Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

Laidback Al · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

 Curiosity raises an interesting question about whether or not the 2009 pandemic would have been considered a pandemic without the genetic information about A(H1N1) pdm09. While we have made tremendous advances in the science of virus research, we have not yet developed a theoretical model that integrates this information with our more traditional understanding of the demographic/epidemiological dimensions of disease outbreaks and pandemics.
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Pathfinder · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

1 May 2013 Last updated at 10:55 ET

H7N9 bird flu is a 'serious threat' - researchers warn

By James Gallagher
Health and science reporter, BBC News

...
There is concern over both the pace and severity of the outbreak.

There has been a relatively high number of known infections since the first case was detected in April.

Prof John McCauley, the director of a World Health Organization (WHO) collaborating centre in the UK, said: "It is unusual to get these numbers."
...
"The WHO considers this a serious threat," said Prof McCauley, "but we don't know at this stage whether this is going to spread from human to human."
...
The last major bird flu, H5N1, made the jump to people in 1997 and killed more than three hundred people -yet, it is still unable to spread between humans.

Predicting which viruses will become deadly on a global scale is impossible.
...
Often in pandemics older people have some immunity as they have lived longer and have been exposed to similar viruses before.

However, in this outbreak the ages of those infected ranges from two to 81.

Prof Farrar said: "That suggests there truly is no immunity across all ages, and that as humans we have not seen this virus before.
...
Prof Wendy Barclay, an influenza researcher at Imperial College London, said: "H7N9 might be one step closer to being able to become a pandemic than H5 is in nature at the moment."

It already has one of the five mutations when it is infecting birds.

Full text:
http://www.bbc.co.uk/news/health-22364628

Giuseppe · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

I don't think we have to wait until the H7N9 will have gained the putative mutations described in the article from BBC.

If health experts are growing a consensus opinion that this virus is poised to become pandemic, then the only thing to do is to increase pandemic alert level and proceed with vaccine manufacturing and preparedness acitivities without any further dealy.

Giuseppe · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

Since this H7N9 seems to grow well in chicken's eggs, it is not much more simple to start monovalent vaccine production? Even with immunogenicity constraints, a moderately effective vaccines would be better than nothing.

gsgs · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

vaccine is usually less efficient than a real infection.
And a vaccine doesn't replicate and spread by itself ...

And Indonesia can probably not afford a vaccine

JimO · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

I agree. If there is this much concern in the minds of the public health experts, they need to use the pandemic alert system as it was designed.

Unfortunately, because pdmH1N1 was much more mild than feared, the WHO came under tremedous criticism for declaring a Pandemic. I'm concerned that they will be much more hesitant to raise the pandemic alert level.

Giuseppe Michieli said:
Since this H7N9 seems to grow well in chicken's eggs, it is not much more simple to start monovalent vaccine production? Even with immunogenicity constraints, a moderately effective vaccines would be better than nothing.

Giuseppe · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

It is the same thing current seasonal strains did.

A part the antigens, the interference between these viruses may alter the course of H7N9 infections and its spread.

It was suggested that H1pdm09 could have started an evolutionary pressure with unknown consequences on H5N1 viruses circulating in Asia at the time of pandemic onset in 2009.

This could be true also for this novel pathogen.

H3N2v in the US started to decline in human at the beginning of the 2012/13 winter flu season dominated by H3N2.

The weeks ahead will pave the way for the tropical summer flu season in some SE Asia regions: how will behave H7N9 under the pressure of H1pdm09 or H3N2?

Is it possible to advance hypothesis on this?

Bugonwindshield · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

One of the assertions in the article, that caused some debate, was that known infections are "the tip of the iceberg".

While this claim was not supported by any data, and I'm sure China is not hiding mass infections, some thoughts come to mind:

1. The first human cases must have happened well before the first 3 published cases.

Even the first 3 cases reported already demonstrated significant genetic diversity. With more data complied, a research comparing current outbreak to previous H7 type viruses in Netherlands and Italy concluded that the current H7N9 has been circulating for a long period.

http://www.reuters.com/article/2013/04/19/health-birdflu-circulation-idUSL5N0D54WN20130419

The news brief by CDC Taiwan, shows how difficult is was to confirm H7N9 infection, even when using the best technology RT-PCR and while already knowing about the virus and suspecting its presence based on clinical observation.

Therefore, it is safe to assume that unknown number of people were infected for unknown period before the identification of the novel H7N9.

