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Tracking the next pandemic: Avian Flu Talk

Briefing H1N1 Mutation-Netherlands

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    Posted: October 02 2009 at 8:04am
Originally posted by TipKat TipKat wrote:


Dr. Nancy Cox, who heads the influenza division at the U.S. Centers for Disease Control, warns people should not take too much comfort from the fact this change doesn't seem to make the virus more virulent at this point.

"We just know that influenza can change in unpredictable ways through mutation and reassortment," she said, referring to the process by which flu viruses swap genes with each other.

"The unexpected can arise, and arise very quickly. So we shouldn't write this off. It is causing hospitalization. It is causing fatalities. And in every single case that you hear about, it's a tragedy."



The statement is frequently made that H1N1 has not mutated since its outbreak. This is an untrue statement. We have found, especially in Brazil mutations of the virus. It is significant whether or not the patients recovered. One five year old boy recovered and the died 3 days later.

Some can become asymptomatic carriers. There is a need for postings proving that statements such as the virus has not mutated are false and misleading.

Despite hundred of post I have made on the Brazil mutation which also had the highest death rate in the world after the mutations, these findings and information have been silenced.

Whenever I do uncover sometime that is contraspin- then it is usually declared unimportant or nothing to worry about. The mutation in Brazil eventually may have resulted in a virulent strain and the strand change while not only producing a spreader- when intentional combined at CDC with H5N1 to see what would happened created a virus extremely dangerous.

We have about 5 confirmed mutations of this and in one case a county coroners report of 8 flu deaths which had no similarities hardly at all which could have been five different strains.

Most of everything I have posted for months since the near blackout of data on April 28th has met with resistance. Yet almost every post- has a link to the information and many of them to WHO and CDC.

Medclinician


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Post Options Post Options   Thanks (0) Thanks(0)   Quote TipKat Quote  Post ReplyReply Direct Link To This Post Posted: October 01 2009 at 8:18pm

By: The Canadian Press

 
Date: Wednesday Sep. 30, 2009 12:45 PM ET
 
Mutation not causing greater virulence in swine flu
 
COMMENT: this sure looks like nothing to worry about...not now anyway TIP.

TORONTO — Dutch scientists have reported they have found what was thought to be a key mutation in some swine flu viruses from the Netherlands, a change many virologists feared would give the viruses the ability to cause more severe disease.

But so far the evidence seems to suggest this mutation does not make the new H1N1 virus more virulent, the researchers said Tuesday.

The change, at position 627 on the PB2 gene of the virus, is known to increase the ability of flu viruses to replicate; prolonged viral replication can lead to more serious illness. The mutation has been found in all known human flu viruses, including the three that caused the pandemics of the last century.

"Everybody predicted that this mutation is going to have a big impact on virus replication of the new H1N1," said Dr. Ron Fouchier, one of the authors of the report and a molecular virologist at Erasmus Medical Centre in Rotterdam.

"If you would have asked me three months ago, I would have bet my car on it. But nobody placed that bet because everybody was sure that it would increase (virulence)."

If they had, it seems they might have been able to claim the keys to Fouchier's SUV.

Three people either known or suspected of having been infected with the mutated H1N1 viruses suffered only mild disease. And ferrets infected with a laboratory synthesized H1N1 virus with this change also did not suffer more severe disease. Ferrets are the standard animal model for human flu.

"Given the information that we have at present, we have no indication for increased virulence," said Dr. Marion Koopmans, chief of virology in the infectious diseases laboratory of the National Institute of Public Health, The Netherlands.

"This is a mutation that is in the textbooks as something to look out for, but whether it really confers something to these (H1N1) viruses remains to be seen."

Koopmans, Fouchier and a number of colleagues disclosed the surprising findings through ProMed, a website and mailing list that serves as an early warning system for infectious diseases developments. It is closely scrutinized by scientists and public health officials in the infectious diseases sphere.

The Dutch scientists reported finding two viruses with this change that appear to have been transmitted between mid-July and mid-August in the West Frisian Islands in the north of The Netherlands. The area is a popular destination for Dutch and German campers.

One of the mutated viruses was recovered from a male who had been there and who started developing symptoms on Aug. 9. The second was found in a girl who hadn't been to the area, but whose sister had been camping there at the time. The sister was also sick, but there was no specimen from her to test. Koopmans said the working assumption is that the sister who went camping was also infected with this virus.

The first virus was only discovered in mid-September, when it made its way to Koopmans' lab. An investigation at that point showed the male and the sister had been part of a group of 24 who shared two tents on the island. Most of the members of the camping party reported having been ill.

Koopmans said officials have looked at specimens from the area and from the regions from whence the campers came, but haven't found more viruses with this change.

"There's no evidence yet that this virus has spread any further in Holland," Fouchier said. "Of course we're currently still looking for it. Every virus we get our hands on we check (position) 627. But we haven't found any more."

