Saturday, 19 April 2014

MERS-CoV detection: Cases by week and cumulative average still rising thanks to 2 healthcare clusters

Click on image to enlarge.
This chart, cases by week, really tells the story of a super-cluster driven by Jeddah's hospitals. Why this is still rolling along is unclear.

Perhaps, just perhaps (and I'm hand waving here), we can say that because MERS-CoV cases are not popping up all over Saudi Arabia, and because it seems, so far, that the contacts of the imported Malaysian (ex Jeddah) and Filipino (ex UAE) cases are testing negative for MERS-CoV, that a significant change to create MERS-CoV MkII may not have occurred. If it had, seeing positive test results among contacts and family members would be a good indirect alarm bell. But we have not seen much of that in cases to date, and in past umrah and Hajj pilgrimages. 

The clock on the maximum incubation period has probably run out for the Malaysian fatal case who became ill 4-April. The Filipino case may also have run down his clock. He tested negative for MERS-CoV 11-days after his exposure in the UAE. As far as we know there are no positive contacts or family members from these 2 exported cases.

But then there was SARS....

If we could for a minute use that absence of new cases in those new international sites (also watching Greece now) to cross off viral change (still need to see viral sequences to be able to do that conclusively; Spike please!), that could leave us to focus on a breakdown in infection control and in the prevention of infection in hospital settings. 

I understand that healthcare workers don't walk around in full gloves, goggles, gowns and N95 masks for their entire shift (fyi, as lab researchers, we have to wear gloves, safety goggles and back fastening lab coats while we work in a PC2 laboratory environment with these viruses which we handle in a Class II Biosafety Cabinet), but I do wonder why we have guidelines for managing patients with certain signs and symptoms, if, and emphasise if, they are not to be followed. 

Such a guideline can be found in the very comprehensive publication listed below [1]...Table 1 about handling SARS patients seems particularly relevant. I wrote about this publication back in August 2013 [3], with the help of Mike Coston who has an extensive range of expert information on preventing infection over at his Avian Flu Diary blog.[2]

The recent spate of MERS-CoV cases is a grim but timely reminder of why HCWs need to be extra cautious when dealing with respiratory infection cases; you never know what might come through the door.

  1. Infection prevention and control measures for acute respiratory infections in healthcare settings: an update | Seto et al | Eastern Mediterranean Health Journal
  2. Avian FLu DIary | search for N95
  3. Infection Prevention and Control measures for MERS..mostly as per other ARIs

Watching zoonoses evolve...

Special guest writer: @influenza_bio

For the first time in human history, we are watching diseases jump from animals to humans on a large scale. We've seen diseases appear for the first time in humans before; that's not new. We've seen HIV and several new strains of influenza emerge over the past century or so, for example. What is new is that we can now watch this process as it happens. We are able to watch animal diseases trickle case by case into humans, and we wonder whether any of these diseases might some day become human diseases. We wonder whether we might be watching pandemics develop in real time.

A disease that jumps from a non-human animal to a human (or the other way around) is called a "zoonotic" disease or a "zoonosis." Individual cases are called "zoonotic" cases. When a zoonotic disease is trying to make the jump to us permanent, we call this disease an "emerging infectious disease."

We have certainly been watching a lot of zoonotic MERS coronavirus and bird flu (e.g., H7N9 and H5N1) cases develop in people lately, along with Ebola virus cases. Zoonotic cases of other diseases, including infections with various strains of bird and swine flu, occasionally develop, as well, and are watched closely.

When the 2009 H1N1 flu pandemic started, we had no clue much beforehand that it was on its way.  We didn't even have surveillance data about swine flu strains that were even particularly close to the strain that emerged in us. A large animal flu surveillance gap blindsided us that year.

And we will undoubtedly be blindsided again by other emerging infectious diseases that we won't even see coming, although people are doing their best to see what's out there.

