Tuesday, 20 May 2014

MERS-CoV detections: The April wave recedes...

So welcome to the 114th Week of MERS-CoV among us. That week numbering may change shortly. Stay tuned if week numbering is your thing.

We currently have a tally of 649 detections of MERS-CoV or viral antibodies in humans. I don't list camel numbers. My count says 192 fatalities among infected people, resulting in a proportion of fatal cases of 29.6%. That seems high. Because, until very recently, the Kingdom of Saudi Arabia's Ministry of Health did not regularly report deaths alongside their date of illness onset, it has been an interesting hobby to try and link them. The number is solid so along as the MOH has not been doubling up in the reporting or coming back later to re-report deaths. You'll be familiar with these issues if you follow me on Twitter.

I made a point of saying antibodies earlier because I am going to be including these sorts of laboratory data in my tally when produced by trustworthy laboratories who have described their methods and shown some validation data and an understanding of what the cross-reaction issues are when dealing with MERS-CoV serology. This will be despite the current WHO MERS case definition not allowing for inclusion of people who only have antibody but no virus or viral RNA detected in their samples. There may be some hiccups with MERS-CoV antibody testing along the way, but we need these data in humans and it's good to see the wheels rolling on this at last.
[One of those hiccups occurred 28-May-2014, when the test result from an Illinois man who had originally tested positive in an Ab test, was retracted.]

In my estimation though, serology (the testing of human sera for antibodies against a virus here, the main target being IgG which takes a couple of weeks to become detectable after infection) is a much more reliable way of defining an infection by MERS-CoV virus than by relying on patient recall bias of symptoms 2-weeks ago, or from directly observing signs and symptoms that are nondescript and difficult to distinguish, alone. The latter approach has been the mainstay of identifying cases of human infection for a very long time; still is. This approach is especially important during times of outbreak and pandemic when labs are swamped by testing requests and it must be assumed that cases are due to the bug of interest; if it looks like a camel, slobbers like a duck and walks like a duck, then it is a MERS-CoV infection yeah? No. If you can clinically characterise and laboratory test then you will more often know the virus the patient has/had than if you don't test. But I'm sure that's clear to everyone anyway.

For MERS, as for H1N1pdm09 influenza and perhaps SARS, finding a reliable pathognomonic set of signs or symptoms capable of reliably distinguishing a respiratory virus of interest from another virus capable of the same disease is not possible. These viruses cause a spectrum of illness. Testing is paramount if you want to know what's there and to address other aspects relevant to public health during an infectious disease cluster/outbreak/pandemic. There are a couple of issues here (at least!)...

From a patient management perspective, who really cares what is making my patient very ill anyway? It really doesn't matter right now if it's this respiratory virus or that one; there are few vaccines and I don't have an antiviral for most of them anyway. I and my healthcare team are already taking respiratory infection precautions and I just want to direct my supportive therapy and resources to the problems they have, right? I'll be (well...you, experienced medical types of which I am not one) doing that before many lab results show up anyway. 

From the perspective of interrupting and understanding viral transmission however, nondescript signs and symptoms are a nightmare. And in the early days of a new virus where we seem to know very little about what path(s) transmission is taking (and perhaps we're also learning some more about those possibilities in general), any infection by whatever method it is empirically determined should, I believe, be recorded as an infection in order to provide the biggest picture possible; a process we have seen unfolding in the United States with its 2 3 detections (1 locally transmitted) of MERS-CoV or its spiky little footprints.
THIS RESULT WAS RETRACTED 28-May-2014 FOLLOWING A NEGATIVE NEUTRALIZING ANTIBODY TESTING.

Given that many viruses cannot be distinguished by signs and symptoms alone, a clinical diagnosis to define a case is less reliable than any pathogen-specific laboratory test. I hope the WHO alters their case definition in the near future. Infectious disease is always teaching us - seems we learned a heap from SARS but even the relatively a few cases of MERS are presenting interesting issues and testing us in new ways. 
[While the US antibody-positive result above has since been retracted, I stand by these comments-Ab testing requires rigor, but that can be provided using several assays and applying a good understanding of Ab technologies and limitations to produce reliable results]

Anyhooooo...been stewing on that for a few days apparently. Let's move on and have a look at the 3 updated charts below. 

We are definitely through to the other side of the Jeddah outbreak (see weeklies chart). While cases do keep accruing each and every day (see dailies chart from 20-March), the downward trend of smaller numbers of illness onsets each day also continues. 

Weekly MERS-CoV detections.
Click to enlarge.

Daily MERS-CoV detections from 20-March.
Click to enlarge.

For perspective on the size and the influence of what 1 hospital cluster can turn into and how that can influence how a virus "looks", take a gander at the extent of the April outbreak. Case are still falling out into April as we get more data. If you look at the monthlies chart at the bottom, I've readjusted that y-axis scale again such that it's maximum value is now 10x higher (350 vs 35) than the scale used for 2012 or 2013's charts. May's tally is currently 4x greater than any month from 2012 or 2013. 

