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Norway - H1N1 "Mutation" Announced by Health Department

Re: Norway - H1N1 "Mutation" Announced by Health Department

Although this might be nothing like the Ukraine "plague" going on in the last few days the Norwegian Institute of Public Health has said that they detected the first to three cases of the mutation in two people that have died and one person that is seriously ill.
Only three mutations have been detected in more than 70 samples and no other mutations have been found. The virus is still sensitive to antiviral durgs including oseltamivir and zanamivir.

Similar mutations have been detected in Brazil, China, Japan, Mexico, Ukraine and the US according to the WHO. They also said

"Although information on all these cases is incomplete, several viruses showing the same mutation were detected in fatal cases, and the mutation has also been detected in some mild cases. Worldwide, viruses from numerous fatal cases have not shown the mutation. The public health significance of this finding is thus unclear."

"The mutations appear to occur sporadically and spontaneously. To date, no links between the small number of patients infected with the mutated virus have been found and the mutation does not appear to spread."

"The significance of the mutation is being assessed by scientists in the WHO network of influenza laboratories. Changes in viruses at the genetic level need to be constantly monitored. However, the significance of these changes is difficult to assess. Many mutations do not alter any important features of the virus or the illness it causes. For this reason, WHO also uses clinical and epidemiological data when making risk assessments."

What is strange is that they say that the H1N1 mutations have been detected in Norway and Ukraine but last week they said something different, the WHO said that the H1N1 strain in Ukraine was the same as in other parts of the world. Suddenly they have changed their tune and now apparently there was a mutation in the Ukraine.

http://fto.co.za/news/h1n1-has-mutated-norway-2009112015848.html
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

Norwegian scientists detect mutated form of swine flu


By Rob Stein
Washington Post Staff Writer
Friday, November 20, 2009; 3:53 PM


Scientists in Norway announced Friday they had detected a mutated form of the swine flu virus in two patients who died of the flu and a third who was severely ill, the most recent report of mutations in the virus that are being watched closely for any change that could make it more dangerous.



<script> <!-- var rn = ( Math.round( Math.random()*10000000000 ) ); document.write('<s\cript src="http://www.washingtonpost.com/wp-dyn/content/article/2009/11/20/AR2009112001820_StoryJs.js?'+rn+'"></s\cript>') ; // --> </script><script src="http://www.washingtonpost.com/wp-dyn/content/article/2009/11/20/AR2009112001820_StoryJs.js?6859715742"></script><script src="http://www.washingtonpost.com/wp-dyn/content/article/2009/11/20/AR2009112001820_StoryJs.js?4258038602"></script><script src="http://www.washingtonpost.com/wp-dyn/content/article/2009/11/20/AR2009112001820_StoryJs.js?1236387777"></script>
In a statement, the Norwegian Institute of Public Health said the mutation "could possibly make the virus more prone to infect deeper in the airways and thus cause more severe disease," such as pneumonia.

The institute said there was no indication that the mutation would hinder the ability of the vaccine to protect people from becoming infected or impair the effectiveness of antiviral drugs in treating people who became infected.



Scientists have analyzed about 70 viruses from confirmed Norwegian swine flu cases and found the mutation in only those three patients, Geir Stene-Larsen, the institute's director general, said in the statement.



"Based on what we know so far, it seems that the mutated virus does not circulate in the population, but might be a result of spontaneous changes which have occurred in these three patients," the statement said.



A top U.S. health official said the mutation was no reason for alarm.


"I don't think that it yet has the public health implications that we worry about," said Anne Schuchat, director of the federal Centers for Disease Control and Prevention's Center for Immunization and Respiratory Diseases. Schuchat noted that some patients have gotten severely ill, including developing pneumonia, after being infected with strains of the virus without the mutation.



The World Health Organization said viruses with a similar mutation had been detected in several other countries, including Brazil, China, Japan, Mexico, Ukraine and the United States. "No links between the small number of patients infected with the mutated virus have been found and the mutation does not appear to spread," the WHO said in a statement.



The Norwegian institute has been analyzing H1N1 virus from "a number of patients as part of the surveillance of the pandemic flu virus," and has detected several mutations, the statement said.