Labs have been looking for this mutation from the moment the new H1N1 virus was fully analyzed and it was seen it didn't have the same amino acid at position 627 as other human viruses have.

Some scientists even suggested the virus might not be fully adapted to spread among humans because it didn't have this change, but instead had an amino acid at position 627 that is normally seen in avian flu viruses. The pandemic virus, which is a never-before-seen hybrid of swine, avian and human genes, has an avian PB2 gene.

Dr. Richard Webby, head of the World Health Organization's influenza collaborating centre at St. Jude Children's Research Hospital in Memphis, Tenn., said there is good evidence this mutation is associated with adaptation of avian influenza viruses to humans, but the proof that it is linked to severity of disease is less clear.

Viruses with this change show increased virulence in mice and sometimes in ferrets, but not always, he said, suggesting the ferret data probably are more reliable. "I think this is one instance where mice are probably lying a little bit," Webby said.

In some flu viruses this change is known to allow the virus to replicate at cooler temperatures, meaning they can infect the upper airways, rather than the warmer deep lung area preferred by avian flu viruses.

That might actually be a good thing with this H1N1, Webby said, noting autopsies have shown that in severe cases the pandemic virus wreaks havoc deep in the lungs.

Dr. Nancy Cox, who heads the influenza division at the U.S. Centers for Disease Control, warns people should not take too much comfort from the fact this change doesn't seem to make the virus more virulent at this point.

"We just know that influenza can change in unpredictable ways through mutation and reassortment," she said, referring to the process by which flu viruses swap genes with each other.

"The unexpected can arise, and arise very quickly. So we shouldn't write this off. It is causing hospitalization. It is causing fatalities. And in every single case that you hear about, it's a tragedy."

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Post Options Post Options   Thanks (0) Thanks(0)   Quote ops144 Quote  Post ReplyReply Direct Link To This Post Posted: October 01 2009 at 6:40am
post all of the info med
both pt's fully recovered fine






 
< value="Retour" ="doSubmit'Back';" id="Back" ="">
Numéro d'archivage 20090928.3394
Date publiée 28-SEPT.-2009
Sujet PRO/AH/EDR> Influenza pandemic (H1N1) 2009 (58): Netherlands, PB2 mutation
INFLUENZA PANDEMIC (H1N1) 2009 (58): THE NETHERLANDS, PB2 MUTATION
******************************************************************
A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>

Date: Mon 28 Sep 2009
From: Marion Koopmans
<Marion.Koopmans@rivm.nl>


We would like to report 2 patients in The Netherlands, diagnosed with
influenza pandemic A(H1N1) 2009 virus infection that had a mutation (E627K)
in the basic polymerase 2 (PB2) protein. This mutation has previously been
associated with increased efficiency of replication and possible virulence
changes in other influenza A viruses.

The investigation identified a specific geographic region in the north of
The Netherlands as the place where viruses with the same genetic background
have circulated between mid July and mid August [2009]. No other cases
carrying the PB2 mutation have been identified.

On 15 Sep 2009, the 1st influenza A(H1N1)v virus with a glutamic acid to
lysine mutation at position 627 (E627K) in PB2 was identified through
routine sequence analysis of clinical samples from a diabetic patient
infected with A(H1N1)v virus. The 1st day of illness was on 9 Aug 2009,
when the patient was vacationing on one of the West Frisian Islands in the
wetlands north of The Netherlands (Waddenzee). He had a relatively mild
course of illness. Subsequent retrospective tracing of geographically
linked A(H1N1)v cases from the national databases led to the identification
of 24 additional A(H1N1)v confirmed cases throughout the country that had
stayed on the same popular holiday island during July and August. Sequence
analysis of 12/24 clinical specimen available at the institute identified
10 A(H1N1)v viruses that clustered with the virus obtained from the
diabetic index patient based on unique mutations in the NA gene and PB2
gene. Only one of these had the PB2 E627K mutation. This virus was isolated
from a family contact of an adolescent girl who returned from a one-week
stay on the same island on Mon 20 Jul 2009 with high fever and coughing.
This girl had been camping with a group of 16 boys and 8 girls that shared
2 tents. Almost all members of this group reportedly had been ill, and
influenza A(H1N1)v infection had been diagnosed in 2 other persons
belonging to the same camp. The girl was ill for a week, with full recovery
after 2 weeks. Our 2nd case with a virus shedding carrying the PB2 mutation
is the younger sister and became ill on Thu 23 Jul 2009. She was treated
with oseltamivir and recovered fully after one week. Both parents remained
free from symptoms.

As the mutations were identified more than one month after initial
detection, no further contact investigations were done. Municipal health
services were informed about the local disease activity. Since 15 Aug 2009,
mild influenza cases are no longer notifiable in The Netherlands, so we
have no information on possible onward transmission. No clusters of illness
(for example, from schools) were reported in the health regions involved
(including the island), and surveillance data from a national
physician-based sentinel network showed low ILI activity for the
Netherlands. Samples from 22 patients hospitalized with influenza A(H1N1)
in July and August did not have the PB2 mutation.

