Middle East respiratory syndrome coronavirus (MERS-CoV): unhappy trails...

An updated map of the countries that have had a visit from, and in 52% of those, had some local transmission of, the MERS-CoV.

South Korea is the first country I have seen that has jumped three colour levels between updates. No mean feat.

So we have 25 countries that have hosted a MERS-CoV infected person, and 13 of those have gone on to have local transmission - new cases from that case on their soil.

Click on it!
It gets bigger!!!

In the meantime, 7,000,000 pilgrims are expected in Saudi Arabia to perform Umrah between mid-May (around the 19th May) and mid-July.[1] Over 2,000,000 had already performed the Umrah pilgrimage to The Holy City of  Makkah in Makkah province, between November 2014 and May 2015.[1,2] We're in the second phase of Umrah now - in the lead-up to the fasting month of Ramadan which begins on the 18th June 2015. 

Remember Saudi Arabia? That's where over 80% of all MERS-CoV cases have originated. That percentage has dropped a little of late thanks to the clusters in South Korea. Given the amazingly, incredibly, ultra-tiny (yes, that small) number of cases that have reportedly arisen during Umrah or Hajj (Septembee 21-26 in 2015)  in previous years, there is absolutely no reason to think 2015 will differ. Even if there have been recent cases in Makkah province. And a hospital cluster in Ash Sharqiyah (eastern province).

Clearly, MERS-CoV is not easy to catch even when so many different people, so many different states of underlying chronic disease, immune compromise, pre-existing infection, height, weight, age all come into contact within the zone of hotness that is Saudi Arabia.  

Which leaves me with one comment after a large batch of 23 cases was announced this morning - bringing the total to 87 from South Korea....look to the infection control South Korea!

References..

1. http://english.alarabiya.net/en/News/middle-east/2015/05/19/7-million-Umrah-pilgrims-expected-in-Saudi-in-next-2-months.html
2. http://english.alarabiya.net/en/News/middle-east/2015/01/28/Over-one-million-Umrah-pilgrims-pass-through-Jeddah.html

MERS case-control study during the Hajj

Dr Ziad Memish, Deputy Minister of Health, Kingdom of Saudi Arabia, has made a welcome comment about some analysis of ill cases that went on during the Hajj. In the Saudi Gazette..

He added that in addition to detailed investigations of every suspected case, case-control studies for index cases and intensive follow-up of contacts with serological testing to improve understanding of the critical features of MERS-CoV infection were carried out.

I'm not clear on whether that indicates there were MERS-CoV cases during the Hajj, or if he is referring to probable cases that were not confirmed (no contacts then?) or to respiratory illnesses in general. He unfortunately wasn't quoted as saying whether any of those results were positive for MERS-CoV infection. 

Given that 997,3709 pilgrims apparently partook in some degree of medical healthcare service while in the KSA for Hajj, this study should provide some very useful information about what MERS-CoV was doing both in the ill and the healthy in mid-October. I might even be able to stop whingeing about lack of testing of all but those who are severely ill (or their contacts)!

The case-control study protocol is likely to follow that defined by the WHO in July - which can be found here.

The controls (best if >1 per case) will be randomly selected people of equal age (leeway varies with age band) and sex ("matched"), living in the same neighbourhood (to ensure try and capture the same environmental exposures; difficult for visiting pilgrims so general are of pilgrimage might suffice) that are not presenting with the same illness as the confirmed "case" at the time of sampling. Sampling (described in the lab testing WHO document here) which is recommended to include material from the lower respiratory tract - which may prove difficult from otherwise well controls. Informed consent is recommended as part of the (any such) study so controls will know what they are in for ahead do time.

Interestingly the WHO document comments that...

Currently, circulation of this virus in the community is thought to be nonexistent or minimal at most and the numbers of infections low. For that reason, prospective controls who have not had recent respiratory illness can be enrolled without laboratory

This study will address whether this is an accurate premise.

MERS update: WHO catches up but passes along no detail - and Hajjis look clear

The World Health Organisation updated it's MERS-CoV tally. The total (144 cases) is the same except for the confirmation of 2 deaths (to 62) hinted at in my last update. 

Disappointingly and once again, the update doesn't allow any analysis because there are no specific details with which to cross-check against our case lists.

Even CIDRAP is heading to the newspapers to try and identify which existing cases have died.

With my arbitrary deadline for emergence of new MERS cases being the 27th of October (this Sunday)  only 2-days away, I think its pretty safe to say that there has been no major symptomatic MERS-CoV transmission event associated with the peak assembly period of the Hajj in 2013 (just like there was none in 2012 when MERS-CoV was already in play). 