While the existence of mutations is normal, and most "will probably have little or no importance . . . one mutation has caught special interest."



The two patients who had the mutation and died were the first swine flu fatalities in Norway. The third patient found to have the mutated form of the virus also became severely ill.



Several flu experts said that the mutation should not cause widespread alarm. "Influenza is a mutable virus, and changes are to be expected," said Arnold S. Monto of the University of Michigan in an e-mail. "This is typical early in the spread of a pandemic virus."


Scientists around the world have been tracking the virus carefully for any signs that it had mutated into a more dangerous form. While a variety of mutations have been detected, most have not appeared to have affected the virus in any significant way.



There have been some mutations that make the virus more resistant to antiviral drugs, experts said, but -- like the mutation that may cause more severe illness -- those, too, seem self-contained.

"It is, at the moment, reassuring that this appears not to be spreading," said William Schaffner, of Vanderbilt University. He said ."mutations that make episodes of swine flu more severe are most dangerous only if they are "easily transmissible." "That's a different characteristic," Schaffner said. "And apparently that does not appear to have happened to this virus. It does not seem to be spreading in the general populatio.

Detection of the mutation should be reassuring, Schaffner said, because it illustrates the intensity of the global effort to monitor the virus. "The virologists are keeping an eye on H1N1 and this is evidence of that," Schaffner said. "We should be pleased the virologists are doing such a good job of tracking this flu virus."


The CDC, meanwhile, is investigating a cluster of four cases of patients at the Duke University Medical Center in Durham, N.C., who were found to be infected with H1N1 virus that was resistant to the antiviral drug Tamiflu. All four patients were treated with another antiviral drug, known as Relenza.



The news of virus mutations came as the level of flu activity in the United States appeared to be declining. The number of states reporting widespread flu activity dropped from 46 to 43 in the past week, and had dropped in all 10 regions across the country, the CDC said.



But Schuchat said flu cases were still rising in some states and it was too soon to know whether activity would surge again. Officials were especially worried about the upcoming Thanksgiving holiday, when many people would be traveling and families will be gathering, increasing the chances of the virus spreading.
 
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Re: Norway - H1N1 "Mutation" Announced by Health Department

I believe it's been seen in the U.S. But associated with mild disease. I believe. I might need to verify that.

I thought there was no testing of 'mild' disease...


Roehl_JC, I agree, the tune keeps changing.
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

Norway Flu Strain May Make Disease Worse; Wales Mutation Seen
http://www.bloomberg.com/apps/news?pid=20601087&sid=aEhvd7R2HL80&pos=8

By Michelle Fay Cortez and Marianne Stigset

Nov. 20 (Bloomberg) -- European public health officials are investigating a handful of swine flu infections in Norway and Wales in which the virus mutated to a form that?s more severe or less sensitive to drug treatment.
Five patients at a hospital in Wales contracted swine flu that resisted treatment with Roche Holding AG?s Tamiflu, and three more infections are still being analyzed, the U.K. Health Protection Agency said today. Another mutation that may trigger a more severe infection was discovered in Norway among two patients who died of the flu and one who was severely ill with the disease out of 70 cases tested, the Oslo-based Institute of Public Health said.
The mutated virus is more difficult to pass from person to person, according to David Mercer, acting head of the communicable diseases unit of the WHO?s European region, and Geir Stene-Larsen, the head of the Norwegian institute.
?We take this development seriously, but the HPA currently considers that the risk to the general healthy population is low,? the U.K. Department of Health said in a statement about the Wales cases. ?The Tamiflu-resistant virus has emerged in a group of particularly vulnerable individuals. These patients are known to be at increased risk of developing resistance to the drug.?


more at http://www.bloomberg.com/apps/news?pid=20601087&sid=aEhvd7R2HL80&pos=8

 
Re: Norway - H1N1 "Mutation" Announced by Health Department

We have post about the precedent in U.S. on mutations

Didier Raoult - 2 cases of H1N1 deaths in U.S. by a mutated H1N1 - More in India? (
multipage.gif
1 2)

It has not gone like a WildFire
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

Although this might be nothing like the Ukraine "plague" going on in the last few days the Norwegian Institute of Public Health has said that they detected the first to three cases of the mutation in two people that have died and one person that is seriously ill.
Only three mutations have been detected in more than 70 samples and no other mutations have been found. The virus is still sensitive to antiviral durgs including oseltamivir and zanamivir.

