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Showing posts with label Editor's Rant. Show all posts
Showing posts with label Editor's Rant. Show all posts

Editor's Rant: Communicating the data and about the data...

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It is pretty damn hard work trying to get hold of data on virus outbreaks around the world. 

When it is, it may be available in unfriendly formats. It may not be made public at all. When it is available, it is often slow to appear or it may have random reporting gaps, or be partially incomplete. The style of the released data can change overnight as well, sometimes going from detail to summary.

So why bother about trying to get hold of these numbers at all? It's not like I work in the field. Well, that is a question I'm increasingly asking myself of late too. My personal reason has been because I think there need to be more voices in the vacuum between the numbers being reported and the often dry public health reports. I think scientists, even if they are not lifetime experts on a given virus or outbreak, still have much to offer when they come out from behind their manuscripts and apply their skills to interpreting what's happening. Well, many do anyway. And they should do it more. Now, perhaps more than ever, science needs steer away from its cold, dense and boring niche writing to a chattier, more helpful and community-based style of engagement. It astonishes me how often the public's interpretation of outbreak numbers must come from the media or from hobbyists, or even professionals who work in other areas and give of their own time to help explain something to us in their personal time. Helpful and engaging information and better access should come from the source of the data.

So it becomes really annoying (you would have to know me quite well to know how many times I just rewrote those words) when data are given out for public use that are a total mess...and there is not one tiny mote of explanation for it. I called it appalling on Twitter tonight. And at other times there are no explanations for why there are gaps, why data are delayed, why the format may have changed today compared to last week, why a line list is missing a case, using a new and totally independent numbering scheme or suddenly reshuffled, why there is no news about a new outbreak. No word. No contact. No-one taking the lead. No...communication.

I have met a lot of people since I have been blogging who, in various ways, have put in their own personal time to help out bigPublicHealth, to help take up the slack in communicating to the media and to the public. It is hard to quantify the impact of that combined help-but I can assure you that it reaches far and wide and is not insignificant. One would think that it should be easier to provide this help when one is willing to make use of their own time and use their own resources, or that those people should be shown enough respect to be able to simply find and apply reliable raw data so they can help out. But one would be an idiot. I very clearly remember a time when I could send a public Tweet to WHO's Head of Public Relations, Gregory Haertl, and get an informed reply. Those days have passed. I remember there being an #AskEbola channel on Twitter that gave answers. That engagement is just not there anymore. I'm sure its funding and resources and blah blah...but not as sure as I could be if that were spoken about in public. Communication. Someone needs to step up on this. As the quotes above allude to, 2015 is not 2014. And one of those differences is that everyone wants timely and comprehensive information they can rely on during times of outbreak. This hasn't been discusses enough but it should be.
 

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Ebola double vision....

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A quick post to crudely highlight that total (suspected+probable+laboratory confirmed) Ebola virus disease case numbers have been doubling approximately every month  since June (as far back as I went). 
Click on image to enlarge.
The reality is that the most recent reports from the World Health Organization (WHO) may be even less accurate than the underestimated numbers we have become used to during the epidemiological fog-of-war that surrounds any outbreak, epidemic or pandemic. 

Apart from the most recent update, WHO Situation Reports (SitReps) of late have made a point of highlighting that the numbers have been lower than what those in the field expect is real.
"It should be emphasized that the reported fall in the number of new cases in Liberia over the past three weeks is unlikely to be genuine. Rather, it reflects a deterioration in the ability of overwhelmed responders to record accurate epidemiological data. It is clear from field reports and first responders that EVD cases are being under-reported from several key locations, and laboratory data that have not yet been integrated into official estimates indicate an increase in the number of new cases in Liberia."

So, if you are a senior influencer or a decision-maker in your country and if that country, in which you are a citizen, has offered only limited, financial, or non-existent support to this unprecedented outbreak of infectious disease, I suggest the following: Stop disproportionately worrying about the few sporadic but simply controlled EVD cases that your already-straining healthcare budget has to look forward to. Stop worrying about how those budgets will cope with the unnecessary burden of your feel-good but near-pointless rollout of temperature monitoring resources at entry ports. Stop thinking that by blocking flights out of West Africa you will somehow protect your country and the rest of the world from exported cases.


Think about this instead: If you are not doing your damnedest to insist that your country has put people and equipment on the ground in Liberia, Sierra Leone or Guinea, then you do a disservice to humanity, and on your shoulders be the burden of the many deaths to come. 

We individual citizens can't do this. You and our governments can.

Complain about and hide behind who didn't react fast enough if you must, but do be very, very clear in your own mind that now, right this minute, if you are not acting, calling someone, pleading a humanitarian case, then it is you and those like you who are to blame for some of our global villages burning out of control. 

I don't care a damn if the currency for today's political action is "security" - you find a way to bring it back to being about humanity. 

We live in an interconnected world and some of those country's citizens are your constituents.

The global calls have gone out, the Resolution has been passed, the pleas have been made, the situation is clear to all. And you are failing. 

Get up and do something. Now.


References..
  1. Ebola Virus Disease in West Africa � The First 9 Months of the Epidemic and Forward Projections.
    New England Journal of Medicine. 23-Sept. WHO Ebola Response Team
    http://www.nejm.org/doi/full/10.1056/NEJMoa1411100
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Epidemiology without dates is just -ology...

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Click on image to enlarge.
Data from the Kingdom of Saudi Arabia Ministry of Health MERS website.[1]

The above images give an indication of what the Kingdom of Saudi Arabia's Ministry of Health (MOH) considers to be case detail of immediate relevance to the public according to Prof. Tariq Madani, head of the scientific advisory board within the MOH's Command and Control Centre (CCC). 