When an emerging infectious disease jumps to humans, it can cause either a relatively local outbreak or a worldwide outbreak, called a "pandemic." If a disease becomes a pandemic, that just means that it's spreading worldwide; the word "pandemic" doesn't imply anything about how bad the disease might or might not be. In some sense, the worst case can be when a disease jumps to humans and becomes "endemic" in humans, meaning that it gets established in people and regularly infects people, year after year. Endemic diseases can circulate worldwide (e.g., influenza) or in more restricted geographical regions (e.g., malaria).

Our knowledge and resources have grown to the extent that we are currently able to monitor some significant zoonotic outbreaks of disease. We are currently watching the MERS coronavirus and the influenza A(H7N9) virus both try to become human viruses.

Will either one succeed? We can't say. We've never watched this process happen before. We don't know how long such a process "usually" takes, or whether there even is a "usual" amount of time that it takes. We don't know how long it might take, or how quickly it has happened before. We do know that the process is "stochastic," meaning that it involves a lot of chance. A pathogen that in one situation might cause a pandemic might just die out in another situation. Everything depends on the specific changes in a pathogen that get a chance to develop and on whether those changes end up getting passed on. We don't know how often pathogens "fail" when they "try" to make the jump to humans.

A lot of us have watched the recent surge in MERS coronavirus cases with some amount of concern. As of April 19, 2014, there are two large clusters of cases in the Middle East, and at least one of them is still growing. One cluster, in Jeddah, Saudi Arabia, now has 60 cases; 7 cases were added to this cluster today, and 6 were added yesterday. There are perhaps over a dozen cases in another cluster in the UAE. One patient who became ill with MERS in Jeddah at the end of March flew to his home country of Malaysia while ill and subsequently died in Malaysia; 79 of his contacts are now being watched closely in Malaysia. Test results are starting to come in for a number of these contacts, and thankfully all are negative for MERS so far. An asymptomatically infected Filipino health care worker traveled on an airplane back to the Philippines a few days ago. Yesterday, a MERS case was announced in Greece; a Greek man who had been living in Saudi Arabia was recently in Jeddah and presumably became infected there before flying back to Greece. He arrived in Greece with a fever; his contacts are now being monitored. In other words, MERS case numbers are growing quickly right now, at least in part through human-to-human transmission, and infected – and potentially infectious – patients are getting on airplanes to travel around the globe.

Does what we're seeing now represent changes in the virus that are making it more transmissible among humans? Or are we seeing a random fluctuation in the numbers of cases? Or, are we seeing more cases simply as a result of improved surveillance? I would argue that what we're seeing likely reflects one or more changes in the virus, simply because
  1. We've been seeing so many more symptomatic cases recently, 
  2. We've been seeing significantly larger clusters than we've ever observed before,
  3. A greater number of health care workers appear to be getting infected than ever before, and
  4. A greater proportion of cases are in health care workers than ever before. 
It's not that we've been seeing a rise only in the number of asymptomatic cases detected, which could suggest that we're only seeing the effects of improved surveillance. Moreover, while surveillance does seem to be picking up more mild and asymptomatic cases, it is difficult to know whether we are seeing more of these cases because of improved surveillance or because there simply are more such cases now. A lot of variables are being changed at the same time, and we don't have perfect information.

Nonetheless, the sheer numbers of recent cases suggest to me, at least, that the virus is changing and becoming more transmissible among humans. Until recently, we rarely saw evidence for human-to-human transmission of MERS; most cases may have been zoonotic. Now, however, large clusters involving roughly 1 to 4 dozen people are being seen, with single infected individuals infecting possibly up to a dozen or more other people. This is new. I don't think that we're seeing these clusters just as a result of improved surveillance, although I would be very happy to be wrong.

What does the future hold for MERS? We can't know. We might be watching MERS become a pandemic, and we might not. We might be watching the current relatively small MERS outbreak develop into a larger outbreak that eventually gets contained, as was seen with SARS. Or, the whole outbreak might all just simmer down or go away. Even if the virus were currently changing to become more transmissible, the current spate of cases could still simmer down or go away, just stochastically, just through sheer chance.

