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‘Avion Flu’: Bush and the Senate mark the Year of the Rooster

Are the billions promised to global AIDS in jeopardy? A more convincing and immediate alarm, with a simple story that anyone can understand, is pushing AIDS aside in the roster of international health concerns.

Suddenly it’s Bird Flu that is the Pandemic of the 21st Century, with the avian flu virus A/H5N1 now in the headlines daily and on the front burner, politically speaking. Bird flu’s dominance of the news has happened quite fast. It’s less than two weeks (Monday Sept 26) since we had the complaint from the Rome based UN agency FAO that not enough money was being spent on bird flu. The paltry figure they had in mind was $150 million.

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The New York Times

September 26, 2005′

U.N. Warns of Lack of Bird Flu Funding

By THE ASSOCIATED PRESS

Filed at 12:36 p.m. ET

ROME (AP) Donors have pledged just a fraction of the $150 million needed to tackle the threat of bird flu and prevent a possible human pandemic, a U.N. agency said Monday.

The Rome-based Food and Agriculture Organization said that just $20 million has been pledged. The money is needed for the vaccination of poultry and the exchange and analysis of virus samples in affected countries, including Thailand, Vietnam and Indonesia, it said.

”It makes sense to stockpile antiviral drugs to protect humans against a potential avian influenza pandemic, but at the same time we have to contain the virus at source, in animals, to reduce the risk to people,” said Joseph Domenech, the agency’s chief veterinary officer.

The H5N1 strain of bird flu has swept through poultry populations in large swathes of Asia since 2003, jumping to humans and killing at least 65 people — more than 40 of them in Vietnam; and resulting in the deaths of tens of millions of birds.

Most human cases have been linked to contact with sick birds. WHO has warned that the virus could mutate into a form that spreads easily among humans; possibly triggering a global pandemic that could kill millions.

Domenech said the response to a $100 million appeal launched in May had not been sufficient, and that without further funding ”the cycle of bird flu infection that will occur in poultry this winter will not be stopped.”

The agency said another $50 million was needed to cover the costs of bird flu prevention over the next three years.

While Thailand had successfully controlled the avian flu crisis, Vietnam and Indonesia needed financial help for their vaccination programs, the agency said. It added that Vietnam alone needed $10 million to implement its program.

The agency also urged countries in the pathways of wild bird migration – including India and Bangladesh and countries in central Europe, the Middle East and Africa – to set up early warning, surveillance and rapid response programs.

It said a large part of the requested funds should be used to finance such control programs, warning that national governments would not be able to manage on their own.

* Copyright 2005 The Associated Press

and only a week ago on Oct 1 the WHO tried to reduce the alarm a notch.

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the World Health Agency Tones Down Alarm on Possible Flu Pandemic

The New York Times

October 1, 2005

World Health Agency Tones Down Alarm on Possible Flu Pandemic

The World Health Organization moved Friday to drastically revise downward what it considered alarming predictions that a possible pandemic from the avian influenza virus ravaging parts of Asia could kill as many as 150 million people.

The health organization, a United Nations agency, was deluged with inquiries after Dr. David Nabarro, who was appointed Thursday as the United Nations coordinator for avian and human influenza, cited the 150 million estimate during a news conference.

While the health organization’s flu spokesman at its Geneva headquarters did not say the estimate was wrong, he said 7.4 million deaths would be more realistic. Scientists have made predictions ranging from fewer than 2 million to 360 million. Last year the health organization’s chief for the Asia-Pacific region predicted 100 million deaths, but until now that was the highest figure publicly mentioned by one of the organization’s officials.

”We’re not going to know how lethal the next pandemic is going to be until the pandemic begins,” the Geneva spokesman, Dick Thompson, said Friday. ”You could pick almost any number” until then, he said, adding that the organization ”can’t be dragged into further scare-mongering.”

Experts agree there will be another flu pandemic – in which a new human flu strain spreads globally – but it is unknown when it might happen or how bad it might be. It is also unknown whether the flu strain circulating among Asian poultry, known as H5N1, will be the origin of the next pandemic.

But experts are tracking it just in case, and governments across the world are preparing themselves for such a possibility. Two factors will have a major influence on how many people will die from the next flu pandemic, experts say. One is the attack rate, the proportion of the population that becomes infected. The other is the death rate, the proportion of the sick who die.

Normal seasonal flu viruses have an attack rate between 5 percent and 20 percent, but a death rate of less than 1 percent. Between 250,000 and 500,000 people die from flu every year, according to the health organization.

Based on evidence from the three pandemics that occurred during the 20th century, scientists have determined that pandemic flu strains tend to infect 25 percent to 35 percent of the population.

The worst death rate was suffered in the 1918 pandemic of Spanish flu. That killed 2.6 percent of those who got sick, or about 40 million people. The two other pandemics were less severe. The 1957 one killed two million and the most recent, in 1968, killed one million.

Forecasts that change the assumed attack rate or death rate will yield different predictions. Other assumptions, like whether anti-flu drugs will work against the virus, also would change the figures. Dr. Thompson, the health organization spokesman, said it considered the most likely outcome to be a death toll of 2 million to 7.4 million.

The H5N1 strain of bird flu has swept through poultry populations in large swaths of Asia since 2003, jumping to humans and killing at least 65 people — more than 40 of them in Vietnam — and resulting in the deaths of tens of millions of birds.

Most human cases have been linked to contact with sick birds. But the health organization has warned that the virus may mutate into a form that spreads easily among humans, changing it from a bird virus to a pandemic human flu strain.

Copyright 2005 The New York Times Company | Permissions | Privacy Policy

Come on guys! Why the caution? This is a political opportunity no one here was going to miss. After a closed door briefing early last week that one Senator said “scared me to death”, the Senate kicked off US spending with a hefty $3.9 billion amendment just for starters, and President Bush is today (Fri Oct 7) conferring with the vaccine companies.

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Bush Urges Companies to Produce Bird Flu Vaccine” The New York Times

October 7, 2005

Bush Urges Companies to Produce Bird Flu Vaccine

By REUTERS

Filed at 10:21 p.m. ET

WASHINGTON (Reuters) – President George W. Bush asked vaccine makers on Friday to do their utmost to boost flu vaccine production, while officials from 80 countries and the United Nations wrapped up a meeting on ways to fight a feared influenza pandemic.

Neither session provided any immediate solutions, but U.S. officials said they served to raise the profile of the potential crisis and start setting up the networks needed to deal with outbreaks.

“I think what this is, is ratcheting this up,” said Dr. Bruce Gellin, vaccine coordinator at the U.S. Department of Heath and Human Services and coordinator of the federal influenza preparedness plan.

The H5N1 avian influenza virus has killed millions of birds across Asia and infected 116 people, killing 60 of them.

If it acquires the ability to pass easily from person to person, it could kill millions in the space of a few months, experts say. The world does not have enough vaccine to fight off annual flu, let alone a pandemic of avian flu, and part of the problem is that very few companies make the vaccine.

Antiviral drugs can reduce the severity of a flu attack, but are in short supply.

Democratic members of Congress expressed concern about this and asked Bush to detail his preparations.

“While other nations have ordered enough antiviral medication to treat between 20 and 40 percent of their populations, the federal government has only ordered enough to treat less than 2 percent of Americans,” Nevada Democratic Sen. Harry Reid and five colleagues wrote in a letter to Bush.

Last year there was a shortage of annual flu vaccine. Congress and HHS agencies have been working to find ways to lure companies back into the business of making it.

So Bush met with the chief executive officers of some of the top corporate makers of vaccines.

They included Richard Clark, president and CEO of Merck & Co. Inc.; Robert Essner, chairman, president and CEO of Wyeth; Jean-Pierre Garnier, CEO of GlaxoSmithKline; David Mott, president and CEO of MedImmune; Howard Pien, chairman, president and CEO of Chiron Corp.; and David Williams, CEO of sanofi pasteur, the vaccine unit of Sanofi-Aventis.

“We talked about what’s necessary to get to the goal of having enough vaccine in the shortest possible amount of time,” Health and Human Services Secretary Mike Leavitt, who attended the meeting, told reporters.

“I firmly believe that the efforts the United States puts into place now also will contribute to improved pandemic preparedness worldwide,” sanofi pasteur’s Williams said in a statement later.

“The best preparation for a possible influenza pandemic is to help ensure the public is aware of the current, annual threat of seasonal influenza and the need for vaccination — starting with this season — with a goal toward universal immunization before a pandemic arrives,” Williams added.

Only a few blocks away, the U.S. State Department wrapped up a meeting of diplomats and United Nations experts.

“This initiative on the part of the United States government has solidly placed the avian influenza and the very real threat of a pandemic very high on the global agenda,” said Kang Kyoung-wha, director general of the South Korean Foreign Ministry’s international organizations bureau.

Leavitt was preparing to leave on Saturday for a weeklong visit to Thailand, Vietnam, Laos and Cambodia.

“We have advanced offers to a number of governments in the region to partner with them in the development of a number of assets,” Leavitt said.

Dr. Anthony Fauci, head of the U.S. National Institute of Allergy and Infectious Diseases, said one carrot the United States and other countries could offer in exchange for cooperation would be help in developing a better public health infrastructure.

Fauci, who will accompany Leavitt, said one possible plan being worked on would be to test antiviral drugs in Vietnam, where there have been 91 human cases of H5N1 infection and 41 deaths.

to see what the needed investment has to be to protect us from a new version of the 1918 flu, which killed more people than any other plague in recorded history, if the 50 to 100 million guesstimate of historians is correct.

Bird flu 21st Century style is thought to be potentially capable of removing anywhere from 2 million to 350 million persons from the planet in short order, and even that may be an underestimate, according to our own possibly flawed logic. This flu virus has killed about half the 116 or so humans it has brought down so far, and it seems possible that no vaccine at all will be available for it after it mutates and finally spreads in humans for at least six months, during which it will have plenty of time to circle the globe and dispose of half the souls on the planet, at that 50% ratio. And this is the Year of the Rooster in the Far East, rather ominously.

One thing is sure. Vast sums will be spent to mount the crash program that leading commentators such as Laurie Garrett of the Council of Foreign Relations, and experts at the FAO, WHO, and CDC, together with front page headlines have now convinced world leaders is needed to avoid “millions upon millions” of people dying of a global flu pandemic worse than in 1918. (We here insert a picture of Laurie, who has us wondering if the Secretaryship of Health and Human Services is not in her future. We believe it is.)

The pandemic will occur just as soon as H5N1 mutates so that it can jump from human to human instead of using wild birds as a reservoir and take off platform. Hasn’t happened yet, even though this virus has been around for many years, but the general feeling is that it will sooner or later. That is what the 1918 flu virus did, according to accepted theory.

Yesterday’s Times front page story by Gina Kolata of the reconstruction of the 1918 virus

The bird flu viruses now prevalent share some of the crucial genetic changes that occurred in the 1918 flu, scientists said, but not all. The scientists suspect that with the 1918 flu, changes in just 25 to 30 out of about 4,400 amino acids in the viral proteins turned the virus into a killer.

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(Experts Unlock Clues to Spread of 1918 Flu Virus by Gina Kolata

The New York Times

October 6, 2005

Experts Unlock Clues to Spread of 1918 Flu Virus

By GINA KOLATA

The 1918 influenza virus, the cause of one of history’s most deadly epidemics, has been reconstructed and found to be a bird flu that jumped directly to humans, two teams of federal and university scientists announced yesterday.

It was the culmination of work that began a decade ago and involved fishing tiny fragments of the 1918 virus from snippets of lung tissue from two soldiers and an Alaskan woman who died in the 1918 pandemic. The soldiers’ tissue had been saved in an Army pathology warehouse, and the woman had been buried in permanently frozen ground.

“This is huge, huge, huge,” said John Oxford, a professor of virology at St. Bartholomew’s and the Royal London Hospital who was not part of the research team. “It’s a huge breakthrough to be able to put a searchlight on a virus that killed 50 million people. I can’t think of anything bigger that’s happened in virology for many years.”

The scientists painstakingly traced the genetic sequence, synthesized the virus using tools of molecular biology, and infected mice and human lung cells with it in a secure laboratory at the Centers for Disease Control and Prevention in Atlanta. The research is being published in the journals Nature and Science.

The findings, the scientists say, reveal a small number of genetic changes that may explain why this virus was so lethal. It is significantly different from flu viruses that caused the more recent pandemics of 1957 and 1968. Those viruses were not bird flu viruses but instead were human flu viruses that picked up a few genetic elements of bird flu.

The research also confirms the legitimacy of worries about the bird flu viruses, called H5N1, that are emerging in Asia. Since 1997, bird flocks in 11 countries have been decimated by flu outbreaks. So far nearly all the people infected – more than 100, including more than 60 who died – contracted the sickness directly from birds. However, there has been little transmission between people.

The 1918 virus, in contrast, was highly infectious, and in recent weeks the fear that a transformation of one of the current bird flus could make it infectious in humans has prompted politicians of both major parties to scramble to demonstrate that they are taking the threat of an avian flu outbreak seriously.

Bush administration officials have been talking about pandemic flu preparedness for years, and they say they will soon release a pandemic flu plan, in the works for more than a year. Senate Democrats say that the administration is not doing enough, and they are writing their own bills that call for more spending and coordination.

