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Maths says MERS-CoV still doesn't have pandemic potential

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Breban and colleagues note in the Lancet that even with their most optimistic number crunching, there is only a low risk that that the coronavirus causing MERS could jump from an infected case to a naive person. Certainly not enough to pose a serious possibility of pandemic spread at this stage, based on what we know of the virus now and the case numbers and details we have to work with. The basic reproduction number (R0), or number of secondary cases (see the orange circles below), is still calculated to be less than 1. When >1, we consider epidemic potential reached.

Apparently that is despite clusters that may sometimes suggest otherwise.

Keeping in mind that a pandemic is largely about numbers - how many secondary infections occur  in close or other contacts - and how far and fast that transmission chain continues (the yellow circles and beyond).  
For me, this really reinforces just how important it is to have a full picture of a virus's transmission pathway. Not just the severe cases that show up in hospital, not just their contacts but also mild and asymptomatic cases in the community and the rest of the hospital. Prospective screening without regard to signs and symptoms in fact. 

Each and every person positive for the virus may represent a link in the transmission chain. 

You address whether mild cases can spread virus in another study. Oh, and we should probably keep monitoring all the viral strains we detect for genetic changes that occur in parallel with family clusters or upticks in transmission - which might signal increased potential to spread.

Don't test, don't find. Know nothing.
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MERS-CoVs: South African bats vs Saudi Arabian bats

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The latest sign of MERS-CoV in an animal, the Taphozous perforatus bat, is based on a 181 basepair (bp) fragment amplified from the viral RNA collected from a bat's droppings. 

The sequence is not yet available on the public sequence database, GenBank, and I haven't asked Prof Lipkin et al. for it. In the meantime though, I've aligned the primers mentioned in the new Emerging Infectious Diseases article by Memish and et al., against a full genome of MERS-CoV (EMC, the Munich strain). Sorry the image doesn't come out perfectly-if you click on it it will expand to the size of your browser.

Click then expand browser for full size. The expected position of the Memish et al. Taphozous perforatus bat MERS-CoV sequence is shown as a grey box. Primer locations for the nested RT-PCR are shown as red (outer primers) and orange (inner primers; the sequence region depicted in the phylogenetic tree in the recent EID paper) boxes. The recent South African bat CoV relative of MERS-CoV is show in pink (not overlapping) and the same region of full length CoV genomes are shown in blue (MERS-CoV EMC Munich) and green (HKU5 bat CoV)

For fun (yeah, I should get out more) I wanted to see just how close the "Close Relative of Human Middle East Respiratory Syndrome Coronavirus in Bat, South Africa" was, as described from another recent EID paper, to the new bat CoV. '

Unfortunately, as you can see above, the two fragments don't overlap. So my fun is ruined! 
We do know from yesterdays article however, that the 181bp fragment was 100% identical to human MERS-CoV over this short span (about 0.6% of the length of the entire MERS-CoV EMC genome). 

As Prof Andrew Rambaut noted to Helen Branswell in the Vancouver Sun, we need a whole genome to get more information that will better place the T. perforatus into the clade of viruses that seem related to MERS-CoV.
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MERS-CoV updated graphs...

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With all the movement in case numbers after a 3-week hiatus, I thought it worth checking what the charts look like.

This is graph (above), is based on dates of onset combined with dates of reporting to fill data gaps. We can see the Proportion of Fatal Cases (PFC) has settled. There are some data gaps that prevent this from being an ideal graph - this is why dates of reporting were also used to give a better, but general, idea of the status of case and death changes: 44/102 (or 103) are missing. Also, details for 3 deaths, 7 ages and the sex of 5 patients are not available (or I have not found them at least!).

In this chart (right) we can see the Kingdom of Saudi Arabia has most cases 0 the proportion has remained about the same as it was for my last update July 9th - around 80%.


Below, we see the regional accumulation of cases. I may need to research what exactly has been imported and what acquire locally in Qatar - or change the numbering to reflect country "dealing with"the case to make things simpler. But you get the gist. KSA continues its steep growth of MERS-CoV case numbers.



I'll update my main MERS-CoV page with these soon.
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MERS-CoV case tally bursts through 100...

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1st Source I saw: FluTrackers
FluTrackers has noted that the Kingdom of Saudi Arabia Ministry of Heath site has another batch of cases and a death among people infected with Middle East respiratory syndrome coronavirus (MERS-CoV).

