MERS in the UAE...

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

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

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

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

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

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

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

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

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

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

References...

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

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MERS-CoV snapdate...

MERS-CoV detections by month and year

As can be seen from the graph below, the peaks of MERS-CoV detection have been driven by humans and their infection prevention and control issues - but what maintains the virus in between those lapses? 

It seems clear that MERS-CoV is entrenched among camels in the Middle East and Africa but how is it getting to humans, and how is it dong that in such small numbers over such a wide area? These have been questions for 148 weeks. 

It's a good thing this infection transmits so poorly between humans.

Click on image to enlarge.

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Are MERS cases in Saudi Arabia and the UAE linked to camel imports?

Special Guest writer: @influenza_bio

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

CC BY 2.0

Looking at the history of MERS coronavirus infections to date, many puzzling questions come to mind.

Evidence of MERS infection has been detected in dromedary camels from Spain to Egypt to the Arabian Peninsula. Why have we seen human cases arise only in a handful of countries in the Arabian Peninsula?

Why have nearly all MERS cases originated in Saudi Arabia (KSA)?

As of June 22, 2014, 718 cases are thought to have been contracted in KSA. The UAE, a distant second, has had 69 cases. Jordan has had 17; Qatar has had 9 (although 1 had a travel history to KSA), Kuwait 3, Oman 2 and Yemen 1. All of these countries have a lot of camels.

• Has KSA had more cases just because its population is larger? Have other countries had just as many cases, per capita?

No.

Figure 1. MERS cases per capita (2012 data)

• Is it just an accident that cases have appeared primarily in KSA, followed by the UAE?
  
  It could be.

• Is it an artifact of surveillance that most cases have appeared in KSA, followed by the UAE? Are KSA and the UAE just better at detecting MERS cases?
  
  This would seem unlikely. It's certainly possible that all countries with MERS have missed some to a lot of cases, especially milder ones, and that some countries are better at detecting MERS cases than others. However, the fact that all cases detected outside the Arabian Peninsula also follow the same general pattern of country of origin suggests that we probably have the big picture at least close to right.

• Have KSA and the UAE had more cases because they have more camels or more camels per person?
  No. First of all, these countries don't have the biggest domestic camel stocks in the region. Second, when you look at the number of MERS cases as a function of the size of domestic camel stocks (not including imported camels, which are typically slaughtered), there is no relationship.
  
  

  

  Figure 2. MERS cases as a function of the size of domestic camel stocks, not including imported camels (2012 FAO data[1])

  
  Alternatively, when you look at the number of MERS cases per capita as a function of the number of camels per capita (again, considering only domestic camel stocks, not imported camels), there is also no relationship. KSA and the UAE also do not have the greatest numbers of camels per person in the region.

Figure 3. MERS cases per capita (2012 data) as a function of the number of 
camels per capita (domestic camel stocks only; 2012 FAO data[1])

• Are there more camels with MERS in KSA and, to a lesser extent, the UAE?
  
  We have no idea, as there has been almost no camel surveillance. But hopefully new surveillance and studies underway in KSA and the UAE will help us to understand the situation in camels in these countries better.

• Is the large number of cases in KSA due only to nosocomial transmission (i.e., transmission in health care settings)?
  
  Not really, even though a very large proportion of its cases have been nosocomial. Many of the cases that KSA has had are from April and May 2014 and were in Jeddah, and the WHO has published an estimate that 75% of the cases arising in KSA in April-May 2014 may have resulted from nosocomial transmission.[2] Subsequently, the WHO wrote that, "Approximately one-third of these Jeddah cases are considered to be primary cases, although investigations are currently ongoing to determine whether these patients had contact with another confirmed case."[3] In other words, the WHO may end up revising the 75% nosocomial estimate upwards. Looking at graphs of MERS cases over time[4] suggests that cases may dip a bit in the winter and surge a bit in the spring, although MERS hasn't been around long enough in humans to know this for certain. Depending on the final WHO estimate for the rate of nosocomial transmission in April and May, anywhere from the "expected" number of zoonotic cases (i.e., the average monthly rate before April 2014) to almost double this number (if 75% of cases were nosocomial) may have appeared in April and May. However, even if it turns out that zoonotic cases have appeared in KSA at a more or less steady rate over time, this large amount of nosocomial transmission still wouldn't explain why most zoonotic cases are in KSA. Moreover, it would not seem likely that the effectiveness of infection control and prevention is vastly different across the Arabian Peninsula, and, in fact, there is evidence of nosocomial transmission in KSA, the UAE and Jordan, the countries with the most cases. However, it is puzzling that nosocomial transmission has seemed to peak in the spring of both 2013 and 2014 in many different settings; some environmental factor, analogous to winter for the flu, may be at work here.

