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Home > ABOUT THE INSTITUTE > News > A group of Slovenian researchers first to show evidence that fetal brain damages are caused by Zika Virus.

A group of Slovenian researchers first to show evidence that fetal brain damages are caused by Zika Virus.

Prestigious The New England Journal of Medicine published breakthrough research paper on Feb 10th on strong evidence that congenital CNS malformations, associated with Zika virus infection in pregnancy, are a consequence of viral replication in the fetal brain. A group led by Prof. Dr. Tatjana Avšič Županc (Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana), Dr. Nataša Tul (Department of Perinatology, University Medical Center Ljubljana), Dr. Jože Pižem (Institute of Pathology, Faculty of Medicine, University of Ljubljana) led extensive study on a case of fetus of young woman infected by Zika virus from mid October 2015 to mid January 2016.

Results of the study present strong evidence of the teratogenic potential of Zika virus. Demonstration of viral particles and high load of Zika virus RNA in the brain samples, absence of other possible pathogens and complete viral genome sequence present the most compelling evidence to date that congenital CNS malformations, associated with Zika virus infection in pregnancy, are a consequence of viral replication in the fetal brain.

Zika virus, a flavivirus transmitted to humans by predominantly daytime-active Aedes mosquitoes, has been known to cause sporadic disease cases in a narrow equatorial belt from Africa to Asia since the first recognized human case in the 1950s. Up to 80 % infections are asymptomatic, and symptomatic infections are usually characterized by short self-limiting febrile illness. In 2014, the virus spread across the Pacific and in 2015 dramatically affected the Americas.

In October 2015, Brazilian health authorities reported an unusual increase in the number of cases of microcephaly in the Pernambuco state, and further retrospective analyses identified a substantial rise in the cases of microcephaly compared to previous years that coincided with ongoing Zika epidemic. WHO Director-General, following the advice of an Emergency Committee, convened on 1 February 2016, declared the cluster of microcephaly and other neurologic disorders reported in Brazil to be a Public Health Emergency of International Concern.

There is substantial and growing evidence of causal relationship between Zika virus infections in pregnancy and congenital central nervous system malformations. Zika virus has been recently found in the amniotic fluid of fetuses diagnosed with microcephaly demonstrating the intrauterine transmission of the virus. In a report published online by The New England Journal of Medicine, Slovenian researchers present for the first time the fetal brain pathology, associated with Zika virus vertical (e.g., from mother to fetus) infection.

Research paper reports a case of previously healthy European female, who had developed a febrile illness with a generalized rash at the end of the first trimester of pregnancy while living and working in Brazil. Fetal anomalies were first observed by ultrasound in the 29th week, and she was referred to Department of Perinatology in Ljubljana, Slovenia where the examination in the 32th week of gestation revealed intrauterine growth retardation, microcephaly and brain anomalies and calcifications with no other fetal defects. Brain pathology and microcephaly were severe, so a poor prognosis for neonatal health was given to the mother and she requested a medical termination of pregnancy, which was further approved by the National and hospital’s Ethics Committees.  A fetal autopsy exposed severe cerebral structural abnormalities (small brain, almost complete absence of brain folds and grooves, hydrocephalus) while microscopic examination revealed features, consistent with viral infection of the brain. Electron microscopy demonstrated clusters of virus-like particles and particles with morphological characteristics of flavivirus replication complexes (suggesting viral replication in the brain) in the brain samples.

Virological examinations with reverse transcription-polymerase chain reaction (RT-PCR) confirmed the presence of Zika virus RNA and (relatively) high viral load in fetal brain samples. Numerous autopsy samples of brain and other tissues were extensively tested by PCR for other flaviviruses (including dengue and yellow fever viruses), other viruses (including chikungunya virus, cytomegalovirus and herpes viruses) and other possible pathogens. Zika virus was the sole pathogen detected, and it was only demonstrated in brain tissue. We further confirmed the result with complete viral genome sequence recovered from the brain tissue that was in 99.7 % identical with Zika virus strains detected in French Polynesia in 2013 and Sao Paolo, Brazil, in 2015.

Ljubljana, February 10th 2016

Article available at: NEJM - Zika Virus Associated with Microcephaly

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