The United Arab Emirates is reportedly not checking pilgrims for symptoms, although they have their own 2-week clock running to monitor for signs and symptoms of new cases of flu-like illness in pilgrims.

Thankfully, there are studies performing actual laboratory testing, although the details remain unclear. Such studies will tell us whether MERS-CoV is among us already, but not causing the serious disease we've become used to associating with the virus.

Dr Jake Dunning (@OutbreakJake) noted on Twitter...

@MackayIM We're testing here in London. Trying to raise awareness, but needs to be balanced against more typical local infections e.g. flu.

— Dr Jake Dunning (@OutbreakJake) October 22, 2013

He also went on to say that...

@MackayIM We also have an active MERS observational study in UK, ready to recruit willing patients. @ISARIC1 protocol can be used by anyone.
— Dr Jake Dunning (@OutbreakJake) October 22, 2013

ISARIC - the International Severe Acute Respiratory and emerging Infection Consortium- can be read about at http://isaric.tghn.org/about/.
So my next question becomes, have we been watching the emergence of a new endemic human coronavirus? That question is based on a hypothesis that we have a lot more undetected cases and on Dr Ziad Memish's earlier assertion that MERS-CoV cases are already out and about in other countries. Time, and some testing, will tell.

Hajj pilgrims return around the world...is lab testing happening?

Media and Ministry reports are filtering in from many different countries that their Hajj pilgrims have been safely returning from their pilgrimage. 

To date there have been no reports of Middle East respiratory syndrome (MERS) disease in any pilgrim. 

I presume this is all observational diagnosis? It would be very interesting to read whether any actual laboratory testing is occurring in any of these States. If it is, are the pilgrims PCR-negative?

What observation alone cannot tell us is whether a pilgrim infected but not showing signs. 

Self-reporting of mild disease without overt signs, can be problematic and may bias away from capturing all cases in the absence of laboratory testing. If cases do enter a State "under the radar" they may still shed virus to others in their new locale. Some of those others may be older males with comorbidities; the MERS coronavirus's (MERS-CoV) highest impact population. Of course we don't really know if mild and asymptomatic cases can transmit effectively. We might if their was more widespread testing. Since we haven't seen that level of testing coming from the site of most MERS-CoV infections, the Kingdom of Saudi Arabia, perhaps there is an opportunity for other States to step up and test not just returning pilgrims but their families and other contacts and see whether their upper respiratory tract's are free of MERS-CoV RNA?

These media reports also don't tell us what definitions are used by each State to define a pilgrim as being free of MERS-free. It may be the absence of any sign of any respiratory disease, or it be just absence of severe signs and symptoms, or perhaps a combination of signs and symptoms e.g. fever+cough or cough+difficulty breathing.

Too many knowledge gaps. 

One thing's for sure. The headlines are only scratching the surface.

Australia on watch for illness among Hajj pilgrims

A report from Radio Australia highlight the ongoing need to be watchful for acute respiratory infections developing among pilgrims returning from Hajj.

Gregory Härtl (spokesperson, World Health Organisation) noted the need to keep an eye out... 

It could well be that a returning pilgrim gets back, starts feeling sick and is found to be diagnosed with MERS, and what we consequently are asking countries to do is to increase their surveillance and to know what symptoms to look for on the one hand, and for pilgrims to be on alert and to tell their doctors they were on Hajj if they start to feel sick.

Professor Charles Watson (Curtin University) noted that disease is most likely to be an issue when pilgrims return to their countries rather than while they were within the Kingdom of  Saudi Arabia.

Thanks to Crawford Kilian for bringing this report to my attention via Twitter and on his blog.

MERS-CoV cases begin to tick over again after the Hajj....but not related right?

So by all accounts, Hajj2013 was a very successful event. A lot of lifelong wishes may have been fulfilled and the event went off without any apparent major hitch. A huge undertaking on many fronts.

However, during the Hajj it was hard to avoid seeing  Middle East respiratory syndrome (MERS)-related headlines like...

No cases of MERS virus among pilgrims so far

and my particular favourite...

No infectious disease found

...at all that is. None. Not even bad influenza-like illnesses. No coughs or colds among 2,000,000 people gathered together; 1,300,000 having at some level, shared transportation into the Kingdom of Saudi Arabia (KSA)?

Seriously?

That second quote makes me realise just how important it was for the KSA ministry of health to control this aspect of the Hajj's message; no MERS-CoV disease here. So important, that the message was, to say the least, a little heavy handed.

