Corona counts continue to clarify...

From Mackay & Arden [1]
Click on image to enlarge

The Kingdom of Saudi Arabia's (KSA) Ministry of Health (MOH) has, over the past week, made a few changes to its Middle East respiratory syndrome coronavirus report layout. Good changes. Nice additions. And I say bravo. In fact - as we've said in the scientific literature [1] - the KSA data are far better than  those we have seen from other recent emerging infectious outbreaks. In particular, China's efforts for the avian influenza A(H7N9) virus cases over many months or Egypt's communication about its avian influenza A(H5N1) virus outbreak(s), have been relatively simplistic, uninformative and hidden from public view, by comparison.

Since the 17th of September, the reports have been undergoing constant change. These range from the subtle tweaks in colour, the addition of pie charts (I particularly like the strong colours in the latest!), inclusion of a marker to identify an asymptomatic MERS-CoV positive sample (are these now included as a "cases" by the MOH?) and the breakdown of how MERS-CoV positives were likely to have acquired their infection.  

Some things I'd still very much like to see added...

1. In the 'Deaths' table, a column for the date that the deceased person was first described by the MOH - that is, the reporting date. Currently there is not always enough information to go back and say with conviction which e.g. "60 year old male Saudi from Riyadh" died when there may have been several cases with the same description, listed over the preceding days and weeks (even months as some MERS cases have been hospitalised for a very long time before eventually dying of complications)
2. The number of samples tested each week, as listed by the Infection Prevention and Control-KSA webpage
3. Details added retrospectively for those 'found' cases. Those data are clearly in the system somewhere as they were summarised back on the 3rd June 2014 [4] and the 18th September 2014. This would be a nice 'rounding off' of all the data to date.
4. An explanation for what constitutes a "primary case". Currently, the suggestion is that over a third of cases are primary cases. To my mind, after excluding healthcare acquisition, this implies infection from animals. But only a touch over 7% (91 of over 1200 virus detections) of cases reported publicly have any animal contact described. So what does a primary case" mean to eh KSA MOH?  
5. A single, regularly updated and downloadable line list of these deidentified detections, each with a unique identifier, for all 1200+ detections (akin to what the World Health Organization did for the South Korea cases...but better). This would be a resource that could be of use to future publications (which should cite the source appropriately), conversations whereby we could all discuss the same case using the same code, for student projects and for those number nerds the world over

Screen captures from the KSA MOH Command and Control Centre (CCC)[2]
Date of report is shown below each screen capture.
Compiled using Adobe Photoshop
Click on image to enlarge

But that little wishlist aside, it is fantastic to see this response from the MOH. I have no problem at all with the formats changing, even if it is day by day by day. I'm just happy to see a responsive data sharing outlook. And the willingness to put these changes up, and leave each version in public view is also a promising sign of openness from the MOH. There is nothing wrong with showing the process.

These website is becoming a great example of how we can and should communicate outbreak data in the future.

References...

1. The Middle East respiratory syndrome puzzle: A familiar virus, a familiar disease, but some assembly still required
   Mackay IM, Arden KE. J Infect Public Health. 2015 Sep-Oct;8(5):405-8. doi: 10.1016/j.jiph.2015.07.001.
   http://www.ncbi.nlm.nih.gov/pubmed/26278813
2. http://www.moh.gov.sa/en/CCC/pressreleases/pages/default.aspx
3. http://www.gdipc.org/
4. http://www.moh.gov.sa/en/CCC/PressReleases/Pages/mediastatement-2014-06-03-001.aspx
5. http://www.moh.gov.sa/en/CCC/PressReleases/Pages/Statistics-2014-09-18-002.aspx

Happy 3rd birthday Middle East respiratory syndrome coronavirus (MERS-CoV)...