Since the newly revised CCC MOH website came online, dates that describe key information have been absent (red dashed outline in the screen capture above). These dates include:
  • Date when symptoms began
  • Date of hospital admission
  • Date when a new fatal case was first reported (allowing a link to be made)
    • Click on image to enlarge.
    Where the re-defined 113 cases fall out across 2013 to
    1st week of May, 2014.[3]
  • Date when a recovered case was first reported (allowing a link to be made; actually this one hasn't ever been present)
Sure, we only had these dates for a short period, and relied heavily on the World Health Organization's (WHO) Disease Outbreak Notifications (DONs) to fill in and "scrub" the data once it was submitted to them, but it was so great while it lasted. 

I have had many emails and Tweets noting how useful it's been to others to see those data distilled into more digestible graphs and charts. These notes have come from both the public and from other scientists too.

This latest change to the MERS information provided us, came after a report on 3-June [2,3]. That is also the entry between where there were dates included [orange] and where dates stopped being included [red] again, in Part A above. The report described a review which started in May and found 113 un(publicly)reported MERS cases (see the bar chart above). Interestingly, 55 of these cases were either not sent to, or were not confirmed by, KSA governmental laboratories (thus should be better listed as probable cases IMO) while 58 results just hadn't been sent to the MOH, who "sign off" on the final reporting of MERS-CoV detections. Great that the CCC is able to track these down and admit to them. Good work. 

Not so great that 33 of the 55 cases are included in this tally despite not being able to be confirmed. 

In response to the "found 113", I halted my charting activities for MERS-CoV that week. I won't be resuming charting until the very long-awaited WHO's DON fills in the gaps on over 400 cases[6].

Much has been made by the media, some of it with comments from me[2,8], of these events. Some have noted that there is now a new sense of transparency about. While I don't argue with reports and comments about a range of collaborative efforts now/already underway (which is great news) and the need to acknowledge things when they improve, I do question how the retraction of some key data, essential for public epidemiology efforts, data that were fine to be included (inconsistent as they were even then) previously, can be labelled as transparency. I certainly don't think those actions meet up to this statement (bolding is mine)[3]...
"Based on the findings of the review, the Ministry has already put in place a number of measures to ensure that best practices of data gathering, reporting, transparency are being strictly observed.."
I've stated before, for H7N9[4] and for MERS[5] that we, the public, do not have a right to such data, even though its deidentified and the privacy of the patient is protected. We may feel entitled, but we are not. As long as the WHO and appropriate Committees or experts are aware of the facts and can judge the risk to the world, then that is the main issue.

Of course, I'd much rather we lived in a world where such relatively innocuous data were available, and complete. But whether or not we get to play with useful and rich data is a separate issue to the difference between saying something is so and it actually being the case. 

There has been an increase in the presentation quality (prettiness) of data but a decrease in the data presented, since the CCC website came online. That's a fact. 
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Google Flu Trends: What did you expect?

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I posted this on Crawford Kilian's H5N1 blog in response to his positing yet another story whacking Google Flu Trends for its "failure".

In case you can't tell - I'm a little sick of the number of electrons being wasted on writing the same thing about this paper in Science. I know, there is no shortage of electrons. Still, I hope to see this same degree of ire elicited by and directed toward other places, corporations and States who have trouble providing data to the public within the expected realms of accuracy. I'd also hope for more focus on what and how we test now and how representative that is of what a virus is doing; or what we might be missing.

I think Olson et al said it well when noting GFT's earlier failure to predict the H1N1 2009 pandemic's influenza-like illness activity..
"Current internet search query data are no substitute for timely local clinical and laboratory surveillance, or national surveillance based on local data collection"
The post...

Okay. Google Flu Trends (GFT) was not 100% accurate. Wow. Who'd would have thunk it? Who could possibly have guessed this would happen? The disappointment is clearly widespread. A predictive computer-based system set up for devising regulatory guidelines, formulating vaccine formulations, ensuring suitable laboratory testing capacity and preparation or national surveillance guidelines failed. Wait. What? It wasn't setup for any of that! It�s really just a pretty thing you can go look at to get an estimate of flu activity near you; much easier to wade through than some country's public health efforts. Estimate. When did we expect an estimate to be perfect?

Come on people-interpreting-this-paper. GFT isn't a failure unless you were honestly expecting it to be 100% correct.

Of course it couldn't ever be that. THERE. WAS. NO. VIRUS. TESTING. Not done by GFT anyway. Some lab testing went into it apparently, but even that was a sliver of a slice of a shard. And if you know anything about respiratory virus testing, then you know that even the testing we do, represents only a tiny fraction of the amount of virus-positive cases out there, extrapolating from those. That testing even varies from place-to-place in type, quantity and extent of reporting. The choice of what to test (sampling) is itself biased in a number of ways, not the least of which is that we favour testing pretty sick people or those that feel crook enough to present to a Doctor. We�re comparing GFT�s �fail� to an estimate. You�re all comfortable with using that to lambaste GFT? You�re comfortable to call that a total fail?

"The folks at Google figured that, with all their massive data, they could outsmart anyone."

Really? Is that what the folks thought? Did Google really get bitten by the flu bug?; can Google truly not track the flu? Certainly catchy headlines one and all. I guess no-one would read something entitled "Google Flu Trend's estimates not in agreement with some national testing data which also represents only a portion of those who get infected". I can see where that might not be a real mouse-wheel turner.

