Three weeks ago, I published a piece on the Zika virus, and how it is transmitted by the Aedes mosquitoes. Well, since then, there have been some new breakthroughs in the Zika virus, and as I mentioned in that piece, for each thread that we untangle, we are stuck untangling three more. But of all the issues that have since come up, perhaps the most contentious is whether or not there is a relationship between Zika and microcephaly.
The biggest response to the Zika virus, and the one that had people the most concerned, was in relation to the seeming spike in cases of microcephaly in regions affected by the Zika virus. While the remaining symptoms seemed relatively benign, this one could have long term ramifications, and led to statements such as the CDC advising pregnant women to not travel to areas infected by the Zika virus and several Latin American countries advising women to avoid pregnancy (an impractical decision given the lack of birth control options available).
However, new information is coming to light as researchers examine the data on microcephaly in Brazil. Reported cases are being reviewed to determine whether those suspected cases of microcephaly are actual cases of microcephaly. As pointed out in this excellent piece by Christie Aschwanden over on FiveThirtyEight, there are 5,280 suspected cases, but of the 1,345 that have been determined, only 508 are confirmed cases of microcephaly. The remaining 3,935 are still under investigation. This is further complicated by different definitions. Depending on the definition that you use to define microcephaly, the prevalence markedly changes: The estimated number of cases can change from 602,000 to 114,000 – almost an 80% reduction – depending on the definition used (Lancet). More sensitive definitions suggest the number could be even lower (only 3,000). The infants haven’t changed, their head sizes haven’t changed. Only the definition for what constitutes “microcephaly” has changed.
But the question that is being asked, and will continue to be asked is: Was this the right conclusion to draw?
At the time, this was a prototypical Kobayashi Maru scenario. The rate of microcephaly in 2015 was 20 times higher than previous years, and the Zika virus was found in the amniotic fluid of two women who had fetuses diagnosed with microcephaly. On the surface, the only thing that had changed from previous years was Zika. If there is a link, not taking action would be irresponsible at best, and negligent at worst. As we discussed last time, you can’t test the relationship in animals, as there’s no good animal model to use. And you definitely can’t run a study on pregnant women and inject them, because if there is a link, you could seriously harm your participants and their babies. So what do you do? There’s no easy answer, and it’s as much as philosophical debate as a public health debate. When is the appropriate point to act – is it when you suspect a relationship exists, preventing further health problems from arising? Or is it only when you know an adverse reaction or relationship exists if one is exposed to that substance?
One solution is to start using case-control studies to determine prior exposure. Select babies with microcephaly, select babies without microcephaly that are similar, and retroactively see if they have similar exposures. Maybe they do. Maybe it’s Zika. Maybe it’s a third factor we haven’t considered. Large scale case-control studies may be the only way to establish this relationship. However, this isn’t without problems. One part of case-control studies is asking people to remember exposures from 6 months ago or more, depending on the critical time period for exposure, e.g., recalling how much you smoked 30 years ago, or whether you ate the chicken salad at the party you were at last night. We can attempt to use biologic measures where we can, but in some cases, no biologic measure exists, or if one did, it’s since been eliminated from your system. Another option is to look at other countries with the Zika virus, and see what makes them different and unique to Brazil, or are we on the cusp of outbreaks on these countries too?
Contrary to what some might think, this isn’t a failing on public health. This sort of iterative approach is not an accident, this is by design. Public health professionals need to act when the first evidence came out of a link, and it would have been unethical not to. The public needs to be informed of the risks, and what we know. But now public health researchers are uncovering more information and will eventually determine if a relationship exists between Zika and microcephaly. If the evidence suggests an alternate mechanism, they’ll update the guidelines accordingly. On the other hand, if it doesn’t, then we’ll be happy we acted early.
