H7N9 discussion thread: January 24, 2014 to Feb 5 2014 (closed)

[Shannon Bennett]

Re: H7N9 Discussion thread : recent (2014/01/23) increase in cases

One batch of infected chickens does not a vector make. At least if we are to believe that 1,000s of tests have been done on multiple chicken farms over the last year. Something doesn't add up.

The thought occurred to me that chicken 'farms' are supposed to be clean, while chicken from backyard operations are a possible source of infection. Repeated testing on farms continually shows no infection but, no country would have the ability to test every backyard operation. I believe wet markets are supplied by local small farm operations. Not the big chicken farms. That said, it still does not answer the question of why the virus has stayed only in eastern China, and why some of the victims have no association with chickens.

Pigeon, known as squab when it is on your dinner plate, might be the culprit. Pigeons flock together whenever they see a feeding opportunity. Close proximity would mean the disease would spread fairly quickly. Pigeons are ubiquitous to cities and to non urban environments. The pattern of infection should then move steadily outward from the epicenter, as each uninfected birds range is gradually intersected with an infected bird. I am somewhat skeptical the virus has spread less than 800 miles from its origin in any direction if pigeons are the carriers. Either we have a lot more cases outside of the known spread or, pigeons are not the vector. Either scenario is plausible. In any case time is growing short.

The spread of the disease and the caseload of infected continues to grow. It is inevitable that someone harboring both the H1N1 virus and the H7N9 simultaneously will provide the perfect vessel for reassortment. Hospitals would be a perfect for the two to meet and marry. Two people in the same hospital ward, both assumed to be sick with H1N1 but, one actually harbors the H7N9 virus, comingle their viral loads. Schools are just as likely a place for the two to intermingle. Either scenario spells pandemic. A year has gone by, the disease is grave and we still have no answer to the burning question of how and where people are getting infected. Random occasional testing on chicken farms has turned up nothing. It is past time to include more tests on more subjects (not chickens) in more places. The world waits with baited breath for answers.

[JJackson]

Re: H7N9 Discussion thread : recent (2014/01/23) increase in cases

Re. Where to swab?

This has also been an ongoing discussion since it was found that cloacal swabs were less effective in H5N1 collection. I forget who was being interviewed (I think it was Fauci or David Swayne) but it was just after the WHO team visit to China re H7N9 and they were saying that both swabs were being taken - at that time. As a side note on the testing regime Fauci gave an interview to the NEJM at about the same time was asked about the need for new investigative tools but I remember him saying the tools were fine the problem was in the way they were being used.

Re. Passerines
There were some relevant papers on H5N1 transmission. In one Sparrows and Chickens were infected and the contaminated drinking water from each given to an uninfected group of the other species. The sparrows infected the chickens but not vice-a-versa. They tested both cloacal and oropharyngeal samples and found slightly higher readings form the cloacal in both species. Another paper looked at pigeons and sparrows - again swabbed from both ends - the upshot of which was that pigeons were not a good host but sparrows were.

Re. H7N9 wild bird sampling
This link is to Technical Appendix Table 1. from Global distribution and prevalence of influenza H7N9 virus in wild birds.
The data covers the period 1998 to 2012 globally and I would recommend spending a few minutes scrutinising it carefully as you will learn a lot about the testing regime.
For example the Asia total test were 96,702 of which 72 were H7 (0.0745%), 41 were N9 (0.0424%) and 9 were H7N9 (0.0093%).
So for H7N9 they found 9 Asian samples (8 of which came form Taiwan. 1 from Mongolia and none from China). Again look at the samples taken China 158 but the tiny island of Taiwan 44,786. There is lots of information here about the way wild bird sampling is occurring - or not occurring - it just needs a little time to sort through.

P.S. Welcome to posting Skeeter. I see you have been a member for a few years but saved your first post until now.

[Shannon Bennett]

Re: H7N9 Discussion thread : recent (2014/01/23) increase in cases

Most interesting find JJackson. Far more questions than answers here. I am flummoxed when it comes to Chinese testing. According to these test results there is no H7N9 in China! Why so little? Is this not a complete list? Why not a lot more tests in the last year? Have they just not published their results yet? Are the papers being withheld from publication by Chinese authorities? Are market decisions in sole control of what is tested? i.e. Chickens are food and mallards far less so, therefore, only chickens are tested? Is there a mindset that wild birds are out of the countries control therefor it is pointless to test wild birds? If the last is true it would explain why we still have no idea how people are getting infected.

[sharon sanders]

Re: H7N9 Discussion thread : recent (2014/01/23) increase in cases

The only option they leave us is:

humans are the animal vectors...as humans are the most widespread (time + geographically) acknowledged outbreak.

I guess this is the direction of the Ministry of Agriculture....

