease and death from pH1N1infection. Clin Infect Dis. 2011;53:326-333.http://www.ncbi.nlm.nih.gov/pubmed/21810744?tool=bestpractice.com糖皮质激素可用于其他适应症(例如,哮喘发作,肾上腺机能不全,早产)。