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Antibodies in 10-year old UAE camel sera suggestive, but not evidentiary, of the presence of MERS-CoV a decade ago

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Click on image to enlarge. 
I've cobbled together a graphic of the assays
that have come from Prof Christian Drosten group and
colleagues, mostly for the detection and
confirmation of MERS-CoV in human samples.
632 of 651 (97.1%) dromedary camel serum samples collected in 2003 and 2013 in the United Arab Emirates (UAE) have been found to react with Middle East respiratory syndrome coronavirus (MERS-CoV) or key pieces thereof.

Meyer and colleagues from the Netherlands, Germany and the UAE also tested 16 control samples from German zoo camels but none reacted to MERS-CoV in their testing system. This indicates that the camels have not been infected by the MERS-CoV (or something very much like it) leading the authors to suggest that the virus is relatively isolated to Arabian peninsula's eastern edge...as far as we know from the testing performed to date. 

This is a potentially huge piece of good news because it suggests, to me at least, that there is a very strong chance that the spread of MERS-CoV can be contained. It will however, take a collaborative effort to "stamp out" MERS-CoV the same way SARS-CoV was stopped in its tracks (to partly quote Mike Coston) through effective infection prevention and control measures being created, implemented and enforced. 

In the absence of further testing from other regions around the world, we hold information in our hands that suggests a region-specific isolation to the MERS-CoV. And we know that right now it does not seem to be very good at all at transmitting from human-to-human. Perhaps reflecting that it is currently a camel virus and not a human one? Of course, it may never evolve into a human virus.

From what we do know today of the MERS-CoV, stamping out human infections may involve some of the following steps:


  • Being aware of the risk of contact between humans and camels and seeking to limit such contact if it could occur in the absence of suitable precautions including personal protective equipment
  • Testing camels for active infection, which may not result in notable disease in camels, and isolating those camels from other camel herds to try and "burn out" infection in camels altogether. The horse racing industry might have some good advice in this department
  • Learning more about all aspects of MERS-CoV acquisition, spread and disease in camels and perhaps in other animals. This will be influenced by future screening projects results which will hopefully identify any other animals that also a close relative/immediate ancestor that is passed to camels and then humans, or perhaps directly to humans
  •  Implementing ways to break the chain of spread from a putative other animal host to camels to people. 

Hopefully such steps could be achieved without any long term impact to camel interaction in the region as they are an essential source of social, economic and dietary enrichment.

A recombinant MERS-CoV Spike immunofluorescent assay was used to screen samples for reactive antibodies. Vero cell s expressing a recombinant Spike protein from MERS-CoV or HCoV-OC43 (used to detect cross-reactive antibodies) were fixed and then incubated with diluted animal or control serum samples (1:20 - 1:80 at 37'C for 60-min). Captured antibody was labelled with an anti-llama antibody fragment labelled with a fluorescent tag (FITC). A MERS-CoV human protein microarray assay was used to confirm screening results (I've noted this assay previously here). Virus neutralization studies were also conducted using a method I've previously written about. 

Meyer's study also screened 182 camel's faecal samples collected in 2013 using broad-ranging CoV RT-PCRs which, upon nucleotide sequence confirmation, yielded 2 bovine coronavirus (BCoV) positives, but no MERS-CoV positives. We learn from this that recently stored faecal samples can yield CoV RNA that can also be sequenced.

It's also worth a quick hop back to looking at the bigger picture of animal testing for a moment. Succeeding in detecting MERS-CoV RNA among the relatively small numbers of samples tested to date is akin to finding the Arkenstone among Erebor's piles of gold (even if it looked easy in the movie). Sure, a decent number of different animal species have been tested so far, but only small numbers from each. And even though there is a high proportion of camels with MERS-CoV (or its antigenic kin) antibodies, we still have to strike it lucky enough to sample during what may well be an acute virus replication period lasting only days to a couple of weeks. So far, it looks like luck has been as slippery as a woodland elf on a riverbank. Larger numbers of each animal species, camels especially, should land a hit or two in the near future I'm betting.

There is still much testing to be done, but perhaps it's possible to shut the gate before the camels have truly bolted.

Hat-tip to Helen Branswell on Twitter and her article here.
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The weather in eastern China...

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Just a random snippet form a paper I was skimming that helps us southern hemispherans get a grip on the seasons and weather elsewhere...