GFT was and could only ever be a predictive system. Just like that shiny App you have on your phone that predicts the weather forecast. Let's drag "big weather" through the interwebs flailing it at every turn so we can suitably express our righteous indignation at its failure to predict the rain we wanted on the weekend. It failed! OMG! Now I have to water my lawn to stop it from drying up. But that's all I have to do. No-one died when the clouds held their watery payload. My child was no more or less safe because the weather bug bit the Bureau of Meteorology here in Queensland. I didn�t have to get a new lawn because it is now 24-hours drier.

Does GFT's overestimate of the number of predicted cases by 0.5-2 fold (depending on the story you read) really have a real-world impact on anyone? Seriously? Keep in mind that its estimates still followed the trend of flu activity pretty closely; they peaked when actual flu was peaking, just not (my other estimates) perfectly. But apparently someone 100% concordance between lab sampling and GFT estimate data.

GFT has been doing a perfectly good job given what it is and what it could ever hope to be in its current setup. Perhaps centralizing and plotting the WORLD'S lab-based data alongside Google �flu�-related search-result data would be a useful next step for GFT. Then we could make up our own
minds.

In the meantime, keep it in context people.

References...
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I care what the H7N9 numbers are...


This was the Tweet from Crawford Kilian (hereafter "Crof") a couple of days ago. 

I respect Crof. He has been as much of a mentor in my year doing this as has anyone. He even sent me his book on "Writing for the Web". I immediately changed a few things that I did after reading parts of it. Unfortunately nothing can help my appalling typing skills.

So when I saw that Tweet I thought it must have been a hook to get people to come read the full story. Twitter is a great way to attract readers to my blog; its a top referring site. Among other things, it's an important tool for promoting what we write to a wider audience. Sometimes a catchy title can be as good a bait as something more straight down the line. So, hooked, I dutifully read on.

What I found has been disappointing me ever since I read it 2 days ago, because I care about these numbers, and I thought you did too, Crof.

The article is of a type that I have read several times from Crof. It reminds those of us getting carried away with small, confined disease outbreak that hey, it's a great big world of misery out there and many more people are suffering and dying of all manner of diseases, a lot of which we forget about. Sometimes we don't forget though, we just focus on other things for a time.

I think it is a very valid point to make; and to make it over and over again is also fine with me. Points made in a blog post are very quickly forgotten, if they are ever read in the first place. At least a search engine may lead some back to that post or online newspaper story, unlike a printed newspaper which if not read may never have existed.

What really disappointed me I think...and I've been trying to work out why this has stuck with me for 2-days now, even causing me to give up on writing this last night or on blogging about viruses at all...is that Crof's post never did back away from the message of that original Tweet. Who cares about those numbers? It continued to hammer home that to follow such small numbers of deaths needed a special kind of justification, even for Crof. He said....
When I see WHO's H7N9 updates extending to 10 or 15 cases, it looks a bit alarming, I grant you. But let's put it in proportion.
and
Yes, I pay more attention to avian flu than to lung cancer and malaria. So, unfortunately, does everyone else...if you define "everyone else" as affluent, educated, vaccinated individuals living in countries with excellent public health systems and drinkable tap water.
and 
For us, it's the implicit threat of some clever virus that holds our attention: we don't have a vaccine for this one, so we ourselves are as vulnerable as some kid in Cit� Soleil or Asunci�n or Gorakhpur.
and
I suppose we can justify our interest by arguing that by studying these new diseases, we learn more about other diseases, and ourselves, as well. And that's a plausible argument.

Finishing with
Meanwhile, since I posted a few minutes ago that 768 mothers died in childbirth today, the number has risen to 775.

So Crof, are there so few people on the planet that some cannot keep an eye on one disease, some on another? I get that we do have to prioritise certain diseases over others. We have limited resources and human nature seems such that we never get everyone to pull in the same direction for long enough to truly solve our problems. But there is no definition of a suitably attention-worthy number of lives lost to infection. Every infection that takes a life, or even those that make life miserable, are worthy of our attention, our study, our understanding and eventually, our efforts in defeating it. I care about those numbers.

You cited a number of examples of other causes of far greater human death and disease. I remember a post or comment of yours with similar information that has always sat in the back of my mind as a check and balance of over-reacting.  Yet I have also read many other posts from you that champion the need for better information about MERS and MERS-CoV cases, for example. You often provide "granular" (my word of the month) detail on individuals with infections. You followed the story of a single French MERS patient for many weeks. And so did we because of you. So I simply don't "get" how this post fits, if not to remind us that ALL the numbers are always worthy of our care. 

Yes. There are very few cases of H7N9 compared to the world�s population. But there could be many more, as I know you are more aware than many, with only a few bits of bad luck and circumstance lying between "sporadic" and "sustained". Why not have more eyes rather than fewer on such risks?

There were very few cases of SARS, H5N1 or even now, few new cases of polio or measles compared to such a huge denominator. But each and every one of those diseases has been and should be watched, followed, tracked and its every aspect quantified. 

Every death that could be prevented now with vaccination or in the future by better education, better research, better understanding of the patterns and changes to those patterns, and better awareness by the public themselves, is one more person who remains a living family member. I don't dwell on every death I've reported but I know what it would be like if it happened to someone close to me.  


So I leave you with these 2 thoughts...

And if a little pandemic porn helps all of us protect our health, and outgrow the need for such porn, then maybe it's worthwhile.
..the attention we pay to these fringe viruses is certainly worth the effort..

...and I hope to read many more like them in the future Crof. 

