Showing posts with label variant. Show all posts
Showing posts with label variant. Show all posts

Friday, 2 May 2014

MERS-CoV detected in asymptomatic people....

Maia Majumder has put by recent charting and charting efforts to shame. She is all over the latest Middle East respiratory syndrome coronavirus (MERS-CoV) numbers. So if you're not following her on Twitter or watching her charts on piktochart or her blog, Mens et Manus, then you may be missing the latest numbers as well as some interesting ideas and chats and some self-described wild guesses (one other letter to the acronym which I won't spell out here).

Maia has been covering some subsets of the MERS-CoV positive population of the Arabian peninsula of late; particularly to do with healthcare workers (which I also like to cover), those with comorbidities and those with no disease at all (asymptomatics) who are still in some way positive (PCR or antibody) for the MERS-CoV.

Click on image to enlarge.
So I've created a new chart for the asymptomatic detection of MERS-CoV. And it's interesting.

We can see more cases per week (blue line) being reported recently, and this naturally fuels a steep (but linear) climb in the cumulative tally (orange line) of asymptomatic detections. These are largely related to the Jeddah healthcare outbreak.

What's particularly interesting to me is what we see when we look at the proportions of cases each week that are described in the public domain as being asymptomatic.

Thanks again to Maia for a chat about the following definitions. Week #105 of the MERS epidemic contains the 1st case with "Jeddah" i its notes and an illness onset date of 22-Mar. Thus, we define the Jeddah outbreak (for now) as starting in the week beginning 17-Mar. We have seen 13-50% of cases in 5 of those past 7 weeks being described as asymptomatic (grey bars; this week not yet being complete).

Can this information be used to support thoughts that the virus and/or the way it is spreading, has changed? 
No. 
Why? 
Because this jump is not so different from the higher weekly proportions we saw in Sept-2013 and Dec-2013 (well before Jeddah). Oh, and because so far, there is no sign in the 3 complete genomes or 30 partial spike gene sequences that the Jeddah viruses are anything special. In saying that, keep in mind that we don't know how many cases are part of/linked to the "Jeddah outbreak". We do know of 245 distinct viral detections (31 fatal cases) made among humans since 22-Mar and so perhaps 3 genomes is not yet sufficiently representative for us to say there have been no viral changes at all, yet - if we even know what those changes will look like for the MERS-CoV.

As it stands, we are not seeing a disproportionate increase in MERS-CoV-positive people without signs or symptoms of disease. And that is good to know. It would also be good to know if asymptomatic people can shed MERS-CoV. The obvious answer is, no they cannot, because how would the virus get out of them? No coughing or sneezing means no easy way to excrete a respiratory virus. Perhaps there are short periods of signs that just get missed/forgotten/not reported? We do still need to test human urine, faeces, blood and saliva for infectious virus (virus that can be grown, not only identified by detection of its possibly non-replicating or contaminating nucleic acids). But I suspect that is all still a ways down the track.


So, as ever, we keep watching to see what the next few weeks bring to the knowledge base of MERS and the MERS-CoV...as we've been doing for over 110 weeks now.

Sunday, 20 April 2014

Naming the new Zaire ebolavirus variants

The recent NEJM paper [1,2] on the Guinea Ebola outbreak listed 3 full genome sequences (detected from infected people using standard "Filioviridae-specific RT-PCR assays" and published "real-time RT-PCR assays targeting the glycoprotein (GP) or nucleoprotein (NP) gene".

My thanks to Dr Stephen Gunther for answering my email and giving permission to list these names. They should be on Genbank now he tells me (I have not found them as yet). We now know that these virus variants of the species Zaire ebolavirus are called:

  • Ebola virus H.sapiens-wt/GIN/2014/Gueckedou-C05
    GenBank accession number: KJ660346, 
    KJ660347 or KJ660348
  • Ebola virus H.sapiens-wt/GIN/2014/Gueckedou-C07
    GenBank accession number: 
    KJ660346, KJ660347 or KJ660348
  • Ebola virus H.sapiens-wt/GIN/2014/Kissidougou-C15
    GenBank accession number: 
    KJ660346, KJ660347 or KJ660348

See more one the way the Filioviridae Study Group prefers to name ebolaviruses in a recent post here.[2]

On the issue of whether these variants can still be detected using published diagnostic PCRs, the answer is yes they can (they were detected using them after all!). To look more closely at that, I aligned the 3 new full genomes and also the primer sequences for 2 diagnostic reverse-transcription real-time polymerase chain reaction (RT-rtPCR) assays mentioned in the NEJM article by Baize and colleagues [3,4]. They target the nucleoprotein (NP; [4]) region of the genome and the glycoprotein (GP; [3])

The two PCR assay regions targeting GP and NP PCR oligonucleotides
(primers and fluorogenic probes) primers. The yellow stars in the NP assay
highlight a 2 nucleotide mismatches between the forward primer or probe
(T in oligo, A in genome) and the 3 genomes. These shouldn't decrease
assay sensitivity too much at all.
Click on image to enlarge.

References...
  1. Emergence of Zaire Ebola Virus Disease in Guinea — Preliminary Report
    http://www.nejm.org/doi/pdf/10.1056/NEJMoa1404505
  2. http://virologydownunder.blogspot.com.au/2014/04/update-on-ebola-virus-disease-evd-case_17.html
  3. Development and Evaluation of a Fluorogenic 5 ' Nuclease Assay To Detect and Differentiate between Ebola Virus Subtypes Zaire and Sudan | Gibb and colleagues | J Clin Microbiol. 2001 p4125-30
    http://jcm.asm.org/content/39/11/4125.full.pdf+html
  4. Rapid detection of filoviruses by real-time TaqMan polymerase chain reaction assays.| Huang and colleagues | Virologica sinica 2012 p273-7
    http://www.ncbi.nlm.nih.gov/pubmed/23001480