Similar mutations have been detected in Brazil, China, Japan, Mexico, Ukraine and the US according to the WHO. They also said

"Although information on all these cases is incomplete, several viruses showing the same mutation were detected in fatal cases, and the mutation has also been detected in some mild cases. Worldwide, viruses from numerous fatal cases have not shown the mutation. The public health significance of this finding is thus unclear."

"The mutations appear to occur sporadically and spontaneously. To date, no links between the small number of patients infected with the mutated virus have been found and the mutation does not appear to spread."

"The significance of the mutation is being assessed by scientists in the WHO network of influenza laboratories. Changes in viruses at the genetic level need to be constantly monitored. However, the significance of these changes is difficult to assess. Many mutations do not alter any important features of the virus or the illness it causes. For this reason, WHO also uses clinical and epidemiological data when making risk assessments."

What is strange is that they say that the H1N1 mutations have been detected in Norway and Ukraine but last week they said something different, the WHO said that the H1N1 strain in Ukraine was the same as in other parts of the world. Suddenly they have changed their tune and now apparently there was a mutation in the Ukraine.

http://fto.co.za/news/h1n1-has-mutated-norway-2009112015848.html

Who did likely refer to the antigenic properties of the H1N1 2009 viruses isolated so far.

Mutation in HA could alter the antigenicity and thus an hemagglutinin inhibition test with vaccine reference strain antisera should be performed in order to dispel this new concern.
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

I would also make a further note: in Italy we have had a spike in number of fatalities due to H1N1 2009.

From Nov. 9 to date, the number passed from around 30 to near 70.

Half of these fatalities occurred in Campania region.

More on FT: http://im.ly/af42d/
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

the CDC just didn't recognize that D225G is associated with more severe
illness or the virus/hosts/weather/... is different in Europe ?


if D225G is now more dangerous on the current genetical background
then it may spread or it may signal potential for further such
changes, where D225G is expressed differently again



Norwegian research isn't better than US-research
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

H1N1 Mutation Detected Earlier, Not Widespread, WHO Says


By BETSY MCKAY

The Norwegian Institute of Public Health said Friday it has identified a mutated form of the H1N1 flu virus in two patients who died and a third who developed a severe form of the disease.


In a statement posted Friday on its Web site, the institute said the mutation appeared to make the virus cause infection deeper in the respiratory system, thereby causing more severe disease. The two patients who died were the country's first confirmed fatalities.

Flu viruses are notoriously fickle and mutate frequently, producing new strains every year to cause seasonal flu. Scientists and public health officials from around the world have been watching closely for possible mutations of the new flu virus, particularly for changes that might make the disease more severe or a vaccine currently being manufactured less effective, but haven't identified any major changes.


The World Health Organization and the U.S. Centers for Disease Control and Prevention said the mutation has been seen before, not always in severe cases. It's not widespread, and the current H1N1 vaccine and antivirals oseltamivir and zanamivir are effective against it, the WHO said in a statement.


The mutation has been detected before in Mexico, the U.S., Brazil, China, Japan, and Ukraine, with the earliest detection dating back to April, the agency said.


Geir Stene-Larsen, director general of the Norwegian Institute of Public Health, said the mutation had been found in only three of 70 viruses from cases in Norway examined by scientists, and doesn't appear to have spread.


"Based on what we know so far, it seems that the mutated virus does not circulate in the population, but might be a result of spontaneous changes which have occurred in these three patients," Dr. Stene-Larsen.


"There is no indication that this change in the virus is of any importance for the effect of the vaccine or the effect of antiviral treatment," Dr. Stene-Larsen said.


"This mutation has been seen sporadically, sometimes in patients who had very mild disease," said Anne Schuchat, director of the CDC's National Center for Immunization and Respiratory Diseases.



While an important finding for scientists who study viruses, she said its implications for public health weren't clear. "It's too soon for us to say what this is going to mean long term."