Just like you care about the words that you masterfully write, I think you like me, also really do care about what the H7N9 number are.
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Helix...a show about dual use research of concern (DURC), black goo, pretty people and an absence of grounding in good virology [EDITED]

I'm not really here to critique TV shows but this one has some "virology' in it, so I'm making an exception. 

Plus, I've been yelling at people about it. So time to rant in print and get it out of my system.

I was really looking forward to this show turning up. 

Let me start by saying that I really enjoyed the tension and the creepiness of the first 3-episodes. I really liked the old school music counterpoint and the potential paleovirology which could make for a great premise for some really mystical creepy virus stories. I'm enjoying the 70s-style Arctic accommodation, somehow made made modern, and I'm a fan of Billy Campbell, Hiroyuki Sanada and Ron Moore's work. I've had many hours of enjoyment and great story telling from Lost, Contact, The X-Files, 24 and BSG. But Helix is not any of them because it doesn't convey respect for its audience.

But mainly? Dude. The "virology" is a major fail and really pulls me out of any willing-suspension-of-disbelief I'm trying (hard) to get going. I think that may also be a problem for a (majority) non virologist audience. A general audience knows what "feels" like professional science and what feels just plain flaky. 

I guess I'd been hoping for something more Contagion'esque; grounded in today's reality, well informed, taking itself seriously and telling interesting stories using believable characters. Having watched 3 eps, I sum it up as more Outbreak-meets-28-days-later with dual-personality-but-still-angry zombies. I reckon it needs to make the material stand apart or at least do more to improve on what's come before. We probably have enough zombie+virus variations to not need another one unless it stands out. Maybe that's what the unmoving snow-plough is for. Or maybe there are some huge twists coming that will make me look like like an idiot (or perhaps the typos have already done that). Hope so.

Some (by no means all) nerdy comments and questions follow. Spoiler alert also, if you haven't seen the 3 eps that have gone to air so far.

  • What is it about this, or any retrovirus outbreak for that matter, that shouts "hey, I'm a retrovirus and I'm breaking out" to Arctic non-virologists? What retrovirus symptoms are so acute and worrying that a CDC team would have been called in? What retrovirus causes you to bleed out and die? Oh, and melts the flesh from your bones as well? How did the Arctic guys identify it was a retrovirus before asking for help?
  • A "Spherical" worm virus? Clearly nothing like a retrovirus.
  • "The cells are heavily damaged almost totally deformed, it's like..Armageddon down there." says senior post-doc.
                        "But no sign of a virus?" says junior whizz-kid post-doc. Ouch. C.P.E. I'ma geddin outta here.
  • 15nm (?could have been 5 or 150 - was hard to hear) on an electron microscope (EM) screen...that clearly shows a scale of 8,000nm...pretty good on-the-fly size estimation young whizz-kid post-doc.
  • Portable, real-time, high-magnification scanning electron microscope (SEM), adjustable with a focus knob, that can also show CG wormy virus entering cells that then instantly shrivel without the SEM killing/breaking down the cells or the virus? Also totally unlike the Helix show logo which looked more like the cell, but was black yet not shrivelled. I'm so confused.
  • What's with the unofficial CDC logo - or lack of the official logo? The show is not even supported by the CDC but uses "CDC" a lot?
  • "...screened for all current viral structures..", "...even icosahedrons". What are the chances that they even looked for icosahedrons??? Its not like they are a hugely common presence in the virus world or anything...Oh.
  • This unknown illness caused by a "retrovirus" or whatever, is to be worked with under Biosafety Level 4 conditions (BSL4) and yet considerable work is done on open benches without any significant personal protective gear. Of course that's all after the pathogen is defined as not being capable of spreading via an airborne route. Apparently there is just one type of airborne spread and droplets and aerosols generated by a number of techniques and procedures...and gunshots...don't count.
  • You take off your BSL4 suit because a mouse doesn't what? Die in a matter of minutes...perhaps hours? If wormy virus is enacting annihilation upon it's human hosts then I'd like to at least see a monkey if not some decent primary human (because that's the host we're most worried about it annihilating) cell-culture results and inflammatory marker data before I started breathing that air! We do see a (creepy, angry) monkey later, but the protective gear doesn't go back on, or ever get put on in some cases, and then in later episodes it does, then it's off again, then a non-sealing surgical mask turns up...argh! BSL4 being optional must be part of the working-without-regulations mantra up there in BigPharma Arctic world 
  • In a later Ep we develop a test using green fluorescent protein. GFP is  from the jellyfish Aequorea victoria our over-sharing young whizz-kid post-doc states; although she states nothing about how this bloody rapid bedside test works nor how she produced it without any cloning at all. It gets combined with an infected patient's white blood cells. A huge volume of the GFP-containing, virus-sensitive, previously infected patient cell solution glows green (under normal light) just seconds after a huge volume of the infected patient's sample is added. 96-well plate guys? Mind you this was all developed without validation and within half an hour or so; exemplifying how great the 26-year old whizz-kid post-doc with 2 Masters degrees is in the lab. She told us she was earlier. Later we see why unvalidated tests based on poor science and rushed to market fail so spectacularly. More on that in Ep 4 I suspect.
  • Hey, anyway, let's go conduct a monkey autopsy with just a face shield that is in no-way sealed to our face. And what the hell, why even bother doing up that lab coat? It would just ruin the belligerent devil-may-care researcher vibe we're aiming for. Aerosolized bits of diseased freaky-monkey tissue in your eyes/mouth/nose/lung anyone?
Where World War Z succeeded in providing a great story about a virus wanting to transmit by driving its host to infect more potential hosts, Helix fails by clubbing us over the head with a show that feels like it's leveraged science thawed from an Arctic vault constructed in the 90s. 