It would have been interesting if China looked at death stats from pneumonia related complications over the last 12 months, comparing to seasonally adjusted historical data.

2. There are probably significant number of severe cases that are left without diagnosis.

The vast majority of identified cases are from cities. As far as I understand, even the identified farmers are from areas within metropolitan areas. I suspect many people in more remote villages has no access to modern medical services.
Naturally, these people are more exposed to poultry in small/domestic farms.
Again, China must have some stats on pneumonia related deaths.

3. As many already observed, mild or asymptomatic cases are obviously left undiagnosed.

One last comment about predicting the odds of pandemic.

Mathematically, prediction could be made, using the odds of getting a specific mutations, taking into account the rate of mutations as observed so far from genetic diversity. no one expect an exact number, but at least an order of magnitude can be calculated (i.e. 0.1%, 1% or 10%)

In my mind, if the odds were extremely low, we would know about it.
Nobody wants to alarm the public, when there is still nothing that can be done about it.
Hopefully, a vaccine will be developed soon and tested quickly and when it's time to decide if to make it en masse, some predictions would pop up, if only by interested parties

Giuseppe · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

The clue is about the pattern of severe acute respiratory infections currently observed in China.

Is this pattern substantially changed?

To calculate the pdm risk is also possible through R0 count, provided than the virus ability to transmit between human is not completely effective.

It seems there is little willingness to use Mathematical models previously employed to evaluate for example Nipah virus spread or H3N2v in the US.

We should ask the reason behind this cautious approach...

Shannon Bennett · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

Welcome Bugonwindshield.

All very pertinent observations and ones some of us have considered as well. Sharon and I have discussed the distinct possibility of multiple cases of infections prior to those published.

sharon sanders · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

Welcome Bug!

I have to say that I do not believe that the family cluster in early March were the first cases.

I do not care what TPTB think. I am laying it out here. FT is not affiliated with anyone. We do our own thing.

If you look in the forums noted below you will see articles that we have found regarding ILI/Pneumonia/Respiratory/Other illnesses. Without anything to tie these articles to we just posted them for posterity.

Looks like posterity is here now:

China - Pneumonia, Respiratory, and Influenza Like Illnesses (ILI)

China - Emerging Diseases, & Other Health Threats

jeffrey · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

I must tell you that I have been reading all the thread and comments and I am terrified of this turning into a Pandemic! I do agree with Sharon and looking at all the posts, that I think there was something going on before the first 3 cases were diagnosed.

I find it very odd that no one knows or can trace the cause for this illness. With all the professionals, virologists, scientists, Mds, etc. and we cannot as a world figure this out. It is unreal to me or maybe someone knows and no one is talking for different economic reasons.

I just hope and pray every day, that I will wake up and this will get a resolve, as it really has disrupted my life.

I want to say to all of you that have such great knowledge, it is wonderful to see such a group work together and bring the most up to date news here on FT. :tiphat:

sharon sanders · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

Jeffery do not let this disrupt your life. This is human history repeated. The difference now is that science/technology/communications are advanced so that we can watch this.

Go about your normal life but prepare for the natural disaster that typically occurs in your area. It should be something that you are familiar with. This way you are prepared for 2 or 3 days on your own. I am preparing for hurricane season and in addition I have a 90 days supply of my maintenance drug.

jeffrey · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

Have done, as we live in California and been through many earthquakes.

Thank you for the kind words, Sharon!

Bugonwindshield · May 1, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

Sharon,

I looked at the initial Mar 8 report of the family cluster.
It is quite obvious that because it was a family cluster and because it started rumors, the case was reported to the District Center for Disease Control sampling and epidemiological investigation.
The ball started rolling and eventually they figured it out.

It's almost certain that unknown number of middle aged or older men died of respiratory failure in different cities and nobody connected the dots.

I guess we'll never know when was the first human infection, and this is irrelevant now.

JJackson · May 2, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

Giuseppe Michieli said:
It is the same thing current seasonal strains did.

A part the antigens, the interference between these viruses may alter the course of H7N9 infections and its spread.

It was suggested that H1pdm09 could have started an evolutionary pressure with unknown consequences on H5N1 viruses circulating in Asia at the time of pandemic onset in 2009.

This could be true also for this novel pathogen.

H3N2v in the US started to decline in human at the beginning of the 2012/13 winter flu season dominated by H3N2.

