Clinical and Preclinical Evidence for Adverse Neurodevelopment after Postnatal Zika Virus Infection

Abstract

Although the Zika virus (ZIKV) typically causes mild or no symptoms in adults, during the 2015−2016 outbreak, ZIKV infection in pregnancy resulted in a spectrum of diseases in infants, including birth defects and neurodevelopmental disorders identified in childhood. While intense clinical and basic science research has focused on the neurodevelopmental outcomes of prenatal ZIKV infection, less is known about the consequences of infection during early life. Considering the neurotropism of ZIKV and the rapidly-developing postnatal brain, it is important to understand how infection during infancy may disrupt neurodevelopment. This paper reviews the current knowledge regarding early postnatal ZIKV infection. Emerging clinical evidence supports the hypothesis that ZIKV infection during infancy can result in negative neurologic consequences. However, clinical data regarding postnatal ZIKV infection in children are limited; as such, animal models play an important role in understanding the potential complications of ZIKV infection related to the vulnerable developing brain. Preclinical data provide insight into the potential behavioral, cognitive, and motor domains that clinical studies should examine in pediatric populations exposed to ZIKV during infancy.

Descriptive analysis of surveillance data for Zika virus disease and Zika virus-associated neurological complications in Colombia, 2015–2017

“…For these reasons, pregnant females are considered a high-risk group for ZIKV infection. Infants and children can also become infected with ZIKV during the postnatal period through mosquito bites and possibly breast milk; however, few studies have evaluated postnatal ZIKV infection prospectively [ 24 ].…”

Advances in congenital Zika syndrome and its pathogenesis

“…CZS在妊娠期感染ZIKV的妇女中的发生率为5%1 4% [4] , 其特有的临床症状包括: (5) 明显的早期高张力和锥体外系受累的症状 [5] . 癫痫 图 1 (网络版彩色)寨卡病毒颗粒结构与基因组组成 Figure 1 (Color online) The particle structure and genome of ZIKV 是CZS的主要神经学特征, 在患有CZS且临床表现为小 头畸形的儿童中, 48%~96%被检测出患有癫痫 [6] .…”

Systemic inflammation, innate immunity and pathogenesis after Zika virus infection in cynomolgus macaques are modulated by strain-specificity within the Asian lineage

“…Although ZIKV is primarily spread through the Aedes mosquito vector, other means of transmission have also been reported [3,4]. Maternal-to-fetal vertical transmission of ZIKV through the placenta during pregnancy have been linked with increased risk of preterm birth, stillbirth, as well as a number of debilitating neurological congenital pathologies collectively grouped under the term congenital Zika syndrome (CZS) (which includes microcephaly, abnormal development of the brain, ocular pathologies, limb contractures and other neurologic abnormalities) [5][6][7] [8]. Conversely, acute ZIKV infection in adults often remains unnoticed, and symptomatic cases are characterized by a mild flu-like disease, inluding fever, headaches, myalgia and arthralgia, and occasionally conjuncivitis, rash, and gastro-intestinal signs, with an onset at 3-12 days after exposure [9,10].…”

“…Although ZIKV is rarely associated with mortality or severe acute disease, based on epidemiological data ZIKV infections have also been linked with rare neurological diseases and autoimmune Guillain-Barré Syndrome (GBS) [5,6,11,12].…”

“…Conversely, acute ZIKV infection in adults often remains unnoticed, and symptomatic cases are characterized by a mild flu-like disease, inluding fever, headaches, myalgia and arthralgia, and occasionally conjuncivitis, rash, and gastro-intestinal signs, with an onset at 3–12 days after exposure [ 9 , 10 ]. Although ZIKV is rarely associated with mortality or severe acute disease, based on epidemiological data ZIKV infections have also been linked with rare neurological diseases and autoimmune Guillain-Barré Syndrome (GBS) [ 5 , 6 , 11 , 12 ].…”