While I don't expect the general audience to know that centrifuging a drill core of frozen solid monkey butt will not just transform it into a homogeneous black liquid in 5-sec (or ever), I do think they will notice something is amiss. Off beat. Out of  sync. Even if it is set 5-min into the future or something.

Try making Helix smarter. I like that there is a story about DURC that may get to a wider audience. That and the suspense are probably the biggest draw-cards for me. 

This needed/needs an infectious disease expert on the advisory team. A virologist in this case. Just as disease outbreaks do in real life. Just as the movie Contagion had - and for that movie, it really paid off.
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Are we testing enough?

I had written this as part of my last post but it didn't fit in with that topic...

Yes there was a case of pneumonia in the Kingdom of Saudi Arabia that apparently went untested for all possible/emerging/out-of-the-box pathogens - does that never happen elsewhere?

In defence of the current MERS-CoV hotzone's testing, there are plenty of research and review papers in the scientific literature that show pneumonia is one of those diseases that could really do with better testing and characterisation. Acute brain inflammatory diseases are another bunch. They are scary diseases, they have an immediate impact and sequelae that may not yet be well defined and they are likely to be triggered by 1 or more viruses and or bacteria. And all that sits on top of the highly variable milieu of our genetic (immune defects?), physiological (prior predisposing tissue damage or changes?) and immunological (previous exposures or lack thereof) background.

Is it possible to effectively manage disease prevention and ill patients if you don't know the cause of the disease? Sure, there are no treatments for most viral diseases - but that's an excuse not to uncover the agent likely causing a patient's ills and not a reason. One can never learn the cause if there has been no testing for the most pertinent bugs. Its a vicious and really annoying cycle that seems to be part of a disconnect between the bed and the lab. At least in some places. I'm deliberately leaving aside being unable to prove causality through detection alone. That's for another day.

In the case of diseases that are poorly tested, that list of bugs should include everything relevant and everything that could be relevant. 

It feels (oh very scientific) like its been a while since we've really looked hard at the testing of some acute diseases - we tend to stick with what we knew when it comes to testing panels. Over time new technologies have been developed (PCR - kinda old now) and a lot of new bugs have been (and keep being) found. Are we in need of a shake up? I think "paradigm" should really be a dirty word in the testing for infectious agents right now.

I would personally love to get some good collaborations going and do some comprehensive testing for everything under the sun, plus some next-generation sequencing to find things we don't yet know of, on a large number of such cases (and controls). Finding the funding - and the interested collaborators - now there is a trick worthy of Loki and one I have yet to attain.

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Kingdom of Saudi Arabia is MERS-free...is it MERS-CoV free though?

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An article on news site France24 notes that no MERS cases are to be found in the KSA ahead of the imminent commencement date of the hajj; a gathering of pilgrims that is already well under way.

Great. And may that remain the case for the next few weeks.

And I tend to agree that there will not be any "mass spread" of a virus that still does not show that potential.

But the story avoids an important fact - while inadvertently spelling it out. 

There have been no severe cases of MERS - the disease - in the KSA in the lead up to the hajj. Severe enough to warrant triggering the strict measures...


"Employees have been given strict orders to isolate any suspected case and carry out the necessary laboratory tests" to ensure the safety of pilgrims on the hajj. 

To suspect, the Ministry of Health employees will first have to eyeball a fairly sick individual.

What about mild and asymptomatic cases of MERS-CoV infection? We know that they happen. We know that means at some point the person is likely to be shedding virus (at some level for some time period). We know transmission between humans is possible, albeit limited. We know of millions of pilgrims visiting the KSA so while the chance of a limited transmission event happening may remain the same, the total number of such events could rise. We know that we don't know where MERS-CoV is coming from. We know we have no idea how much, or little, MERS-CoV infection is in the "normal healthy" population in the KSA because that testing has not been done. We don't know much about the circulation or proportion of cases due to the other endemic CoVs in the KSA because epidemiology publications about general respiratory virus testing is limited.

So why is testing and isolation of patients still limited to severe cases? We don't yet know that mild/asymptomatic cases don't shed virus. So what we may potentially see in the coming weeks is many ambulatory new cases walking around shedding virus until they transmit to one of those older males who have 1 or more comorbidities. Then we see a 2:5 chances of that person dying from an infection they cannot explain getting because they were not in contact with a severe case or a likely animal.

While we do not know the primary source of the MERS-CoV - we do know that testing less ill people would let us answer an important secondary question; are the sporadic infections actually due to human-to-human transmission events that are simply not being identified or sought? This method of spread doesn't discount the viral genetic diversity we've recently learned of either. There could still have been multiple spillover events from animals - each may simply have spread more widely throughout the community than we know.

Please, please do some prospective testing. It would be an answer - and we have too few of those for MERS.

Thanks to @makoto_au_japon fr posting the link to the France24 article.
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Happy 1st birthday Middle East respiratory syndrome coronavirus (MERS-CoV)

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A coronavirus schematic. The spiky bits give the virus
its name(corona=crown) and represent the
receptor binding, antigenic Spike protein. 
...I can remember when you were just a novel little thing.
How you have grown young prince and how clever of you to emerge in a Kingdom of all places (corona=crown, named for it's spikey appearance). You've certainly garnered attention worthy of a King given the relatively few cases of disease you gave been associated with in the first year we've known of you.

