China - H7N9 Human Isolates on Deposit at GISAID

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

No public health thought leader has been given permission to admit that tiny birds are transporters because they can't trot an exterminator onto the dais and announce an eradication program. They'll stick to chickens until their credibility is scorched and then they'll move to migratory ducks.

All of these animals play certain roles. Determining the structure, elasticity, interplay and heteroskedasticity of each role is where the answers lie, but that foe of all bureaucrats, actual work, even creative work, is required. Public health tasking at this point should be to observe the vectors, to gather data and to build hypotheses AFTER validating that data.

Brilliant message management over social media has a place, but offers little to protect families and children when employed as a primary strategy. Though practiced often, pacification has not yet become a plausible plan against zoonotic disease.

[Vibrant62]

Re: China - H7N9 Human Isolates on Deposit at GISAID

NS1 - unfortunately, all too often in life the message 'manager' and associates end up believing their own propoganda, and get trapped in a wonderful circular logic chain that becomes increasingly divergent from reality.

That is why it is important that people like you keep calling things as they are based on hard evidence. I wish I understood more of what you say, but I get the top 10% - not enough for a deep understanding but enough to get the picture! Thank you.

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

NS1 - unfortunately, all too often in life the message 'manager' and associates end up believing their own propoganda, and get trapped in a wonderful circular logic chain that becomes increasingly divergent from reality.

That is why it is important that people like you keep calling things as they are based on hard evidence. I wish I understood more of what you say, but I get the top 10% - not enough for a deep understanding but enough to get the picture! Thank you.

And, Vibrant, if we watch closely what appears to be a circle we realise that the expected circle never forms at all, but that a spiral emerges of increasing radius elevating distance from fact over the temporal progression. At some point, the standing structure is so far distant from the foundation that stability is at question because the message-giver has little opportunity to even see the facts due to their investment in multi-layered imprecations obscuring the truth.

We are often told that "perception is reality".

In the world of marketers, wafting the ether of manipulation, that much may be considered as passable. But in the physical world, perception is meaningless when the laws of nature are violated.

No more evident than gravity is the fact of an emerging H7N9 zoonotic virus that is lytic to multi-tropic cell types while dysregulating human cytokinic expression. The transitional virus is not interested in press releases indicating species "boundaries", "reservoirs" or "dead-ending". The transitional virus is doing what transitional virus systems have always done . . . searching for new data that creates a better fit.

Our "Gain of Function" scientists would do well to ask themselves if conducting science after some bias restructuring might be a wiser investment of their expertise at this stage than allowing themselves to be marginalised by being proctored into salting the pacification press releases with psalmic science quants.

We all depend on the bench scientist in these matters. Will you turn away from the scribes and turn to the experiment table when so much is at stake?

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

China - H7N9 found in chickens says Harbin Veterinary Research Institute: wet markets and farms

From infected (including asymptomatic) vendors?

.

Unlocking
a
3 Piece 4D Puzzle

Existence of Keys to Emergent H7N9

A sub-clinical disease pattern in most host subjects of emergent H7N9 with low-to-no morbidity allows "silent spread" between the 3 vector classes with the various mammal species being the most important vector at this time. The genetic evidence presented on this thread and these forums should guide lab heads to task principal investigators with re-examining conventional conclusions about sub-segment viral interchange between terrestrial birds (primarily commercial poultry), mammals (people, canines, felines, mink, seals and whales) and roving birds (anseriformes and passerine).

Historical Method of Reservoir Identification

The emergent H7N9 dynamic may appear unusual in the area of pinpointing a reservoir, but is, in fact, no more unusual than the emergent 2009 H1N1 pandemic where no valid cornerstone reservoir was ever defined, though the public has been consistently led to believe the disease originated in swine. Effort has been expended at every level of virology, extensive effort, to validate the conventional science assumption of swine as the 2009 pandemic base.

