title: Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study.
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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust.
authors.affiliation: Unit of Emerging Infectious Diseases, Institut Louis Malardé, Papeete, Tahiti, French Polynesia.
authors.forename: Van-Mai
authors.initials: VM
authors.lastname: Cao-Lormeau
authors.affiliation: Institut Pasteur, Emerging Diseases Epidemiology Unit, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Blake
authors.affiliation: Service de Réanimation Polyvalente, Centre Hospitalier de Polynésie Française, Tahiti, French Polynesia.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Mons
authors.affiliation: Clinical Laboratory, Centre Hospitalier de Polynésie Française, Tahiti, French Polynesia.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lastère
authors.affiliation: Unit of Emerging Infectious Diseases, Institut Louis Malardé, Papeete, Tahiti, French Polynesia.
authors.forename: Claudine
authors.initials: C
authors.lastname: Roche
authors.affiliation: Institut Pasteur, Laboratory for Urgent Responses to Biological Threats, Paris, France; Unit Environment and Infectious Risks, Institut Pasteur, Paris, France.
authors.forename: Jessica
authors.initials: J
authors.lastname: Vanhomwegen
authors.affiliation: Institut Pasteur, Emerging Diseases Epidemiology Unit, Paris, France.
authors.forename: Timothée
authors.initials: T
authors.lastname: Dub
authors.affiliation: Service de Réanimation Polyvalente, Centre Hospitalier de Polynésie Française, Tahiti, French Polynesia.
authors.forename: Laure
authors.initials: L
authors.lastname: Baudouin
authors.affiliation: Unit of Emerging Infectious Diseases, Institut Louis Malardé, Papeete, Tahiti, French Polynesia.
authors.forename: Anita
authors.initials: A
authors.lastname: Teissier
authors.affiliation: Service de neurologie, Centre Hospitalier de Polynésie Française, Papeete, Tahiti, Polynésie Française.
authors.forename: Philippe
authors.initials: P
authors.lastname: Larre
authors.affiliation: Direction de la Santé, Bureau de Veille Sanitaire, Papeete, French Polynesia.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Vial
authors.affiliation: Service de santé des forces armées, Papeete, French Polynesia.
authors.forename: Christophe
authors.initials: C
authors.lastname: Decam
authors.affiliation: Unit Environment and Infectious Risks, Institut Pasteur, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Choumet
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Halstead
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Hugh J
authors.initials: HJ
authors.lastname: Willison
authors.affiliation: Department of Immunology, Laboratory of Immunochemistry & Autoimmunity, Pitié-Salpêtrière Hospital (AP-HP), Paris, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Musset
authors.affiliation: Institut Pasteur, Laboratory for Urgent Responses to Biological Threats, Paris, France; Unit Environment and Infectious Risks, Institut Pasteur, Paris, France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Manuguerra
authors.affiliation: University of Reunion Island, La Reunion, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Despres
authors.affiliation: Département de Neurophysiologie, Pitié-Salpêtrière Hospital (AP-HP), Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Fournier
authors.affiliation: Direction de la Santé, Bureau de Veille Sanitaire, Papeete, French Polynesia.
authors.forename: Henri-Pierre
authors.initials: HP
authors.lastname: Mallet
authors.affiliation: Unit of Emerging Infectious Diseases, Institut Louis Malardé, Papeete, Tahiti, French Polynesia.
authors.forename: Didier
authors.initials: D
authors.lastname: Musso
authors.affiliation: 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.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Fontanet
authors.affiliation: Department of Immunology, Laboratory of Immunochemistry & Autoimmunity, Pitié-Salpêtrière Hospital (AP-HP), Paris, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Neil
authors.affiliation: Service de neurologie, Centre Hospitalier de Polynésie Française, Papeete, Tahiti, Polynésie Française.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ghawché
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003716:Dengue Virus / Q000302:isolation & purification; D004196:Disease Outbreaks / Q000706:statistics & numerical data; D005260:Female; D020275:Guillain-Barre Syndrome / Q000453:epidemiology* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011114:Polynesia / Q000453:epidemiology; D019595:Severe Dengue / Q000150:complications / Q000453:epidemiology; D000071244:Zika Virus / Q000302:isolation & purification; D000071243:Zika Virus Infection / Q000150:complications* / Q000453:epidemiology*