Cao-Lormeau Van-Mai, Blake Alexandre, Mons Sandrine, Lastère Stéphane, Roche Claudine, Vanhomwegen Jessica, Dub Timothée, Baudouin Laure, Teissier Anita, Larre Philippe, Vial Anne-Laure, Decam Christophe, Choumet Valérie, Halstead Susan K, Willison Hugh J, Musset Lucile, Manuguerra Jean-Claude, Despres Philippe, Fournier Emmanuel, Mallet Henri-Pierre, Musso Didier, Fontanet Arnaud, Neil Jean, Ghawché Frédéric
Unit of Emerging Infectious Diseases, Institut Louis Malardé, Papeete, Tahiti, French Polynesia.
Institut Pasteur, Emerging Diseases Epidemiology Unit, Paris, France.
Lancet. 2016 Apr 9;387(10027):1531-1539. doi: 10.1016/S0140-6736(16)00562-6. Epub 2016 Mar 2.
Between October, 2013, and April, 2014, French Polynesia experienced the largest Zika virus outbreak ever described at that time. During the same period, an increase in Guillain-Barré syndrome was reported, suggesting a possible association between Zika virus and Guillain-Barré syndrome. We aimed to assess the role of Zika virus and dengue virus infection in developing Guillain-Barré syndrome.
In this case-control study, cases were patients with Guillain-Barré syndrome diagnosed at the Centre Hospitalier de Polynésie Française (Papeete, Tahiti, French Polynesia) during the outbreak period. Controls were age-matched, sex-matched, and residence-matched patients who presented at the hospital with a non-febrile illness (control group 1; n=98) and age-matched patients with acute Zika virus disease and no neurological symptoms (control group 2; n=70). Virological investigations included RT-PCR for Zika virus, and both microsphere immunofluorescent and seroneutralisation assays for Zika virus and dengue virus. Anti-glycolipid reactivity was studied in patients with Guillain-Barré syndrome using both ELISA and combinatorial microarrays.
42 patients were diagnosed with Guillain-Barré syndrome during the study period. 41 (98%) patients with Guillain-Barré syndrome had anti-Zika virus IgM or IgG, and all (100%) had neutralising antibodies against Zika virus compared with 54 (56%) of 98 in control group 1 (p<0.0001). 39 (93%) patients with Guillain-Barré syndrome had Zika virus IgM and 37 (88%) had experienced a transient illness in a median of 6 days (IQR 4-10) before the onset of neurological symptoms, suggesting recent Zika virus infection. Patients with Guillain-Barré syndrome had electrophysiological findings compatible with acute motor axonal neuropathy (AMAN) type, and had rapid evolution of disease (median duration of the installation and plateau phases was 6 [IQR 4-9] and 4 days [3-10], respectively). 12 (29%) patients required respiratory assistance. No patients died. Anti-glycolipid antibody activity was found in 13 (31%) patients, and notably against GA1 in eight (19%) patients, by ELISA and 19 (46%) of 41 by glycoarray at admission. The typical AMAN-associated anti-ganglioside antibodies were rarely present. Past dengue virus history did not differ significantly between patients with Guillain-Barré syndrome and those in the two control groups (95%, 89%, and 83%, respectively).
This is the first study providing evidence for Zika virus infection causing Guillain-Barré syndrome. Because Zika virus is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity to manage patients with Guillain-Barré syndrome.
Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust.
2013年10月至2014年4月期间，法属波利尼西亚经历了当时有记录以来最大规模的寨卡病毒疫情。同一时期，有报告称格林-巴利综合征病例有所增加，这表明寨卡病毒与格林-巴利综合征之间可能存在关联。我们旨在评估寨卡病毒和登革病毒感染在格林-巴利综合征发病过程中的作用。
在这项病例对照研究中，病例为疫情期间在法属波利尼西亚帕皮提的法属波利尼西亚中心医院被诊断为格林-巴利综合征的患者。对照为年龄匹配、性别匹配且居住地区匹配的患者，其中一组为因非发热性疾病到医院就诊的患者（对照组1；n = 98），另一组为年龄匹配的急性寨卡病毒病且无神经症状的患者（对照组2；n = 70）。病毒学调查包括针对寨卡病毒的逆转录聚合酶链反应（RT-PCR），以及针对寨卡病毒和登革病毒的微球免疫荧光检测和血清中和试验。采用酶联免疫吸附测定（ELISA）和组合微阵列研究格林-巴利综合征患者的抗糖脂反应性。
在研究期间，42例患者被诊断为格林-巴利综合征。41例（98%）格林-巴利综合征患者有抗寨卡病毒IgM或IgG，且所有患者（100%）均有针对寨卡病毒的中和抗体，而对照组1的98例患者中有54例（56%）有此类抗体（p<0.0001）。39例（93%）格林-巴利综合征患者有寨卡病毒IgM，37例（88%）在出现神经症状前的中位时间为6天（四分位间距4 - 10天）经历过短暂疾病，提示近期感染寨卡病毒。格林-巴利综合征患者的电生理检查结果符合急性运动轴索性神经病（AMAN）类型，且疾病进展迅速（发病期和平台期的中位持续时间分别为6天[四分位间距4 - 9天]和4天[3 - 10天]）。12例（29%）患者需要呼吸支持。无患者死亡。入院时，通过ELISA检测发现13例（31%）患者有抗糖脂抗体活性，其中8例（19%）患者尤其针对GA1有抗体活性；通过糖芯片检测发现41例患者中有(19%) 19例（46%）有此类抗体。典型的与AMAN相关的抗神经节苷脂抗体很少出现。格林-巴利综合征患者与两个对照组患者的既往登革病毒感染史差异无统计学意义（分别为95%、89%和83%）。
这是第一项为寨卡病毒感染导致格林-巴利综合征提供证据的数据。鉴于寨卡病毒正在美洲迅速传播，有风险的国家需要准备足够数量的重症监护病床，以应对格林-巴利综合征患者。
新兴传染病综合生物学实验室，欧盟第七框架计划PREDEMICS以及惠康信托基金会。