It has been 3-years since Prof. Ali Mohamed Zaki sent his email to ProMED notifying them, and the world, of a novel coronavirus (15-Sept-2012). That email was published 20-Sept 2012.[1,7,8] 

Two years ago at this time we had 138 cases and 58 deaths, last year 856 cases with perhaps 306 fatal (36%). Today, we have heard of 1,588 cases worldwide of which at least 551 (35%) have been fatal.[2,3] A higher proportion of fatal cases occur in the Kingdom of Saudi Arabia (KSA) than were recorded in the 2015 South Korean outbreak. The type and extent of a nation's community that has comorbidities may play a role in these differences. The young seem nearly untouched by MERS. To date, 26 countries have harboured a MERS-CoV infected person and 13 of those have hosted ongoing transmission.[4]

Thankfully, the diagnostic tools described very early on are as useful today as they were in 2012.[5,6]

Three years on we still see no sign of that virus patenting issue manifesting into a real problem.[3] 

For me, this past year in MERSville has been about:

• How amazing it was that MERS cases didn't occur during or as a result of one of the world's largest mass gatherings, the Hajj. Really. Amazing.
• The absence of asymptomatic cases included in reporting from KSA. The World Health Organization's (WHO) definition of a case does not rely on the presence of symptoms but on the presence of virus or past viral infection. Withholding or not seeking these data produces an overstated value for the proportion of cases that die from infection and could confound efforts to interrupt transmission during an outbreak. In reality, the higher percentages may just be what we should expect among infection of older males and females with one or more comorbidities
• The continuing appearance of large hospital-based MERS-CoV outbreaks driven by circumstances we create through unsatisfactory understanding of respiratory viruses, as well as poor preparation for their arrival in an emergency department. This occurred again in South Korea and Riyadh over the past year as it did in Jeddah the year before. In South Korea, the financial, economic, social and trust impacts were significant; communication once again a big loser from public health authorities and governmental agencies
• The big question over our MERS-CoV antibody detection tools' capabilities. Can they detect the prior presence of a MERS-CoV infection when that infection did not result in symptoms in its human hosts, or caused only very mild symptoms? A 4-week study enrolling the contacts of confirmed cases and collecting daily nose/throat swabs, weekly bloods, filling in a daily symptom and temperature diary, followed by an 8-week blood sample, would help address this I think
• Slow acceptance that camels are the main, albeit sporadic, source of MERS-CoV spillover infections of humans. Bats may have been involved in the distant past but for 30 or more years we have strong data to say that a MERS-CoV (or closely related virus) has resided in and spread among dromedary camels in Africa and or the Arabian peninsula causing mostly a 'common cold' like upper respiratory tract illness. The precise role of importation on moving MERS-CoV around the region remains poorly explored
• Other animals, on paper, look like they could host MERS-CoV, but experimental infection studies are still lacking. Similarly, a camel birth cohort study (h/t @newprof1) would add additional information to the story of how this virus spreads between camels in herds or holding pens after importation or during festivals
• We did not see any resolution to the missing data from 2014 - despite assurances from the KSA MOH.[12] Comprehensive data on cases that were just 'found' - remained incomplete.[11] Also, trying to identify deaths from among previously announced MERS cases is a task fraught with frustration, despair and dismay. And then there are the unexplained errors and differences in reporting when comparing MOH data to World Health Organization data. Yes, those cases that are reported are likely to be the tip of an iceberg of indeterminate size, but at least get right what is being reported-or...GASP...fix it up later
• It was reported that among those humans listed as being 'asymptomatic' - over three quarters of such cases, when later interviewed, recalled having symptoms.[6] This, to me, casts a darker shadow over the quality of other clinical and epidemiology data too
• We still have not seen any data from the testing of human samples, prospectively or retrospectively, from non-Arabian countries that play host to high numbers of MERS-CoV antibody-positive camels, for example, Egypt, Sudan, Somalia or Ethiopia
  