Currently the case tally is at 103 with 48 deaths; the proportion of fatal cases is 46.6%


  • 31, Male, underlying conditions, in an intensive care unit, stable, Asir region
  • 55, Male, underlying conditions, contact of another case, asymptomatic
  • 51, died, Riyadh
FluTrackers MERS case list also notes a discrepancy in the KSA tally which suggests another case is positive - but no details whatsoever exist for that. I've added it to the tally for now.

Do we have a MERS-CoV outbreak in Riyadh? Most of the cases in the past 3 days have come from this region.

There is also noise of a case in a Jordanian hospital - I will be updating this post as these data coalesce and we get some more info on the cases.
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Two new MERS-CoV cases and the death of an existing case, all from Riyadh

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FluTrackers reports on two new MERS-CoV cases and the death of a previously infected person.

The Kingdom of Saudi Arabia's English and Arabic Ministry of Health (MOH) notes a 50-year old male (50M) and a 70-year old female (70F), both with underlying diseases and without dates of illness onset or hospitalisation. Both are in an intensive care unit.

On the Arabic-language site only, is the announcement of the death of a 54-year old "citizen". No sex or date of illness onset or hospitalisation or anything else that gives a clue as to who this may be. I have no 54-year old people on my list. 

There is still no English-language MOH version of the announcement of the previous 2 MES-CoV cases (50M and 59M) 2-days ago. The last English update, prior to the cases tonight, was August 1st.

A very piecemeal way of disclosing public health information. I can't imagine this gives many prospective visitors a good sense of the situation being under control and carefully managed.
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Most hajj pilgrims are elderly...

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...this is according to a story in today's Arab News, chair of the national establishment of pilgrims fro Arab countries was quoted:

We noticed, however, that most of the pilgrims who arrive from these countries are elderly

This follows on from yesterday's post about Russian pilgrims whose numbers have been limited by request, using a ballot system. 

Whether they were also restricted by age according to the "rules" is less clear.

It is also worth noting that many pilgrims plan far ahead and spend considerable time saving for the costs of the journey to Saudi Arabia for their hajj pilgrimage. It is perhaps not surprising that many are older people.
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Taphozous perforatus - The Egyptian Tomb Bat

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File:Egyptian Tomb Bat area.png
Rage of Taphozous perforatus.
Image from the IUCN Red List, via Wikipedia

This furry little fella '(~10cm long, 6cm forearm, 34cm wingspan and weighing in at 28g) occurs  throughout northern and sub-Saharan Africa, the Arabian peninsula and Asia, east to India. 

It's name, "tomb bat" comes from the genus name Taphozous which is derived from the Greek word for tomb/grave (Taphos). Also, males don't have beards like T. hildegardeae males do...apparently...just in case you meet one in a dark alley.

It is an insectivorous bat (moths and beetles) found in small colonies that avoid forest and preferring open woodland along rivers and wooded savanna. It roosts under rocks (e.g. sea caverns, deep caverns, old wells, tunnels,) or in buildings (e.g. old disused structures, castles, forts,mosques) during the day.

This bat is a member of the Order Chiropetera, Family Emballonuridae, Genus Taphozous, Species T.perforatus.

Specific countries where the bat has been found include: Benin, Botswana, Burkina Faso, The Democratic Republic of the Congo, Djibouti, Egypt, Ethiopia, Gambia, Ghana, Guinea-Bissau, India, Iran, Israel, Kenya, Mali, Mauritania, Niger, Nigeria, Oman, Pakistan, Saudi Arabia, Senegal, Somalia, Sudan, Tanzania, Togo, Uganda, Yemen, Zimbabwe

This bat is a threatened species.

Some more information, and the references:
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MERS-CoV genetic sequences found in Taphozous perforatus bat

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Profs Ziad Memish and Ian Lipkin, and a team of collaborators including researchers from the EcoHelath Alliance, have published, in Emerging Infectious Diseases, their discovery of viral sequences in the faecal pellet of an Egyptian tomb bat.
Taphozous perforatus bat
Photo courtesy of Dr Jonathan H. Epstein.

MERS-CoV was only found in 1 of 29 Taphozous perforatus (Egyptian tomb bat, see some more detail on these in my next post) animals. These and 67 other bats captured in mist nets for this study, were observed nesting in abandoned ruins.

