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The book of MERS has several chapters yet to write

Epidemic is a big word, and while it generally means "a rise in the number of cases above what you'd expect", you can see from the definitions below that there are many ways to spin the meaning. For the public at large, it generally means "bad scary stuff" and so it's important that we use this word sparingly.

An epidemic is defined by Oxford Dictionaries as:


a widespread occurrence of an infectious disease in a community at a particular time

..or more applicably..



a sudden, widespread occurrence of an undesirable phenomenon

...from Merriam Webster online...


affecting or tending to affect a disproportionately large number of individuals within a population, community, or region at the same time

...from Wikipedia...


In epidemiology, an epidemic (from ep? (epi), meaning "upon or above" and d?�?? (demos), meaning "people") occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience.

The Middle East respiratory syndrome (MERS) was so-named back in May 2013, and prior to March 2012, there had been no known cases of the coronavirus (CoV) named for the disease it was associated with.

Yesterday we saw a detailed publication by Cauchemez and colleagues in the Lancet Infectious Diseases (LID). Accompanying that was an excellent piece in the Canadian press written by Helen Branswell which included some comments from the authors.

Click to enlarge. 
Accumulation of MERS-CoV lab detections by week (blue
mountain, 
left y-axis) and the accumulating deaths
(red line, left y-axis). The proportion of fatal cases is slowly
declining as fewer cases have died recently (ratio; black line,
right y-axis). No data exist for ~3 or so deaths and I include
the unconfirmed 2nd case in Kuwait for now.

Feel free to use, just cite me and here.

The key phrase slowly-growing epidemic, used by both, has been not-so-slowly appearing everywhere since then. Does that phrase accurately represent MERS to the world?

Yes, it does. If you have a look at the chart above, its been a steady increase ("blue mountain"), but despite the apparent steep slope of new cases, the steepest part of the mountain, extracted and plotted below, is in fact very linear. A steady but slow growth in cases. No exponential take off. No major deviations. So yes, there is an epidemic. And yes, it is slow. 156 (157 if 2nd Kuwaiti instance is confirmed) cases over 87 weeks in a country of 20,000,000+; a country that just hosted the biggest human gathering of the year (the Hajj) and a country which provides a launch point for around 18,000,000 travelers and a destination for almost as many



Click to enlarge.
A slowly growing outbreak of an emerging  coronavirus.
Cases have been accumulating worldwide but at a
linear rate since the week beginning April 7th.
Why the spike from this week? I'm not sure.
Feel free to use, just cite me and here.
But I think we need to be careful when throwing around the "E" word. An outbreak of an emerging virus may still be the best term to describe this chapter in the book of MERS. When someone asks on Twitter "to panic or not to panic"? (this was in reference to the latest MERS-map I posted) then I wonder if the correct message is being conveyed.
Another central message of the new LID paper was a no-brainer; well it was to me but perhaps I'm just too close to it all - in which case take this with a grain of salt.


I thought it was as obvious as the hump on a camel that where 1 case of a respiratory virus infection was detected, others were there to be found. After all, a virus needs us to survive - no us (which means no us actually harbouring infections, acting as a living incubator) then no more cases of the virus). Perhaps that's not obvious at all. Perhaps there is a lack of general understanding that our pathology laboratory systems do not test everyone with illness for even the "standard" endemic human respiratory viruses; that only those presenting to the right place, with the appropriate signs and symptoms, get a sample collected and get tested. This is apparently also true for MERS-CoV-which is by no means a standard virus. Do you go to your doctor if you feel mildly crook? Of course not - you go to work. What if you just have a fleeting headache, a stiff neck, feel a bit hot? Still going to work? Still going shopping? Still packing the kids off to school? Of course you are because we have these all the time and we have an immune system that does a wonderful job keeping it all mostly under control. Life goes on.
But you may be positive for a virus and you are a key part of the transmission chain. You are an incubator. A host.