Prudence would dictate that we remain concerned and vigilant, however, especially as symptomatic MERS cases have had an approximately 40% case fatality rate (CFR). If MERS did cause one or more wider outbreaks in humans, that CFR might or might not change. Even if the CFR dropped to 10% of what it is now, it would still be on the same scale as the CFR for the 1918-19 influenza pandemic.

As a global society, we have an obligation to do everything in our power to prevent the MERS coronavirus from causing larger disease outbreaks in humans. We need more surveillance in affected countries, including much more genetic sequence data. And in countries of the Arabian Peninsula that are currently detecting MERS cases, infection control procedures need to be improved to the point where nosocomial cases in health care workers and patients are prevented. Health care workers in other countries should be educated about the possibility of MERS patients arriving from afar and about how to treat such patients safely. If this virus becomes more transmissible, we should not be caught unprepared. We can see this one coming.

MERS-CoV cases continue steep climb thanks most to 2 healthcare-related clusters...

Click on image to enlarge.
Data are for lab-confirmed cases only, and 

from FluTrackers, Ministries of Health
and the World Health Organisation Disease Outbreak
News reports.
The Jeddah cluster | Jeddah | Kingdom of Saudi Arabia. 

It is the biggest of any of the clusters of MERS-CoV cases within the Kingdom of Saudi Arabia, MERS-central (0 to date. It has seeded at least 2 internationally exported cases (a fatal case in Malaysia and now a case in Greece). It totals 53 cases so far; the tally for this cluster began after the onset of illness in the first case, 6-Apr.

The paramedic cluster | Abu Dhabi | United Arab Emirates

Happening simultaneously and right next door is a cluster of cases that began 28-Mar. It stands at 14 cases as I compose this; most recent with an onset of 14-Apr.

These dates, starting points and information are all up in the air of course. 

There have been no solid answers from either site on how each cluster commenced, so we don't know the actual 1st case nor how they became infected, what their status is or what type of contact occurred (animal or human-to-human). 

We don't know how many cases are linked together or even whether the 2 sites are linked. We don't know whether these focal outbreaks are ongoing nor just how so many healthcare workers (HCWs) can be infected by a respiratory virus that was already well known to the region and its hospitals (Wk 109, 2.1 years since first MERS cases). 

We don't know if this outbreak is just bad infection prevention and control at some hospitals/among some people. We are all wondering how this has continued among HCWs as it seems to be? After a couple of confirmed cases wouldn't masks and gloves and gowns be standard fare - if they weren't already in the management of unknown acute respiratory disease cases? Whether a "super spreader" is involved or not, such measures should have prevented so many healthcare workers becoming infected shouldn't they? 

Is this MERS-CoV Mk II - now with the ability to transmit efficiently and rapidly (before extra prevention measures are in place)? We have no MERS-CoV sequences to answer that. Spike gene sequences would at least help us understand he virus aspects? I don't really care about complete genomes-they are for phylogeny more so than public health; changes in Spike yielded information of value in the SARS-CoV event and for coronavirus in general, and could do so again. Just sequence that region guys! Do it quickly and release that info now. It's something informative. Don't wait for a scientific paper. Start a blog and put the results on there. Not just in Arabic and then in English some time later; with Yemen, the Philippines, Malaysia and Greece picking up cases in the past week, these 60+ cases are not just a Saudi thing (although the case numbers say otherwise-but you know what I mean), it's global village thing. Just tell us what's going on with the virus! 

So many things we don't know. "So what?" you ask Go and Google "MERS SARS" and limit it to the past 24-hours. That's so what. The media are starting to heavily lean towards the "MERS is the next SARS" story again and that stirs up concern at many levels. Is that concern justified. At the moment who the heck knows??? If there is no change in Spike, while not the be-all and end-all for change in the virus, it will allow the experts to make comments that inform the media that may calm a rapidly progressing situation with economically damaging potential for the world, and the region.

For crying out loud Ministry of Health|Saudi Arabia, get ahead of this thing.


  1. The world's greatest resource for tracking MERS-CoV cases, the FluTrackers line list

Friday, 18 April 2014

Update on Ebola virus disease (EVD) case accumulation chart with new WHO African Regional Office SitRep data for 17-Apr-2014.

