Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study.
Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study.
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DOI：
10.1016/s0140-6736(16)00562-6
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发表时间：
2016-04-09
期刊：
影响因子：
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通讯作者：
Ghawché F
中科院分区：
文献类型：
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作者：
Cao-Lormeau VM;Blake A;Mons S;Lastère S;Roche C;Vanhomwegen J;Dub T;Baudouin L;Teissier A;Larre P;Vial AL;Decam C;Choumet V;Halstead SK;Willison HJ;Musset L;Manuguerra JC;Despres P;Fournier E;Mallet HP;Musso D;Fontanet A;Neil J;Ghawché F
2013年10月至2014年4月，法属波利尼西亚经历了当时有史以来最大规模的寨卡病毒（ZIKV）疫情。在同一时期，报告了格林-巴利综合征（GBS）的增加，表明ZIKV和GBS之间可能存在关联。进行病例对照研究以鉴定ZIKV和登革病毒（DENV）感染在发展GBS中的作用。病例为暴发期间在法国波利尼西亚中心医院确诊的GBS患者。对照组为在医院就诊的年龄、性别和居住地匹配的非发热性疾病患者（对照组1 [CTR 1]; n=98），以及年龄匹配的急性ZIKV疾病且无神经系统症状的患者（对照组2 [CTR 2]; n=70）。病毒学研究包括ZIKV的RT-PCR，以及ZIKV和DENV的微球免疫荧光和血清中和测定。使用ELISA和组合微阵列在GBS患者中研究抗糖脂反应性。在研究期间，42例患者被诊断为GBS。98%的GBS患者具有抗ZIKV IgM或IgG，并且全部具有针对ZIKV的中和抗体，而CTR 1组中具有中和抗体的比例为55.7%（P<0.0001）。93%的GBS患者有ZIKV IgM，88%的患者在神经系统症状发作前的中位6天内经历过短暂性疾病，这表明最近感染了ZIKV。GBS患者的电生理结果与急性运动轴索神经病（AMAN）类型一致，并且疾病进展迅速（安装期和平台期的中位持续时间分别为6天和4天）。12例（29%）患者需要呼吸辅助。无患者死亡。抗糖脂抗体活性，特别是对GA 1，发现在13例（31%）患者的ELISA和19/41（46%）的糖阵列在入院时。典型的AMAN相关的抗神经节苷脂抗体很少出现。GBS患者和两个对照组之间的既往登革热病史无显著差异。这是第一项为ZIKV感染导致GBS提供证据的研究。随着ZIKV在美洲迅速蔓延，高危国家需要准备足够的重症监护病床，以管理GBS患者。
From October 2013 to April 2014, French Polynesia experienced the largest Zika virus (ZIKV) outbreak ever described at that time. During the same period, an increase in Guillain-Barré syndrome (GBS) was reported, suggesting a possible association between ZIKV and GBS. A case-control study was performed to identify the role of ZIKV and dengue virus (DENV) infection in developing GBS. Cases were GBS patients diagnosed at the Centre Hospitalier de Polynésie Française during the outbreak period. Controls were age-, gender-, and residence-matched patients who presented at the hospital with a non-febrile illness (Control group 1 [CTR1]; n=98), and age-matched patients with acute ZIKV disease and no neurological symptoms (Control group 2 [CTR2]; n=70). Virological investigations included RT-PCR for ZIKV, and both microsphere immunofluorescent and seroneutralization assays for ZIKV and DENV. Anti-glycolipid reactivity was studied in GBS patients using both ELISA and combinatorial microarrays. Forty-two patients were diagnosed with GBS during the study period. Ninety-eight percent of GBS patients had anti-ZIKV IgM or IgG, and all had neutralizing antibodies against ZIKV compared to 55.7% with neutralizing antibodies in the CTR1 group (P<0.0001). Ninety-three percent of GBS patients had ZIKV IgM and 88% had experienced a transient illness in median six days before the onset of neurological symptoms, suggesting recent ZIKV infection. GBS patients had electrophysiological findings compatible with the acute motor axonal neuropathy (AMAN) type, and had rapid evolution of disease (median duration of the installation and plateau phases was 6 and 4 days, respectively). Twelve (29%) patients required respiratory assistance. No patients died. Anti-glycolipid antibody activity, notably against GA1, was found in 13 (31%) patients by ELISA and 19/41 (46%) by glycoarray at admission. The typical AMAN-associated anti-ganglioside antibodies were rarely present. There was no significant difference in past dengue history between GBS patients and the two control groups. This is the first study providing evidence for ZIKV infection causing GBS. As ZIKV is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity for managing GBS patients.