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

Abstract

Background. The Zika virus (ZIKV) outbreak in the Americas has caused international concern due to neurological sequelae linked to the infection, such as microcephaly and Guillain-Barré syndrome (GBS). The World Health Organization stated that there is "sufficient evidence to conclude that Zika virus is a cause of congenital abnormalities and is a trigger of GBS". This conclusion was based on a systematic review of the evidence published until 30.05.2016. Since then, the body of evidence has grown substantially, leading to this update of that systematic review with new evidence published from 30.05.2016 - 18.01.2017, update 1. Methods. We review evidence on the causal link between ZIKV infection and adverse congenital outcomes and the causal link between ZIKV infection and GBS or immune-mediated thrombocytopaenia purpura. We also describe the transition of the review into a living systematic review, a review that is continually updated. Results. Between 30.05.2016 and 18.01.2017, we identified 2413 publications, of which 101 publications were included. The evidence added in this update confirms the conclusion of a causal association between ZIKV and adverse congenital outcomes. New findings expand the evidence base in the dimensions of biological plausibility, strength of association, animal experiments and specificity. For GBS, the body of evidence has grown during the search period for update 1, but only for dimensions that were already populated in the previous version. There is still a limited understanding of the biological pathways that potentially cause the occurrence of autoimmune disease following ZIKV infection. Conclusions. This systematic review confirms previous conclusions that ZIKV is a cause of congenital abnormalities, including microcephaly, and is a trigger of GBS. The transition to living systematic review techniques and methodology provides a proof of concept for the use of these methods to synthesise evidence about an emerging pathogen such as ZIKV.

Keywords: Guillain-barre syndrome; Zika virus; causality; congenital abnormalities; living systematic review; microcephlay.

Figure 1.. Living systematic review automation.

Blue boxes and arrows represent the conceptual steps in a systematic review process. Automation is divided in three modules. Module 1 is the automation of the searching and deduplication of information from different data sources. Module 2 partly automates screening. Module 3 automates the production of tables and figures and outputs the data to a web platform (Data visualisation). Blue arrows represent automated information flows; red arrows represent manual input. The blue-red dashes arrow represents a blended form where reviewers verify automated decisions of the system. The white boxes show the practical implementation of the system and the data flow.

Figure 2.. Timeline of review conduct, publication and transition to a living systematic review.

The baseline review (BR, ) and Update 1 (U1) this version classic, manual systematic review. During 2017 automation of the workflow was conducted resulting in a projected Update 2 (U2) and 3 (U3) with more rapid throughput. LSR, living systematic review.

Figure 3.. PRISMA flow diagram of included studies.