The presence of Zika virus in fetal brain tissue on HWN ZIKA VIRUS UPDATE

An autopsy of a fetus with microcephaly, whose mother had traveled to Brazil and had symptoms of Zika virus, revealed the presence of Zika virus in fetal brain tissue, a case report from Slovenia showed.

The fetus had a head circumference of 26 cm (4 standard deviations below average), which classifies as microcephaly, and samples of fetal brain tissue tested positive for Zika virus, reported Jernej Mlakar, MD, of the University of Lubljana in Slovenia, and colleagues.

Interestingly, Zika virus could not be found in any other organs, including the placenta, they wrote in a brief report in the New England Journal of Medicine.

Michael Greene, MD, of Massachusetts General Hospital in Boston, and co-author of an accompanying NEJM editorial, told MedPage Today that, for the first time, this provides a biological association between Zika and microcephaly where previously there had only been an epidemiologic link.

Up until now, all of the evidence suggesting that these cases of microcephaly [are] related to the Zika virus infection is temporal and geographic. Areas where Zika has become prominent are areas where kids with microcephaly are born," he said. "This is the first demonstration of the virus in brain tissue and the kind of damage to brain tissue that you would expect in a fetus with microcephaly.

Genomic sequencing was performed on the fetal brain tissue samples, which showed a similarity to findings in a woman who had died with Zika infection during a Polynesian outbreak.

PCR (polymerase chain reaction) assay ruled out infection with other mosquito-borne viruses including dengue, yellow fever, and chikungunya. It was also negative for other viruses that can cause birth defects like microcephaly, such as rubella, Toxoplasma gondii, and herpes simplex virus.

The fetus mother had been working in the affected area of Brazil when she became pregnant. She then returned home to Slovenia and reported fever, rash, muscle aches, and pain behind the eyes at 13 weeks gestation. Ultrasounds at 14 and 20 weeks were unremarkable, but by 29 weeks, there was evidence of poor fetal growth (both head and body), as well as calcifications on the brain.

At 32 weeks, fetal calcifications were observed on the brain and placenta. Doctors treating the patient had also observed the fetal brain had abnormally large ventricles. The large size of the ventricles compared to the small size of the head suggested that the brain tissue had degenerated, allowing more space for the fluid in the ventricles. The patient then requested a pregnancy termination and the fetus was autopsied.

The autopsy found that the weight of the whole brain was 84 g, which, like the head circumference, was 4 SDs below average, and described as "grossly diseased." Researchers observed numerous calcifications in the cortex and subcortical white matter on the frontal, parietal, and occipital lobes. There was also evidence of degeneration to the cerebellum and degeneration of the nerve axons that travel from the brain to the spinal cord.

Clinical Implications Unclear:
The editorial by Greene and two colleagues indicated these autopsy findings do not yet have immediate clinical implications.

Assuming the association between Zika virus and microcephaly exists, we do not know whether the timing of the infection during pregnancy has an effect on the risk of fetal abnormalities, nor do we have any idea of the magnitude of that risk, they wrote.

They added the fact that, in this case report, severe fetal abnormalities were noted on ultrasound very late in gestation -- and in many cases, that would be too late to terminate the pregnancy.

Is there a sensitive test that can be applied earlier? And is previous infection protective? they wrote.

To that point, Greene told MP that it is unclear whether Zika is an organism that causes infection the first time the mother is exposed or can cause a fetal infection if the mother was previously exposed. Still, he added that none of these findings should change the current guidelines for clinicians treating pregnant women who may have been exposed to Zika virus.

This case pretty well close to nails the biological causality of the virus and disease," said Greene. "As a practical matter, it seals the deal on what we knew, but it really doesn't change any of the CDC or WHO recommendations for pregnant women.

Source: MedPage, HWN Africa.