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Reconsidering human-to-human transmission of H7N9 in China, April 15, 2013
.......If there were human isolates without E627K or bird isolates with it, that would support the theory that this has so far been primarily a bird to human outbreak.
"The next major advancement in the health of American people will be determined by what the individual is willing to do for himself"-- John Knowles, Former President of the Rockefeller Foundation
Why would they hoard sequence data? There is so much talent on this site alone, you would think they would share all the information to get a better understanding from MANY minds.
Privacy
for
Public Health Leaders
The disease is well established as a crisis matter on the world stage; however, detailed statements concerning the causal factors have been slow and incomplete.
Pathways to success are being actively avoided. For example, any transitional disease is understood, even defined, via passage studies with the new host obviously serving as one passage medium. Properly managed serial samples display presence or absence of variation, diversity and perhaps adaptation. Serial samples of human cases may demonstrate actionable data. Calendar time has elapsed that would allow for 50% of the hospitalised cases to have had serial samples sequenced and deposited.
At this moment, exactly zero serial studies have had results discussed and, to be certain, precisely zero serial sequences have been offered.
That's just "Business as Usual".
Perhaps public health leaders would be appreciative if they were allowed to proceed privately.
One piece of information we have that is relevent to the virus's adaptation is that all four human isolates had E627K, while none of the bird isolates had this change. More sequences of both human and bird isolates would be very helpful in determining if this difference is persistent. If E627K causes a higher viral load, then that might partially explain why some cases progress more quickly or are more severe. If human isolates are found that do not have E627K and that correlates with milder cases, that would be an important discovery.
If there were human isolates without E627K or bird isolates with it, that would support the theory that this has so far been primarily a bird to human outbreak.
Primarily Bird->Human, multiple independent introductions. At this time.
Human->Bird reversal is seeding lightly human-adapted Influenza genetics (with step-wise Gain of Function toward alpha2,6 receptor specificity) to the bird strains for the bird strains to reprocess and accumulate. Slowly.
PB2 aa627 is one of many signals and should not be held as the prime determinant in this emergent H7N9.
PB2 aa627 is sensitive to host species, previous passage, sample location, sample incubation, et al. As such, the Lysine may vary at or below the trace threshold indeterminately, even when sampled from a mammal.
100% Correlation of Lysine to Mammal does not exist.
Curiosity: to me your theory sounds very plausible.
I have another element I would like to add, but it may just be a different way of saying what you were trying to!
If the early cases were caused by a less human adapted H7N9, then it could explain the longer time to hospitalisation. It would be expected that multiple mutations would occur within a single host over the course of infection. Natural selection would favour propogation of better adapted viruses within that host as the infection progressed, leading to accelerated replication in that individual host over time - until a critical viral mass/load is reached of better adapted viruses, leading to accelerated disease progression, which then goes on to cause serious disease = hospitalisation.
However, in the later cases, if the virus that infected these individuals had acquired some additional mutation/s at the time of infection, then fewer changes would be needed in a single host for it to acquire efficient replication = shorter time to hospitalisation.
We really need sequence data from all human cases to see how the H7N9 virus is changing, and see if there are any consensus variations that could explain things .. and as soon as possible.
If this theory were true we may continue to see a shortening of time from symptom onset to hospitalisation as new cases appear, and as full adaptation occurs i.e cases where onset to hospitalisation is 1 - 2 days could be a large red flag and herald the onset of a pandemic.
Dysfunctional Behaviour
is the Norm
In influenza, a linear relationship does not exist between speed of replication and host adaptation success level. Conversely, the transitional virus (early to mid-stride alternating between host species) may replicate at a distinctly higher rate (50% to 1,000%) causing advanced morbidity in the non-dominant genetic pairing, generally the human host.
At GeneWurx, we use the delightfully simplified term, "confused", to describe a virus moving into a new host before acquiring the necessary tools for a traditional life cycle in that host. This emergent H7N9 HA is genetically confused and emerges from a chain of genetic confusion reaching at least 4 years into the past and spanning more than 2 dozen host species (many mammalian).
Because unusual viral behaviours will occur during host-transition periods, application of equilibrium-based concepts is not generally advised. Dysfunctional behaviour is the norm. You are looking a new organism that may now be partially blind with inaccurate targeting, but H7N9 still has active weapons systems with lytic impact. Expect outlier behaviour and strong punctuation.
Your technique here of examining calendar durations from onset to critical care to recovery / fatality is entirely useful when taken against the specific genetic markers associated with each case and against the individual host pre-infection health status. However, even using the "less" and "more-adapted" terminology promotes the concept that science has previously understood the bounding elements of this particular emergent H7N9 background . . . and we haven't.
