Is H7N9 Spreading from Human to Human in China?

[gsgs]

Re: Is H7N9 Spreading from Human to Human in China?

curiosity,
I assume flu in birds is similar to humans, ~2 weeks, then immunity kills it and they
have increased immunity for some months which then may wane.
That's what they find in lab-tests.

Pirante,
we have no indication for foodborne spread. It only happened in H5N1 so far.
They will soon feed it to ferrets or tigers to test it
Watch for sick cats

Roehl JC,
E627K may emerge spontaneously within the host, no transmission necessary

Vibrant62,
it's one of those few mutations that adapts to the host.
Remember E627K in ****** ? Wasn't it also in Shanghai
ahh, jumping polymorphism

> A research paper obtained by Caixin
secrecy ...
> The N9 gene was identical to a virus found in wild birds from South Korea.
I believe it when I see the sequence at genbank

 

[AlaskaDenise]

Re: Is H7N9 Spreading from Human to Human in China?

...............Based on the genetics, I dont 'buy' a poultry to human transmission chain until we get an avian/ poultry sequence that includes E627k.

(drum roll, please....)(actually the Chinese DID point to the Korean wild birds)

polymerase PB2, partial [Influenza A virus (A/wild bird/Korea/A3/2011(H7N9))]

GenBank: AEK84613.1

LOCUS AEK84613 757 aa linear VRL 23-MAY-2012
DEFINITION polymerase PB2, partial [Influenza A virus (A/wild
bird/Korea/A3/2011(H7N9))].
ACCESSION AEK84613
VERSION AEK84613.1 GI:341610035
DBSOURCE accession JN244105.1
KEYWORDS .
SOURCE Influenza A virus (A/wild bird/Korea/A3/2011(H7N9))
ORGANISM Influenza A virus (A/wild bird/Korea/A3/2011(H7N9))
Viruses; ssRNA negative-strand viruses; Orthomyxoviridae;
Influenzavirus A.
REFERENCE 1 (residues 1 to 757)
AUTHORS Kim,H.R., Park,C.K., Lee,Y.J., Oem,J.K., Kang,H.M., Choi,J.G.,
Lee,O.S. and Bae,Y.C.
TITLE Low pathogenic H7 subtype avian influenza viruses isolated from
domestic ducks in South Korea and the close association with
isolates of wild birds
JOURNAL J. Gen. Virol. 93 (PT 6), 1278-1287 (2012)
PUBMED 22422062
REFERENCE 2 (residues 1 to 757)
AUTHORS Kim,H.R., Oem,J.K., Kang,H.M., Choi,J.G., Lee,Y.J., Lee,O.S.,
Kwon,J.H. and Bae,Y.C.
TITLE Direct Submission
JOURNAL Submitted (05-JUL-2011) Animal Disease Diagnosis Division, Animal
Plant and Fisheries Quarantine and Inspection Agency, 175 Anyangro,
Manangu, Anyangsi, Gyeonggido 430-757, Republic of Korea
COMMENT Method: conceptual translation.
FEATURES Location/Qualifiers
source 1..757
/organism="Influenza A virus (A/wild
bird/Korea/A3/2011(H7N9))"
/strain="A/wild bird/Korea/A3/11"
/serotype="H7N9"
/host="wild bird"
/db_xref="taxon:1055175"
/segment="1"
/country="South Korea"
/collection_date="Feb-2011"
Protein 1..>757
/product="polymerase PB2"
Region 1..757
/region_name="Flu_PB2"
/note="Influenza RNA-dependent RNA polymerase subunit PB2;
pfam00604"
/db_xref="CDD:109652"
CDS 1..757
/gene="PB2"
/coded_by="JN244105.1:1..>2272"
ORIGIN
1 merikelrdl msqsrtreil tkttvdhmai ikkytsgrqe knpalrmkwm mamkypitad
61 krimemiper neqgqtlwsk tndagsdrvm vsplavtwwn rngpttstvh ypkvyktyfe
121 kverlkhgtf gpvhfrnqvk irrrvdinpg hadlsakeaq dvimevvfpn evgariltse
181 sqltitkekk eelqdckiap lmvaymlere lvrktrflpv aggtssvyie vlhltqgtcw
241 eqmytpggev rnddvdqsli iaarnivrra tvsadplasl lemchstqig girmvdilrq
301 npteeqavdi ckaamglris ssfsfggftf krtsgssvkr eeevltgnlq tlkirvhegy
361 eeftmvgrra tailrkatrr liqlivsgrd eqsiaeaiiv amvfsqedcm ikavrgdlnf
421 vnranqrlnp mhqllrhfqk dakvlfqnwg iepidnvmgm igilpdmtps temslrgvrv
481 skmgvdeyss tervvvsidr flrvrdqrgn vllspeevse tqgtekltit ysssmmwein
541 gpesvlvnty qwiirnwetv kiqwsqdptm lynkmefepf qslvpkaarg qysgfvrtlf
601 qqmrdvlgtf dtvqiikllp faaaprkqsr mqfssltvnv rgsgmrilvr gnspvfnynk
661 atkrltvlgk dagaltedpd egtagvesav lrgflilgke dkrygpalsi nelsnlakge
721 kanvligqgd vvlvmkrkrd ssiltdsqta tkrirma
//

