Highlights
- •GBS cases in case reports likely included ZIKV infection as a diagnostic criterion.
- •Outbreaks of ZIKV infection were not consequentially followed by outbreaks of GBS.
- •Major biases were likely in all but one analytic study of the ZIKV-GBS association.
- •The average ZIKV-GBS odds ratio in analytic studies was 1.57 (95% CI: 0.86–2.86).
- •The available evidence is insufficient to claim ZIKV infection causes GBS.
Abstract
Objective
Findings from studies of the association between Zika virus (ZIKV) infection and Guillain-Barré
syndrome (GBS) are inconsistent. I conducted a systematic review and meta-analysis
to clarify the nature of this association.
Methods
I searched PubMed, Scopus, Cochrane, CINAHL, Web of Science, Scielo, and DOAJ for
case report, ecological, and analytic studies with “Zika” and “Guillain-Barré syndrome”
as keywords, published up to July 1stth 2018. I evaluated if ZIKV infection status influenced the diagnosis of GBS (detection
bias) in case-report and analytic studies; assessed if changes in weekly number of
cases of ZIKV infection during outbreaks were followed by changes in number of GBS
cases 1–8 weeks later; gauged the likelihood of selection, confounding, information,
sparse data, and time-dependent bias (i.e. when ZIKV infection was ascertained after
GBS onset) in analytic studies; and calculated the average ZIKV-GBS odds ratio (OR)
in studies without time-dependent bias.
Results
In case reports, ZIKV infection prevalence in GBS cases was 2.4 to 25 times higher
than expected. Changes in the number of ZIKV-infection cases during outbreaks were
not consequentially followed by changes in the number of GBS cases (OR: 1.01; 95%
CI: 0.99–1.03). Major biases were likely in all but one analytic study, which showed
a non-significant ZIKV-GBS association. The average ZIKV-GBS OR in studies without
time-dependent bias was 1.57 (95% CI: 0.86–2.86).
Interpretation
These findings indicate the available evidence is insufficient to claim ZIKV infection
causes GBS. Therefore, stakeholders may want to reconsider current ZIKV-GBS public
health and patient care recommendations.
Keywords
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Article info
Publication history
Published online: June 20, 2019
Accepted:
June 17,
2019
Received in revised form:
May 23,
2019
Received:
March 25,
2019
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.