• Are there environmental factors in KSA more conducive to infection with MERS, especially around April and May (when we have seen a large number of infections this year, and to a far lesser extent, last year)?
  
  As mentioned above, there may be something special about spring. It is also possible that something about KSA and the UAE are particularly conducive to human infection with MERS.

• Is anything else going on?
  
  There are probably many other factors at work that we don't know about. For one thing, we still do not know how MERS is transmitted to humans � whether it is transmitted by camel kisses, milk, urine or meat, among other possibilities, for instance. Once we know the routes of transmission and have some estimates of how much each route contributes to the numbers of infections, then we may have a better chance of teasing out even more differences across countries. Yet other factors may be at work, as well.

Is the number of MERS cases in a country related to the number of camels it imports?

At this point I would like to introduce a very speculative hypothesis: that the number of MERS cases in countries of the Arabian Peninsula is related to the number of camels that are imported into those countries. Significant oil wealth in some of these countries has fueled a greater demand for meat over time, and in particular, camel meat. Over recent years, this demand has been met by slaughtering primarily imported camels. 

• KSA and the UAE are the dominant importers in the region.
  
  KSA imports the most camels in the region, followed by the UAE. No other country in the region comes close.

Figure 4. Camel imports in 2011 (FAO data[5])

• Camel imports to KSA and the UAE have been increasing dramatically over the past few years, and the dominant sources of these imports are ports in the Horn of Africa.
  
  It is difficult to find hard numbers on the numbers of camels imported into KSA or the UAE broken down by country of origin. Also, the most recent FAO import data is from 2011. However, in the absence of access to recent export and import data from a variety of governments, a combination of FAO import data, FAO export data and news reports over the past few years paints a picture of vast and vastly increasing camel exports from northeastern Africa into primarily Saudi Arabia.
  
  First of all, it should be noted that, according to the FAO,[1] Somalia had 7,000,000 camels in 2012 and Ethiopia had 915,518, while KSA had 260,000. Sudan also had 4,571,000 camels.
  
  On November 25, 2013, the Financial Times reported in an article entitled, "Somali meat exports to Saudi Arabia soar,"[6] that, 

"Including goats, cattle and camels, total livestock exports from the civil war afflicted territories rose to 4.8m in what is the world�s largest on-the-hoof movement in the live animal trade. 

�There�s no single time that they ever exported such large numbers before,� says Ernest Njoroge, livestock expert at the EU's Somalia Unit. �If the ports in Berbera, Bosaso and Mogadishu become very, very efficient, then that will even increase.

�A lot of Ethiopian livestock is also coming through Berbera. It�s a very big market for us and it�s time for us to increase the capacity of Berbera port,� says Mr Yonis, who hopes planned investments will deliver a terminal dedicated to livestock for export to the Middle East."

A recent article by National Geographic[7] examines the huge and growing livestock trade from, in particular, Somaliland, and notes that, "While livestock�including cattle and camels�are exported year-round from Somaliland, the seasonal Hajj is the busiest time of year." A photo is shown of animals being herded onto a ship bound for Jeddah, KSA. Another photo shows animals in quarantine at the port of Berbera. During both quarantine and transport, animals are packed so closely together that it is hard not to imagine any diseases in the herds spreading like wildfire.

A news article[8] in March, 2011 discussed an announcement by KSA that the Kingdom planned "to increase livestock imports from the Horn of Africa two-fold by 2012," to close to 2 million heads of livestock, composed of sheep, goats, camels and cattle. Perhaps ironically, the article states that, "The decision to increase imports follows after Saudi Arabia's quarantine officials at the Port of Jeddah declared animals from the Horn were disease free, great in quality and strong demand in the local market." The article also notes that, "In October 2009, Saudi Arabia relaxed a eleven-year ban on Somaliland livestock and Somaliland animals have been steadily on high demand in the Saudi Kingdom ever since�. The main markets for livestock from Somaliland are Saudi Arabia, UAE, Oman and Yemen." FAO import data for 2000-2011, however, shows Yemen not importing any camels and Oman importing between 0 and 8,114 camels (which is very few camels).... Perhaps they don't import many camels.