It was September 20th when Dr Zaki 1st alerted the world to the death of a Saudi man due to what looked to be a new coronavirus (CoV). Today we have over 135 cases 58 deaths (43%).

I've previously covered Zaki's disocvery and the problems posed for the Kingdom of Saudi Arabia (KSA) by the way in which he announced that discovery, apparently without the Ministry of Health's (MOH) foreknowledge. The way in which the sample was exported from the KSA without their prior consent was also problematic for them.
Soon after we heard of it, we had virus-detection assays with which we could seek out new cases. Were they used as they might have been in the days of the SARS-CoV? Nope. And there still seems to be only a single laboratory in KSA testing for MERS-CoV (despite reports of 3), with Dr Abdullah Al-Aeeri (a director of hospital infection control) claiming a 72-hour reporting turnaround time.

Is there an antibody detection assay that has been validated using a panel of known positive sera? Nope. There are some innovative antibody-detection methods around but why do they only include a single positive control? Is there no collaboration at all? Why is the KSA not leading the charge to develop these diagnostics and to hunt for an animal host? Why wait on advice from external organizations to screen samples? Why has the necessary testing capacity not been built well before now? Is it to do with that pesky material transfer agreement? I hope not because there is little evidence for that being a real block to anything from a public health standpoint.

At least we have some new MERS-CoV sequences to celebrate the birthday with. Although they and the 9 preceding them represent less than half of the relatively small number of cases described to date. Why can't the typing region sequences be released? That should really be part of the diagnostic process. Okay, those may not inform us about the evolution of key regions of the virus but they do confirm it is the strain we know. Why not focus on full or subgenomic Spike gene sequences? They might be a better sentinel for keeping tabs on MERS-CoV change over time.

Most of the detail about MERS-CoV and cases of MERS has come through the peer-reviewed scientific literature. That is pretty normal for respiratory viruses that are not notifiable. But it's generally a slow medium. Is MERS infection a notifiable disease? It is in some countries (e.g. the US and New Zealand), but is it at the epicenter of the outbreak, the KSA? I'm not sure. It's not obviously stated as such anywhere I looked on the KSA MOH website.

The World Health Organization politely notes:

WHO encourages all Member States to enhance their surveillance for severe acute respiratory infections (SARI) and to carefully review any unusual patterns of SARI or pneumonia cases. WHO urges Member States to notify or verify to WHO any probable or confirmed case of infection with MERS-CoV.

How's that been working out? In a nice summary of the lack of communication, Helen Branswell and Declan Butler highlight that, as usual, everyone  who was asked agreed that it's not working out well at all. In fact it's pretty woeful. And to add to matters, the latest WHO Disease Outbreak News (DON) takes the form of a summary of 18 "new" cases; no extra or confirmatory detail to be had from it. SO the KSA MOH is now the source for detail.

If we were talking about wanting more data on the monthly proportion of rhinovirus infections, the KSA would be justified in saying that the world doesn't need to know (I'd like to but that's my thing). 

If we were talking about influenza, then there are plenty of international public health sites publishing these notifiable data on the internet; here's Queensland, Australia's for example.

But we're talking about an emerging disease which kills half of the people it infects, is caused by a novel virus for which no host is known, which transmits between people in a way we don't yet understand, which is shed from ill (or well) people for an undefined period of time (if at all), which remains infectious in the environment for who knows how long, which jumps to other countries, which may only cause severe disease in those who are already ill with another disease, which may be endemically spreading within the community as mild or asymptomatic infections, for which there is no vaccine or proven antiviral therapy available..I'd say it's a no-brainer that at the very least the WHO deserves regular and detailed updates of what's going on. Reading between the lines, that does not seem to be happening even behind closed doors.

The mass gathering of pilgrims known as the Hajj is fast approaching. This may trigger a large increase in MERS cases or, in the worst case, a pandemic. I personally believe it won't go that far. We shouldn't forget is the 2nd Hajj for MERS. But perhaps the virus is much more widespread than it was in October 2012. But without testing data, we can only guess.

So, it's your 1st birthday MERS-CoV. But instead of wishing you a happy birthday you opportunistic, spiky little killer, I'm wishing Dr Zaki well and congratulating him on co-parenting the birth of this novel coronavirus. Going by what we've seen to date, his actions may have been the only way we would have ever heard of this virus otherwise.

And, as noted previously, but not given much air to in the above rant (thanks to @MicorbeLover for straightening me out)...

It's very sad that there are real people in these numbers who have died from MERS. You may have noticed that I try and stick with the cold number-crunching aspect of these outbreaks. It's not because I'm a heartless b&^$# but because that is not what this blog is about. That and my editorialisation and expositionary writing consume what little time I have spare. But I don't feel that I have enough information to make any other comments about these or any other lives lost to infectious disease. I personally feel that any unexpected and acute loss of life (if I had to scale loss of life) is the worst kind of loss; it's a waste of potential, a source of great sorrow for all involved and it's something we should all strive to prevent, if we can. I know that's not much to convey, but it's all I can offer from my kinda comfy chair in Brisbane. 

The MOH says it better in anyway; May Allah have mercy upon the deceased.
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A memo to the Saudi Minister of Health...

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Crawford Kilian has written a memo to Abdullah Abdulaziz M. Al Rabeeah, MD, Minister of Health, Kingdom of Saudi Arabia.

It is brilliant. 

Please read the entire thing. I have an excerpt below, but it is only a fragment of the whole glorious piece.


Your government, Minister, is now risking a similar problem. Both medical experts and the media are growing impatient at the erratic flow of information on MERS, and I hear rumours that Saudi hospital staff are as alarmed as those in Canadian hospitals afflicted with SARS ten years ago. And well they might be, when this virus seems to thrive in healthcare settings.

