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.

MERS-CoV by the numbers: recent weekly case activity...

Click to enlarge.

Confirmed MERS-CoV cases (green) and

deaths (red) each week. Case numbers

are listed on the y-axis (side), days of each

week along the x-axis (bottom). Case dates

are derived from announced date of onset

but if absent, on the date of reporting.

This follows on from my previous post (you can follow its links to earlier weekly charts) about lab-confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) cases, plotted by week.

These charts are based on the reports that get into the public domain. Those of us trying to follow and deconvolute MERS-CoV case information pretty much all agree that the data are terrible, but they are what they are. For example, the data are currently absent details on 2 MERS-related deaths for which no links to our case lists can be found. There are 85 cases missing date of disease onset data (which makes these charts imperfect), 8 without an age, 10 without a sex and most have no date of hospitalisation or date of lab confirmation. As I've bemoaned before, a standardised numbering of cases would be helpful too. Among other things.

The charts suggest there is not a lot of activity in terms of new cases, and the number of deaths, thankfully, remain much lower than during the weeks preceding my post in early September.

You can see that during the Hajj (13th-18th of October), there were 3 cases and a death described but in the weeks immediately afterwards, there has been no spike in cases of MERS. What makes this a significant development is that, for the second time since we learned of MERS-CoV, countries outside the Kingdom of Saudi Arabia (KSA) have had a direct hand in the observation and testing of pilgrims. This adds some confidence that severe symptomatic MERS is a relatively rare disease and one that does not spread quickly and efficiently. We have no real data to say that virus doesn't spread quick, widely and efficiently however, just that the severe infection outcomes don't.

So, no sign of a major jump in new cases. In this 4-week period there have been 13 cases which is up 2 from the 4-weeks before that. There have been 3 deaths (PFC of 23.1%, well below the total average of 41.3%) in this period, down from 4 in the previous month.

These numbers still have to be considered with care. This week's Spanish case really shone a light on the issue of laboratory unconfirmed cases of clinically diagnosed pneumonia circulating in the KSA. And where there is one such case there are likely to be others. Many others? We don't know.

So with 155 cases and 64 deaths in 87-weeks, MERS seems to be ticking along, but it shows no signs of becoming a widespread health issue. While it has a PFC of 41%, that is a meaningless number until we start testing more widely than is being done now. There are still many questions to answer about its host, how humans acquire it, whether its widespread in the community - but on the topic of transmission, MERS does not look likely to become a pandemic any time soon.

MERS-CoV case in Spain, imported from Saudi Arabia during visit for Hajj pilgrimage [UPDATED]

Spain's Ministry of Health, Social Services and Equality (Ministerio de Sanidad, Servicios Sociales e Igualdad) has been reported via the media (not yet on their website) as describing the first case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection.

Click to enlarge.
MERS map of the world. Countries hosting internal
transmission for MERS-CoV are shown in red. Those
hosting imported cases in orange.

The case is being presumed to be imported from the Kingdom of Saudi Arabia (KSA). The subject, a 61-year old Moroccan woman (61F; presumably FluTracker's #153) living in Spain, had spent a month in the KSA (Oct 2 to Nov 1; the Hajj specifically occurred during Oct 13-18) and was showing signs and symptoms of a febrile cough illness on the 15th of October. She did attend the Hajj according to Helen Branswell's article. So can now put the "no cases during the Hajj" story to bed? We don't technically know when the virus was acquired.  61F was in the KSA for a long period so acquisition may have occurred before or after but let's not split hairs, it was a Hajj-related acquisition. 

61F is stable with a diagnosis of pneumonia (chest X-ray) which was made sometime around 28/29 October in a hospital in the KSA.

Timeliness is a big concern here. It seems that 7-days passed between a clinical diagnosis of pneumonia in KSA, a flight from Jeddah to Madrid and a laboratory diagnosis (at the National Center for Microbiology in Spain) of MERS-CoV infection on Nov 5th. That's perhaps 21-days between onset and laboratory confirmation. Spanish contact tracing commenced at the time of confirmation (6-Nov). 

I guess we'll see if there are any more details to be had about the transport process (isolation/containment procedures?). We do know that 61F was symptomatic and needed oxygen during the flight. 

It's a good thing MERS-CoV does not seem to transmit efficiently - there may have been many exposures between the 15th and the final diagnosis and hospitalisation in Spain. And why could the laboratory testing not have been completed in the KSA? Was a swab/aspirate/lavage taken for any testing there? Either this is a political thing or there are (?many) cases of pneumonia in the KSA that are going untested for MERS-CoV....or for any virus or bacterium?

The current MERS-CoV tally is 151 cases, 64 deaths (42.3%)

See Mike Coston's posts of the early reports here and here. Thanks to Helen Branswell (@HelanBranswell) for tweetification.