Another news article,[9] in October, 2012, discusses the livestock export trade from Somaliland, and quotes a local official as saying, "Saudi Arabia sells barrels of oil to the world. We make our money selling livestock to Saudi Arabia." This article also mentions animals being shipped to Jeddah, KSA.

Camels from Somalia that are slaughtered for meat have typically been >5 years old.[11]

In addition to importing camels for meat, the UAE may also import some camels from Central Asia for milk production.[10]

Examining the relevant FAO camel import and export statistics for the Horn of Africa and the Arabian Peninsula, it becomes clear that most, and potentially nearly all, camels have been imported into the Arabian Peninsula from the Horn of Africa, meaning largely from Somalia, to an unknown extent from Ethiopia and to a lesser extent from Djibouti; that these imports have been primarily for slaughter, for meat; and that these imports have been increasing rapidly in recent years.

• The dominant port for animal imports into Saudi Arabia is Jeddah.
  
  "Jeddah Islamic Port is the largest port in the world of handling of livestock."[12]
  
  Jeddah is also the second largest city in KSA, but is it a coincidence that the largest number of MERS cases this year have been in Jeddah, just as camel imports have been surging over the past few years?

• Three camels imported into Egypt from Ethiopia and Sudan were found to be infected with MERS. MERS is in African camel populations.[13]
  
  One study examined 110 nasal swabs from apparently healthy camels, >6 years of age, in abattoirs in Egypt in June-December, 2013. Serum samples from 52 of these camels were also examined. Forty-eight of the serum samples were positive for MERS antibodies. However, when the nasal swabs were tested for the presence of the MERS virus, it was found that "The animals positive for either MERS-CoV or BCoV-like virus were all imported from Sudan or Ethiopia for slaughter." One of these virus samples was sequenced, and it was found that this virus was of a different lineage than the other MERS virus sequences known to date, from the Arabian Peninsula.
  
  Some amount of surveillance for human MERS cases is occurring in Sudan. The WHO has stated that, "health authorities are in active search for any suspected MERS-CoV cases by strengthening surveillance in the state general hospital, private clinics and hospitals."[14] I have seen no reports of surveillance in Ethiopia, Djibouti or Somalia; I hope that at least some exists.

• A fairly close relative of the MERS virus also circulates in bats, and a close bat relative to MERS CoV viruses isolated from humans has been found in South Africa.[15]
  
  A portion (816 nt) of the genome of a virus from a bat in South Africa was sequenced, and the protein version of this viral fragment was found to differ from human MERS by only 1 amino acid (0.3% difference). The protein versions of two other, shorter fragments of the genome differed by 10.9% and 14%. Other, related viruses have been found in bats from around the world; this virus, from South Africa, was found to be closer to human MERS than any other virus known at the time this work was published. The authors of this study wrote that the "relatedness [between human MERS and the South African bat fragment] was as close as that of SARS-CoV and the most closely related bat coronavirus known." They also write that their finding "enables speculations of an African origin for bat reservoir hosts of MERS-CoV ancestors."
  
  Subsequently, a short fragment (182 nt) of a virus was isolated from a bat in KSA, and that fragment had 100% identity with the corresponding fragment of human MERS.[16]
  
  Together, these findings suggest that MERS may have originated in bats in the Arabian Peninsula or Africa. Further sampling in bats in both regions, along with sequencing greater portions of viral genomes, as they become available, would help us to understand the evolution of this virus in bats.
  
  

• The number of MERS cases in each country may be related to the number of camels that are imported.
  The figure below shows that a potentially strong relationship may exist between the number of MERS cases in a country and the number of camels that that country imports. The more camels that are imported into a country, the more people that have been infected with the MERS virus. However, the numbers of data points are small; only KSA and the UAE stand clearly away from zero imports and zero cases. Thus, this graph is what I would call intriguing, but not completely convincing.

Figure 5. MERS cases as a function of number of camels imported (FAO 2011 data[5])

• The number of MERS cases per capita in each country may be related to the number of camels that are imported per capita.
  
  If we "normalize" the data examined above to the population size of each country, a relationship between the number of camels imported and the number of MERS cases still holds.

Figure 6. MERS cases per capita (2012 data) as a function of the number of camels imported (2011 FAO data[5]) per person

• The number of MERS cases in each country is not strongly related to the total number of camels (domestic stocks plus imported camels) in each country.
  If we compare the number of MERS cases in each country to the total number of camels that set hoof in that country in a given year (approximately), there is a possible suggestion of a relationship. Yemen is problematic, though, because it has more camels than any other country in the region but has had only one recorded human MERS case. Thus, there aren't more MERS infections in KSA and the UAE because they have the most camels in the region; they don't have the most camels. 
  
