MERS-CoV on the farm...

I'm going to spend a few posts catching up on some excellent papers showing the role of camels in harbouring and transmitting the Middle East respiratory syndrome coronavirus (MERS-CoV). There also seems to be some confusion remaining about what we know, what we don't know, and also how bats fit in to the picture. I'll finish the next few posts with a summary.

Please do check out my previous listing of the literature around MERS-CoV and camels.[1]

I'll republish an updated literature list in the summary post as well.

First up, an article from the scientific literature which was published by Hemida et al. in the July 2014 edition of Emerging Infectious Diseases, but would have gone online much earlier (CDC don't list that date for some reason I cannot fathom).[2]

This authors first remind us that MERS-CoV RNA has been detected in humans and dromedary camels (DCs) before and that DC infection has been shown to precede human infection in one study (well, two but they both analyse the same camels and humans).[3]

This study collected and froze nasal, oral or rectal swabs and blood samples from DCs on 2 farms in Al-Ahsa in the Kingdom of Saudi Arabia (KSA). The authors then looked for MERS-CoV RNA and antibodies.

• Farm A:
• 70 DCs
• 4: 1 month of age
• 8: approximately 1 year of age
• 58: adults
• Sampled 5 times between NOV2013 & FEB2014
• Herd never grazed in the desert (so wasn't exposed to other camels)
• November 30th 2013 results
• 10 DCs were MERS-CoV RNA positive; 8 of 9 DCs that had both nasal and faecal samples tested were only positive in the nasal swab, 1 DC only in the faecal swab
• December 2013 results
• No positive DCs December 4th; the following resulted from December 30th
• 7 of 8 calves and 2 of 3 adults
• 12 adults with sera collected before this testing were seropositive - this include 2 that were MERS-CoV RNA positive suggesting DCs can be reinfected
• 2 seronegative 1-year old calves had the highest nasal loads of MERS-CoV RNA suggesting maternal antibody may not be protective
• 4 DCs had the equivalent of a human cold - cough, sneeze, discharge, elevated temperature and were off their food
• February 14th 2014 results
• No MERS-CoV RNA was detected in DCs
• All 3 MERS-CoV RNA-positive DC calves who had sera collected on December 30th and February 14th, were MERS-CoV RNA negative in the February sample (thus an acute not chronic infection in camels) and all had a four-fold or great rise in antibody titer
• Farm B:
• 20 DCs
• 3: calves
• 17: adults
• Sampled once, FEB-2014
• Herd sometimes grazed in the desert
• No MERS-CoV RNA was detected in DCs

Samples were tested by 2 MERS-CoV specific real-time RT-PCRs and a broadly reactive coronavirus conventional RT-PCR. MERS-CoV positive samples were re-extracted (nucleic acids were purified from another aliquot of the original sample) and re-tested to confirm.

Conventional (Sanger) full genome sequencing was also conducted generating 3 genomes from Farm A, KFU-HKU 13, KFU-HKU 19Dam (faecal swab) and KFU-HKU 1. These were identical in sequence across the full 30,100 nucleotide genome and across the spike gene of 4 more viruses.

Virus isolation using the Vero E6 cell line was successful from 2 nasal swabs and 1 faecal swab - all with high amounts of viral RNA (culture is nowhere near as sensitive as PCR-based detection methods) - collected on December 30, 2013.

• A genome sequence from the faecal swab and the 2nd passage of culture isolate from the same faecal swab were directly compared - 3 nucleotide changes were identified, 2 of which led to an amino acid change (spike and membrane proteins)

So we learned from this study that DC MERS-CoV (genetically near identical to virus found in humans) doesn't mutate within a given DC herd (genetically stable in DCs), but does change a little upon cell culture in the laboratory. That change is not unexpected as cell lines in a flask are not camel/human cells in a complex microenvironment in the body. It's also not the first time such mutation has been seen.

We can also see that not all farms in a region of KSA have MERS-CoV when one does but that infections spreads within and around the herd - not persisting once it has moved through. However this herd and others in the region is one from which DCs can be moved to the via Buraidah in the KSA to the United Arab Emirates. Imports and exports and movement to shows and festivals being a problem when your animal is carrying an infectious agent - just as it is when an infected human hops on a plane and travels to Nigeria, or South Korea or the United States...or anywhere. We saw that adult DCs could probably be reinfected despite a pre-existing antibody response. But we learned nothing about the cell-mediated immune response - a gap in our knowledge that extends to the human immune response to MERS-CoV infection also.

