Wednesday, 19 February 2014

H7N9 human case #1 - 1-year ago...

A year ago, on the 18-Feb-2013, the first human case of avian influenza A(H7N9) virus infection started showing signs of an illness; coughing with sputum. 

That person was an 87-year old retired male with hypertension and chronic obstructive pulmonary disease (COPD). By the time he presented a week later he had fever and shortness of breath. He sadly died of acute respiratory distress syndrome (ARDS).

No other cases of infection were noted to have resulted. 

He was treated with oseltamivir, an antiviral flu drug to which H7N9 is generally susceptible, 7-days after he became ill. He was in hospital for 6-days. 

His infection, along with those of 2 others, were reported to the World Health Organization on 31-March (2)


  1. NEJM Article on First 3 human cases of H7N9.
    http://www.nejm.org/doi/full/10.1056/NEJMoa1304459
  2. WHO Overview. 31-05-2013.
    http://www.who.int/influenza/human_animal_interface/influenza_h7n9/WHO_H7N9_review_31May13.pdf?ua=1

Sunday, 16 February 2014

Shanghai and Hangzhou to permanently stop live poultry markets.

According to the report on CNTV.com ENLGLISH linked below, the poultry industry in Shanghai and Hangzhou (the capital of Zhejiang province) is about to change significantly (h/t Crawford Kilian's H5N1 blog post and Tweet on this).

A new plan for the use of processed poultry in place of live or freshly butchered birds will be rolled out in late February.

Brilliant news!

As you can see in the short news video, some (n=1) of the public see the sense of a change as well as the benefits of not having to deal with slaughtering and plucking chickens while others (n=1) complain that there will be a taste difference. 

I've never known much truly fresh chicken (I'm more a fan of the flavours its cooked in) so in my ignorance I don't know whether I'm missing something special or not. 

I do know what it is to miss a bad bout of the flu though. That's something I'd go the long way around to avoid crossing paths with.

This change seems so much more in concert with a China made of glass and steel. Good work. I hope it catches on elsewhere.

Sources...

  1. CNTV Report
    http://english.cntv.cn/program/newsupdate/20140215/103244.shtml
  2. H5N1 blog
    http://crofsblogs.typepad.com/h5n1/2014/02/china-hangzhou-to-build-h7n9-prevention-system.html


H7N9 snapdate: latest hotzone map

Avian influenza A(H7N9) virus human cases by region of acquisition.
Click on image to enlarge.

Looking at the age and sex difference between H7N9 Wave 1 and Wave 2...

Thanks to CIDRAP's Dr. Nicholas Kelley for asking the question of whether I'd looked at the epidemiology of the H7N9-related deaths between Waves 1 and 2.

So that led to the charts below.


Click on image to enlarge.
Only laboratory confirmed cases and the fatal cases with enough data to identify them are shown.
Wave 1 was defined as from weeks beginning 18-Feb-2013 to 20-May-2013.
Wave 2 as from Week beginning 7-Oct-2013, until today.
Top row: total cases; surviving and fatal.
Bottom row: fatal cases. Approximately 17 are missing sufficient data to identify.
If we look at numbers, because eyeballing these charts can be misleading we see some differences, although not huge.

The average age (in years) is divided as below:

  • Wave 1
    • All cases: 56.9
    • Fatal cases: 64.5
  • Wave 2
    • All cases: 52.8
    • Fatal cases: 63.0
The proportion of Males (%) is divided thus:
  • Wave 1
    • All cases: 72.0
    • Fatal cases: 75.0
  • Wave 2
    • All cases: 66.3
    • Fatal cases: 82.1

Saturday, 15 February 2014

H7N9 snapdate: accumulating cases by region of acquisition

Click on image to enlarge.
This is what happens when you do nothing to stem the possible source of an influenza outbreak in your back yard. 

Nothing. Nothing changes.

The infection keeps spreading. 