An aggressive, open communication policy is now urgently called for. Rather than indulge in a litany of past problems, I would like to recommend some steps your ministry could take right now to ease concerns around the world while also ensuring solid support from Saudi professionals and public. 1. Frame a detailed, standard format for reporting each case. At a minimum, this should include:

1. Frame detailed, standard format for reporting each case. 
At a minimum, this should include:
  • the age, gender, and occupation of the patient;
  • mention of specific underlying medical conditions, if any;
  • place and date of onset;
  • a description of treatment and place of treatment;
  • the specific relationship, if any, to previous cases;
  • tests administered and results of those tests;
  • if possible, a statement by a Ministry spokesperson putting this case in the context of recent events.
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Is there a better smoking bat or camel?

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That teensy fragment of Middle East respiratory syndrome coronavirus (MERS-CoV) sequence (yes, I called it a fragment of that virus) from a Taphozous perforatus bat caused a lot of hassle last week,certainly a disproportionate amount to it's representation of only 0.5% of a MERS-CoV genome. Similarly, the report of MERS-CoV protein-reactive antibodies in camels some weeks back.

In a New York Times (NYT) article discussing the discovery of the 180-203 nucleotide (nt) gene fragment in a Saudi Arabian tomb bat, Donald McNeil opened with..


Health officials confirmed Wednesday that bats in Saudi Arabia were the source of the mysterious virus that has sickened 96 people in the Middle East, killing 47 of them.

The size range represents numbers used in various articles and of the fragment from the public sequence database GenBank (203nt) -"~190 nt" noted in the actual scientific publication). By the way, has so much ever before been written about so tiny a sequence?

Because he did not include in this line, or his article, a list of all the various possible scientific shortcomings, he didn't write in more detail about the difficulties with linking a virus in any sample to the cause of a disease  in humans, he forgot to specify that this was not the actual virion that caused MERS in the human index case in Bisha, he left out the PCR-101 section on why detecting a genetic sequence is not the same as isolating an infectious virus or how to interpret a PCR fragment's sequence....he was, in some circles, criticised. 

Okay, so the bat study did not isolate infectious virus, could not obtain any other sequence, found sequence in a bat from the family Emballonuridae rather than the "expected" Vespertilionidae bats and the positive sample was from bat faeces rather than blood or some other sample more convincing. Perhaps insects, food for T.perforatus, carry MERS-like CoVs? No-one has ever found that though. Is there evidence for 2 CoVs to be completely different except for a stretch of ~100% identity? Don't know, but don't think so. As Prof Andrew Rambaut noted in his very detailed analysis of this fragment, it does differ by 1 nucleotide from many MERS-CoV sequences (so its 99.5%-100% identical). Is there a more likely animal carrying a more similar MERS-CoV strain of virus that is spilling over to humans causing MERS cases? None that has been publicised to date. And therein likes my beef with some of the criticisms I have read this week. 

So far, this finding is the best lead we have in finding an animal source. There is no evidence to dispute the link, any more than there is evidence to prove it. Yes, there may be a another smoking bat or camel or something else out there. But it hasn't been found yet. And the public might like to hear how researchers are progressing rather than wait the very long time it will take to dot Is and cross Ts on the final MERS-CoV life-cycle, once they determine it.

And by the way, there is no other CoV sequence on GenBank that has >90% nucleotide identity with the T.perforatus sequence, except for the human MERS-CoV sequences. That doesn't exclude there being some other recombinant or novel CoV out there, but that is pure speculation; more so than saying that this new sequence represents a strain of the MERS-CoV found in humans.

In succinctly summarising some of the criticism, an article in CIDRAP presents a great overview and hints at what this criticism implies; that stories in the media must get every detail spot on or the writer may be portrayed as a poor scientist.

What? Wait. Seriously??

This was a newspaper article in the New York Times people. It was about 870 words long. It won't be setting global health policy nor will it be creating a WHO disease notification stating Taphozous perforatus bats, in particular, are the primary source of all MERS cases. Or of any cases. I don't doubt this is a prestigious newspaper but this story will likely be nest week's fish 'n chip wrappings (does anyone still use newspaper to wrap fish 'n chips? Is there a digital equivalent of - "yesterday's homepage, tomorrow's archive"?). In my opinion, and I don't mean to speak for all, scientists and health policy makers know that a newspaper is not a peer-reviewed scientific journal and that it's intent is to inform it's readers so they'll come back.

Were the many readers of the NYT misinformed? Perhaps the "health officials" could have been better defined by the NYT article. Presumably it's the authors-researchers may have been a better descriptive (as was used in a follow-up piece), probably more in tune with the public's perception of us. Beyond that the article did a good job of presenting the results of a research paper's relevant findings to the wider audience. They also both caution against over-interpreting the data. The NYT article has that well covered; a transmission route is not clear, more testing needed, more work being done, sample degradation due to a break in the cold chain, it was only 1 bat.

I very much agree with comments in Robert Roos CIDRAP article; the critics are getting carried away. There are many different levels of science communication that reach the general community - the popular press are not Lancet, and vice versa.

If you really want to pick holes in a part of the coverage, you might well ask why so many are looking at a 180-190nt fragment when the ends of that PCR-amplified fragment actually reflect the commercially made oligonucleotide "primers", not the (likely) viral template at all.  The actual fragment that should be analysed from the T.perforatus bat droppings is, at best, 156nt (but only 137nt if the internal nested PCR product was sequenced but the product on GenBank, 203nt long, includes both internal and external primer sequences in it-PCR speak here, sorry). Probably won't change the outcome of any analyses to date (156 still encompasses the nucleotide variation and is still differs by 11% from any non-MERS-CoV sequence), but it is a different number. 

