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Norway - H1N1 "Mutation" Announced by Health Department

Re: Norway - Virus has changed "slightly"

Re: Norway - Virus has changed "slightly"

Yes. We have no idea what "mutation/variant" they are talking about. 225 is not the only position to look at.

There is also something epidemiologically wrong with the picture of mild and severe variants of virus co-circulating for the past few months - many people caught the virus from a severe case and still only had a mild case (for example, Matt McIntosh and his sister, who both died, infected both parents, a friend, and the friend's sister - but all four had mild cases). Perhaps most people get infected with both viruses and for some reason, in severe cases the "mutated" virus dominates? I have a feeling it will be months until we know this for sure, as these has been very little study done on this so far.

Either way, D225G is not something new, we are just seeing it now.
 
Re: Norway - Has Virus has changed "slightly"?

Re: Norway - Has Virus has changed "slightly"?

Dr. Schuchat said something along these lines, I didn't get every word but this is the jist about Norway:

We are aware of reports of an unusual virus that was identified, a mutation in a few virus isolates. I don't want to underplay those results because it's so important to track these viruses. The mutation that was identified has no implications for the match of the vaccine or antiviral treatment. We look for spread of this particular mutation and whether it was in large numbers associated with virulent disease.

She was asked a follow up about whether the change had produced a more virulent virus?

The mutation has been seen sporadically, here and there throughout the world, sometimes in patients with mild disease, sometimes in fatal cases. There are lots of viruses where this mutation was seen. There's some theoretical reasons why this particular mutation may lead to the influenza virus living easier in the deep part of the lungs but the virus is already causing disease there. It's an important finding for virologists who are studying it.

She said she found that the change had been seen in US but only with mild disease when she checked.

(rough transcript)
 
Re: Norway - Has Virus has changed "slightly"?

Re: Norway - Has Virus has changed "slightly"?

Flu Cases in Norway Show Mutation, WHO Says
By Michelle Fay Cortez

Nov. 20 (Bloomberg) -- Cases of the H1N1 virus have been found in Norway with a mutation, said David Mercer, acting head of the communicable diseases unit at the World Health Organization?s European region. The mutation makes the virus more severe. :tiphat:http://www.bloomberg.com/apps/news?pid=20601103&sid=acB0Piy3IMds
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

Mutation May Make Disease More Severe, Norway Says
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By Marianne Stigset

Nov. 20 (Bloomberg) -- Norway?s Institute of Public Health discovered a mutated form of the H1N1 influenza virus that may make it more prone to infect deeper in the airways and cause more severe disease.
The mutated virus has been detected in two patients who died of the flu and one who was severely ill with the disease out of 70 cases tested, the institute said today in a 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,? Geir Stene-Larsen, the head of the institute, said in the statement. ?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.?
Norway has had an estimated 700,000 cases of infections of H1N1, with 21 reported deaths. The Institute of Public Health estimates about 25 percent of the population of about 4.7 million to be at risk of contagion.
?It?s most likely that the virus?s capability to mutate is not just specific to Norway; it will occur in other countries as well,? Stene-Larsen said in an interview on broadcaster TV2 today.
To contact the reporter on this story: Marianne Stigset in Oslo at mstigset@bloomberg.net :tiphat:http://www.bloomberg.com/apps/news?pid=20601124&sid=aSX1GIK04VWc
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

Norway says found H1N1 mutation in flu fatalities

Reuters November 21, 2009, 5:59 am
OSLO (Reuters) - Norwegian health authorities said on Friday they have discovered a potentially significant mutation in the H1N1 influenza strain that could be responsible for causing the severest symptoms among those infected.
"The mutation could be affecting the virus' ability to go deeper into the respiratory system, thus causing more serious illness," the Norwegian Institute of Public Health said in a statement.
Authorities added they had no reason to believe the mutation had any implication for the effect of flu vaccines or antiviral drugs made by groups such as Roche, GlaxoSmithKline, Novartis or AstraZeneca.
H1N1, a mixture of swine, bird and human viruses, has killed more than 7,000 people globally.
In Norway the mutation was found in the bodies of two people killed by the virus and of one person made seriously ill.
The two people infected by the mutated virus were among the first fatalities from the H1N1 pandemic in Norway, the institute said.
It was unclear whether the mutated virus was transmitted among humans, the health authorities said.
"Based on what we know so far, it doesn't seem like the mutated virus is circulating in the population, but rather that spontaneous changes have happened in the three patients,":magnify: director Geir Stene Larsen at the public health institute said in the statement.
In some later fatalities linked to H1N1 that were studied, the same mutation was not found. It had found other mutations in some other cases, but the mutations found in two of the first fatalities and one seriously ill patient had been of "particular interest," it said.
Norway has seen relatively more fatalities in the flu pandemic compared to the size of the population versus other European countries, with 23 confirmed deaths.
Public health authorities have said this could be due to the country being hit early in the pandemic's northern hemisphere winter wave, before a mass vaccination programme got underway.
"Nevertheless, it is important to study if there's still something about the Norwegian fatalities that separate us from other countries, and that make us learn something that strengthens our treatment of the seriously ill," director Bjorn-Inge Larsen at the Norwegian Directorate of Health said.:tiphat:http://nz.news.yahoo.com/a/-/world/6499306/norway-says-found-h1n1-mutation-in-flu-fatalities/
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

