ObjectiveWith 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.MethodsWe 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.ResultsThe 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.ConclusionThe 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 numberCRD42018091087.
Background Zika virus (ZIKV) has generated global interest in the last five years mostly due to its resurgence in the Americas between 2015 and 2016. It was previously thought to be a self-limiting infection causing febrile illness in less than one quarter of those infected. However, a rise in birth defects amongst children born to infected pregnant women, as well as increases in neurological manifestations in adults has been demonstrated. We systemically reviewed the literature to understand clinical manifestations and health outcomes in adults globally. Methods This review was registered prospectively with PROPSERO (CRD 42018096558). We systematically searched for studies in six databases from inception to the end of September 2020. There were no language restrictions. Critical appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools. Findings We identified 73 studies globally that reported clinical outcomes in ZIKV-infected adults, of which 55 studies were from the Americas. For further analysis, we considered studies that met 70% of critical appraisal criteria and described subjects with confirmed ZIKV. The most common symptoms included: exanthema (5,456/6,129; 89%), arthralgia (3,809/6,093; 63%), fever (3,787/6,124; 62%), conjunctivitis (2,738/3,283; 45%), myalgia (2,498/5,192; 48%), headache (2,165/4,722; 46%), and diarrhea (337/2,622; 13%). 36/14,335 (0.3%) of infected cases developed neurologic sequelae, of which 75% were Guillain-Barré Syndrome (GBS). Most subjects reported recovery from peak of neurological complications, though a small proportion endured chronic disability. Mortality was rare (0.1%) and hospitalization (11%) was often associated with co-morbidities or GBS. Conclusions The ZIKV literature in adults was predominantly from the Americas. The most common systemic symptoms were exanthema, fever, arthralgia, and conjunctivitis; GBS was the most prevalent neurological complication. Future ZIKV studies are warranted with standardization of testing and case definitions, consistent co-infection testing, reporting of laboratory abnormalities, separation of adult and pediatric outcomes, and assessing for causation between ZIKV and neurological sequelae.
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