Very clearly the H7N9 hotzone in China has now shifted from Zhejiang province to Guangdong province (the brown line that represent the second highest number of human cases of disease..75 cases representing 21.3% of all H7N9 cases.

As we read today, this province has just shut some of its poultry markets. By the look of this rate of new cases, the people of Guangdong province could be in for a tough 2-3 weeks and will be hearing a lot more about "bird flu" much to the poultry industry's disgust.

Zhejiang province leads the way in H7N9 cases and their decline 3-weeks after market closures...

Click on image to enlarge.
It's the Province in China that has seen more H7N9 cases confirmed in human than any other Province (39% of all cases have originated here). 

It reached 50 cases faster in 2014 than 2013. 

It closed its markets back in 24-Jan. And for a little while it kept finding new cases. 

But the past 2-days have see no new cases announced from Zhejiang province. Eerily reminiscent of 2013 sudden disappearance of cases announcements.

If we look at the data by date of onset of illness (pretty much all of the second wave data are this thanks to WHO's reporting and data fill-in) in the chart above, we can see this decline clearly depicted. 

After three weeks of cases nearing 20/week, they've dropped to less than half and then a quarter of that rate. 

Cases are still coming out of Guangdong Province though, but I don't have market closure dates to hand for Guangdong. 

Actually - now I do. Guangzhou's markets have just been shut (Friday, 15-Feb but only until 28-Feb) according to a timely update at Crawford Kilian's H5N1 blog as I write this. Well, that's pretty late in the game and will certainly not be a long term solution. 

I'm surprised that the vocal poultry industry has not yet realised that this sort of money-haemorrhaging close-disinfect-open-restock cycle of events will continue to recur so long as this way of presenting chickens continues. 

Instead of crying fowl (oh yes I did) it would be worth investing that energy and money into educating the population about the freshness and safety of factory-prepared refrigerated/frozen poultry. To my mind anyway. 

Create and promote new oversight and checks and balances to assure the population that the chickens won't be prepared in some dodgy way; about the cold chain; about the benefits in the longer run. 

Of course those assurances would rightly need to include some proof that concerns were unwarranted that poultry were being presented that had:


  • died from disease or poisoning due to pesticide, melamine or grain fumigants
  • been treated with harsh chemicals such as bleach or other disinfectants (credit: anonymous). 
A long road a ahead if this path is ever chosen but it would life-saving benefits both at home and worldwide. Hopefully the industry will find a way to evolve and still make a profit when it is able (or is forced) to see past its grief and current anger at everyone else. 

But back on topic, if Zhejiang is anything to go by - expect to see the Guangzhou (who knows about the rest of Guangdong province?) cases decline steeply within 3-weeks.

Zhejiang remains as my sentinel Province for watching the potential impact of live bird market closures. Last year, daily case numbers dropped by 97-99% within about 3-days of market closure in different Provinces.

Will the drop we've seen recently in Zhejiang be maintained in 2014 as it was in 2013, or will cases take off again? If so and in the absence of data to support any other reason for human cases declining, I think Zhejiang should be used by China's Ministry of Health as an example with which to "educate" the poultry industry on what happens to an emerging lethal infectious disease when you take the live poultry markets out of the equation.

Stay tuned.

H7N9 case announcements dropping: is Wave 2 under control? [UPDATED]

Its a very tough question to answer. There has been public pressure by China's poultry-farming groups on China to take measures to stem the industry's financial losses. These have been driven by the public concern that H7N9 can seriously afflict people and in about a fifth of recorded instances, kill them. 

