Introduction: The primary focus of pediatric Zika virus (ZIKV) research has been the sequelae of congenital infection. While animal data suggest that ZIKV infection in infancy may cause neurodevelopmental abnormalities, relatively few reports describe post-natally acquired infection in infants and children, which is important for case recognition and prognostication. The objective of this study was to understand health outcomes in pediatric post-natally acquired ZIKV infection.
Methods: A systematic review was conducted by searching MEDLINE, Embase, PubMed, CINAHL, LILACS, and WHO's ICTRP clinical trials registries database using terms related to “Zika virus” and “Zika infection” from inception until December 2018. Two independent reviewers conducted screening and data extraction for primary studies reporting outcomes (clinical signs/symptoms and complications) of pediatric (<18 years) post-natal ZIKV infection. Conflicts were resolved by consensus or a third reviewer. Joanna Briggs Institute checklists were used for quality appraisal.
Results: Twelve case series representing 10 study populations met inclusion criteria and described acute infections. Data originated from Brazil (1), Caribbean islands (4), Colombia (1), Singapore (1), and United States (3) from 2015-2017. Many studies were small (range 11-18,576 participants, median 158; total participants 20,049). All ages 0 to <18 were represented with relatively even distribution. 70% of studies universally tested and confirmed ZIKV infection by laboratory methods, with variability in methods between studies. Fever and rash were common (71-93% and 94-100%, respectively), potentially reflective of case definitions. Clinical signs and symptoms were similar between age groups. Hospitalization ranged from 0-100% (median 2.8%). Severe acute complications were rare (Guillain- Barré Syndrome (GBS) 0-0.2%; any neurological complication including GBS 0-0.5%; mortality 0-0.05%). No long-term outcomes including neurodevelopmental outcomes were reported. 45% of studies fulfilled >80% of quality appraisal criteria. No meta-analysis was performed.
Conclusions: While ZIKV infection in children is likely not rare, there are limited robust, high-quality data on post-natally acquired pediatric ZIKV infection. Acute severe disease and death appear to be rare. Large studies in low- and middle-income countries with broader clinical case definitions, ZIKV and co-infection laboratory testing, and longitudinal assessment of neurodevelopmental sequelae are needed to inform clinical care and preventative measures.