2014-05-25 ~ Medical News Blog

Snapdate MERS-CoV chart update

case accumulation, epidemic curve, epidemiology, MERS-CoV, snapdate

Just a quick look at some updated Middle East respiratory syndrome coronavirus (MERS-CoV) detection figures.

For 2-days this past week we had zero cases reported, but we still had a number of deaths. On the 27-May alone there were 5 deaths across 3 regions.

Weeklies chart.
Number of lab-confirmed cases on the left upright (y-axis), the cumulative weekly
average can be read from the right y-axis and the bottom (x-axis) lists data by week, usually week when signs & symptoms onset otherwise by hospitalisation date or
reporting if nothing else is available.
Click on image to enlarge.

The dailies chart shows that detections have reached zero. Been a while since that happened-earl April was the last time. This will possibly change as cases from coming days fall out with onset dates in this week.
Or perhaps there won't be any cases in the coming week. We can only hope.

Dailies chart.
Number of lab-confirmed detecteions on the left y-axis and the x-axis lists data by day,
usually day of when signs & symptoms onset otherwise by hospitalisation date or reporting
if nothing else is available.
Click on image to enlarge.

I haven't added a healthcare worker (HCW) to my line list for the past 63-detections. That's the longest period without an HCW in the history of MERS! Is that true or are those data now withheld form the Kingdom of Saudi Arabia's numbers? Don't know. But here's what it looks like as yet another healthcare-related outbreak subsides.

Cumulative number of lab-confirmed detections among HCWs on the left y-axis while the right y-axis shows the proportion of MERS-CoV detection who were HCWs that week. The x-axis lists data by week, usually day of when signs & symptoms onset otherwise by hospitalisation date or reporting if nothing else is available.
Click on image to enlarge.

The MERS week in snapshots...

humour, meme, MERS-CoV

MERS-CoV in the Netherlands...a detail analysis of cases

faeces, laboratory confirmation, MERS, MERS-CoV, serum, The Netherlands, throat swab, urine, viraemia

Red arrow indicates where Dutch
MERS-CoV case sequences sit.
Click on tree to enlarge

This comes from a shiny newly released Eurosurveillance report from Dutch researchers.

I've marked up my earlier tree to show where (based on partial 4,000nt fragment) the sequence from the Netherlands MERS-CoV positive cases (near identical) sits.

I've also charted Case 1's laboratory testing course, to show the variability of virus detection when a very thorough sampling and testing investigation is conducted.

Viral RNA remained detectable in the blood for all days tested demonstrating viraemia (well, RNAaemia technically) from day-4 onwards. Urine was not positive but a faecal sample was, on day-5. The latter has implication for infection control in hospital settings whereby flushing toilets creating aerosols could be another contributor to spread.

Reverse transcription real-time polymerase chain reaction (RT-rtPCR) results are shown as positive (tall bars), negative (stumpy bars) or not tested (empty space) plotted against day of sampling.
Click on image to enlarge.

This is, as far as I'm aware, is only the second time human faeces or urine have been found to contain signs of MERS-CoV.

A throat swab was positive early on and then again after a 2-day period of negativity. This points to the possibility of shedding for over a week, when associated with cough. But given that this case was part of a tour group and they didn't all become symptomatic, MERS-CoV still didn't spread efficiently or result in disease very often (if it did spread), for whatever reason(s). Antibody testing would be interesting here too.

It would also be very interesting to know whether virus was being shed during the initial diarrhoea in Case 1, which predated his return to the Netherlands by about 8-days, or whether that was unrelated to the MERS-CoV infection. Perhaps testing faeces for gastrointestinal viruses would be useful, or interesting, here.

First Aid Response Training in Mbarara, Uganda

Emergency Medicine, First Aid Training, trauma, uganda

The incredible need for such a course was immediately apparent to me on my first day in the Accidents and Emergency (A&E) Ward, MRRH�s equivalent of an Emergency Department. It was clear that the majority of patients were being evaluated for traumatic injuries, most from recent encounters with a boda-boda. Half of them had their heads wrapped in gauze to either cover their head wound or to secure the post-surgical drain from their recent hematoma evacuation. Upon walking in, you were hit with a wave of a distinct scent of old, crusted blood mixed with the smell of purulent drainage and the natural odor of the human species, when one is unable to take a shower for days, all combined in a hot, humid air that is caught in a building that is located on the equator with no air conditioner. It was a difficult scene to process, at first, especially when a 13 year-old boy comes in with his peritoneum exposed and a deep abrasion to his scalp after being hit by a boda-boda. His eyes filled with fear and confusion as he holds tightly to his mother�s arm and lets out cries of suffering. Unfortunately, you become slightly desensitized after a few days because such a sight is not uncommon.