[Giuseppe]

Re: H7N9 Discussion thread : recent (2014/01/23) increase in cases

Other H7 strains spread quite rapidly among poultry farms premises, as demonstrated by Italy recent H7N7 outbreaks. In few weeks millions of chickens have been affected and huge losses reported by owners.

And this was a HPAI strain.

If you have a non-pathogenic strain, the spread would be like wildfire and in the last twelve months the distribution in a large geographic area should have been reached with a big number of farms, both of small scale and industrial.

A vaccine for poultry has not been devised since the a-pathogenicity for animals.

Culling was not an option since this would have meant a massive stock destruction.

Humans, conversely, are quite expendable.

[sharon sanders]

Re: H7N9 Discussion thread : recent (2014/01/23) increase in cases

At least China is consistent. For each H5N1 case announced in the last several years the Ministry of Health denies any human source and the Ministry of Agriculture denies any animal source. Year after year......same old thing....and now we have H7N9.....and what's new?......nothing.....

[JJackson]

Re: H7N9 Discussion thread : recent (2014/01/23) increase in cases

Most interesting find JJackson. Far more questions than answers here. I am flummoxed when it comes to Chinese testing. According to these test results there is no H7N9 in China! Why so little? Is this not a complete list? Why not a lot more tests in the last year? Have they just not published their results yet? Are the papers being withheld from publication by Chinese authorities? Are market decisions in sole control of what is tested? i.e. Chickens are food and mallards far less so, therefore, only chickens are tested? Is there a mindset that wild birds are out of the countries control therefore it is pointless to test wild birds? If the last is true it would explain why we still have no idea how people are getting infected.

While China is an economic super power, in terms of total GDP, it is also a a population super power so the per capita GDP is not so great and all of this is relatively new. The Wild bird survey covers the period 1998 to 2012 and in that time Chinese per cap GDP went from US$ 821 to 6,762. In a list of countries this puts China currently about 90th of 187 adjacent to the likes of Macedonia or Belize now (for comparison Taiwan, who produced most of the samples, is 18th with $38,357, S Korea $31,950) or in 1998 it would have been more like 180th which is down with Mali and South Sudan. For a poor country like it was - and to a certain extent - still is it is unreasonable to expect a lot of general scientific research.
Coming back to the situation with sampling at present there are three streams of data.
MDs submitting human samples.
Vets submitting samples form commercial flocks.
Research into circulating strains.
The first two are generating a steady sequence stream but the latter is what we need at present and is not being systematically collected - as far as I can tell.
In human seasonal flu to understand what is happening in the wild we realised we could not rely on this kind of data and that a sentinel system taking representative population samples regularly was required and the richer countries all run these now.
The genetic pool of type A viruses most likely to re-assort into a human problem washes around primarily in Anseriformes (ducks et al) in SE Asia. If you want to know what is happening in this gene pool you need a surveillance system which is continuously collecting data in this region and producing monthly reports with a consistent format.
No Sampled - species - location (GPS) - % infections by Hn & Nn - Nos of dual infections and which sero-types involved in which species - for sequenced samples a # to tie sequences back to this meta-data etc.
I would particularly like to see a switch to GPS for location in all flu samples. In this day and age getting sampling and submitting labs to use an accurate and consistent time/date/location code does not seem like too much to ask. This change would allow for easy GIS representation and pin point sampling to specific rivers, lakes and migratory fly-ways.
I would read this more avidly than the MMWR or Euroflu reports.
I am not sure it is fair to ask the SE Asian countries covering the primary area to foot the full expense of this undertaking as it is of global importance.

[NS1]

Re: H7N9 Discussion thread : recent (2014/01/23) increase in cases

We know the Canadian case was H5N1, not H7N9, since the NML actually released the sequence from it.

What that means is that something in Beijing is capable of infecting humans with both H5N1 and H7N9. Asymptomatic poultry? Wild birds? Asymptomatic humans? A laboratory accident?

Trans-SeroType
Activity

Emergent H7N9 is in asymptomatic high circulation in humans at this time as is pH1N1, although in many more geographies. We have placed H7N9 on record as influencing pH1N1 development over the past 16 months. H5N1 is now and has been prevalent in Asia due to Wet Markets creating millions of interactions between H5N1 and humans everyday.

The Alberta H5N1 Human Fatality genetics openly demonstrate acquisition influence / homology from Emergent H7N9 and pH1N1, a Triple SeroType Confluence.

Unless the reservoirs for H5N1 and H7N9 happen to be somehow completely separated in the wild, co-habitation is implicit and the influenza system dynamic, although poorly characterised by standing institutions, is trans-sero active at this time. If passerines are a significant reservoir of each H5N1 and H7N9, then the trans-serotype activity should be expected at a delivery level, generating diversity in each viral classification.