Samples from Bisha, Unaizah and Riyadh (Kingdom of Saudi Arabia) were snap-frozen on site, collected during October 2012 and April 2013. The October shipment was opened and thawed by US customs. Samples included wing biopsy, blood, throat swab, rectal swab and faecal pellets were collected for testing. Apart from RNA virus testing  bats were speciated by DNA analysis (cytochrome B gene). The T. perforatus bat identity could not be confirmed genetically because there was no reference sequence on GenBank - but it was similar to another member of the genus.

Helicase, RNA-dependent RNA polymerase (RdRp) and nucleocapsid or envelope regions were targeted for amplification and sequencing. 227/1003  samples (22.6%) were positive for an alpha or beta-CoV. 

The find, represented by a phylogenetic tree using on a 181nt RNA sequence fragment from the RNA-dependent RNA polymerase gene (100% identical to a sequence from the index case in Bisha, betaCoV 2c EMC/2012 over this region), secures bats as the/a primary animal source. So long as there was no contamination at customs or that the sequence actually came from a food source. Not too likely for either of those. 

Obviously more work will need to be done to find more instances, complete the genome (or at least sequence larger genetic fragments to make everyone happy) and isolate infectious virus - but this finding is a significant step in confirming a starting point for understanding how humans get infected by the MERS-CoV.

It's a shame this new fragment of the RdRp does not overlap with that sequence from the recent South African "nearest match" to MERS-CoV. In adjacent regions of the RdRp though, the South African virus does seems more genetically distant than this T. perforatus find.
 Perhaps we can re-visit the transmission chain issue with a view to how bats might infect a (probable) secondary host - say the camel for now - I'd suggest that palm trees might have a role in this as well as a possible role in direct human infections if sap/dates/drinks were consumed by the most at risk groups; elderly men with underlying conditions. Perhaps this consumption even has a role in them developing a chronic kidney-related disease? I previously wrote a little about this 19th June and on risk in a post 28th July.


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2nd French MERS-CoV patient still in serious condition

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1st sources: @makoto_au_japon & @HelenBranswell

Nord Pas-de-Calais reports that the patient remains in intensive care in serious condition. He is not in isolation as he is MERS-CoV free.

The 51-year-old male (51M) patient was locally infected, showing signs on May 8th 2013. He was believed to have been infected after sharing a 20m2 room and single bathroom, with the MERS-CoV index case, 64M from the United Arab Emirates. 

51M was admitted to hospital in Lille May 9th. He has been there for 104 days or 3-months and 12 days.

The index case died May 28th.
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16,000 Russian hajj pilgrims September 6 - October 9

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1st source: @makoto_au_japon

Russia and India Report also notes that..

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

According to my list and among those with details available:

  • 53% of MERS-CoV cases and 65% of deaths are older than 55-years
  • 74% of cases and 57% of deaths are 65-years or younger
  • 2 cases and 1 death are under 12-years of age
I'd say the rules miss a large proportion of the populations most at risk of poor clinical outcomes.
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New MERS-CoV case, likely imported, reported in Qatar

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1st source: @makoto_au_japon

France 24 reported a case of MERS-CoV in a 59-year-old (59M) Qatari man. He is currently stable.

He is reported by the Qatari Supreme Council of Health (SCH) as having arrived from "another country" and of having symptoms while abroad, so this is then an imported case leaving Qatar's local acquisitions at 2, by my count.

This brings the tally to 97 cases with 46 deaths and the proportion of fatal cases (PFC) drops to 47.4%.
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Taihu lake & influenza viruses Part II: people, pigs, poultry and migratory birds

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Source of H5N1/H7N9 spatial overlap figure: Many thanks to Dr Ricardo J. Soares Magalhaes, The Univeristy of Queensland.

The figure below, from the Letter I talked about yesterday, published by Wang and colleagues in Emerging Infectious Diseases, Vol 19(11) shows the Lake Tai region.

To clarify, the paper talked about an area of high risk of infection. It did not specify whether the risk was due to exposure to poultry or wild birds. The issue of visiting LBMs and exposure to poultry and their excrement was secondary to the finding of overlapping regions of human cases and proposed region of greater risk.