 

[AlaskaDenise]

Re: Is H7N9 Spreading from Human to Human in China?

There may a yet-undiscovered connection with the 8 Asian Human H5N1 2011 cases - all containing 627K. Bangladesh=1, Cambodia=2, Singapore=5.

.

 

[NS1]

Re: Is H7N9 Spreading from Human to Human in China?

There may a yet-undiscovered connection with the 8 Asian Human H5N1 2011 cases - all containing 627K. Bangladesh=1, Cambodia=2, Singapore=5.

.

Cross Serotype Homology
Hemagglutinin Amino Polymorphisms
Emergent H7N9 to H5N1 Human 2011 ​

We acknowledge the authors, originating and submitting laboratories of the sequences from GISAID?s EpiFlu? Database on which this research is based. The list is detailed in the attached PDF entitled "GISAID_Citations_H5N1_2011".

You are right on target. From a population of 38 human HA sequences in the H5N1 serotype in 2011, we find the following homology between human H5N1 2011 and human H7N9. The details were reported in a wider format at the noted post.

1. HA 189A WildType all 2011
2. HA 202V China Fatal 2008 (1), 2011 (1), 2012 (1), 2013 (2), Recovered 2009 (2) / Egypt Human 2011 / Vietnam Fatal 2004 (1), Human (4)
3. HA 277N WildType all 2011
4. HA 401N WildType all 2011, except Indonesia (3)
5. HA 533V WildType all 2011, except Indonesia (4)

Verify HA 189A, 202V, 277N, 401N, 533V (~H7 198A, 211V, 285N, 410N, 541V) at China - H7N9 Human Isolates on Deposit at GISAID - GeneWurx Cross Serotype Homology - Post #12

H5N1 2011 also shows polymorphic behaviour at related positions of HA 313T (Cambodia), 401S (Indonesia) & 533I (Indonesia).

 

[Vibrant62]

Re: Is H7N9 Spreading from Human to Human in China?

AD/ NS1 thanks, and this does demonstrate that the PB2 E627k can be found in wild birds; however it should make it less fit in those birds and therefore easily replaced in bird populations.

I was however thinking that I would like to see an avian H7N9 sample from currently infected fowl in China within the outbreak area that hosts the E627K mutation before I 'buy' a direct avian to human transmission chain i.e without there being an intermediate mammalian host.

 

[Pirante]

Re: Is H7N9 Spreading from Human to Human in China?

I like what Gsgs said about sick cats.

Could the transmission chain work like this?

Pigeon > Cat
(cat kills and eats an infected pigeon and gets infected)

At this point could the virus gain the mammal adaptation?

Then
Cat > Human (because seriously who wouldnt pet the pretty kitty that likes to wipe its cold wet infected nose all over your hand)

or the cat dies, and you go to
Cat > Chicken, (since they eat everything)
and then Chicken > Human

 

[camster]

Re: Is H7N9 Spreading from Human to Human in China?