Some studies have claimed that climatic factors, particularly temperature, have a clear impact on seasonal influenza outbreaks [34,35]. The weather in eastern China is very cold between December and January, and temperatures begin to rise in late February. It is usually relatively warm in March and April, and starts to get hot from May. The temporal characteristics of human infections with influenza A(H7N9) virus suggest that temperature has some association with incidence of this disease. The prevailing mild climate may have been particularly suitable for influenza A(H7N9) virus infection since there was an increase in the number of cases in March�April. If there is a relationship, attention must be paid as there could be a potential outbreak in the same period (March�April) in the future.



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H7N9 median time between events: the story of average disease

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From Clinical Findings in 111 Cases of Influenza A (H7N9) Virus Infection, Gao et al, Volume No 368, Page No. 2277-85. Copyright � (2013) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
This is a supplementary figure from the New England Journal of Medicine article entitled "Clinical Findings in 111 Cases of Influenza A (H7N9) Virus Infection" published May 2013 by Gao and colleagues working at a host of Chinese institutions around Eastern China.

It presents key median times between virus acquisition through to death among 62 influenza A(H7N9) virus-infected patients.

It struck me as a very clear way of summarizing the timeline to death among those with this outcome ascribed to infection by H7N9 earlier in 2013.

It is noteworthy that the median time for antiviral therapy to commence was 7-days, ostensibly too late to have an effect on severe infection and disease....but then a definite diagnosis took 8-days on average so antiviral treatment would have to have been commenced without lab confirmation, in order to be most effective. 

It seems that quite a few H7N9 patients present to at least 2 facilities once they become symptomatic. From the figure above, antiviral treatment is usually started at the second, tertiary care facility. Could it be started earlier?

This really stresses the key role of the first Doctor an H7N9 patient presents to, an event which itself occurs 48-hours after symptoms develop. The high end of when antiviral treatment needs to be administered to have its greatest impact.

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Keeping patient privacy to the fore...

Crawford Kilian (CK; with one "l") and Andrew Rambaut (AR) passed a couple of tweets a couple of evenings ago (my time), and I chipped in my 5c worth (inflation and all) at the time.

I wasn't really meaning to be argumentative, my comment was asking, cynically, whether a suggestion to improve patient privacy suggested by AR would help unstopper the cork of oft-times incomplete and sometimes slow or non-English information on cases of MERS-CoV infection in Saudi Arabia.

Yesterday afternoon CK penned some more detailed thoughts on the issue of patient privacy, stigma and microbial infections. The overall message from all related communication's (including Saudi Ministry of Health's [MOH] Dr Ziad Memish's comments to CK on patient privacy back in September) is that patient personal space was being encroached upon by media who had deduced their identity from the amount of detail in the Saudi press releases
about cases. This may have led to these patients, who had apparently complained to the Saudi MOH, being identified to their community and perhaps being stigmatised just because of their viral passengers. As Dr Memish wrote....


Over the last year we had patients and families complain to us about intrusion of their privacy by media reporters who recognized their identity through the transparency of reporting their case details.

He had said a similar thing a few days earlier in an interview I wrote about here.

I offer some thoughts and arguments below; and yes, this time I am being argumentative. There are a few issues here...
  1. Patient privacy must always be protected
  2. Is patient privacy being breached?
  3. Should we expect to have MERS-CoV data available for hobbyist bloggers and interested scientific parties?
As someone who has worked in a research capacity with patient samples for 2 decades, I've seen the ethical sands shift constantly towards improved patient privacy. I'm painfully aware that the need to ensure the patient's privacy is paramount. I can't pipette from a sample unless I have the appropriate external ethical approval to do so - every funded project in our lab is conducted this way today. I have not one problem with that whatsoever. At the end of the day, whether in a research or public health capacity, I want to try and help sick people - not make their lives more difficult.

When you submit yourself as a patient to a Doctor's care you do not expect to have your results show up in the local newspaper or on a tinpot blogger's column (I'm talking of mine not yours CK or AR!), or to be hounded by the media as you exit your hospital. Of course there may be exceptions to those people - we saw quite a few H7N9 cases wheeled or walked to the waiting press pack earlier this year. Being a patient puts us at a level of vulnerability that none enjoy and for it to be taken advantage of is absolutely unacceptable. I would have thought that keeping a patient's result details private is part of the Duty of Care. 

Still, I do wonder at the extent to which MERS-CoV patients are stigmatised because they are MERS-CoV-positive which was deduced by the media from the "transparency of reporting their case details". Let's take the best case scenario for MERS-CoV case details...age, sex, region, hospital name, underlying conditions, perhaps a couple of other items on a good media release. How does the media find out about that person to the extent that they track them down and hound them for an interview? They don't have access to medical records. Is the media release (see below) enough or should a bony accusatory finger be pointing towards a leak from one of the patients' sources during their travel through "the system"; someone not all that fussed about maintaining patient confidentiality, for whatever reason(s)? 