A new World Health Organisation (WHO) Situation Report on the Ebola Zaire outbreak in Western Africa has filled in all my whinges from last night (see them here).

I've updated my chart and finally worked out how to show negative case number adjustments - just to show that numbers have not always been going upwards, highlighting that the numbers will change as suspected and probable cases are discarded if laboratory testing does not support the suspicions.

As a reminder - this charts are made for general interest. It may be that I have misinterpreted the language (sometimes a little tricky to wade through these reports) but the trends should still be informative even if  number is out of place. If that is the case, feel free to pick me up on it - it will hopefully be corrected during my next update anyway.

Because ebolavirus...

Click to enlarge and copy if you want to use.
Please just cite Dr Ian M Mackay,
An updated version of my earlier rushed graphic now with extra peplomers and proteins and stuff!

Feel free to use if you want to. It comes with no restrictions (just a citation please) and is drawn by me using Adobe Illustrator.

With help from...

  2. Field's Virlogy, 5th Edition, Kinpe and Hopwley.
    Chapter 40, Filoviridae: Marburg and Ebola Viruses

Thursday, 17 April 2014

Update on Ebola virus disease (EVD) case accumulation chart with new WHO African Regional Office data for 16-Apr-2014.

Click on image to enlarge.
Since the last update [2] there looks to have been a big jump in cases, but that is mostly be because its been a while since that WHO update. 

You could draw a straight line between the dot from the update on 11-Apr and it would maintain the overall gradual slope. 

Total suspected/probable/confirmed cases: 227
Total suspected/probable/confirmed deaths: 135 (59.5%)
Total lab confirmations: 114 (50.2% of 227)

What I find encouraging in the latest numbers [1] is that the lab confirmations have jumped up by nearly 10% so we now have 50.2% of all the (227) cases listed having been confirmed up from 41.6%. Also, none of the Mali suspect cases tested positive for this variant of the Zaire ebolavirus species (by the way, you can tell I meant species because I called out the full species name and used italics - just fyi). And the proportion of fatal cases has dropped because the suspect/probable case numbers have gone up faster than the fatal case number. A good thing for now, but that may well change in the future for reason I've written about recently.[4]

Less encouraging is that I couldn't find the number of lab confirmations for Liberia so that number may shift a little. When the most recent case became ill was not listed. Also, healthcare worker (HCW) numbers have jumped from 15 suspect and confirmed with 11 fatalities to 24 and 13 fatalities but I'm not sure just how many are currently lab confirmed. HCWs suffer a lot to be at the forefront of these outbreaks. We should never forget that.

We also learned today, thanks to a very speedy and nicely laid out New England Journal of Medicine article [3] by Baize and colleagues from Europe and Africa, that the particular variant of this species that has ravaged Guinea is a virus distinct from those found in other African Ebola virus outbreaks. I wonder if it has evolved in the local bats of Guinea or the greater West African region? I'm ignorant of how wide-ranging bat travels are or how friendly different region's bat colonies are. More testing is needed to answer the virology underneath all always. 

The Guinea Ebola virus variant is still a member of the species Zaire ebolavirus, genus Ebolavirus, family Filoviridae, but it has enough genetic variation across its genome to mark it as different from those found variants of Zaire ebolavirus identified in 1976, 1994-1995, 2002, 2007-2008.[3] How different? That will take more research to answer. What's its new name? We don't know yet but the Filoviridae Study Group can tells us that they would rather not use a country or patient name, prefer to avoid any "unusual" characters, choose easy to pronounce designations - and contact them for guidance! They'd like to see something that rolls off the tongue and includes...

<virus name> <isolation host-suffix>/<country of sampling>/<year of sampling>/<genetic variant designation>-<isolate designation> 

e.g. Ebola virus H.sapiens-tc/COD/1995/Kikwit-9510621


  1. Ebola virus disease, West Africa (Situation as of 16 April 2014)
  2. Update on Ebola virus disease (EVD) case accumulation chart with new WHO African Regional Office data for 11-Apr-2014.
  3. Emergence of Zaire Ebola Virus Disease in Guinea — Preliminary Report
  4. Ebola virus disease and lab testing...