Am I doing enough?

I'm very guilty of suffering from this. The darker side of my nature shoves this question up to the surface, as I'm sure it does for many of us at times..

Have I done enough today? 

But its not the only one to answer during a busy day. What about, am I making an impact? Will I leave a suitably ugly but well-respected corpse? Do I see enough of my kids? Do they see enough of me? Am I doing enough to help out around the house? Why can I not get that grant? Am I doing enough on the grants I currently hold? How many ethics renewals are coming up? What about that GMO renewal? How could viruses fit into those new funding opportunities I read about on Friday? Did that PhD student get a rough review because I was tired? How many manuscripts am I shepherding - was it 3 or 4, was that a new request last night? Should stop checking eMail last thing at night so I don't let them slip down the InBox. When are those 2 manuscript reviews due? I hate when my reviewers drag their heels. How do I get that preliminary data now that I've lost my research assistant? How many more hours do I need to spend at night to get these papers out? Does sleep deprivation really do that?  Is glymph build up irrevocably ruining me? I'd have called it blymph. How can I make them see that testing for some viruses but not other misses the point of testing at all? So now salt is okay but statins aren't? I always suspected sugar was the enemy but damn I'd love some chocolate. When is my next cholesterol review due? Garfield always had it right; "die" with a 't' ". Should I stop writing content reviews and instead initiate more content? Why am I writing any of this stuff anyway? Is it a waste? Can I finally spare a little time to play some more Crysis (I see they are up to #3 now). Will I miss Thor on the big screen? Do those plants need watering? Is lawn grub causing that? Need groceries. 

So it was with great interest that I caught this article on news.com.au written by Keija Zhu and posted on his blog. Take a couple of minutes to read the entire post. It's a tale laden with wisdom and calm sensibility. It's written in such a way that it just makes sense and could easily translate to a mantra...

Don't be in so much of a rush. Be easier on yourself. Comparing yourself to what others are doing is a waste of time. He also adds an old Chinese saying "大器晚成" - A big construction is always completed late.

Excellent advice. 

Right. What's next?

Infection prevention and control and MERS

Harriman, Brosseau and Triverdi have written to the Editor of the New England Journal of Medicine (NEJM) to express their concerns over the lack of apparent preventative measures undertaken during the Al-Ahsa Middle East respiratory syndrome (MERS) coronavirus outbreak communicated by Assiri et al (previously reviewed here).

The new letter indicates that with so little known about MERS-CoV transmission route(s), a safer bet would have been to protect healthcare workers as much as possible. They suggest use of  respirators rather than surgical masks (see Mike Coston's reviews of the differences here, here, here, here and here...likes his masks does Mike). 

Possibly eye protection as well given the transmission unknowns. 

I've previously listed these and other precautions for managing patients with endemic or with less well-defined respiratory pathogens. Worth a reminder read.

The authors highlight it would be prudent, in a well-resourced country like the Kingdom of Saudi Arabia, to roll out as many extra personal protective safeguards for the front-line healthcare workers as possible; at least while the slow hunt to understand how the virus is acquired and transmitted seeks some answers.

The reply to this letter by Memish, Al-Tawfiq and Assiri did not specifically agree with its specifics or address enhanced care for HCWs, instead restating what was done to respond. The key comment summing up the use of respirators indicates a reactive rather than proactive approach to HCW care in trying to prevent a case from spreading their laboratory confirmed infection. 

...putting surgical masks on all patients undergoing hemodialysis and particulate respirators (N95 masks) on any patient with confirmed MERS-CoV who was undergoing an aerosol-generating procedure...

As we've seen over and over again during this outbreak and others, by the time a laboratory confirmation is available, it is far too late to halt early transmission events. 

When those events occur in a hospital environment it's not just the relatively (to the MERS-CoV case averages) younger and more healthy HCWs that are at risk of infection and disease. MERS-CoV and other respiratory viruses are at their most lethal among the elderly with comorbidities. Delays in lab testing, in waiting for something to happen or in following other's guidelines to the letter rather than modifying or creating new ones based on front-line experiences, can have severe consequences.

I take the message from this letter as: Be proactive not reactive.

MERS-CoV and the host: a serious disease of those with disease

Case total currently stands at 150 including 64 deaths (PFC of 43%), with the World Health Organisation's latest update adding in the recent death (their tally says 149/63) and the Oman case and a new death being reported from eastern Saudi Arabia. The details for this latest patient are (FT#152):

• 56-year old male
• Comorbidities
• Contact of a previous case.

So, as the Oman case showed, transmission from a previous case can lead to mild illness. The Qatari case before that showed that a contact can be asymptomatic. This latest fatality highlights that under the right pre-existing disease conditions, even a 2nd "passage" of virus from a human to another human, can lead result in death. 