Having said that, it appears (and these are all web sources so take them with a grain of chicken salt) that a domestic breed of pig and poultry may be farmed around this lake, one of China's largest fresh water bodies containing dozens of islands. Water quality and its levels algae and contaminating animal and human waster have also been issue for the lake, which supplies drinking water to approximately 30-million people in cities within Jiangsu and Zhejiang provinces. 

Expansion of poultry farm seems to have been stopped, if not contracted, and better management of aquaculture and livestock and poultry wastes has been recommended.

However, wild waterfowl as well as duck and goose farms seem to remain around the lake according to at China Travel and the maps at the bottom of this post. There seem to be monkeys and caves (bats?) too and as you would expect, this is also a thoroughfare and winter stopover for wild birds. It's also about 380km north-east of Poyang lake, another important wintering ground for wild waterbirds and one that is known to harbour influenza viruses.
  • A study by Duan and colleagues  of >11,500 cloacal swabs from migratory ducks and >36,400 swabs from sentinel ducks identified 90 and 1,681 influenza isolates, respectively during 2002-2007. he sentinel duck seasonal influenza peak overlapped with the migratory duck over-wintering period. Major haemagglutinin (HA) types included H3, H4, H6 and H10. H5N1 was detected during 2005. H7 was also found. The major neuraminidase (NA) type was N6. N9 was not identified. These combined to form 27 HA/NA antigenic combinations.



You can see the overlap between areas of human infections with influenza A(H7N9) virus (green circles; area bounded in blue and green) and H5N1 (red triangles; area bounded in pink).

Below, I have excerpted 2 maps from William Wint and Timothy Robinson's document, Gridded Livestock of the World 2007 written for the Food and Agriculture Organization (FAO) of the United Nations1. They show using livestock data modelling (which is described in the full document) that there were certainly lots of pigs and poultry in that region in 2007. 

So, the 3-Ps are in place: People, Pigs, Poultry probably kept freshly supplied with out-of-town influenza by migratory birds. 




  1. FAO. 2007. Gridded livestock of the world 2007, by G.R.W. Wint and T.P. Robinson. Rome, pp 131.
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H7N9 and H5N1 may have emerged from birds around Taihu Lake

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Wang and colleagues from the Institute of Disease Control and Prevention of People�s Liberation Army, Beijing, China and from The University of Queensland, Australia writing in Emerging Infectious Diseases, note that most (71%) people in China infected with influenza A(H5N1) virus (spanning from 14/10/2004-17/05/2013) had direct contact with poultry or their excrement. That contact includes work-related handling of live and dead birds and their urine and faeces.
However, most of those infected by influenza A(H7N9) virus had indirect exposure to live birds, mainly through visiting live bird markets (LBMs).

Also of interest, most H7N9 cases were more closely clustered  compared to the more widely spread H5N1 cases.

The authors were looking for an overlap between the earliest known cases of infection of both viruses - perhaps to find a common source of the emergence of these zoonoses - and their studies suggested Taihu (Tai Lake) Lake which is near Anhui province and Shanghai municipality and borders Jiangsu and Zhejiang provinces. All place names that were foci of a lot of H7N9 activity earlier in the year.

The authors conclude that this region may be a key hotspot for spillover of avian influenza to humans. This would be a useful place to add to the emerging influenzavirus watch list and bird sampling/genotyping list. They also reaffirmed the role of LBM visits were another key risk factor for acquiring H7N9.
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Nearly half the Indonesians performing Hajj may be over 60-years of age

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

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

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

Globally mobile at-risk population + site of most infections + little knowledge of basic levels of virus source/community load at that site = less than ideal situation.
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MERS-CoV: 2 new severe disease cases in Riyadh

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Last night, Mike Coston's Avian Flu Diary revealed a notice of two new MERS cases in Riyadh. These were reported on the Arabic-language version of the Kingdom of Saudi Arabia's Ministry of Health website.
  • 50-year male in an intensive care unit (ICU)with pre-existing underlying disease
  • 59-year old ?suffering pre-existing underlying diseases and continues (how long has this case been ill) to receive care in ICU
At the time of this post, 12-hours after Mike's reveal, there is still no mention of this on the WHO site, no obvious sign of Arab News and still no sign on the KSA MOH English language version.

Total cases now at 96 with 46 deaths and the proportion of fatal cases (PFC) at 47.9%.

