Vial Pablo A, Valdivieso Francisca, Calvo Mario, Rioseco M Luisa, Riquelme Raul, Araneda Andres, Tomicic Vinko, Graf Jerónimo, Paredes Laura, Florenzano Matias, Bidart Teresa, Cuiza Analia, Marco Claudia, Hjelle Brian, Ye Chunyan, Hanfelt-Goade Diane, Vial Cecilia, Rivera Juan C, Delgado Iris, Mertz Gregory J
Facultad de Medicina Clínica Alemana Universidad del Desarrollo, Santiago, Chile.
Antivir Ther. 2015;20(4):377-86. doi: 10.3851/IMP2875. Epub 2014 Oct 15.
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.
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.
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.
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.
在智利，安第斯病毒（ANDV）是汉坦病毒心肺综合征（HCPS）的唯一病原体，年平均发病率为55例，病死率（CFR）为32%，且尚无特效治疗方法。入院时的中和抗体（NAb）滴度与HCPS严重程度呈负相关。我们设计了一项开放试验，以探索免疫血浆作为该疾病治疗策略的安全性和有效性，并评估其药代动力学。
我们对HCPS发病至少6个月后的献血者进行了血浆置换，并通过蚀斑减少中和试验测量NAb滴度。入住10个研究地点且疑似/确诊为HCPS的受试者有资格接受静脉输注免疫血浆治疗，ANDV NAb剂量为5000 U/kg。通过免疫球蛋白M血清学或逆转录酶聚合酶链反应确诊HCPS。主要结局是30天内的死亡率。
2008年至2012年，我们招募并治疗了32例患者，其中29例确诊为HCPS。接受汉坦病毒血浆治疗病例的CFR为4/29（14%）；同期智利未治疗病例的CFR为63/199（32%；P=0.049，OR=0.35，CI=0.12，0.99）；2005年至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），在先前一项甲泼尼龙治疗研究中的CFR为20/60（33%；P=0.052，OR=0.32，CI=0.10，1.00）。我们未检测到与血浆输注相关的严重不良事件。接受者体内的血浆NAb滴度各不相同，病毒载量保持稳定。
输注人ANDV免疫血浆对HCPS似乎是安全的。我们观察到治疗病例的CFR有所下降，具有临界显著性，这需要进一步研究予以证实。