What does MERS-CoV hold for us in the coming months? 

Daily detections of MERS-CoV, 2012-current.
Click to enlarge. 

Monthly detection of MERS-CoV 2012-current.
Click to enlarge.


Saturday, 17 May 2014

Editor's Note #19: Just a pause...

Hi all,

Nothing fills me with more self-loathing than seeing VDU's charts being used when they are out of date...and I only have myself to blame! 

Generally speaking of course, I love seeing the charts used - that's what I make 'em for. But for some events, like the MERS-CoV localised epidemic, VDU's posts are out-of-date as quickly as the front page of yesterdays newspaper. So there is a need for a lot of night work.

I've been a little occupied with (drowning in) other paperwork of late - I do have a day-job after all - including a review of the fairly diverse MERS-CoV literature for a manuscript I'm writing.

As a result, I've fallen behind in updating my MERS-CoV (detections consistently roll in overnight but in smaller numbers than during April) and H7N9 (not many to add) charts.

I'll remedy this as soon as I can.

Cheers,
Ian


Wednesday, 14 May 2014

Welcome to the Netherlands MERS-CoV...

Click on map to enlarge.

New map format coming. The Netherlands enlarged.
Click on map to enlarge.

The 19th country for the Middle East Respiratory syndrome coronavirus is the Netherlands. The virus was carried in on an (?elderly) male returning from a visit to the Kingdom of Saudi Arabia.[1,2]

And it occurred in amongst the announcement from the Fifth Meeting of the International Health Regulations (IHR)Emergency Committee concerning MERS-CoV, which concluded that conditions have not been met to require the declaration of a Public Health Emergency of International Concern (PHEIC, pronounced "fake").[3]

In the meantime I'm sticking with Public Health Epidemic of International Eyebrow Wrinkling (pronounced "phew").

References...

  1. http://www.rtlnieuws.nl/nieuws/binnenland/eerste-geval-levensgevaarlijke-mers-virus-nederland
  2. http://www.rivm.nl/Documenten_en_publicaties/Algemeen_Actueel/Nieuwsberichten/2014/Eerste_MERS_patient_in_Nederland
  3. http://www.who.int/mediacentre/news/statements/2014/mers-20140514/en/

Keep calm and call the lab...without it, you know less than you think you do [UPDATED x2]

This morning there are 2 symptomatic healthcare workers (HCWs) in the United States (of America; I'm just going to use the "US" from from here on) who came into contact with the recently diagnosed MERS-CoV positive 44M (age and sex confirmed yet?) imported case.

The news has driven something of a twitter storm in the #MERS channel. Not unexpected I guess. The implication is that these 2 have acquired MERS-CoV from contact with the imported MERS-CoV-positive person. 

But that link is still far from proven yet. [UPDATE: both HCWs tested negative for MERS-CoV [1]]

This is a slightly revised version of that which I posted 18-March.
Thanks to Dr K Arden for helpful advice.
Click on image to enlarge.
VDU images are free to re-use. I can provide a better quality if needed.
Please just cite Dr Ian M Mackay, and this blog, http://virologydownunder.blogspot.com.au/,

if used elsewhere.
...Something to remember, or become aware of...

There are >200 known human viruses that have at one time or another been linked to patients with signs and symptoms that defined an 'influenza-like illness" (ILI). No-one can predict what these HCWs are infected with, but they have been or currently are infected by something. Lab tests are essential to know this.

I've asked Orlando Health's social media team (@orlandohealth) if these 2 HCWs are also being tested for the more "standard" 8 or 9 endemic human respiratory viruses/virus groups in parallel with MERS-CoV testing. I'll update this post with what I learn.

These standard viruses include influenzaviruses (A and B; red above), respiratory syncytial virus (dark pink), adenoviruses (orange), human metapneumovirus (pale pink) and parainfluenzaviruses 1, 2, 3 (purple). I'd also hope the rhinoviruses (in green above) since they are numerous and a frequent cause of ILI that can confound the very broad ILI tag. This panel of viruses comprise a standard testing menu which may be further extended, or shrunk, depending on the lab and they are included in commercial PCR-based kits. 

Keep in mind too that a positive PCR (if that's what is used) result does not mean the virus found is the cause of the illness. It may be that another virus, that has since dropped below the limit of assay detection was the cause, or a couple of viruses working in series or parallel, or a virus & bacterium working in synergy or a virus that wasn't tested for, or a virus that is not even known yet...pant.

But if these 2 HCWs do test positive for the MERS-CoV, it's not all that unexpected. Respiratory viruses on the scale you see above have not co-evolved with us/been introduced to us recently because they are easy to get rid of or stop from spreading between/to us.

