Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: A living systematic review

Michel Jacques Counotte; Kaspar Walter Meili; Katayoun Taghavi; Guilherme Calvet; James Sejvar; Nicola Low

doi:10.12688/f1000research.19918.1

Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: A living systematic review

F1000Res. 2019 Aug 14:8:1433. doi: 10.12688/f1000research.19918.1. eCollection 2019.

Authors

Michel Jacques Counotte¹, Kaspar Walter Meili¹, Katayoun Taghavi¹, Guilherme Calvet², James Sejvar³, Nicola Low¹

Affiliations

¹ Institute of Social and Preventive Medicine, University Bern, Bern, Switzerland.
² Acute Febrile Illnesses Laboratory, Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro, Rio de Janeiro, Brazil.
³ Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.

Abstract

Background: The Zika virus (ZIKV) caused a large outbreak in the Americas leading to the declaration of a Public Health Emergency of International Concern in February 2016. A causal relation between infection and adverse congenital outcomes such as microcephaly was declared by the World Health Organization (WHO) informed by a systematic review structured according to a framework of ten dimensions of causality, based on the work of Bradford Hill. Subsequently, the evidence has continued to accumulate, which we incorporate in regular updates of the original work, rendering it a living systematic review. Methods: We present an update of our living systematic review on the causal relation between ZIKV infection and adverse congenital outcomes and between ZIKV and GBS for four dimensions of causality: strength of association, dose-response, specificity, and consistency. We assess the evidence published between January 18, 2017 and July 1, 2019. Results: We found that the strength of association between ZIKV infection and adverse outcomes from case-control studies differs according to whether exposure to ZIKV is assessed in the mother (OR 3.8, 95% CI: 1.7-8.7, I ²=19.8%) or the foetus/infant (OR 37.4, 95% CI: 11.0-127.1, I ²=0%). In cohort studies, the risk of congenital abnormalities was 3.5 times higher after ZIKV infection (95% CI: 0.9-13.5, I ²=0%). The strength of association between ZIKV infection and GBS was higher in studies that enrolled controls from hospital (OR: 55.8, 95% CI: 17.2-181.7, I ²=0%) than in studies that enrolled controls at random from the same community or household (OR: 2.0, 95% CI: 0.8-5.4, I ²=74.6%). In case-control studies, selection of controls from hospitals could have biased results. Conclusions: The conclusions that ZIKV infection causes adverse congenital outcomes and GBS are reinforced with the evidence published between January 18, 2017 and July 1, 2019.

Keywords: Disease outbreaks; Guillain-Barré syndrome; Zika; arboviruses; causality; congenital abnormalities.

Publication types

Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Americas
Brain / abnormalities*
Brain / virology*
Female
Guillain-Barre Syndrome / congenital*
Guillain-Barre Syndrome / virology*
Humans
Infant
Pregnancy
Pregnancy Complications, Infectious / virology*
Zika Virus
Zika Virus Infection / complications*

Grants and funding

This work was supported by the Swiss National Science Foundation [320030_170069], end date: 31/10/2021