Re: expert opinions
http://health.groups.yahoo.com/group/Flu_Pandemic/files/Experts on Flu/
Fauci, Anthony
Jan 3, 2006
Garrett, Laurie
Mar 2, 2006
Hayden, Frederick
University of Virginia
Jan 1, 2006
Avian Flu Warnings Warranted
Gary Tallarita 7 KB
Nov 15, 2005
Grattan Woodson
Emory University School of Medicine 15 KB
Dec 1, 2005
Anderson Roy M Chair in Infectious Disease
Imperial College London 14 KB
Feb 5, 2006
Barry John M
Author, The Great Pandemic 14 KB
Feb 5, 2006
Blumenthal, Susan J.
former assistant surgeon general 7 KB
Jan 6, 2006
Chan, Dr. Margaret WHO Assistant
Director General Communicable Diseases 8 KB
Feb 5, 2006
Colin Blakemore, chief executive
British Medical Research Council 3 KB
Dec 19, 2005
Crovari, Professor Pietro
University of Genoa Influenza Centre Italy 6 KB
Jan 14, 2006
David Nabarro
UN's coordinator on avian influenza 2 KB
Dec 19, 2005
Dimitris Trichopoulos interviewed
Leading Greek epidemiologist 9 KB
Jan 27, 2006
Fedson Dr. David Medical Director
Vaccines Division, Sanofi-Aventis 11 KB
Feb 5, 2006
Gary Butcher University of Florida
College of Veterinary Medicine 7 KB
Dec 18, 2005
GUAN YI
Time Magazine 2005 6 KB
Nov 4, 2005
Henry Niman
Fox Chapel researcher says bird flu coming 6 KB
Nov 21, 2005
How Avian Flu is transmitted by Bob Doneley
Queensland's School of Veterinary Science 2 KB
Nov 6, 2005
International veterinary experts meeting 2006
OIE director-general Bernard Vallat 2 KB
Mar 2, 2006
Jeremy Farrar director of Oxford University
Hospital for Tropical Diseases in Ho Chi Minh 3 KB
Dec 16, 2005
Jones Dr. David Butler Chief of Public Health
Public Health Agency of Canada 11 KB
Feb 5, 2006
Keiji Fukuda
Flu Hunters By GRETCHEN REYNOLDS 44 KB
Nov 24, 2005
Ken Alibek
Bird flu threatens East Asia 3 KB
Nov 22, 2005
Lekan Ayanwale
College of Veterinary Medicine, Tuskegee U 5 KB
Dec 19, 2005
McGeer Dr Allison Director Infection Control
Mount Sinai Hospital Toronto 15 KB
Feb 5, 2006
Nguyen Thu Van
11 KB
Dec 21, 2005
Osterholm, Dr. Michael Director
Center for Infectious Disease at U Minnesota 14 KB
Feb 5, 2006
Oxford, John
St. Bartholomew’s & Royal London Hospital 11 KB
Feb 5, 2006
Peiris, Mailk professor of microbiology at
Hong Kong University 4 KB
Feb 19, 2006
Potter, Prof Chris
More dangerous strain of bird flu? 2 KB
Jan 21, 2006
Predicting a pandemic is an uncertain science
Harvey Fineberg 6 KB
Nov 4, 2005
Prognosis of avian flu looks grim
Joxel Garcia, Pan-American Health Org 7 KB
Nov 15, 2005
Samaan, Gina WHO Epidemiologist
Three Days With a Bird Flu Sleuth 10 KB
Feb 17, 2006
Taubenberger Dr. Jeffrey Medical Pathologist
Armed Forces Institute of Pathology 24 KB
Feb 5, 2006
UCF Professors sound-off on bird flu
Central Florida Future 8 KB
Dec 19, 2005
UK Bird-Flu Experts Gather
Pandemic Not Matter Of If, But When 5 KB
Dec 7, 2005
US prepares for worst-case scenario with bird
flu by US Health & HS Secretary Mike Leavitt 3 KB
Dec 6, 2005
Virginia-Maryland Regional College of
Veterinary Medicine 4 KB
Nov 10, 2005
Viruses, Viruses, Viruses
by David Baltimore 34 KB
Nov 4, 2005
Webster, Robert Dept of Infectious Diseases
St. Jude Children’s Research Hospital 16 KB
Feb 5, 2006
WHO head sees human-to-human avian flu
flu inevitable 4 KB
Dec 1, 2005
Worries about avian influenza overblown
Va Md College of Veterinary Medicine 3 KB
Nov 21, 2005
Yale professors question spending on flu
John Rose 5 KB
Nov 6, 2005
http://www.curevents.com/vb/showthread.php?t=34780
Webster
Oxford
Osterholm
Barry
Butler Jones
Fedson
McGeer
St.John
Anderson
MacKenzie
Plummer
Chan
Taubenberger
Chokephaibulkit
http://www.fluwikie.com/index.php?n=Science.OpinionAboutAFluPandemic?
Nabarro
Narain
Ungchusak
Osterholm
Fauci
Omi
Oxford
Niman
Gerberding
Palese
http://www.fluwikie.com/index.php?n=Forum.WhatExpertsAndOfficalsAreSayingAboutATheEmergingPandemic
March 3 - Chinese Vice-Premier Hui Liangyu
March 6 - Michael Leavitt
Niman
March - Masato Tashiro
Febr. - Nabarro
Febr. - Oxford
Febr. - Nabarro
Febr. - Osterhaus
March : Lvov
March 7 - Perdue
March 7 - Seehofer
March 6 - Chan
March - Thompson
March 1 - Leavitt
March 8 - Nabarro
March 8 - Nabarro
March 6 - Domenech
March 10 - Fukuda
1) March 3 (Reuters) - Chinese Vice-Premier Hui Liangyu has warned that China could see more human cases of bird flu during the spring season when migratory birds return, increasing the risk of spreading the virus. http://<br />
http://www.alert?k/PEK206840.htm
To at least one expert, the Chinese statement sounded like a hint that avian flu in China is more widespread than the government has been acknowledging. ?Many of us believe that this type of discussion by someone as high as the vice premier really indicates that this situation is already occurring,? said Michael T. Osterholm, PhD, MPH, director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of the CIDRAP Web site.
http://www.cidrap.umn.edu/cidrap/co?r0206avian.html
2) U.S. Secretary of Health and Human Services Michael Leavitt said on March 6 that, ?The H5N1 virus has continued to [evolve] over the past 18 months. We continue to monitor its evolution.? Leavitt said. ?We will have seed viruses reflecting this drift that can be quickly available for vaccine testing and production.?
http://usinfo.state.gov
3) Dr. Niman says recombination has been steadily occurring and this Spring we might be presented with some nasty consequences.
http://www.recombinomics.com
4) Masato Tashiro, director of the Department of Viral Diseases and Vaccine Control at the National Institute of Infectious Diseases in Tokyo, warned that cases in which the virus transmitted from birds to humans had begun to rise recently and human-to-human virus transmissions are likely to be seen in the near future. ?Avian-human transmission happens sporadically, but the number of cases are increasing,? Tashiro said, ?Flu viruses are constantly undergoing mutations, which could result in human-to-human virus transmissions, which is the worst case scenario.? Tashiro added that an avian flu case needs to be contained within three weeks. After three weeks, the infection will accelerate to the extent that makes it difficult to contain. - March 2006
http://www.taipeitimes.com
5) ?Only two mutations are needed for it to become easily transmissible among humans,? thus sparking a pandemic in which millions of people could die, David Nabarro, the world body?s coordinator on avian influenza, told Portuguese newspaper Expresso in February 2006.
http://news.xinhuanet.com
5a) earlier Nabarro statements, not yet mentioned:
http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/sep2905avian2.html
Nabarro , Sep 29, 2005
I am nearly certain that a pandemic will erupt soon and it could kill
anywhere from 5 million to 150 million people
it is very likely that the H5N1 virus will soon acquire the ability to spread readily
from person to person. I am almost certain there will be another pandemic soon
6) John Oxford, Professor of Virology at Barts, claims the likelihood of a human avian flu pandemic was ?high and within a span of, say, 18 months?. -Feb 2006
http://www.24dash.com
7) ?Still, epidemiologists have been stunned by the rapid advance of the disease. ??The virus is moving quite substantially into new locations,? said David Nabarro, the official responsible for coordinating the UN response to avian and human influenza. ??The truth is, this virus is undergoing changes. This warning that nature is giving us has to be heeded.? ?Feb 2006
http://www.boston.com
From the same article: ??The danger is grave, the threat is real,? said Dr. Albert Osterhaus, a virologist at the Erasmus Medical Center in Rotterdam, head of the Netherlands National Influenza Center, and one of Europe?s top virus hunters.? Another pandemic is probable, not just possible. It?s only a matter of time,? he said in a telephone interview. ??Whether [the H5N1] virus will be the basis of the next pandemic is impossible to say. But the virus is already highly pathogenic.? -Feb 2006
9) ?One amino-acid replacement in the genome remains to make the virus transferable from human to human,? said Dmitry Lvov, the director of a virology research institute at the Russian Academy of Medical Sciences?.?Lvov said the pandemic virus could strike at any moment, and would most likely come from China, leading to tens of millions of human deaths, or one third of the global population. He added quarantine measures could delay the pandemic for a few days but not prevent it, and that vaccination would not stop people getting sick.? ?March 8, 2006
http://en.rian.ru
10) Reports that cats have contracted bird flu could mean the virus is adapting to mammals and poses a potentially higher risk to humans, a World Health Organisation official says. Michael Perdue, a scientist with the organisation?s global influenza program, said ?If it is true, it would imply the virus has changed significantly.? ?March 7, 2006
http://msnbc.msn.com/id/11710674/
Also on the same note?