More than 7,000 H1 swine sequences appear in the database today with 5,800 after 2004 and 4,900 since 2008. More swine sequences are on file for H1 serotypes than all H5 sequences of all species combined and 3 times the number of all H7 sequences for all species combined.

This costly pursuit of their assumption has not returned a positive finding, but has been prosecuted to adverse effect for surveillance on more probable subjects. The idea that science can conclude so rapidly on a complex problem with diminishing support data and with readily available confounding information defies the very concept of science, of knowledge discovery. This vehement adherence to traditional conclusions, nothing more than blind faith in practice, has no place in disease investigation.

Footing for H7N9 Emergence

The world entered this emergency with a toolkit built around the vast observational database for H7N9 of 26 sequences with analytic-limiting geographic and temporal dispersion (only 6 with 8 complete segments). Today, 4 weeks after announcement of a potential pandemic and 8 weeks after confirmed cases, a total of 15 H7N9 genomes are on file with 8 complete segments (47 HA, 36 HA+NA) and 2 of those are unacknowledged and unannotated practical duplicates with conflicting metadata.

Understanding the disease and preventing potential spread to 1.6 billion people (25% CAR) hinges on a count of pathogen specimens produced by the stellar international virology labs loitering at a population slightly higher than a baker's dozen box of doughnuts.

That's neither good eating, nor sufficient fuel for analysis. Confidence is not generally inspired by those striking so limited a foundation. Perhaps more remains to be understood concerning the initiation, development and maturation of pandemic virus reservoirs. And then again, perhaps the data is of no import to this matter:

Dys-Contiguous emergence in Hunan province was predicted on the 14th of April using the aforementioned limited genetic database. Yesterday, emergence was verified in Hunan as early as April 14th on a positive test confirmation.

System Dynamics of Vector Classes

Complex interplay exists between the three vector classes. Bi-directional transmission will eventually be understood at each level using the proper necropsy procedures and with revision of human testing sensitivity.

• Poultry incubates (chicken, duck with emphases on quail, chukkar, partridge & ratite)
• People incubate (male /female, both tails of the age-to-population curve: very young and very old)
• Passerines incubate and transport over distance (magpies, crows, jays, martins, swallows with emphases on pets & pigeons).

Emergent H7N9 with the proven movement of genetic data involving common passerines may appear daunting and fall outside standing models now, but the ΣH7N9 may be found at some point in the future to be using a very normal form of step-wise genetic acquisition for a pandemic goal-seeking organism. But we may never know because new models arise from data and H7N9 data is sparse geographically, sparse temporally and austerely sparse in every area but sparsity.

Exchange Proposal: Keys For Data

We'd like to propose an exchange: keys for data.

Participants are invited to explore anywhere you want with whatever vehicle you can start with these keys (Open Access, Full Text). Just report back what you find on your trek (GISAID with any ethical clinicals in any language). We've asked for specific data on many previous occasions and have offered the keys as well, but we'll give it another try:

Passerines: Pets & Pigeons
3P's of the emergent H7N9 Puzzle
These 3P's are not dissimilar to 3 keys.

Summary of RFI

One puzzle, four dimensions, three keys . . . all that's missing is one bright lab head. Who will invest the fourth dimension, take these keys, wrinkle the fabric and approach the puzzle?

[JJackson]

Re: China - H7N9 Human Isolates on Deposit at GISAID

NS1 I have to say I fully agree about trying to say any thing definitive from the sequence database. It has been like looking for a needle in a haystack.

We have both been trying to answer the question 'where did it come from, what is the reservoir?' by looking at the historical record but the real question is 'what historical record?'.

Looking at the geographical spread, of human infections, it would appear there has been a reassortment to create this H7N9 probably in the last couple of years and probably in SE China creating a reasonably fit virus. It has established itself in some natural reservoir.

