Zika virus: The Criterion Collection

If you're not familiar with the link between the recent outbreak of Zika virus and an increase in microcephaly cases, I highly suggest you read this post first (mainly because I like tooting my own horn). Basically, the World Health Organization and the Centers for Disease Control and Prevention have both concluded that being infected with the Zika virus during pregnancy likely causes birth defects. However, this is based on a scientific consensus, rather than direct proof, due to the difficulty in getting that kind of data and the pressing need to minimize risk for babies. So let's talk about how scientists come to a consensus in situations like this.

In the absence of a “smoking gun” (which in this case means definitive proof of causation, not a murderer), scientists have to lean on each other more. There are several lines of evidence that point to Zika virus causing microcephaly, but none of them are strong enough to stand on their own. They’re suggestive, not absolute proof. But if you’re doing something (such as playing a sport) and enough people suggest that you’re terrible, at some point you have to realize it’s probably true! This is why I was always picked last for teams.

And of course researchers aren’t happy with just a vague definition of what constitutes “enough suggestions”. There are lists! The main two being discussed are Shepard’s criteria and Bradford Hill criteria. Hill is from 1965 and quite general, but can still be useful in these situations. Shepard’s was established in 1994 and is specific for teratogenicity (things that cause birth defects), so I’ll focus on that one. Keep in mind, not all 7 points on the checklist have to be met, as it’s more of a framework for discussion. So I’ll paraphrase what others have said on this (and published in the high end journal, The New England Journal of Medicine) to make it easier to understand.

1. Proven exposure to agent at critical time(s) in prenatal development.

Yes. The timing of Zika virus outbreak coincides with the microcephaly epidemic. Like I’ve said before, not strong evidence but it’s a start. Additionally, there have been proven reports of maternal Zika virus infection prior to several microcephaly cases.

2. Consistent findings by two or more epidemiologic studies of high quality: (a) Control of confounding factors; (b) Sufficient numbers; (c) Exclusion of positive and negative bias factors; (d) Prospective studies, if possible; and (e) Relative risk of six or more.

Partially. Two studies have been published of sufficient quality, one on the outbreak in Brazil and one on the French Polynesia, as well as several lesser studies. None of them are perfect studies, which is why this gets a “partially satisfied” rating. Notice what is taken into consideration for high quality: controls, numbers, bias. All important issues to think about when evaluating data and things we’ve discussed before.

3. Careful delineation of the clinical cases. A specific defect or syndrome, if present, is very helpful.

Yes. To be honest, this is one of the things I haven’t looked into much because it would require me to see pictures of the afflicted babies. I’m just not willing to do that. So I’ll have to trust the doctors and researchers when they say that the Zika-associated microcephaly has distinct features and patterns.

4. Rare environmental exposure associated with rare defect.

Yes. There are reports of women who have been exposed to Zika virus on a trip, then returned to a non-epidemic country and still had a child with microcephaly, which is normally a rare disorder.

5. Teratogenicity in experimental animals (important but not essential).

No. There is no animal model for Zika infection during pregnancy yet.

6. The association should make biologic sense.

Yes. Zika virus can cross the pacent, infect neural cells and it’s been found in brain tissue of fetuses with microcephaly. Plus, there’s precedence as other viruses (rubella, etc) are able to cause neural birth defects.

7. Proof in an experimental system that the agent acts in an unaltered state.

Not applicable. This refers to a medication or chemical agent, not a virus.

So there we go, 4 out of 6 applicable criteria are fully met and 1 is partially met. I’m not going to go into the Hill criteria, but you can read about it here, here and here. Basically, that checklist had 7 out of 9 fully met, 1 not applicable (biological gradient, for those looking at the links) and 1 not met (which was also about the animal model). Overall, pretty much a solid case for Zika being a real jerk of a virus.

And now I’m sad and need a cute animal gif. Here we go! This puppy has as much athletic ability as I do! Possibly more.