  

  

  Figure 7. MERS cases as a function of the total number of camels (domestic stocks [2012 FAO data] plus imported camels [2011 FAO data[5]])

• The number of MERS cases per capita in each country is not related to the total number of camels (domestic stocks plus imported camels) per capita in each country.
  
  The UAE does have the most camels per person in the region, but KSA is very far from having the most camels per person. Thus, there is no apparent relationship between the total number of camels setting hoof in a country per capita and the number of MERS cases per capita in that country.

Figure 8. MERS cases per capita (2012 data) as a function of the total number of 
camels (domestic stocks [2012 FAO data[1]] plus imported camels [2011 
FAO data[5]]) per capita

Taken together, this data supports the hypothesis that the number of human MERS cases in a country may be driven by the number of camels imported into that country, and perhaps that what matters is how many camels are imported from the Horn of Africa. Correlation is not causality, of course; this is only a hypothesis, not a fact.

In May, KSA stopped importing camels from Somalia, Ethiopia and Sudan.[17] So, I'm clearly not the first person to have had this idea. It's not clear whether camels currently being imported into KSA are being tested for MERS, though; one recent Arab News article[18] discusses how "all livestock" in KSA are now going to be tested for MERS, but it was not entirely clear to me whether imported camels would be tested. Subsequent echoes[19] of this news article, however, stated that, "Imported camels would also be tested for MERS and quarantined, Arab News reported him [the Agriculture Minister] as saying;" in reality, the Arab News article made no such direct statement. It would be nice to get total clarity on this issue.

The UAE, on the other hand, has not suspended any camel imports.[20] However, the UAE is now testing camels being imported from Saudi Arabia, Qatar, Oman, Kuwait and Bahrain.[21]

It should also be noted that MERS appears to circulate in domestic camel stocks in at least some countries in the Arabian Peninsula at at least some times; I am not by any means suggesting that MERS is likely to be only in imported camels.

For further information on animal husbandry practices for camels in northeastern Africa, see here.[22] For further information on the Livestock Trade in the Djibouti, Somali and Ethiopian Borderlands, see here.[23]

How can we know whether camel imports are actually a driving force behind human MERS infections?

This part is a little bit complicated. As a first step, it would be important to determine whether MERS is circulating in areas exporting camels to the Arabian Peninsula, and if so, whether the MERS virus in these regions is genetically the "same" as (i.e., extremely similar to) MERS in the Arabian Peninsula.

Ideally, we would need to try to find camels with active MERS infections on the verge of being exported to the UAE, and we would need to sequence their MERS genomes. Such sampling would probably best be done in the ports of Mogadishu, Bosaso and Berbera in February, March and April. It would also be great to see sampling done in the UAE in, say, February through May. If the sequences from the camels on the verge of export were to match the sequences seen in camels or people in the UAE, then this would suggest that MERS is circulating between the Horn of Africa and the Arabian Peninsula. It might be possible from such sequence data to determine which direction the virus is traveling, i.e., whether the virus is traveling from Africa to the Arabian Peninsula or from the Arabian Peninsula to Africa. The fact that the animals are traveling primarily, if not exclusively, in one direction, though, would suggest that the virus would be moving primarily from Africa to the Arabian Peninsula.

On the other hand, if MERS sequences from export ports in the Horn of Africa would turn out to be of lineages different from those of MERS sequences seen in the UAE at the same time, then we could safely conclude that MERS is not being imported from Africa.

Is there any other way that imported camels could be driving MERS infections in the Arabian Peninsula besides by bringing more MERS virus with them? Possibly. For instance, it's possible that imported camels provide a large, susceptible pool for new MERS virus infections in their destination country. Travel may make such camels more susceptible than usual, as well. Depending on how long these camels are alive in their destination countries and on how MERS is transmitted to humans, a role for new infections of imported camels in their destination countries could turn out to be more or less relevant. For instance, if it is found that most human MERS infections develop after contact with camel meat, then new MERS infections in imported camels would be important. If no such link of this sort could be found to imported camels, then this apparent correlation would be likely to be spurious, i.e., correlated with MERS infections but for no real, underlying reason.