In Germany, Agriculture Minister Horst Seehofer said on March 7 that the discovery of the dead cats a week after the first feline infection in Germany signalled a heightened risk of infection for humans. ?This means that the virus is not confined to a single case of a mammal but has spread to several cases. Therefore, bird flu has clearly moved closer to humans,? he told Bayerischer Rundfunk radio.
http://en.chinabroadcast.cn/706/200?9/189@59646.htm
11) The U.N. agency met in Geneva to discuss global efforts to prepare in case bird flu mutates into a form easily passed between humans, potentially triggering a global pandemic. ?Dr. Margaret Chan, who is spearheading WHO?s efforts against bird flu, told more than 30 experts that the top priority was to keep the deadly H5N1 strain of bird flu from mutating. ?Should this effort fail, we want to ensure that measures are in place to mitigate the high levels of morbidity, mortality and social and economic disruption that a pandemic can bring to this world,? she said.? March 6, 2006
http://www.mercurynews.com
12) Bird flu might spread more with the arrival of spring, said the spokesman from the World Health Organization (WHO), d**k Thompson, who added in an interview for a radio station that the risk of humans being infected with the virus is very small. ?What worries us,? he said, ?is that a mutation of the virus could transform the H5N1 into a human virus.? He ?warned that many experts believe there is a strong connection between the weather and the spread of the virus, explaining that cold weather hinders its spreading and warm weather makes it easier.?
http://www.daily-news.ro
13) U.S. Health Secretary Michael Leavitt told a Senate committee March 1, 2206 that the H5N1 virus might spread to the U.S. ``soon. The virus? appearance is ``just a matter of time; it may be very soon, he said in his testimony.
http://www.bloomberg.com/apps/news??refer=australia
14) `There will be a pandemic sooner or later, Nabarro said during a news conference today at the UN. `It could start any time. We have a virus capable of replicating inside humans. We have a virus that humans are not resistant to. We have a virus about which we don?t understand everything. It is at this stage of a pandemic alert that we have the luxury of being able to be prepared. ?March 8, 2006
http://www.bloomberg.com/apps/news??top_world_news#
15) ?I think it?s within the next six to 12 months,? (h5n1 in America)Nabarro (WHO) told a news conference, ?And who knows ? we?ve been wrong on other things, it may be earlier.? ? March 8, 2006
http://www.cbsnews.com
16) ?In 2004 we said it will be an international crisis if we don?t stop it in Asia, and this is exactly what is happening two years later,? said Joseph Domenech, head of FAO?s Animal Health Service. ?We were asking for emergency funds and they never came. We are constantly late.? ?March 6, 2006
http://www.localnewsleader.com/olber?news&id=153308
17) ?If we try to contain a pandemic,? said Keiji Fukuda, coordinator of the global influenza program at the World Health Organization, ?there really is a very good chance we will fail, that we will not be able to stop it.? He added, ?However, there is also a very good chance that if we mount this kind of effort, we may slow down the spread of a pandemic virus early on.? March 10, 2006
http://www.iht.com/articles/2006/03/10/business/flu.php
13.March 2006
Bush
Fauci
Webster
Thompson
Treanor
Thiermann
King
Fedson
Blaser
Pavia
Gerberding
President Bush
"If the virus were to develop the capacity for sustained human-to-human transmission, it could spread quickly across the globe."
"Our country has been given fair warning of this danger to our homeland -- and time to prepare."
Dr. Anthony Fauci, director, National Institute of Allergy and Infectious Diseases at the National Institutes of Health
"Americans need to know that it is a threat, a real threat. It is an unpredictable infection, a pandemic flu, which really means a kind of flu to which the American public or the whole world, the global population has not been exposed to before. It is very different from the seasonal flu."
"So you have to walk that balance of being prepared for something that may not come this year, may not come next year, but sooner or later knowing the history of how pandemic flus evolve over a period of time, over decades and decades, it will occur. So we need to be prepared."
Robert Webster, world-renowned virologist at St. Jude Children's Research Hospital, consultant to the World Health Organization and the National Institute of Allergy and Infectious Diseases
"About even odds at this time for the virus to learn how to transmit human to human. As the virus continues to expand its range as it's continuing to do into Africa, India and so on, I think it's got about a 50-50 chance of acquiring those characteristics. It's done so before, why not this time?"
"What should the average person do? The average person should be prepared to live in their family unit for three months. You have to have food, dried food, resources to live for 3 months in your unit. And so that's the maximum we can do."
Dr. d**k Thompson, World Health Organization spokesman on communicable diseases
"It's very unusual that a virus with pandemic potential actually appear. So, that has us concerned from the beginning. But have we seen any change in the last two years that makes us think that this is on the edge of mutating into a pandemic strain? ? Definitely not."
Dr. John Treanor, professor of medicine, Infectious Disease Unit, University of Rochester Medical Center
"If nothing else, [flu in U.S. birds] may present a very severe problem for agriculture in the Western Hemisphere."
"I think there is a real possibility that we will have a pandemic of flu due to one of these bird flu viruses. There are a lot of things we don't know about the epidemiology of flu and how flu pandemics get started. I think it is definitely something that we need to take seriously and worry about and be prepared for, but I don't know that it is inevitable."
Dr. Alex Thiermann, special adviser to the director general of the World Organisation for Animal Health (OIE)
"The H5N1 virus has resulted in the killing of 150 million chickens, and it has only infected 169 people. We need to remind everybody that we're dealing with a poultry disease, and we need to deal with it in the poultry. And of course it has a pandemic potential, but we have very good measures to prevent it by acting in poultry. Our concerns are in the countries that have very weak veterinary infrastructure, and don't have the resources or technical personnel to fight it."
Professor Sir David King, chief scientific adviser to the British government and head of the Office of Science and Technology
"It is very important to keep things in proportion, and to make a distinction between the virus in birds and the virus in humans." "Your chances of winning the lottery are about one in 14 million. Your chances of catching bird flu are more like one in 100 million, even if we had H5N1 among the chicken population in Britain."
Dr. David Fedson, retired medical director of Sanofi-Aventis, the world's third largest pharmaceutical company that's working on developing a human bird flu vaccine
"It's really impossible to say how close we are to the next pandemic. Everyone who is knowledgeable about this will say the pandemic is inevitable. We know the pandemic clock is ticking. We just don't know what time it is. As each day, week, month goes by we are getting closer to the inevitable next pandemic."
Dr. Martin Blaser, president-elect of the Infectious Disease Society of America
"Although the world needs to be prepared for a flu pandemic in the future, it's important to keep in mind that there is no pandemic right now. Even the H5N1 virus that is currently circulating in Asia and Europe primarily causes a disease affecting birds. There have been very few cases of bird-to-human transmission."
Dr. Andrew Pavia, chairman of the Infectious Disease Society of America's Pandemic Influenza Task Force
"Most bird flus emerge briefly and are relatively localized. The most worrisome thing about H5N1 is that it has not gone away."
"We should be worried but not panicked."
Dr. Julie Gerberding, director of the Centers for Disease Control and Prevention
"Even if it does enter through a migratory bird at some point, which won't be surprising, we have a wonderful system of surveillance and a Department of Agriculture and a Department of the Interior here that know what to do and have been handling bird viruses for many, many decades."
Hier ist ein aktuelles Interview mit Webster, _dem_
wahrscheinlich bekanntesten und renommiertesten
Virologen der Welt.
http://en.wikipedia.org/wiki/Robert_Webster
---------------------------------
Bekannter Vogelgrippe-Experte warnt : Seid vorbereitet.
"Die Chance dass der Virus lernt von Mensch zu Mensch ueberzuspringen
ist etwa 50% " sagt Webster in ABCs "World News Tonight"
"ich persoenlich glaube, es wird passieren und mache persoenliche
Vorbereitungen", sagt Webster, der einen 3-Monate Vorrat an
Lebensmitteln und Wasser in seinem Haus gespeichert hat fuer den Fall
eines Ausbruchs.