I had arrived in Mbarara with nothing but a small set of slides and the knowledge I had obtained from reading about similar courses done around the world in the last 10 years. Yet, one step into the A&E Ward gave me the motivation required to make any apprehension I had, about my ability to execute such a course, completely disappear. I realized that even though a one-day first aid course for only 40 drivers would be a drop in the ocean, it would still be the first step towards improving prehospital care in a city where that concept was barely being introduced. I had the responsibility of creating the first aid course from the ground up in 14 days. Along with the mentorship from Dr. Hilarie Cranmer, Director of Disaster Response at MGH Center for Global Health, Dr. Miriam Aschkenasy, Deputy Director of Disasater Response at MGH Center for Global Health, Dr. Anna Baylor, Program Director for MUST Research Collaboration, and Dr. Jon Mousally, EM Faculty at MGH who is working on a similar project in Bangladesh, Sarah Graham, who is the Program Manager for the MUST Research Collaboration, was my main collaborator on the ground.

The first stage of planning was focused on the logistics of the course. We wanted to formulate a small course which did not over-extend our resources and risk the quality of the course. Additionally, we were executing a project that we had never done before to a community that was new to the concept. Our target population were the drives and staff of the MUST Research Collaboration. This was a good group to start with because they were familiar with MGH and had a stable handle on the English language. Preference was given to collaboration drivers. Within the first six hours of opening up the course, all available positions were filled. The demand was so great that we were forced to turn down requests to take the course. Furthermore, after the course, participants were asking when the next course would be available. The primary emphasis of the course was for it to be hands-on with minimal lecture time. Given resource and time constraints as well as the local cultural customs, we elected to make the course four hours long with a 20-minute break in between. In order to ensure participants had adequate one-on-one instruction, the course was implanted over two days in two four-hour sessions with 20 positions for each course. After having the basic logistical skeleton for the course, our attention shifted to finalizing the curriculum, response cards, and first aid kits.

The curriculum was focused on subjects that had proven to be universally valuable in low-resource settings. It centered on scene safety, universal precautions, airway, recovery position, wound dressing, tourniquets, splints, and cervical spine precautions. Using current literature, I used the small set of slides I had prepared prior to arriving to Mbarara and expanded them to create a four-hour course. We then created a response card based on the pictures used for the course. Our end-goal was to make this course self-sustaining, so the involvement of Ugandan physicians was critical from the conception of the course. We recruited four Ugandan physicians: three interns and one Mmed, the equivalent of a resident. On average, there was a one to four or five ratio of instructors to participants. The curriculum was taught using materials from a first aid kit that was made from locally-sourced supplies. We spent three days searched for the best supplies available and negotiated for the best price. The only out-sourced portion of the kit was the bag in which the supplies were packaged; it was donated by Global Disaster Response at MGH Center for Global Health. Supplies included: gauze bandages packages � 3 units, gauze Pads � 12 units, elastic Bandage � 3 units, medical tape � 2 units, medical gloves � 10 pairs, scissors � 1 unit, hand sanitizer � 2 units, 1ft wooden dowels � 4 units, crowbar � 1 units, water bottle � 1 unit. The participants were taught using only these materials and resources that would be available to them in case of an accident (e.g., a towel, shirt, sheet). Each kit also included a first aid response card that illustrated each skill taught in the course in addition to the list of supplies and location where they were obtained. Each driver received a first aid kit, a portable water bottle (also donated by Global Disaster Response at MGH Center for Global Health), and a certificate. The participants were made responsible for restocking their kits as supplies were used. A six-question test was completed at the end of the course to evaluate the participants� knowledge retention. This test showed that scores were lower in the session in which collaboration drivers made up 80% of the participants. In Uganda, drivers tend to have lower education levels than other professionals. The lower test scores of this session could be attributed to lower education levels, language barrier, and less exposure to the medical field.

