Is H7N9 Spreading from Human to Human in China?

[AlaskaDenise]

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

Following the links (at another site of the same paper), I found another paper referencing an updated test with 100% accuracy on wild birds. See:

Analytical Validation of a Real-Time Reverse Transcription Polymerase Chain Reaction Test for Pan-American Lineage H7 Subtype Avian Influenza Viruses

.

 

[jflorida]

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

Overall it was around 92 percent under controlled conditions and a small test size. But it does look much better and like you said it appears it can work with most of them. The whole paper:

Analytical validation of a real-time reverse transcription polymerase chain reaction test for
Pan-American lineage H7 subtype Avian influenza viruses [ http://naldc.nal.usda.gov/download/21378/PDF ]

 

[gsgs]

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

> The disease is a reassortment - perhaps just recently

molecular clock says > 1year ago

> A relatively mild avian disease with a rapid spread would move much more quickly
> than a pathogenic avian disease that kills off over half the population carrying it to others (i.e. H5N1).

there were subsequent reassortments and changes. It may have become a lethal human
spreader only recently (Chinese new year ?)

 

[Pathfinder]

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

Currently no positive samples of H7N9 found in pigs: WHO​

English.news.cn 2013-04-09 23:09:35​

...
WHO spokesperson Gregory Hartl ...

"At this point, there is no evidence of sustained human to human transmission," he said, adding that there are some "suspected but not yet confirmed cases of perhaps very limited transmission between close family members."

"They are still being investigated," he said.

Hartl told Xinhua one of the suspected family clusters was in Shanghai, with three family members having similar symptoms and one of them being confirmed of H7N9.

The confirmed case died, so has another suspected family member, according to Hartl.

The other suspected family cluster, which included two family members with one of them being confirmed, was in Jiangsu Province, he said.

Hartl said that even if the infection of H7N9 is confirmed in other family member, further investigations are still needed to make sure whether that's a human to human transmission between constant and close contacts or an infection with virus from the same environmental source.

...
http://news.xinhuanet.com/english/health/2013-04/09/c_124559399.htm

 

[curiosity]

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

> The disease is a reassortment - perhaps just recently

molecular clock says > 1year ago

> A relatively mild avian disease with a rapid spread would move much more quickly
> than a pathogenic avian disease that kills off over half the population carrying it to others (i.e. H5N1).

there were subsequent reassortments and changes. It may have become a lethal human
spreader only recently (Chinese new year ?)

Are avian hosts infected with an avian influenza virus always a reservoir or are they no longer infectious once they have fought off the infection?

If the fowl are only infectious while they are sick - and not simple "carriers" (like bats with other diseases), the rate of infection as it moves through a flock of susceptible birds would affect the rate of infection in the secondary, exposed, susceptible hosts (humans for example).

If there is a "seasonal" attack rate - say 5% (an arbitrary estimate) among fowl vs. a drifted variant that creates a 20% or more attack rate among fowl, the potential to expose the secondary host increases significantly.

Example: if the avian host's susceptibility is high (i.e. a drifted sequence bypassing last season's antibodies) the epidemic will move faster and through more flocks thereby increasing the geographical spread and amount of potentially infectious exposures. The infections would likewise increase in the secondary host.

Scenario One: Virus was reassorted a year ago (give or take a few days), but genetically drifted (perhaps by altering those very genes that make it suddenly susceptible to humans) to create a larger epidemic in wild birds that in turn increased the amount of exposure to humans.

Scenario Two: Virus was reassorted a year ago (give or take a few days), has remained genetically similar, but was inefficiently spreading among fowl. There were limited human exposures thereby limited opportunities to identify the illness in the occasional "unusual" fatality (people die from unexplained, atypical pneumonias and ARDS all the time - clusters are where investigations begin.) And only now, because the environment is just right, or the population in birds is just right, or any of those other chaotic factors are just right, the virus can move through the fowl efficiently and again - as last scenario - increasing the amount of infections in flocks that in turn increase the amount of exposure to humans.

Of course, still can't rule out H2H or foodborne. They are all hypothetical scenarios that can not be tested until a virus is detected outside of China or it becomes unmanageable and they ask for help from the international community.

There should be some indication ten days after the first poultry culling and market closures that cases are decreasing - IF - domestic poultry are the source.

It would be nice if there was more information on the "retired" population becoming ill. Actually, more epidemiological information on all the cases would be helpful in general.

Is there something to hide? For what possible and sane reason would the Chinese withhold and limit epidemiological information? Even in the interest of controlling "alarming" information - if there are not any epi links and no known H2H - why withold the information?

Informed people are much less scared than uninformed persons creating hypothesis that may or may not be realistic. Or worse, assuming they are not divulging information BECAUSE there is something disastrous happening.

Open up China! :magnify:

 

[Pirante]

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

This is not necessarily related to h2h transmission, but I just had an odd thought about transmissability in general. I've been wondering at the vector for the virus and a recent remark about it being potentially foodborne sparked the idea.