This resets the clock on "time since last MERS-CoV case announcement", which has nearly reached 3-weeks. Crof has a couple of great rants on this here and here.

The post itself carries the usual level of detail - lots of exposition with limited epidemiology. Its clear once again that the cases being detected most often are those that shout "servee disease". We still lack prospective laboratory (yes, that's underlined, italicised and in bold, and here's an exclamation mark...!) screening data to identify whether the virus is circulating more widely.


Took a while to post this due to a strange error in Blogger overnight: bX-pdmn3h and bX-kp6fkh for those interested. Seems to have been resolved today.
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Understanding phylogeny....how virus sequence relate to each other through time

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Over at Edinburgh University, there is an awesome Molecular evolution, phylogeneticis and epidemiology's website. 

On it's "epidemic" blog, run by Prof. Andrew Rambaut, there is a fantastic new primer on how to read a phylogenetic tree.

I highly recommend this for all levels of skill. It provides a great and colourful background to what a phylogenetic tree does, and does not, convey. 

Of particular interest, an example includes bat and camel virus sequences. Also relevant to interpreting future MERS-CoV trees as part of the infection source/animal host debate.

These trees were drawn in FigTree (Mac and Windows versions avail,able) and polished using Adobe Illustrator.
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H7N9 vaccine update...[UPDATED]

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Hat tip to Dr. Nicholas Kelly for JAMA link reminder.

Earlier in the month, Zou Yong, quality directer of China based Sinovac Biotech Ltd  the Chinese Center for Disease Control and Prevention, noted that preliminary work on an adjuvanted (see bwlow) H7N9 vaccines was complete and are ready for safety  stability and clinical trials. It has already completed been through animal testing and the vaccine seems to work in our furry little friends.

In July, Novavax commenced Phase I clinical trials in adults of its adjuvanted virus-like particle (VLP) H7N9 vaccine. This trial assesses vaccine safety and immunogenicity (ability to make the recipient mount a useful immune response to the virus - A/Anhui/1/2013 (H7N9))

Helen Branswell (listed as one of Wired's best sources of infectious diseases info), writing at the Vancouver Sun, notes that 4 companies, have or will be conducting trials on H7N9 vaccines - all up costing the guy footing the bill, the US government, $1oo-million. Sanofi Pasteur, Novartis and MedImmune (using live, weakened ["attentuated"] H7N9 virus) also have products in near clicnial trial stages while GSK, CSL, Protein Sciences and Vaccinate are catching up.

As I've written before, H7N9 is a stealth virus in humans as well as chickens. In the latter instance - stealth refers to producing little disease in chickens while in the former, stealthiness is to do with problems in creating a vaccine based on H7N9 that will trigger a suitably effective immune response to what is a relatively weak trigger of human immunity.

But Branswell notes, there remains the need to define the best adjuvant (a vaccine additive "booster" that allows the manufacturer to use the minimum amount of antigen [the virus bit] while still obtaining the best immune reaction to it) however Sinovac has shown that with one, the vaccine works better than was previously expected. Its not unexpected that avian influenza viruses to need help to trigger a good immune response for a human host according to Dr. John Treanor's comments in the article.

The impact of using an adjuvant is known as "antigen sparing". The makers would like to spread the viral antigen out as far as possible to make the greatest number of doses from what they have, as quickly as possible so adjuvants are very important...and a science unto themselves.

So, a lot of work for H7N9. As Osterholm, Ballering and Kelley wrote back in May, for any pandemic vaccine to be of benefit, development time needs to be small while production scale and distribution capacity need to be big. And don't forget, the companies with the big vaccine production capacity still make our seasonal influenza vaccines too - and its no mean feat to switch off production of one product and switch on another. New vaccine technologies are required, and are being developed. Once a vaccine platform has had a successful clicnial trail path, it should be easier to leverage that as the basis for similar vaccines protecting from different viruses/viral strains, in the future.

For influenza A(H1N1)pdm09 virus, a vaccine arrived nearly 2-months after the season wave of infections had crested. Thankfully  H7N9 has not managed the adaptations required for rapid and efficient human-to-human spread.

While a licensed, killed influenza A(H5N1) virus vaccine was prepared some time back, I'm not sure about their current capacity to scale up (shelf lives being what they are)  if H5N1 is the influenza to jump to pandemic status rather than H7N9. If either do.
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