MERS-CoV numbers by week...

There is a lot of buzz about the Middle East respiratory syndrome coronavirus (MERS-CoV) right now.

Laboratory-confirmed MERS-CoV Cases per week
(dark green, left y-axis) and the cumulative average of cases
(pale green; right y-axis). Note: recent cases have yet to 

have date of onset reported. Last 2 points may drop as 
cases are assigned to onset in earlier weeks; trend 
will likely remain.
Click on image to enlarge.
This is because the number of human cases appear to be sky-rocketing. Charting those numbers, as I've done here with a new cases/week and accompanying cumulative average (at each weekly data-point I calculate the average of all cases before it and plot that average). The chart does support the feeling of a spike although see my caveat in the chart's legend.

But there are a few things to remember when looking at these charts:

  1. We're talking about ~270 cases in a region  (the "Middle East) with ~400 million[1] inhabitants; just 0.0000675% of people are noted as positive for this virus. While the recent surge in cases makes the chart look steep (and is definitely worthy of being watched, analysed and some work done to understand it), laboratory confirmed MERS-CoV cases are still a drop in the ocean of humanity
  2. The surge in numbers is being driven by two clusters; One in the United Arab Emirates involving ~12 healthcare workers (HCWs) and an unidentified source (proposed as 1 or more ill patients) and the other in Jeddah, Kingdom of Saudi Arabia involving ~38 cases (from 2,517 suspect cases and contacts having been tested) in a hospital outbreak, also with many HCWs.[2]
  3. In these 2 clusters, as in other MERS clusters, we may be seeing a much more representative spectrum of the clinical impact which infection by MERS-CoV is capable of. This, in my opinion anyway, is important because it tells a very different story to that of the severe disease we have mostly seen in cases among older males weakened by pre-existing disease, a group in which the virus wreaks a special kind of havoc
  4. We still have very little to no data on what "normal" respiratory viruses do among older males with underlying disease in the KSA. That will significantly inform our understanding of the capacity of MERS-CoV to cause disease. Perhaps many of the >200 human respiratory viruses we know of cause just as much severe disease as MERS-CoV seems to. Don't bother pointing and laughing - show me the data to support your argument against that statement.
  5. Has testing changed and is it contributing to the numbers? Early on, contacts of a confirmed case were "observed" (looked at for overt signs of disease - a sometimes subjective  process) and now they are being more actively sampled and tested using laboratory methods; the only way we know what virus is present in a patient...when the sample is correct and they work and other caveats. It would be helpful to know when that testing process changed and whether testing bias, along with sporadic clusters, is a big contributor to the continually climbing cumulative average seen in the chart above.
Finally just a comment. 2-years after the discovery of MERS-CoV we are still seeing large scale hospital-related outbreaks like this one in Jeddah and the one among HCWs in the UAE. 

Potentially these outbreaks are triggered when 1 case infects many people. Perhaps these are so-called "super-spreader" events (1 person infects many). I need to read more to understand those better and whether they happens with any virus but we focus more on it in emerging virus outbreaks. 

But why is this happening? It's not as though hospitals are not well aware of standard infection prevention and control practices for handling patients with respiratory illnesses of unknown origin. Respiratory illnesses make up a big part of hospital business. MERS-CoV is not the only, nor the most frequent, pathogen in this class. I suspect seasonal respiratory viruses kill many people in the region too. But do we know that do or that they don't when compared to MERS-CoV? Some contrast here would be very valuable. Studies of respiratory viruses, using PCR-based methods to look at cases of pneumonia, from the Arabian peninsula are more rare human cases of MERS-CoV. 

What's more scary than rising case numbers for me is the fact the these hospital clusters keep on happening. 


Wednesday, 16 April 2014

MERS-CoV case accumulation chart continues to ascend steeply...

Click on image to enlarge.
I updated this chart just 3 days ago and we've seen around 2-dozen cases reported since then. Crazy.

