MERS-CoV in camels... [CORRECTED]

The top pie chart shows the distribution
of all human cases containing the word 
"camel" in their case notes, by the site where
the human was likely to have acquired their 
MERS-CoV infection. The bottom bar 
graph shows those data in terms of the
 proportion of cases at that site for which
"camel" contact was possible.
Click on chart to enlarge.

Thanks very much to Nicholas Evans (@neva9257 via Twitter) for asking me to back up my gut feeling about there having been more camel-links among MERS-CoV cases outside the Kingdom of Saudi Arabia (KSA) compared to inside.

I live to serve and so using those data I have to hand I've made a couple of charts. I'll keep these updated from now on too. 

I'd be grateful if anyone wanted to shout out human cases where camel contact was mentioned. I currently have 8 in total on my list of 201 lab confirmed MERS-CoV cases. (see the figure up there for where my cases are sourced). There may be many I have missed though.

One obvious question arising from the bottom bar graph is why does such a low proportion of camel-associated cases occur in the KSA but not elsewhere? 

For the sake of simplicity, I'll exclude the possibility that MERS-CoV jumps off its camel hosts at a border. Because the latest 68M from UAE may well have acquired his infection while visiting his camels in the KSA I have now listed him as a KSA acquisition...until I hear differently). We also know that camels in the KSA get actively infected (see earlier posts, listed below, on these findings [1,2,4]). 

So do these charts, by highlighting that so few camel links are to be found in the KSA (site of >80% of MERS-CoV human cases), discount camels as a source of infection? I don't think so. We have some very compelling evidence for camels hosting MERS-CoV [4], for camels being present in mass gatherings [5], and nothing but an absence of epidemiology to counter their role as a host and source.

I suspect the graph shows that MERS cases in the KSA won't admit to camel contact. Alternatively, perhaps contact, in its many possible direct and indirect forms is not being adequately sought or listed in case reports and in "gumshoe epidemiology" efforts (Ian Lipkin's comment, [6]). But why would camel contact not be listed, reported or collected? Perhaps it is seen as a bad thing? There may be stigma associated with acquiring an illness from a camel. Or perhaps stigma attached to the way in which that illness was acquired.

Perhaps it is a simpler explanation. There is likely to be fear, or a real risk, of social and economic fall-out of "naming and-shaming" camels as a major source of infection/disease. Camels fill many important and significant roles in the lives of those around the Arabian peninsula; from food, drink, religion to tourism and fun. But not identifying camel links in the spread of MERS-CoV, if indeed more links do exist, won't stop KSA's locals from acquiring infection and MERS. 

If there is a deficit in reporting camel exposures in the KSA, for whatever reason, it does one thing particularly well; it delays the understanding of how to protect people and reduce their exposure to MERS-CoV. I think that understanding is probably inevitable, so it may be better for the KSA Ministry of Health to get out in front of the issue; be proactive in finding the source of infections and openly discuss and plan for the implications. But I may be seen as living in a world of unicorns and fairies (again) to suggest that will eventuate. My cynicism is based on 2-years and 201 cases of a virus that's been very well virologically and molecularly detected and characterised outside the KSA, while its basic aetiology and epidemiology inside the KSA has left much to be desired.

I would very much like some locals to weigh in on this topic. Here (in the comments below) or by email or on Twitter. The bar graph simply highlights a discrepancy that could be cleared up with a better understanding (perhaps just by me) of what may  underlie the difference in the apparent roles for camels among countries sharing borders.

References...

1. Dromedary camels are a host of MERS-CoV...
   http://virologydownunder.blogspot.com.au/2013/12/middle-east-respiratory-syndrome.html
2. Middle East respiratory syndrome coronavirus (MERS-CoV): camels, camels, camels!
   http://virologydownunder.blogspot.com.au/2014/02/dromedary-camels-are-host-of-mers-cov.html
3. MERS in the UAE....[UPDATED]
   http://virologydownunder.blogspot.com.au/2014/03/mers-in-uae.html
4. Dromedary camels are a host of MERS-CoV...
   http://virologydownunder.blogspot.com.au/2014/02/dromedary-camels-are-host-of-mers-cov.html
5. Middle East respiratory syndrome coronavirus (MERS-CoV) cases rise in march: Festival-related?
   http://virologydownunder.blogspot.com.au/2014/03/middle-east-respiratory-syndrome.html
6. Receptor for new coronavirus found: Virus might have many animal reservoirs.
   http://www.nature.com/news/receptor-for-new-coronavirus-found-1.12584

MERS in the UAE....[UPDATED]

For the second time this month, there has been a case of Middle East respiratory syndrome coronavirus (MES-CoV) infection confirmed in the United Arab Emirates (UAE; Abu Dhabi to be precise). 