So if routine testing is not geared towards finding out this extra information how do we find out what's going on in those who are not presenting with kidney failure or pneumonia; a relative small sliver of the population? Someone has to run a research study in which you enrol or get permission from people who are not very ill and sample them. Then you know something new about how widely the virus you are interested in is spread, for how long a person sheds it (if you sample the same person a few times during a month) and even how many other people get it (because all of a sudden your "contacts" become those of a less ill person and the numbers go up and you capture more of a picture of what's happening). So where are the research studies doing this?

When the illness is just some fleeting thing its no real problem. Especially when it's due to a virus we know all about and don't track for public health reasons (we track influenza virus positives, but the reality is you have to be sick enough to be tested in order to add to that pool of data). 



Click to enlarge.
A very exaggerated example of how failing to test mildly ill or asymptomatic
cases of infection in the community may confound our ability to make a link
between cases of severe illness leaving knowledge gaps. These gaps prevent our ability
to track spread of the pathogen and thus interrupt spread of disease.
Feel free to use, just cite me and here.

But if that virus is not yet in a textbook, not yet understood, not yet weighed and measured against the viruses we are more familiar with, emerges from an unknown place, is not considered endemic and is often notifiable, then not knowing this basic stuff becomes a major hole in our knowledge and our ability to respond appropriately. This is where we (still) are, 87-weeks after the first known MERS-CoV positive. Guessing (however educated) at what's happening by extrapolation and modelling.

I guess not everyone knows that for every time there is a noticeably ill person infected with a "respiratory virus", it's fair to assume that there will be at least 1 or other who gave it to them, got it from them or got it from the one who gave it to them and who are not as sick or even considered sick at all. For MERS-CoV, they are missed and thus we have no idea how the virus is spreading. Just models. But we can make mathematically supported guesses to back up gut instinct, fair assumptions and logic.


The hallmark of, and big problem with, the MERS outbreak (an epidemic mostly for the Kingdom of Saudi Arabia [KSA]), is that testing has been LIMITED to those who have pneumonia, or another severe disease, and their close contacts. Back in August Memish noted that surveillance was focused on those with pneumonia which was again noted by a WHO representative yesterday.


Why, why oh why not test more people? Why?! Is it because "it's too costly to prospectively test people by RT-PCR unless they are (very) ill"? It might be for some nations, but the KSA is not one of those. 


If you don't test others then you see these modelling publications arise. Idle hands and all that. Yes, it is great to have a model to support what many of us think to be true. And as Fisman and Tuite note in their editorial accompanying the LID article..



..inferences based on the best available data, even if those data are imperfect, allow decision makers to follow optimum courses of action based on what is known at a given point in time.

The question is, can decision-makers sign off on any actions if they don't have actual data? If those data are not forthcoming, how can we ever test the validity of the MERS models?

For now at least, I think we can agree that there is just too little testing to know enough to write more than a few chapters of the MERS-CoV textbook. A book for which we do have a table of contents. Many viruses have emerged before this one and they have each taught us what pages to skip ahead to. Unfortunately, we seem to have a recalcitrant author for 1 or 2 chapters. 

OB/GYN MGH/MRRH Collaboration

I�m now almost at the end of my first trip to Mbarara Regional Referral Hospital. It�s been quite the whirlwind and time always flies so fast.  As I�ve gotten to know this hospital and in particular the obstetrics and gynecology department I have realized there is a trail of hospital equipment that tells the tale of visitors past and perhaps present.


On the antenatal ward for example I came across two digital fetal doppler machines. These are handheld, very portable and useful in finding and listening to fetal heart tones in utero. They are essentially a digital replacement of the pinard (fetal stethescope).