President Bush this week asked the leaders of the world’s top vaccine manufacturers – Chiron, Sanofi-Aventis, Wyeth, GlaxoSmithKline and Merck – to come to the White House on Friday to discuss preparations for pandemic flu, said people with knowledge of the meeting who insisted on anonymity because the White House has not yet announced the meeting.

The research on the 1918 virus is directly applicable to current concerns, Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, and Dr. Julie L. Gerberding, director of the Centers for Disease Control and Prevention, said in a joint statement. “The new studies could have an immediate impact by helping scientists focus on detecting changes in the evolving H5N1 virus that might make widespread transmission among humans more likely,” they said.

The bird flu viruses now prevalent share some of the crucial genetic changes that occurred in the 1918 flu, scientists said, but not all. The scientists suspect that with the 1918 flu, changes in just 25 to 30 out of about 4,400 amino acids in the viral proteins turned the virus into a killer. The new work also reveals that 1918 virus acts much differently from ordinary human flu viruses. It infects cells deep in the lungs of mice and infects lung cells, like the cells lining air sacs, that would normally be impervious to flu. And while other human flu viruses do not kill mice, this one, like today’s bird flus, does.

Other scientists said the new work was immensely important, leading the way to identifying dangerous viruses before it is too late and to find ways to disable them.

The 1918 flu, which killed as many as 50 million people worldwide, showed how terrible that disease can be. It had been “like a dark angel hovering over us,” said Dr. Oxford, the virology professor at St. Bartholomew’s. The virus spread and killed with terrifying speed, preferentially striking the young and the healthy. Alfred W. Crosby, author of “American’s Forgotten Pandemic: The Influenza of 1918,” said that it “killed more humans than any other disease in a similar duration in the history of the world.”

The research, and its publication, raised concerns about whether scientists should actually resurrect this killer that vanished from the earth nearly a century ago.

“It is something we take seriously,” said Dr. Fauci, whose institute helped pay for the work. The work was extensively reviewed, he added, and the National Science Advisory Board for Biosecurity was asked to decide whether the results should be made public. The board “voted unanimously that the benefits outweighed the risk that it would be used in a nefarious manner,” Dr. Fauci said.

Others are not convinced.

Richard H. Ebright, a molecular biologist at Rutgers, said he had serious concerns about the reconstruction of the virus. “There is a risk verging on inevitability, of accidental release of the virus; there is also a risk of deliberate release of the virus.” And the 1918 flu virus, Dr. Ebright added, “is perhaps the most effective bioweapons agent ever known.”

But Dr. D. A. Henderson, a resident scholar at the University of Pittsburgh Center for Biosecurity and a leading expert on bioterrorism, said he agreed with the decision to reconstruct the virus and publish its genetic sequence. “This work is of the greatest importance, and it is very important that it be published,” he said.

The story of the resurrection of the 1918 flu began in 1995. Until then, scientists had thought the task hopeless. Viruses had not been discovered in 1918, so no one had isolated and saved the one that caused the flu.

But Dr. Jeffery Taubenberger, chief of the molecular pathology department at the Armed Forces Institute of Pathology in Washington, had an idea for finding that ancient virus. He recalled that his institute had a warehouse of autopsy tissue, established by President Lincoln.

Dr. Taubenberger investigated and found tissue from two soldiers who died of the 1918 flu, one in Massachusetts, one on Long Island. The tissue was snips of lung soaked in formalin and encased in little blocks of wax. In that tissue was the virus, broken and degraded, but there, untouched for nearly 80 years.

Then Dr. Taubenberger received a third sample, from a woman who had died in Brevig, Alaska, when the flu swept through her village, killing 72 adults and leaving just five. The dead were buried in a mass grave in the permafrost. A retired pathologist, Johan Hultin, hearing of Dr. Taubenberger’s quest, had traveled from his home in San Francisco at his own expense. He dug up the grave with the villagers’ permission, extracted the woman’s still frozen lung tissue and sent it to Dr. Taubenberger.

Dr. Taubenberger and his colleagues spent nearly a decade carefully extracting and piecing together the viral genes, like putting together a jigsaw puzzle. Along the way, they published findings that they and others used to try to understand the 1918 flu, but until now they had published only the sequences of five of the eight genes that make up the virus. The last three, which make up half of the virus’s length, are published today in their paper in Nature.

In August, Terrence M. Tumpey of the Centers for Disease Control and his colleagues used the viral genome to reconstruct the 1918 virus, and they wondered what would happen if they infected mice and if they infected tissue from human lungs. And, they asked, would the virus remain as lethal if they switched some of its genes with genes from today’s influenza viruses?

The scientists took great precautions, Dr. Gerberding said, using special labs that were designed to protect the researchers and prevent the spread of the viruses. “We have erred on the side of caution at every step of the process,” she added.

And now, the scientists say, the work is starting to unmask that virus’s secrets.

In gene-swapping experiments, the scientists found that small substitutions weakened the reconstructed virus so that it could no longer replicate in the lungs of mice, kill animals, or attach itself to human lung cells in the lab.

The ultimate goal, Dr. Taubenberger says, is to make a checklist of changes to look for in the bird viruses. “Now you have all these viruses going around and we don’t know, is it going to adapt to humans? Is it going to cause a pandemic? We don’t understand the rules,” he said. “There is a lot of science to go.”

Gardiner Harris contributed reporting from Washington for this article.

is the big scientific development that brings home the drastic potential of A/H5N1 to turn rogue and become a human flu virus. The achievement of the scientists concerned was to piece together the 1918 flu genes from lung samples from two soldiers kept in jars and another unearthed from the burial ground of a settlement in Alaska, and it is hailed as a great achievement in virology, even if some worry that it could have very nasty consequences if it gets loose.

The data yield of the reconstruction is worrying enough. For the 1918 flu virus reborn shares all too many genes with H5N1, the current bogey, and both have the nasty ability to kill fertilized bird eggs, which most flu viruses cannot.

In sum, the spate of media coverage over the past few months has now had its effect, and all eyes in Washington are now on H5N1.

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Fear of Flu Outbreak Rattles Washington.

The New York Times

October 5, 2005

Fear of Flu Outbreak Rattles Washington

By GARDINER HARRIS

WASHINGTON, Oct. 4 – Health officials have warned for years that a virulent bird flu could kill millions of people, but few in Washington have seemed alarmed. After a closed-door briefing last week, however, fear of an outbreak swept official Washington, which was still reeling from the poor response to Hurricane Katrina.

The day after the briefing, led by Michael O. Leavitt, the secretary of Health and Human Services, and other senior government health officials, the Senate squeezed $3.9 billion for flu preparations into a Pentagon appropriations bill.

On Wednesday, Senate Democrats plan to introduce another bill calling for the creation of a flu pandemic coordinator within the White House and a federal buy-back program for unused flu vaccines, among other measures, according to a draft of the bill. Its authors include the Senate minority leader, Harry Reid of Nevada; Senator Barack Obama of Illinois; and Senator Edward M. Kennedy of Massachusetts.

Thirty-two Democratic senators sent a letter to President Bush on Tuesday expressing “grave concern that the nation is dangerously unprepared for the serious threat of avian influenza.”

Mr. Bush spent a considerable part of his news conference Tuesday talking about the risks of an outbreak and the measures the administration is considering to combat one, including whether to use the military to enforce quarantines.

“I take this issue very seriously,” he said. “The people of the country ought to rest assured that we’re doing everything we can.”

But after the administration’s widely criticized response to Hurricane Katrina, such assurances are no longer enough, several Democratic senators said.

” ‘Trust us’ is not something the administration can say after Katrina,” Senator Tom Harkin, Democrat of Iowa, said in an interview. “I don’t think Congress is in a mood to trust. We want plans. We want specific goals and procedures we’re going to take to prepare for this.”

So far, Mr. Harkin said, the administration has provided neither, despite requests from Congress.

Mr. Leavitt acknowledged in an interview that the United States was not prepared for a pandemic flu outbreak. He plans to spend next week touring Thailand, Vietnam, Laos and Cambodia, the countries most likely to be the source of an avian flu outbreak, and talking with health ministers there about a coordinated surveillance of outbreaks.

“No one in the world is ready for it,” Mr. Leavitt said. “But we’re more ready today than we were yesterday. And we’ll be more prepared tomorrow than we are today.”

Since 1997, avian flu strains seem to have infected thousands of birds in 11 countries. But so far, nearly all of the people infected with the disease – more than 100, including some 60 who died – got the sickness directly from birds. There has been very little transmission between people, a requirement for an epidemic.

An outbreak, therefore, may be years away, or may never occur. And if a strain does jump to people, such a mutation may make it far less lethal than it has been to those who have contracted it from birds.

Mr. Leavitt warned in the briefing last week that an outbreak could cause 100,000 to 2 million deaths and as many as 10 million hospitalizations in the United States, one person who was present said. Those numbers have been presented publicly many times before. But hearing them in closed session gave them urgency, some who were at the meeting said.

The briefing “scared the hell out of me,” Senator Reid said recently.

The Senate majority leader, Bill Frist of Tennessee, said he had been delivering speeches about improving the nation’s preparedness for a flu pandemic since December. But as more birds have been discovered with the virus, concerns have grown.

The poor response to Hurricane Katrina is also a factor, Mr. Frist said. “People watching on TV see that the government wasn’t there in times of need,” he said.

Irwin Redlener, director of the National Center for Disaster Preparedness at Columbia University, called the sudden interest in preparing for a flu epidemic the latest “post-Katrina effect.”

“I don’t think politically or perceptually the government feels that it could tolerate another tragically inadequate response to a major disaster,” Dr. Redlener said. He said a flu epidemic was the “next big catastrophe that we can reasonably expect, and the country is phenomenally not prepared for this.”

Mr. Leavitt said several steps must be taken to prevent a flu pandemic. First, he said, there must be an effective global surveillance program for the disease, something he will discuss in his trip to Asia next week.

Second, the United States must construct its own comprehensive disease surveillance system, he said. And third, antiviral drugs like Tamiflu, made by Roche Laboratories, and Relenza, made by GlaxoSmithKline, must be made available.

The government has purchased “millions of courses” of treatment, said Christina Pearson, a spokeswoman for the Health and Human Services Department, and it has a goal of having on hand 20 million. A course includes enough doses for a full treatment.

Finally, the government is underwriting research that it hopes will speed the creation of vaccines against the disease, Mr. Leavitt said. Flu vaccines take nearly nine months to be manufactured.

Democrats say the Bush administration has failed to spend the money needed to prepare for a flu pandemic. Though Mr. Leavitt said that preparations by state and local health officials were vital to flu planning, Mr. Harkin said that the administration had proposed cutting the financing needed for such planning.

And the Democrats said in their letter to President Bush that it was past time for the administration to finish its flu plan, which has been under review for a year.

Mr. Leavitt responded: “We need a plan. I’m resolved to make sure we have one and so is the president.”

But we already knew that change was on the cards. Our favorite not too scientific Washington commentator, Andrew Sullivan, was our weathervane in this respect. Only a couple off weeks ago he wrote that he had followed up his renewed swallowing of AIDS pills (following an downtick in his T cell count a couple of months ago) with a shot of Tamiflu, since after Katrina flooded New Orleans he decided that George W. Bush was not the man to prepare for the flu pandemic in time.

The only problem was that Andrew apparently failed to realize that Tamiflu is an antiviral directed at the flu virus after it has been in the body for a couple of days. It is not a preventive vaccine. But then, embedded as he is in the cosy confines of the Beltway the English-born political commentator seems unaware after 21 years that there is any valid questioning of the HIV paradigm, so it is probably useless to inform him of the difference between Beltway beliefs and the scientific facts in any sphere.

Actually, we sympathize with his confusion since it seems to be becoming daily harder to discern the difference between belief and facts in any of the media reports on flu or any other virus these days. The spate of reports on flu this week and last brought a new sensation almost every day, amoing them that a A New Dog Flu has Mutated from Horses….

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The New York Times

September 22, 2005

A New Deadly, Contagious Dog Flu Virus Is Detected in 7 States

By DONALD G. McNEIL Jr. and CARIN RUBENSTEIN

A new, highly contagious and sometimes deadly canine flu is spreading in kennels and at dog tracks around the country, veterinarians said yesterday.

The virus, which scientists say mutated from an influenza strain that affects horses, has killed racing greyhounds in seven states and has been found in shelters and pet shops in many places, including the New York suburbs, though the extent of its spread is unknown.

Dr. Cynda Crawford, an immunologist at the University of Florida’s College of Veterinary Medicine who is studying the virus, said that it spread most easily where dogs were housed together but that it could also be passed on the street, in dog runs or even by a human transferring it from one dog to another. Kennel workers have carried the virus home with them, she said.

How many dogs die from the virus is unclear, but scientists said the fatality rate is more than 1 percent and could be as high as 10 percent among puppies and older dogs.

Dr. Crawford first began investigating greyhound deaths in January 2004 at a racetrack in Jacksonville, Fla., where 8 of the 24 greyhounds who contracted the virus died.

“This is a newly emerging pathogen,” she said, “and we have very little information to make predictions about it. But I think the fatality rate is between 1 and 10 percent.”

She added that because dogs had no natural immunity to the virus, virtually every animal exposed would be infected. About 80 percent of dogs that are infected with the virus will develop symptoms, Dr. Crawford said. She added that the symptoms were often mistaken for “kennel cough,” a common canine illness that is caused by the bordetella bronchiseptica bacteria.