• In the past year we learned that MERS-CoV variants, like other CoV variants, can recombine when multiple variants co-infect the same host (probably in camel herds but perhaps in crowded hospital outbreaks in places like Riyadh which appears to be a nexus for mixing of variants [13,14]) producing a new variant.[9,10] To date there has been no proven impact on clinical presentation or course, virus reproduction or immunomodulation or transmission. But have wee looked hard enough lately? While it is not immediately obvious from observing whole genome sequences - most of the kind of sequencing produced since MERS-CoV was discovered - sites of recombination can be predicted when we look with more specific software tools. Yet, what happens if this recombination happens between a contemporary human/camel variant and a more ancestral camel variant? Could the resultant recombinant virus change in transmissibility or become more or less clinically severe? Is that recombination scenario even possible? Are even older bat variants too genetically distinct to allow easy recombination? It is important we find out more about the diversity of MERS-CoV and CoVs among camels outside the Arabian Peninsula and seek them out in other animals there too. Just as it is important to measure what is happening in people there
• Advances in therapeutic antibody preparations and in vaccine candidates. It remains to be seen whether camels will respond as immunologically required for a camel-based vaccine to prove effective, but as Ebola virus disease showed us, there is obvious benefit to having a ready-to-deploy arsenal of weapons in case of invasion by a viral foe that just 'shouldn't be capable of doing that thing'

It would be stupid to predict what will happen with MERS and MERS-CoV in the next 12 months. We can take some educated guesses though. 

But for now the focus is still largely on what the KSA will do about the problem on their doorstep. It may also be that MERS-CoV cases are percolating outside the Arabian Peninsula without our knowledge. Let's not leave this virus to its own device any longer. Let's act to make sure it doesn't comes back to bite us. The clues are all there. There are patterns that are clearly visible. Let's get the work done ahead of the panic for a change. How about we meet back here this time next year, same batch channel, same camel topic?

References...

1. http://www.promedmail.org/direct.php?id=20120920.1302733
2. https://flutrackers.com/forum/forum/novel-coronavirus-ncov-mers-2012-2014/146270-2012-2015-case-list-of-moh-who-novel-coronavirus-mers-ncov-announced-cases?t=205075
3. http://www.who.int/csr/don/17-september-2015-mers-saudi-arabia/en/
4. http://virologydownunder.blogspot.com.au/2015/09/mers-around-world.html
5. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20285
6. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20334
7. Happy 1st birthday Middle East respiratory syndrome coronavirus (MERS-CoV)
   http://virologydownunder.blogspot.com.au/2013/09/happy-1st-birthday-middle-east.html
8. Happy 2nd birthday Middle East respiratory syndrome coronavirus (MERS-CoV)...
   http://virologydownunder.blogspot.com.au/2014/09/happy-2nd-birthday-middle-east.html
9. http://biorxiv.org/content/early/2015/06/12/020834
10. http://mbio.asm.org/content/6/5/e01280-15
11. http://virologydownunder.blogspot.com.au/2015/03/where-did-mers-cov-comorbidity-and.html
12. http://virologydownunder.blogspot.com.au/2014/09/mers-cov-data-request-response-from.html
13. http://www.ncbi.nlm.nih.gov/pubmed/24055451
14. http://mbio.asm.org/content/5/1/e01062-13.abstract

MERS around the world...

China was the 26th country to host a MERS-CoV infected person, when a 44-year old symptomatic male (onset 21-May-2015) travelled from South Korea, through Hong Kong to Huizhou in Guangdong Province,  China on 26-May-2015.[1] 

Click on it!
It gets bigger!!!

Reference...

1. http://www.who.int/csr/don/30-may-2015-mers-china/en/

MERS by month, camel and mass gathering...