Additionally, the human mixing vessel allows the infecting viral reservoir (multi-serotype) final preparations against mammal receptors. Current pH1N1 shows homology to early H1N1 genetics that from 1918 to 1933 developed particular tropism to neurological tissue in laboratory settings.

Confused, or highly polymorphic H5N1 (probable co-infection), has been shown to elicit neurological manifestations as in the young nurse from Red Deer, Alberta. pH1N1 is long on record with neurological manifestations in strongly avian strains and on base backgrounds given certain host conditions.

A single reservoir is not required for overlapping in a dynamic, multi-host system . . . only a single receptive host. These promiscuous reservoirs have proven that many combinations are possible. The only laboratory accident is the failure of prominent institutions to consider the dynamism of these serotype reservoir interactions.

[NS1]

Re: H7N9 Discussion thread : recent (2014/01/23) increase in cases

I do not believe the official central government announcements that H7N9 has not been found on poultry farms. I think it is a matter of food supply and the government not wanting to cut that important source of protein due to social unrest fears. Their actions indicate that their position is to warn people about poultry contact by advising them to thoroughly cook poultry and wash eggs before eating/handling.

After all, if wild birds land in live bird markets - they land on farms too.

How dumb do we look?

Absolutely correct.

Although the central planners have prepared arguments that seem perfectly reasonable in focus against each of these concerns, no totalitarian government should be considered transparent or forthcoming.

During the early phases of emergence, they regularly reported testing farms at rates into 5 and 6 figures of samples (10,000 to 300,000+). That's a production line that I'd like to see validated in a lab. How accurately can testing be done at those speeds when we are aware the tests are fallible?

[NS1]

Re: H7N9 Discussion thread : recent (2014/01/23) increase in cases

We know the Canadian case was H5N1, not H7N9, since the NML actually released the sequence from it.

What that means is that something in Beijing is capable of infecting humans with both H5N1 and H7N9. Asymptomatic poultry? Wild birds? Asymptomatic humans? A laboratory accident?

The case sampling and testing indicated H5N1.

However, absence of a positive test or genetic sample for H7N9 is not Evidence of Absence.

H7N9 cannot be excluded from influence in this case due to a negative result on a tarnished test.

[NS1]

Re: H7N9 Discussion thread : recent (2014/01/23) increase in cases

Video - Thousands of chickens escape after lorry overturns in China, Guizhou province

Some of the police are not wearing gloves as they collect chickens:

http://www.theguardian.com/world/vid...ns-china-video

Based on current genetic evidence, Guizhou is probable to suffer a focally intense outbreak of H7N9. In this scenario, H5N1 sub-segment influences will produce clinically-exceptional types of fatality in certain individual hosts.

By all estimations, severe H7N9 infections have been occurring there since April 2013, but are specifically not being reported.

[NS1]

Re: H7N9 Discussion thread : recent (2014/01/23) increase in cases

The spread of the disease and the caseload of infected continues to grow. It is inevitable that someone harboring both the H1N1 virus and the H7N9 simultaneously will provide the perfect vessel for reassortment. Hospitals would be a perfect for the two to meet and marry. Two people in the same hospital ward, both assumed to be sick with H1N1 but, one actually harbors the H7N9 virus, comingle their viral loads. Schools are just as likely a place for the two to intermingle. Either scenario spells pandemic. A year has gone by, the disease is grave and we still have no answer to the burning question of how and where people are getting infected. Random occasional testing on chicken farms has turned up nothing. It is past time to include more tests on more subjects (not chickens) in more places. The world waits with baited breath for answers.

A human or a bird.

Mixing vessels are everywhere.

As you may be aware, our research abhors the view that pH1N1 is considered to have originated in swine when no evidence has been presented even after the most extensive and expensive search in genetic history (4,000+ pig sequences).

pH1N1 avian analogues and direct infections certainly outdistance the official record.

Flocks of birds are a far more likely host mechanism for co-mingling of anything (H7N9, H5N1, et al) with pH1N1, the current dominant human infective strain.

A ReAssortment is not our major concern at the moment. As much focal damage can be done by a virus that has obtained useful transmission / replication genetics at the sub-segment level. pH1N1 is gaining information homologous to H7N9 and the street is apparently two-way.

Billions of experiments in living birds are underway at this time that will determine the outcomes of these sub-segment transfers. Nothing is new here except the managed messaging wave intended to quell the facts. The dynamic biological system is multi-host; regardless of the simplified graphics showing friendly roosters and suckling pigs.

The Red Deer, Alberta fatality is likely to have matched your co-mingling scenario, Shannon. In that case, H5N1 was just happened to be the fastest replicator of the multi-sero infective inputs.