Although I had originally proposed to execute a 3-week first response training course for about 200 participants and a disaster drill, I was only able to take a small first step towards this grand goal. As you know, international emergency medicine is a very dynamic world. When dealing with communities of low resources, especially abroad, it is difficult to execute a project without the full understanding of the local culture, community, and infrastructure, which is what I was able to accomplish during my 4 weeks in Mbarara. The course laid the foundation for a better product because of community engagement and capacity building of Ugandan physicians. Additionally, my trip also focused on meetings with key stakeholder in the city and medical community of Mbrarara. Dr. Cranmer, Dr. Baylor, and I met with the Vice-Chancellor of MUST, the Dean of the MUST Medical School, the Chief of Police, the Chief of Fire, the heading of nursing for both the hospital and the university, and the Department Chiefs of MRRH. These meetings were integral to the development of disaster preparedness in Mbarara. The intent is to organize and establish a self-sustained, Ugandan-led pre-hospital training course that will culminate in a city-wide disaster preparedness and response plan, including mass-casualty exercises and drills. As the Vice-Chancellor of the Mbarara University of Science and Technology put it, �Our hope is to make Mbarara the model for country and hopefully East Africa.�

In order to start working towards our long term goal, in November 2014, we will conduct a risk and needs assessment focused on formulating a basic first response training course tailored to the specific needs of the Mbarara community. The assessment will address the capabilities of the local Ugandan taxi drivers, fire, police, University and Hospital staff, and healthcare workers. It will quantify the types of injuries they come across and qualify the skills they feel they are able to offer. The modes of transportation injured patrons utilize to go to the hospital will be measured and reviewed. By the end of this long-term project, we seek to create capacity in pre-hospital care and emergency health care delivery. Hopefully, in a couple of years, a 13 yr-old boy with an exposed peritoneum will come in at least partially stabilized and with proper wound dressings.

Updated MERS-CoV full genome tree...

camel, MERS-CoV, phylogeny

With thanks to @arambaut for some tips, and for tying my home computer up for 2-days running PHYML on the sequences (super-computer it ain't) - this is a slightly more robust tree of the MERS-CoV complete (or near-complete) genome nucleotide sequences published to date. This follows from my previous post and tree here.

Very little from 2014 despite the majority of MERS-CoV variants circulating then. But of course we have to wait because next generation sequencing is the main way we roll with MERS-CoV.

Alignment of 56 complete or near complete MERS-CoV genomes and an Egyptian divergent variant from a camel. Alignment made using Geneious v6.1.7. The PHYML v2.2.0 plug-in was added to make this tree, using 1000 bootstraps. Red stars indicate
virus which is reportedly from the same patient (seems doubtful). Vertical bars to the right indicate Clade A (dark blue) and B (pale blue). Sequences from the the 2013 Al-Ahsa hospital outbreak are boxed in pink; from the Jeddah 2014 hospital outbreak in blue; from the Hafr Al-Batin community cluster in green. Camel icons indicate genomes from camel variants for MERS-CoV. GenBank accession numbers are indicated at the end of each sequence name which also includes region of detection, host (human if not specified) and year of sample collection.
Click on image to enlarge.

The tree really highlights how remarkably interwoven the camel and human MERS-CoV genome sequences are; remembering that these 30,000nt genomes don't differ from each other by more than 1% at the nucleotide level.

Some new sequence analyses from the Netherlands cases should be coming out in the next issue of Eurosurveillance so get a tab ready and keep hitting refresh. Or, ya know, go get a life or something (I'm hitting refresh).

Updated MERS map moves stars around....

epidemiology, Iran, MERS, United States of America

This new version adds a blue star to Iran, as it seems likely there has been some local transmission.

That star has been taken away from the USA (it's been a bad boy) since there has now been no sign of local transmission after the overnight retraction of the Illinois man's positive antibody test result.

Click on image to enlarge.

There must be a couple of internally relieved people around the US CDC today. Relieved. Why? Because they have got off their chest something they must have had a growing inkling about for at least a few days now. That being the news result that the Illinois 3rd US case was in fact not infected by MERS-CoV via a handshake and 2 meetings, 1 lasting 40min.

So that didn't happen.

And the implications for much simpler transmission of MERS-CoV did not result. And that all kinda makes more sense in the broader scheme of things MERS-related. This result always looked like an outlier.