The weeks ahead will pave the way for the tropical summer flu season in some SE Asia regions: how will behave H7N9 under the pressure of H1pdm09 or H3N2?

Is it possible to advance hypothesis on this?

I do not see how a virus circulating in birds could apply selection pressure on a virus circulating in mammals, or vice-a-versa.

Re. analysing the ILI deaths data I am not sure this will help - it is too blunt an instrument. As H7N9 still seems to be an avian virus causing sporadic zoonotic infections I suspect the up-tick in deaths would not be statistically significant against variations in background. I am sure there are many undiagnosed/misdiagnosed cases, both currently and prior to first identification, but even if our 100 odd cases is really 1000 or 10,000 against a population of 1.2 billion it is still tiny. I am in the UK, and scaling for population, those numbers become 5, 50 and 500. Unless, and until, it perfects h2h the numbers are too small and if it does become even moderately good at human transmission the clusters will become obvious first.

Re.

Bugonwindshield said:
Even the first 3 cases reported already demonstrated significant genetic diversity. With more data complied, a research comparing current outbreak to previous H7 type viruses in Netherlands and Italy concluded that the current H7N9 has been circulating for a long period.

I am not sure I would agree that there is much genetic variation in the sequences released and there is almost no data on circulating flu viruses in the potential host reservoirs. Rather than repeat all the reasoning again here if I could link to two previous posts. The first is to post #85 in the H7N9 - Discussion thread which has a table of sequence changes and some discussion of what they may mean and the second to the China - H7N9 Human Isolates on Deposit at GISAID thread and looks at how few relevant sequences there are.

Giuseppe · May 2, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

Ask WHO for the H1pdm09 and H5N1 connection!

They played this song back and forth at the time H1 became pandemic...

JJackson · May 2, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

It is all a numbers game. For a reassortment or recombination event you need a dual infection in the same cell.

For the HPAI H5N1 and H1N1(2009) case we can assume that danger is in a zoonotic H5N1 human infection which then gets human H1N1 (or H3N2) and the virus then has an extend palette to play with. The fact they got H1N1(2009) rather than the previous H1N1 seasonal flu, that it has largely displaced, seems to me to make little difference. We have no way of knowing which of the 3 - H3N2 and old or new H1N1 - is the greatest potential danger so swapping old for new could have increased, decreased or left the risk unchanged. Personally I think the change was a good thing based on the fact the old H1N1 was oseltamivir resistant and the new one is not, yet.

Regardless of this the number of zoonotic infections is small and both H5N1 and H7N9 are fit enough to retain their reservoirs in birds. At the same time they are also sufficiently well adapted to mammals to cause occasional zoonotic infections. The greater danger is that they will drift, or shift, in their avian reservoir - where they have far more infected hosts and many more serotypes to mix'n'match with - until a strain is created that causes a zoonotic infection with improved h2h and so clusters with pandemic potential.

gsgs · May 2, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

but ... we have all these reassortment studies in mice,ferrets,cell-cultures

H1 seems to be the most compatible candidate

http://www.flutrackers.com/forum/showthread.php?t=203696

JJackson · May 2, 2013

Re: Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

gsgs said:
but ... we have all these reassortment studies in mice,ferrets,cell-cultures

H1 seems to be the most compatible candidate

http://www.flutrackers.com/forum/showthread.php?t=203696

No disrespect to the studies but it has to happen in nature. A recombination with a mammalian adapted flu like, H1N1, has the great advantage - for the virus - in that any sequence picked up is going to already be mammalian adapted. Its problem is that there are so few occasions that a zoonotic and simultaneous human flu infection are going to occur it is going to have almost no opportunity to try and get it right. Given that it is already close enough in its current incarnation to cause human infections my guess, for that is all it can be, is that the greater likelihood is that the strain will genetically drift about in birds and some quasi-species package will seed an infection with a selection capable of giving it that small h2h edge it needs to form a small cluster. Once a short h2h chain is formed the honing of this skill would be rapid. So far whatever it perfects in one host is being lost if it does not seed an new infection and the virus has to reinvent the wheel each time - long may it continue like that.
What we need to hope for is that the strain which has this zoonotic ability will be at a fitness disadvantage to variants that are more avian and the current H7N9 will drift back towards the avian index and zoonotic infections will peter out.

Discussion - Chinese researchers speculate that Influenza A(H7N9) could cause a severe pandemic

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