Sunday, 8 May 2016

Zika, twins and complexity...

The media reported yesterday on a study underway in Sao Paolo, southern Brazil.[1] The study is looking at five pairs of twins so far - each pair includes one with a diagnosis of microcephaly, and one borne completely healthy. There is no detail on whether any less externally obvious Zika virus related central nervous system (CNS) disease has been sought so far.


From the Australian twin registry website.[8]
In the case discussed in the article, the mum of one such set of twins recalled symptoms of a Zika virus-like infection early in her pregnancy.[1] As you can see in the image to the right (and read at the linked website[8]), "twins" is a pretty broad description. It isn't hard to see how even one monozygotic twin (MZ twins develop from an egg fertilized by a single sperm) that one could become infected when another wasn't. This may be informative to the Three Parent Hypothesis.[9]

With around 3 million live births a year (roughly 8,500 live births average per day; 360 an hour [11]), there is likely to be a goodly number of twins when around 1.5% to 3.4% of live births result in twins of some type.[2,3]

I'm clearly no expert in the area of obstetrics, neonatology or congenital central nervous system disorders. But this finding, certainly not the first or only disease/healthy split between twins of this sort,[4,5,6,7] is fascinating.

To me, this finding highlights how rare the microcephaly and CNS disorder outcome seems to be after a suspected Zika virus infection of a mum at some point in her pregnancy. With so many births and just 1,300 M&CD diagnoses, its clearly nothing like as simplistic as "Zika virus infection while pregnant results in microcephaly".


A visualization some of the things that may have to occur for a maternal
Zika virus infection to result in an M&CD diagnosis.
This assumes that a mother's 
rash/fever/joint pain illness at some
time in her pregnancy prior to delivery, was due to Zika virus and
not one of the many other possible causes of such non-specific illness. 

The order of everything in  the grey box - which is not an exhaustive
list - is not intended to carry any meaning.
It is to indicate that there seem to be a large 
range of things
that must occur in a certain order, at a certain time, at a certain
strength or for a certain period of exposure, for the final outcome of
M&CD to occur in a newborn infant, or aborted foetus. 

It may be a different mix that results in different Zika virus-related
disorders - or even in M&CD in one infant compared to the next. 
What is for sure though, is that sometimes release of preliminary Zika virus disease study data without more detail and discussion, can give the appearance that things are more simple than they are.

The following tweets were a result of listening to Dr Celina Turchi Martelli, of the Brazilian Ministry of Health’s Fundação Oswaldo Cruz Foundation (FIOCRUZ)-Pernambuco, Brazil.[10] 

She gave a little insight into two case-control studies she is involved in, while speaking to the Cura Zika symposium hosted by The University of Pittsburgh.[10]


In response to those, Dr Andrew Lover crunched some numbers and highlighted that those data, when viewed in isolation, suggest that a Zika virus infection alone is almost guaranteed to result in microcephaly. 
But that is clearly not the case. Remember that total of 1,300 confirmed M&CD diagnoses amidst 8,500 live births a day? It was very probably not the intended meaning of Dr Martelli either. 

This all just exemplifies how confusing the Zika virus epidemic can be to the public, how complex finding a cause(s) to the M&CD surge will be and how much time may yet pass before we get anywhere near that goal. 

It's all a bit confusing for scientists too!

References...
  1. http://www.reuters.com/article/us-health-zika-twins-idUSKCN0XX1V2
  2. .https://www.twins.org.au/twins-and-twin-families/about-twins/facts-and-figures
  3. http://www.cdc.gov/nchs/fastats/multiple.htm
  4. http://learn.genetics.utah.edu/content/epigenetics/twins/
  5. http://www.ncbi.nlm.nih.gov/pubmed/7847025
  6. http://www.nature.com/pr/journal/v61/n5-2/full/pr2007129a.html
  7. https://www.technologyreview.com/s/406200/when-only-one-twin-gets-a-disease/
  8. https://www.twins.org.au/twins-and-twin-families/about-twins/facts-and-figures
  9. http://virologydownunder.blogspot.com.au/2016/04/the-three-parent-hypothesis-mum-dad-and.html
  10. https://pitt.hosted.panopto.com/Panopto/Pages/Viewer.aspx?id=a9abb64a-6f84-43d3-ac50-144b96fe67a4
  11. http://countrymeters.info/en/Brazil