Zika goes under the radar

The emergence of Zika virus in Brazil in recent years has led to millions of people becoming infected. The majority of them had no symptoms at all, but some individuals were pregnant and the infection led to devastating damage to their baby’s brains and caused a condition called microcephaly. But this only affected a small number of them so did the other infants escape harm? A new paper published this week suggests not. Chris Smith spoke to obstetrician Kristina Adams Waldorf, who says that Zika virus infection can still do lasting damage to the developing nervous system without causing obvious microcephaly.

Kristina - Early 2016 I was reading a newspaper and it showed an infant with a very small head in Brazil and the question was, on the front page, could this be related to the Zika virus? I knew immediately that my life would change and we began to study intensively whether Zika virus could, in fact, be causing small heads in infants that were exposed to Zika virus in-utero.

But how was Zika virus actually infecting the foetus, and what was the spectrum of injury, and could we detect some of the early signs of this injury in the foetus? For the study we used a non-human primate model - a pig-tailed macaque - which we could use to model a Zika virus infection in pregnancy by inoculating Zika virus under the skin of the mother, and then we could follow what happened with ultrasound and then see what happened at the time of delivery in the foetal brain.

Chris - Did the virus get into the foetuses in these monkeys?

Kristina - It did. And we found that Zika virus did indeed cause significant damage to the foetal brain even when the head size was normal, and the regions in the brain that were hardest hit were areas that generated new brains cells. One very important injured part of the foetal brain was something called the hippocampus and cells in this part are very important for memory and learning, and they contribute to brain health through at least adolescence. So loss of these brain cells is expected to cause problems with learning, memory, behaviour and may not show until the child might be even one or two years old.

Chris - Are you saying then there might be a sort of clinical iceberg here where we know that there’s the dramatic effect microcephaly - small head small brain, and we know that happens in 5% of cases where there’s been an infection, but there may be this enormous burden of diseases out there that we don’t know about where there has been some subtle injury to the brain during development and that may not manifest until the individual starts to miss developmental milestones or starts to show deficits once they grow up a bit?

Kristina - Exactly. We think that this is akin to an iceberg type of phenomenon. And what it also means is that our current clinical criteria that we use, such as head size, to diagnose the Zika virus related brain injury really fails to capture this more subtle, but very significant, brain damage.

Chris - Does this mean then that we urgently need to be going and appraising cases where there wasn’t overt, obvious michrocephaly but there was evidence of infection having occurred, to follow up those kids and see if they do end up with some kind of deficit along the lines that you’re suggesting?

Kristina - Absolutely. And not only do we need to follow children where we know that they had a Zika virus infection, but also in cases where we weren’t so sure. We need to look for neural cognitive delays in learning and neurological disorders that develop over time. I think that a broader segment of the population that are exposed and at risk for Zika virus should ideally be screened in this way over a longer period of time.

Chris - What should parents look out for then if you’re someone who has been exposed because they didn’t have the benefit of knowing what you’ve shown in this study beforehand? They’re probably quite worried.

Kristina - There are neurocognitive specialists that have testing that can be performed in young children to assess for delays in learning, changes in behaviour, and things that we can actually pick up in this way. Unfortunately, these specialists don’t exist in large parts of the world where Zika virus is locally transmitted but, to the best that we can, we should try to make some of these tools available. I think that we need to also be sure to let paediatricians know that the infant’s head size at birth should not be the main criteria for determining if a child had a brain injury related to Zika. Many children might not then benefit from these developmental and neurocognitive tests to identify deficits.