What added to my confusion (as you'll know if you were following me on Twitter this morning) was that both cases, apart from being from Abu Dhabi, were also 68-year old males and both have had camel contact. 

Today's 68M UAE case frequently visited his camel farm in the Kingdom of Saudi Arabia (KSA; had just returned from there 5-days earlier, thus in my mind making this a likely KSA acquisition) while the earlier 68M UAE case owns his farm in the UAE where he contacted animals including camels which he breeds.

This raises another question from me; why do we see proportionately more camel contact outside the KSA than we do inside the KSA (I haven't done the maths so this may just me my unfounded gut feeling)? Is it something simple like better epidemiological investigations conducted by Qatari and UAE investigators or are things, yet again, different somehow inside the KSA than they are outside the KSA? 

Surely there are some clues in there for investigators to use either to either improve how the epidemiology investigations are conducted or to look beyond camels in the KSA at other sources of acquisition?

Dutch researchers in collaboration with Qatar are at work sequencing MERS-CoV from camels...

And from the WHO comes confirmation of some of my earlier bits and pieces about the MERS-CoV in camels story from earlier....

The three camels which have tested positive with #MERS in #Qatar were detected in a barn linked to two confirmed human infections
— WHO (@WHO) November 28, 2013

Further, some very interesting titbits from a Twitter exchange this evening.

Firstly Prof. Marion Koopmans, Head of Virology at the Laboratory for Infectious Diseases of the National Institute of Public Health in the Netherlands confirmed that this was the MERS-CoV and not something requiring lengthy sentences filled with "probable" and "MERS-CoV-like"...

@MackayIM working on it. Qatari's are fast, samples came in last weekend, but yes, confirmed
— Marion Koopmans (@MarionKoopmans) November 28, 2013

..and that for the most useful conclusions to be drawn from any sequencing being undertaken..

@arambaut @mackayim Yes, but requires sufficient sequence of sufficient quality. We are working on it
— Marion Koopmans (@MarionKoopmans) November 28, 2013

..but that despite all sorts of great leaps in technology, not to mention in distance-spanning scientific collaborations, things don't just happen overnight. 

We should all be mindful that there are many steps between taking a (hopefully adequate) sample(s) from a human or animal, and reaching any useful conclusion about how the molecularly characterized virus might have travelled (human to dromedary, vice versa or via some other vector or intermediate)...

@arambaut @mackayim Yes, but we DO need some time. We are 4 days into the labwork. ;>)
— Marion Koopmans (@MarionKoopmans) November 28, 2013

As Prof Andrew Rambaut, Institute of Evolutionary Biology, University of Edinburgh, noted...

@MarionKoopmans @mackayim Indeed - I don't think people realise how much work it is to sequence these (and how much work to get good seqs).
— Andrew Rambaut (@arambaut) November 28, 2013

And on the subject of whether the new sequences will lead to an indication of which direction this particular cluster of infections is travelling i.e. from human-to-camel or camel-to-human, Prof. Rambaut had this thought on following the viral genome's sequence variations (polymorphisms)...

@MackayIM @marionkoopmans Look for polymorphisms that are not fixed in the putative donor but fixed in the recipient...
— Andrew Rambaut (@arambaut) November 28, 2013

This is all really great to watch. A fast and fruitful collaboration between sample holders and laboratory researchers, expert in their fields.

Click on image to enlarge.
Those POS for a fragment of MERS-CoV or
MERS-CoV-like virus sequence are highlighted
in red. Whether there are other intermediates
remains to be confirmed.

At this point, I believe (and it is just a belief) that the camel is looking good for a source of MERS-CoV acquisition by humans. Is it an endemic camel virus? Well, we still have the knowledge that bats seem to harbour a lot of CoVs, and there is that pesky Taphozus perforatus sequence discovered from earlier in the year. It looked an awful lot like a fragment of the MERS-CoV genome. Baboons - I'm holding out for them to be the link between bats and camels...but that is a hope in the absence of any data whatsoever!

Today's confirmation of a cluster of 3 POS camels among 14 represents 21% of the animals POS in a single area. 

If we consider this to be human-to-camel transmission, then this would be a much steeper proportion of positives than we normally see when we look at studies of close contacts of human MERS cases. Camels must be very susceptible to MERS-CoV infection because human contact testing just does not show this level of onward transmission. More susceptible to humans? No, I think we're getting closer to confirming that it's a camel-to-human thing...but we are not there yet.