While the peak of infection at Farm A occurred in late December in this study, only a limited time periods was sampled and too few farms to know if this is the pattern throughout the Arabian Peninsula, or just chance in Al Ahsa in 2013/2014. But there is another study that has looked a little longer and I'll review that soon. 

Sadly, there were no human farmers involved. The study would have been made more valuable if it had also followed any and all humans in contact with these camels over this period as well. More examples of camel-to-human infection would be great to have since there are still those who don't "believe" camels play a role in MERS. Of course, it's not belief that's needed, it's the willingness to sit down and listen to the scientific facts we have at hand. And that comes down to finding a way to pitch the facts in a way that works for each type of audience.

References...

1. http://virologydownunder.blogspot.com.au/2014/05/camels-and-mers-links-to-peer-reviewed_27.html
2. MERS Coronavirus in Dromedary Camel Herd, Saudi Arabia
   Hemida MG, Chu DK, Poon LL, Perera RA, Alhammadi MA, Ng HY, Siu LY, Guan Y, Alnaeem A, Peiris M.
   Emerg Infect Dis. 2014 Jul;20(7):1231-4
   http://www.ncbi.nlm.nih.gov/pubmed/24964193
3. http://virologydownunder.blogspot.com.au/2014/06/1-of-these-papers-is-pretty-much.html

MERS-CoV jumps a flight to South Korea...but from where?

It could be Qatar, Bahrain, the United Arab Emirates (UAE) or the Kingdom of Saudi Arabia (KSA). Any of these may have been the country of origin for the infected person who returned with a bunch of microscopic passengers, to the 24th country to host a case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection - South Korea. 

The infected man then passed the spiky parasites on to his 63-year old wife and to a 76-year old man with whom he shared his hospital room. Close contact. From what we know of the MERS-CoV - it's a pretty ineffective transmitter among us humans types, preferring instead to give the hump to dromedaries.

Qatar seem less likely as it appears to have only been an airport transit point. If it's Bahrain, then we have 25 countries as Bahrain has not yet reported a MERS-CoV positive person. Both the people and the camels of the UAE and KSA are well known to this virus both in humans and camels. 

We await the clarity of the World Health Organization's analysis in a Disease Outbreak News (DON) article - although this might be a tough one to unravel.

Click on image to enlarge.

MERS in the UAE...

Over my weekend, the Robert Koch Institute (RKI) in Germany reported that they had a Middle East respiratory syndrome case (65 year old returning German) under their care, imported from the United Arab Emirates (UAE).[1,2]

There have been two other MERS cases hospitalized in Germany - 1 from Qatar and the other originating from the UAE, where infections are presumed to have been acquired.

This latest case is nothing astonishing but it does act as a warning that there most likely are other MERS cases circulating in the UAE. Alternatively, this person may have visited the Kingdom of Saudi Arabia (KSA) before travelling to Germany, acquiring an infection there. 

When cases emerge in other countries they can be very telling. They speak of what might be happening in the host country. The UAE has only reported (this is the important word for any outbreak observation) a single case since July last year. Was RKI just "lucky" to pick up the only other MERS-CoV case in the UAE over the past 8 months? Highly doubtful. In the absence of other information (WHO detailed data will surely follow soon), it is much more likely that MERS-CoV is circulating in the UAE, as it is in the KSA and possibly neighbouring countries, but that cases are going either undetected or unreported.

When animals were described alongside human cases.
Click on graph to enlarge.
Taken from MERS number page.

Current MERS-CoV circulation would be in keeping with the popular theory that MERS is a seasonal zoonosis (animal infection that spills over to humans causing disease on occasion), and that more primary human cases, although still relatively rare, emerge during periods when more infections are occurring in camels - which seems to occur around this time of year. That seasonality in camels has not really been established yet and still it is one popular theory among those who do not completely deny any involvement of camels in MERS whatsoever. Also worth repeating is that MERS-CoV appears to be inefficient at transmitting between people - at least so far as the testing done to date has revealed.

From the rare spillover cases acquired by humans from camels, humans proceed to do the lion's share of the work in continuing to spread MERS-CoV among humans. Yay us. 