MERS-CoV is just one of a long line of (probable) respiratory viruses that keep taking us to school to teach us just how sneaky and effective they can be at spreading and just how much our preconceptions trip us up, letting them finish with the best grade.

To stop the spread of them in an environment full of sick people, like a hospital, or even a school, a daycare centre, a long term care facility, a cruise ship, a plane, bus, or even a living room, is no mean feat. It's worth remembering that no single virus does only one thing. There is no "pneumonia virus", no "bronchitis virus", there's not a "common cold virus", there's no "droplet-only" spread, there's not "only replicates in nasal cells", there are just respiratory viruses and their very complex multicellular hosts. I'm happy to argue any of these points, but come prepared to show me that every avenue has been exhausted to support your argument beforehand. I'll give you the drum right now, they really haven't.

Respiratory viruses can each do lots of things and the outcome on our health is heavily determined by usour previous exposures, our age, our general health, our maternal antibody levels, our underlying diseases, our genetic makeup, our environment, our climate, our animal and human contacts, our personal hygiene and our habits.

End of monologue.

Reference...

  1. http://www.flutrackers.com/forum/showpost.php?p=534975&postcount=49

Tuesday, 13 May 2014

MERS-CoV on a plane!

"Assessment of the MERS-CoV epidemic situation in the Middle East region."
Reprinted with kind permission of author (Dr Vittoria Colizza, pers comm).
Click on image to enlarge.

This is perhaps a timely reminder of where cases of MERS-CoV may pop-up if we look at the author's analysis of destinations from major departure airports in the Kingdom of Saudi Arabia, Jordan, Qatar and the United Arab Emirates. 

The figure above also goes to show that the numbers and predictions are great, but biological systems and bad luck  prevail. The US gets 2 cases so far, the same as all of Asia. Still, the point is valid; that we live in a highly interconnected world where no 2 points are separated by more time than it takes to silently incubate a respiratory virus and produce signs and symptoms, and virus, after arriving at a new destination.

Reference...

  1. Chiara Poletto, Camille Pelat, Daniel Levy-Bruhl, Yazdan Yazdanpanah, Pierre-Yves Boelle, Vittoria Colizza,
    Assessment of the MERS-CoV epidemic situation in the Middle East region. arXiv:1311.1481 [q-bio.PE]

Snapdate: MERS-CoV detection by month...

We are living in the 2.17th year, or 113th week, since the first known MERS-CoV-related illness affected a 25-year old Jordanian.

April stands out as the biggest MERS-CoV detection month ever, with 286 cases either becoming ill, being hospitalised or being reported as positive. But don't be confused by the differing values on the axes in the chart below. For all that May looks like a smaller cousin of April, its tally has already outstripped every other month of 2012 or 2013. 

72 cases so fall into May. But the rate of cases this month is slower than in April (see previous post). 

The tally of detections announced officially through WHO (which remains in a galaxy far, far, far away when it comes to detail on April-May cases) and from various Ministries of Health brings my worldwide tally to 580 MERS-CoV detections listed of which ~166 people have died of MERS. I'm still awaiting detail from WHO or UAE on 4 MERS-CoV cases that I do not list.

38% of May's case have died compared to 13% of April's (where I'm able to assign fatal cases to a month).

Click on image to enlarge.

Middle East respiratory syndrome coronavirus detections on the downward trend under Acting Health Minister Fakeih..[UPDATE]

Click on image to enlarge.
Apart from the looming spike in MERS-CoV detection among farmers who have taken to YouTube to kiss their camels in proof of their obviously over-stated role in being a viral source (sigh; that's a post unto itself*), the trend, after accounting for last nights cases is still one of declining case numbers since the change in management at the KSA Ministry of Health.

Some brief thoughts on the very early morning (my time; AEST) case reports from the KSA.[1] There were 8 cases announced which included 2 deaths plus another 3 deaths from previously announced cases. No asymptomatic cases (h/t @HelenBranswell) or healthcare workers and few mentions of comorbid disease were included; all bucking the recent trend. There were 4 possible hospital-acquired infections listed too, including illness onset from 11-May. Clearly infection prevention and control (ICP) messaging/action is still not succeeding, at least in Riyadh and Al-Madinah. 


Also announced this morning was a second imported case into the USA.


  • The Patient (possibly a 44-year old male[2]) was symptomatic - including a cough, (later some diarrhoea), fever and chills (1-May) -  during flights from Jeddah to London, from London to to Boston>Atlanta>Orlando, Florida.[2,3]
  • Symptomatic does not necessarily mean infectious [3]
  • Patient was a healthcare provider (?worker, HCW)
  • Patient was admitted to hospital in Orlando 9-May and is isolated.
  • Over 500 potential contacts from the US-based flights are being contacted and after 1,000 person hours by CDC staff over the weekend, no-one has been found to be reporting illness so far.[3]
  • Little risk of spread from casual contact.[3]

*I'm being sarcastic

References...