PB2 627K is consistently found in human influenza A viruses, but rarely in
avian-derived viruses. The E627K mutation may result in enhanced virus
replication efficiency in humans, possibly by adjustment to host body
temperature or cellular cofactors, and has previously been shown to be
associated with fatal cases of HPAI H5N1 and H7N7 virus infection in
humans. Until now, A(H1N1)v viruses with Influenza pandemic (H1N1) 2009
(57): in PB2 have not been reported, and the clinical and epidemiological
relevance of our finding remains unclear.

Preliminary experiments in ferrets using reverse genetics-derived new
influenza A(H1N1)v viruses with the E267K mutation in PB2 did not indicate
increased shedding, virulence or transmissibility. Further experiments as
well as increased molecular surveillance to monitor the situation are ongoing.

[byline: M Jonges 1, A Meijer 1, J van Steenbergen 2, T Oomen 2, H Vennema
1, J Spaargaren 3, Kampman 4, P van der Tas 5, R Ter Schegget 6, Wim van
der Hoek 7, J Tjie 8, R Benne 9, Sander Herfst 10, Salin Chutinimitkul 10,
Ab Osterhaus 10, Ron Fouchier 10, Marion Koopmans 1, 10.
At:
1 National Institute for Public Health and the Environment, Centre for
Infectious Disease Control, PO Box 1, 3720 BA, Bilthoven, The Netherlands
2 Preparedness and response unit, Center for infectious disease control,
Bilthoven
3 Laboratory for Microbiology, Enschede
4 Municipal Health Service, Twente
5 Municipal Health Service, Friesland
6 Municipal health service, Brabant
7 Epidemiology and surveillance unit, Center for infectious disease
control, Bilthoven
8 Microbiological laboratory Veldhoven
9 Laboratory for infectious diseases, Groningen
10 Laboratory for Virology, ErasmusMC, Rotterdam]

--
communicated by:
Marion Koopmans
Chief of Virology
Laboratory for Infectious Diseases and Screening, Center for Infectious
Disease Control
National Institute of Public Health
The Netherlands
<Marion.Koopmans@rivm.nl>

[ProMED-mail thanks Dr Koopmans and colleagues for providing this
interesting information recording the detection of the same E267K mutation
in the basic polymerase 2 (PB2) protein of 2 independent isolates of
A(H1N1)v in the north of The Netherlands. The functional relevance of this
mutation remains to be determined. - Mod.CP]

[see also:
Influenza pandemic (H1N1) 2009 (57): case counts 20090925.3367
Influenza pandemic (H1N1) 2009 (56): antiviral resistance risk 20090925.3363
Influenza pandemic (H1N1) 2009 (55): vaccine formulation 20090925.3359
Influenza pandemic (H1N1) 2009 (54): vaccine availability 20090921.3325
Influenza pandemic (H1N1) 2009 (53): vaccine donation 20090919.3290
Influenza pandemic (H1N1) 2009 (52): WHO update 66 20090918.3272
Influenza pandemic (H1N1) 2009 (51): antibody deficiency 20090917.3261
Influenza pandemic (H1N1) 2009 (50): oseltamivir-resistance 20090917.3260
Influenza pandemic (H1N1) 2009 (40): global update 20090906.3138
Influenza pandemic (H1N1) 2009 (30): assumptions 20090813.2879
Influenza pandemic (H1N1) 2009 (20): Peru, 33 percent asymptomatic
20090730.2668
Influenza pandemic (H1N1) 2009 (10): vaccine 20090720.2577
Influenza pandemic (H1N1) 2009 - Viet Nam: patient data 20090708.2450]

....................cp/ejp/sh



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Post Options Post Options   Thanks (0) Thanks(0)   Quote Medclinician Quote  Post ReplyReply Direct Link To This Post Posted: September 30 2009 at 7:41pm
http://www.promedmail.org/pls/otn/f?p=2400:1001:459702117466596::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1010,79432

Archive Number 20090928.3394
Published Date 28-SEP-2009
Subject PRO/AH/EDR> Influenza pandemic (H1N1) 2009 (58): Netherlands, PB2 mutation
INFLUENZA PANDEMIC (H1N1) 2009 (58): THE NETHERLANDS, PB2 MUTATION
******************************************************************
A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>

Date: Mon 28 Sep 2009
From: Marion Koopmans
<Marion.Koopmans@rivm.nl>


We would like to report 2 patients in The Netherlands, diagnosed with
influenza pandemic A(H1N1) 2009 virus infection that had a mutation (E627K)
in the basic polymerase 2 (PB2) protein.
This mutation has previously been
associated with increased efficiency of replication and possible virulence
changes in other influenza A viruses.


The investigation identified a specific geographic region in the north of
The Netherlands as the place where viruses with the same genetic background
have circulated between mid July and mid August [2009]. No other cases
carrying the PB2 mutation have been identified.

Medclinician






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