A model of MERS-CoV acquisition (ver1)

With thanks to David Spalten (@dspalten) for discussion and considerations and AtRG for advice.

First we heard about Middle East respiratory syndrome coronavirus (MERS-CoV)-related viruses in bats in South Africa, then we read of antibodies in camels that reacted to MERS-CoV more than the most likely (known) other CoV to infect cattle, and most recently we were absorbed by the discovery of a probable parental strain of the MERS-CoV in the faeces of a Taphozous perforatus insectivorous bats.

We've also heard that most patients have not had direct or obvious contact with bats and we also know that pasteurised camel milk products should be safe. But that still leaves many stones unturned.

So if we can assume that the most likely route of acquisition of MERS-CoV is through the upper respiratory tract and that the spillover events come from animals (I'm including human-to-human exposures in this figure) then we need to consider how that might happen. I've included the animals above as well as baboons as they seem highly mobile, interact well with humans, visit mountains and caves (where bats are likely to hang out") and are found in the KSA. I've added ingestion but I don't really imagine how this could result in a respiratory infection, and MERS-CoV gastrointestinal involvement seems infrequent.

I don't live in the Kingdom of Saudi Arabia or in the Middle East and I do not profess to know much of the environment so what follows is "remote guestimation" at best. But I've thrown together some of the possible routes and animal players into a figure which may have some degree of reality buried in there somewhere. It may also spark an idea or two among those who do know what they're talking about.

So, here is my model of how humans may indirectly get a zoonotic infection from a primary or secondary animal host...

A model of MERS-CoV acquisition. Click to enlarge.

I'd be most happy to take suggestions for improvement of the figure. I know some of you like to use the graphics from the blog and Virology Down Under (which I strongly support, asking only for a specific reference to their source) so if they can be made more robust, I am very happy to do so. Get to me via the comment section below or on Twitter (see top right).

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Bats are the host to a lot of viruses but do we know much about that?

In an article in Science today, Kai Kupferschmidt reminds us that while the chiropterans (bats belong to the Order Chiroptera which comprise >1,200 species) are a fascinating bunch. As you might expect from animals that make up a fifth of all mammals and reside on all continents except Antarctica  they harbour a lot of viruses and yet we still know very little about how the flying fuzzballs interact with their own virome.

Bats have been found to harbour or were the likely source of a virus that became what we know as:

• Nipah virus 
• Hendra virus
• Rabies virus
• Australian bat lyssavirus
• Severe acute respiratory syndrome coronavirus (SARS-CoV)
• Numerous other bat CoVs
• Ebola virus
• Marburg virus
• Kasokero virus
• Duvengae virus
• Menangle virus
• Middle East respiratory syndrome virus

Intermediate hosts play a big role when these infections get to humans, mostly because we don't really have bats on our list of cute and cuddly animals with which we spend a lot of close contact time. 

Bats also live for decades, probably first emerged 50-million years in the past, may have a primitive immune system and seem to have an ability to host viruses without getting ill. This may have to do with a reduced repertoire of foreign (in this case, viral) gene-sensing molecules. In humans, these sentinel are always on or in cells, keeping a "non-specifically specific" lookout for bits and features of DNA or RNA. When found the sentinels act to scale up the body's immune response to the virus. But for bats, little of this process is really known because bats are a difficult animal to study. There are some bat cell lines that have been successfully used to examine bat immune responses in labs, but nothing beats observing and understanding the viral life cycle in its natural host.

Even very basic knowledge is lacking. Viruses have been isolated from bat urine successfully, and detected using sensitive PCR-based techniques (which don't prove an infectious virus is present) from bat urine and faeces etc, but do we know if bat faeces is infectious and if so, for how long? That knowledge may solve some riddles about transmission cycles for bat viruses. When I recently asked Prof Linfa Wang about this, he was pretty clear on what we don�t know:

�This is a tough question to answer. I don't think anybody has done any "hard science" on this and the answer will vary with viruses anyway.�

As humans move into or remove bat territories, we may be increasing our contacts with them by forcing them to move into areas shared with us. We may be forced to learn more about bats in the future; perhaps now would be a good time to fill in some of our knowledge gaps to make that learning curve a little less steep.

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

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

In a strong piece by Maryn McKenna on Wired a bit over a week ago, she posited that "Censorship Doesn�t Just Stifle Speech � It Can Spread Disease".

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

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

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

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

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

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

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

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

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

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

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New WHO update on MERS cases

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

Click to enlarge.

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

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

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

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

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

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MERS-CoV case numbers: WHO knows???

With the WHO's latest update we see that body's official MERS-CoV case count rise to 102 cases and 49 deaths. Its clear that even WHO is suffering from a lack of information - most cases listed here have no sex, date of onset of illness, hospitalisation or date of death. And its clearly not their role to dig into the minutiae of why the Saudi Arabian Ministry of Health reports deaths among previously reported cases....that clearly have not been previously reported

My count  with details available sits at 105 cases and 48 deaths. FluTrackers, who spend a lot of time sorting through  up-to-the-minute numbers, tweeted this morning that the case count was 106 and deaths were at 49. There is also a good comparison of the variability in a post by Pathfinder, a Senior Moderator, which really highlights how everyone has their own number. Some have new datasets that include probable cases - that's a very slippery slope, open to far too much interpretation and the potential for confusion. I favour the FluTrackers method of leaving a case list as a list of cases....anything else can be described and discussed separately.

And let's not even get into where we say a case is geographically based - do we do that based on whether it was detected there or acquired there (my prefence)?

There clearly is a need to consolidate case reporting and streamline the definition of case locations. Perhaps WHO could take a lead on proposing something here? 

Realistically it wouldn't change things too much. Since the internet provides the data for home-brew epidemiology (like my own MERS and H7N9 data!), its not surprising that we end up with this spectrum of figures.

While it might take longer to report on the cases, I think the WHO numbers are probably what we fall back on for reliability. These are people in direct contact with the sites of infections and reporting. For speed (and great accuracy as well!), FluTrackers cannot be beat.

In terms of MERS at least, at the end of the day we know it is not spreading with pandemic-level efficiency, we have a good idea of how to stymie its spread in healthcare settings, research is ongoing to find the host and then work out how humans get infected. We have only just crossed the line of 100 cases, worldwide. Not knowing about the dates and ages of a small number of MERS-CoV cases doesn't really impact on public health decisions, so long as the data are added to the total before a reasonable period of time has passed. Days not weeks lets say.

It's worth keeping everything in context when there are much larger and more devastating outbreaks of infection and disease happening elsewhere in the world. Polio and cholera are examples well covered by crofsblogs for example. 

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Two new MERS-CoV cases including new death

1st source for this post: FluTrackers (FT)

FT has found that the Arabic language version of the Kingdom of Saudi Arabia (KSA) Ministry of Health (MOH) website has added a new MERS-CoV case; that of a 55-year old with underlying disease (kidney failure) who is currently in an intensive care unit in Medina (along the western edge of KSA).

Sadly a 2nd notification is that of a confirmed MERS-CoV case who died of respiratory failure after pneumonia; a 38-year old from Batin (Hafar Al-Batin? - if so, in the north of KSA, near the border with Kuwait).

Sex for both cases is unknown. Update not yet on MOH English language site.

This brings the total to 105 (including a mysterious case that FT is still following . 49 cases have died. The proportion of fatal cases (PFC) now stands at 46.7%

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