Digital Fetal Doppler

As handy as the digital dopplers are, their portability and attractiveness were their downfall when it came to their use on the antenatal ward. Concerned about their inherent, �walkability�, the donors/department created small metal cages, with no openings and attached to the metal IV to host the handheld devices. Unfortunately this has meant that the devices cannot be cleaned, or the batteries changed, so now the devices simply sit there, tugged along whenever the IV pole is in use, but unable to perform their ascribed function. Fixing this issue seems a simple undertaking, but perhaps it is a measure of their lack of desirability by local clinicians that the dopplers continue to sit there, literally gathering dust, and the pinard continues to be the preferred mode of auscultation. Indeed although it may seem like the digital device is an improvement, this very scenario prompts me to question if there is any evidence that demonstrates one is better than the other and if such evidence is relevant in the local setting.


This picture of forlorn and non functioning equipment is seen again and again all over the hospital. Most often, it is not a simple matter to fix the equipment � the expertise or the parts needed are simply not available. In the medicine department for example, there are several donated light boxes with a similar fate. Each is made up of a box, with a white screen and a light bulb to illuminate � technology that is seemingly simple and therefore easily transferrable from one setting to another. Unfortunately these boxes are manufactured with specialized light bulbs with unique sockets and shapes that are unavailable locally, rendering the light boxes unusable once they burn out. Another example is seen in the operating rooms where I noticed several electrocautery machines sitting quietly in corners. They are handy when available, but clearly not essential, and without any local expertise trained in fixing them and almost no hope of company technicians coming out to fix them,  more than likely they will go on sitting in the corner -too expensive to discard, and yet not essential enough to find a solution to.


This is not to say that such equipment is unnecessary or fated to be relegated to an iron cage. I also saw several examples of machines both donated and bought integrated successfully into clinical care.  Nonetheless, the trail of quietly forgotten equipment should remind us to be careful in what we wish for or even in some cases introduce as visitors. It�s very easy to think that x instrument or y machine would make such a difference and let�s do what we can to get it here. It might even work for 6 months or perhaps 1 or 2 years, and perhaps that is worth it, but often it appears that they don�t even make it that far and clinicians revert to their known and perhaps more reliable methods.


Perhaps a more exciting and more sustainable approach is that taken by new institutions like CAMtech. Its stated goal is to to improve and accelerate high-quality, affordable medical technology development for low- and middle-income countries (LMICs)�. CAMtech�s very first innovation lab is currently growing roots in Mbarara, Uganda.  I had the opportunity to see it in action when I went in search of their first engineer. 


Patrick Ssonko at CAMTech
I was lucky enough to meet Patrick Ssonko.  He recently graduated from engineering school and just this past summer was hired as the engineer in house at CAMTech.

Patrick's monitor in development
 I was very impressed and encouraged by his enthusiasm, creativity and zeal. During my visit, he demonstrated his self developed heart rate and temperature monitor and even let me test it out. The instrument is in its early phases but the potential is huge. He plans to build in a component that can relay the values to a separate screen and more importantly have the ability to send text message alerts to clinicians.


The potential for this kind of enterprise to positively impact clinical care in MRRH is huge. First of all if engineers like Patrick are connected to and collaborate with physicians and nurses working on the ground in Mbarara , devices created are much more likely to be directly applicable to the clinical setting within which they work. Home grown devices also likely mean cheaper components and more importantly that the replacement components and the local expertise on how to replace them are available.  

Adeline Boatin, MD MPH
OB/GYN Global Health Fellow


Camel cough, coronavirus caught? [UPDATED]

Are camels the main source of human infection
by the Middles East respiratory syndrome
coronavirus (MERS-CoV)?
I awoke to find the world has learned of a camel that tested positive using a Middle East respiratory syndrome coronavirus PCR. According to the Kingdom of Saudi Arabia's Ministry of Health announcement (on the Arabic language and not English language page), the camel was owned by by a recent case (43M from Jeddah, reported on 7th of Nov- FluTracker's #156) and was showing signs of disease. The fact that it was ill may suggest it was the source, but we don't yet know which illness came first, the camel or the man. We do know (from CIDRAP/WHO) that 43M became ill on Oct-27 and has been in hopsital since Nov-3.

This is in line with recent studies finding antibodies to a MERS-CoV-like virus. I've previously reported on that here and here.

