Zika continues to damage infant's brain after birth

The virus can remain active in a newborn's body for two months, according to detailed study by Brazilian researchers published in the New England Journal of Medicine.

By Ricardo Zorzetto  |  Pesquisa FAPESP magazine – A new piece of bad news has marred the winter lull in Brazil’s Zika epidemic: findings suggesting that the virus can continue to damage a newborn’s brain for weeks after delivery.

Scientists do not yet know precisely how long Zika virus can remain active in a child’s body, but one of the first empirical findings that the virus can remain active long enough to worsen the lesions formed during gestation came to light on August 24, when the correspondence section of the New England Journal of Medicine, one of the world’s most prestigious medical science publications, published a letter by a group of 20 researchers affiliated with institutions in São Paulo, Brazil, describing the case of a male child who was infected by Zika virus during gestation and continued to present with viremia for at least 67 days after birth.

“No descriptions of such a prolonged infection after birth have been published before,” said Edison Durigon, a virologist at the University of São Paulo (USP) and one of the authors of the study.

The boy was born on January 2, 2016 in a São Paulo hospital at 40 weeks’ gestation. He weighed 3,095 g and was 48 cm in length. However, his head circumference was 32.5 cm, considered borderline microcephalic (Brazil’s Ministry of Health classified 32 cm or less as suspected microcephaly until March 2016). The attending physicians noticed that the forehead was narrower than normal, as is usual with microcephalic newborns. Imaging scans showed small areas of brain tissue calcification that are characteristic of Zika infection acquired during gestation.

The baby was transferred to São Paulo’s Santa Casa Hospital, where pediatrician Eitan Berezin took on the case. In late February, Berezin sent blood samples from the boy to Durigon’s group at USP. Previous tests had been negative for cytomegalovirus, toxoplasmosis and congenital rubella, all of which can also cause brain damage. No tests for Zika had yet been performed because these are more complex and time-consuming and are not available free of charge from Brazil’s public health services.

A molecular test confirmed that the virus was active in the baby’s body, and serological tests showed that the infection had occurred during gestation. At 26 weeks of gestation, the mother had presented with fever, rash, headache, conjunctival hyperemia and joint pain. Her husband, who had recently been to the Northeast, reported having the same symptoms three weeks earlier. “Congenital infections are often considered more dangerous when they occur early in pregnancy, but in this case infection by Zika apparently occurred later and also caused damage,” Berezin said.

The first analysis showed a high level of Zika virus in the baby’s blood, so Durigon decided to measure the levels in the boy’s saliva and urine. “At that time, around 54 days after birth, the virus was still reproducing and being excreted in the infant’s urine,” said the virologist, who is a member of the Zika Virus Research Network (Rede Zika), a São Paulo State task force supported by FAPESP.

Tests repeated during the ensuing weeks detected the presence of Zika virus until the child was 67 days old, while rising levels of several antibodies showed that his immune system was learning to combat the virus as he grew older.

The researchers are unable to say how long Zika remained active in the baby’s body. Around mid-March, the parents could no longer continue going to the hospital and care had to be provided remotely. An MRI scan performed late in February showed that the brain lesions remained active, however. “The virus continued to reproduce and damage the baby’s brain tissue well after birth,” Durigon said.

The medical team evaluated the boy again in August, in response to a request from the editors of the New England Journal of Medicine. They found no trace of Zika virus, but a clinical examination evidenced motor problems, particularly right-sided hemiplegia (paralysis) and hypertonia (muscle rigidity). “These effects are only noticed as the infant develops and should begin to acquire certain abilities,” Berezin explained. “In this specific case, I believe physical therapy could help improve the child’s motor skills so that he eventually becomes sufficiently independent.”

For Durigon, the case should ring alarm bells. “We don’t know anything about what happens to infected children after birth,” he stressed. “We’re experiencing a lull in the epidemic just now, but very soon there could well be a second wave of Zika, and we must be prepared to examine these babies in great detail.”

The article “Prolonged shedding of Zika virus associated with congenital infection” by Danielle B.L. Oliveira et al., published in the New England Journal of Medicine on August 24, 2016, can be read at nejm.org/doi/pdf/10.1056/NEJMc1607583.