In recent WHO disease outbreak news reports [3,4], the detailed information reveals multiple instances of cases having shared wards with laboratory-confirmed MERS-CoV cases - and despite assurances that the same healthcare workers did not attend both people, some form of contact has apparently occurred somewhere, somehow. The precise details of what that contact was, still seem to be beyond the capacity of the Saudi disease detectives to capture. But in that detail lies some important hospital (or community) transmission clues - even if those clues are as simple as revealing that the wring question are being asked, too few contacts are being tested, healthcare workers movements are not being tracked sufficiently, or finding that people (patients, contacts and healthcare workers) do not answer the question fully. 

A little thing called infection prevention and control is apparently still not being adequately adhered to in some parts of the region. 

In other words, MERS is a rare but preventable disease.

References...

1. Flutrackers post
   https://flutrackers.com/forum/forum/novel-coronavirus-ncov-mers-2012-2014/germany-coronavirus/726247-germany-reports-3rd-imported-mers-cov-case?_=1425773133137
2. Robert Koch Institute [German]
   http://www.rki.de/DE/Content/InfAZ/M/MERS_Coronavirus/MERS-CoV.html
3. WHO MERS DON 06MAR
   http://www.who.int/csr/don/6-march-2015-mers-saudi-arabia/en/
4. WHOMERS DON 23FEB
   http://www.who.int/csr/don/23-february-2015-mers-saudi-arabia/en/

Snapdate: MERS-CoV detections near 500...

MERS-CoV detection by day; Jeddah outbreak.
Click on image to enlarge.

Welcome to the beginning of MERS-CoV's 112th week (2.15 years). We sit at 497 cases (probably over 500 if the United Arab Emirates would confirm their cases with some extra data that made them more identifiable and "real". For now, I'm not including them after the recent issue around theUAE12. For now my count says at 497 with ~131 deaths (26.3%).

Judging by tonight's announcement of only 3 cases (only 1 with an onset date which was 24-Apr), let's hope this is the week where the Jeddah outbreak gets put to bed.

MERS-CoV detection by week 2012-present.
Click on image to enlarge.

Also, make this the week that the Kingdom of Saudi Arabia's(KSA) Ministry of Health adds some consistency to its releases. They've been doing a 100% improved job in the past weeks, adding much more detail, but it needs to be the same detail for every case, every day. And the listing of deaths and recovered cases is also great; but is currently not able to be linked to the original announcements so we don't know where they these people were from, comorbidities, HCWs etc as there are often 2 or more people from the same region with the same age. A date of affliction is needed to permit the linkage between original announcement and death/recovery. Just 1 more variable guys. Pleeease.

Nonetheless the dailies seem to be slowing, although the cumulative average still strolls upwards but in a linear, not exponential manner.

We stay tuned.

An update on the April outbreak of MERS-CoV...

We are in week 110 of the MERS-CoV outbreak event, that's 2.12 years and 386 cases including approximately 113 deaths (PFC of 29.3%, the lowest to date) since the first known cases became ill in Mar of 2012.

Just a few quick charts to keep track of things.

http://www.flickr.com/photos/xikita/48647105/in/photostream/

CC BY 2.0

Virus detections continue to accrue at a double-digit rate, as has been the case each day except 2 (one of which was blip) between 18-Apr and 25-Apr this year. Thanks mainly to the Jeddah outbreak (no more calling it a "cluster")

Click on image to enlarge.

I've added the Mazayin Dhafra camel festival (United Arab Emirates; UAE) to the regional acquisition chart. It's a gathering that brings together ~17,000 camels. [1-6]
Thank you to @_abdullah88 and David Leith

Click on image to enlarge.

In the next 2 charts we can see the large and rapid rise in number of detections over the past 3 weeks, firstly by week. The cumulative average has also jumped (now at 2.88 cases per day across the entire period of MERS-CoV's emergence) as detections continue in higher numbers than ever before.

The underlined region (green) includes those detections which have
not yet passed through the World Health Organisation and
been "officially" announced to the world. His process usually,
and until late March, consistently, added valuable additional data.
Click on image to enlarge.

In the next chart we can see the zoomed in daily story for late March to April detections. That cumulative average (grey line) is steadily climbing but not at an exponential rate. We wait and see if human-to-human transmission increases as each of these cases makes contact with other people and the incubation period clock starts. If the virus is spreading even more efficiently than in 2013, that daily curve might start to look more like the weekly curves. Another few weeks should answer that for us.