  1. http://www.moh.gov.sa/en/CoronaNew/PressReleases/Pages/mediastatement-2014-05-12-001.aspx
  2. http://www.latimes.com/science/sciencenow/la-sci-sn-mers-florida-20140512-story.html
  3. http://www.cdc.gov/media/releases/2014/t0512-US-MERS.html
  4. http://www.orlandosentinel.com/health/os-mers-case-central-florida-20140512,0,5928176.story
  5. http://crofsblogs.typepad.com/h5n1/2014/05/us-a-little-more-on-the-florida-mers-case.html

Monday, 12 May 2014

VDU Quote for the night...

From:
Z.A. Memish et al. 
Screening for Middle East respiratory syndrome coronavirus infection in hospital patients and their healthcare worker and family contacts: a prospective descriptive study.
Clinical Microbiology and Infection, 2014.
"Surveillance studies also help in defining and monitoring transmission rates, case load, and epidemic risk assessment, and assist in instituting infection control measures with new diagnostic methods and treatments."

MERS-CoV detections and deaths: is the war on MERS making headway?

For a few days now its felt as though we are seeing a more deaths in each Kingdom of Saudi Arabia (KSA) Ministry of Health (MOH) report, than we had been for a while. All very precise language there.

Currently there are about 161 fatalities among the 571 MERS-CoV detection. According to those numbers, 28.2% of people testing positive for MERS-CoV have died.



NOTE: Specific dates for some deaths are missing; date of reporting has been used instead.
The chart use 151 of approximately 161 deaths.
Click on image to enlarge.

Earlier in April, when the case numbers exploded thanks to a healthcare-associated outbreak, I wondered on Twitter if we'd see deaths "catch-up" to announcements as cases struggling for life in hospital, eventually succumbed to the damage started by their MERS-CoV infection. This is a virus with an apparently determined ability to wreak havoc in the lungs and kidneys of those who often already have an associated underlying disease of these tissues, and/or the cardiovascular system.

From the chart above, it looks like that catch-up is happening as the number of fatal outcomes (red dots) among the total of laboratory-confirmed MERS-CoV detections (green mountain) has been rising from mid-April onward. 

Most notable to me is that the proportion of fatal cases (PFC) is now also rising as the number of new detections no longer outstrips the number of deaths being reported. 

This is the first rise (rise >1% in PFC at least) since the beginning of March and reverses a trend of relatively stable PFC which dated back to late Aug-2013. 

This bears watching both at face value but also in light of the recent concerns about extra testing and its impact on straining the KSA healthcare system. It might be more prudent to discuss the significant strain being placed on the KSA healthcare system by filled hospital beds and intensive care units and the supportive management of severely ill people detected as result of that testing. 

The testing  should be telling the MOH (even if it no longer tells us) in which hospitals the problems lie. At this stage, 21-days after the KSA Health Minster was replaced (21-April-2014), we'd expect to see the case numbers dropping as (hopefully) changes have been implemented that (hopefully) focused a stern gaze toward (hopefully) improving healthcare worker safety and (hopefully) infection prevention and control (IPC). 

21-days into the new Health Minister's watch lies well outside the upper limit of the known MERS-CoV incubation period. If changes were sufficiently sweeping and if the war on MERS was entering a phase, detection numbers should be dropping as steeply as H7N9 cases do after a wet market closure. But they are not. Not yet anyway. 

The accumulating MERS-CoV detections (green mountain) are looking to be slowing a little, which is good news. But of course with that slowing, I expect we'll see those red and back lines rise in the weeks ahead as deaths keep occurring. Which is not, and will not be reported as, good news. About the only thing to stop that numerical marker from rising would be a new outbreak of cases. Not something we want to see. And of course, it would only be a smoke-screen for the fact that MERS-CoV positive people are still dying from MERS-CoV infection and the complications that ensue.

Last point for this post. Recent KSA MOH reports are more up-to-date than they have been for a while so we can see that MERS-CoV infected people are still being admitted to hospital, even in recent days (e.g. 7-May), and MERS-CoV infected people are dying relatively recently too (e.g. 10-May).


Snapdate: MERS-CoV detected among asymptomatic people

A quick look  at the numbers of people without symptoms who have tested MERS-CoV positive, presumably by reverse-transcription real-time polymerase chain reaction (RT-rtPCR).

MERS-CoV detection cases are up to 571 worldwide, (575 once we get some detail of 4 UAE cases that are still AWOL) of which 117 are asymptomatic (20.4%) based on public data.  
While the number of asymptomatic detections spiked along with the recent healthcare-associated outbreak, the proportions of asymptomatic detections in a week are not that different from other periods in 2013.


Click on chart to enlarge.