So I talked a little bit about this yesterday in a different thread and I'm not trying to pick on anyone here, I just want to establish that this line of thinking is incorrect.

You have to stop thinking of sequence data in an "absolute" sense and think of it as probability fields with the most likely probability being represented. What is reported for a sequence is the majority consensus, but it doesn't represent the entire population. THIS IS ESPECIALLY TRUE FOR INFLUENZA which has built in diversity generation. In any given infected animal, human or otherwise, there is a very diverse population of virus sequences, intentionally created by a sloppy polymerase.

You can see that in actual sequence data, if you look at the picture here:
http://cnx.org/content/m44555/latest/?collection=col11448/latest

You see a sequence trace representing the determined sequence. You can also see MANY MINOR PRODUCTS underneath the larger majority bands. Some of these could be due to spurious reaction products, but most actually represent minor sequence variations in the population. And those are only the ones above the limit of detection. Anything less than 10% of the population will likely not be seen.

In any given bird influenza infection, the majority of the viruses may have E627, but a small percentage WILL HAVE K627. And those will be the viruses that propagate better in a human host when transferred, and the population dynamics will switch, causing K627 to now be the majority consensus sequence.

Staying in one host is a dead-end situation for the virus, it MUST transmit to survive, and to do so, it needs a variety of potential viruses that it generates via an error-prone polymerase. Transfer from bird to human is a basic evolutionary selection event. The minor population becomes the major as it is more fit in the new environment.

There is a good representation of how this sequence probability data is represented visually here:
http://molbio.mgh.harvard.edu/sheenweb/PromoterATAK&MZ06_.html

Having reviewed the sequences and the comments on sequences taken from poultry, pigeon & quails and comparing them with the known sequences of humans with the H7N9, here's my thinking:

1. None of the bird H7N9 sequences contain the PB2 E627k sequence.
2. All of the human H7N9 sequences contain the PB2 E627k sequence.

therefore IMHO none of the bird vectors are causing human infections.

H7N9 MUST have been evolving before the human cases were announced...it must have been evolving in MAMMALS....thus likely to have been in pigs, or rats or dogs or some other local hosts long enough to pick up this sequence from simultaneous H5N1 mammal cases.

It's much more likely that there is sustainable H2H infections going on.

 

[Vibrant62]

Re: Is H7N9 Spreading from Human to Human in China?

Many thanks Camster for furthering our understanding of this very complex area.

 

[camster]

Re: Is H7N9 Spreading from Human to Human in China?

Roehl HC's post is very valid IMHO.

What are the odds of the PB2 E627k mutation independently arising in each human case? This is what would be required to happen to explain the gene sequences and the fact that this mutation has not been found in the animal sequences... which leads us back to a mammalian intermediate host (which has a high level of exposure to the human population), or h2h transmission.

Based on the genetics, I dont 'buy' a poultry to human transmission chain until we get an avian/ poultry sequence that includes E627k.

The odds of independent mutations arising in so many locations is indeed very low. The odds that the starting material, a diverse virus population, held the mutation at a low percentage to begin with and that it was successfully selected out of the pool once transferred multiple times are very high.

In China, over 700 close contacts have been tested and the virus has not been found in them. For the 2009 pandemic, the virus was found twice when less than a dozen close contacts were tested.

 

[camster]

Re: Is H7N9 Spreading from Human to Human in China?

Many thanks Camster for furthering our understanding of this very complex area.

My pleasure, just trying to keep the discussion on track. None of this rules out H2H btw, just some of the evidence that is being presented.

We had a very similar situation in the states last year with H3N2v. The virus was popping up all over the place with no seeming connection in between (Maine, Indiana, Ohio, Hawaii) and people had similar difficulties believing there was no H2H to spread it so far. But when you recreate an almost identical environment multiple times, its almost silly to think you WON'T get the same result multiple times. H3N2v never took off. if there had been real H2H we would have seen it this past flu season.

 

[Shannon Bennett]

Re: Is H7N9 Spreading from Human to Human in China?