Click on image to enlarge.

Healthcare worker (HCW) numbers have risen sharply (see below) during the April outbreak to a total of 84 detections, 7% of whom have died. 

Deaths (left) among HCWs now represent 1.6% of all MERS-CoV positive deaths. This jump in HCW detections has been fuelled by the Jeddah outbreak but also by the parallel HCW cluster among paramedics in the UAE; two as yet completely unexplained events.

Click on image to enlarge.

As ever I must note that the data are full of holes. 

In particular, the past 140 or so detections, despite being announced through a Ministry, lack sex, date of illness, date of hospitalisation or precise dates of detection if they were not ill (of which there have been a number of late).

This increasing number of detections may simply be due to increased testing of contacts, as we learned from comments by Dr Memish this past week.[7] Apparently until relatively recently, and despite comments that suggested more KSA laboratories were coming online made as far back as July/August 2013, contacts of confirmed cases have been mostly observed for signs of disease, and not sampled for laboratory testing. Testing has been limited to cases of pneumonia. This seems to conflict with recent accounts of larger sample numbers being tested (which I don;t have citation for right now), unless pneumonia is far more widespread in the Kingdom of Saudi Arabia (KSA) than we understand. 

Testing is key to understanding how widespread MERS-CoV is in the community and how well it actually transmits from human-to-human (-to-human-to-human- etc). 

It's not at all surprising that clusters spread and are not shut down quickly if no-one knows who has MERS-CoV and who has influenzavirus or rhinovirus or another coronavirus or even who has a MERS-CoV-positive mild yet perhaps still contagious infection that doesn't rate a second look. You can never understand an emerging virus when you miss out people that are infected-whatever their clicnial presentation. 

The previous level of limited and biased (toward only the most severe of disease) testing is reserved for say, annual influenza surveillance; a well known virus that circulates seasonally, as we fully expect it to, and for which we sample a sliver of the community pot. This are the cases that go to hospitals or just to family doctors, get tested, some viruses go on to get subtyped and we can use those proportions to extrapolate what's going on with that well-known human virus, to the rest of the community. We cannot do that with MERS-CoV yet because we don't know our enemy like we know influenzavirus.

Another point to make is that right now, the flurry of detections may be just a flurry of testing; better testing more accurately representing MERS-CoV circulation among humans in the KSA. A community-based study testing milder disease is essential to answer that. 

In the meantime we're left hanging between wondering whether changes to testing approaches is the reason for being about to reach the 4th 100 MERS-CoV detections in record speed, or whether it is a change in the virus that lets it spread better and further. Of course we don't know how many "rounds of infection" are going on with MERS-CoV just now because we are lacking information about how cases are linked together; who got infected from whom? Is it from a case to just a single close contact, or from a case-to-person-to-person-to-person....? 

Also, what is happening in camels during the first quarter of the year when MERS-CoV detection in humans seem to be at their lowest? It's now pretty clear that humans can acquire MERS-CoV from camels thanks to a recent article in Emerging Infectious Diseases by Dr Memish and colleagues that indicate a quite clear direction to acquisition.[8] But do camels undergo a seasonal outbreak of MERS-CoV and is that a regular and recurring thing? Is it related to camel festivals? Is it what has started the human infection waves in in April 2013 and 2014? We'd need widespread and ongoing camel (and human) testing to understand that. What about camel milk and urine; drunk regularly or used / collected / drunk for various reasons, respectively? Is it harbouring untold reserves of infectious MERS-CoV that gets ingested, then manifests in the vast majority of cases as a respiratory disease? We'll need some testing of those fluids to answer that, and perhaps a little common sense to interpret the results.

As usual, I present you the best of the data that I can lay my hands on yet find myself unable to give you many actual answers. At least I'm not alone in that so enjoy the hand-waving! 

One fact that I can share; the communication of events during what might be the most significant outbreak and cluster of cases of MERS-CoV to have happened in 2-years has been horrible, even by MERS epidemiology standards. 

Couldn't happen at a worse time really. Let's hope the new management at the KSA Ministry of Health have been awakened in time to avert an event on a much more global scale.

Sources...

