Emerging Role of Zika Virus in Adverse Fetal and Neonatal Outcomes

Abstract

The rapid spread of the Zika virus (ZIKV) in the Americas and its potential association with thousands of suspected cases of microcephaly in Brazil and higher rates of Guillain-Barré syndrome meet the conditions for a Public Health Emergency of International Concern, as stated by the World Health Organization in February 2016. Two months later, the Centers for Disease Control and Prevention (CDC) announced that the current available evidence supports the existence of a causal relationship between prenatal Zika virus infection and microcephaly and other serious brain anomalies. Microcephaly can be caused by several factors, and its clinical course and prognosis are difficult to predict. Other pathogens with proven teratogenicity have been identified long before the current ZIKV epidemic. Despite the growing number of cases with maternal signs of infection and/or presence of ZIKV in tissues of affected newborns or fetuses, it is currently difficult to assess the magnitude of increase of microcephaly prevalence in Brazil, as well as the role of other factors in the development of congenital neurological conditions. Meanwhile, health agencies and medical organizations have issued cautious guidelines advising health care practitioners and expectant couples traveling to, returning from, or living in affected areas. Analogous to dengue virus (DENV) epidemics, ZIKV has the potential to become endemic in all countries infested by Aedes mosquitoes, while new mutations could impact viral replication in humans, leading to increased virulence and consequently heightened chances of viral transmission to additional naive mosquito vectors. Studies are urgently needed to answer the questions surrounding ZIKV and its role in congenital neurological conditions.

FIG 1

Sagittal MRI image of the head of an infant who was born with a head circumference below the third percentile (microcephaly), under investigation. The arrow shows a collapse of the skull, inducing cranio-facial disruption, an exuberant external occipital protuberance (*), and redundant scalp skin (**). (Courtesy of Anita Truttmann, Lausanne-CHUV, Switzerland; reproduced with permission.)

FIG 2

Second-trimester ultrasound images of congenital infections: toxoplasmosis (A and B) and cytomegalovirus (C and D). (A and C) Sagittal plane; (B and D) coronal plane. (A) Dystrophic calcifications in the junction between cortical and subcortical white matter (horizontal arrow), with the enlargement of the subarachnoid space (vertical arrows). (B) Image for the same patient as in panel A. (C) Severe fetal cytomegalic inclusion disease (arrows at top) with ventriculomegaly (v) and calcification (c). There is a noticeable reduction of the brain parenchyma thickness. (D) Image for the same patient as in panel C, showing calcifications (arrow). (Courtesy of Yvan Vial, Lausanne-CHUV, Switzerland; reproduced with permission.)

FIG 3

Example of a pruritic maculo-papular rash on a traveler coming back from New Caledonia (2014).