> And there have obviously also been fatal cases without this change

do we know this ?
it may just happen in some sort of cells while D225
is still dominating and usually found
maybe D225 spreads better in the body, while
G225 is more virulent

or cells are infected by both, G225 opens the door
but doesn't replicate so well


apparantly in USA,Mexico they considered it also but didn't link it to
increased virulence as Norway did now.


Is it the same mechanism as in 1918 1st wave --> 2nd wave ?
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

Helen Branswell says it's position 222 in HA but I think it's D225G

-----------------------------------

Public health significance of virus mutation detected in Norway


Pandemic (H1N1) 2009 briefing note 17
20 NOVEMBER 2009 | GENEVA -- The Norwegian Institute of Public Health has informed WHO of a mutation detected in three H1N1 viruses. The viruses were isolated from the first two fatal cases of pandemic influenza in the country and one patient with severe illness.

Norwegian scientists have analysed samples from more than 70 patients with clinical illness and no further instances of this mutation have been detected. This finding suggests that the mutation is not widespread in the country.

The virus with this mutation remains sensitive to the antiviral drugs, oseltamivir and zanamivir, and studies show that currently available pandemic vaccines confer protection.

Worldwide, laboratory monitoring of influenza viruses has detected a similar mutation in viruses from several other countries, with the earliest detection occurring in April. In addition to Norway, the mutation has been observed in Brazil, China, Japan, Mexico, Ukraine, and the US.

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.

Although 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.

Laboratories in the WHO Global Influenza Surveillance Network closely monitor influenza viruses worldwide and will remain vigilant for any further changes in the virus that may have public health significance.
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

it's just only one mutation in HA. The vaccine already has 2
and it doesn't affect the efficacy much.

It depends on whether an important epitope just happens to include that
position. And even then, there are other epitopes
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

Yes in terms of vaccine, obviously they tested it with ferret antisera. The WHO has said that the Ukrainian sequences were sequenced not only at Mill Hill but also at CDC so they probably checked out efficacy of vaccines there.
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

> Helen Branswell says it's position 222 on HA.


all genbank ****** has K at 222 (H3-numbering)



or, if she uses H1-numbering we usually have R, except:


K >A/Mexico/InDRE13547/2009/04/27
K >A/South Australia/2001/2009/05/
K >A/Mexico City/008/2009/05/10
K >A/Victoria/2001/2009/05/19
K >A/Darwin/2001/2009/05/29
K >A/Singapore/ON193/2009/06/14
K >A/Singapore/ON226/2009/06/15
K >A/Athens/992/2009/06/16
K >A/Nanjing/1/2009/06/18
K >A/Hiroshima/230/2009/06/25
K >A/Singapore/ON496/2009/06/25
K >A/Singapore/ON899/2009/07/04
K >A/Singapore/ON923/2009/07/05
K >A/New York/4565/2009/07/08
X >A/Singapore/GP2312/2009/07/31
X >A/Singapore/GP2316/2009/07/31
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

Isn't it far more likely to be at position 225 and the change is D225G?
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

yes, seems to be 225=222=239

yet another numbering system
we need a norm




the cat is out of the bag


they don't mention, that we saw it in 1918
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

gsgs, can you please provide a link, to Helen Branwells' statement?
 
Re: Change in virus in Norway- no reason for panic

Re: Change in virus in Norway- no reason for panic

If D225G is where they were looking at, then add Spain to the country list. It could be one reason of why there were 115 deaths in official count yesterday (+27 in last week).