1. Avaxnews | Mazayin Dhafra Camel Festival | 21-Dec-2013
   http://avaxnews.net/touching/Mazayin_Dhafra_Camel_Festival.html
2. Mazayin Dhafra Camel Festival | ABC Australia news | 21-Dec-2011
   http://www.abc.net.au/news/2011-12-21/emirati-men-look-through-a-fence-at-the-mazayin-dhafra-camel-fe/3741618
3. Daly Mail UK | Even the winner of this competition will have the hump: Hundreds of camels snake their way through the desert for a beauty contest | 24-Dec-2013
   http://www.dailymail.co.uk/news/article-2528868/Theyve-got-humps-Hundreds-camels-snake-way-desert-theyre-driven-beauty-contest-Abu-Dhabi.html#ixzz2zxdhAqNb 
4. DailyMail
http://www.dailymail.co.uk/news/article-2528868/Theyve-got-humps-Hundreds-camels-snake-way-desert-theyre-driven-beauty-contest-Abu-Dhabi.html
5. Newser.com | Dubai Sheik Pays $2.7M for Camel | April 2008
   http://www.newser.com/story/23945/dubai-sheik-pays-27m-for-camel.html
6. Sydney Morning Herald photos of Mazayin Dhzfra festival| 23-Dec-2013
   http://www.smh.com.au/photogallery/travel/the-spectacular-mazayin-dhafra-camel-festival-20131223-2zu5b.html
7. Soaring MERS Cases Cause Pandemic Jitters, but Causes Are Unclear
   http://news.sciencemag.org/health/2014/04/soaring-mers-cases-cause-pandemic-jitters-causes-are-unclear
8. Human Infection with MERS Coronavirus after Exposure to Infected Camels, Saudi Arabia, 2013
   http://wwwnc.cdc.gov/eid/article/20/6/14-0402_article.htm

Dump the garbage...

Sharon from @FluTrackers and I had an exchange on Skype this morning - always a useful way to message, even with my high rate of typos - and we agreed (or perhaps I bullied) that there was little point to keeping  "TheUAE12" (as I've taken to calling the 12 cases announced in the Kuwaiti News Agency [1]) on the list. 

In the past I've also argued that if samples get dropped, such as when Spanish or other cases could not be confirmed as MERS-CoV-positive, for whatever reasons, that FluTrackers retain their case numbers and "count around them". So the numbers become discontinuous. Those arguments are based on the numbers having already become embedded among flublogians/coronablogians and this way they could continue to be trackable by those who have used them. For example, FluTrackers makes a note saying this case is now a probable case, not included in the tally as it could not be suitably confirmed or somesuch. This is akin to not making wholesale changes to the name of a virus because you no longer like the "look" of the name when it already has decades of published literature behind it and is in the head of every researcher in the field. 

I proposed to Sharon that the MERS-CoV detections over the past few days were not yet embedded enough to be missed. So we've cleaned our lists. The FluTracker's tally [2] now sites at 360 cases using Ministry and WHO data. And I follow that excellent list.

So my Tweets this morning (AEST) were about those numbers having now been deleted and the case list comprising ~6-days and 70 cases has been "moved up" to fill the gap, but the numbers remain continuous. The new list [2] is thus 12 cases down from a few hours ago, but that has little impact on April's surge of new cases. 

We think that some of TheUAE12 are included in recent WHO Disease Outbreak News posts but they are not linked to the announced 12, no-one could/would link them to the announced 12 and so retaining them as empty case numbers was pointless.

On with the show.

Resource...

1. UAE Media Report: 12 New (Asymptomatic?) MERS Cases Detected
   http://afludiary.blogspot.com.au/2014/04/uae-media-report-new-asymptomatic-mers.html
2. FluTrackers MERS-CoV line list | MASTER LIST
   http://www.flutrackers.com/forum/showthread.php?t=205075

MERS-CoV detection: Cases by week and cumulative average still rising thanks to 2 healthcare clusters

Click on image to enlarge.

This chart, cases by week, really tells the story of a super-cluster driven by Jeddah's hospitals. Why this is still rolling along is unclear.

Perhaps, just perhaps (and I'm hand waving here), we can say that because MERS-CoV cases are not popping up all over Saudi Arabia, and because it seems, so far, that the contacts of the imported Malaysian (ex Jeddah) and Filipino (ex UAE) cases are testing negative for MERS-CoV, that a significant change to create MERS-CoV MkII may not have occurred. If it had, seeing positive test results among contacts and family members would be a good indirect alarm bell. But we have not seen much of that in cases to date, and in past umrah and Hajj pilgrimages. 