"The mutations appear to occur sporadically and spontaneously," the WHO said. "To date, no links between the small number of patients infected with the mutated virus have been found and the mutation does not appear to spread."
"Athough further investigation is under way, no evidence currently suggests that these mutations are leading to an unusual increase in the number of H1N1 infections or a greater number of severe or fatal cases," the WHO said.
Meanwhile, the number of states reporting widespread influenza activity in the U.S. declined for the second straight week, suggesting H1N1 illnesses may have peaked.


Forty-three states reported widespread influenza activity for the week ending Nov. 13, a decline from 46 states the previous week. CDC officials also said reports have been increasing in a few states, including Maine and Hawaii.


Some 11 million additional doses of H1N1 vaccine became available since last week, bringing the total number of doses made and shipped to 54.1 million. Dr. Schuchat said the states are ordering the vaccine as fast as it's being made available.


<cite class="tagline">?Jennifer Corbett Dooren contributed to this article.</cite>
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

> There is no indication that this change in the virus is of any
> importance for the effect of the vaccine or the effect of
> antiviral treatment,"

but maybe virulence in the first place

4 from 10 Ukraine viruses from fatal cases at GISAID
are said to have it. CDC,WHO must know that...
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

#69:
" The mutation has been detected before in Mexico, the U.S., Brazil, China, Japan, and Ukraine, with the earliest detection dating back to April, the agency said."



Now it is obvious that when at the same time the official public mantra was "the virus is stable"/"slightly diferent", it already had deadly mutations worldwide.

We could only imagin the minimizations if worst wave events starts,
but the free travel mantra remains as a rock:
"the spice must flow".
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

2009-11-20

225G New to Norway and Ukraine; Worldwide Evaluation Concerning Range and Co-Circulation with 225E

?? viruses with a similar mutation had been detected in several other countries, including Brazil, China, Japan, Mexico, Ukraine and the United States. "No links between the small number of patients infected with the mutated virus have been found and the mutation does not appear to spread," ...?

If the official statement in today?s Washington Post is accurate concerning the circulating geography of the Norway polymorphism associated with several fatalities, then the only probable selection is 225G. Evaluating the meta-data of available published and partially public sequences, no other SNP of interest corresponds to the range stipulated.

The positive statement indicating low transmissibility of 225G, however, is not supportable at this time by solid evidence due to lack of surveillance using the proper tools and testing protocols. The statement is perhaps intended to assuage rather than inform.

Countries with Probable * or Confirmed 225G


While 225G is probable or confirmed with very limited depth in 12 countries, our team is more concerned about the extensive range of 225E at the moment, documented with considerable penetration in at least 21 countries, including island nations and prominent international tourism hotspots. At any measure, the 225E circulating range is wider and deeper than 225G though the two overlap geography in at least 6 countries. Linked SNPs of interest appear to be more involved, as 225E demonstrates several clear acquisition paths that are not apparent with 225G.

Though the clinical attributions are not presently noted as a corollary to fatal cases like 225G, the accompanying changes and multiple backgrounds onto which the Glutamate at 225 (225E) is found may eventually provide a substantially more capable viral strain and most certainly is providing co-circulating sub-species of high interest alongside the 225G.

225G does, of course, merit scrutiny due to patterning with 230I on H1N1 Seasonal 2008 and 2009 sequences. If the range of 225G continues to smoulder, an attractant effect may draw 230I due to co-infection in areas that continue to have Seasonal H1N1 strains in circulation. The very high level of bird involvement in transporting genetics across serotypes may provide proximity, attraction and opportunity for H5N1 as a donor candidate for 230I due to verified H5N1 ranges at geographic inflection points for PF11. The world may not yet be seeing this permutation (225G & 230I) because the shortened infection to expiration timing also provides less time for viral recombination.

This 1918 and Avian SNP travels with H1N1 and H5N1 Avian polymorphisms indicating potential wild bird transport vectors. In a human host, the Avian modifications may find advantage at certain tissue types due to body core proximity providing basal temperature increases and may drive replication behaviour. The human lung may be precisely the correct temperature to promote rapid replication, more efficient binding or improved cleavage capability.