Additional lab tests indicate IL resident wasn�t infected by IN MERS patient. No evidence of spread of #MERS in US.
� Dr. Tom Frieden (@DrFriedenCDC) May 28, 2014

Not a fun thing to have to report. Kudos to the team though for going back to correct an error. MERS reporting could definitely do with some more dynamic editing, and ownership, of it's mistakes.

That said, for the life of me this morning, I cannot work out why the CDC announced part of the antibody (Ab) testing result without having put such an important preliminary piece of diagnostic information, with so many epidemiological implications, through an even more rigorous testing pipeline first. I had certainly assumed that had happened when I previously wrote in support of antibody-testing on the back of this result over a week ago...and made note that that hiccups in the Ab testing process could follow!

Let's look at what we know publicly about this test method. The CDC team have published 2 different papers [1,2] where they use an enzyme-linked immunosorbent assay (ELISA) first (the same one as used in the Illinois case I presume), then confirmed those results with either an imunofluorescence assay (IFA) or a virus neutralization (NT) test. The latter is the most specific method of showing that the MERS-CoV antibodies in a patients serum, if present, can block, or "neutralize", the ability of a virus to infect permissive cells in the lab. However, there has been a previously recorded issue with sera from SARS-CoV positive people cross-reacting in a MERS-CoV neutralization test. [3]

So the 2 papers have the following definitions relevant to antibody testing (my highlighting).

In the study of a possible MERS-CoV related stillbirth, the CDC team used the definition..

"MERS-CoV antibody positivity was defined as having positive a serologic result from the HKU5.2N Enzyme Immunoassay (EIA) and a correlated test-positive result from either the MERS-CoV Immuno-fluourescent assay (IFA) or MERS-CoV microneutralization titer assay (MNt) developed at CDC."[1]

*The HKY5.2N is a bat CoV antigenically related to MERS-CoV.

When they went back to the original Jordan cluster from 2012, the same definition was used..

"To maximize specificity, we defined MERS-CoV antibody positivity as subjects having correlated, positive laboratory results from the HKU5.2N screening ELISA as well as confirmed positive results by either the MERS-CoV immunofluorescence assay (IFA) or the MERS-CoV microneutralization assay (MNT)."[2]

What we know in the Illinois retraction story is that the IFA results did support the ELISA (less specific test) results (both were positive) before that result was announced.[4] They were clearly not supported by virus-specific MNT though. So the definitions above will need to be changed, perhaps to include all 3 results for a definitive answer or definitely have MNT in the tetsing mix somewhere. This has an impact on a result from the Jordan retrospective study[2] since 1 of those "positive" cases was defined using only ELISA and IFA-reactive without support from MNT (see Outbreak member 11; Table 1).[2]

Oh well. Just goes to show, no-one is perfect and everyone is subject to a little hysteria when the pressure is on.

I've gone back to strike-through the text relating to this retraction in my previous posts (might take me a little while to complete). I'm leaving the text in place as it was, but adding new comments in red. I've also deleted this line from my personal MERS-CoV line list.

While this sadly incident does nothing to help people trust antibody testing in the future, at least for MERS-CoV, the literature for MERS-CoV antibody testing contains good examples of well-validated assays that require and conduct multiple tests to yield robust results. I still think rigorously determined positive antibody test results should still be considered as valid indications of a MERS-CoV positive result. Clearly not in this instance because this seems to be a pipeline "in process".

References...

Stillbirth During Infection With Middle East Respiratory Syndrome Coronavirus
http://jid.oxfordjournals.org/content/early/2014/02/17/infdis.jiu068.full
Hospital-associated outbreak of Middle East Respiratory Syndrome Coronavirus: A serologic, epidemiologic, and clinical description
http://cid.oxfordjournals.org/content/early/2014/05/14/cid.ciu359.short
Cross-reactive antibodies in convalescent SARS patients' sera against the emerging novel human coronavirus EMC (2012) by both immunofluorescent and neutralizing antibody tests.
http://www.ncbi.nlm.nih.gov/pubmed/23583636
CDC concludes Indiana MERS patient did not spread virus to Illinois business associate
http://www.cdc.gov/media/releases/2014/p0528-mers.html

Iran reports 2 MERS-CoV cases: 20th country [UPDATED]

case announcement, Iran, MERS, MERS-CoV

Click on map to enlarge.

Head of Communicable Disease Control (CDC) at the Iran Ministry of Health (MOH), Dr. Mohammad Mahdi Reports seem to indicate 2 sisters, one critically ill, have been confirmed as cases and 2 suspected cases, perhaps family members, are being observed/investigated for MERS-CoV.