The clock on the maximum incubation period has probably run out for the Malaysian fatal case who became ill 4-April. The Filipino case may also have run down his clock. He tested negative for MERS-CoV 11-days after his exposure in the UAE. As far as we know there are no positive contacts or family members from these 2 exported cases.


But then there was SARS....

@MackayIM Hey, remember they guy with SARS who got on plane from China to Singapore, plane had to stop in Vietnam, & he died in Vietnam 1/2
— A biologist (@influenza_bio) April 19, 2014

@MackayIM That was 2/2003. No one on plane apparently got SARS, but HCWs in Vietnam did. & that was SARS -we may not be there yet with MERS.
— A biologist (@influenza_bio) April 19, 2014

.@MackayIM @EllenKnickmeyer @Fla_Medic transfer of undetected #MERS patients between hospitals could really fuel spread. Seen in SARS.
— Helen Branswell (@HelenBranswell) April 19, 2014

If we could for a minute use that absence of new cases in those new international sites (also watching Greece now) to cross off viral change (still need to see viral sequences to be able to do that conclusively; Spike please!), that could leave us to focus on a breakdown in infection control and in the prevention of infection in hospital settings. 

I understand that healthcare workers don't walk around in full gloves, goggles, gowns and N95 masks for their entire shift (fyi, as lab researchers, we have to wear gloves, safety goggles and back fastening lab coats while we work in a PC2 laboratory environment with these viruses which we handle in a Class II Biosafety Cabinet), but I do wonder why we have guidelines for managing patients with certain signs and symptoms, if, and emphasise if, they are not to be followed. 

Such a guideline can be found in the very comprehensive publication listed below [1]...Table 1 about handling SARS patients seems particularly relevant. I wrote about this publication back in August 2013 [3], with the help of Mike Coston who has an extensive range of expert information on preventing infection over at his Avian Flu Diary blog.[2]

The recent spate of MERS-CoV cases is a grim but timely reminder of why HCWs need to be extra cautious when dealing with respiratory infection cases; you never know what might come through the door.

References..

1. Infection prevention and control measures for acute respiratory infections in healthcare settings: an update | Seto et al | Eastern Mediterranean Health Journal
   http://applications.emro.who.int/emhj/v19/Supp1/EMHJ_2013_19_Supp1_S39_S47.pdf
2. Avian FLu DIary | search for N95
   http://afludiary.blogspot.com.au/
3. Infection Prevention and Control measures for MERS..mostly as per other ARIs
   http://virologydownunder.blogspot.com.au/2013/08/infection-prevention-and-control.html

MERS-CoV cases continue steep climb thanks most to 2 healthcare-related clusters...

Click on image to enlarge.
Data are for lab-confirmed cases only, and 
from FluTrackers, Ministries of Health
and the World Health Organisation Disease Outbreak
News reports.

The Jeddah cluster | Jeddah | Kingdom of Saudi Arabia. 

It is the biggest of any of the clusters of MERS-CoV cases within the Kingdom of Saudi Arabia, MERS-central (0 to date. It has seeded at least 2 internationally exported cases (a fatal case in Malaysia and now a case in Greece). It totals 53 cases so far; the tally for this cluster began after the onset of illness in the first case, 6-Apr.

The paramedic cluster | Abu Dhabi | United Arab Emirates

Happening simultaneously and right next door is a cluster of cases that began 28-Mar. It stands at 14 cases as I compose this; most recent with an onset of 14-Apr.

These dates, starting points and information are all up in the air of course. 

There have been no solid answers from either site on how each cluster commenced, so we don't know the actual 1st case nor how they became infected, what their status is or what type of contact occurred (animal or human-to-human). 

We don't know how many cases are linked together or even whether the 2 sites are linked. We don't know whether these focal outbreaks are ongoing nor just how so many healthcare workers (HCWs) can be infected by a respiratory virus that was already well known to the region and its hospitals (Wk 109, 2.1 years since first MERS cases). 

We don't know if this outbreak is just bad infection prevention and control at some hospitals/among some people. We are all wondering how this has continued among HCWs as it seems to be? After a couple of confirmed cases wouldn't masks and gloves and gowns be standard fare - if they weren't already in the management of unknown acute respiratory disease cases? Whether a "super spreader" is involved or not, such measures should have prevented so many healthcare workers becoming infected shouldn't they? 