Influenza Flux will eventually find the appropriate or optimal combination of genetics to achieve stasis, but until that stasis of PF11<sub>>Ω </sub>is achieved, these sub-species will continue to be quite dangerous, demonstrating varying levels of Cytokinic Dysregulation according the host-pathogen interplay and the viral strain's capacity for temporarily suspending early catalysts to the innate immune response.

As the data are released, including the sequences, presentation and progression, testing protocols, sampling protocols, prognoses, sequencing lab procedures and epidemiology, a higher level of interpretation may be made concerning these polymorphisms based on facts, rather than speculation.

A present 225G sequence set of less than 25 instances within ΣPF11 and those few having little to no associated clinicals does not provide a stable foundation at this time for determination of emergent characteristics such as rate of transmissibility, probability of co-infection with wildtype or spontaneous revision from wt due to tropism upon attaining deep lung infection.
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

hat tip FT Resident Revere -
Trying to understand the Norwegian swine flu mutations

Category: Genetic sequences ? Influenza treatment ? Surveillance ? Swine flu ? biology
Posted on: November 21, 2009 6:03 AM, by revere
The Norwegian Institute of Public Health is reporting sporadic occurrences of a mutation in a portion of the flu virus that is involved with the process by which it attaches to cells. I use the word "sporadic" because at this point there is no evidence that the cases where the genetic change has been found are epidemiologically linked. Therefore we don't see it spreading from person to person but rather arising in people after they have been infected. At least that's how it appears from reports, but we have only preliminary information at this point. According to WHO, the mutation has been seen before, again sporadically and as early as April, in Brazil, China, Japan, Mexico, Ukraine, and the US. Should we be worried about it?
For me that's not exactly the right question because I worry about everything when it comes to influenza. Just like auto accidents, flu infections come in a huge range of severity from barely visible scratches to fender benders to whip lash to multiple disabling injury to death. I don't take the potential of being hit by a car lightly either. Any instance could kill me or someone I love. The right question is whether I am especially worried about this report. Not yet. As more information becomes available I might get more worried or dismiss it entirely as the kind of change we see when a virus isn't very fastidious about how it reproduces. Because it's not about the specific mutation but about the biology and we don't know how to read the biology from the genetic sequence. Much of what we thought was important with respect to transmissibility or virulence or something else has been shown wrong by the virus itself. Every time we think we have a fix on it, it shows us otherwise. Here's what we wrote two months ago when the Dutch found the E627K mutation in PB2 in one of their isolates:
Even though this virus has been described as relatively stable genetically, individual viruses, even within the same patient, often have small differences in the thousands of letters that make up their genetic code. Influenza A virus is a very sloppy reproducer, and while its only objective in life is to make a copy of itself it often does single task very badly. But it's like the guy who was asked how he could sell his gasoline for a penny less than he paid for it, his answer was, "volume." The flu virus makes so many copies of itself when it infects a host cell that it can afford to make a lot of mistakes. Usually those mistakes are disastrous for the copy and it doesn't replicate any more. Very many of the little mistakes are just little mistakes and don't affect the virus at all. And some of them turn out to be good for the virus and possibly bad for the host in that they allow the virus to replicate faster, infect more and different kinds of cells and increase its ability to transmit from one host organism to another (transmissibility). (Effect Measure, October 1, 2009)​
The Dutch mutation was thought to strongly determine whether the virus would be more avian or more human, but swine flu went ahead and infected humans all over the globe with the version thought to be more avian. It apparently hadn't read that it needed this mutation to be adapted to humans and so far E627K hasn't taken root. In the case of the Norwegian mutation (D225G) we don't even have a theory about its significance, although it is in the part of the virus that binds to the host cell for entry.
What are the possibilities? This change isn't likely to make this virus more transmissible. It's already transmissible as hell and doesn't need any help in that department. It isn't in the part of the viral protein that the vaccine is directed against, so I doubt it would make the vaccine unusable. The same is true for antiviral activity, even though resistance to antivirals is likely to emerge via other mutations. CDC and the UK are both reporting some instances of Tamiflu resistant virus spreading from person to person. What the virus means for virulence, however, is unknown. The Norwegians speculated it could make the virus more prone to infect the lower respiratory tract but they are speculating. That would seem to be the major concern at the moment but there isn't much to go on.
Having said these somewhat reassuring things, however, I don't want anyone to be reassured. We are in the early stages of a pandemic with a dangerous virus and there is just too much we don't know to be able to be either alarmed or reassured by any particular piece of news. In our view focussing on particular mutations is not especially valuable in the current state of our knowledge. The flu virus isn't especially big but it is still too complicated for us to understand. There are eight genetic segments, each of which undergoes both mutation and reassortment, i.e., some of the internal segments mix and match between viruses and new combinations emerge.
The best way to think about this is that these eight functional segments act as a team. When one member of the team acquires a new skill, the value of that skill depends upon how the whole team works together. Sometimes a superstar isn't the best thing, but a group of less talented but smoothly working players is what is needed. But there's no rule about this. Some years teams make it to the Superbowl because of having one or two outstanding athletes ("stars") while other years it's the team that makes the fewest mistakes and works best together that wins out. We don't know how to predict this for sports teams, an easier problem than for the team of eight in the influenza virus.
The mutation is being widely reported to be D222G (this is H1 numbering; it is 225 in H3 numbering). What this designation means is that in the spikes of hemagglutinin protein on the outside of the virus (parts of which elicit the primary immune response), the amino acid 222 places in from one end has changed from "D" (aspartate) to "G" (glycine). Does this change in one of the team members make the virus operate much better? Does it change the biology in any way, and if so, in what way. We don't know. And what does "better" mean in terms of the virus? We aren't sure of that either. The bottom line for the virus is that it make more copies of itself, but the factors that allow it to do that (e.g., should it become more virulent or less virulent?) are unpredictable and largely unknown. This is what this statement by WHO means:
The significance of the mutation is being assessed by scientists in the WHO network of influenza laboratories. Changes in viruses at the genetic level need to be constantly monitored. However, the significance of these changes is difficult to assess. Many mutations do not alter any important features of the virus or the illness it causes. For this reason, WHO also uses clinical and epidemiological data when making risk assessments.​
In other words, when it comes to genetic sequences, it's not what the sequence says but what the sequence does. And we can only know that by watching. This is the first time we have watched a pandemic unfold in real time and we still don't know how to interpret many of the things we are seeing.
The virus will tell us, eventually. We'll just have to stay tuned.
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