I'll await the WHO report (which will hopefully appear soon) with more details but what we have so far suggests local spread, so the pink (unknown origin of case acquisition) will change to another colour of some sort, in the future.

The WHO were awaiting official notification from Iran's MOH about 10-hours ago.

@HelenBranswell Aware of reports on this, but have not receive official notification as per International Health Regulations (IHR)
� WHO (@WHO) May 26, 2014

A story from AFP [7] notes that the 2 sisters are being treated in the same hospital in Kerman, where they were believed to have acquired their infection from a pilgrim returning to Iran from Saudi Arabia. No mention of whether that pilgrim was tested and found to me MERS-CoV positive.

h/t to @Malaekeh and @HelenBranswell for alerting us to the CDC report.

Resources...

Crawford Kilian's post..
http://crofsblogs.typepad.com/h5n1/2014/05/iran-reports-first-mers-cases.html
MOH announcement..
http://www.behdasht.gov.ir/?siteid=1&fkeyid=&siteid=1&pageid=127&newsview=108713
FluTracker's thread..
http://www.flutrackers.com/forum/showthread.php?t=223788
Treyfish's post
http://swineflumagazine.blogspot.com.au/2014/05/iran-identification-of-novel-virus-2.html
Mike Coston's post..
http://afludiary.blogspot.com.au/2014/05/irans-moh-reports-2-mers-cases-testing.html
PressTV - English detail
http://www.presstv.ir/detail/2014/05/27/364327/iran-confirms-two-cases-of-mers/
AFP Report
http://www.interaksyon.com/article/87818/iran-reports-first-2-mers-cases

Camels and MERS: links to peer-reviewed scientific literature...[UPDATE #1]

camel, Literature Review, MERS-CoV, Reference resource

Add caption
Camels at the centre, aerosol all around...

I thought this might be a useful page for anyone who would like to know just how much data has been generated that supports a link between camels and MERS-CoV, and studies that have shown near identical viral genomes from camels, and the humans in contact with them.

Its also worth nothing only 1 ~180nt PCR fragment from 1 bat in 1 study has had a MERS-CoV sequence detected in it and yet they are still considered the most likely ancestor of the MERS-CoV because bats seem to be the ancestral source of many CoVs.

No studies have found MERS-CoV or infection-blocking (neutralizing) antibodies to MERS-CoV in any non-human or non-dromedary camel animal despite investigation of:

horses
llamas
alpacas
bactrian camels
guanaco
goats
sheep
water buffalo
cows
birds
pigs
chickens

While rats and mice have not been tested in the wild, deliberately inoculated lab mice and Syrian hamsters do not support growth of MERS-CoV and 2 rat cell lines (Chan et al. J Infect Dis. 2013;207:p1743-52) did not support viral transcription or growth. Not the end of the small animal story of course and more testing of small animals is a good thing, but neither has the camel story been completed yet (finding infectious virus in milk, urine and meat and some air sampling and testing from around camels would be nice). However, the camel story does already have some very solid chapters suggesting humans could be coming into sporadic contact with the virus.

So a few quick thoughts to put camels in context with sporadic infections that are not traceable to contact with a known human case.

I don't think any scientist has ever suggested every camel is carrying/shedding MERS-CoV all the time. Nothing supports that.
Most MERS-CoV cases have been from spread between humans and most of those are now linked with hospital-based settings (thanks Jeddah outbreak!). Whether community spread is ongoing is completely unknown until someone tests the community, post-Jeddah outbreak, and not people linked to hospitalized confirmed cases (they only bias the results).
As we saw in 2nd and 3rd US MERS-CoV detections, 2 face-to-face business meetings, 1 with at least 40-min of face time, and a handshake, was sufficient to pass along MERS-CoV between humans when the index case was not all that ill.

~~I hope the R0 guys can build this sort of event into their predictive models and~~
~~I think this has real and major implications for what "contact" with a~~ camel ~~actually means. I have serious doubts that people who are RT-rtPCR positive and being interviewed and asked about their exposure to camels would think of~~ being near a camel ~~as contact with camels.~~ Is ~~that how they are being asked?~~
THIS RESULT WAS RETRACTED 28-May-2014 FOLLOWING A NEGATIVE NEUTRALIZING ANTIBODY TESTING.