So what is the reservoir? I certainly agree that the virus is selecting what works best once in the victim but how did the victim get sick in the first place? Pigs, mice, cats, dogs, chickens, bramlings, pigeons are all possibilities. Whatever it is there is obviously a heck of a lot of it out there. This is a huge geographic area and a lot of people are getting sick who appear to be reclusive and/or invalids. What did they come into contact with, if not who?

 

[Nika]

Re: Is H7N9 Spreading from Human to Human in China?

You say 700 (more?) have been tested.

I think not.

Its my understanding that MANY of them were surveyed by phone. I do not think that many of these were assayed via rtPCR or other tests.

We need to not assume high quality veracity on our data points coming from China.

They have a massive conflict of interest. They - reflexively - censor/control all message. Second nature. This is the nature of a totalitarian government.

We assume that pigs (dead floaters or ones in ditches in farms or living ones) have been properly sampled and tested - 34 tested out of more than 20,000 floating in the river, countless more in the countryside.

What precisely was sampled? tested how?

Once the WHO and the US CDC is on the ground doing science & evidence based investigations (versus face-saving investigations) THEN we can begin to understand this entire situation.

 

[Vibrant62]

Re: Is H7N9 Spreading from Human to Human in China?

Nika - agreed. I gather that the WHO cannot send in an expert team until invited and that as yet, that invitation has not been forthcoming. I am not confident it ever will be.

 

[JimO]

Re: Is H7N9 Spreading from Human to Human in China?

Their not inviting the WHO just increases my mistrust. If they are being transparent, then they should have nothing to fear. Also, with the reports of arrests related to "spreading rumors", it wouldn't surprise me if people who are sick with a milder case are keeping their mouths shut out of fear of spreading panic.

I can imagine the phone interview:

"Hello, sir, this is the government and we're here to help you. Are you feeling sick?"

"Uh *cough* *cough*, no, why do you ask?"

"We're looking for traitors to imprison....uh....er....I mean, we are looking for people who might be sick and need medical care - so we can help you, of course." (throat clearing)

"Nope *cough cough*, nobody sick here *cough*. Everything is fine *cough cough - hack!*

"That's what I thought. You stay inside and don't talk to anyone ok."

"Yes sir *cough cough cough HACK!* you can count on me *GAG*.

Sorry, I've become a little jaded when it comes to China.

 

[camster]

Re: Is H7N9 Spreading from Human to Human in China?

So what is the reservoir? I certainly agree that the virus is selecting what works best once in the victim but how did the victim get sick in the first place? Pigs, mice, cats, dogs, chickens, bramlings, pigeons are all possibilities. Whatever it is there is obviously a heck of a lot of it out there. This is a huge geographic area and a lot of people are getting sick who appear to be reclusive and/or invalids. What did they come into contact with, if not who?

Most likely the birds, especially if it causes asymptomatic infection.
From the WHO (apologies for the lousy pasting):

Possible origin of the virus
It is considered likely that the new virus stems from a reassortment of three virus strains that infect
only birds:
?
The 6 genes coding for the internal proteins are similar to recent H9N2 viruses found in
China and South Korea. H9N2 viruses are endemic in birds, including poultry, in Asia and
elsewhere.
?
The gene for the N protein is similar to avian H11N9 viruses found
in South Korea in 2011; in
Hongze, Jiangsu, in 2010; and in the Czech Republic in 2005.
?
The gene for the H protein belongs to a Eurasian group of H7 avian influenza viruses.

Found here:
http://www.euro.who.int/__data/asse...fluenza-viruses-Virologic-features_update.pdf

 

[Nika]

Re: Is H7N9 Spreading from Human to Human in China?

Nika - agreed. I gather that the WHO cannot send in an expert team until invited and that as yet, that invitation has not been forthcoming. I am not confident it ever will be.

Yeah I have seen how WHO and US CDC are making entreaties.

Also, Taiwan has publicly rejected (or was turned down? who can know) working with China on a vax.

 

[camster]

Re: Is H7N9 Spreading from Human to Human in China?

You say 700 (more?) have been tested.

I think not.

Its my understanding that MANY of them were surveyed by phone. I do not think that many of these were assayed via rtPCR or other tests.

We need to not assume high quality veracity on our data points coming from China.

