|Zika virus (ZIKV) disease had been described as a mild, self-limiting illness associated with fever, rash, joint pain, and conjunctivitis.1 However, during the outbreak in French Polynesia, 42 patients with ZIKV disease were found to have the Guillain–Barré syndrome, which represented a marked increase from the approximately 5 cases detected annually during the previous 4 years.2 A connection with the Guillain–Barré syndrome had previously been described in association with other flavivirus illnesses3,4 but not with ZIKV infection.
From April 1, 2015, to March 31, 2016, a total of 164,237 confirmed and suspected cases of ZIKV disease and 1474 cases of the Guillain–Barré syndrome were reported in Bahia, Brazil; Colombia; the Dominican Republic; El Salvador; Honduras; Suriname; and Venezuela. To examine the temporal association between ZIKV disease and the Guillain–Barré syndrome, graphical and time-series analyses were applied to these two independent data sets, which were collected through official International Health Regulations channels or from ministry of health websites (see the Supplementary Appendix, available with the full text of this letter at NEJM.org). The data obtained from country reports contained no personally identifiable information and were collected as part of routine public health surveillance; therefore, the analysis was exempt from review by an ethics board. Differences between the observed and expected numbers of cases of the Guillain–Barré syndrome during the ZIKV transmission period, as well as differences in the incidence of the Guillain–Barré syndrome and ZIKV disease according to age and sex, were analyzed with the use of Poisson regression models (see the Supplementary Appendix).