Looking at the sequences for China - as the only source of information - you get no hits for H7N9 prior to its identification in humans. The box below (taken from my post #77 in the H7N9 - discussion thread)

Out of interest I thought I would query the GSAID database to see what the dominant avian serotypes in China were. I limited my search to 1/1/2010 or later.
Chickens returned several hundred sequences with H9N2 very dominant.
Ducks about 100. H9N2 also dominant but a lot more other subtypes so significantly more variation.
Geese 7 with 3 H5N1 and the others all different.
Turkeys, Quail, Guineafow and Paserines all none.
The 'other birds' category had 3 returns the current H7N9 pigeon, and two H9N2s an egret and our Bramling which has featured in this thread.
I ran the alignments for the egret and the bramling on the RNP genes and they are very different with 60 amino acid changes across the 4 strands.
Given the dearth of available sequence it is amazing we found the Bramling which is such a good match for the internal gene sequences.

.
If you assume domestic poultry are not the reservoir you can rule out the chickens and most of the ducks and geese which leaves you with 1 sample each from a pigeon, an egret and a brambling. Repeating the search in mammals for the same area and time period you get 178 hits and no wild animals at all. They were almost all swine with a few dogs and horses.

With 1.2 billion people and

Livestock in 2003: Cattle: 106 million; pigs: 465 million; sheep and goats: 300 million; chickens, ducks and geese: 14.2 billion. China is the world’s top consumer of meat and grain.

plus an astronomical number of wild animals and birds we have 3 relevant sequences with which to pin down what happened and in what species.

I hope these facts and figures will help those who do not look at the sequences databases to realise how speculative drawing any kind of definitive conclusions from the available data is.

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

NS1 I have to say I fully agree about trying to say any thing definitive from the sequence database. It has been like looking for a needle in a haystack.

We have both been trying to answer the question 'where did it come from, what is the reservoir?' by looking at the historical record but the real question is 'what historical record?'.

Looking at the geographical spread, of human infections, it would appear there has been a reassortment to create this H7N9 probably in the last couple of years and probably in SE China creating a reasonably fit virus. It has established itself in some natural reservoir.

Looking at the sequences for China - as the only source of information - you get no hits for H7N9 prior to its identification in humans. The box below (taken from my post #77 in the H7N9 - discussion thread) .
If you assume domestic poultry are not the reservoir you can rule out the chickens and most of the ducks and geese which leaves you with 1 sample each from a pigeon, an egret and a brambling. Repeating the search in mammals for the same area and time period you get 178 hits and no wild animals at all. They were almost all swine with a few dogs and horses.

With 1.2 billion people and plus an astronomical number of wild animals and birds we have 3 relevant sequences with which to pin down what happened and in what species.

I hope these facts and figures will help those who do not look at the sequences databases to realise how speculative drawing any kind of definitive conclusions from the available data is.

We will be able to identify a development pathway for emergent H7N9 using fewer than 200 sequences (with the characteristics we've requested).

Those BLAST outputs that are under 99% homology do not support the types of declarative statements being made in the major lab papers, especially on the HA and NA development.

A "good" match should be defined as a nucleotide distance in single digits. Recently the term has, unfortunately, been actively applied down to 92%, well outside the precision required for probable ancestry, because the viral geneticists are practicing under a technology base that is 25 years removed from today's platforms and thought leadership.

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

Preliminary
Prime H7N9 Emergence Geography
within
North America, Europe & Asia

Administrative Notice:
Human to Human transmission via airline travel is not being factored into this analysis as we calculate those effects to become more pronounced during a later phase. Others hold the city-pair data required to weight those functions and their models yield valuable logistics. Genetic host-transition phase effectors most active during early zoonoses inform the following rankings for contemporaneous, de novo human H7N9 emergence.

We recognise that sparsity may skew these evaluations and have called for more data. With this population of data, we fully understand that we are doing the equivalent of "looking for our keys under the streetlamp". That being said, we expect in the near future to revise these evaluations based on new information.