There is quite a chain of links between the patient and many others when that patient is sampled for disease diagnosis; a chain made longer when the disease is an unknown like MERS, driven by a newly discovered virus like the MERS-CoV. The lab techs will receive and process the sample, matching a patient slip to a specimen which is tested and linked to a result which may then be repeated externally for reliability. The clinical team(s) providing care and the hospital administrative staff, perhaps ambulance services, public health officials, international scientific and clinical experts such as World Health Organization and perhaps a panel of experts in a working group may or may not all have more patient detail than was released to the media. The family and those friends that are told will also be among the knowing. All this is just the same as in other countries around the world. How is it that reporters can identifying the patients? Is it happening differently in other parts of the world to the way it is in the Kingdom of Saudi Arabia; as CK noted, is it a cultural thing?
 If you take a look at a recent English language MERS-CoV case media release, from the Saudi MOH, we still see that some key patient details are continuing to be reported...

Within the framework of the constant monitoring and epidemic surveillance of the novel Coronavirus (MERS-CoV), the Ministry of Health (MOH) has announced that five new cases have been recorded.

The first case is for a 57-year-old male citizen, who has been suffering from some chronic diseases. Now, he is at the IC unit, receiving the proper treatment, may Allah grant him speedy recovery. 

The second case is for a 73-year-old male citizen, who has been suffering from some chronic diseases. He passed away, may Allah have mercy upon him.

As for the third (43-year-old resident), fourth (35-year-old resident) and fifth (27-year-old citizen) cases, they work at the health sector. They were in contact with confirmed cases of this virus, and didn�t suffer from any symptoms. May Allah, Almighty, heal the injured cases and bestow upon them the cure they so earnestly desire.

If this little amount of detail is not considered a problem now, then I don't see why a slightly expanded media release should be any more of a patient identifier; expanded along the lines of what I've listed previously here. Extra information is, I firmly believe, useful for "crowd-sourced epidemiology" - that which provides many fresh sets of eyes to perhaps help analyze aetiologies, peruse pathological puzzles and delve diagnostic dilemmas. It also allows for the re-presentation of all manner of complex infection and disease issues, after filtering through the minds of others, some of whom are very good at extracting points of interest for a much wider audience, thus contributing to keeping the world informed. 

But I'm drifting.

What about that "mysterious outbreak" in Montgomery County, Texas, USA back Dec-19? We didn't get each and every case's details and sure, that didn't raise too much ire did it? In fact, I don't think we've officially heard whether all 8 people (50% of whom sadly died) were influenza A(H1N1) virus positive or not. Yet it was assumed by the press and some others to be the case within hours. What then is the "So What" question from such an absence of patient information for you and I and the rest of the world who are not part of the patient chain? It's simply "so what??" We didn't need to know more than that. Yes, its horrible that people should die when they may not have had to. And yes, a US citizen's cultural affiliation with the media may be as different from that of a Saudi Arabian citizen as chalk is from cheese, but so long as the experts on the ground know the details, that's what really matters isn't it? So long as the treatment and management of the patients, the informing of their loved ones and the prevention of further viral spread is being attended to (including reinforcing the message that flu is a vaccine-preventable disease in the Montgomery instance) then people outside the loop of patient-doctor-scientist-admin-loved ones don't need to know anything further do they?

If such data could be released without identifying the patients at all - great, and I would have thought that quite possible in a country of 20+ million. The contents of current media releases seem to support that thinking too. But if it is not possible, then perhaps we should wake up to the fact that no one outside that list above needs to know. I've written about entitlement previously. 

Personally, I doubt that if the MOH stopped printing these tiny snippets of deidentified case detail, like those quoted above, it would halt the media from seeking interviews with people who had been afflicted with a "mystery" illness. But what do I know?

As we know from Dr Hatem Makhdoom, who accepts the description of an an experienced virologist on the Saudi Ministry of Health team said...
..in other words the experts in the scientific world are getting the knowledge they need, even if we bloggers are not.

At the end of the day, its about current and potential future patients; caring for the former, and preventing illness among the latter.

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H9N2 confirmed in 86-year old Hong Kong citizen living in Guangdong province...

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Influenza A(H9N2) virus, another "bird flu" but this usually causing mild signs and symptoms of infection, has been confirmed in an 86-year old man reported Dec-30.

The man's underlying illnesses were added to by chills and productive cough from 28-Dec when he was admitted to hospital with a fever.

Sputum tested positive for H9N2. Not sure if an upper respiratory sample was tested.

He had no recent contact with poultry and no contacts have shown signs of illness.

