Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study

Abstract

Background 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. Patients and Methods 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. Results 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. Conclusion 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.