Better understanding the proximity-possibility needs experimental testing but in the meantime it is also very important for those who are asking infected people about their animal exposures and contacts to understand that respiratory viruses don't just spread by physical contact. I am unaware of what is being asked and in how much detail - this may already be well understood.

If people being asked about past contact with camels are thinking "hey, yeah, I was walking between camel pens for 20 minutes, but no I didn't kiss one or lick its nose or feed it or anything touchy-feely" (I'm 100% certain those would be exactly the words in their heads) - then they may well say "no contact". To my mind, that level of proximity in that example, especially if 1 or 2 of those camels was symptomatic, would be contact.

Anyway, do let me know if I've missed any papers below - or if new references come out.

Camels in the literature...

Reusken CB, Haagmans BL, Muller MA, Gutierrez C, Godeke GJ, Meyer B et al. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. Lancet InfectDis 2013 October;13(10):859-66.
Perera RA, Wang P, Gomaa MR, El-Shesheny R, Kandeil A, Bagato O et al. Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013. Euro Surveill 2013;18(36):ii.
Hemida MG, Perera RA, Wang P, Alhammadi MA, Siu LY, Li M et al. Middle East Respiratory Syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013. Euro Surveill 2013;18(50):20659.
Reusken CB, Ababneh M, Raj VS, Meyer B, Eljarah A, Abutarbush S et al. Middle East Respiratory Syndrome coronavirus (MERS-CoV) serology in major livestock species in an affected region in Jordan, June to September 2013. EuroSurveill 2013;18(50):20662.
Haagmans BL, Al Dhahiry SH, Reusken CB, Raj VS, Galiano M, Myers R et al. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect Dis 2014 February;14(2):140-5.
Alexandersen S, Kobinger GP, Soule G, Wernery U. Middle East respiratory syndrome coronavirus antibody reactors among camels in Dubai, United Arab Emirates, in 2005. Transbound Emerg Dis 2014 April;61(2):105-8.
Alagaili AN, Briese T, Mishra N, Kapoor V, Sameroff SC, Burbelo PD et al. Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia. MBio 2014;5(2):e00884-14.
Meyer B, Muller MA, Corman VM, Reusken CB, Ritz D, Godeke GJ et al. Antibodies against MERS coronavirus in dromedary camels, United Arab Emirates, 2003 and 2013. Emerg Infect Dis 2014 April;20(4):552-9.
Hemida MG, Chu DKW, Poon LLM, Perera RAPM, Alhammadi MA, Ng H-Y et al. MERS Coronavirus in dromedary camel herd, Saudi Arabia. Emerg Inf Dis2014;20(7).
Nowotny N, Kolodziejek J. Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels, Oman, 2013. Euro Surveill2014;19(16).
Raj VS, Farag EABA, Reusken CBEM, Lamers MM, Pas SD, Voermans J et al. Isolation of MERS Coronavirus form a Dromedary Camel, Qatar, 2014. EmergInf Dis 2014;20(8).
Corman VM, Jores J, Meyer B, Younan M, Liljander A, Said MY et al. Antibodies against MERS Coronavirus in Dromedary Camels,Kenya, 1992-2013. EmergInf Dis 2014;20(8).
Chu DKW, Poon LLM, Gomaa MR, Shehata MM, Perera RAPM, Zeid DA et al. MERS coronaviruses in dromedary camels, Egypt. Emerg Infect Dis 2014;20(6).

Camels and MERS: links to peer-reviewed scientific literature...[UPDATE #2]

camel, Literature Review, MERS-CoV, Reference resource

Add caption
Camels at the centre, aerosol all around...

horses
llamas
alpacas
bactrian camels
guanaco
goats
sheep
water buffalo
cows
birds
pigs
chickens

I don't think any scientist has ever suggested every camel is carrying/shedding MERS-CoV all the time. Nothing supports that.
Most MERS-CoV cases have been from spread between humans and most of those are now linked with hospital-based settings (thanks Jeddah outbreak!). Whether community spread is ongoing is completely unknown until someone tests the community, post-Jeddah outbreak, and not people linked to hospitalized confirmed cases (they only bias the results).
As we saw in 2nd and 3rd US MERS-CoV detections, 2 face-to-face business meetings, 1 with at least 40-min of face time, and a handshake, was sufficient to pass along MERS-CoV between humans when the index case was not all that ill.