We do know that variation at certain positions on certain backgrounds may be associated with a set of viral behaviours. Those studied positions and values are neither exclusive, nor exhaustive. Those positional changes' outcomes are very dependent on the backgrounds (or surrounding genetics) in many cases and are confounding reversed in instances that remain inexplicable.
The standing viral science community has characterised far less than 10% of the functionality for the influenza genome matrix. Cross-referencing of those functional themes remains elusive in most cases. And this emergent H7N9 is novel in many ways. The HA is distant at important residues from all existing H7N9 and all existing H7N7 with the further compounding effects of voluble interaction with human H3N2, human and avian H5N1 including Wet Market surveillance sequences and human pH1N1.
Thoughtful and deliberate data gathering now, as each of you have so adroitly employed yourselves, creates possibility in the future of correlating to the specific fingerprints of each disease-causing organism based on the sequences.
Centre for Health Protection, Department of Health
I don't see the announcement there but could be missing it.
(When I tried to go to the source link in the headlineasia summary, (caijing), my virus software said it caught a script injection exploit or something like that and it wouldn't translate.)
"...there’s an obvious contest that’s happening between different sectors of the colonial ruling class in this country. And they would, if they could, lump us into their beef, their struggle." ---- Omali Yeshitela, African People’s Socialist Party
(My posts are not intended as advice or professional assessments of any kind.) Never forget Excalibur.
Re: Reconsidering human-to-human transmission of H7N9 in China, April 15, 2013
It's all right, all agreeable but with too many unknowns conclusion can't be correct.
Last year a triple (or quadruple) reassortant (H3N2v) started suddenly to spread in the US: in days it reached 300+ confirmed cases (without counting likely 'very mild' unnoticed cases).
The news of a swine-origin virus went almost unnoticed, out of the well known circle of flublogia.
However, we know as a even regional outbreak of H3N2(x) virus may cause severe damage especially in the older people.
Further, the instability of its structure (as demonstrated by the insertion of the M segment from H1pdm09) may put it into the list of suspected pandemic candidate.
Most of the H3N2v patients had a pig exposure but not all.
H3N2v, also, went unnoticed in pig population.
We have an immense domestic birds population in China and daily animal-to-human contacts.
The diffference between the US and the China story resides mostly in the antigenic conserved properties of the H3N2v (so that some degree of immunity exists into population), but this is not true for H7N9 (even though it is not known the level of exposure to prior H7/H9 in youngsters).
We cannot say whether H3N2v will pick up other genes from animal or human viruses and by this way, increasing its virulence and pathogenicity and transmissibility.
Despite this lack of knowledge, people went sooner distracted from this H3N2v, focusing on the Chinese strain (very Dangerous, indeed).
There is a clear bias in the evaluation of the events.
It is at the basis of the facts itself of being struck by surprise again and again by this novel H7N9: world was seeing obsessively toward H5N1 (or pdm09) when well other was smoldering elsewhere.
Re: Reconsidering human-to-human transmission of H7N9 in China, April 15, 2013
post #20, JetStuuby Today, 06:35 AM
post #21, Emily Today, 06:51 AM
post #22, Giuseppe Michieli, Today, 06:58 AM
post #23, JetStuuby, Today, 08:10 AM
post #24, Giuseppe Michieli, Today, 08:12 AM
post #25, JetStuuby, Today, 08:15 AM
post #26, gsgs, Today, 08:16 AM
(FT loads a bit slowly for me currently, maybe ~30% slower than normal)
that link freezes my browser :-( (but I can still go back to the previous page :-) )
OK, it worked with another browser (K-Melion) :
> The H7N9 virus because of the Q226L genetic variation when combined with upper respiratory
> tract cell protein alpha-2, can multiply in the upper respiratory tract similar to other seasonal
> influenza virus. When a person coughs the virus can be ejected from upper respiratory tract
> and infect another person, which increases opportunities for human-to-human transmission.
looks more like an opinion than an analysis or news event
Re: Reconsidering human-to-human transmission of H7N9 in China, April 15, 2013
Originally posted by JetStuuby
A good discussion of why it is h2h
link to PNG
Why has Emergent H7N9
NOT Gone Viral?
I can't believe that I'm arguing this side of the issue, but the facts are not elusive at this time.
If the statement and general direction found on the forum you mentioned held veracity:
Quote Redacted, My Paraphrase = H2H is the cause of ALL current H7N9 cases in China.
then probability suggests we would be seeing a far more rapid spread with considerable divergence in age groups. Spread has been slow for at least 6 weeks.
Without question, H2H has occurred, is occurring and will occur again. No one can argue against the fact that this disease has a special dispensation toward pandemic potential. But this thing at the moment must have a prima facieR0 approaching zero where 1.1 is a minimum for chained transmission.
B2H is the more probable primary route based on the sequences, the genetic history of the sequences and the epidemiology that is available at this time.