These isolates in Genbank have D225G (includes Brazil/Japan/China/USA)

gb|GU189649.1| Influenza A virus (A/Zhejiang/DTID-ZJU03/2009(... 34.2 3.0
gb|GU112090.1| Influenza A virus (A/Zhejiang/DTID-ZJU02/2009(... 34.2 3.0
gb|GU108486.1| Influenza A virus (A/Zhejiang-Yiwu/11/2009(H1N... 34.2 3.0
gb|CY047074.1| Influenza A virus (A/Catalonia/NS1706/2009(H1N... 34.2 3.0
gb|GU014750.1| Influenza A virus (A/Hiroshima/201/2009(H1N1))... 34.2 3.0
gb|GQ915018.1| Influenza A virus (A/Sao Paulo/53225/2009(H1N1... 34.2 3.0
gb|GQ915017.1| Influenza A virus (A/Sao Paulo/53206/2009(H1N1... 34.2 3.0
gb|GQ457487.1| Influenza A virus (A/Texas/05/2009(H1N1)) segm... 34.2 3.0
gb|GQ379822.1| Influenza A virus (A/Mexico/InDRE4114/2009(H1N... 34.2 3.0
gb|GQ374893.1| Influenza A virus (A/reassortant/IDCDC-RG18(Te... 34.2 3.0
gb|GQ280121.1| Influenza A virus (A/reassortant/NIBRG-121(Cal... 34.2 3.0
gb|GQ232076.1| Influenza A virus (A/Texas/11/2009(H1N1)) segm... 34.2 3.0
gb|GQ200237.1| Influenza A virus (A/Georgia/01/2009(H1N1)) se... 34.2 3.0
gb|GQ162194.1| Influenza A virus (A/Mexico/3955/2009(H1N1)) s... 34.2 3.0
gb|GQ160568.1| Influenza A virus (A/New York/04/2009(H1N1)) s... 34.2 3.0
gb|GQ132145.1| Influenza A virus (A/Mexico/InDRE4114/2009(H1N... 34.2 3.0


------

Florida1,

Norway released three isolates into Genbank on September 22nd from May/June.
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

17 November 2009 -- Preliminary tests reveal no significant
changes in the pandemic (H1N1) 2009 virus based on
investigations of samples taken from patients in Ukraine
http://www.who.int/csr/don/2009_11_16/en/index.html



http://twitter.com/cp_branswell



The HA plasmid cloned from A/CA/7/09 that did not have amino acid changes at
residues of 222 or 223 could be rescued to produce progeny virus (V4 in Table 1). This
indicated that T197A change in A/CA/7/09 was responsible for the efficient rescue of the
6:2 reassortant. Other A/CA/7/09 HA clones had an additional change of either D222G or
Q223R, and viruses containing D222G (V5) or Q223R (V6) in HA were also rescued.
Due to the high degree of similarity between the HAs of A/CA/4/09 and A/CA/7/09, and

http://jvi.asm.org/cgi/reprint/JVI.02106-09v1.pdf
 
Last edited by a moderator:
Re: Norway - H1N1 "Mutation" Announced by Health Department

yes, seems to be 225=222=239

yet another numbering system
we need a norm




the cat is out of the bag


they don't mention, that we saw it in 1918


Just because a amino acid's presence in a particular spot in the 1918 pandemic flu caused a certain characteristic in that virus, does not mean it will do the same thing now.

Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2746-51.

Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes.

Basler CF, Reid AH, Dybing JK, Janczewski TA, Fanning TG, Zheng H, Salvatore M, Perdue ML, Swayne DE, García-Sastre A, Palese P, Taubenberger JK.
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Comment in:

The influenza A virus pandemic of 1918-1919 resulted in an estimated 20-40 million deaths worldwide. The hemagglutinin and neuraminidase sequences of the 1918 virus were previously determined. We here report the sequence of the A/Brevig Mission/1/18 (H1N1) virus nonstructural (NS) segment encoding two proteins, NS1 and nuclear export protein. Phylogenetically, these genes appear to be close to the common ancestor of subsequent human and classical swine strain NS genes. Recently, the influenza A virus NS1 protein was shown to be a type I IFN antagonist that plays an important role in viral pathogenesis. By using the recently developed technique of generating influenza A viruses entirely from cloned cDNAs, the hypothesis that the 1918 virus NS1 gene played a role in virulence was tested in a mouse model. In a BSL3+ laboratory, viruses were generated that possessed either the 1918 NS1 gene alone or the entire 1918 NS segment in a background of influenza A/WSN/33 (H1N1), a mouse-adapted virus derived from a human influenza strain first isolated in 1933. These 1918 NS viruses replicated well in tissue culture but were attenuated in mice as compared with the isogenic control viruses. This attenuation in mice may be related to the human origin of the 1918 NS1 gene. These results suggest that interaction of the NS1 protein with host-cell factors plays a significant role in viral pathogenesis.


