Postnatal symptomatic Zika virus infections in children and adolescents: A systematic review

Abstract

Background Recent Zika virus (ZIKV) outbreaks in the Pacific and the Americas have highlighted clinically significant congenital neurological abnormalities resulting from ZIKV infection in pregnancy. However, little is known about ZIKV infections in children and adolescents, a group that is potentially vulnerable to ZIKV neurovirulence. Methods We conducted a systematic review on the clinical presentation and complications of children and adolescents aged 0 to 18 years with a robust diagnosis of ZIKV infection. We searched PubMed, Web of Science, LILACs, and EMBASE until 13 February 2020 and screened reference lists of eligible articles. We assessed the studies’ risk of bias using pre-specified criteria. Findings Our review collated the evidence from 2543 pediatric ZIKV cases representing 17 countries and territories, identified in 1 cohort study, 9 case series and 22 case reports. The most commonly observed signs and symptoms of ZIKV infection in children and adolescents were mild and included fever, rash, conjunctivitis and arthralgia. The frequency of neurological complications was reported only in the largest case series (identified in 1.0% of cases) and in an additional 14 children identified from hospital-based surveillance studies and case reports. ZIKV-related mortality was primarily accompanied by co-morbidity and was reported in one case series (<0.5% of cases) and three case reports. One death was attributed to complications of Guillain-Barré Syndrome secondary to ZIKV infection. Conclusions and relevance Based on the current evidence, the clinical presentation of ZIKV infection in children and adolescents appears to be primarily mild and similar to the presentation in adults, with rare instances of severe complications and/or mortality. However, reliable estimation of the risks of ZIKV complications in these age groups is limited by the scarcity and quality of published data. Additional prospective studies are needed to improve understanding of the relative frequency of the signs, symptoms, and complications associated with pediatric ZIKV infections and to investigate any potential effects of early life ZIKV exposure on neurodevelopment.

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

“…Children account for 10−31% of ZIKV infections in various studies [ 50 , 51 , 52 ]. However, the data on ZIKV in children are still sparse; many studies include a wide age range in their pediatric population (1 month to 18 years), and few include significant numbers of children infected with ZIKV at <1 year of age [ 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. Acute neurologic complications of ZIKV infection in children have been described, including Guillian-Barre Syndrome, polyneuropathy, encephalitis, demyelinating disease, and inflammatory diseases of the central nervous system (CNS) [ 58 , 59 , 61 ].…”

“…Acute neurologic complications of ZIKV infection in children have been described, including Guillian-Barre Syndrome, polyneuropathy, encephalitis, demyelinating disease, and inflammatory diseases of the central nervous system (CNS) [ 58 , 59 , 61 ]. A meta-analysis of pediatric ZIKV infection found that these cases are primarily mild, and most present with a fever and rash [ 56 ], but severe neurologic complications and death have also been reported [ 59 , 62 , 63 , 64 ].…”

The legacy of ZikaPLAN: a transnational research consortium addressing Zika

“…In addition to reporting on the findings from individual cohorts, our team of investigators has also been actively engaged in wider evidence synthesis and data sharing efforts, leading to two systematic reviews [ 51 , 52 ] and contributing to four critical commentaries [ 6 , 53–55 ] and three planned individual participant data meta-analyses. The first systematic review collates evidence from 34 studies of ZIKV co-infections, and suggests that, while ZIKV co-infections, especially with other arboviruses, are frequently reported, they do not appear to materially alter the clinical presentation or enhance the severity of uncomplicated acute ZIKV disease [ 51 ].…”

“…The first systematic review collates evidence from 34 studies of ZIKV co-infections, and suggests that, while ZIKV co-infections, especially with other arboviruses, are frequently reported, they do not appear to materially alter the clinical presentation or enhance the severity of uncomplicated acute ZIKV disease [ 51 ]. The second systematic review of 32 studies on postnatal ZIKV infections in children and adolescents highlights the scant evidence base in this age range and the need for population-based studies quantifying the associations of pediatric ZIKV infections, especially those occurring in infancy, with neurologic complications and later neurodevelopmental outcomes [ 52 ]. Individual-level data from our cohort studies has also been shared for joint analyses as part of the Zika Brazilian Cohorts Consortium [ 56 ], the European Commission-funded Zika Cohorts Vertical Transmission Study Group [ 57 ], and the World Health Organization-led Zika Virus Individual Participant Data Consortium [ 58 , 59 ].…”

The Neurobiology of Zika Virus: New Models, New Challenges

“…Therefore, gestation trimester plays a pivotal role in the outcomes due to the intrinsic dynamics of brain development. Apparently, infection in pediatric populations result in mild complications but biases must be considered ( Ramond et al, 2020 ), such as the fact that most studies devoted attention to the prenatal exposure. The early postnatal ZIKV infection may be crucial to the neurodevelopment ( Mavigner et al, 2018 ), but it remains largely unknown in humans, particularly regarding the subtle alterations within the gray and white matter.…”