Suppose that camel imports do drive human MERS infections. What could this tell us? What questions would this raise?

Suppose, for the moment, that some causal relationship does exist between the number of MERS cases in a country and the number of camels imported into that country. This would raise many questions, including the following:

If infected camels are being imported�

• Are there human MERS cases in the Horn of Africa?
• How big of a problem are human MERS cases now?
• How many years back can we trace human infections?
• Are imported camels infecting people in the Arabian Peninsula?
• How?
• Do people becoming infected through eating camel meat?
• Is meat a more important source of human infections than other forms of camel contact (direct, milk, urine, �)?
• How can we prevent imported camels from infecting people?
• Are imported camels infecting camels in the Arabian Peninsula, who then infect humans in the Arabian Peninsula?
• How are imported camels infecting domestic camel stocks?
• How are domestic camels infecting people?
• How can we prevent imported camels from infecting domestic camels?
• How can we prevent infected camels from being imported?
• Does the import process increase the incidence of MERS among imported camels?
• Does contact with other camels at the sites of export and/or import increase the incidence?
• Does quarantine at the sites of export and/or import increase the incidence?
• Does shipping increase the incidence?
• What are the dynamics of MERS transmission in camels in the Horn of Africa and the Arabian Peninsula?
• Have we been looking for MERS in the light under the lamppost?

If infected camels are not being imported�

• Are imported camels becoming infected in their destination countries?
• Are infected imported camels infecting people?
• Are infected imported camels infecting domestic camels?

And finally, what will happen over the coming year, if KSA continues to ban camel imports from Somalia, Ethiopia and Sudan, while the UAE does not? Will KSA find other sources of camels? New human cases continue to arise in KSA; MERS is clearly still in KSA. But without camels imported from the Horn of Africa, will human cases die down, and will we see no surge next spring? Time will tell.

In the meantime�

We don't know whether imported camels affect MERS transmission in the Arabian Peninsula. We don't know whether any camels exported to the Arabian Peninsula are infected with MERS. We don't know for absolute fact whether camels give MERS to people.

In short, many more studies are needed to discover where people and camels are becoming infected with MERS, to learn how MERS is transmitted to people and to understand local and global MERS transmission dynamics in camels.

It would be good to do some surveillance in Somali ports, though.

References

1. http://faostat3.fao.org/faostat-gateway/go/to/download/Q/QA/E
2. http://www.who.int/csr/disease/coronavirus_infections/MERS_CoV_RA_20140424.pdf?ua=1
3. http://www.who.int/csr/disease/coronavirus_infections/MERS_CoV_Update_09_May_2014.pdf?ua=1
4. http://newsmedicalnet.blogspot.com.au/2014/06/snapdate-mers-by-month.html 
5. http://faostat3.fao.org/faostat-gateway/go/to/download/T/TA/E
6. http://www.ft.com/cms/s/0/a5c38622-37db-11e3-8668-00144feab7de.html#ixzz35TEHV5sD
7. http://proof.nationalgeographic.com/2014/06/16/robin-hammond-the-largest-trade-on-the-hoof/
8. http://somalilandpress.com/horn-of-africa-to-double-livestock-exports-to-saudi-arabia-21259
9. http://somalilandpress.com/somalilandbustling-livestock-trade-boosts-somalias-economy-36695
10. http://www.uaeinteract.com/docs/UAE_set_to_import_camels/45348.htm
11. http://www.researchgate.net/publication/256297268_Improving_mature_camel-meat_quality_characteristics_with_calcium_chloride_injection
12. http://www.jeg.org.sa/data/modules/contents/uploads/infopdf/1090.pdf
13. http://wwwnc.cdc.gov/eid/article/20/6/14-0299_article
14. http://www.emro.who.int/sdn/sudan-news/sudan-dengue-outbreak2014.html
15. http://wwwnc.cdc.gov/eid/article/19/10/13-0946_article
16. http://wwwnc.cdc.gov/eid/article/19/11/pdfs/13-1172.pdf
17. http://www.albayan.ae/one-world/arabs/2014-05-06-1.2116311
18. http://www.arabnews.com/node/582041
19. http://www.reuters.com/article/2014/06/05/us-health-mers-saudi-camels-idUSKBN0EG1FT20140605
20. http://www.khaleejtimes.com/kt-article-display-1.asp?xfile=data/government/2014/May/government_May17.xml&section=government
21. http://www.uaeinteract.com/docs/Camel_shipments_from_GCC_to_undergo_strict_screening_for_MERS-CoV_MoEW/61573.htm
22. http://www.mbali.info/doc199.htm
23. http://www.fao.org/fileadmin/user_upload/drought/docs/chatham%20house%20majid%20djibouti%20livestock.pdf

NOTE: I (Ian M. Mackay, VDU Editor) did not have a hand in writing this post and thus take no credit for it. This was entirely the work of the Guest Writer. 