And rightly so. The concern for those of us outside China is that reporting may be artificially halted, reduced or stemmed to calm the public - while doing nothing to stop the march of H7N9. This concern extends into thoughts about why we have so very few 2014 H7N9 sequences to date. Background for this paranoia about non-biological reporting limitations takes the form of :


  • MOA noting no evidence of H7N9 in poultry farms (1). Perhaps time to propose an alternative source then?
  • Poultry industry writing to demand that descriptors like "H7N9 bird flu" or "people infected with H7N9 avian flu" be changed to "H7N9 influenza" (2)(4). No argument from me there - bird flu is not part of the WHO nomenclature anyway. It's a media thing. Seriously though, will the name change the infections? Of course not. Same virus, same bird/poultry association with human disease. Call it Frank if you like but the process of infection, morbidity and mortality in 1:5 cases will go on.
  • Poultry industry groups asking Guangxi and Guangdong provincial governments to stop reporting each H7N9 case (3). Not acceptable and not addressing the problem at the source.

Click on image to enlarge.
Cases per day for all of Wave 2 (arbitrarily selected as
Oct-7-2014) and specifically for 2014. 

Orange and blue dots mark the rolling average
(each dot [data point] is the average of all data points
before it). The grey dots are the cases with illness

 onset on that day. The green bar reflects he current
laboratory turnaround time; the time between date
of illness onset and the date of reporting which we
hear about 2-3 days after the case is reported by
the jurisdictional Ministry. The pink bar indicates
that 2-3 day WHO delay period. Please allow for the 

fact that I am doing this from Australia which is 
ahead in time from the Northern hemisphere so my 
data are from "yesterday" and the x-axis extends into
a day you haven't had yet. The date the Hangzhou bird
markets in Zhejiang closed, my sentinel Province for a
market impact, is indicated. 
So, when we see a chart like this one, we may have those doubts at the forefront of our minds; more so than other reasons for what appears to be a constant decline in case reporting in recent days.

One such reason would be that the market closure (22-days ago for Zhejiang) and the laboratory reporting delay (currently 8.7-days for Wave 2) have finally caught up to the present day - and we are seeing a real impact of reduced exposure of humans to birds (poultry or market-based wild/song birds). 

As @influenza_bio (please follow him if you have an interest in flu - a real repository on influenza) noted on Twitter, it may also reflect a change in bird migration patterns. To me that that seems to be 2 coincidences in a row given a similar relationship between cases dropping and markets closing last year. The different could be that weather changes helped speed up the case decline in 2013. Maybe.

None of you reading this (since I believe the blog cannot be accessed in China) know the actual reason for this decline. 

In the absence of any other data or a change in climate, I'm proposing that the case decline to a direct effect from the market closure. If that hypothesis is correct, we will see continued decline in cases in Zhejiang and wherever else markets were closed. 

That decline in total H7N9 human case announcement began 3-days after Hangzhou markets closed. Given that most cases were accruing from Zhejiang province, I still think that's a good place to watch.

Sources.
  1. Xinhua story.
    http://news.xinhuanet.com/english/china/2014-01/27/c_133078220.htm
  2. Xinhua story (needs translation)
    http://news.xinhuanet.com/2014-02/04/c_119212598.htm
  3. South China Morning POst
    http://www.scmp.com/print/news/china-insider/article/1421319/chinas-poultry-industry-wants-hush-bird-flu-news-damage-control
  4. China Animal Husbandry Association
    http://www.caaa.cn/show/newsarticle.php?ID=329866

Friday, 14 February 2014

H7N9 keeps changing and mingling and mixing...

A new report in Eurosurveillance out today has once again raised the spectre of a pandemic H7N9 spread. 

Not just for what the Meng and colleagues from China and the United States have shown in their detailed analysis of the PB1 gene segment of (mostly) avian influenza A(H7N9) viruses from humans birds and the environment in 2013, but also for what they have indirectly highlighted: a massive absence of 2014 H7N9 sequence data on GISAID or GenBank sequence databases. 

Being asked for comment, which I provided in 2 stories linked below (2 and 3), I dug into the sequence databases and was stunned (yes, really!) to find that there are hardly any sequences available from H7N9 gene segments or genomes this year.
Given that this year's human case tally of H7N9 infections has surpassed that of 2013's 1st wave, I find that really surprising, and confusing. Also given a few subtle pattern changes that I've been writing about of late including the shifting age balances, sex ratios, fewer farmers, more family clusters, apparently limited impact on human case numbers from market closures >2-weeks ago...I would have said keeping our eye on the genetic ball was more important right now than ever.