Both diseases can cause coughing and gagging for up to three weeks, but dogs with canine flu may spike fevers as high as 106 degrees and have runny noses. A few will develop pneumonia, and some of those cases will be fatal. Antibiotics and fluid cut the pneumonia fatality rate, Dr. Crawford said.

The virus is an H3N8 flu closely related to an equine flu strain. It is not related to typical human flus or to the H5N1 avian flu that has killed about 100 people in Asia.

Experts said there were no known cases of the canine flu infecting humans. “The risk of that is low, but we are keeping an eye on it,” said Dr. Ruben Donis, chief of molecular genetics for the influenza branch of the Centers for Disease Control and Prevention, which is tracking the illness.

But with the approach of the human flu season and fears about bird flu in Asia, there is much confusion among some dog owners who have heard about the disease.

Dr. Crawford said she was fielding calls from kennels and veterinarians across the country worried that they were having outbreaks.

“The hysteria out there is unbelievable, and the misinformation is incredible,” said Dr. Ann E. Hohenhaus, chief of medicine at the Animal Medical Center in New York.

Dr. Hohenhaus said she had heard of an alert from a Virginia dog club reporting rumors that 10,000 show dogs had died.

“We don’t believe that’s true,” she said, adding that no dogs in her Manhattan hospital even had coughs.

Dr. Donis of the disease control centers said that there was currently no vaccine for the canine flu. But he said one would be relatively easy to develop. The canine flu is less lethal than parvovirus, which typically kills puppies but can be prevented by routine vaccination.

Laboratory tests, Dr. Donis said, have shown that the new flu is susceptible to the two most common antiviral drugs, amantidine and Tamiflu, but those drugs are not licensed for use in dogs.

The flu has killed greyhounds at tracks in Florida, Massachusetts, Arizona, West Virginia, Wisconsin, Texas and Iowa. Tracks and kennels have been forced to shut down for weeks for disinfection.

In Chestnut Ridge, north of New York City, about 88 dogs became sick by early September, and 15 percent of those required hospitalization, said Debra Bennetts, a spokeswoman for Best Friends Pet Care, a chain of boarding kennels. The kennel was vacated for decontamination by Sept. 17.

About 17 of the infected dogs were treated at the Oradell Animal Hospital in Paramus, N.J., where one died and two more were still hospitalized, a staff veterinarian said.

The Best Friends chain owns 41 other kennels in 18 states, and no others have had an outbreak, Dr. Larry J. Nieman, the company’s veterinarian, said.

In late July, at Gracelane Kennels in Ossining, N.Y., about 35 dogs showed symptoms, said the owner, Bob Gatti, and he closed the kennel for three weeks to disinfect.

About 25 of the dogs were treated by an Ossining veterinarian, Glenn M. Zeitz, who said two of them had died.

“The dogs came in very sick, with high fevers and very high white blood cell counts,” Dr. Zeitz said, making him suspicious that they had something worse than kennel cough.

A spokesman for the New York City Health Department said that there were “a few confirmed cases” in New York but that the city was not yet tracking the disease.

Veterinarians voluntarily sent samples to the Animal Health Diagnostic Center at the Cornell School of Veterinary Medicine, which was the only laboratory doing blood tests.

The New York Times

September 25, 2005

Dogs Cough, and Owners Worry

By JANE GORDON

AS leading veterinarian virologists announced that a new canine influenza virus was spreading across the country, Connecticut veterinarians, and kennel and dog owners, said last week that they have been worrying for a while about an unusually persistent and contagious cough in dogs this year, particularly in puppies. The illness, they said, mimics the symptoms of kennel cough, a common, highly contagious canine illness. But this year’s cough spreads more rapidly and makes the dogs sicker.

The question is: Is this the canine influenza virus that was isolated by a University of Florida scientist and that has sickened and even killed dogs in several states, including in the New York suburbs?

As of last week, Connecticut officials said they were not sure what the disease is, or even to what extent it is affecting dogs in the state.

But Dr. Edward J. Dubovi, head virologist in the diagnostic laboratory at the Cornell University College of Veterinary Medicine in Ithaca, N.Y., said the illness seemed to be the new virus, canine influenza, which first surfaced at greyhound racing parks in Florida in 2004, and was identified by Dr. Cynda Crawford at the University of Florida in Gainesville.

There are no known cases of the virus’s infecting humans. It is not related to typical human flus or to the avian flu that has killed about 100 people in Asia.

The virus, Dr. Dubovi said, had not been seen in dogs before and mutated from an influenza strain that affects horses.

“We’re talking about a different virus that had not been identified prior to a little over a year ago,” Dr. Dubovi said. “The virus that is currently sitting in dogs has its origin probably in the influenza virus of horses. We have potentially a new infectious process that will have to be dealt with in the dog population.”

Dr. Dubovi is one of more than a dozen authors of an article on the virus for the journal Science, which has not yet been published.

The Connecticut state veterinarian, Dr. Mary Jane Lis, said the state did not have a test for the virus.

Local veterinarians who suspect the disease is present in their patients should get in touch with Dr. Dubovi at Cornell, who at the moment is conducting the only tests for the virus. “It’s a relatively new problem, but there are protocols in place on how to make a diagnosis,” Dr. Lis said. “We’ve already disseminated information to the Connecticut Veterinary Association and to our own diagnostic lab.”

“We’re kind of on the fringes here, waiting for information,” Dr. Lis added.

Connecticut’s Department of Agriculture, which regulates animal health, does not require reporting of any unusual illnesses in animals, Dr. Lis said.

Meanwhile, dog owners like Laura Bosco of Glastonbury have been trying to figure out why their pets are sick.

Mrs. Bosco left her healthy Pembroke corgi, Casey, at a kennel for a few days in August while she traveled to Block Island with her family. When she returned to pick up the dog, kennel employees told her Casey had contracted kennel cough. Mrs. Bosco was puzzled, because Casey had been immunized against that common disease.

“They told me the kennel cough was going around, and that every kennel had it,” Mrs. Bosco said. “He would cough so much he spit up quite a bit of phlegm. This went on for days and wasn’t going away.”

Kennel owners and veterinarians who have recently seen sick animals have been as puzzled as Mrs. Bosco.

“As a whole, the industry needs to educate the public about what’s going on,” said Christian Suter, owner of Candlewick Kennels in Glastonbury, where Mrs. Bosco boarded Casey. “And certainly the public thinks it’s only kennels, it’s only grooming shops. But you’re seeing this in any community environment of dogs, from kennel facilities, doggie day cares.”

“There needs to be a study done on it,” Mr. Suter added. “That’s what everybody wants.”

When canine influenza virus was found in Florida greyhound racing parks, it infected 24 greyhounds and killed 8. According to an article in the fall 2004 issue of the Kansas Veterinary Quarterly, the disease spread quickly through greyhounds in Florida, and traveled to greyhound parks in Rhode Island, Kansas and Texas. The article was written by Dr. William Fortney of Kansas State University, who participated in diagnostic testing for the virus. He wrote that

in one case, two dogs that were fine at bedtime were dead the next morning, lying in a pool of blood. The cause was severe hemorrhagic pneumonia.

There is no treatment for canine influenza virus; Dr. Dubovi recommended that veterinarians prescribe antibiotics to treat possible secondary infections like bacterial pneumonia, which can be fatal.

Dr. Patricia Hart, a veterinarian at County Veterinary Hospital in Fairfield, said she has been seeing a more tenacious form of kennel cough in puppies, which persists for days and does not respond easily to antibiotics.

“Kennel cough is typically a glorified cold, like putting 10 kids in a classroom and closing all the windows,” Dr. Hart said. “You need to have the right conditions to start passing it around. But I’ve been seeing a type of kennel cough not associated with kennels and not associated with any big holidays.”

Kennels are generally busier during holidays when pet owners are away.

Dr. Hart said puppies she had treated with the illness had responded to the antibiotic Zithromax.

“But they need a long course of it,” she said.

Dr. Stacy Robertson, a veterinarian in the South Wilton Veterinary Group in Wilton, said she had not seen more kennel cough lately.

“But the kennel cough I’ve seen seems to be a bit more potent, and mostly in younger dogs,” Dr. Robertson said. “Over the past year I have seen some more puppies than usual that need to have stronger medications or longer treatment than your typical average kennel cough.”

She said that when a dog has not responded to antibiotics, she has checked it into the hospital for nebulization treatments, in which the dog is placed in a chamber. Medicine is administered through a mist into the chamber.

Candlewick Kennels has posted signs alerting dog owners to what employees believed to be a mutant strain of kennel cough and warning them that the vaccine for common kennel cough would not offer protection.

Mr. Suter, the kennel’s owner, said he had posted the signs because many clients believed that once their dog received the vaccine, known as the bordetella vaccine, they would be protected against any strain.

“Vets say that the bordetella will guard against some strains, but not all strains,” Mr. Suter said.

Mrs. Bosco’s veterinarian, Dr. Lenka Babuska of the Manchester Veterinary Clinic, prescribed Cipro, a strong antibiotic, to fight the illness in Casey, Mrs. Bosco’s dog. She said she realized early on that Casey did not have a standard case of kennel cough, nor did the four to five dogs a day she was seeing this summer with the same illness.

“It wasn’t the typical cough that the laymen’s term has been coined for,” Dr. Babuska said. “My feeling is that one dog that has been exposed to a dog with this bronchitis may not be terribly symptomatic, but it can certainly infect another dog that will be symptomatic. I prescribed Cipro because it is strong, and I was finding that nothing else was working for these respiratory issues.”

Casey has recovered. But Mrs. Bosco said she was not sure what to do about boarding him again in any kennel if the ailment persists.

“Here the dog was, expectorating on my carpet, and the vaccine wasn’t helping,” she said. “I have to figure out what I’m going to do in the future. Is this a problem that is going to continue? Are they devising a new vaccine? The kennels are requiring the vaccine to board the dog, and now the vaccine is doing nothing.”

or today’s news about Three Ducks Dead in Romania….or earlier that SARS virus hides in Chinese horeshoe bats

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The New York Times

September 30, 2005

2 Teams Identify Chinese Bat As SARS Virus Hiding Place

By LAWRENCE K. ALTMAN

The SARS virus, which has killed 774 people worldwide, has long been known to come from an animal. Now two scientific teams have independently identified the Chinese horseshoe bat as that animal and as a hiding place for the virus in nature.

The bats apparently are healthy carriers of SARS, which caused severe economic losses, particularly in Asia, as it spread to Canada and other countries. In Asia, many people eat bats or use bat feces in traditional medicine for asthma, kidney ailments and general malaise.

The Chinese horseshoe bat does not exist in the United States.

The finding is important in preventing outbreaks of SARS and similar viruses carried by bats because it provides an opportunity for scientists to break the transmission chain.

One team from China, Australia and the United States reported its findings yesterday in the online version of Science. The other team, from the University of Hong Kong, reported its findings on Tuesday in The Proceedings of the National Academy of Sciences.

”It’s pretty pleasant to see two teams that did not know each other reach similar findings,” Dr. Lin-Fa Wang, a virologist at the Australian Animal Health Laboratory, said in a telephone interview. After collecting hundreds of bats from the wild and from Chinese markets, each team reported identifying different viruses from the coronavirus family that are very closely related to the SARS virus.

SARS, or sudden acute respiratory syndrome, first appeared in China in 2002. It spread widely in early 2003 to infect at least 8,098 people in 26 countries, according to the World Health Organization. The disease died out later in 2003, and no cases have been reported since.

SARS now appears to join a number of other infectious agents that bats can transmit. Over the last decade, bats have been found as the source of two newly discovered human infections caused by the Nipah and Hendra viruses that can produce encephalitis and respiratory disease. In the SARS outbreak, attention focused on the role of Himalayan palm civets in transmitting it after scientists identified the virus in this species and in a raccoon dog sold in markets in Guangdong. But W.H.O. officials and scientists elsewhere cautioned that these species were most likely only intermediaries in the transmission, largely because no widespread infection could be found in wild or farmed civets. So, the teams assembled a variety of specialists, including veterinarians, zoologists, virologists and ecologists.

Dr. Wang said his group focused on bats largely because of the team members’ earlier pioneering work on the Hendra and Nipah viruses. One member, Dr. Jonathan H. Epstein, a veterinary epidemiologist at the Consortium for Conservation Medicine in Manhattan, led the scientists in gathering bats from the wild and market places.

After obtaining fecal and blood samples, the scientists released the bats into the wild or returned them to the markets. The specimens were tested for a variety of viruses that infect animals.

Laboratory analysis of the coronaviruses’ makeup provided strong genetic evidence of the close relationship between those found in the bats and the SARS virus.

Although it is logical to assume that the bat viruses infected the animals in the live markets to cause the outbreak, the studies were not planned to prove that point.

”The genetic relationships do not tell you anything mechanistically about if or how the virus moved from the bats to civets and from the civets to the humans,” said Dr. Donald S. Burke, a virologist and professor at Johns Hopkins. ”It’s not a perfect story yet. But until I see otherwise, the working assumption will be that this is the reservoir species.”

Dr. Wang said that ”there is no rule” to establish proof that a certain species is the reservoir, or hiding place, of a virus, but that scientists make the judgment based on criteria like how widely the infectious agent is distributed in a species, the absence of symptoms among the animals and finding high levels of antibody but low amounts of virus in the animal.

The Chinese horseshoe bat fits those criteria and the civets do not, Dr. Wang said. The bat feeds on moths and other insects and generally does not bite animals. It was highly unlikely that insects transmitted the SARS viruses to bats, because the viruses do not grow in insect cells in the laboratory, Dr. Wang said.

