Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities

Abstract

The current outbreak of Zika virus (ZIKV) infection has been associated with an apparent increased risk of congenital microcephaly. We describe a case of a pregnant woman and her fetus infected with ZIKV during the 11th gestational week. The fetal head circumference decreased from the 47th percentile to the 24th percentile between 16 and 20 weeks of gestation. ZIKV RNA was identified in maternal serum at 16 and 21 weeks of gestation. At 19 and 20 weeks of gestation, substantial brain abnormalities were detected on ultrasonography and magnetic resonance imaging (MRI) without the presence of microcephaly or intracranial calcifications. On postmortem analysis of the fetal brain, diffuse cerebral cortical thinning, high ZIKV RNA loads, and viral particles were detected, and ZIKV was subsequently isolated.

Zika virus: what do we know about the viral structure, mechanisms of transmission, and neurological outcomes?

“…Similar results were obtained for Zika virus isolate that infected a Slovenian woman in Brazil (30) . The long viral persistence in the mother and fetus, from 13 th to 32 nd week of pregnancy, deserves attention and has been reported in other Zika microcephaly cases (37) . The virus replicates in the rough endoplasmic reticulum membranes, as demonstrated in brain cells in vivo (30) (37) and in neurospheres in vitro (38) .…”

“…These phenomena, associated with the presence of activated microglial cells and macrophages in most of the cerebral gray and white matter, and mild perivascular infiltrates composed of T cells and some B cells, indicate immunological involvement in tissue damage (30) . Recruitment of macrophages expressing the scavenger receptor CD60 contributes to the removal of cellular debris (37) (74) . Neurogenesis would be impaired by viral aggression and immune activation, explaining, at least in part, the drastic reduction in the bulk of the central nervous system in microcephalic fetuses and newborns.…”

Neuroimaging findings of Zika virus infection: a review article

“…Microcephaly seems to depend on the timing of prenatal ZIKV infection, with infections early in pregnancy i.e., in the first and early second trimesters being mostly associated with microcephaly. Fetal microcephaly is most likely due to increased developmental neuronal apoptosis secondary to early ZIKV infection of progenitor cells [17][18][19][20][21][22]. The risk of ZIKV infection associated fetal microcephaly is estimated to be 95 (95 CI 34-191) per 10,000 pregnant women that are infected in the first trimester of pregnancy [17].…”

Abbreviations and acronyms

“…In 2015, ZIKV was shown to be associated with microcephaly and birth defects in children exposed in utero following infection of mothers during their pregnancy in Brazil (Zanluca et al, 2015;Calvet et al, 2016;Mlakar et al, 2016). Other studies evidenced the link between ZIKV infection during pregnancy and congenital cerebral malformations in newborns as microcephaly and other dysfunctions (Besnard et al, 2016;Driggers et al, 2016), and this was experimentally supported (Cugola et al, 2016). Moreover, the infection consequences in newborns can cause a range of different pathologies, which were described as the congenital Zika syndrome (Martines et al, 2016).…”