I'm sure a newspaper headline "156 nucleotides of a 30,130 nucleotide genome possibly related to the mystery virus that may have directly or indirectly killed 47 people in Saudi Arabia" would be a real page turner.

So, let's keep up the good work of presenting and trying to deconvolute our own studies, let's keep the public interested and informed without overcooking the message, let's allow for imperfection (as readers of this blog will be all too familiar with), but perhaps let's keep the peer reviews to the scientific literature where they are in demand and required...and keep perspective on these new findings when they come to our attention through the popular press.

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Editor's rant: Why testing the few may not benefit the many...

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Prospective screening without regard for whether the person is sick. That's what I think we need more of, in order to truly understand respiratory viruses and acute respiratory infections (ARIs).

And I don't just mean the scary ones like MERS-CoV or influenza A(H5N1) virus or H7N9 or H7N7 (zoonotic flu). 

I also mean the rhinoviruses, influenza A(H3N2) virus, H1N1 (seasonal flu), endemic coronaviruses (CoV; 229E, OC43, NL63, HKU1), metapneumoviruses (MPV; I use the plural because there are 4 genotypes and who knows how many immunogenetically distinct clades), respiratory syncytial viruses (RSV; same plural), adenoviruses, enteroviruses, Saffold viruses, parechoviruses, polyomaviruses, bocaviruses...etc.

Sure, there have been studies in birth cohorts and in the community among "normal"'healthy people. But they sometimes have limitations that may blur our view of what is really happening in the community. For example, such studies may:

  • Exclude certain diseases that viruses are involved in.
  • Only sample when there are signs and symptoms of disease. 
  • Only call "disease" when a certain number or combination of symptoms are present (this one irks me no end - pedantically, if your body deviates from its physiological norms, you are diseased).
  • Sample too infrequently to catch whats going on between sampling points. We don't get one virus, recover, then get another - we're a virus's favourite hang out - but because of our awesome immune system, only some of those infections make us ill enough to stop and groan.
  • Employ insensitive detection methods (cell, tissue or organ culture). In fact, if a study used culture you might as well ignore those data - they will have missed many fastidious viruses (those that don't grow easily or in the cell lines used) rendering any conclusions associating detection of a virus and disease weak or wrong.
  • Sample for too short a period or just focus on a particular season etc. 
  • Only include a pet virus or a few viruses or just those viruses known about at the time. 
Much of our understanding of each virus comes from hospital-based studies. People in this environment, whether admitted (inpatients) or presenting but being allowed back home (outpatients), represent the "tip of the iceberg" of the disease spectrum. The pointy end. The most severe cases. We may make the assumption that the viruses circulating in the community are represented by what's happening in a hospital environment - or vice versa. But how often have we tested that? Do we know if there is a lag or lead time? Does it differ by climate? Could we go further and perhaps use those numbers to predict what the burden of disease in hospital will be this "season"?

And then there's the ongoing testing issue. Research dollars generally do not fund epidemiology. Certainly not ongoing epidemiology. Even big hospitals and private testing labs cannot afford the personnel and cost of testing all respiratory samples for all "likely" viral pathogens, all the time. "Likely" having been defined with the caveats above. 

And so our epidemiology data have holes. Big ones. We read of complaints about some countries not being able to identify a viral/bacterial cause (not that a POS lab test does prove cause) of pneumonia or encephalitis...but many patients in more "developed"countries also leave hospital without ever being attached to a lab-confirmed positive result. We could reduce that, even if we could not specifically treat them. And therein lies another issue. We test for some viruses based on historical precedent - do those precedents accurately stand up today? Do we even have the data to answer that? If you are a health professional, have a look at what your local testing lab offers - does it cater for the most likely causes of ARI or just what's been used before? 
Click image to enlarge. Respiratory virus infections among the community
and in hospital-based populations. Generally more males than females
present to hospital  with clinically-defined acute respiratory infections
(ARIs). Infections in the hospital setting are shown in red, those in the
community in orange.  Most ongoing virus testing is from
hospital-based populations as is our contemporary
understanding of viral season.

Notifiable viral diseases are kept track of, and if they occurred by themselves without interaction with, or interference from, other viruses that might be enough. But they don't. 

The "One World" concept of infectious disease study - looking at animals and humans and the environment together - is great; what about the concept of "One Virus"? The days of a study looking at just one virus and from that, without testing for any other respiratory virus that may cause the same signs and symptoms, concluding what that virus is capable of, it's severity and how many cases of disease are lessened by a drug for it, in a human should be far behind us. But they are not. 

So, do we really know the viruses that call us home? And if the answer is no, how can we possibly hope to be prepared for the next virus that emerges, the next local viral outbreak of ARI or encephalitis or gastroenteritis, or the next pandemic? How can we protect our population from viral threats if we're always on the back foot?

If I ruled the world, we would do more testing we'd try not to bias our attentions toward any 1 virus, we'd screen everything for everything, we'd sample the community, we'd make the data publicly available in real time, we'd understand ARI epidemiology better and we'd use all those data to prioritize some antiviral drug development or other viral interventions. At the very least, we'd re-jig our testing panels and create a new paradigm or 2.

But I don't rule the world - nor do I have input into these sorts of decisions - perhaps you do?

Feel free to weigh in below.
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