Health Outcomes in Post-natally Acquired Pediatric Zika Virus Infection: A Systematic Review

Laura Erdman1,2, Lauren Ramsay2,3, Clare Whitehead4,2, Raphael Ximenes3,2, Joanna Bielecki3, Justin Boyle2, Panashe Tombindo2,3, Ryan O’Reilly3,2, Carsten Krueger1,2, Shannon Willmott1,2, Rafael Neves Miranda3, Kellie Murphy4,2, Beate Sander3,5,6,7, Shaun Morris1,2
1Hospital for Sick Children, Toronto, ON, Canada. 2University of Toronto, Toronto, ON, Canada. 3Toronto Health Economics and Technology Assessment (THETA) Collaborative, University Health Network, 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/Objective: The primary focus of pediatric Zika virus (ZIKV) research has been the sequelae of congenital infection.  ZIKV acquired post-natally has generally been described as asymptomatic or a self-limited febrile illness; however, there has been minimal research into the clinical course and potential complications. Animal studies suggest that ZIKV acquired in infancy may have neurodevelopmental sequelae. We aim to summarize the literature on health outcomes in post-natally acquired pediatric ZIKV infection using systematic review methodology. Methods: We are conducting a systematic review following PRISMA guidelines and Cochrane systematic review methodology. MEDLINE, Embase, PubMed, CINAHL, LILACS, and WHO's ICTRP clinical trials registries database were searched using terms “Zika virus” and “Zika infection”. Editorials, letters, news articles, and experimental animal studies were excluded. Case series required 10 or more cases for inclusion. Two independent reviewers conducted title/abstract screening, full text screening, and data extraction. Conflicts are resolved by consensus or consultation with a third reviewer. Results: Initial search up to April 30, 2018 recovered 7394 references. 9 case series met inclusion criteria and present data from Brazil (N=1), Colombia (N=1), Dominica (N=1), Singapore (N=2), and US (N=4). N ranged from 11-18,576, and age from 1 month-18 years. Laboratory confirmation of ZIKV infection was inconsistent across regions. Overall, there was poor reporting of clinical symptoms. The most common symptoms were fever (71-93%) and rash (94-100%), in part reflective of case definitions. Severe complications were rare (Guillain-Barre Syndrome 0-0.2%; meningitis/encephalitis 0-0.09%; mortality 0-0.05%). No neurodevelopmental outcomes were reported.  Literature search will be updated to December 31, 2018 and data analysis completed by the time of the conference. Conclusion: This up-to-date systematic review of health outcomes in post-natally acquired pediatric Zika virus infection will summarize current knowledge and identify research gaps for optimization of clinical care and public health interventions.