We must continue to consider that retrospective reporting may be intentionally delayed by public health officials due to our discussing these findings drawn from genetic tracing heuristics. Note that each government has different detection capabilities, reporting capacities and directions. Political motivations having little to nothing to do with the health and safety of citizens vary widely in sovereign states and coordinating health organisations.

If the United States chose to announce emergent H7N9 cases, prime emergence geographical candidates ordered by descending potential for appearance are the Carolinas, Colorado, Southern California and states in the Great Lakes area, with emphasis on Illinois, Pennsylvania, Wisconsin and Minnesota. Mid-Atlantic states group into the top 10 risk areas.

European signals include Spain, Sweden, UK, Germany and Austria at this time in that order of risk. The Baltics and Italy closely trail Austria followed by what was once the Eastern Bloc.

These geographies discussed are quite capable at the moment of hosting sub-clinical human infection that does not surveil at the upper respiratory tract for emergent H7N9, but that does co-infect at the level required to exchange emergent H7N9 sub-segment genetic data with a primary sH3N2 or pH1N1-infecting quasi-species.

Based on the sparse data, Colorado in the United States and Spain trailed closely by Sweden in Europe show the strongest regional signals, but are a full quartile beneath the predicted Hunan / Guizhou in China and Gyeonggi / Chungnam / Gyeongnam in Korea for human risk factors.

Dys-Contiguous emergence in Hunan province was predicted on the 14th of April using the aforementioned limited genetic database. Yesterday, emergence was verified in Hunan as early as April 14th on a positive test confirmation.

These signals concern multi-species geographic appearance & availability for genetic interplay. These early geographic emergences are not necessarily indicative of immediate human danger. Consistent accurate confirmation of emergent H7N9 is unlikely at the moment in these locations using the currently employed sub-par testing materials and procedures.

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

I do not believe that the wet markets are the source of H7N9.

It is not credible.

No source of the H7N9 infection has been identified by the government of China.

So what is it?

Memorable
Magpies & Martins

Probable
Pets & Pigeons

Tasty
Swallows & Swiftlets

We've been thinking a lot about Yàn Wō.

Cultural Delicacy and Healing Ingredient

Bird's Nest Soup is used for many infirmities including for age-related, male libido concerns and to restore a woman's skin to youthfulness. Chefs handle the raw materials; nests are soaked in room-temperature water as the first step in preparation, then are hand shredded and re-cleaned. Harvesters encounter small nests with significant amounts of feces and feathers. Though white nests are most common, the red "blood nests" command the highest prices.

The Golden Nest ® company lists the various species and nest types in their marketing literature (c). Many categories of dishes use bird's nest as primary ingredients including cold drinks. Preparation instructions are provided by Golden Nest that include Step 3: Rinsing:

rinsing step

For about few minutes, rinse the expanded, shredded nests under running water. While the previous Shredding Step exposes any left-over impurities that were buried deep inside the nests (if any), this step will remove it.

Habitat Disruption at Avian Source

Due to the heavy demand, many risk life and limb to climb for the highly-priced natural nests. In the past, most collections occurred from the natural roosting habitats of vertical cliffs and massive caves. Market changes have changed those earlier practices. Factory farms using Roku or giant artificial bird houses are located in coastal areas near urban populations to exploit the swiftlet's nests. Indonesia appears to be the world's largest exporter and generates a large market through Hong Kong exporting to the United States and China.

As China has grown wealthier and exhibition of status symbols has become more common, the demand for Yàn Wō has skyrocketed and coastal Indonesia has responded by building hundreds of multi-story buildings as artificial habitats for the swiftlets, including the White-Nest Swiftlet (Aerodramus fuciphagus). Water and insect attractant are provided. The avian diet will likely vary from normal fully wild, ranging birds.

Bird's nest soup has created a boom economy in Indonesia (North Sumatra) and the bird populations are counter-intuitively soaring.

