It's been months since Brazil first reported a possible link between the zika virus and a surge in cases of microcephaly, a condition where babies are born with abnormally small heads. In that time, the virus has spread to 25 other countries, been linked to a rise in reports of a rare neurological disorder called Guillain-Barré Syndrome, and has spurred the World Health Organization to declare the virus's spread a public health emergency.
But we still don't know for sure if zika even causes microcephaly.
The best way to find that out is to do more research on the virus, which is happening around the world at this very moment. But as more details about zika, microcephaly, and Guillain-Barré Syndrome emerge, more questions are bubbling up with them. In Colombia, where more than 30,000 people have contracted the virus since it arrived there this fall, there have been no reported cases of zika-related microcephaly, according to Colombian health officials. In Brazil, a retroactive review, published in the WHO Bulletin, of birth records for one zika-affected area shows the number of babies born with microcephaly was much higher than previously reported as far back as 2012, long before zika arrived. And the women giving birth to microcephalic babies are disproportionately from impoverished communities. It begs the question: is zika really to blame? Or could the timing be merely a coincidence?
"I don't think we can rule out the possibility that zika is just a coincidental at this point," said Stephen Morse, the director of infectious disease epidemiology program at Columbia University's Mailman School of Public Health. "But right now the hypothesis is that there is an association, it's just not clear what that association is."
Scientists, as a general rule, don't throw around the term "causes" lightly. That's why you're still seeing doctors and researchers describing zika as "linked" or "connected" to microcephaly and Guillain-Barré. The thing is, no one can conclude that one causes the other yet because we simply don't have enough information. The link right now is largely one of time and place: zika arrived, and then reports of microcephaly and Guillain-Barré started to go up. A handful of fetuses and newborns with microcephaly have also tested positive for the zika virus. The correlation is significant enough to raise the alarm bells and find out what's going on, but still not enough to say definitively that one causes the other.
There are a couple of obstacles that have made it difficult to define the connection. One problem is that zika had only ever been documented as causing mild, flu-like symptoms.
It wasn't a major threat, so it wasn't closely tracked or studied, and efforts weren't put into making vaccines or treatments. The thinking was that it's better to focus our energy on viruses like dengue, which cause painful illnesses and can lead to death. The other issues is that both microcephaly and Guillain-Barré are relatively rare, so we haven't amassed a deep understanding of these conditions.
"Both of these conditions appeared in the past in the absence of the zika virus," Morse said. "We know little enough about the causes of microcephaly and Guillain-Barré as it is, and we don't really know enough about the true incidence of these conditions. When you're looking this carefully, you're more likely to find them, so you have to account for that."
Microcephaly is particularly difficult because it's not a disease, it's a condition that literally just means an abnormally small head. What is considered "abnormally small" differs, depending on who you ask, and the impact of this condition varies widely. Some microcephalic babies have skulls so small it impairs the development of their brain, which can lead to physical and cognitive impairment and even death. But other microcephalic babies grow up healthy and normal, like Ana Carolina Caceres, a Brazilian-based journalist who recently wrote about her experiences growing up with microcephaly.
There is also some uncertainty over how big of a surge there actually was in microcephalic births in Brazil. The public health agency reports an average of about 160 cases of microcephaly in a year—or around six cases per 100,000 births—but saw more than 4,000 cases since just October of last year. But a report published this month in the WHO Bulletin looking at births in one of the most zika-affected areas of Brazil as far back as 2012, and found microcephaly made up as much as 8 percent of all births even before zika's emergence. Another paper in Bulletin compared Brazil's previously reported microcephaly rate to those around the world and concluded there must have been underreporting prior to the current outbreak, and that rates were more likely 92 cases per 100,000 births. If microcephaly was more common than initially thought, the increase post-zika may have been much smaller.
Yet there's still evidence there's some kind of link between zika and microcephaly as well as Guillain-Barré, but it's likely more complex than A causing B.
"It does raise the question of why it's being seen in certain circumstances more than others," Morse told me. "That suggests that other factors may be involved, like chemical exposures, nutritional or health status. At this stage, it's not possible to say."
To solve this puzzle, Morse said the best bet is a case control study: a study that compares individuals with a disease (like a zika infection) with those who do not have it. Through carefully comparing similar groups of people with and without the virus, researchers will be able to verify once and for all if there is a scientifically-significant link between zika and these conditions, and even more importantly, determine the risk factor. If 100 women contract zika in their first trimester, for example, how many of them will give birth to a baby with microcephaly? This will also allow the chance to isolate those other contributing factors, if indeed they exist, which will improve our chances of prevention and treatment.
The good news is that, because of the wide spread of zika and the increased attention to the problem, getting these kinds of studies done should be a little easier than in some other cases. Case control studies on zika and both microcephaly and Guillain-Barré Syndrome are already underway. Morse said we could have results on this front in a matter of months. For now, we'll just have to treat zika as a risk factor, and wait patiently until scientists are able to give us more answers than questions.