Review: Evidence of Neurological Sequelae in Children With Acquired Zika Virus Infection

Abstract Limited information is available on health outcomes related to Zika virus (ZIKV) infection acquired during childhood. ZIKV can cause severe central nervous system malformations in congenitally-exposed fetuses and neonates. In vitro studies show ZIKV's capacity to infect neural progenitor cells, induce central and peripheral neuronal cell death, and target different brain cells over the course of brain development. Studies of postnatally-infected mice and non-human primates have detected degradation of neural cells and morphological brain cell changes consistent with a broad neuroinflammatory response. In addition, case reports of central nervous system disease in adults and adolescents secondary to ZIKV infection suggest that ZIKV may have a broader impact on neurological health beyond that observed in congenitally-exposed newborns. Long-term neurological complications have been observed with other acquired flaviviral infections, with clinical symptoms manifesting for years after primary infection. The extent to which postnatal ZIKV infection in humans negatively affects the central and peripheral nervous systems and causes long-term neurological damage and/or cognitive effects is currently unknown. To better understand the potential for neurological sequela associated with acquired ZIKV infection in children, we reviewed the biological, clinical, and epidemiological literature and summarized the evidence for this link. First, we review biological mechanisms for neurological manifestations of ZIKV infection in experimental studies. Second, we review observational studies of congenital ZIKV infection and case studies and surveillance reports of neurological sequela of ZIKV infection in adults and children. Lastly, we discuss the challenges of conducting ZIKV-neurological sequelae studies and future directions for pediatric ZIKV research.