What's going on?

Meng and colleagues use the PB1 gene to highlight changes to H7N9 resulting in 4 genetically distinct clusters with links through time and geography. 

There seems to be continued and active change in H7N9 based on analysis of this 1 segment. Not surprising for a virus whose genes exist as a deck of 8 cards, each capable of its own drift changes, just waiting to be shuffled but the next already-occupied host it enters.

I really wonder how much of the virus we knew of as H7N9 in 2013 has changed and what the virus we know in 2014 is like by comparison. 

The only way to answer that will be to see and analyse the sequences from 2014. And hopefully, do that soon. 

These bits of viral genetic material don't just make pretty trees (or hard to see ones like in he Eurosurveillance article), they identify significant changes to the virus that signal potential for, or real, change in transmission, disease type and severity, site of preferred replication and our likelihood of successfully detecting the virus using sequence-dependent, PCR-based diagnostics.

Sources...

  1. Eurosurveillance article.
    http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20699
  2. CIDRAP story
    http://www.cidrap.umn.edu/news-perspective/2014/02/h7n9-cases-pause-new-report-details-reassortants
  3. Bloomberg News story
    http://www.bloomberg.com/news/2014-02-13/pandemic-potential-seen-in-gene-changes-of-bird-flu.html

Wednesday, 12 February 2014

First Taiwan, then Hong Kong, now Malaysia becomes a holiday destination for an H7N9 case...[UPDATED x2]

Mike Coston has just made us aware via a Tweet that avian influenza A(H7N9) virus has escaped its usual roosting ground in southern eastern China by hitching a lift in a tourist to Malaysia

A more detailed post on his Avian Flu Diary wrangles the issue of language very nicely and tells us that the infected Chinese tourist has been hospitalized and is currently in a stable condition. 


Brief details..

  • 66-year old female
  • Fever, 01-Feb prior to leaving China
  • Travelled from Guangzhou City in Guangdong province to Peninsular Malaysia 04-Feb then to Sabah, Malaysian Borneo 06-Feb then to Kota Kinabalu
  • Hospitalised 07-Feb in Kota Kinabalu, Sabah, Malaysia 
  • Laboratory confirmed 11-Feb and remained positive 13-Feb and 22-Feb
  • No sign of R294K (N9 numbering) mutation associated with oseltamivir resistance despite virus "persistence" wihc may have been related to treatment with steroids
  • 191 contacts; 6 were symptomatic but tested negative for H7N9
It is worth highlighting here that this sort of export is not unexpected and not even surprising. We live in a hyper-connected world. It's nigh on impossible to stop respiratory viruses from spreading. This case highlights that even when we're ill, we still feel the pressure to continue on with our jobs, our daily routine or our holiday. After all, we've all been a bit crook before and it has mostly been nothing much to speak of. Why should this time be any different? 

To date, H7N9 does not jump easily between humans as far as we know. The 20 negative contacts stand in testimony to that. But if you see some articles or posts or Tweets in the coming hours and days which suggest that the sky is falling...I think you can rest assured that this is not it falling. 

Not yet anyway!  

Now, go follow Mike via @Fla_Medic if you are not already.

Sources...

H7N9 snapdate: H7N9 totals by month, 2013 vs 2014 to date

Click on image to enlarge.
January has so far tallied 1.6x more cases than the peak month of 2013 which was April. And those cases are still being reported.

But only 2 lab-confirmed cases were added to the list last night, perhaps things have started to slow at last? 

That is extrapolating a bit much from 1 night of reporting with low numbers, but let's wait and see what happens tonight (today for you guys up north!). Seems to be the mantra for this sort of stuff.