They have a massive conflict of interest. They - reflexively - censor/control all message. Second nature. This is the nature of a totalitarian government.

We assume that pigs (dead floaters or ones in ditches in farms or living ones) have been properly sampled and tested - 34 tested out of more than 20,000 floating in the river, countless more in the countryside.

What precisely was sampled? tested how?

Once the WHO and the US CDC is on the ground doing science & evidence based investigations (versus face-saving investigations) THEN we can begin to understand this entire situation.

Regarding the testing, a fair point and likely true. However, let me bring in some logistical arguments that I would have as a lab manager: If I were staring down the barrel of a potential pandemic, the last thing I would do is burn through all my limited reagents on some 'maybe they have its". Surveys are a very effective tool in disease surveillance, and I would use them to help focus the testing on the most likely suspects. (The point below someone else makes about open admissions in China is another fair one that would complicate things.)

Also, if you told me that my lab's job for the week was to go swab a bunch of dead pigs that had been floating around in some river for who knows how long and report back what we find, I'd smile and go do it, but I'd be very doubtful I'd find any surviving virus that hadn't already been munched by host nucleases or bacteria no longer under immunological suppression. Also we'd have to thoroughly test the river water they were find in to make sure that whatever we found wasn't just floating about to begin with. In other words, I wouldn't waste a lot of my time and resources on it when I'm more worried about what's going on in humans. I'd probably test about 50 or so and make a decision. The last thing I would want to say is "Sorry I'd love to investigate your outbreak, but we went through everything testing dead pigs."

And as far as suppression of information goes, the Good ol' US of A wouldn't let us even mention the fact that we'd 'discovered' the swine flu until the pandemic was well under way. Their motivation was slightly different, they figured that if the DOD came out and said we'd found a new virus, someone would say we'd planted it in the first place. Turns out they were right! But, hey people do love a good conspiracy theory.

 

[Vibrant62]

Re: Is H7N9 Spreading from Human to Human in China?

The dead pigs are gone, cremated or buried.

What would be useful however is testing the surviving swine from identified originating herds (i.e the farms that have admitted to dumping the dead swine) for either active virus testing or carrying out serology testing to detect past infection in the survivng swine. Trapping and catching vermin and testing a few of those at the same farms would also not go amiss, along with tests on any other resident mammalian wildlife.

Allowing a WHO expert team to work alongside Chinese expert teams would also not go amiss, and such an action would rule in or out pigs as a transmission vector for once and for all.

 

[Vibrant62]

Re: Is H7N9 Spreading from Human to Human in China?

Well this is good news. Better still if a WHO team were to be involved. Then there is no room for any doubts.

Pigs to be tested for virus

China's agriculture authority has expanded the monitoring for the H7N9 strain of bird flu to pigs in order to have a better understanding of the virus that had infected at least 33 people by Wednesday.

snip

Experts said that pigs have been included in the plan in an effort to better explore the transmission route, since it is still unknown why and how the bird flu virus infects human beings.

The World Health Organization said on its website that its analyses of the genes of influenza A H7 viruses have shown signs of adaptation to grow in mammalian species.

"These adaptations include an ability to bind to mammalian cells and to grow at temperatures close to the normal body temperature of mammals (which is lower than that of birds)," it said.

snip
Yao Jiezhang, a veterinarian and spokesman for the Beijing Bureau of Agriculture's animal husbandry and veterinary station, said that if pigs were found carrying the virus, people would get infected more easily.
http://europe.chinadaily.com.cn/china/2013-04/11/content_16391663.htm

 

[jflorida]

Re: Is H7N9 Spreading from Human to Human in China?

This investigation doesn't seem to be going in any solid direction as of yet it seems. I honestly cant say for sure even if H2H infection has occurred or not. Im not sure about the most basic characteristics of this virus or where it came from. Can/did it infect other animals besides some birds and how were they infected. I cant even say for sure if its just one unique virus is involved.

Today :

Until Wednesday, the source of the virus was not known but Chinese researchers said they had traced it to wild birds and chickens, Xinhua reported.

That sounds like a simple statement of fact but I honestly dont know what it means or if it is even really true.