But now, coinciding with the Hajj ending, we see MERS-CoV detections popping up (3 in 3-days). It's very hard to take seriously the MERS-message. Rest assured we're told, those cases are not at all linked to the Hajj - no travel to that region (now so specific that we are told there is no travel outside of Riaydh) in the previous 14-days. Ironic how that longer incubation period is useful in these happy reports, but not remembered in others, such as when the press note:

Saudi Hajj ends successfully with no reports of MERS virus

Click to enlarge. This graph is from September - highlights a similar case
reporting lull around umrah which then climbed rapidly and steadily
immediately afterwards.

The (longest) 14-day incubation period means we're not out of the woods yet (see my earlier post on timelines). 

Maybe we'll see no new cases among any of the pilgrims. Cool. I doubt that. We have seen 7-day or more breaks in reporting of new MERS-cases before, so this past week is not "out of character". Time will tell, especially from now on for a week or so. Watch that curve closely.

I still wish we could lay off the "everything is fine here right now" message, and instead tell us what's happening to find the host or what testing is being done among those who are not severely ill (take a look at China and H7N9 - include MERS-CoV in your regular respiratory virus testing panel for a little while and see what comes of it). That would be treating us a little less like we are so easily distracted by shiny baubles.

The Hajj begins

The Kingdom of Saudi Arabia showing the major sites of MERS-CoV
infections and the site of Mecca.

Al Riyadh reports that on Saturday and Sunday 13th the 1,379,000 international pilgrims (94% arriving by air) moved into Mina Valley from the holy city of Mecca (Makkah) located in the Mecca province, the most populated province of the Kingdom of Saudi Arabia (over 5.8 million people). The number includes 752,424 males (55%).

The Hajj starts at sunset (Mahgrib) on Sunday, but many have begun on the Saturday evening.

Pilgrims perform “Tawaf Al-Qudoom” at Mecca (initial round of circumambulation [the act of moving around a sacred object, in this case the cuboidal Kaaba at Mecca]) then move to Mina prior to midday. They sleep there and then move to Arafat after morning prayers. Temperatures were expected to reach 37-41° C yesterday and throughout the week.

Given a 14-day incubation period (most lengthy estimate), if the MERS-CoV is going to show up any differently among hajis this year than it did as a result of last year's Hajj (you may have noticed that no pandemic ensued), we should see those cases having presented with symptoms by 
Sunday the 27th. If we really want to get a feel for how easily transmissible this virus is, then this is the opportunity to observe and test.

Of course, this is an artificial date, given pilgrims have been assembling and mingling for some time during the lead-up to Sunday evening, but I'm using that date as the outer limit for appearance of symptomatic cases using a timepoint in which many people definitely congregated together in large numbers.

We may also see a rise in cases appearing outside the KSA as retuning pilgrims picking up infection just before they depart, become symptomatic on home soil. Or we may not.

Thanks to FluTrackers for posting this link.

Kingdom of Saudi Arabia (KSA) issues health regulations for hajj visitors

The Saudi Gazette has the full list of regulations to be aware of if you have planned to arrive in the KSA for your hajj pilgrimage. Some of these will require some prior organization.

Age, personal health, updated vaccination and concerns over spikes in polio transmission are all covered.

16,000 Russian hajj pilgrims September 6 - October 9

1st source: @makoto_au_japon

Russia and India Report also notes that..

According to the rules, pilgrims should be no older than 65 years of age and no younger than 12 years of age.

According to my list and among those with details available:

• 53% of MERS-CoV cases and 65% of deaths are older than 55-years
• 74% of cases and 57% of deaths are 65-years or younger
• 2 cases and 1 death are under 12-years of age

I'd say the rules miss a large proportion of the populations most at risk of poor clinical outcomes.

Nearly half the Indonesians performing Hajj may be over 60-years of age

On top of that, a quarter may have underlying illnesses. This, according to an article on Arab News, is an estimate based on comments from the Indonesian Ministry of Health and Religious Affairs, Haj Health Center.

As we know, age and underlying diseases, or "co-morbidities", are significant risk factors for more severe disease following MERS-CoV infection.

These data give an the world an insight into one visiting population, does it hold true for other countries as well? If so, we get a snapshot of why public health officials are concerned for the health of their country's Hajj pilgrims in the coming months. MERS-CoV transmission efficiency may be low, but the clicnial impact from this gathering may be high.

Globally mobile at-risk population + site of most infections + little knowledge of basic levels of virus source/community load at that site = less than ideal situation.