Mild human cases in Hong Kong have previously been reported in 1999, 2003 and 2007 and imported cases in 2008 and 2009.

As ProMED moderator CP (Craig R. Pringle) noted, enhanced surveillance in the region is likely to continue to pick up all sorts of H and N viruses and variants. Interesting watching these pop up - especially if they remain as mild infections, unlike H7N9 has so far.

Sources...

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Qatari camels clear coronavirus

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The camel herd that was previously Middle East respiratory syndrome coronavirus (MES-CoV) RT-PCR-positive is no longer positive for viral RNA according to an OIE report (OIE=Office International des Epizooties; the world organisation for animal health).
In there report they note that retesting of the herd, subsequent to the initial testing presumably, has yielded no positive this time around.

So it looks like the MERS-CoV infection is an acute infection (it is contracted, it causes illness - perhaps - and then it goes thanks to an immune response - perhaps), as are many/most) viral infections of animals and humans.

An interesting comment within the report states that...

The planned massive survey for MERS-CoV in animals is under implementation and the same herd is under systematic retesting. Follow-up reports will be submitted when there will be new data.

I do like a statement that includes the words "massive study" in it!

Hat tip to CIDRAP.
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Influenza A(H7N9) virus case accumulation for 2013...

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Sure a full 12-months of H7N9 in humans hasn't passed yet, but 2013 is coming to a close. 

I have 148 H7N9 cases worldwide including deaths and the asymptomatic boy from Beijing who seems to still be off the official tallies for some reason. WHO have not had an official tally of fatal cases in their recent 2 disease outbreak news posts, the last with a tally was 6-Nov in which 45 deaths were recorded with 6 cases remaining in hospital and 88 having been discharged. Hong Kong's Centre for Health Protection (CHP) maintains a running tally of mainland China cases With the recent death of a Hong Kong man the tally of fatal cases rest around 46 (PFC of 31.1%).

I've just changed my spreadsheet to a weekly format from the daily version and the first chart it reveals is shown above. 

This includes the lay of the land for all H7N9 cases from the beginning of the outbreak, 11-Feb (date of pneumonia for son of index case), through to 29-Dec. Date data employ dates of reporting if no date of illness onset could be found.

We can see from this 47-week inclusive dataset that the principle period of activity was in late March to late April. Whether that will also be the case in the new year is anyone's guess really.

What we can say from the vast amount of influenza virus research data in the scientific literature, is that each and every new combination of 8 gene segments that comprise a distinct influenza A virus seem capable of their own distinct "personality".
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What to watch for with human parechovirus (HPeV) infections...

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With HPeV infections generally around during summer (see specific earlier story arising from cases in babies from New South Wales), it's well worth mirroring the advice form NSW health on what to look for. 

The full sources of this information can be visited at the pages listed below.

A brief agglomeration of the information...

HPeV (closely related to enteroviruses) has been detected in a number of neonates and young infants admitted to NSW hospitals during October and November 2013. Infants present very unwell with a rapid onset of acute sepsis-like (whole-body or systemic inflammation to a widespread infection) symptoms and can infect teh central nervous system. This is often followed by an erythematous, often confluent rash. Children under 3 months of age are the group most likely to develop severe disease, but most recover with supportive treatment.

Suspect HPeV infections in neonates (newborn) or young infants can present with a fever (>38.0�C) and:
  • Irritability and appearing to be in pain 
  • Tachypnoea
  • Maculopapular or erythematous rash 
  • Encephalitis
  • Diarrhoea or loose stools 
  • Myoclonic jerks
  • Tachycardia 
  • Hepatitis

How is it diagnosed?

Stool samples, nose and throat swabs, cerebrospinal fluid (CSF), or blood can be tested for HPeV at a specialist laboratory.

Initial Management and Treatment

Children presenting with a fever, sepsis-like signs &/or neurological signs, including irritability, should be assessed and treated for suspected sepsis using local protocols and discussed with an Emergency Consultant or Paediatrician.
There is no specific treatment for HPeV, treatment is supportive only.

How is HPeV disease prevented?

There is no vaccine to protect you from HPeV infection.

Good hygiene is the best protection: wash hands with soap and water after going to the toilet, before eating, after wiping noses, and after changing nappies or soiled clothing
Ensure the mouth and nose are covered when coughing and sneezing. Wipe the nose and mouth with tissues, dispose of used tissues and then wash your hands.

People who are unwell with colds, flu-like illness or gastro illness should stay away from small babies. 

If you are caring for a small baby and are unwell, wash your hands or use an alcohol-based hand rub before touching or feeding the baby.

Further reading...
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