As a result of the demand in Asia, the swiftlet's habitat has been dramatically disrupted in the past 10 years. Zoonosis is frequently found at those types of inflection points where habitat is disrupted due to human - animal interchange. Factory farms always create host-species transition events between humans and animals. Profit acceleration / animal exploitation schemes typically draw individuals without proper training in wildlife interaction / handling.

Swiftlet Biology and Ecology

Additional factors may be a work in this situation. Perhaps an avian specialist could give us an overview here? We do not know the bird-to-bird interaction pattern with swifts, but we do know that they do not generally spend unnecessary time on the ground. Breeding periods appear to span ~35 days and may occur 1 to 4 times a year. We do not know if the calendar cycle of the breeding periods.

If caves are natural habitats do swiftlets share space with bats or do they take over previous bat roosts? Echolocation is an unusual skill found in these edible-nest-building species. Should we, in the viral research community, even concern ourselves with bat interactions?

The male of the species is the nest-builder, generating saliva as the primary material, not just as the glue, but as the primary material. Is it possible that hormonal changes in the male during breeding season may create an immune variance allowing advanced replication or higher shedding of Influenza virus that are then incorporated unwittingly into the matrix of the nest?

If Ann Reid and JKT were able to rescue hundred year old virus RNA from AFIP paraffin blocks, then potential may exist that the viral deposits made by the male swiftlet during nest-building may be resuscitated in the incubation media of, well, broth.

Current Import Bans

Due to this concern, Australia and New Zealand ban imports with the expressed interest to protect their citizens from Avian Influenza.

Actionable Intelligence

As you may realise by now, precisely zero emergent H7N9 genetic samples are evident in the host species of various edible nest builders. You may be surprised to know that exactly zero Influenza isolates of any serotype are represented in GISAID from edible nest builders. One of mankind's newest intensively, factory-farmed species (~50 years) that interacts in host ranges with most H5N1 geographies is not studied at all?

Wildlife management experts should now be provisioning a basic kit of chalk, D-rings, quickdraws, nuts, cams, harnesses, ATCs, webbing and 24 pounds of 11mm dry rope next to a few sample bags.

Don't forget your swabs.

Please let us know what you find.

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

Request for Information
from
Veterinary Pathogen Storage Facilities

Perhaps your laboratory or university is interested in novel emergence vectors? A rough sketch is being developed concerning the threat of Pandemic H7N9. A potential host species reservoir / genetic development modulator has been surfaced for investigation and data is required in order to facilitate experimental design.

We have proposed a study direction concerning cave- and cliff-dwelling avian species with a coastal range that have come under intensive factory farming practices. Does your organisation or associated university hold pathogen samples of any kind or perhaps have biological insight / expertise concerning the potential avian emergent H7N9 reservoir host group of various Swiftlet species (edible bird nest builders)?

We understand that this concept is economically and culturally sensitive and somewhat counter-intuitive due to the strong adverse behavioural correlation of these species away from the ground. However, the target population of the product from these birds answers an unexplained age concentration of emergent H7N9 epidemiology and an occupation that continues to arise (chef / food service).

Recent disruption at the human-animal interaction boundary for this phenotype is unmistakable. The various species are grouped in taxa similarity to hummingbirds, an obvious behavioural & biological outlier group. Biological impact of the breeding cycle within Avian influenza host-species on viral genetic maturation and transmission is not well characterised, so we may wish to delve into swiftlet hormonal changes during breeding (corresponds temporally to nest-building activity multiple times per calendar year).

An investigation that determines if creatures with higher respiration / cardio rates (hummingbirds and perhaps swiftlets) also vary in various cell-rejuvenative genetic expression during breeding may be beneficial in characterising the "bildungsroman" of emergent H7N9. Potential replicative increases in commensal viral organisms during breeding may result in higher rates of viral genetic acquisition and in higher virus shedding in feces evacuation and upon egg laying, thus producing a more contaminated nest and a potential higher MOI for the human end-user / consumer of the nests that are often incubated in restaurants and homes, rather than cooked.