Is this MERS-CoV Mk II - now with the ability to transmit efficiently and rapidly (before extra prevention measures are in place)? We have no MERS-CoV sequences to answer that. Spike gene sequences would at least help us understand he virus aspects? I don't really care about complete genomes-they are for phylogeny more so than public health; changes in Spike yielded information of value in the SARS-CoV event and for coronavirus in general, and could do so again. Just sequence that region guys! Do it quickly and release that info now. It's something informative. Don't wait for a scientific paper. Start a blog and put the results on there. Not just in Arabic and then in English some time later; with Yemen, the Philippines, Malaysia and Greece picking up cases in the past week, these 60+ cases are not just a Saudi thing (although the case numbers say otherwise-but you know what I mean), it's global village thing. Just tell us what's going on with the virus! 

So many things we don't know. "So what?" you ask Go and Google "MERS SARS" and limit it to the past 24-hours. That's so what. The media are starting to heavily lean towards the "MERS is the next SARS" story again and that stirs up concern at many levels. Is that concern justified. At the moment who the heck knows??? If there is no change in Spike, while not the be-all and end-all for change in the virus, it will allow the experts to make comments that inform the media that may calm a rapidly progressing situation with economically damaging potential for the world, and the region.

For crying out loud Ministry of Health|Saudi Arabia, get ahead of this thing.

Sources...

1. The world's greatest resource for tracking MERS-CoV cases, the FluTrackers line list
   http://www.flutrackers.com/forum/showthread.php?t=205075

MERS-CoV numbers by week...

There is a lot of buzz about the Middle East respiratory syndrome coronavirus (MERS-CoV) right now.

Laboratory-confirmed MERS-CoV Cases per week
(dark green, left y-axis) and the cumulative average of cases
(pale green; right y-axis). Note: recent cases have yet to 
have date of onset reported. Last 2 points may drop as 
cases are assigned to onset in earlier weeks; trend 
will likely remain.
Click on image to enlarge.

This is because the number of human cases appear to be sky-rocketing. Charting those numbers, as I've done here with a new cases/week and accompanying cumulative average (at each weekly data-point I calculate the average of all cases before it and plot that average). The chart does support the feeling of a spike although see my caveat in the chart's legend.

But there are a few things to remember when looking at these charts:

1. We're talking about ~270 cases in a region  (the "Middle East) with ~400 million[1] inhabitants; just 0.0000675% of people are noted as positive for this virus. While the recent surge in cases makes the chart look steep (and is definitely worthy of being watched, analysed and some work done to understand it), laboratory confirmed MERS-CoV cases are still a drop in the ocean of humanity
2. The surge in numbers is being driven by two clusters; One in the United Arab Emirates involving ~12 healthcare workers (HCWs) and an unidentified source (proposed as 1 or more ill patients) and the other in Jeddah, Kingdom of Saudi Arabia involving ~38 cases (from 2,517 suspect cases and contacts having been tested) in a hospital outbreak, also with many HCWs.[2]
3. In these 2 clusters, as in other MERS clusters, we may be seeing a much more representative spectrum of the clinical impact which infection by MERS-CoV is capable of. This, in my opinion anyway, is important because it tells a very different story to that of the severe disease we have mostly seen in cases among older males weakened by pre-existing disease, a group in which the virus wreaks a special kind of havoc
4. We still have very little to no data on what "normal" respiratory viruses do among older males with underlying disease in the KSA. That will significantly inform our understanding of the capacity of MERS-CoV to cause disease. Perhaps many of the >200 human respiratory viruses we know of cause just as much severe disease as MERS-CoV seems to. Don't bother pointing and laughing - show me the data to support your argument against that statement.
5. Has testing changed and is it contributing to the numbers? Early on, contacts of a confirmed case were "observed" (looked at for overt signs of disease - a sometimes subjective  process) and now they are being more actively sampled and tested using laboratory methods; the only way we know what virus is present in a patient...when the sample is correct and they work and other caveats. It would be helpful to know when that testing process changed and whether testing bias, along with sporadic clusters, is a big contributor to the continually climbing cumulative average seen in the chart above.

Finally just a comment. 2-years after the discovery of MERS-CoV we are still seeing large scale hospital-related outbreaks like this one in Jeddah and the one among HCWs in the UAE. 

