Pathological Changes Associated with Congenital Zika Virus Infection

Dear Colleagues,

Zika virus, a member of the family of Flavivirus, has become a source of great concern in terms of public health in recent years, with ZKV spreading to Caribbean and Latin American countries.

The virus is particularly harmful during pregnancy, especially if the mother develops a primary infection at the time of organogenesis (five to ten weeks of gestation) when the virus infects both the placenta and the fetus. The placenta might represent a reservoir of ZKV and thus contribute to the spreading of the ZKV, especially to the central nervous system. ZKV has shown a high trophism for the brain tissue, usually affecting the cerebral cortex, leading to severe brain atrophy and lissencephaly, brain calcifications. In addition, the diencephalon, the lateral ventricle, and the cerebellar hemisphere can be affected. There has been a significant statistical surge of cases of perinatal microcephaly, especially in the northern counties of Brazil, and the Brazilian health authority has estimated that 500,000 to 1,5 million mothers were affected by congenital ZKV infection during the 2015 outbreak.

Congenital ZKV infection is highly associated with fetal–neonatal microcephaly, which should be genetically distinguished from primary microcephaly. The clinical diagnosis of congenital ZKV infection relies upon a positive serologic test based on r-RT-PCT (real-time transcription polymerase chain reaction) and direct demonstration of ZKV-RNA on a cultured cortex specimen during autopsy, in cases of perinatal death. Prenatal diagnosis of brain malformations, through specific findings, may be detected by means of 2D/3D ultrasound as well as by means of fetal MR imaging. The main severe anomaly associated with ZKV congenital infection is microcephaly, which it is usually detected during the third trimester of pregnancy. Fetal MRI may be more accurate than ultrasound and may enhance the prenatal detection of polymicrogyria, laminar necrosis, and brain-stem anomalies. Neuropathology is mandatory, and demonstration of RNA virus in brain cells is critical to demonstrating a causative effect of ZKV congenital infection.

Prof. Dr. Gabriele Tonni
Guest Editor

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