The PCR positive has not yet been genotyped (had its DNA sequence determined, and by inference, any of its RNA genome - a way of measuring the similarity, or not, to known "human" MERS-CoV). That work is ongoing. Hopefully we won't have to wait until the entire genome is achieved as that can be a lengthy process.

For the record, if you are relying on Google translate, the Arabic for beauty (jamaal, ??????)  is derived from the Arabic word for camel - so read "beauty" as meaning camel (h/t Mike Coston).

I found it interesting that 43M was a healthy adult and yet he was ill enough to require intensive care. He wasn't old and had no underlying comorbidities. Does this hint towards his acquisition of MERS-CoV being from an animal source rather than a secondary human exposure? The latter often seems to result in milder disease or asymptomatic detection (mostly based on contacts of known cases). It's as if passage to another healthy human is via a smaller dose (reduced viral load after growth in 1st human?) or is the virus changed by growth in a human rendering it less capable of severe disease (perhaps seen as less "foreign" by our immune system?)?

A model of possible MERS-CoV acquisition. Is the camel the
central player or a secondary host?
The KSA Ministry of Agriculture is helping to try and grow the virus. MERS-CoV is certainly culturable - and with a positive camel at hand, getting fresh samples should yield results quickly.

Its great to hear about this in real time. No waiting on the publication process. 43M was only reported 5-days ago (my time; not sure when he became symptomatic of course). Well done KSA MOH!

We don't need to find every camel to be MERS-CoV-positive for them to be a likely source of infections. We know that cases have been sporadic and widespread and that genetically, a number of different introductions of MERS-CoV have occurred into the Arabian peninsula's human population.

Could this finding be used in a quick retrospective analysis? Among otherwise healthy MERS-CoV-positive humans, does evidence of contact with camels more often link to severe disease outcomes than if when there has definitely been no contact at all? The corollary then is that milder disease results when acquisition is via a human-to-human route among the otherwise healthy and tell us something more about the MERS-CoV? Keeping in mind a quote from Dr. House, M.D. "I don't ask why patients lie, I just assume they all do." Patients may not always want to own up to something, for whatever reason.


Some questions that remain from this finding:

  • Which diagnostic PCR was used? Presumably the well-validated version suggested by the WHO. We don't yet know if this assay cross reacts with any as-yet-unknown-but-very-closely-related CoVs such as one that may reside in camels. My bet is that it doesn't.
  • Is it MERS-CoV or a camel cousin to that virus?
  • Does this virus, MERS-CoV or very close relative, actually cause disease in camels? It's possible that 43M's ill camel was symptomatic due to another viral or bacterial infection.
  • Did the camel transmit to the human or did the human transmit the virus to the camel?
  • If acquired via camel-to-human (seems most likely), how did 43M acquire the infection from the camel? Airborne drops or aerosols, faecal-oral, scratch/broken skin, direct contact with secretions...?
  • Where did the camel get its infection from? Another camel (enzootic within the camel population?) or from a primary host or other secondary vector (bat, baboon...whatever?)
References for further reading
  1. PCR assay for MERS-CoV.
    http://newsmedicalnet.blogspot.com.au/2013/09/mers-cov-who-testing-guidelines.html
  2. KSA MOH report on camel MERS-CoV-assay. positive
    http://www.moh.gov.sa/CoronaNew/PressReleases/Pages/mediastatemenet-2013-11-11-001.aspx
  3. 43M report by KSA MOH.
    http://www.moh.gov.sa/en/CoronaNew/PressReleases/Pages/mediastatemenet-2013-11-07-001.aspx
  4. Helen Branswell's article.
    http://www.theprovince.com/health/Saudi+officials+find+camel+infected+with+MERS+owned+disease/9152077/story.html
  5. BBC health news article.
    http://www.bbc.co.uk/news/health-24901531
  6. MERS-CoV can grow in cell culture.
    http://newsmedicalnet.blogspot.com.au/2013/10/the-mers-receptor-story-to-date.html
  7. Mike Coston's Avian FluDiary Post.http://afludiary.blogspot.com.au/2013/11/ksa-mers-investigationtesting-beast-not.html
  8. MERS-CoV-like antibodies in Omani and Spanish camels.
    http://newsmedicalnet.blogspot.com.au/2013/08/camels-carry-signs-of-coronavirus.html
  9. Most MERS cases may not have met a camel.
    http://newsmedicalnet.blogspot.com.au/2013/09/most-mers-may-not-have-met-camel-but.html
  10. CIDRAP on camel case and WHO update.
    http://www.cidrap.umn.edu/news-perspective/2013/11/reports-mers-cov-found-saudi-patients-camel