Schreckerregende Warnung : "Die Gesellschaft kann einfach
die Idee nicht akzeptieren, dass 50% der Bevoelkerung sterben
koennten, und ich denke, wir muessen dieser Moeglichkeit ins
Auge schauen." sagte Webster. "Es tut mir leid, wenn ich die
Leute damit ein wenig erschrecke, aber ich denke, das ist
meine Rolle".
Die meisten Wissenschaftler wuerden es nicht so frei heraus sagen,
aber viele geben zu, dass Webster richtig liegen koennte, dass der
Virus von Mensch zu Mensch uebertragbar werden wird, obwohl sie
glauben dass 50% zu hoch sein koennte.
...
--------------------------------------------
vollstaendiger Artikel hier:
http://abcnews.go.com/WNT/print?id=1724801
Renowned Bird Flu Expert Warns: Be Prepared
There Are "About Even Odds" That the Virus Could Mutate to an
Easily Transmitted Form, He Tells 'World News Tonight'
By JIM AVILA and MEREDITH RAMSEY
March 14, 2006 — - Robert G. Webster is one of the few
bird flu experts confident enough to answer the key question:
Will the avian flu switch from posing a terrible hazard to birds
to becoming a real threat to humans?
There are "about even odds at this time for the virus to learn
how to transmit human to human," he told ABC's "World News Tonight."
Webster, the Rosemary Thomas Chair at St. Jude Children's Research
Hospital in Memphis, Tenn., is credited with being the first scientist
to find the link between human flu and bird flu.
Webster and his team of scientists are working to find a way to beat
the virus if it morphs. He has even been dubbed the Flu Hunter.
Right now, H5N1, a type of avian influenza virus, has confined
itself to birds. It can be transmitted from bird to human but
only by direct contact with the droppings and excretions of infected birds.
But viruses mutate, and the big fear among the world's scientists is
that the bird flu virus will join the human flu virus, change its
genetic code and emerge as a new and deadly flu that can spread
through the air from human to human.
If the virus does mutate, it does not necessarily mean it will be as
deadly to people as it is to birds. But experts such as Webster say
they must prepare for the worst.
"I personally believe it will happen and make personal preparations,"
said Webster, who has stored a three-month supply of food and water
at his home in case of an outbreak.
Frightening Warning
"Society just can't accept the idea that 50 percent of the population
could die. And I think we have to face that possibility," Webster said.
"I'm sorry if I'm making people a little frightened, but I feel it's
my role."
Most scientists won't put it that bluntly, but many acknowledge that
Webster could be right about the flu becoming transmissible among
humans, even though they believe the 50 percent figure could be too high.
Researcher Dr. Anne Moscona at New York Weill Cornell Medical Center
said that a human form may not mutate this year or next -- or ever --
but it would be foolish to gdgs the dire consequences if it did.
"If bird flu becomes not bird flu but mutates into a form that can
be transmitted between humans, we could then have a spread like
wildfire across the globe," Moscona said.
No one knows how long or how many mutation changes it would take
for bird flu to become a direct threat to humans.
"It may not do it. There may just be too many changes. The virus
may not be able to be a human virus," Moscona said.
But that hasn't stopped Moscona from searching for new types of
anti-viral treatments that both prevent and slow the spread of bird flu.
"I don't think that once we have human-to-human transmission, it's
going to be possible to contain it," she said.
That is why nearly every viral scientist in America, perhaps the world,
is waiting and watching the avian flu virus
to see if it remains just a threat to birds or changes its genetic code
and becomes a deadly threat to humans as well.
The CP interview: Dr. Michael Osterholm of the University of Minnesota's Center for Infectious Disease Research and Policy talks about the flu bug that could bring the world to its knees.
BY STEVE PERRY
Scare headlines about the possibility of a deadly flu pandemic have been with us for a few years now, ever since the H5N1 bird-flu virus that first appeared in Hong Kong in 1997 resurfaced in the region in 2003. But in the past month the drumbeat of such stories has grown faster and louder: Avian Flu Arrives in Poland. Turkey. Azerbajian. Germany. Denmark. And, just last Friday, Israel. The good news, according to Dr. Michael Osterholm, the director of the University of Minnesota's Center for Infectious Disease Research and Policy, is that the arrival of infected birds in North America—sometime this year, in the estimation of most experts—is not likely to result in large numbers of human infections with the virus, because most domestic poultry in this part of the world is raised in factory-farm isolation units that prevent contact with wild birds.
The bad news is that that's pretty much the only good news. What matters in judging the prospects for a human pandemic version of H5N1 (the name is shorthand for the chemical structure of two of the virus's key components, hemagglutinin and neuraminidase) is not so much the global reach of the bird version, but the question of if or when the virus mutates to a form that's easily passed from human to human. If that happens anywhere in the world, says Osterholm, the virus would likely start hitching rides with travelers and seed itself around the globe in a matter of days or weeks.
Of the hundred-plus human cases of H5N1 flu recorded so far, the vast majority have involved bird-to-human transmission, mostly among open-air poultry handlers in Asia. In addition, there are confirmed clusters in which it has passed from person to person, though none of those has yet resulted in a breakout of the virus. One thing is clear, however: In its present form, H5N1 has killed over half of the people it's infected. The great flu pandemic of 1918-19, by contrast, killed about 5 percent of its victims.
Will it cross over? If it does, can it possibly remain as deadly? Though Osterholm notes that viruses usually do lose strength as they spread—it's not really in their own evolutionary interest to kill the majority of their hosts—he believes the only responsible answer on both counts is we don't know. But it's not just the characteristics of the virus that worry him.
One of the things that sets the former Minnesota state epidemiologist apart from other public health officials is his attention to the fate of the medical and social infrastructure in any serious contagious outbreak. With respect to bird flu, his outlook recapitulates in many ways what he had to say in his 2001 book about bioterrorism preparedness, Living Terrors—much of the human toll in death, hysteria, and anarchy would be exacted not by infection but by the wide-scale breakdown of global supply chains and just-in-time delivery systems for vital goods and services. "I think [Health and Human Services] Secretary [Mike] Leavitt has been brutally honest in telling American communities, you're going to be on your own," says Osterholm. "And I think he's right."
City Pages: Let me start with the question of the likelihood of a global flu pandemic. Yesterday alone, I saw two wire service headlines with radically different-seeming implications, one indicating that the H5N1 avian flu is likely to go global within six months, and another speculating that the threat of human transmission may be passing as we speak. Is it possible to say, based on the epidemiological evidence, how likely a human flu pandemic is in the next six months, the next year, the next two years?
Osterholm: "H5N1 is the most powerful influenza virus we've seen in modern human history"
Courtesy of CIDRAPMichael Osterholm: First of all, let me take a step back and say that's a typical question we hear from the public. But it's almost like asking, how many apples can you harvest from the ocean? Because flu pandemics are like earthquakes, hurricanes, and tsunamis—they occur. There's going to be another one. There have been 10 in the last 300 years. What you're really asking, I think, is will it be H5N1? It's important to understand that when you're preparing for pandemic influenza, you're preparing for something that will happen. To say anything to the contrary would be like saying, now that Katrina's happened, we'll never have another hurricane like it.
Will H5N1 be the pandemic strain, and will it occur in the next six to twelve months? The answer is, we don't know. What is troubling about this virus is that this thing has continued to mutate from its earliest days, in Hong Kong in 1997. And what is very, very troubling to us is that it's mutating in very similar fashion to the way the 1918 virus did. We went back with the 1918 virus and found all eight genes of that virus in tissue samples—five from soldiers' pathology slides that had been stored away, three from the recovered corpse in Alaska. They didn't have any live virus, but they've been able to make the virus from those eight genes. And by studying that, they could determine how it actually mutated and jumped directly to humans from birds. It didn't go through other species as the 1957 and 1968 viruses did, where a bird and a human virus got together, most likely in a pig lot, because pigs happen to be the universal recipients for both [birds and humans].
They combined to make a third, dumbed-down virus that caused mild pandemics.
The 1918 virus jumped right from birds to people. There was no combining with other viruses. One of the problems we've had is, if you look at the 1918 virus and this one, they're in essence kissing cousins. Genetically, these things look very similar. Frank Obenauer and colleagues just published a paper the last week of January in Science, and they actually have gone back and looked at the full genetic codes for 169 avian virus genomes, dating way back. They looked at 2,169 distinct avian virus genes. There were two viruses that showed a protein tag at the end of one of the nonstructural genes that actually looks to help cause the cytokine storm that makes this a unique illness.* And guess which two viruses they were: 1918 H1N1, and the current H5N1.