http://www.ncbi.nlm.nih.gov/pubmed/11226311
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

Didn't the isolate from London in 1918 have a D at position 225 while the isolate from London in 1919 had a G?
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

it did

both could have been mixtures
the prevalence could depend on the timing of sampling
or the tissue selected or the way to grow the virus
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

UPDATE 1-Norway says found H1N1 mutation in flu victims


* 3 H1N1 cases found with potentially significant mutation * Two cases found among first fatalities in Norway
* Says disease's mutation could cause more serious illness
* WHO says mutated virus sensitive to antivirals, vaccines


(Adds WHO statement in new paras 4-6; CDC comment paras 15-17)


OSLO, Nov 20 (Reuters) -



Norwegian health authorities said on Friday they have discovered a potentially significant mutation in the H1N1 influenza strain that could be responsible for causing the severest symptoms among those infected.
"The mutation could be affecting the virus' ability to go deeper into the respiratory system, thus causing more serious illness," the Norwegian Institute of Public Health said in a statement.


There was no reason to believe the mutation had any implication for the effectiveness of flu vaccines or antiviral drugs made by groups such as Roche (ROG.VX), GlaxoSmithKline (GSK.L), Novartis (NOVN.VX) and AstraZeneca (AZN.L), the authorities said.


The World Health Organisation said that the mutation did not appear to be widespread in Norway and the virus in its mutated form remained sensitive to antivirals and pandemic vaccines.

A similar mutation had been detected in H1N1 viruses circulating in several other countries, including China and the United States, in severe as well as in some mild cases, it said.


"Although 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 in a statement.


H1N1, a mixture of swine, bird and human viruses, has killed at least 6,770 people globally, according to its latest update.


In Norway the mutation was found in the bodies of two people killed by the virus and of one person made seriously ill. The two infected by the mutated virus who died were among the first fatalities from the H1N1 pandemic in Norway, the institute said.


It was unclear whether the mutated virus was transmitted among humans, the health authorities said.
"Based on what we know so far, it doesn't seem like the mutated virus is circulating in the population, but rather that spontaneous changes have happened in the three patients," director Geir Stene Larsen at the public health institute said in the statement.


Norway has seen relatively more fatalities in the flu pandemic compared to the size of the population versus other European countries, with 23 confirmed deaths.


Public health authorities have said this could be due to the country being hit early in the pandemic's northern hemisphere winter wave, before a mass vaccination programme got underway.

"Nevertheless, it is important to study if there's still something about the Norwegian fatalities that separate us from other countries, and that make us learn something that strengthens our treatment of the seriously ill," director Bjorn-Inge Larsen at the Norwegian Directorate of Health said.


Dr. Anne Schuchat of the U.S. Centers for Disease Control and Prevention said, "This mutation has been seen sporadically."

She said it is sometimes seen in patients who have mild influenza symptoms.


"I think it is just too soon to say what this might mean long term," Schuchat told reporters in a telephone briefing.



(Reporting by Richard Solem; Additional reporting by Stephanie Nebehay in Geneva and Maggie Fox in Washington; Editing by Matthew Jones and Louise Ireland)
 
Re: Norway - H1N1 "Mutation" Announced by Health Department

From today's HHS/CDC press conference -

"Betsy McKay: I just wanted to follow-up on the question about the mutation in norway. I wondered if you could talk a little bit more about is it possible that this mutation has produced a more virulent form and what has CDC uncovered through its own work?

Anne Schuchat: this mutation has been seen sporadically here and there around the world. Sometimes it's been seen in patients who had very mild disease and sometimes it's been seen in people who had more severe or fatal disease.

And, of course, lots of virus without this mutation has been seen in the fatal as well as the milder forms of H1N1 influenza. There's some theoretical reasons why this particular mutation might lead an influenza virus to live easier in the deep part of the lungs and cause lower respiratory infections, but we've actually seen lower respiratory infections in a severe viral pneumonia without this mutation.

So I think it's too soon to say what this will mean long term. It's an important finding and they're looking into it, but I don't think it has the public health implications that we would wonder about. Did you have a second question? Oh, what have we seen so far? I believe it's been seen in the U.S. But associated with mild disease. I believe. I might need to verify that. Do we have another from the room? Okay. We'll go back to the phone..."
 
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