more updates -

2009-11-20

225G New to Norway and Ukraine; Worldwide Evaluation Concerning Range and Co-Circulation with 225E

?? viruses with a similar mutation had been detected in several other countries, including Brazil, China, Japan, Mexico, Ukraine and the United States. "No links between the small number of patients infected with the mutated virus have been found and the mutation does not appear to spread," ...?

If the official statement in today?s Washington Post is accurate concerning the circulating geography of the Norway polymorphism associated with several fatalities, then the only probable selection is 225G. Evaluating the meta-data of available published and partially public sequences, no other SNP of interest corresponds to the range stipulated.

The positive statement indicating low transmissibility of 225G, however, is not supportable at this time by solid evidence due to lack of surveillance using the proper tools and testing protocols. The statement is perhaps intended to assuage rather than inform.

Countries with Probable * or Confirmed 225G


While 225G is probable or confirmed with very limited depth in 12 countries, our team is more concerned about the extensive range of 225E at the moment, documented with considerable penetration in at least 21 countries, including island nations and prominent international tourism hotspots. At any measure, the 225E circulating range is wider and deeper than 225G though the two overlap geography in at least 6 countries. Linked SNPs of interest appear to be more involved, as 225E demonstrates several clear acquisition paths that are not apparent with 225G.

Though the clinical attributions are not presently noted as a corollary to fatal cases like 225G, the accompanying changes and multiple backgrounds onto which the Glutamate at 225 (225E) is found may eventually provide a substantially more capable viral strain and most certainly is providing co-circulating sub-species of high interest alongside the 225G.

225G does, of course, merit scrutiny due to patterning with 230I on H1N1 Seasonal 2008 and 2009 sequences. If the range of 225G continues to smoulder, an attractant effect may draw 230I due to co-infection in areas that continue to have Seasonal H1N1 strains in circulation. The very high level of bird involvement in transporting genetics across serotypes may provide proximity, attraction and opportunity for H5N1 as a donor candidate for 230I due to verified H5N1 ranges at geographic inflection points for PF11. The world may not yet be seeing this permutation (225G & 230I) because the shortened infection to expiration timing also provides less time for viral recombination.

