Clinical manifestations and health outcomes associated with Zika virus infections in adults: A systematic review

Panashe Tombindo1,2, Ryan O'Reilly1,2, Joanna Bielecki2, Justin Boyle1, Laura Erdman3,1, Rafael Miranda2, Shaun Morris3,1, Kellie Murphy4,1, Lauren Ramsay2,1, Clare Whitehead4,1, Raphael Ximenes2, Beate Sander2,5,6,7
1University of Toronto, Toronto, ON, Canada. 2Toronto Health Economics and Technology Assessment (THETA) Collaborative, University Health Network, Toronto, ON, Canada. 3Hospital for Sick Children, Toronto, ON, Canada. 4Mount Sinai Hospital, Toronto, ON, Canada. 5Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada. 6Public Health Ontario, Toronto, ON, Canada. 7Institute for Clinical Evaluative Sciences, Toronto, ON, Canada


Background: Prior to the recent outbreak in 2015, Zika virus (ZIKV) infections in adults were considered to be largely asymptomatic, and characterized by a short, febrile illness. Increasing reports of symptomatic neurologic disease amongst infected adults warrant further investigation into the manifestations and long-term outcomes associated with ZIKV in adults. Objective: To synthesize the literature on clinical manifestations and sequelae of ZIKV infection in adults. Methods: We conducted a systematic search of the MEDLINE, Embase, PubMed, CINAHL, LILACS and WHO's ICTRP clinical trials databases using the search terms “Zika virus” and “Zika infection”. Abstracts and conference proceedings were excluded, along with editorials, letters and news articles. Case series/reports with less than 10 participants and any animal studies were also excluded. Two reviewers followed PRISMA and MOOSE reporting guidelines. We used Joanna Briggs Institute Critical Appraisal tools for quality appraisal. Conflicts were resolved by consensus or consultation with third reviewer. Results: We identified 6248 references in our initial search up to April 30, 2018, of which 38 studies were included [Cross-sectional/descriptive (n=28), case-control (n=5), case reports/series (n=3), cohort (n=2)]. The majority of studies originated from North and South America, with publications from Brazil (n=7), Colombia (n=6), and the USA (n=5) constituting more than half of the data set. The most common outcomes reported were Guillain-Barre syndrome, encephalitis and myelitis. Approximately 37% of the studies reviewed met 80% or more of the quality assessment criteria for their respective study design. We will finalize complete analysis of the data prior to the conference. Conclusion: Based on preliminary results, there is evidence of adverse neurological clinical manifestations and long-term sequalae associated with ZIKV infection in adults. More targeted studies need to be conducted in non-pregnant adults to better understand clinical manifestations and longer term outcomes in this population.