~~I hope the R0 guys can build this sort of event into their predictive models and~~
~~I think this has real and major implications for what "contact" with a~~ camel ~~actually means. I have serious doubts that people who are RT-rtPCR positive and being interviewed and asked about their exposure to camels would think of~~ being near a camel ~~as contact with camels.~~ Is ~~that how they are being asked?~~
THIS RESULT WAS RETRACTED 28-May-2014 FOLLOWING A NEGATIVE NEUTRALIZING ANTIBODY TESTING.

Reusken CB, Haagmans BL, Muller MA, Gutierrez C, Godeke GJ, Meyer B et al. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. Lancet InfectDis 2013 October;13(10):859-66.
Perera RA, Wang P, Gomaa MR, El-Shesheny R, Kandeil A, Bagato O et al. Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013. Euro Surveill 2013;18(36):ii.
Hemida MG, Perera RA, Wang P, Alhammadi MA, Siu LY, Li M et al. Middle East Respiratory Syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013. Euro Surveill 2013;18(50):20659.
Reusken CB, Ababneh M, Raj VS, Meyer B, Eljarah A, Abutarbush S et al. Middle East Respiratory Syndrome coronavirus (MERS-CoV) serology in major livestock species in an affected region in Jordan, June to September 2013. EuroSurveill 2013;18(50):20662.
Haagmans BL, Al Dhahiry SH, Reusken CB, Raj VS, Galiano M, Myers R et al. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect Dis 2014 February;14(2):140-5.
Alexandersen S, Kobinger GP, Soule G, Wernery U. Middle East respiratory syndrome coronavirus antibody reactors among camels in Dubai, United Arab Emirates, in 2005. Transbound Emerg Dis 2014 April;61(2):105-8.
Alagaili AN, Briese T, Mishra N, Kapoor V, Sameroff SC, Burbelo PD et al. Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia. MBio 2014;5(2):e00884-14.
Meyer B, Muller MA, Corman VM, Reusken CB, Ritz D, Godeke GJ et al. Antibodies against MERS coronavirus in dromedary camels, United Arab Emirates, 2003 and 2013. Emerg Infect Dis 2014 April;20(4):552-9.
Hemida MG, Chu DKW, Poon LLM, Perera RAPM, Alhammadi MA, Ng H-Y et al. MERS Coronavirus in dromedary camel herd, Saudi Arabia. Emerg Inf Dis2014;20(7).
Nowotny N, Kolodziejek J. Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels, Oman, 2013. Euro Surveill2014;19(16).
Raj VS, Farag EABA, Reusken CBEM, Lamers MM, Pas SD, Voermans J et al. Isolation of MERS Coronavirus form a Dromedary Camel, Qatar, 2014. Emerg Inf Dis 2014;20(8).
Corman VM, Jores J, Meyer B, Younan M, Liljander A, Said MY et al. Antibodies against MERS Coronavirus in Dromedary Camels,Kenya, 1992-2013. EmergInf Dis 2014;20(8).
Chu DKW, Poon LLM, Gomaa MR, Shehata MM, Perera RAPM, Zeid DA et al. MERS coronaviruses in dromedary camels, Egypt. Emerg Infect Dis 2014;20(6).
Ziad A. Memish, Matthew Cotten, Benjamin Meyer, Simon J. Watson, Abdullah J. Alsahafi, Abdullah A. Al Rabeeah, Victor Max Corman, Andrea Sieberg, Hatem Q. Makhdoom, Abdullah Assiri, Malaki Al Masri, Souhaib Aldabbagh, Berend-Jan Bosch, Martin Beer, Marcel A. M�ller, Paul Kellam, and Christian Drosten. Human Infection with MERS Coronavirus after Exposure to Infected Camels, Saudi Arabia, 2013. Emerg Inf Dis 20(6) (online May 16).
Esam I. Azhar, Ph.D., Sherif A. El-Kafrawy, Ph.D., Suha A. Farraj, M.Sc., Ahmed M. Hassan, M.Sc., Muneera S. Al-Saeed, B.Sc.,Anwar M. Hashem, Ph.D., and Tariq A. Madani, M.D. Evidence for Camel-to-Human Transmission of MERS Coronavirus

NEJM June 4.
NB. This study is the same human case and camel herd tested in #14. Sampling times differ subtly.

Jeddah changed the MERS-CoV age:sex landscape...