Most civets that are sold in China as a delicacy are farmed, Dr. Wang said, and the government should ensure civet farms are distant from bat colonies, monitor farmed civets for SARS-like viruses and allow just noninfected animals to go to market.

Copyright 2005 The New York Times Company | Permissions | Privacy Policy

It all reminds us that viruses were not even known about in 1918, when the Great Flu killed three to six times more people than the Great War. Now it seems that virus hunters are finding them in every nook and cranny of biological existence.

That’s why we are grateful for the reports in sturdy mainstream publications and network reports that have come out about Bird Flu in past weeks. We feel we can trust them to get the whole story straight, if only because they sing so well in unison. First, we had the October 7 issue of Foreign Affairs with two highly informed lead pieces, one by Laurie Garrett which went along with her informed Q/A on the subject (see the bottom of this post for these and other briefings) warning of the new terror on the international horizon, and then the current National Geographic cover story, illustrated with a patient buried under bandages and tubes (actually a fortunate Vietnamese who survived).

Confirming all the main points with eye witness video PBS rebroadcast its bird flu one hour doc on Sunday night, following the Tuesday evening premiere in the series Wide Angle. This week after the Senate move we had Nightline, with Koppel explaining that our “leaders are trying to push us” without causing a panic. “We must act on this yesterday!” Senator Harry Reid told him, “We must nip this in the bud!”

This followed two mentions in public by Bush of a new “avion flu” which could become the “world pandemic of the 21st Century”. The promised starter allocation of $3.9 billion came in Senate Majority Leader Dr Bill Frist of Tennessee’s amendment to a defense bill, backed by the Minority leader Harry Reid and almost every other Senator. “All I know is this stuff scared the hell out of me” said Harry Reid on Nightline, and in front of every other mike.

The Wide Angle film on PBS was certainly scary stuff. Like the National Geographic it featured the same bandaged and tubed Vietnamese man prone and still or sitting up and coughing very badly indeed in the Hospital for Tropical Diseases in Hanoi, although later it proved that he actually survived to stagger out of the hospital. “You are very lucky young man”, said his nurse, “Have you been praying at the temple?”

His family as we recall included a sister who died of it and his father who tests positive for H5N1 but who has never come down with any symptom at all. The vector was duck blood soup, which seems an ill advised dish these days. Evidently the virus is still very bad at jumping the species barrier to humans, however, and some of us are immune, as is the case with every infectious agent, however lethal.

But, as Dr Anthony Fauci explains at the end of the film, if it does jump the species barrier with a new mutation that enables it to leap from human to human, we are likely to be especially vulnerable this time around because we have had no chance to build up any prior immunity, as we have done with ordinary flu.

Can any such outbreak be stopped? According to Wide Angle, it might be difficult. In the previous scare the Vietnamese claim they killed off a million and a half chickens and other poultry and thus stopped the spread of the flu among birds in its tracks. However, Wide Angle found some cock fighting men who said they loved their birds so much (one massaged his bird’s livid red throat and stomach as he talked) they hid them during the crackdown and continued with their matches. A Vietnamese family with a variety of animals and birds explained that they needed every one to maintain their rickety family income. “They blame the birds because they cannot talk,” said a woman in the thriving food market, “I don’t believe they are the source of the flu.”

All in all it was suggested that containing the bird flu if it does begin to flourish again might be more difficult this time. Of course if it gets into the 13 billion chickens in China all bets are off. Thus it likely will have another big chance to mutate into a dangerous killer resident in humans. If it proves impossible to contain then we will have a world pandemic in a few weeks where “millions and millions” of people will be ill and many will die, according to the UNAIDS man in Vietnam, and Dr Anthony Fauci of NIAID, who was interviewed by Bill Moyers in an afterword.

This frightful scenario was repeated in all the reports including Nightline, and under questioning the key major vulnerability finally emerged:

We may never have a timely vaccine

It is not just that we don’t have enough vaccine on hand to deal with an outbreak in the US (we have 2 million of possibly the wrong kind instead of 20 million doses of the right kind). It is that there isn’t much hope that there ever will be enough vaccine, because the precise variant of the flu virus that will attack won’t be clear till it does arrive, and then to make enough vaccine will take six months.

This is the awkward truth which both the trusting Bill Moyers and the skeptical Ted Koppel zeroed in on after they have listened to the basic story. How to make a vaccine in time to do any good if we don’t know which flu mutant version will arrive here?

“That’s a very good question,” says the Health and Human Services Secretary, Michael O. Leavitt, to Ted Koppel on Nightline. “We have to develop the technology.”

“Yes,” pursues Koppel. “But even with the best technology, how are you going to do it in time?”

Leavitt: “Every vaccine starts with a sample. Once it starts to mutate we’ll have the capacity to make a vaccine.”

Koppel: “So when will you have enough if it takes months to do it?”

Leavitt: “The timetable is as soon as we have a sample we will have a vaccine and go into production. It will take six months to have enough for the entire American population, after we have the vaccine.”

Koppel: “So we are really in no position to deal with it at all?”

Leavitt: “We need to have a general capacity to deliver vaccines for pandemic influenza, whatever variety it is!”

Koppel: “Thank you for your frankness even if the news is bad.”

Bad? Dire. Think about this. Vast amounts will be spent on a “general capacity” to make a flu vaccine which even after it is built will take six months to deliver enough vaccine to an American population which will have been exposed to the Superflu for six months.

Are we wrong to imagine that the vaccine delivery will by that time be “superflu-ous”?

Bill Moyers, who ends the Wide Angle film by interviewing Dr. Anthony Fauci, the head of NIAID who is famous in AIDS circles for warning journalists not to take up the topic of the validity of HIV=AIDS theory, asks the smooth tongued bureaucrat the same question but with an extra sting in its tail.

When told it will take vast resources to prepare vaccines and months to do even the minimum, Moyers asks him, ‘If the virus mutates, how will we know that the vaccine will even work when we finally get it?

“Good question”, says Dr Fauci, momentarily derailed. But after spinning the point for a second without actually answering it he returns to his happy vision of the ideal outcome: that a gigantic effort might head off a pandemic “so well that it never happens”.

The conclusion seems to be that IF the virus repeats the supposed trick of the 1918 virus and turns into one that is spread human to human, which it hasn’t done in the years it has been around, the world will come to a screeching halt in most ways. “The world shuts down!” as Koppel cried. “It will be as if the whole world gets hit by a blizzard!”

With no snow ploughs available for six months.

“Yes,” agreed Michael Osterholm, the author of the second Foreign Affairs piece on Bird Flu, who was the last to be interviewed on the Nightline halfhour. “The $4 billion is like filling Lake Superior with a garden hose! It will be months or years before we see any outcome from investment.”

Meanwhile Senator Ted Stevens, the Alaskan Republican shepherding the defense bill through the Senate, rather surprisingly said (according to the Times) he would try to block the provision, even though the money was less than one per cent of the $445 billion allocated to defense by the bill.

Huh? What does he know that we don’t? Surely he won’t argue that the expenditure will be for nought, since it will come up with a vaccine after the virus has wreaked havoc and destroyed up to half the population of the United States, let alone the rest of the world in an era where travelers cross the globe in a day and roads reach into the remotest regions.

Perhaps Senator Stevens doesn’t believe H5N1 will turn into a human flu virus after all.

If so, we like his skeptical optimism, even though we plan further research to see how it might be justified. For one thing, in history most great alarms turn out to be false, if only because they are headed off.

In this case, however, it is hard to see how the Great Bird Flu can be headed off. It either will come or it won’t. There is not much we can do, it seems clear, except prepare for the catastrophe of the millenium if it comes. We predict that AIDS funding is in for a permanent overshadowing.

For a really good rundown on the horrid possibilities, until the huge report which the HHS has been reparing for months finally makes its appearance, read these:

Q&A with Laurie Garrett May 25, 2005

But an H5N1 pandemic with virulence above five percent would be the most catastrophic outbreak in human history

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Laurie Garrett is Senior Fellow for Global Health at the Council on Foreign Relations and is the author of The Coming Plague and Betrayal of Trust.

Q: What would precipitate a deadly flu pandemic and how likely is it to occur in the foreseeable future?

The H5N1 avian flu strain, so deadly to fowl and domesticated poultry, needs to mutate further, acquiring traits that make it a contagious human-to-human strain. We have no idea what exact genetic changes this would require, how difficult it is for the virus to make those changes and whether or not the virus would significantly sacrifice its virulence level in the process. The bottom line for policymakers: Science does not know the answer.

Q: Are there measures that if taken could prevent the deadly flu from spreading globally?

At the recent World Health Assembly in Geneva, this was the number one question on the minds of delegates from 192 nations, especially the U.S. delegates. The World Health Assembly, which governs the World Health Organization (WHO), passed two resolutions to create a worldwide infrastructure of surveillance labs and monitoring and response processes. But funding is nonexistent at this time, and the WHO has only a small permanent rapid response team (although it expands during times of crisis).

Q: If an outbreak does occur, what is the state of preparedness planning between nations, across regions, among departments and ministries of individual governments and throughout the non profit sectors?

Planning is abysmally inadequate, given the likely severity of a pandemic caused by a human-to-human transfer of a virus as virulent as the current H5N1 strain.

Q: Without adequate preparations, what would be the likely toll of such a pandemic globally and in the United States?

The answer depends on the virulence level of the pandemic virus. The 1918 strain, which killed 50 to 100 million people, only killed about two to three percent of the people it infected. The H5N1 strain now in circulation kills 100 percent of the birds it infects and has killed more than 50 percent of the people known to be infected so far. If it manages to mutate into a human-to-human form, and retains even half its current virulence, the death toll would be in the hundreds of millions. The WHO issued a report a few months ago putting the estimate at eight million and has since retracted that estimate, preferring far higher reckonings.

Q: How serious might be the economic, social and political impacts?

One Oxford University computer model, assuming a virus with low virulence, put global losses at two to three trillion dollars. The Oxford team concluded that it is impossible to guess the catastrophic economic toll of a high virulence strain.

Q: In addition to the avian flu that has emerged in Asia, are there deadly diseases already qualifying as global health catastrophes for humans?

Drug-resistant tuberculosis, malaria, and HIV/AIDS are health crises that are not currently being adequately addressed.

Q: How would the effects of an outbreak compare to past pandemics?

It would depend on the virulence of the flu strain. But an H5N1 pandemic with virulence above five percent would be the most catastrophic outbreak in human history, as no living human being has developed immunity to H5 influenzas, as far as we know.

Copyright 2002–2005 by the Council on Foreign R

Laurie Garrett advises the nation

Where will they put all the patients? The bodies? How will they feed house-bound millions? How can they keep the economies and machineries of their jurisdictions running while a deadly pandemic holds them in its grip for more than a year?

(show)

October 7, 2005

latimes.com : Opinion : Commentary

A $3.9-billion first strike

# The Senate has earmarked funds in response to fears of a killer-flu pandemic. Now Washington just has to get its spending priorities straight.

By Laurie Garrett, LAURIE GARRETT is a Pulitzer Prize-winning writer and senior fellow for global health at the Council on Foreign Relations.

PANDEMIC INFLUENZA anxieties have reached fever pitch in Washington amid growing concern that the H5N1 avian flu virus now circulating in Jakarta, Indonesia, may mutate into a human-to-human transmitter that could claim hundreds of millions of lives. After years of relegating flu preparedness to one small office inside the Department of Health and Human Services, the government, from the president on down, seems suddenly in a mad flurry to do something — anything — to prepare for disaster. Perhaps the hurricanes have taught them a lesson.

“The people of the country ought to rest assured that we’re doing everything we can…. And we are,” President Bush said in a news conference Tuesday. But racing around like a chicken with its head cut off (pun intended) won’t put the United States any closer to safety than we were before flu anxiety hit.

For example, on Tuesday, the president suggested we might need to quarantine sections of the nation, adding, “and who best to be able to effect a quarantine? One option is the use of a military that’s able to plan and move.”

But hold on, Mr. President: Even your own top flu experts at the Department of Health and Human Services and the Centers for Disease Control will tell you that human influenzas are so contagious there is little, if any, evidence that quarantine helps. Further, your top military leaders have told me that there is no Defense Department plan in place for the protection of active-duty personnel, much less one aimed at putting the armed forces in charge of domestic epidemic management.

Last week, the also agitated Senate, by unanimous consent, tagged a $3.9-billion “pandemic influenza preparedness” rider onto the 2006 Defense Department appropriation bill. If the House agrees to it, this would, among other things, guarantee a supply of the potentially lifesaving drug Tamiflu for about half of all Americans.

That’s a start, but the White House has threatened to veto the entire bill, saying it considers the flu problem a domestic issue that shouldn’t be addressed in defense appropriation legislation. The Bush administration should back down from its veto threat — especially if the president envisions a military epidemic response.

SCIENTISTS have been nervously following developments in Asia with the H5N1 avian influenza virus since it first emerged in 1996, and anxiety is rising. About three weeks ago, H5N1 broke out in Jakarta, population 9 million. About 60 suspected human cases of H5N1 have been placed under treatment there, and seven people have died. Statistics gathered since 2003 indicate that 55% of those who contract H5N1 will die of it. (In chickens, felines, ferrets and mice, H5N1 kills 100% of the time.)

