Friday, 1 April 2016

Zika, science, impatience and politics...

A lot of things can cause Zika virus disease (ZVD)-like symptoms. Some were listed in a previous post here.

It's very noteworthy, in my  opinion anyway, that there is ongoing Dengue virus (DENV) and Chikungunya virus (CHIKV) circulation across the Americas, and yet if testing is done for these, it is often serology (antibody) testing but not RT-PCR, or RT-PCR but not serology. In other reports there is no Zika virus testing at all, or just antibody testing not RT-PCR, there is no cytomegalovirus, or no toxoplasma or no testing from syphilis or no herpes simplex virus testing, or testing of one but not another and no testing for enteroviruses (poliovirus is an enterovirus) at all that I can recall.

The signs and symptoms that make one suspect a case of ZVD in a person are defined by the World Health Organization (see earlier post on this here) as:

A person presenting with rash and/or fever and at least one of the following signs or symptoms:

  • arthralgia; or
  • arthritis; or
  • conjunctivitis (non-purulent/hyperaemic)
They are extremely non-specific. Diagnosing an infection by one of those viruses listed in the link above using just those signs and symptoms is simply not reliable. You need lab testing.

Apart from those issues, we also haven't seen much at all about bacterial infections in the ill mums and we have yet to see anything other than viral causes, specifically Zika viral causes, reported or discussed in the same detail in the public domain.

Now, all that really boils down to us having little to no idea about how many cases of any given virus infection there are in Brazil or how many coinfections, but it does not detract from the repeated identification of Zika virus in or around foetuses that have microcephaly or brain injuries or growth retardation of different sorts. In fact, of a very wide variety of different sorts. 
What I find ironic is that we would not have found Zika virus in those foetal tissues if we had not responded to a Zika virus outbreak of which there is very little evidence. At least, public evidence. It does beg the question, what would we find in these tissues from foetuses with these brain injuries if we looked for influenza virus during an influenza virus outbreak, or parechovirus during a parechovirus outbreak, chikungunya virus during an chikungunya virus outbreak or...well you get the picture. We're currently looking mostly for this one virus, Zika virus, at a time when there is (reportedly) an outbreak of it.

But having looked, we have indeed found Zika virus in the foetal brain. Well, in some, or a couple. A virus with a liking for a tissue that expresses a lot of a protein that may be its contact point for cellular entry. That's certainly suggestive of a link to the disease also found in those general tissues. 

So is there a chance that Zika virus got to the brain but isn't causing the damage being attributed to it? Yes, there is a chance. 
Do we know it has caused tissue damage in the brain of the foetuses in which it's been found? Not yet. 

Is there a chance Zika virus is not alone in crossing the placenta during a maternal infection? Yes and there are a few viruses of different types that are already well known for doing this. There may be others. Could DENV and CHIKV be among them and if so could that be relevant? 

Should we still be thinking about one virus linked with one disease? First past the post testing? I don't think so. Have we applied any unbiased molecular testing approaches to these foetal brain tissues - deep sequencing for example rather than virus-specific testing by PCR-based methods? No. Is it as simple as one virus, one wide variety of brain injuries? Maybe it is. Perhaps it is not.

As all reading this are probably aware, research studies of foetal tissue research are controversial and far from commonplace today so we really don't know a lot of what is "normal" in the foetal, or adult, brain. It wasn't that long ago we used to think of some body sites as sterile - now we know very differently. 

One of my points here is that there are many things we don't yet know about Zika virus and brain injury - many really important things. Sure, we now know a lot of new things. But those things don't link the presence of Zika virus in the brain to the injuries we've seen described there. Not yet anyway.

We failed to respond quickly enough when a well characterized (well, relatively speaking anyway) viral pathogen ravaged West Africa. I wonder if it's possible to respond too quickly and in so doing miss things? 

Because of all....that...I find today's strong language by the World Health Organization (see box at top) so disappointing and strangely desperate. We haven't made the link yet - but according to the WHO, we have all agreed it is the cause. 

That's not about good science in my mind. That's about politics. While the of course co-exist, science has missed out this time.

Updates...
  1. My thanks to Jack Woodall for pointing out a missing word