I haven't updated this figure in a long while but recently had the chance to add some new camel calving season data [1] and another festival to my earlier lists [2-4] - the Um Ragaiba festival.[6] 

The Um Ragaiba festival is purportedly the largest of the human|camel gatherings, located north of Riyadh and near Buraidah and Hafr Al-Batin - interestingly, are all sites of infamy among the tales told in MERSville.[5]

MERS-CoV detection in humans by month. Also showing spring and
summer seasons in the Kingdom of Saudi Arabia and some key
camel and festival dates.
Click on image to enlarge

The latest version of this figure highlights a few things to me:

1. I don't see a seasonality here which is not surprising. Most human cases are due to human error creating the circumstances by which health care related outbreaks take off. These happen at different times. It is hard to remove that very loud noise and see if a seasonality remains. A seasonality that is presumably due to times when there are more active camel infections increasing the risk of human infections through proximity and direct contact with infected hosts
2. The Kingdom of Saudi Arabia has at last taken the threat posed by MERS-CoV infected camels seriously. In 2015, two big festivals which had camel involvement, Janadriyah and Um Ragaiba were not held. Take note China and avian influenza
3. The bulk of human cases occur within a timeframe bracketed by camel calving season - so, keeping in mind what I said above, rather than season, perhaps we can agree that the period in which higher numbers of MERS-CoV cases occur, seems to be in the Arabian Peninsula's spring and summer - even if that outbreak is in South Korea! When virus activity rises at the source, so does the risk of death and significant economic and social impact beyond the borders of that source

Reference...

1. http://www.ncbi.nlm.nih.gov/pubmed/26256102
2. http://virologydownunder.blogspot.com.au/2014/01/a-date-with-middle-east-respiratory.html
3. http://virologydownunder.blogspot.com.au/2014/04/an-update-on-april-outbreak-of-mers-cov.html
4. http://virologydownunder.blogspot.com.au/2013/09/can-mers-cov-seasonality-tell-us.html
5. https://www.saudiaramcoworld.com/issue/200803/heads.high.htm
6. http://www.ncbi.nlm.nih.gov/pubmed/25714162

Ignore mild and asymptomatic cases at your peril...

Infected but apparently well people may be key points along the transmission chain - not just in spreading infectious virus, but also in contaminating surfaces.

Or they may have no role in transmission at all.

When you have problems that weren't solved by the easy answers - look harder.

Study. Test. Find out. Communicate.

Knowing the full story of how a virus spreads is hard work. But transmission is not necessarily a simple process. Like everything biological, it may be more complex than we care to acknowledge. Such a complex scenario is shown here. Completely fictitious.
Or maybe not.
Testing can answer questions. Communication can provide answers.Click on image to enlarge.

To (type) B or not to (type) B...

Image adapted from Geoscience Australia,

The Australian Government.[13]

The latest weekly influenza statistics for Queensland were made public today.[1] Unfortunately there are no hard public numbers to support claims about the proportion of strains from the two influenza B lineages that affect humans that have been circulating in Queensland - for either July or August.
I was hoping to find some support for comments in the media this week which included...

The Brisbane strain has accounted for 27 per cent of influenza B cases in the year to August 23 [2]

• This is in the latest report,[1] but these are year-to-date proportions -almost pointless for the spike in cases that happened more recently i.e. 48% of 2015 influenza cases occurred in the past 3 weeks [12]. Also not helpful when considering how few influenza Bs seem to be 'lineageanated' (have a lineage determined-further characterised - ?term)

..it was 25 per cent higher this year[3]

• Talking about B/Brisbane strain's rise

Whatever. The upshot is that Australia has had a big influenza B virus-dominated winter in 2015. 

At least some proportion of those Bs have been due to strains of Influenza B virus Victoria-like lineage. That lineage was not included in the sponsored trivalent vaccine - namely the Brisbane strain (first characterised here in Brisbane back in 2008).[3,4,5,6] 

I had expected, based on the earlier Eurosurveillance article from our southern labs[9], that an influenza virus with an already decent presence that had not predominated in a number of years and which was not covered by the current vaccine would take off and cause a big season. But it seems like that hasn't happened. And yet we've had a huge influenza B season here in Queensland, and across Australia, nonetheless. 

Seems a strange mix to me but I'm no flu expert so perhaps this is all very normal for this Rubik's cube of a virus. Here's hoping for some literature on this down the track.