This 1918 and Avian SNP travels with H1N1 and H5N1 Avian polymorphisms indicating potential wild bird transport vectors. In a human host, the Avian modifications may find advantage at certain tissue types due to body core proximity providing basal temperature increases and may drive replication behaviour. The human lung may be precisely the correct temperature to promote rapid replication, more efficient binding or improved cleavage capability.

Influenza Flux will eventually find the appropriate or optimal combination of genetics to achieve stasis, but until that stasis of PF11<sub>>Ω </sub>is achieved, these sub-species will continue to be quite dangerous, demonstrating varying levels of Cytokinic Dysregulation according the host-pathogen interplay and the viral strain's capacity for temporarily suspending early catalysts to the innate immune response, including suppression of RIG-I ubiquination as the viral NS1 protein binds TRIM25 ultimately leading to reduced intra-cellular synthesis of Type I IFN. The timing and the level of RIG-I ubiquination suppression, thus interferon synthesis blocking, may eventually be found as the primary effector of host pathology from this IDRREAV, PF11. We feel that the evidence is well structured toward timing as an effector equal in importance to the level of inactivation / suppression.

225G gets the virus situated in the lung tissue and NS1 blocks the innate response. Add back the rapid replication at a multiplier over the speed of a Seasonal Influenza strain and you find an overwhelming viral load before any cell has signalled for assistance. When millions of viral particles erupt in a concentrated area from the lysed cells, the detritus alone drives an surging cascade of inflammatory cytokines. A slow response creates deadly risk. Then the body must take into account the travelling circus of sub-species that waste no time returning to their hard work of re-engineering the next cell for a viral production line.

As the data on 225G cases are released, including the sequences, presentation and progression, testing protocols, sampling protocols, prognoses, sequencing lab procedures and epidemiology, a higher level of interpretation may be made concerning these polymorphisms based on facts, rather than speculation.

A present 225G sequence set of less than 25 instances within ΣPF11 and those few having little to no associated clinicals does not provide a stable foundation at this time for determination of emergent characteristics such as rate of transmissibility, probability of co-infection with wildtype or spontaneous revision from wt due to tropism upon attaining deep lung infection.
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

does this indicate this flu is now moving in the wrong direction?


2009-11-24

Norway: 1 Mixture of 225D/225G, 5 of 25 have 225E; Spain: 7 of 19 have 225E

225E is becoming fixed.

GenBank Deposits 2009-11-23

Norway: 5 of 25 have 225E
Spain : 7 of 19 have 225E

A/Norway/2924, sampled on 2009-08-10 from a 40F, is a mixture of wt 225D and 225G after canine cell passage. The sample also carries the prevalent 206T.

The data collection must begin in earnest after this development. The first data quality improvement might be to release the sample location and the patient outcome please.

We have no evidence that the cases discussed here are related to the three previously reported instances in Norway of 1 serious illness and 2 fatalities. Sweden is also today reporting 2 cases of 225G that were serious and treated via ECMO during the summer. No outcomes noted as yet on Sweden.

This post will be updated as corroborationg data is made available.

 
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Re: Norway - H1N1 "Mutation" Announced by Health Department

does this indicate this flu is now moving in the wrong direction?

#75:
"Influenza Flux will eventually find the appropriate or optimal combination of genetics to achieve stasis, but until that stasis of PF11<sub>>Ω </sub>is achieved, these sub-species will continue to be quite dangerous, demonstrating varying levels of Cytokinic Dysregulation according the host-pathogen interplay and the viral strain's capacity for temporarily suspending early catalysts to the innate immune response, including suppression of RIG-I ubiquination as the viral NS1 protein binds TRIM25 ultimately leading to reduced intra-cellular synthesis of Type I IFN.
...
225G gets the virus situated in the lung tissue and NS1 blocks the innate response. Add back the rapid replication at a multiplier over the speed of a Seasonal Influenza strain and you find an overwhelming viral load before any cell has signalled for assistance.
When millions of viral particles erupt in a concentrated area from the lysed cells, the detritus alone drives an surging cascade of inflammatory cytokines. A slow response creates deadly risk."
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

update via email -

2009-11-24

Norway: 1 Mixture of 225D/225G, 5 of 25 have 225E; Spain: 7 of 19 have 225E

225E is becoming fixed.

