Is the Zika panic over? Ethics of diagnosis and misdiagnosis

By Dominic Wilkinson @Neonatalethics 

and Keyur Doolabh, Medical Student, Monash University

Towards the end of last year, and over the first months of 2016, there were alarming reports of the explosive spread of Zika virus infection in South America. As many as 1.5m Brazilians were thought to have contracted the virus. More, worrying still, there were reports of thousands of cases of congenital microcephaly – infants born with abnormally small heads because of brain damage in the womb. Each week there appeared to be more reports and larger numbers of infants affected.

But the latest estimates from Brazil have reversed this trend. Last week, the total number of confirmed and suspected cases of Zika microcephaly is reported to be 4,759, 500 less than two months ago.

Why are the numbers of cases falling? Does this mean that earlier reports about Zika were wrong? Is the Zika panic over?

Missed diagnosis

One possibility is that microcephaly previously was underdiagnosed in Brazil. Prior to 2015, there were around 200 cases reported per year in Brazil. However, this rate appears strikingly low. International studies suggest that microcephaly (in the absence of Zika virus) occurs in approximately six out of every 10,000 newborn infants. Based on Brazil’s birth rate of 2.9m babies per year, we would expect there to be 1,700 cases per year.

So part of the initial surge in cases may have been due to recognition of cases of microcephaly that weren’t necessarily related to Zika infection.

Confirming cases

Did the intense attention on microcephaly lead to overdiagnosis?

The latest document from the Brazilian health ministry shows that 7,438 cases of microcephaly had been notified up to May 7. Of the half that have been investigated so far, only about one third (about 1,300 cases) were confirmed as real cases of Zika microcephaly.

This points to the challenge of getting the diagnosis right. Babies can have small heads for a number of reasons, so it isn’t surprising that some cases turned out not to be due to Zika.

Shifting cut-offs

Next, the definition of microcephaly in Brazil has changed. Before December 2015, microcephaly was defined as a head circumference at birth of less than 33cm. In December, experts decided that this was too generous: it would classify more than 600,000 newborn infants in Brazil a year as microcephalic, even though most of these children will be functionally normal. Subsequently, the Pan-American Health Organisation has recommended smaller cut-offs for female babies (who are usually smaller at birth), while another group has recommended the use of newly developed growth standards, the Intergrowth charts. So another reason that cases might have fallen is because criteria for diagnosing microcephaly have become tighter.

Statistically normal

The question of which cut-off we should use to define microcephaly overlaps with a wider philosophical issue – how do we define disease or disability? Some conditions are defined by reference to what is statistically normal for a population. But does it make sense to say that infants whose head is smaller than usual have a “disease”? What we want to know is whether a baby has brain problems that might have been caused by the Zika virus. But some babies with a normal head size may have brain problems from Zika, while other infants may just have small heads because it runs in their family. Determining what is statistically normal or out of the normal range may be useful for researchers, but what matters ethically is whether something affects our well-being.

There is also a trade-off with the use of different cut-offs for identifying medical conditions. Most cases identified using a strict definition will actually have a problem. But these strict definitions may also miss some cases. So it depends on whether we are more worried about healthy babies being wrongly diagnosed with microcephaly or babies with microcephaly not being diagnosed.

If we are conducting research into Zika it would be useful to have an initial generous case definition. That will identify as many cases as possible and enable the most information to be gained about the effects of the infection.

However, if we are concerned about the individual babies, it may be better to have a much stricter definition. One reason is because babies who have microcephaly in Brazil will potentially need further tests, particularly CT brain scans, that can have side effects for the babies. In a health system with limited resources it may be important to focus efforts on the most severe cases.

Zika on the wane?

We don’t know yet whether the reduced reports of Zika microcephaly means that the epidemic is tailing off. Some models of the illness have predicted a fall in cases over the beginning of 2016. Reduced cases might be because of rising levels of immunity to the virus.

However, there are also concerns about the spread of the virus to new areas, and new populations who aren’t immune, particularly with the Rio Olympics later this year and large numbers of travellers to Brazil. The other unanswered question is whether the cases of microcephaly are the tip of the iceberg. It is possible that Zika infection in pregnant women might cause more subtle brain problems in babies (for example causing deafness) that won’t be apparent for some time. So while the news about reduced cases of Zika microcephaly is reassuring, it is too early to relax.

Dominic Wilkinson, Consultant Neonatologist and Director of Medical Ethics, University of Oxford

This article was originally published on The Conversation. Read the original article.