Collaboration is welcomed and will be gratefully acknowledged or discreetly managed according to your personal preference.

Is the field of science tasked with answering the unknowable? Does that spark of curiousity that drew you as a child to your experiments continue to inform your now extensive expertise? Think aloud with us for a few moments. Search for the answer.

Genetic evidence suggests that unchained co-emergent infections beyond Asia are presenting acquiring "Gain of Function" genetics and are incubating in humans and a minimum of 2 additional transmission vector classes. The international airline hubs in America and the UK are primed as human infection accelerators.

We estimate no gift of philanthropy higher than a deposit of influenza isolates at GISAID from edible-nest building Swiftlet host species.

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

America, Spain, UK
2013-05-01

Probability is above 70% that emergent H7N9 is incubating in America and above 63% in the UK as of 2013-05-01. The estimate for Spain lies closer to the US than the UK estimate.

At this time, morbidity and mortality may not necessarily be high or place the human populations at these geographic locales in substantial danger. The failure by public health officials to gather and publish the development of the offending organism does place the public in future danger. Case information is valuable as surveillance and would provide public health benefits as genetic maturation data points if published or communicated directly.

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

Request for Information
from
Veterinary Scientists
of
Britain, Scotland, Wales and Ireland

Even HA fragments from any H7 between 2006 and today would be appreciated.

Wild hosts carrying H7N9 (1990 to present) from the North Sea bordering geography would be an expressed delight if 13 or more total isolates were sequenced and deposited with metadata. We realise that those samples are profoundly rare, yet even the most strident curators of your institutes have been observed allowing observation when utility and common interest calls.

Are the world's deepest frozen collections able to produce 13 samples in the face of a crisis?

Please make no mistake . . . with this disease, utility calls.

[Nika]

Re: China - H7N9 Human Isolates on Deposit at GISAID

Birds nest soup is a luxury item.

Wouldnt we see cases in restaurant patrons and also in birds nest collectors?

(These guys arent just anyone off the street, takes skills to rock climb up to the nests etc)

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

Birds nest soup is a luxury item.

Wouldnt we see cases in restaurant patrons and also in birds nest collectors?

(These guys arent just anyone off the street, takes skills to rock climb up to the nests etc)

As a percentage, few lead climb; certainly some percentage top rope, but most use emplaced bamboo poles or other apparati.

Harvesters would have had "low and slow" exposures over time to the changing genetics of their flocks / harvest locations providing immune challenge and potential for innate and adaptive response. Serology may not have the specificity to detect earlier genetic backgrounds after 2011 and before 2013.

We'd like to see the epidemiology location tracing and contact tracing log books to determine how many times each patient had bird's nest as a food / drink or handled the raw material to prepare food / drink.

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

Low Probability
High Impact
Re-Assortments

H7N1 or H7N2 could certainly cause a severe pandemic.

Ranking, but Not Rating

As of yesterday, new epidemiological discussions, zoonotic outbreaks and sequences deposits have revised our rankings for Re-Assortment potential between emergent H7N9 and circulating human influenza. Due to sparse data on H7N9 and gaps at multiple stages that are essential to document the reservoir's maturation, we cannot reliably tender a quantitative rating for pH1N1 and sH3N2 reassortment potential. We are able to reliably compare potential between the two. Up to April 30, signals ranked sH3N2 as the most probable donor in a Neuraminidase Re-Assortment event with emergent H7N9.

Reversal as of 2013-05-01

Genetic signals today indicate that China, Spain, the UK and the US should be surveilling closely for H7N1 Re-Assortment followed closely by H7N2, very closely in Spain.

[NS1]

Re: China - H7N9 Human Isolates on Deposit at GISAID

A discussion concerning currently unvetted news that China's northern-most province is encountering moderate-scale respiratory illness is occurring around one of Al's great maps.

If you have information, please provide as much detail as possible.

Historical pH1N1 from Heilongjiang Province