Then, when you look at the Turkey virus—that thing mutated. This is the case of the young girl in Turkey who died from her infection, and so did her uncle. We definitely have clusters where it's not just bird contact [spreading the virus]. The uncle's only exposure to this virus was riding in the ambulance with her from hospital one to hospital two. He became ill three days later and died. Her virus has now been fully sequenced, and there were three mutations that occurred in that virus, between the bird version and hers. One was the substitution of a glutamic acid with lysine at the 223-hemagglutinin position. That is what changes it from a bird-receptor virus to a human-receptor virus. The second thing was two other substitutions that served to make it look more and more like a human virus.
So this thing just continues to march. Changes are occurring in it all the time. [Human-to-human transmission] could happen tonight. Or it may never happen. But I don't know what will keep it from happening, because when you have this kind of worldwide bird population as we do now—China's a good example. In 1969, during the last pandemic, China only had about 12 million chickens. Now it's got over 15 billion.
CP: Do you think the rise of poultry farms of vast scale has contributed to the viral soup that influenza viruses grow in?
Osterholm: Not really, and I'll tell you why. When you look at the rise of the really big bird operations, they are actually raised in these bio-security barns, which people have all kinds of problems with for entirely different reasons—humaneness and that kind of thing. They actually are very safe, generally speaking, because they keep the wild birds and the domestic birds separate. It's in Asia where you have all these small 20-, 40-, 50-chicken operations where the birds are living in open space with you—that's where the vast majority of the chicken population is at in the developing world. A good example is Turkey, where we're seeing the first cases outside of Asia now. This is taking the virus out of a tropical area and putting it in a temperate area that gets cold. Every night, those people bring their chickens into the house. It's just a very different mindset.
And for as much as this is going to come here someday, [bird-to-human transmission] is not going to be a big risk factor to humans on this continent, because other than free-ranging organic birds that are out there, domestic birds aren't going to be at big risk.
CP: Can you explain in lay terms what makes a strain like H5N1 novel, and so potentially deadly?
Osterholm: Well, there are three things that make a strain of influenza virus potentially capable of causing a pandemic. First of all, you have to have a situation where you've got a novel or a new strain, meaning you don't have any antibody protection against it. Then you have to have one that is able to go from human to human. That's what we don't have yet. The third thing is, it has some virulence characteristics that make it cause severe illness.
This virus is quite different from what we see with the standard annual flu, and what we saw in 1957 and 1968, because of the cytokine storm it causes. In 1918, the vast majority of the people who died were healthy young people, 20 to 40 years of age. And that was in large part because they had the strongest immune systems.
CP: You're saying that the symptoms that cause fatalities, aside from secondary bacterial infections, are actually a function of the immune system working overtime.
Osterholm: That's it. And that's what we're trying to understand at this point, in terms of how to best prevent this [immune reaction]. And right now it doesn't look like there's much you can do. I mentioned this "kissing cousins" phenomenon. If you put 1918 H1N1 into animal models at very, very low doses, it basically kills all of them in 24 hours. The lab science people had never seen that. At 16 to 24 hours, that virus was different from anything they'd ever seen in killing these animals. The only virus that was similar was H5N1, and it was fatal at much lower doses. H5N1 is the most powerful influenza virus we've seen in modern human history.
What makes them so similar is that they both cause this cytokine storm phenomenon.
The deadly 1918-19 flu pandemic spawned stern public warnings—and widespread panic
Top and right: Courtesy of Temple University Libraries. Bottom left: Courtesy of National Library of MedicineCP: Which essentially results in a person's drowning in his or her own blood as it fills the lungs, right?
Osterholm: It's even worse than that. You get that kind of leakage, yes, but it also goes in and begins to shut down all your vital organs. It's a domino effect. Your kidneys go down, then your liver goes down, you have all this destruction through necrosis of your lungs and your internal organs. Everything goes.
CP: In the limited human sample we've seen so far, this influenza has exacted a much higher mortality rate than the 1918 flu. Are there mechanisms that tend to dilute the virulence of a strain as it spreads?
Osterholm: That's a really critical question. We can only anticipate that this will attenuate. Meaning that once it starts spreading in humans, it will lose some of its punch in order to better adapt to humans. That's traditional with virtually all agents you see like this. The thing that is very difficult to talk about is, we don't know how much. If this were to go human-to-human—we talk about a worst-case scenario in terms of what happened in 1918, when roughly 2.5 percent of the world's population died. Of those who contracted it, roughly 5 to 6 percent of populations died, varying by age.
The mortality rate so far for this virus is around 55 percent, so this virus would have to attenuate a lot to get down to that level. And we do have good data. There are not a lot of mild, asymptomatic infections out there [with H5N1]. We're now aware of six studies involving over 5,000 close contacts of H5N1-infected people, in Indonesia, Vietnam, and Hong Kong, in which less than one person per thousand contacts had evidence of an H5N1 infection that was missed—that is, a mild infection.
This [virus] is not causing a lot of asymptomatic infections right now. Some people are saying there's a lot of mild [H5N1-related] illness all over out there, but it's just not true. That means we're not artificially inflating the mortality rate by missing a lot of infections. I'm actually pretty confident that the real mortality is almost that high.
So for that number to drop all the way down to a couple percent is a pretty big drop. Which says to me that when people talk about 1918 as a worst-case scenario, well, maybe that isn't the worst-case scenario. That's hard for people to hear, because then they think you're really trying to scare the hell out of people. But you know what? It's just the data.
If this virus were to ultimately go human-to-human, none of us know what the human mortality would be.
CP: Does the fact that it seems to be gaining more currency in other mammal species augur one way or the other for its becoming transmissible from person to person?
Osterholm: None of us know. In 1918, for instance, we don't know whether it infected cats and dogs. We've been trying to find that out. Nobody's got that data. There just weren't good reports. It surely can't be good that it's adapting to more species. It says that the lung receptors of chickens aren't the only ones that will take this virus. And we know humans surely will take it, on the off chance that they're exposed [to infected birds].
The bird-to-cat thing is not new. Some people have made a lot out of the German situation. That's not new. The Bengal tigers at the Bangkok Zoo died two years ago. They got fed H5N1-infected chickens, and 50 of the Bengal tigers died. They also transmitted to each other—there were cats there that did not eat the chickens. Even Albert Osterhaus's work of the past couple of weeks, which has been really important to confirm it, was not a surprise.
CP: I wanted to ask you about a scenario you described in your New England Journal of Medicine article from last year, "Preparing for the Next Pandemic." If a flu strain transmitted from human to human did break through in some part of the world, how would you expect events to unfold over the first weeks?
Osterholm: Well, look at what's already happening with the bird situation. You've got countries like South Korea saying, don't go to Egypt. You've got a lot of bird embargoes already taking place. If you saw this morning's Wall Street Journal, the travel industry in Europe is tanking. And this is a non-threat to a vast majority of humans. What we're concerned about is that if this takes off in a given area, it's going to move around the world quickly, just like SARS. Last year 750 million people crossed a national border somewhere in the world, either by plane, automobile, or on foot.
These things move fast. With SARS, we had one physician from China who came to Hong Kong, stayed in the Metropole Hotel on one floor where there were nine other individuals he infected just through breathing the air. They then took it to four different continents in the next two days. That gives you kind of a model, though influenza is much, much more infectious.
I was very critical of those models that came out last fall that suggested you could put a blanket over this with Tamiflu. My whole criticism was practical—that you would never find this quick enough and confirm it. Despite the fact we now know Turkey was going on for weeks before we understood what was happening over there, it was only last week that the uncle's isolates were confirmed, almost eight weeks after the fact.
*Cytokines are a class of proteins produced by white blood cells whenever the body finds itself responding to an infection. They vary in function—some cytokines attack invading microbes directly, others relay chemical messages from cell to cell, still others bind with cells in the hypothalamus region of the brain to produce fevers. Cytokines are toxic not only to infectious agents in the body but to the body itself: Much of the pain and discomfort that accompany illnesses like the common flu, for example, are in effect hangover symptoms from the toxic effects of the body's own immune response. The term "cytokine storm" refers to the immune response that occurs when the body is confronted with an infectious agent that reproduces at great speed and in huge volume. This "viral storm" generates an equally huge immune response—the cytokine storm—that can take such a toll on lung tissue (the main battleground where the virus and the immune system face off) that it deprives vital organs of enough oxygen to function, and sets off cascading organ failure.
CP: There's been a lot of covering up by some governments, hasn't there? It's been repeatedly alleged of the Chinese.
Osterholm: Exactly. So my whole point is that before anyone will have even figured out that this is going on with any certainty, it'll be gone—the cow will be out the barn door. With influenza, that's just...it's something you can't pull back in.
CP: Periodically we see stories about the race to derive vaccines, but that's not conceivable, is it, until we know which viral subtype will break through?
Osterholm: Well, even that's a misconception, I think. The concern we have is that people all want to know if some new vaccine is "the answer." The problem is, we do need a new vaccine. We're dealing with a 1950s-technology vaccine with only one update. Right now, given the amount of virus needed to make vaccines for H5N1—it needs a lot more antigen [than typical flu strains]—our total worldwide capacity right now, in one year's time, is only enough vaccine to protect 100-200 million people worldwide. That's in one year after a pandemic starts. And that's it. You can't make any more, given the limited capacity we have.