Work continues, but today was a significant day and one in which I give thanks for the ability of people from all over the world to work together towards common goals in preventing human disease. 

Flu-like symptoms on the rise in Qatar...

The Gulf Times notes a rise in cases of "flu-like symptoms" in Doha, Qatar. Dr Sameer Kalanden, a general practitioner (GP) notes a rise on cases coming to the clinic. He usually prescribes medication  or "an injection" to reduce the fever (please don't let it be antibiotics..oh. It is antibiotics). 

If there is no sign of improvement, even after a 2nd visit, he refers the case to Hamad General Hospital (managed by Hamad Medical Corporation; HMC).

Another GP confirmed the recent rise in cases with symptoms of "flu and common cold" rising "these days". He also refers cases with more severe respiratory disease to HMC.

So from that we might be able to conclude:

1. HMC may be the testing lab for Middle East respiratory syndrome (MERS) coronvirus (CoV) in Qatar. We also know that may/all MERS-CoV cases are confirmed by UK collaborators
2. That only the most severe cases of illness will be tested for MERS-CoV
3. GPs do not refer any other acute respiratory illnesses for MERS-CoV testing routinely
4. There is considerable concern about MERS in Qatar - but not a lot of structure to resolve that concern

This sort of anecdotal report is a great way to bring attention to what isn't being done, but it would be much more helpful to know what is being done in Qatar, given its recent local cases and deaths. 

As I understand it, Qatar is entering it's cooler months. Looking through the literature, there are not a lot of papers on respiratory viruses from Qatar. In one paper by Wahab and colleagues in 2001 in the Journal of Tropical Pediatrics, we see that HMC testing defined the peak season for respiratory syncytial virus (RSV) in children as November-January in Qatar (data from 1996-1998 combined, included 257 previously healthy children). 59.9% of these cases were diagnosed with bronchiolitis, 17.6% with pneumonia and 35.8% had an infiltrate in their lungs. RSV cases start rising from September though. The authors note this seasonality is similar to other temperate countries in the Gulf region. And this is just 1 virus of 200.

In another study, this year, in Archives of Virology, Althani and colleagues (Qatar University and HMC) tested 200 adults with asthma or chronic obstructive pulmonary disease (COPD) across winter (October 2008 to March 2009). While virus detections were relatively few (18% of patients), most seasonal viruses were present during this period - more so in asthma than in COPD. These included rhinoviruses, HCoV-229E, NL63 and OC43, parainfluenza viruses 1-3, RSV, adenovirus, influenza B virus and human metapneumovirus.

So this rise in cases noted by the GPs above may be nothing more than the usual start to the respiratory virus season, made to look more scary because of the recent MERS-CoV outbreak. Or it may be more than that.

I believe its time to be seriously considering what local laboratory testing capacity exists on the ground in the Arabian peninsula.

If the hajj stirs up case numbers, as many suspect it will, having limited to no ability to quickly resolve a flood of potential cases will result in a management crisis. Cases will accrue quickly and "probable", rather than "confirmed" will become the word of the day while trying to prevent spread in hospital environments.

If it looks like a duck and quacks like a duck, it may be just a rhinovirus. 

Case numbers will also be added to, as they always are when surveillance is heightened for a new agent, because seasonal endemic human respiratory viruses are circulating as well and those infections cannot reliably be discriminated from mild to moderate MERS-CoV using patient observation alone. 

Currently, MERS-CoV results in the Kingdom of Saudi Arabia may take up to 2 weeks to turnaround (if you follow me on Twitter you will have seen this time frame suggested to me last night). 

If the cases seen by the GP today were MERS-CoV positive, they would 1st need to return with a continuing fever before being tested and then that result would be revealed either too late to reduce the risk of a transmission event, or perhaps too late to be of use in applying novel antiviral treatments on that patient.

Time is of the essence. And more testing is paramount.

Thanks to @makoto_au_japon and @dspalten for bringing this to my attention.

Death of a young adult Qatari MERS patient who presented with flu-like illness...

So that last post is out of date already.

The Qatari Supreme Council of Health, as it does, has issued an announcement through the media (it has yet to update it's technically troubled website) announcing the death of the previously described 29-year old male with asthma who had been confirmed by an international (presumably UK-based) reference laboratory.

Asthma occurs in about 5% of the world's population, but in higher proportions in particular countries and regions.

