Is H7N9 Spreading from Human to Human in China?

[curiosity]

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

Several H5N1 cases originated from preparation of slaughtered birds i.e defeathering, where feathers were found to have a high viral load. Therefore, if it is in poultry birds (ducks, chickens, doves - all of which are eaten) then infection would be most likely to occur during food preparation.

The issue with this is that many of the recorded H7N9 cases are in retirement home residents, so they are unlikely to have been preparing food. Several are recorded as 'not going out at all'. Therefore for a food link to apply, it has to be undercooked infected food IMHO.

When food borne outbreaks occur due to ecoli, salmonella, Hepatitis, etc... the source is often fresh, uncooked foods. Three possibilities (though not all) - 1.cook prepares chicken, cross contaminates other fresh, unwashed foods - actually quite common in institutional settings. 2. Chicken poop, duck poop, brambling poop - whatever the actual source is - ends up on fresh produce at a farm that distributes food to the locations - maybe the washing machines weren't working properly? Perhaps the water used for washing was contaminated? Perhaps the cleansing chemicals were ineffective? - The latter is one of the more common causes of food borne outbreak over wide geographical areas and have included lettuce farms, cantaloupes, eggs... 3. The fresh produce next to the chicken stalls at street markets are being contaminated. There have been of positive "environmental" samples.

[Vibrant62]

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

I think the potential for cross contamination of fresh and uncooked food during meal preparation is a valid argument, and one I had not considered before.

However, taking the retirement homes example, for a virus that would appear to be this infectious, how come the chef's and/or staff are not becoming infected during food handling? Or perhaps they have been and these might be 'mild' cases that have not been picked up.

I would hope they are doing serology testing of these contacts to find out one way or the other. It would be good to get positive confirmation from China that they have looked at this aspect, rather than only checking individuals by interview.

[Roehl_JC]

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

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.

[Catbird]

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

Does it strike anyone else as odd that everyday, at about the same time, 2 new H7N9 cases are announced?

It looks like the media is being "handled".

The media is definitely being handled.

Excerpt from an article in Japan's Asahi Shimbun:

"...To prevent groundless rumors from sparking public unrest, the Chinese government required the nation’s media to cover the H7N9 virus issue based on announcements of the Shanghai city government or the state-run Xinhua news agency."

While scanning Chinese language media sites last night (around 0800 Beijing time), I noticed that there was a significant decrease in the number of articles dealing with H7N9. Some of that could be attributed to the fact that the "rush" of the initial outbreak is past. But I also think that there may have been further "instructions" issued to the media in addition to what is mentioned in the article.

xhttp://ajw.asahi.com/article/economy/business/AJ201304080109

[Shannon Bennett]

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

Another thing to consider is that often, birds are dunked in scalding water to make it easier to pluck the feathers. This could partially sterilize the carcass during preparation. Also, although many of the confirmed cases are said to have a link to live poultry, there have to be a wide variation in exposure to poultry. I would guess that a large percentage of the population come into "contact" with poultry on a routine basis - walking through a live market, feeding domestic birds in the back yard, feeding pigeons in the park, participating in pigeon racing, etc. But, if this virus is not easily transmitted from bird to human, as many claim, then many of these poultry connections aren't relevent. This brings us back to one of three possibilities:

1) the virus is readilty transmissible from bird to human, but uncommon in poultry.

2) the virus does not transmit efficiently from bird to human, but is widespread in poultry so that a small percentage of poultry contacts results in serious infection without accompanying mild cases.

3) there is a large number of undetected or unreported mild cases resulting in the typical percentage of severe cases and fatalities for influenza (this scenario assumes H2H transmission).

I suppose there are other scenarios, but each of these can explain the number, distribution, and severity we've seen in confirmed cases.

Interesting thought. I have dunked birds into boing water myself to loosen the feathers prior to plucking. We know that plucking feathers from swans made people sick in the past. Dunking a bird for a few seconds would not be enough time to kill the virus. And, we know that several of the victims were smokers. Might be interesting to see if any of them plucked a bird then lit up a smoke with out washing their hands.

[Vibrant62]

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.

[curiosity]

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

However, taking the retirement homes example, for a virus that would appear to be this infectious, how come the chef's and/or staff are not becoming infected during food handling? Or perhaps they have been and these might be 'mild' cases that have not been picked up.

Either sub clinical or not infected - both viable possibilities and for the same reason not everyone gets sick when they eat the same meal contaminated with ecoli or salmonella - even if there is frank and obvious contamination.

There is more to the infectious process than the virus itself. There has to be:

Right person (susceptible)
Right route (oral mucosa probably not as efficient as respiratory)
Right dose (Enough live virion to make them sick)
Right environment (ph balance, temperature, moisture, etc...)

[curiosity]

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

mice first, then chickens, then ..., then children
(if it works)
I read one report about such chickens some years ago,
but never heard it again. Apparently it didn't work so well
as announced or the chickens were too expensive

I can't find it now

They would have to be genetically altered all at once.
By the time the last were genetically altered, the virus would figure out how to get into the mice again.

Smart, and as stated earlier "promiscuous", non-celled predators that they are.

[JimO]

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

That is a point that few are debating. There is a big piece of this puzzle missing. Swine don't apper to be the culprit, according to WHO.

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.

[jflorida]

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

Its hard to say where the politics and public policy trends end and where the truth and science begins in this. North Korea's issues in this also, if any, remain a big mystery (as a unintentional mixing/staging area).

Flu Genes Linked to South Korean, Chinese Birds [ http://english.caixin.com/2013-04-09/100511405.html ]

Researchers at the Chinese Academy of Science's Laboratory of Pathogenic Microbiology and Immunology say that the likely cause of the mutation is a virus carried by wild birds that migrated from South Korea to the Yangtze River Delta region. That virus then mixed with a virus in local ducks and chickens.

A research paper obtained by Caixin showed that out of the eight genes in the H7N9 bird flu, the H7 gene was found in ducks from the eastern province of Zhejiang that can be traced to wild birds from South Korea. The N9 gene was identical to a virus found in wild birds from South Korea.

The other six genes come from another type of avian flu, H9N2, which came from chickens in Shanghai and the provinces of Zhejiang and Jiangsu.
The research found no evidence of pigs being what scientists refer to as a host reservoir. Avian diseases are usually transmitted to humans through a host reservoir.


There is also no law in nature that demands that it must follow the most direct route from any particular unique perspective.

[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.