For the moment, the pattern of H5N1 infection does not show that avian flu is easily transmitted from human to human. But viruses evolve quickly. The number of suspected cases in Jakarta increases the concern that H5N1 is spreading and mutating. It doesn’t help that scientists studying the virus that caused the 1918 flu pandemic see key similarities between it and H5N1.

Last Friday, the Assn. of Southeast Asian Nations approved a three-year plan that requires its 10 member nations to wage an “all-out coordinated regional effort” to quash the virus in bird populations. Similarly, the Asian-Pacific Economic Cooperation forum is drawing up guidelines for controlling the virus in animals and, should it become a human epidemic, for limiting its effect on populations and economies. Last month, China’s president, Hu Jintao, promised an open, scientific exchange with the United States in hopes of stemming a flu tsunami.

But the United States must do more. Sen. Ted Stevens (R-Alaska) suggested last week that “we ought to wait” because avian flu “has not yet become a threat to human beings.” But waiting until confirmed human-to-human transmission is underway means dooming millions to die. A human-to-human avian flu eruption would spread around our globalized world in a matter of weeks, perhaps days. The lessons of the hurricane season are clear: It costs less in lives and dollars to invest in adequate defenses than to react once disaster strikes.

Does the Senate rider do enough? The overall appropriation, $3.9 billion, may be about right, but the devil is in the details. The Senate plan sets aside 80% of that money primarily for buying Tamiflu. The other 20% would be used for global flu surveillance, bolstering local preparedness and improving flu vaccine production. The ratio isn’t correct.

Tamiflu can suppress H5N1 at the beginning of infection, but it isn’t a cure. It must be taken at the right time or it’s ineffective. It also has not been approved for use in children. And in some adults, it may only partly suppress the virus, leaving them ambulatory carriers of infection. On top of that, the latest scientific studies indicate that some H5N1 viruses may already be resistant to the drug.

That means that instead of spending most of the appropriation on Tamiflu, we should demand that the pharmaceutical industry rev up flu vaccine production and then use some of the $3.9 billion to pull genuine innovations out of the lab and into quick mass production. Further, a hefty percentage of that money should be spent on helping Los Angeles and other cities and states prepare: Where will they put all the patients? The bodies? How will they feed house-bound millions? How can they keep the economies and machineries of their jurisdictions running while a deadly pandemic holds them in its grip for more than a year?

Still, the Senate plan is a step in responding to an urgent need. The House should fine-tune it, and the president should sign it into law. As Sen. Tom Harkin (D-Iowa) said Thursday: “It’s the midnight hour. We have to get moving … now, not next year, not after some study group in the White House bangs this thing around for another three months.” He’s absolutely right.

Council Foreign Relations Panel on Global Pandemics

If you were going to extrapolate 1918 to the United States today in terms of mortality, and with the world population change, today you would expect to see about 1.7 million deaths. And that is unfathomable when you think on a worldwide basis, that’s 360 million deaths. And I think that when you think about HIV/AIDS having killed about 28 million people from the beginning of the pandemic in the early 1980s to now, it gives you a relative perspective, particularly when you think about how these are going to be very healthy people.

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The Threat of Global Pandemics

Authors: Michael Osterholm

Rita Colwell

Laurie Garrett

Anthony S. Fauci

June 16, 2005

Speaker: Anthony S. Fauci, director, National Institute for Allergy and Infectious Diseases, National Institutes of Health

Speaker: Michael Osterholm, director, Center for Infectious Disease Research and Policy, University of Minnesota; associate director, National Center for Food Protection, Department of Homeland Security; professor, University of Minnesota School of Public Health

Speaker: Laurie Garrett, senior fellow for global health, Council on Foreign Relations

Speaker: Rita Colwell, chair, Royal Institution World Science Assembly’s Pandemic Preparedness Project

Presider: . James F. Hoge Jr, Peter G. Peterson chair, editor, Foreign Affairs

Introduction: Nancy E. Roman, vice president and director, Washington Program, Council on Foreign Relations

Council on Foreign Relations

Washington, DC

June 16, 2005

NANCY ROMAN: I will leave the introductions, of course, to Jim Hoge. But I do want to say what a treat it is to have him here. Many of you know him. He is the editor of Foreign Affairs. His impressive journalism career is detailed in the bio that you have, but for the last 12 years we’ve been fortunate to have him running the magazine, which is, one, making money, two, really impressive. We now have 140,000 readers of any given issue, and it is really first-rate. And it’s a treat to have him here, because he’s very much a New York kind of guy.

JAMES HOGE: Thank you, Nancy, very much— although I did spend about eight years here once. I loved it.

Why are we here today? Let me set this in a little bit of context before we get to our panelists, but I’ll keep it brief. If we take the outside concentric circle, history tells us that we are doomed for a major pandemic. There were three in the last century. Time is up, so to speak. A closer concentric circle is that there is one influenza or avian flu that is out there now and operating that presents a particular prospective danger. And you all have been reading about it. Lots of people are now covering this story about the avian flu in Southeast Asia, which is known as H5N1. It is particularly lethal for animals, and unless it was to mutate into a milder form, it would be terribly lethal to human beings, on the scale of the influenza of 1918. And of course, given the much larger population today, and the mobility of populations, the impact of that would be enormous. We’ll get to that in a moment.

But still, why are we here, if everybody else is covering it? It was our feeling at Foreign Affairs, at Nature magazine, and at the Royal Institution World Science Assembly [RiSci] that a catalytic push was needed in addition to coverage that might help inform the public to a problem out there that needs to be addressed. A catalytic push was needed to the agents of change, so to speak, whether they be international organizations, national, or to borrow a phrase from homeland defense, the first-line responders in communities around the world. So we have done a special section in Foreign Affairs. Nature has done special coverage in its May issue, and more follow-up to come. And the two of us were brought together, so to speak, by the Royal Institution. And they are going to follow up as well, and we’ll hear about that before we’re finished.

Now with that as prologue, let’s get to today’s discussion. And we have up here Anthony Fauci, who is director of the National Institute of Allergy and Infectious Diseases at the National Institute of Health. And on my immediate left is Laurie Garrett, who is the senior fellow for global health, Council on Foreign Relations. And next to her is Michael Osterholm, who is director of the Center for Infectious Disease Research and Policy, University of Minnesota; also, associate director, National Center for Food Protection and Defense, Department of Homeland Defense; also a professor at the University of Minnesota School of Public Health. He brings a lot of credentials.

We’re going to discuss it up here for about 20-25 minutes, and then I’m going to ask Rita [Colwell] to explain the ongoing role that RiSci is playing, and then we’ll go to you for questions. So let me just start with— as I say, there’s been a lot of coverage, but what is— Laurie, what is the danger? This is a highly lethal flu virus for animals. Why should we as human beings be so concerned at this time?

LAURIE GARRETT: Well, the major thing to remember is that influenza is an animal virus, a bird virus. So we always see it in birds, and we always need to be watching what is going on with the flu virus in any given season, how it’s mutating, how it’s changing, in the bird population, particularly in aquatic migratory birds in the Asia flyway, a flyway that extends from southern Indonesia all the way up to southern Siberia.

We always see flu emerge from that setting, and we always have to be nervous and anxious about what sorts of strains may be emerging, what may be coming. What we’re very nervous about this year is that particular strain that seems to be emerging as this H5N1, which is 100 percent lethal to chickens, and appears now in a fashion that may be unprecedented. We don’t really know ancient history, but it’s certainly unprecedented in the timeframe in which people have been observing it. It’s also lethal to the usual host species, meaning the very migratory birds that carry it, and to a whole range of ducks and geese and so on. So this is really very, very troubling, and very concerning.

Now why this year or next year, why this particular timeframe in history, should be of special concern, beyond the nature of this H5N1 is that we have— as you said, we are overdue. We also have a whole set of circumstances changing in that ecology, that ecological setting.

First of all, we have far more domestic birds. We have a huge amount of poultry production going on, as the GDPs [gross domestic product] of China in particular and many of its neighbor countries rise. So as Asians become wealthier, they’re able to eat more chicken. And as a result, we have statistical odds that you’re going to have a greater likelihood of transmission from the migratory birds to the chickens, to the humans.

The second problem is that the flyway itself has become severely polluted, severely damaged, so that the migratory animals are forced to land on farms, land near industrial areas, land therefore in greater proximity to our species and to species very close to us, so the odds of any given flu jumping species closer and closer to our level in the pecking order, to use a bad pun, are increasing steadily.

HOGE: Michael, it’s primarily an animal community now. Why are we concerned that it may be mutating, if that’s the proper way to look at it? And if it does, give us sort of an overview of what the consequences will be, how it rolls out.

MICHAEL OSTERHOLM: Well, first of all, thank you for the opportunity to be here. I think that probably if I had to summarize my 30-year career in public health dating back to antibiotic resistance to HIV/AIDS, et cetera, and put it altogether, none of it equals, combined, the potential impact that this will have on society.

First of all, just to follow up, as you laid out, Laurie and Jim, the terms of your question, make no mistake about it, of all the infectious diseases ever in humankind, influenza is the lion king. And we forget that, and that’s been one of the important concerns that in modern medical science today we somehow think that we can either forget about the past, or that we’ve taken care of that past, and we haven’t.

We really have no armamentarium today that is any different on a whole than what we had 100 years ago, at least in terms of what’s available to the world’s population. We have vaccines, we have some antivirals, but they will be in such insufficient quantities as to be what we like to say, “Filling Lake Superior with a garden hose,” in overall impact.

The question you’re asking is, remember that pandemics have been happening dating back to antiquity. This virus emerges out of birds, it goes through genetic changes which then allows it to infect humans. And it takes that right lock-and-key mutation to occur. Typically in the past what’s happened is, the bird virus and a human virus will get together in the same cell. This particular virus is a very promiscuous, very indiscrete, and a very careless virus that will allow it to genetically combine with other genetic material from other influenza viruses. When a human strain and a bird strain get together, they make a third strain, which has many times the principles and properties that are bad for humans, but now also can be transmitted between humans.

That has gone back to antiquity. In 1918, we all know about that particular pandemic. If you look today at the best data we have, based on recent historical review of country-by-country mortality, it’s clear that that virus killed between 50 to 100 million people in 1918 and ‘19, in a world population that was only 1.8 billion in size. We’ve had several subsequent pandemics of much lesser impact. But if you go back in history, 1830 to 1832, the mortality in the world was just as bad as it was in 1918. So what we found is that some pandemics are worse than others, and it depends on the virus that infects the human population.

The difference with this situation is, unlike 1957 and ‘68 where, yes, we had thousands and thousands of deaths, even in a place like the United States, this virus has the characteristics of killing like 1918 did, or 1830, where it actually turns your immune system on its head, and it causes that part to be the thing that kills you.

In 1830— or excuse me, in 1918, the vast majority of deaths were healthy people between 20 and 40 years of age whose own immune system killed them. And it wasn’t the very young and the very old. Today we don’t have much better tools to handle that situation than we did in 1918. As I noted in my article, in this country today we have 105,000 mechanical ventilators. On any one given day, 70-80,000 are in use, just with routine medical care, and during just a mild flu season we get right up to the 105,000, and we’re moving ventilators around like we do donated organs, to make sure that they’re there. We have no capacity. So what we’re worried about is that this virus is due to spin out again of this bird population, as Laurie pointed out. This time, if it is the H5, it has all the bad characteristics of causing this kind of severe problem.

If you were going to extrapolate 1918 to the United States today in terms of mortality, and with the world population change, today you would expect to see about 1.7 million deaths. And that is unfathomable when you think on a worldwide basis, that’s 360 million deaths. And I think that when you think about HIV/AIDS having killed about 28 million people from the beginning of the pandemic in the early 1980s to now, it gives you a relative perspective, particularly when you think about how these are going to be very healthy people. And we have every reason to believe that the H5 situation in Southeast Asia very much could be just that kind of situation.

HOGE: One follow-up question, quickly. There have been in the neighborhood of about 60 human deaths because of this so far.

OSTERHOLM: Right.

HOGE: Describe them, because that’s hardly a pandemic. So what has not yet happened, and what is about to happen?

OSTERHOLM: First of all, the virus to date has made its way in isolated situations from birds to humans, where basically— and I, too, don’t mean to make a pun; this is actually a real term in public-health epidemiology— they have been what we call “dead end” hosts, meaning that the virus ends there because they’re not able to continue to transmit the virus. Not enough genetic changes have occurred. These deaths largely have been, as I said, in previously healthy people, in that age group that we talked about of the 1918 kind of situation. And they died deaths very similar to that of 1918.

Even though these patients have been in Southeast Asia, and you think of a very different healthcare delivery system, let me remind you that there are some outstanding healthcare delivery systems in those areas, and many of these patients received what we would consider in this country high-level tertiary care, and died anyway. And again, the— all the data we have from the virus, from the host, autopsy, and so forth, supports this 1918-like picture.

If I could just add one piece to that, quickly, it used to be— I mentioned— we thought of virus re-assorting, the fact that you had to get these two promiscuous viruses together to recombine. One of the things we’re very worried about in today’s situation versus 1918 is that, in fact, we have so many new hosts available, that virus can transmit between those billions and billions of chickens in one year more so today than it used to be able to do in a whole century.

