MERS case-control study during the Hajj

Dr Ziad Memish, Deputy Minister of Health, Kingdom of Saudi Arabia, has made a welcome comment about some analysis of ill cases that went on during the Hajj. In the Saudi Gazette..

He added that in addition to detailed investigations of every suspected case, case-control studies for index cases and intensive follow-up of contacts with serological testing to improve understanding of the critical features of MERS-CoV infection were carried out.

I'm not clear on whether that indicates there were MERS-CoV cases during the Hajj, or if he is referring to probable cases that were not confirmed (no contacts then?) or to respiratory illnesses in general. He unfortunately wasn't quoted as saying whether any of those results were positive for MERS-CoV infection. 

Given that 997,3709 pilgrims apparently partook in some degree of medical healthcare service while in the KSA for Hajj, this study should provide some very useful information about what MERS-CoV was doing both in the ill and the healthy in mid-October. I might even be able to stop whingeing about lack of testing of all but those who are severely ill (or their contacts)!

The case-control study protocol is likely to follow that defined by the WHO in July - which can be found here.

The controls (best if >1 per case) will be randomly selected people of equal age (leeway varies with age band) and sex ("matched"), living in the same neighbourhood (to ensure try and capture the same environmental exposures; difficult for visiting pilgrims so general are of pilgrimage might suffice) that are not presenting with the same illness as the confirmed "case" at the time of sampling. Sampling (described in the lab testing WHO document here) which is recommended to include material from the lower respiratory tract - which may prove difficult from otherwise well controls. Informed consent is recommended as part of the (any such) study so controls will know what they are in for ahead do time.

Interestingly the WHO document comments that...

Currently, circulation of this virus in the community is thought to be nonexistent or minimal at most and the numbers of infections low. For that reason, prospective controls who have not had recent respiratory illness can be enrolled without laboratory

This study will address whether this is an accurate premise.

Read More

MERS cases swell by 3, information scant...

Middle East respiratory (MERS) coronavirus cases in the Kingdom of Saudi Arabia have increased by 3 according to the latest Ministry of Health update. This brings the tally 147 with 62 deaths, a PFC of 42%. With the data we have, the median age of all cases is at 53-years and that of fatal cases sits at 60-years.

• FT#147. 83-year old female. Contact of previous case. Comorbidities. Stable.
• FT#148. 54y. Healthcare worker. Comorbidity. Stable.
• FT#149. 49-year old. Stable.

Since the update doesn't have much detail to speak of, I'll focus on what the release does not have based on my earlier updated wishlist of useful details from the MOH:

• Sex of cases (subsequently identified via Twitter)
• Dates of onset
• Dates of hospitalisation
• Details of contacts
• Type of comorbidities
• Healthcare worker's role
• Location of acquisition (just town)
• Type of laboratory testing
• Treatments/management
• English translation
• History of contact with animals, types (not detailed) of places visited or other possible exposures that may shed light on acquisition

None of these things would identify the cases (a justifiable concern of Dr Ziad Memish) but would be useful for researchers seeking to better understand the nature and track the spread of MERS. 

There may be clues within those details that alert researchers to a nugget that helps explain spread or acquisition or change in disease.

Thanks to Crawford Kilian's @Crof initial tweet and @HelenBranswell and @azizalhinde for clarifying sex of cases. 

Read More

Influenza A(H7N9) vaccine approved by Chinese food and drug administration for use...[UPDATED]

CNTV English language newshour reports that the home-made first influenza vaccine from China has met local safety standards and is ready for mass production. The vaccine was a collaborative development between the First Affiliated Hospital under the School of Medicine of Zhejiang University, Hong Kong University, Chinese Center for Disease Control and Prevention, National Institute for Food and Drug Control, and Chinese Academy of Medical Sciences.

It will be interesting to read about what the virus is comprised of (seems to use the older influenza PR8 strain as a backbone, employing a reverse genetics approach to add in H7N9) and how the vaccine makers got around H7N9's predicted low immunogenicity issue, what the dosing regimen is and what was used as adjuvant (mentioned here, earlier). As Mike Coston notes on Avian Flu Diary, the announcements don't detail much of the preceding safety trials that should have been carried out for a vaccine to have reached this level of development. 

Mike has an earlier post over on Avian Flu Diary that reminds us about the few that are sick enough to be obviously ill....and perhaps the many that do not seek medical attention because infection resulted in relatively mild disease. Largely, as Mike notes, any numbers assigned to infections that result in milder or even asymptomatic disease are guesstimates for now - at least until some actual testing is reported. History supports that mild infections are likely, but every zoonosis is its own beast.

More coming soon on the vaccine's development path and on testing to understand H7N9's reach.

Thanks to @makoto_au_japon for identifying the vaccine story through Twitter

Read More

Monkeys!

A troup of Hamadryas Baboons (Papio hamdryas) outside

of Riyadh, Saudi Arabia. Hamadryads live for 30 to 35-years

Image from Northwest Wildlife Homepage.

Monkeys I tell ya, monkeys!

Alsharq.net notes that baboons are such a problem in the Kingdom of Saudi Arabia's southwest that electric fences are being erected to keep them out of certain areas.

Is anyone testing baboons for MERS-CoV? Or any other virus hunting going on in them for that matter? 

I've posted on the movements and interactions of these furry troublemakers before, and they also feature in the VDU model of MERS acquisition.

If they are even infrequently in contact with humans, bats and camels - then perhaps we should give them the laboratory once-over. 

