Placental Histopathology and Clinical Presentation of Severe Congenital Zika Syndrome in a Human Immunodeficiency Virus-Exposed Uninfected Infant

Zika virus is a mosquito-borne flavivirus that is related to dengue virus and transmitted primarily by Aedes aegypti mosquitoes, with humans acting as the principal amplifying host during outbreaks. Zika virus was first reported in Brazil in May 2015 (1). By February 9, 2016, local transmission of infection had been reported in 26 countries or territories in the Americas.* Infection is usually asymptomatic, and, when symptoms are present, typically results in mild and self-limited illness with symptoms including fever, rash, arthralgia, and conjunctivitis. However, a surge in the number of children born with microcephaly was noted in regions of Brazil with a high prevalence of suspected Zika virus disease cases. More than 4,700 suspected cases of microcephaly were reported from mid-2015 through January 2016, although additional investigations might eventually result in a revised lower number (2). In response, the Brazil Ministry of Health established a task force to further investigate possible connections between the virus and brain anomalies in infants (3).

Zika virus (ZIKV), a mosquito-borne positive-stranded RNA virus of the family Flaviviridae (genus Flavivirus), is now causing an unprecedented large-scale outbreak in the Americas. Historically, ZIKV spread eastward from equatorial Africa and Asia to the Pacific Islands during the late 2000s to early 2010s, invaded the Caribbean and Central and South America in 2015, and reached North America in 2016. Although ZIKV infection generally causes no symptoms or only a mild self-limiting illness, it has recently been linked to a rising number of severe neurological diseases, including microcephaly and Guillain-Barré syndrome. Because of the continuous geographic expansion of both the virus and its mosquito vectors, ZIKV poses a serious threat to public health around the globe. However, there are no vaccines or antiviral therapies available against this pathogen. This review summarizes a fast-growing body of literature on the history, epidemiology, transmission, and clinical presentation of ZIKV and highlights the urgent need for the development of efficient control strategies for this emerging pathogen.

Purpose To document the imaging findings associated with congenital Zika virus infection as found in the Instituto de Pesquisa in Campina Grande State Paraiba (IPESQ) in northeastern Brazil, where the congenital infection has been particularly severe. Materials and Methods From June 2015 to May 2016, 438 patients were referred to the IPESQ for rash occurring during pregnancy or for suspected fetal central nervous system abnormality. Patients who underwent imaging at IPESQ were included, as well as those with documented Zika virus infection in fluid or tissue (n = 17, confirmed infection cohort) or those with brain findings suspicious for Zika virus infection, with intracranial calcifications (n = 28, presumed infection cohort). Imaging examinations included 12 fetal magnetic resonance (MR) examinations, 42 postnatal brain computed tomographic examinations, and 11 postnatal brain MR examinations. Images were reviewed by four radiologists, with final opinion achieved by means of consensus. Results Brain abnormalities seen in confirmed (n = 17) and presumed (n = 28) congenital Zika virus infections were similar, with ventriculomegaly in 16 of 17 (94%) and 27 of 28 (96%) infections, respectively; abnormalities of the corpus callosum in 16 of 17 (94%) and 22 of 28 (78%) infections, respectively; and cortical migrational abnormalities in 16 of 17 (94%) and 28 of 28 (100%) infections, respectively. Although most fetuses underwent at least one examination that showed head circumference below the 5th percentile, head circumference could be normal in the presence of severe ventriculomegaly (seen in three fetuses). Intracranial calcifications were most commonly seen at the gray matter-white matter junction, in 15 of 17 (88%) and 28 of 28 (100%) confirmed and presumed infections, respectively. The basal ganglia and/or thalamus were also commonly involved with calcifications in 11 of 17 (65%) and 18 of 28 (64%) infections, respectively. The skull frequently had a collapsed appearance with overlapping sutures and redundant skin folds and, occasionally, intracranial herniation of orbital fat and clot in the confluence of sinuses. Conclusion The spectrum of findings associated with congenital Zika virus infection in the IPESQ in northeastern Brazil is illustrated to aid the radiologist in identifying Zika virus infection at imaging. (©) RSNA, 2016 Online supplemental material is available for this article.