Western Kenya - Maternal Ultrasound Screening Programs


This morning I landed in Kisumu, Kenya on a beautiful summer day. Kisumu is the third largest city in the country, located in Western Kenya on Lake Victoria. I traveled via tuk tuk (rickshaw) to the MGH guest house. The road was a little bumpy, as the major road to the airport was under construction. Sometimes the course of growth and development has bumps in the road, but the outcome is undoubtedly worth it.

 


After adjusting to the time difference, I woke up this morning ready for our first day in the field. Our research team embarked for Kaimosi to perform obstetric ultrasound screening. Kaimosi is a small town/village located 40 kilometers NNE of Kisumu. The drive through the Kenyan countryside was beautiful. The natural beauty helped distract me from the narrow, often unpaved roads that seemed quite treacherous at times.

 


Upon arrival, we met the hospital administrator who was very gracious. I had the opportunity to tour the hospital grounds and facilities. The resources were quite modest in terms of physical equipment and human resource availability. Additionally, one of the major challenges that the hospital faced was related to energy. The energy grid in the region was somewhat unpredictable. I learned that it was not uncommon for the hospital to go without power for 2 to 3 days at a time.

It was also clear that inpatient care within the hospital was a family endeavor.  Patient families were often present and assisting in caring for their loved ones. Family members would bring food, wash linens and clothes and attend to various needs that are customarily provided as part of inpatient care in the U.S.

As a radiology resident, I was specifically interested in the imaging equipment. While walking through the courtyard, I saw a radiographic film hanging on a clothesline. The film was still wet; the true origin of the term �wet read.�  In addition to plain film radiography, the hospital had a fluoroscopy unit which was used for barium studies.

Utilizing the portable ultrasound machine we brought, we were able to provide obstetric ultrasound screening examinations. The portability and durability of the ultrasound machine as an imaging tool in resource limited areas became quite evident.
 


 
 
 
 
Today, we went to Bungoma District hospital, which is 102 kilometers NNW Kisumu. There was a significant amount of activity in and around the hospital. Many patients walked to the hospital from long distances or took boda bodas (motorcycle taxis) to the hospital.
 After arrival to the hospital, we were greeted by the head nurse and the hospital administrator. They were gracious and gave us a tour of the facilities.  While touring the hospital, the various departments signs that posted the prices of various healthcare services ranging from basic services to surgical procedures. It was interesting to see the transparency related to the cost of healthcare which is in contrast to the U.S. healthcare delivery system where the actual cost of care is often unknown, even to healthcare providers. However, the costs of various procedures were often prohibitive for most individuals, given that that main economic activity is sustenance farming.
The obstetric wing was particularly active division focused on obstetrics. There were tens of women who were there for prenatal care.  I learned that the midwives and nurses play an integral role in delivery. Complicated or cesarean section deliveries are triaged to the obstetrician. Similarly, most women traditionally delivered at home with the assistance of midwives, but recent changes in Kenya health policy made it possible for any woman to deliver in a hospital if needed or desired.
The obstetric clinic was nearly overwhelmed by the volume of patients who were presenting for prenatal care. However, the staff was quite organized and integrated us well into their workflow to provide screening obstetric examinations. The patients and staff were appreciative of our contributions and we all appreciated the opportunity to add value to their healthcare.
 
 

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