This moves the deaths up to 54 with data, possibly 56 in total (see earlier post today for what that means) with a PFC of 48.3% for 56 deaths.

The presentation of this case on August 17th, was of "flu-like illness" which can be anything from fever + cough to much more. What this case highlights, and it is only a single case, is that cases can present with standard upper respiratory tract infection (flu most often starts off that way) which will make it devilishly hard to discriminate from that caused by many other non-MERS-CoV respiratory viruses. In a study of pilgrims leaving the 2012 hajj, 41% had flu-like symptoms (cough, sore throat and fever). I mentioned this in an earlier post (see #3 in the Prof Memish lit review) and the paper in Feb this year from Clinical Microbiology and Infection can be found behind a paywall here. A subsequent article published in Clinical Infectious Diseases this July, also paywalled and by the same group showed that a number of respiratory viruses were lab-confirmed as acquired while in the Kingdom of Saudi Arabia (showed symptoms of  illness), fewer were brought into the country and fewer were taken out. Not much can be concluded from that as I would expect this in any group tested in this way under these circumstances (travelling to a gathering of lots of people from around the world and from different climates  experiencing different respiratory virus seasons). It is not surprising that when you throw people together, they transmit respiratory infections and the the number of cases spikes.

This will be a big challenge if observation alone, rather than prospective laboratory testing, is used as a method to diagnose MERS among hajjis (thanks to AtRG for this phrase), in the coming weeks.

New MERS-CoV case, a death, in Qatar

The Kuwait News Agency (KUNA) reports that a 56-year old female has died of MERS in Qatar, according to the Qatar's Supreme Council of Health (SCH).

This is the 2nd death from a Qatari-based infection and the 1st female case. She had several comorbidities. In this instance, comorbidities may serve as reminder that the apparent sex bias in MERS cases (more often males) may not be so much about the sex of the cases, but more about the possible bias towards (older) males with more comorbidities. While principally a respiratory disease, the respiratory virus causing MERS deals very harshly with those that already have a disease of some other sort. 

This brings the tally of MERS case to 111 with 51 deaths (PFC of 45.9%. NB. A recent ProMED listed the deaths at 1 more than they were generally accepted to be at that time. There has not been a WHO update since that so I'm sticking with 51.

Local health authorities have probably seen this already, but the impact of MERS may highlight a need to address the risk factors that drive the prevalence of underlying disease in males in this region.

My first source: FluTrackers

A crack in the wall of MERS-CoV case information: new MERS cases, a key, a family cluster with 2 news cases from 1 [AMENDED]

Thanks to Prof Andrew Rambaut for pointing out my incorrect usage of R₀

In a strong piece by Maryn McKenna on Wired a bit over a week ago, she posited that "Censorship Doesn’t Just Stifle Speech — It Can Spread Disease".

Today we see a possible turn of events. In an post on ProMED today, Prof Memish, Deputy Minister for Public Health in the Kingdom of Saudi Arabia (KSA), penned his own update on case details from yesterday's announcement, and added information (including dates of illness onset) on 2 new, asymptomatic MERS-CoV cases!

This is a great sign that more information is starting to flow from the KSA. It was also extremely encouraging to see the appearance of a KSA key for these cases - SA83-the 55-year old male (55M); SA84-38M etc. I will add this numbering to my list in anticipation of this becoming a regular thing. This really does help track and confirm cases and information with much more precision. 

If you take requests Prof Memish - I have a few data gaps I would love to have filled (you can eMail me below)!!

We learned that SA83 (55M) was probably in contact with the recent Qatari patient diagnosed in Qatar. We should be looking a little more closely to Qatar as a source for recent cases - and applying that list from my last post, to there as well.

The new cases are both children who were asymptomatic family member contacts of 38M, who we learn was diabetic, showing signs of disease 8th of August and dying of acute respiratory distress syndrome on the 17th of August.

1. 16M (VDU #107; SA85)
2. 7F (VDU #108; SA86)

This is yet another case of 1 case infecting more than 1 new cases - 2 new cases in fact. Should that be the norm rather than the exception, we would see the basic reproduction number (R₀) creep upwards. We saw this also happen in the United Arab Emirates cluster (4 from 1) - see my earlier post on that.

The potential for transmission is certainly there but the level of contact requires "close" in its description (family). Further, the second passage of virus (from the initial case to the next people) seems to mostly result in milder/no disease - or is that simply a reflection of the odds favouring transmission to a person without comorbidity? In other words, MERS-CoV is an opportunistic pathogen but a bit of a wimp in "normal" healthy younger people.