Potentially these outbreaks are triggered when 1 case infects many people. Perhaps these are so-called "super-spreader" events (1 person infects many). I need to read more to understand those better and whether they happens with any virus but we focus more on it in emerging virus outbreaks. 

But why is this happening? It's not as though hospitals are not well aware of standard infection prevention and control practices for handling patients with respiratory illnesses of unknown origin. Respiratory illnesses make up a big part of hospital business. MERS-CoV is not the only, nor the most frequent, pathogen in this class. I suspect seasonal respiratory viruses kill many people in the region too. But do we know that do or that they don't when compared to MERS-CoV? Some contrast here would be very valuable. Studies of respiratory viruses, using PCR-based methods to look at cases of pneumonia, from the Arabian peninsula are more rare human cases of MERS-CoV. 

What's more scary than rising case numbers for me is the fact the these hospital clusters keep on happening. 

Sources...

1. http://en.wikipedia.org/wiki/List_of_Middle_East_countries_by_population
2. http://www.flutrackers.com/forum/showthread.php?t=205075
3. http://www.promedmail.org/direct.php?id=20140416.2406647

MERS-CoV update: Case accumulation over time and by region of suspected acquisition...

Click on chart to enlarge.

It's been about a month since I last updated this chart. While the situation is perhaps not yet worthy of the Jeff Golblum quote from Jurassic Park..."I'm fairly alarmed here"...it's heading that way for me.

There is quite an uptick in the slope of the Kingdom of Saudi Arabia's case numbers and also that of the United Arab Emirates.

This chart will bear watching and I'll endeavour to keep it updated on at least a weekly basis if the cases keep coming out at the rate they have been of late.

One thing to note though; because the KSA Ministry of Health data are patchy, inconsistent and slow. It may be that some/many of the dates for cases between the final 2 data points would spread into previous weeks. Unfortunately these dates have not yet been passed along to the WHO yet (or from the WHO to the public) and so the dates sometimes have to reflect date reported (which may lag behind onset of signs and symptoms by weeks) or date of hospitalisation rather than the more reliable date of illness onset. So take the chart as a trend...but one which may highlight a change in the speed of new case announcements.

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?

Middle East respiratory syndrome coronavirus (MERS-CoV) cases rise in march: Festival-related?

It's been nearly 3-weeks since my last update so I'm well overdue to look at what's changed.

Click on image to enlarge.

A quick post first up showing the accumulating cases by the region in which the person probably caught their infection and the week in which they became ill - or the week in which the case was publicly reported by a Ministry if no onset date was provided.

Why the recent uptick in cases; ~9 reported this month so far? 

There have been a few things going on in Riyadh (a city of 6 million, in which 10/11 most recent cases have been acquired) that might link people with camels (the likely intermediate or primary host of MERS-CoV in the region). 

I have listed a few other events listed that may also be pertinent for MERS-CoV acquisition &/or transmission, from whatever source, in a post 29-Jan [5]. To add to that there is this:

• The 17-day long 29th annual Janadriyah Festival kicked off Feb-12. It showcases the national heritage and culture of the Saudi lifestyle. Includes camel rides and racing [3,4] and is visited by millions of people from all over the Kingdom of Saudi Arabia (1.4mil by 26-Feb) [2][3]. But not just locals; tourists come from all other regions of the Arabian peninsula too, including the UAE which a "guest of honor" this year. Of note: the recent 68-year old male UAE MERS-CoV case had exposure to animals from his own farm and is not noted as having traveled.

References...

1. What's on in Riyadh
   http://www.expatarrivals.com/saudi-arabia/riyadh/whats-on-in-riyadh
2. Arab News story on Janadriyah festival 2014
   http://www.arabnews.com/news/531351
3. Janadriyah festival at Blue Abaya
   http://www.blueabaya.com/2014/02/guide-to-janadriyah-festival-2014.html
   and
   http://www.blueabaya.com/2013/04/top-ten-things-to-do-at-janadriyah.html
4. Camel racing at the Janadriyah Festival
   http://english.alarabiya.net/en/perspective/photo-gallery/2014/02/13/Riyadh-Camel-Race.html
5. A date with Middle East respiratory syndrome coronavirus (MERS-CoV)..
   http://virologydownunder.blogspot.com.au/2014/01/a-date-with-middle-east-respiratory.html