Thursday, 11 February 2016

Zika virus detected in the brain of a terminated foetus with severe brain injury...

In a new paper in the New England Journal of Medicine, Mlakar and colleagues present some compelling evidence for the presence of Zika virus (ZIKV) in brain tissue of a foetus, probably infected by the mother (vertical transmission), that was medically terminated because of severe brain disease, microcephaly and a poor prognosis.[1] 

This study has a very strong title: Zika Virus Associated with Microcephaly

...and it can make that claim because of several robust findings.

  1. Presence of flavivirus-like particles in foetal brain as imaged using electron microscopy, which the authors suggest may reflect persistence in an immune-privileged site. They don't have data to support that though but presumably infection would need to persist for long enough to cause the structural damage seen in these diagnoses - whether that must begin within the first trimester has not been shown, just hypothesized. We do know that virus in the blood usually clears in a week, with virus detectable in the urine for a little longer
  2. Detection of viral RNA in the brain tissue at levels, or 'viral load', higher than usually reported in adult ZIKV patients
  3. Detection of antibodies in the mother's serum indicating past ZIKV, and also Dengue virus, infections
  4. Determination of a complete, full-length genome of the Asian clade of ZIKV, from the foetal brain tissue (KU527068) using an Ion Torrent deep sequencing approach
  5. Absence of ZIKV RNA in many other tissues
  6. Absence of finding other viral genetic material which were sought and included dengue viruses, chikungunya virus, cytomegalovirus, herpesviruses, enteroviruses, rubella virus and others
This very tightly focussed located finding of ZIKV in brain tissues but not any other tissues, (including the spinal cord?), suggests a strong liking for brain tissue.  

An accompanying Editorial [2] notes that this is not proof of cause, but it definitely adds more and better information building a a stronger case for ZIKV doing something in the brain that we had seen just once before, in the French Polynesia outbreak of 2014.[3]

Virus was not cultured - but the finding of a complete viral genomes is good evidence of intact virus present. There have not yet been any studies to identify whether there are babies with ZIKV in their brain tissues but no brain injury disease (babies who died of other, unrelated causes perhaps?) nor is there any gauge of whether every case of comparatively similar brain injury in the region has ZIKV in their brains. We also don't know if ZIKV may simply be a passenger in the brain, or if whether brain tissue is a last, transient site of an infection that is being dispelled by the body after being acquired my the mum and passed to the foetus during an epidemic of that virus. 

Much work lies ahead, but this is stronger evidence towards an association than we have seen so far.

References...