Despite the completely unavoidable mismatch event there remain a bunch of influenza A virus subtypes and the Phuket strain of the other influenza B virus lineage (Yamagata) that are indeed catered for by this season's trivalent vaccine. While the flu season may be taking a turn downwards,[1] you may want to consider a vaccination if you or your family hasn't had one yet-talk to your GP!

The newer (to us in Australia anyway), less common and not (yet?) sponsored quadrivalent vaccine caters for both influenza B virus lineages.

Figure from most recent State of Queensland (Queensland Health) report found here includes data up to 30th August 2015.[1]
Images excised from PDF and saved using Adobe Photoshop CC 2015.0.0
Click on image to enlarge

Oh, and those age bands I've discussed previously [10,11], are still the highest - school aged kids (5-19 years) got a lot of influenza B in 2015. Compare that to my earlier comparison - those age bands have really shot ahead.[11]

Figure from most recent State of Queensland (Queensland Health) report found here includes data up to 30th August 2015.[1]
Images excised from PDF and saved using Adobe Photoshop CC 2015.0.0
Click on image to enlarge

References...

1. https://www.health.qld.gov.au/ph/documents/cdb/influenza-qld-150830.pdf
2. http://www.couriermail.com.au/news/queensland/brisbane-flu-not-on-the-radar-but-try-telling-that-to-13000-victims/story-fnihsrf2-1227508437647
3. https://www.health.qld.gov.au/news-alerts/news/150901-flu-brisbane-strain.asp
4. http://www.brisbanetimes.com.au/queensland/queensland-flu-season-worst-on-record-20150901-gjc8ie.html
5. http://www.abc.net.au/news/2015-09-01/vaccine-has-not-protected-people-from-the-brisbane-flu/6739996
6. http://www.smh.com.au/national/health/surge-in-unusual-flu-cases-prompts-warning-from-doctor-20150814-giz6s4.html
7. http://www.brisbanetimes.com.au/queensland/queensland-flu-season-worst-on-record-20150901-gjc8ie.html
8. http://www.noosanews.com.au/news/surprise-flu-strain-not-part-of-this-years-vaccina/2759817/
9. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21201
10. http://virologydownunder.blogspot.com.au/2015/08/queensland-influenza-age-shift-still.html
11. http://virologydownunder.blogspot.com.au/2015/08/queensland-influenza-sees-shift-in-age.html
12. http://www.dailymercury.com.au/news/surprise-flu-strain-not-part-of-this-years-vaccina/2759817/

Where do these 'primary' MERS cases come from?

I was just dropping by the General Directorate for Infection Prevention and Control's Middle East respiratory syndrome (MERS) statistics website ([1]; Kingdom of Saudi Arabia) and noticed this graph which I've snipped and labelled below.

What strikes me as very strange is the listing of so many "primary" MERS cases (green). Keep in mind that the Command and Control Center of the KSA Ministry of Health has a case definition that does not allow for a person who has no symptoms as a Case-even if they are laboratory confirmed as being infected [2]. A strict clinical-based definition. In a more real-world definition for reporting a MERS Case, the World Health Organization (WHO) has, since at least July 2014, included any laboratory confirmed person (which includes suitably serologically confirmed) as a Case. 

In other words, the green bars represent KSA-defined Cases that have not acquired MERS-CoV infection from family, friends or house mates (yellow), not from healthcare workers or the healthcare facility (nosocomial; red and purple) and that are not unclassified (magenta). 

Excerpted figure from the General Directorate for Infection Prevention and
Control website.[1]
Blue labelling by me using Photoshop.

Doesn't that just leave camels? 

But camel exposures are not being listed in WHO Disease Outbreak News (DONs) in anything like that number. It's very rare to see a camel contact listed in the current Ar Riyad province outbreak at all (just one, early on).

So where do these primary cases acquire their infection from?

Reference...

1. http://www.gdipc.org/mers-stat.html
2. http://nebula.wsimg.com/9e5c08742ca99231959e266fe5e46ee0?AccessKeyId=56AE5CCCF0799F235A2E&disposition=0&alloworigin=1