Van-Mai Cao-Lormeau1, Alexandre Blake2, Sandrine Mons3, Stéphane Lastère4, Claudine Roche1, Jessica Vanhomwegen5, Timothée Dub2, Laure Baudouin3, Anita Teissier1, Philippe Larre6, Anne-Laure Vial7, Christophe Decam8, Valérie Choumet9, Susan K Halstead10, Hugh J Willison10, Lucile Musset11, Jean-Claude Manuguerra5, Philippe Despres12, Emmanuel Fournier13, Henri-Pierre Mallet7, Didier Musso1, Arnaud Fontanet14, Jean Neil11, Frédéric Ghawché6. 1. Unit of Emerging Infectious Diseases, Institut Louis Malardé, Papeete, Tahiti, French Polynesia. 2. Institut Pasteur, Emerging Diseases Epidemiology Unit, Paris, France. 3. Service de Réanimation Polyvalente, Centre Hospitalier de Polynésie Française, Tahiti, French Polynesia. 4. Clinical Laboratory, Centre Hospitalier de Polynésie Française, Tahiti, French Polynesia. 5. Institut Pasteur, Laboratory for Urgent Responses to Biological Threats, Paris, France; Unit Environment and Infectious Risks, Institut Pasteur, Paris, France. 6. Service de neurologie, Centre Hospitalier de Polynésie Française, Papeete, Tahiti, Polynésie Française. 7. Direction de la Santé, Bureau de Veille Sanitaire, Papeete, French Polynesia. 8. Service de santé des forces armées, Papeete, French Polynesia. 9. Unit Environment and Infectious Risks, Institut Pasteur, Paris, France. 10. Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. 11. Department of Immunology, Laboratory of Immunochemistry & Autoimmunity, Pitié-Salpêtrière Hospital (AP-HP), Paris, France. 12. University of Reunion Island, La Reunion, France. 13. Département de Neurophysiologie, Pitié-Salpêtrière Hospital (AP-HP), Paris, France. 14. Institut Pasteur, Emerging Diseases Epidemiology Unit, Paris, France; Conservatoire National des Arts et Métiers, Paris, France; Institut Pasteur, Centre for Global Health Research and Education, Paris, France. Electronic address: fontanet@pasteur.fr.
Abstract
BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust.
BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust.
Authors: V Ravi; A B Taly; S K Shankar; P K Shenoy; A Desai; D Nagaraja; M Gourie-Devi; A Chandramuki Journal: Acta Neurol Scand Date: 1994-07 Impact factor: 3.209
Authors: E Oehler; L Watrin; P Larre; I Leparc-Goffart; S Lastere; F Valour; L Baudouin; Hp Mallet; D Musso; F Ghawche Journal: Euro Surveill Date: 2014-03-06
Authors: Feng Long; Michael Doyle; Estefania Fernandez; Andrew S Miller; Thomas Klose; Madhumati Sevvana; Aubrey Bryan; Edgar Davidson; Benjamin J Doranz; Richard J Kuhn; Michael S Diamond; James E Crowe; Michael G Rossmann Journal: Proc Natl Acad Sci U S A Date: 2019-01-14 Impact factor: 11.205
Authors: Christa E Osuna; So-Yon Lim; Claire Deleage; Bryan D Griffin; Derek Stein; Lukas T Schroeder; Robert Were Omange; Katharine Best; Ma Luo; Peter T Hraber; Hanne Andersen-Elyard; Erwing Fabian Cardozo Ojeda; Scott Huang; Dana L Vanlandingham; Stephen Higgs; Alan S Perelson; Jacob D Estes; David Safronetz; Mark G Lewis; James B Whitney Journal: Nat Med Date: 2016-10-03 Impact factor: 53.440
Authors: Jinzhao Song; Vikram Pandian; Michael G Mauk; Haim H Bau; Sara Cherry; Laurence C Tisi; Changchun Liu Journal: Anal Chem Date: 2018-03-22 Impact factor: 6.986