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Updated MERS-CoV full genome tree...

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).

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

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. 

1. I don't think any scientist has ever suggested every camel is carrying/shedding MERS-CoV all the time. Nothing supports that. 
2. 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). 
3. 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...

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
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).
10. Nowotny N, Kolodziejek J. Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels, Oman, 2013. Euro Surveill2014;19(16).
11. 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).
12. 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).
13. 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).

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

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. 

1. I don't think any scientist has ever suggested every camel is carrying/shedding MERS-CoV all the time. Nothing supports that. 
2. 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). 
3. 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...

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
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).
10. Nowotny N, Kolodziejek J. Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels, Oman, 2013. Euro Surveill2014;19(16).
11. 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).
12. 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).
13. 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).
14. 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). 
15. 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.

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Camels at the centre, aerosol all around...

v2 12JUN2015

A droplet (and perhaps airborne)-centric view of how the camel could be a source of sporadic human infection by MERS-CoV, a virus that is genetically very similar whether found in camels or humans.

The inner ring (orange) is more about bigger wetter droplets and aerosols-if you must differentiate on size. 

These are potential routes by which a human in contact with, or near to, camels might acquire virus from them, when those camels are actively infected. Keep this in context though- because of a number of large hospital-based outbreaks, most cases of MERS seem to have occurred by virus transmission between humans and their environments rather than from camels to humans.

Camels are not all infected all the time. This is probably why there wasn't a rash of camel herdsmen coming down with MERS after the YouTube camel-kissing outbreak...at least as far as we know there wasn't.

Camels have been found to be actively infected more often when young, but adult camels have also been found actively infected by MERS-CoV as well so there is risk of exposure to camels at any age, when they are infected.

Sometimes camels do not show signs of illness (e.g. no runny nose) but other times they do, so illness alone cannot be used as a warning sign.

There are also some data to suggest adult camels can be reinfected. This makes sense if you remember that MERS-CoV is well entrenched among camels spread over large areas of the Arabian Peninsula and Africa. The virus would disappear if there were no susceptible hosts left among the adults to maintain it in the herds between camel breeding seasons. Plus, there is nothing to physically stop a new infection anyway. That's a conversation about whether that infection leads to notable or debilitating disease or not.

The outer (Blue) ring in the picture above is more about consumption of camel products. As you can see in the inner ring, some of these activities could also generate aerosols and it is important to think about, and recognize, that avoiding consuming of camel products may still be about reducing your risk of exposure to virus that you can breathe in during the process of preparing the camel products to consume, when the camel is infected.

We don't yet have any evidence that the virus can infect after eating/drinking material contaminated with it. Or whether many camel products are contaminated with it. I tend to think that if eating/drinking were a route to acquiring MERS, then a lot more people would be infected by such a deliberate process of viral delivery. Plus. the disease almost always shows up as a respiratory tract illness with gut issues thrown in sometimes, not the other way around. And the physiology underpinning a virus being ingested, disseminating systemically and mostly showing up as pneumonia? Plus the few exported cases that have forward transmitted probably weren't consuming camel products at their destinations. Meh. Droplets. Respiratory

So we still need to find out which bits of the camel actually have virus in them. No milk testing has been done yet but nasal swabs and faeces have been positive for MERS-CoV RNA and have had infectious virus grown from them.

On cleaning this blight from the camels, I'd like to see more talk about quarantine and isolation processes now. Can camel herds be kept separated for long enough that the virus is "burned out" of each herd by limiting its ability to infect new herds? It would be a huge job but it may be a way to rid areas, countries and perhaps the Peninsula of MERS-CoV while routine animal testing can be put in place for imported camels. Just a thought. In the meantime, finding ways to perhaps do this on a small scale for the incoming pilgrims so that they could still visit with "safe" camels, might be a matter of priority.

Make no mistake, camels host this virus and they have done so for at least 20-years.

That's not the end of the story - but it's one chapter of it and it's written in stone.


Version history.

• v2-changed some use of the term 'airborne' as my understanding of the word has mutated over the past year

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