So each time that that virus moves from one infected bird to another— or to a non-infected bird, that’s one more chance for a mutation, that’s one more chance for slow gradual changes. And what we have seen since the 1997 introduction of this virus into Hong Kong is a very rapid change in this virus. Today, the H5N1 in Southeast Asia is not the same one that was in Hong Kong, and everything about it has mutated towards getting close to this human-transmitted virus that may never need a re-assortment. It may get there on its own, because we’ve given it so many ample opportunities at the crap table to basically just throw it and come up with the right set of mutations. And that’s where it’s moving, and that’s why we’re so concerned.

GARRETT: Can I just make a real quick point of clarification, so everybody— we’re all on the same table. We first observed— we, the world community— first observed this virus and recognized that something new was happening in 1997 when a little boy became ill with what was determined to be a super-virulent chicken flu in Hong Kong.

So when we talk about an arc, we’re talking about a time period that starts in 1997, roughly. Where did that virus come from? Best evidence is it came from the province immediately to the north of Hong Kong known as Guangdong Province, China, which seems to be a real cauldron for the emergence of flu viruses, and frankly, was also the cauldron for the emergence of SARS [Severe Acute Respiratory Syndrome].

And the other thing is, a lot of the data points you will hear, and when you— any of the journalists in the audience that may be thinking of writing stories, it may get confusing. You may hear somebody say, “There were 100 cases,” or, “There were 50 cases,” or what have you. It depends on whether the observer is taking their demarcation point from 2003 when this virus made another evolutionary shift and emerged in Vietnam, or are they taking it from 1997, when it first emerged in Hong Kong. Just wanted to make that clarification.

HOGE: Thank you. In a moment, we’re going to talk about the state of preparations and planning, and what has been done and what needs to be done. But before we get there, Tony, I want to address what idealistically would be the best answer, which is, to contain this at its source at the time it is beginning to occur, rather than once it’s going around the globe as a pandemic. What is the likelihood, what are the problems of trying to deal with this particular flu, or any other one, I suppose, but this one at its source, which is primarily in Southeast Asia?

ANTHONY FAUCI: That really is one of the real major problems, is that if you look at what has evolved over the past few years, given the relationship between economies of the countries involved and the relationship between flocks of chickens, the cross-contamination with migratory fowl, and the dependence of individual countries on these chicken flocks, it would have to be almost an economic revolution in the countries to be able to address it in a way that would essentially put a major block in the way of the ultimate progression.

I think the things that people don’t understand, and we were just discussing this outside, we may well— in fact, it is highly likely— that we’ll get away this year without there being a pandemic flu. But then what people will say is, “Well, OK, we’ve dodged that bullet. Let’s move on to the next problem, whatever the next problem is, and likely not influenza.” But the ingredients that have gone into the situation where we are right now, where we have over 100 documented infections, 54-plus deaths, is not going to go away, because the chickens are still infected, the customs and practices of the interaction between fowl, pigs, and humans in these Asian countries is not changing. So that the ingredients that gave us the issue that we have now are going to reappear next year. It may still be H5N1 or it may be H9N2 or it may be something else.

So unless we, as a global effort, get the countries involved to take a look at the conditions in those countries, and how we can alleviate them without destroying the economy of those countries, this problem is not going to go away. So that’s the point source. And then there is a number of other layers of prevention that we— I’m sure we’ll get to talk about.

HOGE: I want to take you back to the source. You described quite ominously what the problem is, which is the nature of farming there, the number of animals, and so on. But, practically, is there anything we can do about that at this stage, since we know that that is at the core of the problem? Are there steps that can be taken? Are there funds that can be invested, and if so, what should they be invested in?

FAUCI: Well, yes, but it has to be not just funds from the Western world to the Asian countries. It has to be a partnership among the countries. And there are enlightened people and organizations and nations there, so it isn’t as if it’s them against us.

But we really need to continue to get the global public spotlight on that, so that transparency is absolutely essential. We cannot have, for example, what we had in the early months of the SARS epidemic in China, and only when it got to Hong Kong was there a degree of transparency.

We can’t have cases in Vietnam or even in China, be they human cases— or even in China, be they human cases or bird cases, without there being a total transparency of what’s going on, transparency not only in the local and then, ultimately, global public health area, but also exchange of isolates. For example, if there is H5N1 now that is percolating in China, we need to know how that relates molecularly to what we know is now in Vietnam, because if it’s drifting a bit to the point where it’s different enough from the H5N1 that’s in Vietnam, those of us like our organization and others that are developing a vaccine, that are looking for resistance or not to Tamiflu and other antivirals, we need to know that. So there needs to be transparency and cooperation, and maybe even economic help. I’m sure that’s part of the equation.

OSTERHOLM: Jim, if I could just add a piece to that. Because I think the question you’re asking is, what can we do right now? And the bottom line message is, almost nothing. Understand that there are 12 billion to 13 billion chickens in China. A chicken basically has a life of about six months before they’re harvested. So even though we talk about having killed off 300 million chickens in trying to reduce it, we turn over billions of chickens a year in China just for food supply. Each one of those that are born and hatched are brand new incubators for the virus, too, so we keep re-supplying this susceptible population, we keep allowing this.

The only thing that will work is one day to have an effective vaccine that is cost effective and effective scientifically. Now first of all, finding something cost effective, it would have to cost pennies at the most in American dollars to be able to be used over there, otherwise it won’t be cost effective and won’t be used.

Second of all, we’re nowhere close to an effective vaccine for birds that will interrupt this wild bird/domestic bird-to-human potential. So what we have to understand is that we’ve got ourselves in this fix. We’ve known for decades that this was going to be a potential. And we didn’t do the research. We didn’t invest in this area. Think about even a human vaccine. Today we’re using a human vaccine with one slight change to it, and an important change, but it’s basically the same basic vaccine we used in the 1950s, 1960s, a vaccine that was common when we used a slide rule as the state of the art for mathematical calculations, and today we use the computer.

Where has the comparable increase in technical ability been? And so, until we make that jump in technical ability for animals or for humans, we are stuck with this immediate situation without an apparent real, just, “Come in, we’ll solve it,” kind of situation.

HOGE: I just want to summarize a point here, because I think it’s important. But I wanted to jump from the moment to, OK, a pandemic starts, what is the state of our preparations and so on? But I think this point is so important I just want to underscore it with a quick summary, and that is the timeline question. As Michael said, if a pandemic involving this particular virus was to start this summer or fall, we are totally unprepared and there is very little we can do about it. If it starts two years from now and we do the right things now, it’ll be bad, but it’ll be— we can at least contain it at some point. If we start preparing now and it doesn’t happen until five years from now, we may be in reasonably good shape. Now, why even think about five years? Because as Tony pointed out, and I’ve read in all the literature, H5N1 and variants thereof are not this season’s dilemma. It will be with us for many years. Now let’s go to the broader questions of preparation in there. Laurie, maybe we can deal with the issue of, why pharmaceuticals have not been doing more than they’ve done? But why don’t you pick up where you wanted to start?

GARRETT: Well, I wanted to just say, I think that the foreign-policy picture here, we could lose a lot of what’s going on if we don’t pay attention to a few key details. First is that, just to underscore something on the scientific level, and that is that this constellation of hemagglutinin type-five and neuroaminidase type one, which is why we say H5N1 flu, these are markers on the flu virus, this particular constellation as far as we know has never ever circulated in the human population before. So there are no naturally immune humans walking around. None of you are immune to this virus. That is a marked difference from anything we’ve dealt with historically, because in the past, there’s always been a reservoir of immune human beings to whatever was circulating around, at least in the past that we know.

UNKNOWN: Not 1918.

GARRETT: Well, why do you say that?

UNKNOWN: Because it was the first explosion of H1N1 in 1918.

GARRETT: But I thought that in the 1880s there had been a similar outbreak among the elderly population.

UNKNOWN: But it’s unlikely it was H1N1, that’s the point. H1N1 was the first— it’s the same thing, you’re experiencing something that just as you said, nobody has experienced.

GARRETT: So you don’t have an immune system that is going to say, “Ah, I recognize this one.” And that is one of the reasons, by the way, that the immune response is so severe. Because if you have a very, very healthy, strong immune system, you’re a young adult, you’re taking good care of yourself, and you have a strong immune system, your immune system will see this extremely foreign thing and actually overreact. You’ll actually have an astonishing response to it, which can lead to this thing called ARDS [acute respiratory distress syndrome], a syndrome in the lungs that is overwhelming.

And it is why for many, many years, skeptics argued— and I know Michael and Tony and I were all in these meetings— in the early days of people warning that flu might be a problem, skeptics said, “Ah, 1918 they didn’t have antibiotics, and that’s why so many people died. But now we have antibiotics, and it won’t be a problem.” Wrong, antibiotics probably would not have made a big difference in 1918, because those young adults that were dying, it was their immune system going bananas, having seen something that their body had never seen before. So I just want to make that side point.

Going into the foreign-policy things, I think there are a number of things that we can look at that are short term, long term, and longer term, foreign-policy interventions that we could be thinking about right now. The ecology is changing rapidly in the fly zone that we’re working about, in that ecological setting in Asia. It’s not just, as Michael points out, this astounding increase in chicken production and the turnover, but it’s how chickens are being raised. It’s the nature of how people are coexisting with their poultry and other farm animals.

It used to be that the paradigm we worried about was the small farmer who lives on the edge of a rice paddy and has a couple of ducks, a pig, and maybe a couple of chickens, and the flying aquatic bird would land in such a setting. Increasingly, of course, we’re seeing poultry operations that rival Purdue in Arkansas, massive-scale poultry operations in Thailand in particular, and southern China, and parts of Singapore, Hong Kong, and Taiwan. And the question is whether those people running those operations have any concept of appropriate hygienic conditions or any attempts to try and create appropriate settings for growing massive amounts of poultry.

These are the sorts of things that one would like to see our USDA [U.S. Department of Agriculture] and counterpart agencies from other advanced industrialized societies, working closely through the Food and Agriculture Organization and OIE [World Organization for Animal Health] to try and facilitate improvements in the nature of how that poultry is being raised. That’s the kinds of interventions that could be going on right now, but they need a lot of support, a great deal of financial support and political support to be executed properly.

And I think the other thing is that the huge ecological difference is that, in Asia, people prefer to buy a live chicken, take it home and slaughter it. We buy chicken meat already chopped up in the market. The difference is huge in terms of human exposure. And any of you who have traveled in Asia have seen the old ladies that think that the right way to tell if a chicken is perky and young is to pick it up and sniff the rear end and check it out— a lot of exposure going on there.

In incredibly densely populated settings like Hong Kong, one would like to see centralized slaughtering going on. One would like to see a discouraging of the live market sales and the stacks and stacks and stacks of chickens in cages right in densely populated walkways. And these are things that the international community in a collegial atmosphere, in a non-judgmental, non-punitive atmosphere could, over time, be encouraging key Asian nations to be thinking about and addressing.

These are cultural issues, though, that are very, very deep, and they’re not going to change just because a lot of Americans are suddenly very nervous. They’re going to change in a concerted process. It’s going to have to engage APEC [Asia-Pacific Economic Cooperation] and other major international institutions in Asia, and there is going to have to be a sense that we’re all in this together. And on the transparency question, that is something that is changing. And China experienced great shame in having been caught in a lie— in a massive lie that killed people outside of its own borders.

HOGE: You’re talking about SARS?

GARRETT: I’m talking about SARS. And we are witnessing a real shift in transparency in China about disease, a shift that I believe is headed in a good direction.

But there has to be some payback for engaging appropriately, for being transparent, for slaughtering chickens, and so on. If you’re looking at an agrarian society like Vietnam, like Cambodia, like Laos, if each one of those individual farmers who may have a chicken flock with bird flu is compelled to or ordered to destroy all those chickens and there is no reimbursement, there is no payback of any kind, all you’re going to see is a steady increase in resentment against those outside powers that be, whoever they may be out there, that— us, America, somebody— angry at them and worried about flu.

There have to be mechanisms in place that do not penalize nations for their openness, and do not penalize at the local level those farmers who willingly are slaughtering infected animals.

HOGE: OK, before we go to the audience, I want to call on Rita Colwell, who is the chairman of the Royal Institution World Science Assembly’s Pandemic Preparedness Project. There are several aspects of this subject we can get into during the Q&A period that we haven’t had time to touch on. One is the wider economic and social concerns that one would have, and the other would be, what are some of the very specific obstacles to getting better preparation? And, what are some of the centers that could be offered up?

Now RiSci, who brought us all together, has these kinds of concerns very much in mind. And Rita, you might explain where we go from here.

RITA COLWELL: Thank you very much, Jim. The RiSci is a 200-year-old institution that is based in Britain but has offices in New York and London. It’s really focused on the highest levels of global leadership, mainly to bridge the gap between policy and science.

Now back in 2004, there was a concern amongst those of us involved with RiSci that this pandemic was going to happen. I was asked to chair. Why did I choose to chair? Well, I worked with cholera my whole career, and there the epidemics, if I may, are puny compared to the description that I’m hearing here today. Having worked in epidemics where we may see 100,000 people in a country like Bangladesh, here we’re talking about millions of people globally. So it became very obvious that we needed to bring the top scientists and politicians and industry leaders together.

Being a private institution, that was possible. So we’ve assembled a steering committee with officials from the WHO [World Health Organization], the U.N., the European Commission, the Chinese, Canadian, South African health ministries, executives from pharmaceutical and biotech corporations, and very importantly, the editor of Foreign Affairs and the editor of Nature, as well as the senior scientists who are expert in influenza, SARS, and HIV viruses. Now we have the issue of Foreign Affairs which has appeared, and to which reference has been made. And the issue that appeared recently by Nature, focused on influenza. Now where do we go from here? The desired outcome really for us is to be able to align the plans of all the countries for the pandemic.