GenBank Deposits 2009-11-23

Norway: 5 of 25 have 225E
Spain : 7 of 19 have 225E

A/Norway/2924, sampled on 2009-08-10 from a 40F, is a mixture of wt 225D and 225G after canine cell passage. The sample also carries the prevalent 206T.

The data collection must begin in earnest after this development. The first data quality improvement might be to release the sample site and the patient outcome please.

We have no evidence that the cases discussed here are related to the three previously reported instances in Norway of 1 serious illness and 2 fatalities. Sweden is also today reporting 2 cases of 225G that were serious and treated via ECMO during the summer. No outcomes noted as yet on Sweden. Finland reports at midday 1 case of 225G in July. The list of recent reports extends with the counts actively growing:

Ukraine
Norway
Sweden
Finland

Our team expects widespread reporting of 225G in the next few days as the revision is most certainly seeded throughout the world and is probable in any European country with a suitable sample size that is investigating.

The most noticable empty slot should be posted as soon as the pizza finishes on the west side of the Adriatic oven.

Islands like Cyprus, Mauritius, Brac (Croatia), Sicily (Italy), Sardinia (Italy), Majorca (Spain), Ibiza (Spain), Corsica (France), Crete (Greece) and Rhodes (Greece) are attractive examination sites in descending order of potential. Our team would be amazed if reasonable sampling had occurred on these islands and more than 3 of the 10 failed to demonstrate 225G. A 50% probability exists in our framework (with a reasonable sample population) that all 10 islands should display at least one case of 225G.

Slovakia, Germany, Iceland, Latvia, Lithuania, Moldova and Bosnia from Europe are candidate areas in order of descending potential.

Africa displays somewhat equal potential at South Africa, Cameroon and Ghana.

The matter of 225G range and transmissibility may best be settled with full sequence publication.

This post will be updated as corroborationg data is made available.
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

2009-11-25

Norway Sequence with 225G Mixture also Carries syn413K Silent Marker found on the 4 fatal flashfire cases

A/Norway/2924, sampled on 2009-08-10 from a 40F, and reported yesterday to carry a mixture of wt 225D and 225G with the 206T pairing also demonstrates syn413K, an Avian H1N1 SNP found in the most recent 225G sequences from the widely reported fatal cases in the ongoing flashfire that is now nearing 1.7 million cases with 397 deaths and 99,661 hospitalisations.

Norway2924 HA

  • 225G *
  • syn413K encoded from A1281G, AAa->AAg *
  • syn464G encoded from A1435G, GGa->GGg
* SNP Matches the 4 fatal flashfire cases

The silent 413K and 464G are both found on a very special bird from Argentina.

ReAssortment is downrated as a 225G transfer mechanism from Norway to the flashfire due to Norway2924 having an additional unmatched silent SNP, A1435G, GGa->GGg, coding for a synonymous Glycine at 464 (syn464G). This SNP is novel to ΣPF11 and is found widely on Swine H1N1 and H1N2, including most recently on A/swine/Hong Kong/294/2009 (H1N2), and Avian H1N1 in the red-winged tinamou/Argentina/MP1/2008 (HA 225G, 277N, 286H, 298V / NA 106I, 248N, 286G).

225G on 5 sequences (Norway2924 and 4 flashfire specimens) all sharing a rare syn413K on 5 distinctly different backgrounds closes the door on spontaneous and / or random mutation in this dataset.

With the two pillars of genetic acquisition impeached, deduction leads us to Dr. Niman's Recombination theory if we seek an explanation based on data.
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

#79:
"225G on 5 sequences (Norway2924 and 4 flashfire specimens) all sharing a rare syn413K on 5 distinctly different backgrounds closes the door on spontaneous and / or random mutation in this dataset.

With the two pillars of genetic acquisition impeached, deduction leads us to Dr. Niman's Recombination theory if we seek an explanation based on data."

___

And recombinations could be natural and artificial.
 
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