So you know what? It doesn't matter if we invent vaccines if we can't manufacture them. This is a point I've tried to make over and over again. We also are approaching this from a very American-centric point of view, which in the end will be the death of us. What's going to happen is, even if we could produce vaccines for our country in a timely manner, this global just-in-time economy we live in today is going to see the rest of the world shut down. Eighty percent of all the drugs we use in this country—all the childhood vaccines, everything—come from offshore. Your cardio drugs, your cancer drugs, your diabetes drugs, 80 percent of the raw ingredients come from offshore. I could go through a whole laundry list of other critical and essential products and services that come from offshore. If the rest of the world experiences a pandemic, we're still screwed. That's what people don't understand. Somehow they have this attitude that we can wall ourselves off in the Eighth District of Minneapolis and be okay.
The bottom line is, it will be years, even at the accelerated rate we're going now, before we even get the right candidate-vaccines. Then they still have to be approved. No company's going to embark on building manufacturing capacity without the certainty of a market. And second of all, they have to know exactly what vaccine will be used and how they need to develop their plant. All this means that an influenza plant, from start to finish, would probably take three to five years to build.
CP: Why don't we have the capacity to produce more in the way of basic vaccines here in the U.S.?
Osterholm: Because it's all about the market. Today, many of the anti-infective antibiotics and vaccines are not considered blockbuster products for any pharmaceutical company. We have a number of our childhood vaccines that are down to a single manufacturer now. If you go to the Society for Health Care Pharmacists' website, you'll see a list of 42 drugs today that are in short supply because of the just-in-time supply chain. Now, you put on top of that products that are marginal in their [profit] return, and it becomes a loss leader for these companies [to make vaccines]. They want out of it.
This is not true just for vaccines, but also for antibiotics. There, we tell people to hardly use them, and only for specific purposes and limited periods. It's not like the lifestyle drugs, where you're taking your statins for the rest of your life. So they just don't see the profitability [in antibiotics]. We're in real trouble. And it's not just with respect to the flu.
CP: The one easy-to-use drug that's been shown to arrest H5N1 in humans is Tamiflu—
Open-air poultry markets in Asia--like this one in Hanoi--put infected birds in routine contact with people
Photo by Hans Wagner
Osterholm: Well, that's not really true. There's no evidence that it makes a difference in H5N1 infection. I have a slide here showing that the case mortality rate in Vietnam was identical for those who got Tamiflu and those who didn't. I actually believe Tamiflu could work, but the problem is, we're applying it in the H3N2 [average seasonal flu] model. Seasonal flu grows up much slower in a human, so that if you get the drug into somebody two days after their onset, you can still have a pretty measurable impact on the severity of their illness and the likelihood they'll have complications. With the H5N1 virus, the virus storm that precedes the cytokine storm is so remarkable in those first 24 hours that if you don't have the drug onboard in those first 24 hours, it may only have limited impact.
The second thing is, we're using the same dosage levels we use for H3N2 [seasonal flu]. This is a very different virus. We may have to double the dosage for twice the length of time. We have anecdotal data on people who got the drug early and appeared to do better, but then, after the typical five-day course was stopped, they died on day ten.
The problem we have is not whether Tamiflu is available and will work, but can you get it soon enough and in high enough amounts? How do you get the drug to somebody in the first 12 hours of their illness? The second thing is, when people talk about having 20 million or 40 million protective doses, what does that mean? If we're going to have to use twice the dose for twice as long, that means maybe you've got one-fourth as much of the drug you think you have.
That's the story on H5N1 and Tamiflu. I think it can work, but it won't work the way we're approaching it.
In the next five years, with [Tamiflu manufacturer] Roche outsourcing all of the production they can, our best guesstimate is that—using the old, low dosage standards—we could probably produce enough Tamiflu to treat about 7 percent of the world's population in the next five years, because of the precursor chemicals needed and the complicated nature of making this stuff. That's the sum total of production capacity. It's no panacea.
CP: How would you rate the public health infrastructure in the U.S. for its ability to deal with massive numbers of very ill people? You wrote in the NEJM last year that our system lacks "surge capacity" to deal with a lot of sick people at once—why is that?
Osterholm: It's much deeper and bigger than the public health system. It's really the total care system. For example, I talked [in that article] about the 105,000 mechanical ventilators? On any given day, 70,000-80,000 of them are in use, and in a normal flu season we butt up against the 100,000 mark. We have no excess capacity there whatsoever. Just right here in our own Twin Cities, we've reduced intensive care beds by 20 percent in the last four years, as a matter of cost containment.
We'll run out of masks and respirators overnight, because it's a global just-in-time supply chain. There are two manufacturers who have the largest share of the market there, but with virtually no surge capacity. We'll run out of IV needles. We'll run out of IV bags. We'll run out of drugs very quickly. Remember I talked about the 80 percent offshore figure? Go to the Society for Health Care Pharmacists' website and you'll see what I'm talking about.
So the whole medical system will collapse, at a time when we still need drugs for heart attacks, cancer, and everything else. We'll be in freefall. That may sound scary, but it's a reality. And unlike Katrina, where the hurricane did some of the destruction and separated people from health care through evacuation or otherwise, the same thing's going to happen here in every city, town, and village in this country as well. We're all going to need things at the same time, and there won't be any products.
At this Business Continuity Summit we just had, we actually had a major discussion in which a lot of voices expressed concern about the internet—that it doesn't have the backbone and elasticity that everyone thinks it has, and just a limited surge could bring down the internet.
Right after Katrina, when FEMA was trying to rescue itself, they put out a call for anyone who had a refrigerated truck unit to come and sit in one of several parking lots in the Gulf states down there, in case they had 10,000 bodies, etc. A contingent of them went. Not all of them, by any stretch of the imagination. Within 72 hours, major food manufacturers throughout the United States reported that they couldn't ship their goods. They had no trucks. We have a razor-thin capacity in this country right now on virtually everything. They had to get FEMA to release the trucks.
Cities like Seattle have already come to the conclusion they won't be able to have refrigerated trucks, because of that issue. For their work with corpse management, for example, they've already mapped out where every one of the ice arenas in Seattle is. Because you won't be able to bury people, either. In 1969, during the last pandemic, the average time from when a casket was made until it was in the ground was about six months. Today it's a little over a month, and in some areas of the country it's less than that. There's no surge capacity in casket manufacturing. Today, crematorium space in this country is a just-in-time situation too. This means we would quickly run out of the ability to handle bodies in a timely, respectful way. That's in a moderate pandemic, not at all like 1918. Everything now is done on the basis of just-in-time delivery systems.
Now, think about Katrina. As horrible as it was seeing the Superdome, seeing shots of bodies rotting would kind of take you over the top. What really offends the sensibilities of most Americans is when you see the dead handled in a disrespectful manner. I worry that one of the tipping points in a panic/fear situation over pandemic flu would come when we can't, in a timely way, handle the bodies or get them into cold storage. Those are issues we haven't dealt with at all.
As of last week, H5N1-infected birds had turned up in over 30 countries, and 178 humans had contracted the virus
Courtesy of PandemicFlu.gov
CP: Your answer to this is partly implicit in all you've said, but let me ask you to sum up how you'd rate the U.S.'s and Minnesota's state of preparedness for a pandemic.
Osterholm: I think the U.S. right now is leading the way in terms of the overall issue of pandemic influenza preparedness. The problem is that, for much of the developing world, they don't have a lot to prepare for. They don't have sophisticated supply-chain issues. In some ways I think they're better off than we are, because they already live a very simple, hand-to-mouth existence. For us, with our complicated supply networks, we have a long, long way to go. And I think that's as much a private-sector issue as a government issue. I think Secretary Leavitt has been brutally honest in telling American communities, you're going to be on your own. And I think he's right. You know how you creep, then you walk, then you run? We're still on our knees.
CP: What kind of measures might we in the Twin Cities expect to see undertaken in the short term if an outbreak did reach the U.S.?
Osterholm: I can't say. I don't know. I know that the governor today, in his State of the State address, said that he's just committed $10 million to influenza preparedness. What that means, I can't say. We don't have the details yet.
When the virus gets to this continent as a bird virus, it's important that we not overreact and misinterpret it to mean that now the pandemic's here. This will be an important issue for poultry, but as I pointed out, I think most of the poultry in this country—aside from the free-range organic poultry—is going to be pretty well-protected.
It's about the birds and it's not about the birds. It's about the birds now, but when real pandemic influenza occurs, the birds become inconsequential. It's human-to-human transmission that matters then. That's where we're not any better prepared here than anyone else in the world.
CP: How would you rate the media's performance in covering this story—too salacious, too understated, just right?
