Friday 28 June 2013

H7N9 diagnostic improvement..

Currently, H7N9 testing of chickens in Hong Kong requires 4 days but a new test will complete testing in hours.

Thursday 27 June 2013

Tuesday 25 June 2013

Editor's Note #8: New influenzavirus page, H6N1.

There isn't a lot to say about the latest avian influenza A (H6N1) virus confirmed in humans, but I've put up a small page on the 20F from Taiwan. See the Taiwanese CDC announcement.

Another stark reminder of why generic virus names like "novel coronavirus" or "bird flu" are pointless. How many novel coronaviruses have been found of late (that haven't made it to the media) and how many bird flu viruses are there now infecting humans...enough to make referring to them using such a generic term confusing.

Wednesday 19 June 2013

MERS-CoV numbers-where are we at?

As the dust settles from several days of new cases, and deaths and retrospective case identifications, I sit waiting for some caped crusader (no capes!) to step from the shadows and announce "I have the numbers you seek!" Okay, I'm a sucker for a caped crusader.
Alas, there are no such wonderful heroes to help fill the data gaps we lack among the MERS-CoV case data. There are plenty trying though. And so we watch the numbers climb, the cases spread, then contract (depending on which reliable source of information is speaking) and we wait for the likely spike in new cases due to the upcoming Hajj which, even with calls to reduce numbers, will likely go ahead as a mass gathering that puts MERS-CoV transmissibility to the test.

Sometimes we seem to hear a proposed new case or a death, and then we hear no more. 


Where is this virus coming from - animals, are older males with underlying conditions (and what precisely are all these conditions?) getting it from Pipistrellus sp. or perhaps Rousettus aegyptiacus bats via contamination of dates, date products of palm sap-derived drinks/alcohol? How can the world prepare, or understand whether it needs to prepare, for a novel virus when the region of its apparent origin (we don't know that either) has trouble sorting out whether members of its own populace are positive or not? A rough - what else can there be - count shows at least 23 dates of onset missing, 9 dates of death, 10 ages, 67 dates of hospitalisation and 11 sexes undefined for around 72 cases.

Isothermal DNA MERS-CoV test

Laurie Garret noted this article about a new, relatively easy to use bedside test to be described at the upcoming Abu Dhabi Medical Congress.

The key piece of information here, as it sometimes is with bedside (Point of Care or POC) testing, is how its real-world (using clinical samples) sensitivity ranks against other testing methods. False negatives provide a sense of false security that can be disastrous for infectious disease management. Also, the types of sample that can be collected at the bedside are presumably weighted towards easier-to-access upper airway secretions. That will not play well for any virus that may be found more often in the lower airways at presentation.

Let's hope the test fits the bill. Fast, sensitive, specific and reasonably priced testing would make great inroads into infectious disease control. Time, and more information, will tell.

Monday 17 June 2013

Stuff from the literature: Don't judge a virus by its worst case [UPDATE].

This article, a Letter in the Journal of Clinical Virology (2013 Sep; 58(1):338-9) is one from our own keyboard. It is entitled Avian influenza A (H7N9) virus: Can it help us more objectively judge all respiratory viruses? Unfortunately it s behind a paywall, but I do not have the funds (they all go into the research) to pay for open access publication.

We try and make
the point that every respiratory virus can be found in severe, moderate, mild cases or even asymptomatic people - H7N9 in a young child earlier this year being an example - but no particular portion of a given virus's clinical severity spectrum should be used to define that virus.

The risk of future prejudgement is real. For example, not all influenza-like illness (ILI) is due to influenza viruses. Expecting it to be so leads to confusion and misunderstanding. But on the other hand, screening for every likely viral culprit in every patient during a pandemic is impractical - or at least, it creates a bottleneck that slows result reporting and infection control. At some stage we'll have better, faster higher-throughput tech to do this, but we're not there yet - so we have to pick and choose.
In the meantime, old labels like the "common cold" virus (human rhinoviruses and coronaviruses) have done little to help anyone really be aware of what a virus is capable of. You may argue they have slowed research into their other roles to the detriment of public health. I do. These labels will never be shaken off. Yet we now know that most asthma exacerbations are triggered by infection with one of these 200 or so little packets of mischief.
Apart from naming viruses to avoid geopolitical, and personal sensitivities, it is also important not to label viruses which at one time may be innocuous...and at another, deadly.

Viruses pack a lot of potential into a small shell-and do a great job of running us in circles.

Cumulative MERS-CoV Cases by area.

This is the latest chart (a cumulative epidemic curve) for my MERS-CoV page

Its a lacking some cases (57 of approx 64 cases are depicted below) - you may have head, data are sometimes hard to come by for the MERS-CoV outbreak. Still, it gives one a clear idea of where most of the cases have been occurring and how quickly they have accumulated.

Of particular interest is the take-off point which occurred from the week beginning April 14th. Over 30 of KSA's reported cases ~49 cases occurred from this point onwards - the exponential part of the red line.

MERS-CoV cases and deaths rising.

FluTrackers report on 3 new cases of infection and 4 deaths among existing MERS-CoV cases.

The numbers are changing rapidly (cases being released in several batches of 3 doesn't help).

Currently there are at least 64 total cases and 34 deaths among people with MERS-CoV. Most cases are in people with underlying chronic medical conditions. The Saudi Arabian Ministry of Health (MOH) regularly accounts for this clinical feature in each press release.

You can get a feel for the spread of MERS-CoV cases on this map

The following sites are useful to keep a check on numbers:

MERS-CoV infection control: the French connection.

A Eurosurveillance article by Mailles and colleagues describes the procedures used to lock down spread of MERS-CoV once confirmed.

