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Thursday, February 04, 2016

Zika, Math, Preparedness and Panic

If your news-feed doesn't have enough to scare you from Donald Trump, then the Zika virus is probably filling the gap.  Once again, Uganda gets the bad rap of being the site of discovery and the source of the name of this virus, which avid colonial-era scientists found in rhesus monkeys inhabiting the Zika forest in 1947.  The virus rarely infected human, but the mosquito which transmits Zika is the same one that transmits other more prevalent diseases like dengue and yellow fever.  The virus also jumped continents via world travel, finding non-immune populations and causing rapid spikes in transmission resulting in epidemics in Micronesia (2007), French Polynesia (2013), and then (courtesy of World Cup football) Brazil and the Americas (2015).  And unless you were a medical student preparing for exams, or a viral research scientist, you had probably never heard of Zika virus until a month ago.

In November 2015, Brazil began to publish reports of an unexpected increase in cases of babies born with extremely small heads.  They collected 4000 reports that year, represented a 20-fold increase in some areas over historical trends.  In a handful of cases, an autopsy or blood tests showed evidence of exposure to the Zika virus.  Temporally the two trends have been associated, so a hypothesis was suggested.  So far so good.

Then in lightening-fast fashion, we went from an observational report to a massive world-wide crisis and panic.


A foreign-sounding name, the vulnerability of pregnant women and young babies, the terrible headlines with words like "shrunken heads".  The culture of blame, so that if officials don't sound the alarm fast they are later liable.  The sense of guilt over the ebola non-response.  The moderate level of anxiety that is whipped up constantly by our access to skewed information.  

First, the math, because truth usually begins and end with some calculations. Brazil has a population of 200 million people (about 2/3 of the US population).  They have a birth rate of about 15/1000 so we'd expect about 3 million babies/year (about 3/4 of the 4 million US births per year).  Now the tricky thing is how do we define normal and abnormal for head size.  Generally we do this by creating a database over time of massive numbers of babies at various ages, documenting their weight, length, and head circumference, and when the number of babies per size and per age are graphed, you get a "normal" curve.  There is an average size, that tails off to the high and the low.  95% of babies fall within 2 standard deviations above and below the mean.  Statisically speaking, about 2.5% of babies would have a head circumference below 2 standard deviations (33 cm), which in Brazil would be 75,000 babies and in the USA would be 100,000 babies.  Most of those would be normal, just the kids on the smaller side.  So for truly talking about microcephaly, we usually take 3 standard deviations below (32 cm) as a cut-off for severe, where only 0.15% of people should be.  That's 4,500 Brazilian or 6,000 American babies.

In America, the teaching is that we have about 25,000 microcephalic babies /year based on a cut-off of 2 standard deviations (link here), which would mean that we are missing 75,000 of those we statistically expected to find.  I'm guessing that's because those are normal kids who are small and don't get reported as microcephalic.  If you look up incidence of microcephaly, they don't always define the problem well, and the numbers range from 1:6000 births to 1:250,000 births (giving expectations in the USA from 16 to 667 babies/year), 10 times below the numbers we would expect statistically.  That also makes sense to me, because while size is normally distributed, at the low low end of head size we don't just have small cute babies who are normal.  That's where we have babies whose heads are small because their brains didn't grow properly in utero.  Babies with chromosomal rearrangements and deletions, babies whose mothers were exposed to teratogenic substances, babies who were infected with diseases known to affect brain growth.  Also in the USA abortion is legal, so it is hard to know how many abnormal babies never make it to birth.

OK if you're lost now, that's just the point.  Do 4000 microcephalic Brazilian babies represent a shocking increase in incidence, or an admirable increase in detection?  Are more microcephalic babies suddenly being born in Brazil, or did the suggested association lead to raised awareness and reporting?  We don't know.  Some states are using head sizes below 33 cm, and some below 32, to report.  Some are reporting all babies, some only those with a suspected Zika association.  This epidemic is still spreading, and 80% of cases are asymptomatic, with the rest being mostly mild.  If there an effect on unborn children, perhaps we never found it before because the numbers were too low (in semi-immune populations) to be noticeable, or the infections were occurring in places with less medical access.  

For now, the panic is escalating way out of proportion to the known risk.  For a factual scientific read on all the details, look here.  Having a baby with microcephaly in most cases means a lifetime of struggle for the family, physical and occupational therapy, feeding challenges, special education.  It is not something to be taken lightly, and if this media frenzy does anyone good, I hope that it leads to increased empathy for families who already have children whose brains have not developed normally.  I hope the surge of attention attracts funding for resources for microcephalic kids of all stripes.  There is a long, long list of potential causes.  Zika virus may be one more cause on the list one day, but a temporal association is not strong enough evidence for causation.  

In the meantime, kudos for global thinking, and it's pretty much never good to get mosquito bites.


Dan Schmidt said...

Thanks for this. This will be great fodder for our AP Stats class discussion next week!

aunty.em said...

Also wanted to say thanks. I had thought that 4,000 cases of microcephaly sounded like a lot.

Unknown said...

An insightful assessment. Shows your MPH training, l venture to say.
Thanks for posting.