[Vibrant62]

Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

NS1

A ReAssortment is not our major concern at the moment. As much focal damage can be done by a virus that has obtained useful transmission / replication genetics at the sub-segment level. pH1N1 is gaining information homologous to H7N9 and the street is apparently two-way.

A second case of human infection with H10N8 has been reported in China, and we have also had a range of novel avian flu's sporadically infecting humans, apparently for the first time, since 2009 - an H6 and an H16 as memory serves are two such examples that have been detected. Is it possible that some humanising characteristics have been introduced into the avian flu gene pool via pH1N1 and that these sub-segments are proliferating amongst a wide variety of avian flu's. Just wondering.

[NS1]

Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

NS1



A second case of human infection with H10N8 has been reported in China, and we have also had a range of novel avian flu's sporadically infecting humans, apparently for the first time, since 2009 - an H6 and an H16 as memory serves are two such examples that have been detected. Is it possible that some humanising characteristics have been introduced into the avian flu gene pool via pH1N1 and that these sub-segments are proliferating amongst a wide variety of avian flu's. Just wondering.

Most assuredly, earlier civilisations had a closer relationship and interchange with avian and other animal species than most humans who live on the earth today. Like the Chinese today, those earlier peoples had a different range and level of immune challenge to animal diseases than do the people now living in the Western world. The people of China are at a distinct advantage to the Western world as the H7N9 and sub-segment facets of H7N9 continue to spread beyond their nation.

Your thinking is logical given the media reporting bias that is in front of our eyes everyday. The establishment would like us all to focus on the one-offs, the exiting new emergent dead-ends, to take pressure off their inability to manage the annual human crises that predictably take millions of lives.

A circumspect introspection reminds us that the world system of influenza is continuously co-infecting and transferring genetic material. Only in the last 3 years has a base level of influenza genetics been available to allow the recognition that patterns of transfer exist and are an important facet of genetic maturation of strains geared toward humans.

While we are grateful that the pandemic that started in 2009 raised the level of surveillance to a usable base for predictive systems, we also accept the responsibility of encouraging a deeper and more actionable type of information gathering and response. Just because bench scientists are only now beginning to notice a process that has been occurring for thousands of years, doesn't make that process novel or imminent.

In fact, we should be cautioned that we know so little, and yet have such access to resources for knowledge acquisition in this immediate human health concern. Sadly, today is the baseline because most prior information has been gathered so haphazardly as to render it incomparable. If we don't modify the process soon, even today will be a poorly functioning baseline for decision makers 5 years from now.

Polymorphisms that move between serotypes do not always correlate to functionally equivalent outcomes. An infective flu reservoir in a certain host determines the outcome. By studying with great scrutiny the disease process, the deepest picture of the pathogen and the human genetics of the host, science will begin to build a foundation around Gain of Function research.

That research will show patterns of polymorphisms, sets, that travel together and correlate to specific outcomes in identifiable scenarios. Although singleton changes at times have a dramatic impact, understanding the set of related changes is much more important to predicting the system.

How that information is used at the policy level will turn the tide of human health, either for the benefit of the citizen or against them.

[NS1]

Re: H7N9 discussion thread: recent increase in cases, January 24, 2014+

NS1



A second case of human infection with H10N8 has been reported in China, and we have also had a range of novel avian flu's sporadically infecting humans, apparently for the first time, since 2009 - an H6 and an H16 as memory serves are two such examples that have been detected. Is it possible that some humanising characteristics have been introduced into the avian flu gene pool via pH1N1 and that these sub-segments are proliferating amongst a wide variety of avian flu's. Just wondering.

You may have been looking for a succinct response, eh, Vibrant?

Humanising polymorphisms do not necessarily propagate well through an avian-to-avian system, so persistence from a single infection chain is limited in most cases. But that biological fact does not preclude the practical outcome of humanising characteristics being transmitted through birds back to humans . . .

Re-Seeding from iterative human-to-avian interactions is a different dynamic and may show the same practical outcomes with commensurate transmission linkages as if the humanising polymorphism were persisting in the flock. Even an assembly line with a high defect rate will produce some viable outputs if a constant source of raw material is available.

These matters are left to be properly surveilled in nature, preferably downtown in large cities, with appropriate meta-data please.

More data from an active zoonosis is usable at this time.

It's not the humanising characteristic moving to H7N9 that is necessarily our deepest threat scenario. A highly diverse and receptive reservoir like pH1N1 gaining just the wrong set of aminos from H5N1, H9N2 and H7N9 is a concern.

As pH1N1 has finally settled on a base background after 5 years, the stage is set for a re-levelling effect that may involve significant avian influx.

Of course, then we have the transient host-switches, a group that doesn't really require transmission, per se, but appear to be in situ modifications based on the "origin-destination" species pair. but transient host-switching is a tale for another day.

How's that for a short answer?