At the moment, the coordination seems to be rudimentary at best. And we would also like to do the cost-benefit analyses that would perhaps be more persuasive to the policy-makers to invest in the preparedness measures that we have been discussing. And then reference materials being made available, and then possibly to force the increased production of Tamiflu— and maybe Tony and Michael and Laurie might want to address that as well— but to build capacity regionally around the world to address this pandemic.

I would point that, as Tony has mentioned, that perhaps we may not have the pandemic this year. It might be next year. But in any case, for any pandemic, we should have a global capacity. So this is an opportunity to do that.

Now the next steps: On July 6th, we’ll have a videoconferencing between Washington, New York, and London, and with Asian current leaders as well, involved as a kind of virtual workshop to address the— to operationalize the actions that we can take to address this pandemic. Now there are websites for all three partners— the Foreign Affairs, Nature and RiSci, which are available and cross-linked, which is very important. I think this is the first time that policy-makers and scientists have been brought together in such a forceful way. And I would just finally just mention that also in the audience are [RiSci President] Dan Sharp, [RiSci representative] Nelson Gonzalez, and [head of the nonprofit consultancy firm, the Ulanov Partnership] Nicholas Ulanov, if you want to speak to them after the meeting.

But this is an opportunity, I think— unprecedented— to work with global leaders and with powerful opinion-makers to address a problem that I think is incredibly difficult and important. Thank you.

HOGE: Thank you, Rita. Raise your hand if you have a question, identify yourself, and wait for the mike. Yes, sir, we’ll start back— yes, ma’am, excuse me.

QUESTIONER: I’m Anne Solomon from the Center for Strategic and International Studies [CSIS]. I’m interested in the question of the role of the private sector and the involvement of the private sector in this problem, in terms of product development, manufacture, and also stockpiling, and the issues in terms of getting the private sector involved not only in this problem, but also in bioterrorism, the development of bioterrorism countermeasures. I’d like to have the panel members make any comments on this, and especially the question of whether or not the government should take over some of the responsibilities for the manufacture of biologics, for which we have a dearth of manufacturing capability globally, and certainly in this country.

HOGE: OK, a big subject, and I think you’re all probably going to want to— let’s start with Tony.

FAUCI: You put up a very good point, the analogy between the incentivization of industry and partnering with industry in the arena of biodefense countermeasures is strikingly analogous to the problem we face with vaccines in general, and much, much more emphatically on influenza vaccines, because of the risks involved on the part of industry, because of the tenuousness of demand and the market, and the fact that industry and the ones that want to get involved could do much better from a profit margin to look at something else other than a countermeasure for a disease that may or may not happen.

So I think that that’s the core of the entire issue. The government cannot do it alone. The government is not going to be a vaccine-manufacturing corporation or a drug-manufacturing corporation. It must, by definition, partner with industry, but industry will not partner unless there are some incentives.

Let’s just take influenza in general, with a subset of a potential for pandemic flu as a specific. We have a problem every year with influenza vaccines, and I think unless we solve that yearly problem, we’re going to be still behind the eight-ball when we need to ratchet up for a pandemic problem. For example, if you look at the number of people that we would ultimately want to get vaccinated on seasonal or what we call inter-pandemic flu, it’s a crazy game that goes on each year. How many vaccine doses are going to be made? How many are going to be used? Will the company know? What happens when they make too much and they don’t sell 10 [million] or 20 million?

They play that minuet every single year. We’ve got to eliminate that. We’ve got to ultimately get a solid market, not of 60 [million], 70 [million], 80 [million], but 180 [million] and maybe 200 million people who would get vaccinated in this country each year, so that the market for influenza vaccine is solid on a yearly basis. Then you have the capacity, at least in this country, to be able to make enough vaccine to really provide protection. And I emphasize this country, because as Laurie and Michael pointed out, if you look at the global capacity and the global need, it’s a drop in the bucket.

But if you just want to address it in this country, we’ve got to push the relationship between industry and the government to its max on a yearly basis, and I think we’ll be able to better tackle pandemic flu if and when it occurs— and get rid of the “if” because it is going to occur.

GARRETT: Three key things: No. 1, even if we could ratchet up our vaccine-production capacity, identify the antigen in time, and make enough so that we actually could vaccinate the American people, we would face the foreign-policy outcome in a truly virulent pandemic of, after the pandemic had passed, the rest of the world saying, “You know, we don’t really love you. You didn’t share vaccine with us. Our people died in huge numbers while yours survived.” We have desperate, unbelievably enormous foreign-policy issues to consider.

The second is that, increasingly when we look around the world right now, we can see that a lot of the industrial sector, the major globalized corporations, are already making plans of their own for pandemic flu. Especially in key industries that were hard-hit by SARS— the hotel industries, the airline industries, those businesses that have highly globalized and dispersed operations, particularly in Asia. There is a little concern on my part that, in a way, we’re creating a kind of privatized infrastructure for response that is not directly linked in any way to WHO or to any government institutions of any kind, and that we’re already seeing a lot of concern from the corporate sector about where do we call, what’s the phone number that says, “Here’s how your company should respond, and now you should be alerted, or you shouldn’t be.” We’re also seeing that a lot of companies are beginning to purchase their own stockpiles for their own employees of Tamiflu. And that leads to the third issue, which is Tamiflu itself.

Tamiflu is a drug which, if taken appropriately, in the first roughly 36 hours of infection, can greatly alter the course of the disease and increase your chance of survival. We don’t know how well it’ll work against H5N1 or its permutation, when whatever the big megillah is, actually comes into the human population on a large scale. But in general, it’s about 84 percent effective if taken properly under the right circumstances. So obviously, if you thought pandemic flu was coming, and you’re a major multinational investment bank with offices all over Asia, you might be right now trying to buy up a lot of Tamiflu and stockpile in key locations for your employees.

But there is a problem. Tamiflu is only made by one company. It’s a patented product. There are significant production problems for that company in terms of its ability to ratchet up on a massive scale production. That leads to an issue that was brought up at the World Health Assembly in May in Geneva. This is the governing body of WHO. It meets once a year in Geneva. And they had passed an massive resolution on pandemic influenza at the meeting. But what I heard in the days and days of debate there in Geneva was all the developing countries and the middle income countries saying, “Yeah, hello, what about us? Anybody buying Tamiflu for us? All your multinational corporations, all your rich countries, are going to buy up all the Tamiflu, and what happens to us?” “And can we not,” said South Africa, “do compulsory licensing, and mandate that Roche yield their patent, and our local generic manufacturers be allowed to try to have their hand at making Tamiflu?” This could turn into a big, bloody mess.

HOGE: Michael.

OSTERHOLM: Well, let me take a step back first, because I think your question on the private sector has to be expanded, in a sense. And frankly, I think pandemic influenza is— to use a very overused term— the absolute perfect storm for our world economy. We live in a just-in-time global economy today, where in this country we depend on the rest of the world for many of the goods and services that we use everyday. Many of them are life-saving services.

So it’s not just the fact that we have to worry about this vaccine capacity, which on a worldwide basis today all the pipes, all the building, all the blocks, could only put out about a billion single doses of vaccine a year, if we stretched it to its max. And even then, if you take two doses or more before you’re vaccinated, that’s 500 million people that would get— of the immunizations— six to 12 months after the pandemic begins, because it takes six months to make the vaccine. That is a drop in the bucket, if 14 percent of the world’s population would have access to vaccine, and that’s only basically made in 12 different countries in the world. I don’t see any increase in capacity there right now, short of a major three, five, to seven year effort. It would take that long.

Tamiflu is the same thing. Tamiflu has been, I think, an unfortunate part of this discussion, because it has been so misunderstood. It may work. We don’t know against the cytokine storm phenomena, the thing where the virus elicits an immune response. It works against garden-variety flu. We hope it will, we think it will, but right now the company makes about 100 million treatment doses a year. They have a plant in Switzerland with a precursor chemical that is critical to this coming from China, that if we shut down world travel and trade, which I think many of us believe we will, and watch the whole global economy sink, all these things, all bets are off.

When you think about today, we actually have many drugs in this country that come from a foreign country. Even though we have this debate about importing, because this was a vaccine from England, for flu, is not going to show up in the way we would like it again this year. If you look today, we have a just-in-time economy in the pharmaceutical industry. We actually have pediatric cancer drugs right now that are in such short supply that patients are actually being given only partial treatments because there is not enough of that drug right now.

If you look on the websites for the American College of Healthcare Pharmacists today, there are eight antibiotics in this country that are in major shortage status because of a single-plant, just-in-time delivery problem. You put flu on top of this, you shut down international travel and trade, and many of the things that we take for granted, light bulbs, everything that you think about, your food supply, will end.

Today, in this country, when you even think about something as simple as, how are we going to take care of the dead? In 1969 in the last pandemic, the average time from the time that a casket was constructed until it was in the ground was almost six months. Today it’s two-and-a-half weeks. Today we have no excess capacity. We [inaudible] caskets overnight. Well, then you move to crematoriums. We don’t have crematorium space, because again, everything is just-in-time delivery. We have food supplies today, where we have two to three days’ supply in our warehouses; that’s it. Even a bad blizzard day causes us to have real problems on a regional basis.

So one of the things I think that’s critical is to take your question one step further, the private sector has to be involved in this in a lot of ways. Because the collateral damage that will occur with the pandemic, and I do have— I have no doubts we will shut down international trade and travel. Just as we saw with SARS regionally, and I talk about that in the article that I wrote, what will happen, overnight we will shut down all these other things.

We won’t have many of the life-saving drugs. We won’t have the antibiotics, we won’t have the food supply, we won’t have the parts of the water pumps that runs our city water supply. Those are all overnight FedEx kind of pieces today, in this just-in-time economy, that won’t exist. So I think the private sector has a much, much larger role to play than even just the discussion of drugs.

Let me just conclude with one last thing: If we protect ourselves in this country, and if some miracle comes about where we could have a vaccine quickly that could protect 300 million people, we would still experience tremendous collateral damage with a lot of people dying. Because those products that we assume that will be there everyday for many of our life-saving kinds of things, many of the chronic disease drugs et cetera, won’t be there. They will stop, because the rest of the world’s economy will tank. And no one has ever figured out how to [inaudible] a just-in-time global economy when there is no electricity for the pump. And so I think this is going to be a critical piece of this discussion.

GARRETT: Let me just— I want to make a point off that, because I think what Michael’s saying is incredibly important. And it almost goes beyond the sort of imagination capacity of all of us here in this room.

Let’s just step back for a second and imagine that in 1918, the influenza that spread had a less than 3 percent mortality rate in human beings. So— and it killed probably up to about 100 million people in the world. This H5N1 that we’re looking at in the people who have acquired it so far, it’s been a 55 percent mortality rate. So we are way out of the ballpark here on mortality.

Let us assume that in order for it to be made— whatever that little genetic change is that it needs to make to become a highly human-to-human transmissible virus, and we don’t know what that change is, but let’s assume that that forces the virus to lose some of its virulence and come down, oh, say only 10 percent from 55. That still is fantastically more virulent than what we saw in 1918.

What would a 10 percent virulence influenza mean to Washington, DC? First of all, think about how you get flu. Most people think, incorrectly, that you get flu because somebody coughed on you. That sort of comes down to our sort of social judgment ways that we deal with disease. But actually, the flu virus is a very, very hardy environmental virus. It loves door knobs. It loves the poles in the Metro. It loves every entrance, every common surface that we touch. And the virus is persistent on those surfaces for hours, even days, depending on the environmental conditions.

So all of Washington, DC, is full of commonly touched surfaces, and all of a sudden, you would see this city utterly paralyzed. Government would stop. You could not imagine, anyway, that people would feel safe commuting in and out of the District, going to government offices, getting on the Metro, all the things that are of the essence of how you keep this place moving around. If you added to it the notion that young people would somehow be particularly vulnerable because they would have these stronger immune systems that would result in this ARDS cytokine storm, this incredibe intensity in response, think about how much this city rests on vast pools of interns that are the essence of how we run this government, right?

UNKNOWN: Right. [Inaudible] feels good. You [inaudible] this point.

GARRETT: All right. All I’m saying is that if you amplify your imagination of what this would mean to Washington, to all the most important hubs of the global economy, you easily can see the impact this would have on the global economy.

HOGE: OK. Given the topic, I don’t think it’s surprising that we’re going to run out of time before I can get to all of you, and I apologize for that. But, in the interest of getting in as much as possible, I’m going to take three questions at a time and rely on the brilliant memories of our panelists. We’re going to start in the back on the right.

QUESTIONER: My name is Steve Hofman. I’m not an expert in this, and after hearing all of this, I think I’m going to get in my car and go move to Montana or something like that.

GARRETT: It won’t help.

QUESTIONER: That’s what my imagination is [inaudible]. But the one thing I do think I know about is how we as a government and other governments respond to these kinds of things. And what they are really not very good at is being proactive. So let’s assume for a second that everything you’ve just said here has absolutely no affect in the short run, including, say, getting 180 million Americans to get proactively vaccinated, which you can produce 180 million vaccine doses, but to get people vaccinated proactively on the idea. Anyway, tell us what are the firewalls, assuming that we will not proactively be effective as a nation in the United States and globally?