Osterholm: It's like talking about the weather, I guess—depends on which day, and where. There have been some outstanding reporters on this issue. Helen Branswell, from Canadian Press, covered SARS and has become the primary person on this. She's done it as well as anybody. On the whole, it has been poorly covered in the sense of distinguishing H5N1 in the bird population from pandemic influenza. That part has not been covered in depth. The issue about covering preparedness—no one has really gone into depth and explored the supply-chain issues to say, okay, what does this all mean? Let's take a community and say, what would happen here? We're so fixated on the news cycle that it's too often about, "what new country has just been infected with bird virus?" and not really get into the issues. Ted Koppel at Nightline did an excellent series of stories and asked good, hard questions. But now he's gone and Nightline hasn't picked it up since he left.
_________________
April 2006:
-------------
Palese
Taubenberger
Donis
Peiris
Osterholm
Fauci
Palese
believes some factor may be blocking this virus from h2h
"I am convinced that pandemics will occur in the future,"
"I'm just not sure it will be H5."
Palese is betting against H5N1,
Taubenberger:
"I think that the best answer is that we do not understand
the rules under which influenza pandemics form,"
"And therefore we don't actually
know if there are biological constraints limiting particular strains
and particular subtypes, that they either can or cannot adapt
to humans and cause pandemics,"
"So I think the jury remains out as to whether
H5 has that ability."
Donis
points out that a flu virus called
H3N8 circulated in horses in North America for nearly 40 years
before jumping into dog populations and triggering the canine
flu that grabbed headlines last fall.
"That's the reality.
We don't know. It doesn't exclude anything,"
Peiris:
"It is fair to say that if it was a simple thing for the
virus to change and to become pandemic . . . that probably would
have happened by now,"
"That I think is a fact. (But) this
applies to all the avian influenza viruses out there."
a pandemic with this flu subtype could be
severe, with enormous public health consequences.
"It would be extremely irresponsible if one did not take
this threat seriously," he says.
Osterholm:
"To conclude that a pandemic
won't occur because it hasn't happened by now is like saying that
because New Orleans hadn't been hit by a hurricane for more than
80 years that it wasn't ever going to get hit again," Osterholm
says flatly.
"Katrina proved the point."
Palese
his position isn't just based on a gut feeling, but on "evidence"
he sees as persuasive but which others argue is far from bankable proof.
In the decade or more since the virus was first isolated,
it has had multitudes of chances to combine or "reassort" with
human or other mammalian genes in ways that in theory could produce
a human-adapted virus.
"I think this is indirect evidence,
"It has infected many, many chickens. And there
would have been ample opportunity to also undergo reassortment
with human genes (to become a human-adapted virus). And it has
not happened."
"Now that alone . . . does not exclude that
it might happen one day. On the other hand, I think by having
had that many opportunities I think that is a fairly strong argument
in my mind."
Millions of people in China
may have been infected, suffering mild or no disease, through
contact with poultry - and still the virus hasn't made the jump.
This is based on a study published in 1992
that suggested up to seven per cent of people in some parts of
rural China had antibodies to H5 viruses.
Fauci:
"I don't dismiss at all the notion that some people
bring up that it is conceivable that the way this virus is genetically
programmed, that no matter how much opportunity you give it, it'
s never going to be able to fully adapt itself to humans,"
"But since we don't know it, I think
it would be somewhat reckless to assume and say 'Ah, it's been
around so long, if it hasn't changed it will never change, let'
s just forget about it and go worry about something else.'
20.6.2006:
Dr. Tom Wittum and Dr. Armando Hoet, associate professors of veterinary preventive medicine with a joint appointment in the Ohio State School of Public Health,
The probability of a pandemic is very low based on what the scientific community knows about the virus, Wittum said.
------------------------------------
10.July 2006 :
Malik Peiris: "pandemic in the next 10 years extremely likely "
------------------------------------------
Michael Steele: (Jan.2006):
20 % for a pandemic starting in 2006
http://www-stat.wharton.upenn.edu/~steele/Pandemic/H5N1 Probability Models.htm
-----------------------------------------
Stephen Salzberg
June 2006)
my expectation value is that H5N1 will NOT turn into a
human flu pandemic. I would give it a chance of 10%,
purely subjective. Reason: it has been around since 1997
and has had many chances to mutate into a human flu, and it
hasn't done yet. Reason 2: the evolutionary pressure on
H5N1 is overwhelmingly focused on keeping it viable in birds,
not people.
However, there is a better chance - maybe 30-50% - that
eventually H5N1 and H3N2 will recombine giving a new
human flu pandemic. This might or might not be especially
deadly, hard to tell.
Other experts agree with me on this - but some bird
flu experts feel much differently. We don't have enough data.
http://www.h5n1experts.org/forum/forumdisplay.php?f=13
http://www.h5n1experts.org/forum/forumdisplay.php?f=14
http://www.h5n1experts.org/forum/forumdisplay.php?f=14
Taubenberger
Fedson
Oxford
Osterholm
Doherty
Fukuda
Fukuda
Osterholm
Webster
Webster
(assmebled April 2006)
http://www.h5n1experts.org/forum/forumdisplay.php?f=13
Lucey
Doctors without borders
Levitt
Fukuda
Guan
Sandman,Lanard
Osterholm
Webster
Barry
Fauci
(assembled April,May 2006)
Palese Interview in Deutsch
--------------------------------------------------------------------------------
Unberechenbare Grippe
Von Sascha Karberg
Vor einem Jahr konnten Virusforscher das Grippevirus rekonstruieren, das w?hrend der Pandemie von 1918 rund 50 Millionen Menschenleben forderte. Peter Palese war einer dieser Forscher.
Der geb?rtige Sudetendeutsche, der in ?sterreich aufwuchs, forscht seit 36 Jahren in den USA vor allem an Influenza-Viren und geh?rt zu den V?tern einer Technik namens Reverser Genetik. Damit l?sst sich das Erbgut der Influenza-Viren gezielt manipulieren, sodass nicht nur die Funktionen der Virusgene genau untersucht, sondern auch geeignete Virusvarianten f?r Impfstoffe hergestellt werden k?nnen. F?r diese Arbeiten erhielt Palese, der an der Mount Sinai Medical School in New York forscht, neben dem Japaner Yoshihiro Kawaoka von der Universit?t Tokio Ende der Woche den diesj?hrigen Robert-Koch-Preis.
Virologen unterscheiden Influenza-Varianten vor allem anhand zweier Gene, die f?r zwei H?llproteine des Virus kodieren, das H?maglutinin (H) und die Neuraminidase (N). 16 H- und neun N-Varienten sind bisher identifiziert, sicher gibt es aber viel mehr. Das 1918er-Virus hatte von beiden Proteinen die Variante 1 und wird deshalb H1N1 genannt. H2-Viren haben die Asiengrippe 1957 und H3-Viren die 1968er-Hongkong-Grippe ausgel?st. H5- und H7-Varianten k?nnen bisher nur zwischen V?geln ?bertragen werden. Mit H5-Influenza infizierte Menschen (bisher rund 250 F?lle) k?nnen andere Menschen nicht infizieren.
TR: Professor Palese, Ihre Kollegen haben den Eindruck erweckt, es sei eine Art Automatismus, dass sich aus dem Vogelgrippe-Virus H5N1 irgendwann ein menschliches Influenza-Virus entwickeln wird, dass eine Pandemie wie 1918 ausl?st.
Peter Palese: Ich halte es f?r sehr wahrscheinlich, dass es in absehbarer Zeit eine Influenza-Pandemie geben wird. Recherchiert man in den vergangenen Jahrhunderten, dann hat es in jedem Jahrhundert drei bis vier Influenza-Pandemien gegeben. Ich glaube nur nicht, dass es unbedingt das H5N1-Virus sein muss, das die n?chste Pandemie ausl?st. Und es muss auch keine so verheerende Pandemie sein, wie 1918. 1968 und 1957 verliefen die Ausbr?che viel milder.
TR: Seit einem Jahr untersuchen Sie im Labor das Influenza-Virus, das 1918 mit 50 Millionen Toten die wohl bisher verheerendste Grippe-Pandemie ausl?ste. Haben Sie im Erbgut des Virus inzwischen eine Ursache f?r dessen ungew?hnliche Aggressivit?t gefunden?
Palese: Wir haben im Labor an M?usen zeigen k?nnen, dass das 1918er-Virus tats?chlich so infekti?s und t?dlich ist wie kein anderer Grippevirus zuvor und danach. Aber es gibt keine besondere einzigartige Signatur im Erbgut, die die alleinige Ursache dieser Aggressivit?t w?re. Alle Virusgene tragen bestimmte Ver?nderungen, und es ist wohl die Kombination dieser Mutationen, die das Virus insgesamt optimieren. Das ist wie bei einem Sprinter: Nat?rlich braucht der besonders gute Beine, aber er braucht auch beide Arme f?r die Balance und gute Brustmuskeln zum Atmen. Sicher lassen sich auch mit nur einem Arm gute Zeiten laufen, aber eben nicht die besten. Das 1918er-Virus ist ein Gewinner, weil zuf?llig alle K?rperteile, alle Gene des Erbguts perfekt zusammengewirkt haben. Dadurch kam eine Grippevariante zustande, wie wir sie noch nie zuvor beobachten konnten. Und vielleicht wird es nie wieder eine so ideale Kombination optimaler Genvarianten geben.