Confirmed cases were isolated in negative pressure rooms (they suck air in, instead of pushing air out of a room as usually occurs in an air-conditioned room, ensuring virus-laden particles cannot escape) with dedicated staff using contact and aerosol precautions (e.g. personal protective gear which may have included back fastening gowns, disposable gloves, filtering masks, glasses etc).

A close contact was asked not to return to work and to wear a surgical mask when with other people. Other close contacts had to carry a ask and do nit if they developed symptoms, but could otherwise continue with life as usual.

Airborne transmission was strongly suspected but other routes, including the possible contamination of surfaces from the stools of the index case who initially presented with diarrhoea.

Wednesday 12 June 2013

New MERS-CoV genomes don't impact on existing PCR assays.

Update: #1 01NOV2015
I've looked at my latest nucleotide sequence alignments that incorporate the new genomes.

Of particular interest to public health laboratories worldwide is that the ORF1a,ORF1b and E gene real-time PCR assays described by Corman and crew (Sept 2012 and Dec 2012), still match their targets with 100% identity - no mismatches and thus no change in detection efficiency expected.


There is a mismatch (C:T) in the NSeq-Rev primer and the RdRpSeq-Rev primer, with some/all MERS-CoV strains, but nothing significant given its position within the primer.


These real-time RT-PCR (screening) and conventional PCR (sequencing and genotyping) assays are in widespread use and are part of the WHO testing algorithm (see 050613 post).


Good targets and well chosen, clearly. Not that one would expect any less from the authors of those two papers......



Multiple alignment of human MERS-CoV variant genomes and
reverse transcription real-time polymerase chain reaction (RT-rtPCR)
assays from Corman et al.[1,2]
Alignments made using Geneious Pro. v6.
Click on image to enlarge.
Reference...

  1. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction.
    http://www.ncbi.nlm.nih.gov/pubmed/23041020
  2. Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections.
    http://www.ncbi.nlm.nih.gov/pubmed/23231891
Updates...
  1. Added graphic back.

Thursday 6 June 2013

MERS-CoV cases by site of virus acquisition.


My first shot at some graphical representations of the MERS-CoV data. Much harder than for H7N9 as the data are scant. Larger versions and more detail can be found on the MERS-CoV page.

MERS-CoV cases by sex.


MERS-CoV cases by sex
MERS-CoV cases by sex.
Larger versions and more detail can be found on the MERS-CoV page.

The H7N9 missing link: testing the wrong end?

Helen Branswell has an excellent piece detailing as yet unpublished work by the Southeast Poultry Research Laboratory in Georgia.

The researchers have found that influenza A(H7N9) virus can be detected from the nasal passages of chickens and quail - both animals implicated in transmission during the H7N9 outbreak in China. The "so what?" factor is that normally avian hosts shed influenza viruses from the gut reflecting that it is the primary site of influenza virus replication in birds.

As Helen writes, an implication is that if the thousands of birds that have been tested in China to date were only sampled at the cloaca and not from the upper respirator tract, H7N9 prevalence in these oft-blamed but seldom-positive hosts could have been grossly underestimated. However, Dr David Swayne, Director of SPRL notes that it is common practice to swab both ends of a bird when testing.

The research also plays down a major role in transmission for pigeons, ducks and geese.

The search for a definitive answer to what animal is the principal host for H7N9, goes on.

Sunday 2 June 2013

H7N9 case dies 67-days after illness onset.



59M native of Anhui province, treated in Shanghai, died on Saturday. Case #19 on the H7N9 page Case list.

3 deaths among existing MERS-CoV cases in KSA.

Two had underlying kidney failure. That's all we know at the moment. The WHO will fill us in later hopefully.

Italy now hosts primary MERS-CoV cases.

Crofsblogs has been posting very informative pieces on these developments. I encourage you to keep an eye his and FluTrackers posts for the latest.

Two confirmed local cases of MERS-CoV infection, both presumed to be contracted from the imported 45M mentioned yesterday, both hospitalized in isolation in Florence (regional capital of Tuscany, population 3.8M).

Neither are severely ill. 45M's granddaughter (1.5-year old; coughing and fever, Meyer Children's Centre) was in contact on Sunday (approximately 6-day incubation) and a work mate have both tested positive.

Especially concerning in this cluster (Cluster #8) are the fact that 45M's flight from Amman Jordan stopped in Vienna and Bologna before landing in Florence. Also worrying is that the work mate and 45M's place of work...is a Hotel.

Metropol anyone?

Possible antiviral strategy to intervene in severe MERS-CoV cases?

FluTrackers posted a link to an article that mentions the negative off-target effects of antibiotics being used in MERS-CoV cases (especially among patients with renal failure).

The story also mentions a MERS-CoV "treatment protocol" (without further clarification) involving antivirals similar to those used for Hepatitis C virus infections. I wonder if this March 2013 paper by Falzarano and colleagues in Nature could be the source of such a protocol? It involves use of interferon-α2b and ribavirin to inhibit HCoV-EMC (now the MERS-CoV) replication.

Independently, each drug was needed at relatively high concentrations in cell culture studies, but when combined, they seemed to synergize and could be used at lower concentrations.

It would be great to have more information on the Saudi Arabian treatment protocol but also to know if the Nature article's approach has been used successfully anywhere to date in treating severe acute respiratory infections (SARIs) testing positive for the MERS-CoV).

A lot of clinicians would like to know this information as soon as possible I suspect.

H7N9 case dies 67-days after illness onset


59M native of Anhui province, treated in Shanghai, died on Saturday. Case #19 on the H7N9 page