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Health outcomes associated with Zika virus infection in humans: a systematic review of systematic reviews
  1. Raphael Ximenes1,
  2. Lauren C Ramsay1,2,
  3. Rafael Neves Miranda1,
  4. Shaun K Morris3,4,
  5. Kellie Murphy5,
  6. Beate Sander1,2,6,7
  7. RADAM-LAC Research Team
    1. 1 Toronto Health Economics and Technology Assessment (THETA) Collaborative, University Health Network, Toronto, Ontario, Canada
    2. 2 Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
    3. 3 Division of Infectious Diseases and Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
    4. 4 Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
    5. 5 Department of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto, Ontario, Canada
    6. 6 Public Health Ontario, Toronto, Ontario, Canada
    7. 7 ICES, Toronto, Ontario, Canada
    1. Correspondence to Dr Raphael Ximenes; raphael.ximenes{at}


    Objective With the emergence of Zika virus (ZIKV) disease in Central and South America in the mid-2010s and recognition of the teratogenic effects of congenital exposure to ZIKV, there has been a substantial increase in new research published on ZIKV. Our objective is to synthesise the literature on health outcomes associated with ZIKV infection in humans.

    Methods We conducted a systematic review (SR) of SRs following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched MEDLINE, Embase, Cochrane and LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde) databases from inception to 22 July 2019, and included SRs that reported ZIKV-associated health outcomes. Three independent reviewers selected eligible studies, extracted data and assessed the quality of included SRs using the AMSTAR 2 (A MeaSurement Tool to Assess Systematic Reviews 2) tool. Conflicts were resolved by consensus or consultation with a third reviewer.

    Results The search yielded 1382 unique articles, of which 21 SRs met our inclusion criteria. The 21 SRs ranged from descriptive to quantitative data synthesis, including four meta-analyses. The most commonly reported ZIKV-associated manifestations and health outcomes were microcephaly, congenital abnormalities, brain abnormalities, neonatal death and Guillain-Barré syndrome. The included reviews were highly heterogeneous. The overall quality of the SRs was critically low with all studies having more than one critical weakness.

    Conclusion The evolving nature of the literature on ZIKV-associated health outcomes, together with the critically low quality of existing SRs, demonstrates the need for high-quality SRs to guide patient care and inform policy decision making.

    PROSPERO registration number CRD42018091087.

    • Zika virus infection
    • epidemiology
    • congenital Zika syndrome
    • neurology
    • Guillain-Barré syndrome
    • microcephaly

    This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

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    • Collaborators RADAM-LAC Research Team members are Beate Sander, Camila Gonzalez, Manisha Kulkarni, Marcos Miretti, Mauricio Espinel, Jianhong Wu and Varsovia Cevallos.

    • Contributors RX: conceptualisation of the study, performed the systematic review, critically appraising the scientific literature, analysis, drafting and revising the manuscript. RNM: performed the systematic review, critically appraising the scientific literature and revising the manuscript. LCR: performed the systematic review and critically appraising the scientific literature. SKM: critical revision of the manuscript. KM: critical revision of the manuscript. RADAM-LAC Research Team: contribution to study conception and design. BS: conceptualisation of the study, critical revision of the manuscript and supervision of the study.

    • Funding This project was funded by the Canadian Institutes of Health Research—Team grant—FRN149784 and the International Development Research Centre (IDRC).

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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