It's a very much about the health of the human host who acquires the virus, as we've seen all along with MERS and also among cases of influenza A(H7N9) virus infection.

The latest WHO update also notes that...

Patients diagnosed and reported to date have had respiratory disease as their primary illness. Diarrhoea is commonly reported among the patients and severe complications include renal failure and acute respiratory distress syndrome (ARDS) with shock. It is possible that severely immunocompromised patients can present with atypical signs and symptoms.

New MERS-CoV laboratory test: takes 10-minutes but what can it tell you?

Back in June we heard of a quick test for MERS-CoV to add to the diagnostic armamentarium. I posted on it here.

Now that the Abu Dhabi Medical Congress & Exhibition it was presented at is over, we are hearing about it again through a story at The National. 

Still no details though, so my original concerns about sensitivity (how often will it miss true positive cases because it is not sensitive enough?) linger on.

Further, it's a "blood test" that also uses DNA amplification so the patient will presumably need to be sick enough to have a viraemia (virus spilling over into the blood) so it may not help at all for screening contacts or less ill people with lower viral loads. It is being described as useful for "identifying the virus in its early stages". 

Another assay that looks similar, described in PLoSONE by these researchers earlier in the year, does not appear comparable to PCR-based methods in terms of its sensitivity. 

For MERS-CoV, as for any newly emerging pathogen with unknown characteristics spreading in ways we are yet to understand, detection sensitivity is a key factor.

I look forward to seeing same real-world evaluation data.

French "probable" case pas vraiment so probable after all

FluTracker's and Mike Coston is busy keeping us up-to-date on the latest with MERS-CoV concerns around the world post-Hajj.

Last night's probable case has tested negative for the MERS-CoV according to media - the Health Ministry website has not released this yet.

The surviving case of MERS-CoV in France, is still hospitalized.

• Mike's post.
• FluTracker's thread
• Le Figaro carrying the MOH announcment
• BFMTV article

First case of MERS-CoV in Oman...home of antibody-positve camels...[UPDATED]

A new country has described, via the media (quoting Mohamed bin Saif al Hosni, Under-Secretary for Oman's Health Affairs), its first Middle East respiratory syndrome coronavirus (MERS-CoV) case, the sultanate of Oman. 

It seems that the case was acquired locally from someone infected outside Oman.

• 68-year old male with diabetes
• Still no detail on the supposed confirmed case he was in contact with or the test type or date of hospitalization
• The Oman Ministry of Health website has not officially confirmed the case at this stage. 
• When confirmed, this will be the 149th confirmed case ("probable" FluTrackers #151)

Oman's Centre for Public Health Laboratory (CPHL) has been testing for MERS-CoV from suspect cases since October 2012 and while prospective laboratory screening of returning Hajj pilgrims was not being undertaken, observation for signs and symptoms of disease was ongoing.

If we remember back to early August, - 50 of 50 retired racing camels from Oman had antibodies to something that was closely related to the MERS-CoV. 

Thanks to Mike Coston, @makoto_au_japon and @Crof for tweets and posts
Thanks to FluTrackers for tweeting & posting the AFP update 

Latest confirmed cases and a probable new MERS-CoV case(s) in France [UPDATED]

It's been a couple of days since the last report of a new MERS-CoV case, that of an expatriate, 23-year old asymptomatic male contact of another case in Doha, Qatar (the 7th seemingly acquired on Qatari soil). 23M (FT#150) was mildly ill and was diagnosed through routine screening of contacts. The man worked with animals in a barn owned by a previous case according to the latest WHO update. Once again this highlights that the MERS-CoV can move on from an infected person and it can do it stealthily. However, the next "round" of infection seems to be (a) milder in severity and (b) the end of the transmission event.

Unfortunately the recently described MERS-CoV-positive 83-year old woman in Jubail on the eastern coast of Saudi Arabia, has reportedly died. Apparently she was hospitalised a month ago.

Buzzing around on Twitter (thanks to @makoto_au_japon) and the web nothing is the story of a probable case in a 43-year old in France. The man returned from a stay in Saudi Arabia and he is currently described as stable. There areno more details on France's Department of Health and Social Affairs website but they have noted it on their Twitter feed (@Minist_Sante) and have the media release. The various translations mention the plural, "cases" (machine glitch?). An article in the Khaleej Times notes it is unclear whether this person was a pilgrim to the Hajj. My Form 3 French is very rusty and didn't covered public health so I eagerly await laboratory confirmation. 

If this imported case is confirmed [UPDATE: it was not] it will be France's 3rd detection, only 1 of which has been transmitted locally.

The MERS-CoV laboratory confirmed count currently stands at 148 cases with 63 deaths (PFC of 45.6%) .