This brings the case tally to 108 by my tally, with 49 deaths and a PFC of 46.7%.

Congratulations to Prof Memish and the KSA Ministry of Health for taking this new path. Long may it last.

New WHO update on MERS cases

The latest WHO disease outbreak news (DON) addresses the 2 recent Qatari cases, noted previously here and here. 

Click to enlarge.

Interestingly, it notes that the 1st case, which showed symptoms while travelling outside of Qatar, in the Kingdom of Saudi Arabia, was only travelling for 6-days. 

That would most likely place the acquisition of infection, which can take as long as 14-days after exposure to the source to manifest with obvious signs of disease, within Qatar. 

I've changed by Qatar case tally to reflect (and recent posts of 59M and 29M cases) that 4 cases have been acquired within Qatar.

Just looking at the latest case curves, we seem to have entered a period of rapid case growth, after a period of quiet. These little spikes are good times to cast a very broad mind over what might be happening with animals, weather, dust/wind, camel movements, bat activities, baboon interactions, festivals, markets...almost anything that could be used to link an uptick in cases with exposure to a possible source. 

There must be something common out there....its just needs to be found. As Sherlock Holmes said in a question, "...when you have eliminated the impossible, whatever remains, however improbable, must be the truth". At this stage, with nothing really ruled out as impossible, that leaves a lot to consider.

New MERS-CoV case in Qatar [UPDATE: CONFIRMED; details for 59M updated]

My 1st source on this: FluTrackers

The Kuwait News Agency reports that the Qatari Supreme

Council of Health (SCH) has logged a 29-year old male (29M) as having MERS-CoV. He is reportedly in intensive care and in critical condition.

No sign of official confirmation as yet though. [UPDATE: The SCH, through a media outlet rather than its own news section, has confirmed the case.] If confirmed officially, this will bring the total lab-confirmed MERS-CoV case number to 103 or 104 (see here last week's Qatari 59M case and for comment about a case numbering issue that might mean another case is positive somewhere in the Kingdom of Saudi Arabia). 

FluTrackers just tweeted that this is the 10th MERS-CoV case reported in a week. Quite a drought breaker.

A history of MERS-CoV cases in Qatar (n=4) 
Dates are of local news reports; not Australian time) noting their age in years, sex , FluTrackers case number, and where they might have acquired there infection:

1. 22.09.12, 49M, #4
• Likely local acquisition (see publication)
• Flown to the United Kingdom
2. 12.10.12, >45M, #6
• Likely local transmission (see publication)
• Flown to Germany for treatment
• Lived in Doha
3. 20.08.13, 59M, #97
• Likely local transmission (see WHO disease outbreak news)
• Only travelling outside of Qatar for 6-days during which he became symptomatic. 
4. 26.08.13 29M, #104
• Likely local transmission (see WHO disease outbreak news)

I am not including the 2 local Tunisian acquisitions in the Qatar list. These 2 adults (34M and 35F) most likely caught their MERS-CoV infection from their father,who most likely acquired it from Qatar. Nonetheless it seems his children acquired their infection in Qatar. Moreover  the father tested negative to the MERS-CoV - despite it being likely that he was truly positive.

MERS-CoV-positive Qatari man did not return from umrah, but developed symptoms while travelling [UPDATED]

Hat tip to crofsblogs and FluTrackers

Perhaps an indication that MERS-CoV was circulating in pilgrims returning home from umrah. 

A recent news article notes that the patient in Qatar was probably infected outside Qatar; probably the Kingdom of Saudi Arabia (KSA) where he was performing umrah. [We now know this person was only travelling out of Qatar for 6-days - more likely he was incubating before he left Qatar]

My epidemiology list (102 confirmed cases; 48 deaths) that this cases is a KSA acquisition and so won't add to the Qatar numbers. [See post 30/08/13; cases now moved to Qatar tally]

Oh well, that still leaves 4,799,999 pilgrims MES-CoV free right?

Updated with information from WHO disease outbreak news update, 29/08/2013.

New MERS-CoV case, likely imported, reported in Qatar

1st source: @makoto_au_japon

France 24 reported a case of MERS-CoV in a 59-year-old (59M) Qatari man. He is currently stable.

He is reported by the Qatari Supreme Council of Health (SCH) as having arrived from "another country" and of having symptoms while abroad, so this is then an imported case leaving Qatar's local acquisitions at 2, by my count.

This brings the tally to 97 cases with 46 deaths and the proportion of fatal cases (PFC) drops to 47.4%.