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

Abstract

Limited information is available on health outcomes related to Zika virus infection acquired during childhood. Zika virus can cause severe central nervous system malformations in congenitally exposed fetuses and neonates. In vitro studies show the capacity of Zika virus to infect neural progenitor cells, induce central and peripheral neuronal cell deaths, and target different brain cells over the course of brain development. Studies of postnatally infected mice and nonhuman primates have detected degradation of neural cells and morphologic brain cell changes consistent with a broad neuroinflammatory response. In addition, case reports of central nervous system disease in adults and in adolescents secondary to Zika virus infection suggest that Zika virus 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 Zika virus infection in humans negatively affects the central and peripheral nervous systems and causes long-term neurological damage or cognitive effects is currently unknown. To better understand the potential for neurological sequelae associated with acquired Zika virus infection in children, we reviewed the biological, clinical, and epidemiologic literature and summarized the evidence for this link. First, we review biological mechanisms for neurological manifestations of Zika virus infection in experimental studies. Second, we review observational studies of congenital Zika virus infection and case studies and surveillance reports of neurological sequelae of Zika virus infection in adults and in children. Lastly, we discuss the challenges of conducting Zika virus-neurological sequela studies and future directions for pediatric Zika virus research.

Keywords: Child development; Flavivirus infections; Malformations of cortical development; Neurological sequelae; Zika virus infection.