Isn't chicken feet (maybe bird feet in general) um a 'delicacy' there? If these birds are walking around through infected feces then they may themselves not be infected, but be able to carry the infection to other locations. For that matter you may not have to eat the feet at all, they'd just need to perch on something you touch then touch your eyes or mouth with.

For example if pigeons are the reservoir, or one of them, they could poop in an area where chickens walk, and the chickens, while testing un-infected (for a time) would then spread the disease to whoever happen to touch their feet. If the food were improperly prepared, that would only increase the infection risk.

Is this off base? I thought maybe it would do something to explain the odd spread and infection pattern clusters.

 

[Vibrant62]

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.

 

[Farmer]

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

Are avian hosts infected with an avian influenza virus always a reservoir or are they no longer infectious once they have fought off the infection?

If the fowl are only infectious while they are sick - and not simple "carriers" (like bats with other diseases), the rate of infection as it moves through a flock of susceptible birds would affect the rate of infection in the secondary, exposed, susceptible hosts (humans for example).

There is some evidence for short term shedding of influenza virus among experimentally infected asymptomatic ducks:

J Wildl Dis. 2012;48(4):991-8. Intestinal excretion of a wild bird-origin H3N8 low pathogenic avian influenza virus in mallards (Anas Platyrhynchos).
Brown JD, Berghaus RD, Costa TP, Poulson R, Carter DL, Lebarbenchon C, Stallknecht DE.

Abstract
Mallards (Anas platyrhynchos) and other dabbling ducks in the genus Anas are an important component of the wild bird reservoir for avian influenza (AI) virus; these viruses are maintained in migratory duck populations through a fecal-oral transmission route. We provide a detailed characterization of intestinal viral shedding in Mallards infected with a wild bird-origin low pathogenic (LP) AI virus. Five of eight, 1-mo-old Mallards inoculated with a high dose of an H3N8 LP AI virus became infected as determined by reisolation and seroconversion. Infected birds excreted high concentrations of virus for up to 14 days postinoculation (DPI) without exhibiting overt clinical signs of disease. The pattern of viral shedding was relatively consistent between individual birds, with peak shedding on 2-3 DPI and a progressive decline over the remainder of infection. Detection of viral shedding varied depending on sample type (excrement sample or cloacal swab) and diagnostic test (virus isolation or real-time quantitative reverse transcription polymerase chain reaction). Our data provide detailed insights into the intestinal excretion of an H3N8 LP AI virus in Mallards and the performance of diagnostic assays commonly used in wild bird surveillance. Such information is valuable for estimating potential risks for spillover of LP AI viruses from Mallards to domestic animals, developing accurate transmission models for Mallard populations and facilitating the interpretation and comparison of surveillance results from different studies.

http://www.ncbi.nlm.nih.gov/pubmed/23060500

 

[curiosity]

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

There is some evidence for short term shedding of influenza virus among experimentally infected asymptomatic ducks:

J Wildl Dis. 2012;48(4):991-8. Intestinal excretion of a wild bird-origin H3N8 low pathogenic avian influenza virus in mallards (Anas Platyrhynchos).
Brown JD, Berghaus RD, Costa TP, Poulson R, Carter DL, Lebarbenchon C, Stallknecht DE.

Abstract
Mallards (Anas platyrhynchos) and other dabbling ducks in the genus Anas are an important component of the wild bird reservoir for avian influenza (AI) virus; these viruses are maintained in migratory duck populations through a fecal-oral transmission route. We provide a detailed characterization of intestinal viral shedding in Mallards infected with a wild bird-origin low pathogenic (LP) AI virus. Five of eight, 1-mo-old Mallards inoculated with a high dose of an H3N8 LP AI virus became infected as determined by reisolation and seroconversion. Infected birds excreted high concentrations of virus for up to 14 days postinoculation (DPI) without exhibiting overt clinical signs of disease. The pattern of viral shedding was relatively consistent between individual birds, with peak shedding on 2-3 DPI and a progressive decline over the remainder of infection. Detection of viral shedding varied depending on sample type (excrement sample or cloacal swab) and diagnostic test (virus isolation or real-time quantitative reverse transcription polymerase chain reaction). Our data provide detailed insights into the intestinal excretion of an H3N8 LP AI virus in Mallards and the performance of diagnostic assays commonly used in wild bird surveillance. Such information is valuable for estimating potential risks for spillover of LP AI viruses from Mallards to domestic animals, developing accurate transmission models for Mallard populations and facilitating the interpretation and comparison of surveillance results from different studies.

http://www.ncbi.nlm.nih.gov/pubmed/23060500

The virus shedding, while longer in some species, still has an average end point? Are there any indications an avian host can merely "carry" the virus continually (over an indescript period of time?), regardless of recent exposure and increasing viral load secondary to infection (albeit asymptomatic?)

 

[JimO]

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.

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.

 

[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.