The link between the Zika virus and microcephaly, which results in babies being born with brain damage and unusually small heads, is still unproven but the evidence is building up. New Scientist explores how much we now know, and what gaps remain
What’s the latest evidence?
For the first time, the complete genome of the Zika virus has been recovered from a fetus with microcephaly.
The fetus was conceived by a Slovenian woman while she worked as a volunteer in Brazil. After returning home 28 weeks into her pregnancy, ultrasound scans revealed such severe brain abnormalities that she had the pregnancy terminated, enabling researchers to analyse the brain.
As well as the Zika genome, the researchers found high levels of viral RNA and viral particles in brain cells. There was no evidence of the presence of other pathogens that could have caused the brain damage, and no other organs were damaged suggesting the virus preferentially attacks the brain. “Microscopic examination revealed that brain cells were destroyed due to infection with the virus. While it can’t be definitive proof, it may present the most compelling evidence to date that congenital brain malformations associated with Zika virus infection in pregnancy are a consequence of viral replication in the fetal brain,” says Tatjana Avšič Županc of the University of Ljubljana in Slovenia, who was involved with the autopsy.
Organisations tracking the problem say the new evidence is of concern. “The case report from Slovenia adds to the body of evidence that trans-placental infections with the Zika virus can cause severe central nervous system damage and microcephaly,” says Giovanni Mancarella of the European Centre for Disease Prevention and Control. “What we lack is how often these infections take place across the placenta and how often it results in brain malformations,” he says. “It’s unlikely all Zika infections during pregnancy result in fetal infection, because if it was, we would seem many more cases in the affected countries,” he said.
MRI scans showing brains of (i) someone with normal brain development and (ii) someone with microcephaly. Image © Yale University.
What other evidence is there of the link?
Zika virus RNA has been found in the amniotic fluid of two women whose unborn babies were diagnosed with microcephaly by ultrasound in Brazil. It has also been identified in
blood and tissue samples, including from the brain and placenta, in babies who were miscarried or died soon after birth, and in spinal fluid from surviving babies with the condition.
The other strand of evidence linking Zika and microcephaly is the pattern of spread. Microcephaly cases in Brazil started to rise around 6 months after authorities confirmed Zika transmission there, hinting that the defect might have been caused by exposure to the virus in the womb. An increase in brain defects was also seen in newborns in French Polynesia in 2014, following a large Zika outbreak there.
Does anyone doubt that Zika is the cause?
Some researchers have said that Brazil has historically under-reported cases of microcephaly. Only 150 cases were reported in 2014. The incidence is two to fourfold higher in countries such as the US. Sceptics say that the surge of almost 4800 cases since October last year is down to increased surveillance since people became aware of the Zika threat. An analysis from the US Centres for Disease Control and Prevention challenges this. It says that the rise from 0.5 to 20 cases per 10,000 live births in the second half of last year goes way beyond this and suggests instead “a sharp increase in birth prevalence”.
However, of the 4783 cases of microcephaly identified as of 5 February, closer examination of 1113 of them by Brazilian health officials revealed that only 404 could be linked to Zika, suggesting the others had other causes such as a genetic predisposition. To get to the bottom of what’s going on, Brazil will follow 6000 women in infected areas in the north of the country to try and better pin down the cause.
What evidence would prove the link beyond doubt?
One approach is comparing rates of Zika infection in babies born with and without microcephaly, but getting a definitive answer could take months or even years.
Catherine Spong, deputy director of the US National Institute of Child Health and Human Development in Bethesda, Maryland, says that it will take several lines of inquiry. “We need to demonstrate what happens when someone has the virus, so we need to identify and follow women from pregnancy through to birth through well-designed studies that compare those that do and those that don’t get infected,” says Spong. “We also need to rule out any other possible causes, such as cytomegalovirus or rubella, and identify all influencing factors, such as whether the stage of pregnancy affects outcomes.” In parallel, we need animal and lab studies to look at how the virus impacts the brain and cells within it, she says.
Journal reference: New England Journal of Medicine, DOI: 10.1056/NEJMoa1600651
Top image: Latin America Science
Source: New Scientist