A non-randomized multicentre trial of human immune plasma for treatment of hantavirus cardiopulmonary syndrome caused by Andes virus
A non-randomized multicentre trial of human immune plasma for treatment of hantavirus cardiopulmonary syndrome caused by Andes virus
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DOI：
10.3851/imp2875
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发表时间：
2015-01-01
影响因子：
1.2
通讯作者：
Mertz, Gregory J.
中科院分区：
文献类型：
--
作者：
Vial, Pablo A.;Valdivieso, Francisca;Mertz, Gregory J.
背景：在智利，安第斯病毒（ANDV）是汉坦病毒心肺综合征（HCPS）的唯一病原，年平均发病率为55例，病死率（CFR）为32%，且无特异性治疗。住院时中和抗体（NAb）滴度与HCPS严重程度呈负相关。我们设计了一项开放试验，以探讨免疫血浆作为这种疾病治疗策略的安全性和有效性，并评估其药代动力学。方法：我们在HCPS后至少6个月对献血者进行血浆置换，并通过减焦中和试验测量NAb滴度。10个研究中心疑似/确诊HCPS的受试者有资格接受免疫血浆静脉滴注，剂量为5000 U/kg的ANDV NAb。通过免疫球蛋白M血清学或逆转录- pcr证实HCPS。主要结果为30天内的死亡率。结果：2008-2012年共入组治疗32例，确诊HCPS 29例。汉坦病毒血浆治疗病例的CFR为4/29 (14%)；智利同期未治疗病例的CFR为63/199 (32%，P=0.049， OR=0.35， CI=0.12, 0.99)；2005-2012年同一研究地点未治疗病例的CFR为18/66 (27%;(P=0.15， OR=0.43， CI=0.14, 1.34)，先前甲泼尼龙治疗研究的CFR为20/60 （33%；P=0.052， OR=0.32， CI=0.10, 1.00）。我们未发现与血浆输注相关的严重不良事件。受体达到的血浆NAb滴度是可变的，病毒载量保持稳定。结论：人免疫血浆输注对HCPS是安全的。我们观察到治疗病例中CFR的降低具有临界意义，这需要进一步的研究来证实。
Background: In Chile, Andes virus (ANDV) is the sole aetiological agent of hantavirus cardiopulmonary syndrome (HCPS) with mean annual incidence of 55 cases, 32% case fatality rate (CFR) and no specific treatment. Neutralizing antibody (NAb) titres at hospital admission correlate inversely with HCPS severity. We designed an open trial to explore safety and efficacy and evaluate pharmacokinetics of immune plasma as a treatment strategy for this disease.Methods: We performed plasmapheresis on donors at least 6 months after HCPS and measured NAb titres through a focus-reduction neutralization test. Subjects admitted to 10 study sites with suspected/confirmed HCPS were eligible for treatment with immune plasma by intravenous infusion at an ANDV NAb dose of 5,000 U/kg. HCPS was confirmed through immunoglobulin M serology or reverse transcriptase-PCR. The main outcome was mortality within 30 days.Results: From 2008-2012, we enrolled and treated 32 cases and confirmed HCPS in 29. CFR of hantavirus plasma-treated cases was 4/29 (14%); CFR of non-treated cases in the same period in Chile was 63/199 (32%; P=0.049, OR=0.35, CI=0.12, 0.99); CFR of non-treated cases at the same study sites between 2005-2012 was 18/66 (27%; (P=0.15, OR=0.43, CI=0.14, 1.34) and CFR in a previous methylprednisolone treatment study was 20/60 (33%; P=0.052, OR=0.32, CI=0.10, 1.00). We detected no serious adverse events associated to plasma infusion. Plasma NAb titres reached in recipients were variable and viral load remained stable.Conclusions: Human ANDV immune plasma infusion appears safe for HCPS. We observed a decrease in CFR in treated cases with borderline significance that will require further studies for confirmation.