TR:Aber das hei?t doch auch, dass sich durchaus ein noch aggressiveres Virus als das von 1918 entwickeln k?nnte?
Palese: Ich w?rde das nicht ausschlie?en. Damit will ich keine Panik machen, aber wissenschaftlich ist das m?glich. Es gibt eben viele M?glichkeiten, ein guter Sprinter zu sein.
TR: Ihr Kollege Jeffrey Taubenberger hat die Bausteinabfolge des 1918er-Virus aus Virusresten rekonstruiert, die er aus exhumierten Opfern der Pandemie gewonnen hat. Anhand dieser Erbgutdaten behauptet Taubenberger, dass das Virus von 1918 Vogelgrippeviren ?hnlicher ist als menschlichen Grippeviren und das 1918er-Virus wahrscheinlich ohne eine Neukombination im Menschen direkt vom Vogel auf den Menschen ?bergesprungen ist.
Palese: Die Erbgutdaten Taubenbergers sind o. k., aber die Interpretation der Daten teile ich nicht. Um wirklich beurteilen zu k?nnen, ob das 1918er-Virus den Vogelgrippeviren ?hnlicher ist als den menschlichen Influenza-Viren zu dieser Zeit, fehlen Taubenberger die Vergleichsm?glichkeiten. Wenn wir menschliche DNA, Zebra-DNA und irgendeine Pflanzen-DNA miteinander vergleichen, dann erscheint der Mensch nat?rlich dem Zebra sehr ?hnlich. Wir m?ssten eine ganze Reihe menschlicher Influenza-St?mme untersuchen, die vor 1918 zirkulierten. Solange wir das nicht k?nnen, ist es unm?glich, diese Aussage zu machen.
Das Problem mit Taubenbergers Argumentation ist, dass er damit suggeriert, auch das H5N1-Vogelgrippevirus k?nnte sich noch im Vogel so ver?ndern, dass es direkt auf den Menschen ?berspringen kann. Da ich nicht glaube, dass das 1918er-Virus Vogelgrippeviren besonders ?hnlich ist, glaube ich auch nicht, dass es besonders wahrscheinlich ist, dass H5N1 kurz davor ist, sich im Menschen zu etablieren.
TR: Also gibt es nach wie vor zwei gleich wahrscheinliche M?glichkeiten f?r H5N1, auf den Menschen ?berzuspringen ...
Palese: Ja. Zum einen die so genannte Antigendrift: Dabei h?uft das Virus erst im Vogel und dann im Menschen Mutationen an, die es irgendwann so ver?ndern, dass es von Mensch zu Mensch ?bertragen werden kann. Zum anderen ein Antigenshift: Dabei wird ein Mensch sowohl von einem Vogelgrippe- als auch einem Influenza-Virus infiziert, so dass sich deren Erbgut neu kombinieren kann. Diese Mischviren sind dann f?r Menschen infekti?s und Ausgangspunkt einer Pandemie.
Aber es gibt noch eine dritte M?glichkeit, die mindestens genauso wahrscheinlich ist: Dass n?mlich der n?chste pandemische Influenza-Stamm nicht H5N1 hei?t, sondern sich aus irgendeinem anderen Influenza-Stamm entwickelt, vielleicht aus einer H7- oder H2-Variante.
TR: Ist die Pandemie 1918 auch deshalb so gravierend gewesen, weil die Menschen durch den ersten Weltkrieg geschw?cht waren?
Palese: Die Menschen starben 1918 im kriegsgeschw?chten Europa genauso wie in Kansas, wo die Menschen keinen Krieg hinter sich und genug zu Essen hatten. Also ist nicht die Ern?hrungslage, sondern der Immunit?tsstatus der Bev?lkerung der wichtigste Faktor f?r die Schwere einer Pandemie. Da wir derzeit gegen Nachkommen des 1918er-H1N1-Virus impfen, ist es sehr unwahrscheinlich, dass das 1918er heute noch eine Pandemie verursachen k?nnte. Im Labor k?nnen wir jedenfalls M?use mit den verf?gbaren Impfstoffen gegen das 1918er-Virus sch?tzen. W?rde eine H2-Variante zur?ckkommen, dann w?rde sie nur Personen infizieren k?nnen, die j?nger als 36 sind. Denn H2-Viren haben 1957schon einmal eine Pandemie ausgel?st und zirkulierten bis etwa 1968 in der Bev?lkerung. Alle Menschen, die j?nger als 36 Jahre sind, sind nicht mehr mit H2-Viren konfrontiert worden, sodass sie keinen Immunschutz gegen?ber H2-Viren haben d?rften. Aber jeder, der etwa f?nf Jahre in einer Population gelebt hat, in der H2 kursierte, d?rfte immun sein. Gravierender w?ren wahrscheinlich H5- oder H7-Pandemien, da Menschen gegen diese Varianten keinen Immunschutz entwickeln konnten.
TR: D?rfen wir denn ?berhaupt noch mit einer Pandemie vom 1918er-Ausma? rechnen angesichts all der medizinischen M?glichkeiten, die es heute anders als am Ende des Ersten Weltkriegs gibt?
Palese: Es ist richtig, dass es anders als 1918 heute antivirale Wirkstoffe wie Tamiflu und auch Antibiotika gibt, die gegen sekund?re bakterielle Infektionen wirken. Au?erdem haben wir heute die Technologie, um Impfstoffe in relativ kurzer Zeit zu produzieren. Diese medizinischen Werkzeuge m?ssen aber in eine Infrastruktur eingebunden sein, um eine Katastrophe verhindern zu k?nnen. In New Orleans h?tte die Regierung die Folgen des Hurrikans verhindern k?nnen, denn die Technologie, einen Damm zu bauen, w?re dagewesen. Wenn wir jedes Jahr nicht nur ein Viertel, sondern die ganze Bev?lkerung gegen Influenza impfen w?rden, dann h?tten wir eine medizinische Infrastruktur aufgebaut, die uns auf eine Pandemie ausreichend vorbereitet. Nicht weil der Impfstoff gegen die saisonale Influenza vor einem Pandemie-Virus sch?tzen k?nnte. Das kann er nicht, weil er nur vor H1-Influenza-Varianten sch?tzt. Aber es w?rde ein Markt entstehen, der die Impfstoffhersteller in die Lage versetzt, die n?tigen Kapazit?ten aufzubauen, die f?r eine rasche Durchimpfung im Falle eine Pandemie n?tig w?re.
TR: In Deutschland wird Gefl?gel nicht gegen das H5N1-Virus geimpft. In China oder auch in Frankreich schon. Wie stehen Sie zu solchen Impfungen?
Palese: Gefl?gel kann und sollte gegen das H5N1-Influenza-Virus geimpft werden. Wir haben ein Gen f?r das H?llprotein H?magglutinin des Influenza-Virus in das Erbgut des Newcastle-Virus eingebaut, um einen Impfstoff gegen beide Erkrankungen zu haben. Gegen die Newcastle-Seuche werden H?hner schon lange routinem??ig geimpft. Dieser chim?re Impfstoff sch?tzt die Tiere nun sowohl vor Newcastle- als auch vor H5N1-Infektionen.
TR: In China hat die Impfung gegen H5N1 die Seuche offenbar nicht einged?mmt, sondern zur Selektion resistenter Keime gef?hrt.
Palese: Der Impfstoff muss in einer relativ hohen Dosis verabreicht werden, weil er aus abget?teten H5N1-Viren besteht. Wahrscheinlich wird die erforderliche Dosis oft nicht eingehalten, weil der Impfstoff verd?nnt wird. Dadurch entsteht nur noch ein partielle Immunisierung. Wenn das Huhn dann infiziert wird, dann hat das Immunsystem des Vogels zu wenig Antik?rper entwickelt, und eine gewisse Anzahl von Viren kann sich vermehren. Es ist wie mit Antibiotika, wenn man nur ein Zehntel der Dosis verabreicht, dann selektiert man resistente Bakterienst?mme. Unser Lebendimpfstoff ist schon deshalb sicherer, weil man nur ein Tausendstel der Menge verglichen mit abget?tetem Virusimpfstoff braucht. Ich bin zuversichtlich, dass die Chinesen diese Technologie in K?rze kopieren werden.
TR: Ein Argument gegen das Impfen ist auch, dass sich infizierte von geimpften H?hnern nicht unterscheiden lassen.