I do wonder what's happening when I have to adjust the axis scale twice in a week. A case in Yemen (whihc may or may not be locally acquired) and earlier this evening 2 cases exported from the Arabian peninsula. Large clusters have swelled the case numbers numbers too but I wonder about seeing (a) so many transmission events from single cases and (b) seeing such a range of disease as a great example of the spectrum of clicnial impact due to 1 virus on a diverse background of age, sex and underlying disease.

2 Middle East respiratory syndrome coronavirus (MERS-CoV) cases emerge in the Philippines and Malaysia [UPDATED]

In a surprising pair of temporally related announcements, there has been an imported and fatal case of MERS occurring in a 54-year old man (54M) originally from Johor, Malaysia [1] and a distinct case in a  recently returned 45-year old [5] Filipino male nurse working in the United Arab Emirates (UAE).[2,3,4]
  • 54M had returned from performing an Umrah pilgrimage ("mini-Hajj")  at Mecca (Makkah), Saudi Arabia on 29-March , becoming ill 8-9-Apr, dying of pneumonia secondary to his MERS-CoV infection, 13-Apr.[8]
    • Passengers on board the same flights are urged to contact the Health Ministry for testing but he was not symptomatic while in transit [8]
    • Diabetic (a comorbidity) [6]
    • Had visited a camel farm but source of infection remains unknown [6]
  • 45M, currently in quarantine with his family, was a friend of the recent fatal MERS case in a Filipino paramedic
    • The nurse was asymptomatic
    • Returning from vacation in the Philippines when retrospective testing results were released to Philippines embassy by UAE authorities  [5]
    • Testing was conducted in the UAE, referred to as a "blood test" ?serology not PCR-based?
    • Source of infection remains unknown
In 2013, Kingdom of Saudi Arabia's (KSA) Health Minister Abdullah Al-Rabeeah, said that 4,800,000 pilgrims visited to perform Umrah and not one left having had MERS-CoV infection. That will not be the case in 2014.


  1. FluTrackers thread on fatal MERS-CoV case in 54M, Malaysia
  2. FluTrackers on Filipino nurse positive for MERS-CoV
  4. OFW who returned home from UAE tests positive for MERS-CoV – DOH chief| article
  5. OFW with MERS arrives in Manila
  6. Health Ministry Confirms Umrah Pilgrim Died Of MERS-CoV
  7. MERS Coronavirus Makes First Appearance In Asia: Malaysia, Philippines Report MERS-CoV Cases
  8. First Mers death recorded in Asia
  9. Mike Coston on Malaysia imported case
  10. Mike Coston on Philippines imported case

Editor's Note #18: VDU on MERS in the media..

Many thanks to Andre Berro, MPH, CPH, SCPM, Public Health Advisor at the Centers for Disease Control and Prevention for pointing out, on LinkedIn, that VDU got some media mentions of late. 

These follow on from a Twitter interview on the weekend with the Wall Street Journal's Ellen Knickmeyer. She and Ahmed Al Omran published an article: Deadly Virus's Spread Raises Alarms in Mideast Saudis Defend Approach to MERS Outbreak, Even as Cases Increase.[1] Part of the article was also quoted in a WebProNews articleMERS Virus Surge Seen in the Middle East [2] and in a story augmented with a VDU chart (Woo-Hoo!) in a Doha News articleAmid regional surge of MERS, official says no new incidences in Qatar.[3]

While missing from 2 of the articles, I will note here that I'm actually a virologist - despite all these charts I keep posting, and that those 3 articles should all be considered to list my affiliation with the Australian Infectious Diseases Research Centre at The University of Queensland. The AIDRC have been very kind in allowing me to affiliate my academic and educational efforts on this blog, conducted on my personal time, to their Centre, to which I am a grateful member.

Thanks to all involved.

  1. Deadly Virus's Spread Raises Alarms in Mideast: Saudis Defend Approach to MERS Outbreak, Even as Cases Increase
    Full article ...
  2. MERS Virus Surge Seen in the Middle East
  3. Amid regional surge of MERS, official says no new incidences in Qatar