Some serology and some next generation sequencing would be a good place to start.


Thanks to FluTracker's Tweet and post on this.

Read More

MERS update: WHO catches up but passes along no detail - and Hajjis look clear

The World Health Organisation updated it's MERS-CoV tally. The total (144 cases) is the same except for the confirmation of 2 deaths (to 62) hinted at in my last update. 

Disappointingly and once again, the update doesn't allow any analysis because there are no specific details with which to cross-check against our case lists.

Even CIDRAP is heading to the newspapers to try and identify which existing cases have died.

With my arbitrary deadline for emergence of new MERS cases being the 27th of October (this Sunday)  only 2-days away, I think its pretty safe to say that there has been no major symptomatic MERS-CoV transmission event associated with the peak assembly period of the Hajj in 2013 (just like there was none in 2012 when MERS-CoV was already in play). 

The United Arab Emirates is reportedly not checking pilgrims for symptoms, although they have their own 2-week clock running to monitor for signs and symptoms of new cases of flu-like illness in pilgrims.

Thankfully, there are studies performing actual laboratory testing, although the details remain unclear. Such studies will tell us whether MERS-CoV is among us already, but not causing the serious disease we've become used to associating with the virus.

Dr Jake Dunning (@OutbreakJake) noted on Twitter...

@MackayIM We're testing here in London. Trying to raise awareness, but needs to be balanced against more typical local infections e.g. flu.

� Dr Jake Dunning (@OutbreakJake) October 22, 2013

He also went on to say that...

@MackayIM We also have an active MERS observational study in UK, ready to recruit willing patients. @ISARIC1 protocol can be used by anyone.
� Dr Jake Dunning (@OutbreakJake) October 22, 2013

ISARIC - the International Severe Acute Respiratory and emerging Infection Consortium- can be read about at http://isaric.tghn.org/about/.
So my next question becomes, have we been watching the emergence of a new endemic human coronavirus? That question is based on a hypothesis that we have a lot more undetected cases and on Dr Ziad Memish's earlier assertion that MERS-CoV cases are already out and about in other countries. Time, and some testing, will tell.

Read More

Influenza A(H7N9) in Zhejiang, Dutch DURC and dogs..

With the second H7N9 case (see FluTracker's thread) in Zhejiang, located only 13km from the earlier case, things seem to be picking up where they left off in late April. Poultry exposure seems key to this latest case who was a farmer who engaged in poultry trading. That word, trading, also sparks concern. It suggests that the farmer was exposed to poultry coming from, or going to, somewhere else. H7N9 is on the move. Both patients are very unwell.

Zhejiang province had the steepest rate of case acquisition back then and reached the highest H7N9-confirmed case number as well. 

Looks like this province is going to be a key battleground for the next wave of H7N9.

Meanwhile, Eurosurveillance continues its fantastic coverage of this and the Middle East respiratory coronavirus  and H7N9 outbreaks. It already has a paper online (less than a week turnaround) of the earlier Zhejiang H7N9 case in a 35-year old male (35M) which includes a note about the subsequent Zhejiang case! Outstanding work to the researchers and the publishing team. Quality publication almost in the time it takes to write blog post!

This journal certainly highlights how quickly detail research results and analysis, when submitted to peer review, can be published. 

Click to enlarge. The laboratory turnaround
times for H7N9 detection (where suitable date
data exist) since the outbreak began in early 2013. 

• 35M was identified though the surveillance system for unexplained pneumonia
• He was not a farmer and had not had close contact with another probable case. The laboratory turnaround times on this case was 7-days. A 2.2 day improvement on the rolling average I stopped calculating May 6th.
• The most likely source of exposures was a trip to rural region of  Ningbo city where he may have been in contact with animals. But that was 10-days prior to onset which would make it a long incubation period. 35M remains unconscious so further detailed tracking of exposures is not possible
• The virus was >95.5% identical to H7N9 from earlier in the year but with 5 hitherto unreported mutations in the neuraminidase (NA) gene. 2/9 bird market samples were also H7N9 PCR-positive but could not be sequenced due to low viral load

Meanwhile, Reuters reports on Albert Osterhaus and Ron Fouchier at the Erasmus Medical Center who are firing up the "gain-of-function" studies to look at what would be required for H7N9 to become a pandemic virus; essentially changing the virus to look for increased transmission. This work will be performed in an highly secure, enhanced biosafety Level 3 lab. Which of course doesn't change the subject matter - but does define how difficult it would be for that to escape. It's not convincingly clear why this virus needs to be given an evolutionary push, rather than "reverse-engineering" those influenza viruses that have previously been pandemic viruses - or some other approach with less risk of creating a virus that if it escaped, would cause a pandemic. Well, to me at least...but I'm no flu expert. You can find much more on dual-use research of concern (DURC) in Laurie Garrett's latest writing over at Foreign Affairs.

And to add to general influenza virus concerns, Sun and colleagues report in Infection, Genetics and Evolution, that infectious H9N2 (isolated using embryonated chicken eggs), strains of which has been implicated in providing genetic material to H7N9, can be isolated from dogs. The isolate was called A/Canine/Guangxi/1/2011 (H9N2). Between 20% 45% of dogs were found to be antibody-positive to H9N2. A range of dogs seem to have been virus-positive with signs and symptoms including loss of appetitie, cough, sneeze, nasal discharge and raised temperture. Some were asymptomatic. Cats next please?

Read More