Guillain Barre Syndrome outbreak associated with Zika virus infection in French Polynesia: a case control study
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 Barre syndrome was reported, suggesting a possible association between Zika virus and Guillain Barre syndrome. We aimed to assess the role of Zika virus and dengue virus infection in developing Guillain Barre syndrome. METHODS In this case control study, cases were patients with Guillain Barre syndrome diagnosed at the Centre Hospitalier de Polynesie Francaise (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 Barre syndrome using both ELISA and combinatorial microarrays. FINDINGS 42 patients were diagnosed with Guillain Barre syndrome during the study period. 41 (98% patients with Guillain Barre 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 Barre 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 Barre 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 Barre 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 Barre 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 Barre syndrome. FUNDING Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust.
The Lancet