Age bias, HCWs, Jeddah, Kingdom of Saudi Arabia, MERS, MERS-CoV, outbreak investigation, sex bias

Note. Not every death or case is listed.
See bottom-left corner for breakdown.
Click on charts to enlarge.

I've broken down the age and sex in these charts.

As usual, it's mostly about males and older people until we get to the Jeddah outbreak.

In the top pair of charts (note the different scale used here compared to that used in the charts below) we see the breakdown for all MERS-CoV detections to date on the left and the fatal cases from among those on the right.
An apple in terms of people shapes.

In the middle pair of charts we look at all cases form 2012 up until the day before the Jeddah outbreak. The total case pyramid shows an older age bulge but the deaths look very similar to those for all fatal outcomes. M:F is similar to the total case charts above.

In the bottom pair of charts we're looking at what happened from the beginning of the Jeddah outbreak until now. We see a marked change in distribution with many more younger adults being positive for MERS-CoV. We also see a major shift towards more females than we'd seen beforehand. All the result of more widespread testing and a greater healthcare worker contribution I presume. Strangely though, given the younger adult demographic here, we see no accompanying jump in numbers of children. Are they not subject to testing? Are the younger adults often foreign workers who do not have children/children with them with them? There is no reason for children to test any less frequently MERS-CoV-positive and they are also just as likely as healthy adults to get mild or asymptomatic disease (as far as we know). If positive, children will have an important potential role in the MERS-CoV transmission story, especially when visiting elderly relatives.

The recent Al Qunfudhah teacher who is MERS-CoV just reinforces that children are shaping up to be a strange data gap. Yeah. I know. Another one.

MERS-CoV cluster in Al Qunfudhah...

Al Qunfudhah, case announcement, Kingdom of Saudi Arabia, Makkah, MERS, MERS-CoV

5 cases in 4 days from a city we haven't seen prior MERS-CoV detection in (as far as I can tell) = a cluster.

The south western coastal city of the Kingdom of Saudi Arabia (KSA) is home to ~200,000 people[1].

While the cases have been asymptomatic when reported, the first, a 65-year old male (65M; was isolated at home [2]), came into contact with another case (see below) while at a government hospital. Which case that was and at what hospital, is unclear.

But there are other worrying issues here:

This city is in Makkah region, home to the 2 holiest Mosques and not a site in which anyone wants to see active spread of this virus again as we get closer to the Hajj; we don't want to see it spread anywhere at all of course.
FluTrackers has a thread on this (when don't they!?; my thanks to Sharon Sanders for pointing me to it) from 21-May and at least one of the 5 cases seems to be a teacher at a school in Al Quoz, 25 km south of Al Qunfudhah. No school-children have been reported positive to date though. The 4 cases after 65M were aged 25, 28, 25 and 45 - could some be teachers or are they all family of 65M? Family accompanied 65M to visit a relative in a Jeddah hospital (presumably the contact for 65M?). We no longer get any information from the KSA's Ministry of Health (MOH) about occupation, so one is left to guess...as usual. There seems to be mention of symptoms among some of these cases?
Could healthcare workers in Al Qunfudhah be among these younger asymptomatic (presumable) contacts of 65M?

This city may be seen written as Al Qunfudah, Qunfudah, Qunfutha, Kunfuda, Gonfodah or Gonfothah. I was helped out on the naming of this city recently - my thanks to @AmboceptorBlog

@MackayIM Arabic only has 3 vowels- usually translated A/I/U (each has short&long forms) This also depends on dialect. Short U -> O in Egypt
� Amboceptor (@AmboceptorBlog) May 22, 2014

Sources...

Medical News Blog

Medical News Blog Information

Snapdate MERS-CoV chart update

The MERS week in snapshots...

MERS-CoV in the Netherlands...a detail analysis of cases

First Aid Response Training in Mbarara, Uganda

Updated MERS-CoV full genome tree...

Updated MERS map moves stars around....

MERS-CoV did not just transmit via 2 meetings and a handshake...the retraction [UPDATED with CDC Press Release]

Iran reports 2 MERS-CoV cases: 20th country [UPDATED]

Camels and MERS: links to peer-reviewed scientific literature...[UPDATE #1]

Camels and MERS: links to peer-reviewed scientific literature...[UPDATE #2]

Jeddah changed the MERS-CoV age:sex landscape...

MERS-CoV cluster in Al Qunfudhah...

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