Palese: Das stimmt f?r den bisher verf?gbaren Impfstoff, aber unser chim?rer Impfstoff beispielsweise hat ja nur den H?magglutinin-Anteil des Influenza-Virus. Testet man die H?hner, ob sie ein anderes Influenza-Protein wie zum Beispiel die Neuraminidase tragen, dann wird man das nur bei infizierten, aber nicht den geimpften Tieren finden.
TR: Im letzten Jahr haben wir die weltweite Verbreitung der H5N1-Vogelgrippe beobachtet. K?nnen Sie sagen, was uns in diesem Jahr erwartet?
Palese: Menschliche Influenza verbreitet sich vorwiegend in den Wintermonaten. Die gleiche Saisonalit?t gilt f?r die Vogelgrippe. Also werden wir wieder einen Anstieg der F?lle in der n?rdlichen Hemisph?re sehen. Mit resistenten V?geln k?nnen wir noch nicht rechnen, weil bisher nur Bruchteile der Wildv?gel-Populationen infiziert wurden.
TR: Werden sich dieses Jahr noch mehr Menschen mit dem H5N1-Vogelgrippevirus infizieren?
Palese: Das ist schwierig vorherzusagen. Der Anstieg der F?lle in den letzten Jahren muss jedenfalls keine biologische Ursache haben, sondern d?rfte zu einem gewissen Teil der besseren Diagnose und Kommunikation geschuldet sein.
TR: Noch gibt es keine Pandemie, wir reden also ?ber eine theoretische Pandemie-Gefahr. Wird die Influenza angesichts so dringender Infektionserkrankungen wie Aids nicht ?bersch?tzt?
Palese: Wir sollten keine H5N1-Panik sch?ren, nur um etwas zu bewegen. Die regul?re Influenza ist eine hinreichend ernste Erkrankung, um sich darum zu k?mmern. J?hrlich infizieren sich etwa f?nf Millionen Menschen allein in Deutschland mit einer Influenza, und sch?tzungsweise 15.000 sterben an den Folgeerkrankungen. Und auch wenn ich die Einsch?tzung einer kurz bevorstehenden H5N1-Pandemie nicht teile, soll das nicht hei?en, dass sich Politiker zur?cklehnen k?nnten. Denn es ist sehr wahrscheinlich, dass die n?chste Pandemie kommen wird, auch wenn niemand vorhersagen kann, wann, durch welche Virusvariante sie ausgel?st wird, und ob sie st?rker oder milder als 1918 sein wird.
Grattan Woodson, MD, FACP ,(
http://www.birdflumanual.com/) 17.Dec.2006:
In my opinion, H5N1 avian influenza will achieve pandemic status soon, say within 2 years. When it does, I estimate that 40% to 50% of the world?s population will experience the flu with 1 in 10 infected dying from the disease. While these numbers are just sophisticated guesses, I have a high degree of confidence in their occurring. That said, no one has a crystal ball including me so we will not be able to know for sure until after the pandemic sweeps through the human race and we can tally up the effects.
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Thank you GS for your interest in learning more about how the coming influenza pandemic might affect humankind.
I have been working on this problem for a couple of years and over that period refined my model to take into consideration various factors that will impact survival during the pandemic. These include the clinical attack rate, treatment setting, severity of illness, and co-morbidities. The clinical attack rate is the percentage of the population that gets the flu. The treatment setting is where the sick person is treated. Severity of illness is an estimate of how ill people will become with influenza. Most will have mild cases, some will have moderate illnesses, and even fewer will become critically ill with influenza. Co-morbidities include factors like age and the health of the patient prior to becoming ill with the flu. These four elements included in the mortality model I am using have powerful and independent effects upon the case fatality rate. This term is simply the number of patients who die after contracting the flu.
The model I have developed together with its mortality predictions are described in an essay published in the Article section on the BirdFluManual website entitled Illness and Death During the Pandemic. I am unable to provide the link as this is my first post and five are required before this is permitted.
Grattan Woodson, MD, FACP
http://www.birdflumanual.com/articles/illnessAndDeath.asp
(link added by gs)
on 25.June 2007 the Doctor said:
>In developed nations is CAR 40%, CFR 8%
>In developing and third-world nations CAR 40%, CFR 12.5%.
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Grattan Woodson 26.June 2007:
> I think that the probability for pandemic within 1 year is 40%,
> 2 yr 60%, 3 yr 70% and 90% within 5 yr.
>I think it is going to much worse than 1918 because the exponential >growth of human populations, their crowding in urban areas, and the >marked increase in global economic interdependence and complexity >since that time. These first factors all increase transmission rate and >the latter will result in global economic collapse and widespread civil >disorder. It is the economic collapse and deaths and destruction for >from civil disorder that will make this pandemic so much worse. The >deaths caused by these factors (starvation, murder etc) are not possible >to predict but it could be two or three times higher than those from the >virus itself. That is why I am so worried and why I am calling the new >book, The Coming Pandemic Catastrophe.
Falkenrath,2005
Nanshan,2005
Fauci,2005
WHO,2005
Corban,2005
A flu pandemic is the most dangerous threat the United States
faces today. It's a bigger threat than terrorism. In fact, it's bigger than
anything I dealt with when I was in government.?
Richard Falkenrath, (2005?) former deputy Homeland Security adviser (2001-2004)
China experts say birdflu bigger threat than SARS (Zhong Nanshan) (Aug.2005)
[true pandemic of avian flu ] Bigger threat than most?
DR. ANTHONY FAUCI (Sept.2005): Well, HIV is a big one. That's something that even though it has a well defined, more limited way of spreading than influenza, which spreads very easily, if you look at the impact of over 20 million people having died already, 40 million people living with HIV, I would think that HIV right now is something that trumps everything.
January 2005. 9. ?Bird flu bigger threat than tsunami:. WHO?, Straits Times, 22 January 2005.
Dec 20, 2005:, Corban:
Treasury says a severe flu pandemic could cost the New Zealand economy up to $30 billion in the first year in lost output.
The H5N1 avian flu virus has killed more than 70 people in Asia since it was identified in 2003 and has sparked fears of a global flu pandemic if the virus gains the ability to pass readily between people.
In a preliminary report on the economic costs to New Zealand, Treasury says there is a low probability of a severe pandemic but there would be a very high impact if one occurs.
Jeremy Corban from Treasury says preparing for bird flu is a prudent thing to do.
Stephen Salzberg
June 2006)
my expectation value is that H5N1 will NOT turn into a
human flu pandemic. I would give it a chance of 10%,
purely subjective. Reason: it has been around since 1997
and has had many chances to mutate into a human flu, and it
hasn't done yet. Reason 2: the evolutionary pressure on
H5N1 is overwhelmingly focused on keeping it viable in birds,
not people.
However, there is a better chance - maybe 30-50% - that
eventually H5N1 and H3N2 will recombine giving a new
human flu pandemic. This might or might not be especially
deadly, hard to tell.
Other experts agree with me on this - but some bird
flu experts feel much differently. We don't have enough data.
----------------
> We wrote to Dr. Salzberg, pointing out that ?the idea that a new vaccine is necessary
> every year because of mutation is a common belief, but it is not actually true.? Dr. Salzberg
> wrote back promptly. Here?s what he said:
>> I know that the vaccine doesn?t change every year. But I was writing for a general audience,
>> and I want to encourage people to get an annual flu shot. I don?t want people to start thinking
>> they only need the shot every few years, or only when the vaccine strains change, as that
>> might have harmful public health effects.
Arpil 12, 2009: Regarding the recent mild cases in young Egyptian children
John Jabbour, who works with WHO in Cairo, told Reuters last week: "There is something strange happening in Egypt. Why in children now and not in adults? We need to see if there are sub-clinical cases in the community." He added that if the research did find such cases, they would be the first to be discovered anywhere in the world.
Professor Robert Webster:
... the WHO in Egypt was raising "a very, very important issue" which should receive "maximum attention". He added: "I hope to hell they are wrong. If this **** thing becomes less pathogenic, it will become more transmissible."
Professor John Oxford, of Queen Mary, University of London:
... any evidence that H5N1 was becoming less deadly would be serious, as the greatest cause for concern was the disease's ability to spread.
http://www.independent.co.uk/news/s...the-danger-of-pandemic-is-rising-1667526.html
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Hat tip to Pathfinder at FluTrackers
VIDEO LINK: Virologist Ab Osterhaus speaks of the mutations and vaccine.
http://www.rnw.nl/english/video/flu-...ons-new-threat
My summary:
He thinks it possible there will be a third peak that will be lower than the second one they have just experienced/still experiencing (the tail of the second wave).
The mutation is probably related to higher pathogenicity; does not seem to spread and definitely not efficiently. Probably additional mutations would be needed for that.
These mutations probably have very little influence on the efficacy and the effectiveness of the vaccine.
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https://twitter.com/mixin1771
erth' strain out there ... 