The combination of polymorphisms on the Hemagglutinin shows certain engagement in active host transition and is definitely acquiring signals that have been previously sampled from other serotypes that successfully adapted in Wet Markets, commercial poultry operations and companion animals.
Try to remember that we are not looking at a continuum or smooth progression between avian and mammal and certainly not a binary selection of avian or mammal.
Based on the data, the disease is alternating hosts and learning at most interactions, but has not yet "gone viral".
If we see emergence in Guizhou or Guangdong, then we'll likely find additional genetic revision within 21 days. At the end of that duration, a direction will be much clearer.
Even before then, if certain genetics are acquired, we must accept the fact of punctuated advancement that we've seen in recent zoonotic emergences. A spark is a spark. pH1N1, a confused reservoir, advanced through the Ukraine and officially put more people in graves over 6 weeks than the US reported in 6 months. Emergent H7N9 has the potential to "go viral" at noon today under the right circumstances.
But due to the intentional slowdown of public data production, we cannot presently quantify that potential.
Chinese police have broken up a criminal ring accused of taking meat from rats and foxes and selling it as lamb in the country's latest food safety scandal. The Ministry of Public Security released results ...
Re: Reconsidering human-to-human transmission of H7N9 in China, April 15, 2013
Okay, I'm just going to throw this scenario out there...
Shanghai and Wuxi City, Jiangsu Province are the central locations for the Rat Ring...
Rat meat for mutton = cheap prices on mutton ... What a deal!
Cooks buy "mutton" because of the great deal.
Retired people buy "mutton" because of the great deal.
Retirement homes serve "mutton" because it's a great deal...
(flaw - doesn't explain farmers, although, they probably like a good deal on "mutton", too - and if I was a chicken farmer, I would want a change of taste once in a while...)
Lamb is prepared in many different ways - sometimes served in "rare" or "medium rare" cooked versions.
Shanghai and Jiangsu are the first provinces reporting H7N9.
Rat Ring is beginning to be busted at end of January - ongoing arrest through February, March, April ...
In an effort to dispose of the product, the Rat Ring starts pushing the product away from the implicated areas - into other provinces surrounding Jiangsu and Shanghai (For a great deal, of course.)
The main ring is apprehended in Shanghai around Mid-late April - cases of H7N9 stop in Shanghai.
Cases across the provinces begin to dwindle (as far as we know).
From the beginning, the pattern of cases, erratic, wide geographic spread look similar to a food borne outbreak.
This scenario is really a bit far fetched... in fact, it's crazy, but my imagination just can't help itself.
Re: Reconsidering human-to-human transmission of H7N9 in China, April 15, 2013
Rats are a natural part of farm life. They are there for the abundant food. Farmers HATE them. If rats are a vector then a farm would be a natural place to encounter rats their feces, urine and saliva.
Please do not ask me for medical advice, I am not a medical doctor.
Avatar is a painting by Alan Pollack, titled, "Plague". I'm sure it was an accident that the plague girl happened to look almost like my twin.
Thank you,
Shannon Bennett
Okay, I'm just going to throw this scenario out there...
Shanghai and Wuxi City, Jiangsu Province are the central locations for the Rat Ring...
Rat meat for mutton = cheap prices on mutton ... What a deal!
Cooks buy "mutton" because of the great deal.
Retired people buy "mutton" because of the great deal.
Retirement homes serve "mutton" because it's a great deal...
(flaw - doesn't explain farmers, although, they probably like a good deal on "mutton", too - and if I was a chicken farmer, I would want a change of taste once in a while...)
Lamb is prepared in many different ways - sometimes served in "rare" or "medium rare" cooked versions.
Shanghai and Jiangsu are the first provinces reporting H7N9.
Rat Ring is beginning to be busted at end of January - ongoing arrest through February, March, April ...
In an effort to dispose of the product, the Rat Ring starts pushing the product away from the implicated areas - into other provinces surrounding Jiangsu and Shanghai (For a great deal, of course.)
The main ring is apprehended in Shanghai around Mid-late April - cases of H7N9 stop in Shanghai.
Cases across the provinces begin to dwindle (as far as we know).
From the beginning, the pattern of cases, erratic, wide geographic spread look similar to a food borne outbreak.
This scenario is really a bit far fetched... in fact, it's crazy, but my imagination just can't help itself.
It will be interesting to see since this is now widely published, if we may have our culprit. I think it is not far fetched at all. I wonder if they ask the patients if they ate lamb, now that we know??? Time will tell, but it is odd that this has just surfaced and no one in the Medical community can figure out the true culprit. Well maybe this is their answer and explains too, why the age group distribution
Last edited by jeffrey; May 3, 2013, 12:37 PM.
Reason: rewording
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