HOGE: What exactly do you mean by firewalls?

QUESTIONER: What can we do if we don’t have—

HOGE: What can we do under that set of circumstances? [Inaudible] All right. So if we haven’t prepared adequately, what still can we do? Terry.

QUESTIONER: Terry Schaffer from CSIS. The previous discussion of the private sector leaves me wondering, don’t we have to reevaluate also the role of government? The U.S. has a particularly small model of what the role of government should be. Is that still appropriate and should one also be thinking in larger terms about reevaluating what international organizations, like the WHO and perhaps others, ought to be doing?

HOGE: I have a question right here. Did you have a question? Yes, right here. Second row.

GARRETT: All the way up front, speaking of the young people of Washington.

QUESTIONER: Without whom, we wouldn’t even have mikes in a meeting. Peter Zimmerman, King’s College, London. I’m a physicist and some of this went by me, leaving me a little puzzled and wanting to ask you a less foreign policy, and more technical questions so that I would understand when I read— Laurie, what you write when I read things in the papers, what I should really gather out of it. You answered very quickly my first question, which was what exactly does H5N1 mean. But Tony mentioned something about, well maybe next year it will be H9, this or that. How many of these markers in each series, and perhaps how many series of markers are there? And how precisely does saying H5N1 pin down the organism itself? It clearly doesn’t get all the way down to the DNA level for the whole structure.

GARRETT: It does.

FAUCI: It does.

GARRETT: It’s RNA, but, yes, it goes down to the nucleic-acid level.

QUESTIONER: But not for the totality, only for a couple of markers.

GARRETT: No, no—

FAUCI: Yes, he’s right, if the hemagglutinin and the neuraminidase are the two major markers for influenza. There are a bunch of other genes. They generally are constant and don’t change as much as the hemagglutinin. The hemagglutinin is the protein on the surface that would designate the difference between what we’re experiencing now in our own country, the H3N2, compared to an H5N1. So both the hemagglutinin and the neuraminidase are different. And the answer to your question, there’s about 16 to 18 variations of it. The humans generally experience H3s, H2s, and H1s. When you get to the fives, sixes, sevens, eights, nines, those are generally more animal, predominately bird flus.

HOGE: OK. We’ve got two other questions. One on government role and the other one, the firewall. Let’s—

OSTERHOLM: Well, I think, to start out with the first question back there, let me just say in my most scientific Iowa farm boy way, describing it to you, I don’t know what we can do right now other than say we’re screwed.

GARRETT: That’s scientific.

OSTERHOLM: And I mean that in a very honest way in the sense that, right now, if it happens tonight, we don’t have the ability to suddenly gear up capacity. For example, the two major companies in the world that make the masks that would protect us, have 80 percent of the market share. They’re running at 95 percent capacity right now for everyday goods. The masks are made overseas, largely. Many of the component pieces come from another third, foreign country. It would take them three to five years to build another plant just to produce more masks.

And I could go through every one of the commodities that we would need tonight. So this idea of stockpiling, in part, is a figment of imagination. When these companies say they have all these Tamiflu, many of these have delivery dates of 2007 and 2008, OK. So don’t let a country off by saying, “We’re covered by having so much Tamiflu.” It hasn’t been delivered yet. And I think that part of it is, we would just have to figure how to get through the panic and fear.

We saw this with SARS in a very limited way. How would we bury the dead? How would we get food to the people? How would we maintain some semblance of order? Not just domestically, but worldwide. We worry greatly what would happen in terms of international security, opportunities for international unrest as might not otherwise occur. So, in essence— but each day we get out farther if we could get planning in place where we could get decisions made.

Are we going to close schools in this country? If we do, how will they handle that? Are we going to go to work? Are we going to have people riding airplanes, subways? Are we going to have goods delivered? We need to start working through that kind of thing now. That’s the best hope we have, is to get through. But it’s not going to change the number.

We will provide healthcare in gymnasiums and schools. Our hospitals right now are down to the bone. Even in this country, when we actually get just a slight increase in influenza every winter, we go on what’s called on-diversion status. Seventeen of the 20 major metropolitan areas last winter were on-diversion status for their emergency rooms, where they’re legally able to close their emergency room, which right now you can’t do without getting permission to do that from a civil authority because of the laws. They’re full. We have no excess capacity. So we’re going to have to figure out how to do that. We don’t have those plans in place. We need that kind of granularity right now.

Finally, on a worldwide basis, this isn’t a WHO issue. The WHO and groups like that are, at best, very, very limited partners for what this is needing. This is a G-8 [Group of Eight] issue that is all about, “Are we going to make a decision that we’re going to invest a tremendous amount of money and resources well beyond what the United States can do to actually create a world capacity for a new vaccine, build it, and then make it available and knowing that it’s going to cost a lot of money?”

The single— just one last point. In Minnesota, one of the very best well-funded fire departments in our entire state is the Minneapolis-St. Paul International fire department. There has never been a major plane crash at that airport since it’s inception over 80 years ago. We pay for that every day because, if there ever is one, we’ve got to have it there. We made a decision that’s an investment we’re willing to make for that very, very remote chance something will happen. Today we have to do that for vaccine. I appreciate what Tony said. I agree with him. I think we need to have the capacity to make 6.5 billion doses or treatments for people around the world just so we don’t have this world economy collapse issue.

FAUCI: Can I just very briefly expand on the firewall issue, because it really relates to the nature of this virus and how it compares to other perceived, frightening public-health threats. Generally, there’s a public-health firewall: identification, isolation, quarantine, things like that. That could be helpful, but the reason why it’s not the answer with influenza is the nature of how influenza spreads.

You take something like Marburg or Ebola; it’s only spread in very, very, very close contact. So identifying, isolating, quarantining, is very good for that. It was even recently good for SARS because of the fact that it’s droplet-transmitted. When you have something like influenza, almost from the get-go, once the virus assumes the capability of efficient spread from human to human, the horse is out of the barn almost immediately, because the kind of public-health measures that would isolate and contain are very inefficient because of what Laurie said about how the virus is there and how it spreads.

Influenza is spread very easily. That’s the combination that is the real killer for us: A, it is a potentially deadly virus, and B, it is very, very rapidly spread, historically over centuries. We know that. That makes a difference from a lot of other killers that are frightening, but are not as readily spread. So firewalls become less effective when you’re talking about public-health firewalls.

GARRETT: I just want to say a couple of things about governance. We’ve spent somewhere in the neighborhood of 3.7 to 5 point something or other billion dollars in the United States since 9/11 bolstering our public-health infrastructure with a heavy eye towards how you would respond to smallpox, how you would respond to bioterrorism issues. And a lot of it has been sold to the American people, in part, as that there’s dual use. That money spent preparing us for smallpox equals money generally spent to bolster our capacity to respond to a range on infectious disease threats and epidemics and so on.

But the truth of the matter is, if you go down the list, smallpox is a whole lot easier to deal with than influenza. And the kind of preparation that was put in place is not necessarily going to be particularly helpful in the case of influenza. Governance is what really matters. It’s hard to think of anything more important than governance at this time, but we haven’t really prepared government. We haven’t prepared our local government institutions. We haven’t prepared internationally. We have no agreed-upon mechanisms of any kind.

And Mike is absolutely right about the limitations of WHO, the idea that somehow we’re going to have sat down and made decisions. No, it won’t work to quarantine off huge populations. No, it won’t be effective to shut your borders. No, you can’t stop this kind of a pandemic by ordering all plane flights and paralyzing the global economy. We’ve not had that decision process. We’ve not had those discussions. They have to take place at all tiers of government, and there’s been no incentive whatsoever to get government moving to have that discussion.

HOGE: I’m sorry to say that we are officially out of time, and I lose a ribbon or two on my lapel if I keep us going. So I’m going to have to call a halt, but I think our panelists have a few moments to continue afterwards for those of you who can hang around, but it is 9:30 and so the meeting has officially got to come to an end. And Rita Colwell will close us out. Thank you.

COLWELL: I think it’s perfectly clear why the Royal Institution has settled on the pandemic project. This is not a trivial action, and the discussions, the interactions, the continuation of this project will be very important in the months to come. And there’ll be additional dialogues, and I really appreciate the opportunity that we’ve had to partner with the Foreign Affairs journal, with Nature, and with the scientists and government workers around the world. Thank you.

HOGE: Thank you all very much.

Laurie Garrett in Foreign Affairs – “The Next Pandemic?

An H5N1 avian influenza that is transmittable from human to human could be even more devastating: assuming a mortality rate of 20 percent and 80 million illnesses, the United States could be looking at 16 million deaths and unimaginable economic costs. This extreme outcome is a worst-case scenario; it assumes failure to produce an effective vaccine rapidly enough to make a difference and a virus that remains impervious to some antiflu drugs.

…..But the snafu raises serious questions: If billions have been spent to improve laboratory capabilities since 2001, why did nobody notice the H2N2 flu until about six months after the kits had been shipped? Why did a private company possess samples of the virulent flu? Why was the sample included in the kits? In the aftermath of the September 11, 2001, attacks and the anthrax scare, many countries reclassified 1957-58 and 1968-69 influenza strains as Level 3 pathogens, requiring extreme care in their handling, distribution, and storage — why did the United States still consider H2N2 to be a mere Level 2 pathogen, a type frequently mailed and studied? Finally, around the world, what other labs — public and private — currently possess samples of such lethal influenza viruses? The official CDC answer to these questions is, “We don’t know.”

(show)

Foreign Affairs

The Next Pandemic?

By Laurie Garrett

From Foreign Affairs, July/August 2005

Summary: Since it first emerged in 1997, avian influenza has become deadlier and more resilient. It has infected 109 people and killed 59 of them. If the virus becomes capable of human-to-human transmission and retains its extraordinary potency, humanity could face a pandemic unlike any ever witnessed.

Laurie Garrett is Senior Fellow for Global Health at the Council on Foreign Relations and is the author of The Coming Plague and Betrayal of Trust.

PROBABLE CAUSE

Scientists have long forecast the appearance of an influenza virus capable of infecting 40 percent of the world’s human population and killing unimaginable numbers. Recently, a new strain, H5N1 avian influenza, has shown all the earmarks of becoming that disease. Until now, it has largely been confined to certain bird species, but that may be changing.

The havoc such a disease could wreak is commonly compared to the devastation of the 1918-19 Spanish flu, which killed 50 million people in 18 months. But avian flu is far more dangerous. It kills 100 percent of the domesticated chickens it infects, and among humans the disease is also lethal: as of May 1, about 109 people were known to have contracted it, and it killed 54 percent (although this statistic does not include any milder cases that may have gone unreported). Since it first appeared in southern China in 1997, the virus has mutated, becoming heartier and deadlier and killing a wider range of species. According to the March 2005 National Academy of Science’s Institute of Medicine flu report, the “current ongoing epidemic of H5N1 avian influenza in Asia is unprecedented in its scale, in its spread, and in the economic losses it has caused.”

In short, doom may loom. But note the “may.” If the relentlessly evolving virus becomes capable of human-to-human transmission, develops a power of contagion typical of human influenzas, and maintains its extraordinary virulence, humanity could well face a pandemic unlike any ever witnessed. Or nothing at all could happen. Scientists cannot predict with certainty what this H5N1 influenza will do. Evolution does not function on a knowable timetable, and influenza is one of the sloppiest, most mutation-prone pathogens in nature’s storehouse.

Such absolute uncertainty, coupled with the profound potential danger, is disturbing for those whose job it is to ensure the health of their community, their nation, and broader humanity. According to the Centers for Disease Control and Prevention (CDC), in a normal flu season about 200,000 Americans are hospitalized, 38,000 of whom die from the disease, with an overall mortality rate of .008 percent for those infected. Most of those deaths occur among people older than 65; on average, 98 of every 100,000 seniors with the flu die. Influenza costs the U.S. economy about $12 billion annually in direct medical costs and loss of productivity.

Yet this level of damage hardly approaches the catastrophe that the United States would face in a severe flu pandemic. The CDC predicts that a “medium-level epidemic” could kill up to 207,000 Americans, hospitalize 734,000, and sicken about a third of the U.S. population. Direct medical costs would top $166 billion, not including the costs of vaccination. An H5N1 avian influenza that is transmittable from human to human could be even more devastating: assuming a mortality rate of 20 percent and 80 million illnesses, the United States could be looking at 16 million deaths and unimaginable economic costs. This extreme outcome is a worst-case scenario; it assumes failure to produce an effective vaccine rapidly enough to make a difference and a virus that remains impervious to some antiflu drugs. But the 207,000 reckoning is clearly a conservative guess.

The entire world would experience similar levels of viral carnage, and those areas ravaged by HIV and home to millions of immunocompromised individuals might witness even greater death tolls. In response, some countries might impose useless but highly disruptive quarantines or close borders and airports, perhaps for months. Such closures would disrupt trade, travel, and productivity. No doubt the world’s stock markets would teeter and perhaps fall precipitously. Aside from economics, the disease would likely directly affect global security, reducing troop strength and capacity for all armed forces, UN peacekeeping operations, and police worldwide.

In a world where most of the wealth is concentrated in less than a dozen nations representing a distinct minority of the total population, the capacity to respond to global threats is, to put it politely, severely imbalanced. The majority of the world’s governments not only lack sufficient funds to respond to a superflu; they also have no health infrastructure to handle the burdens of disease, social disruption, and panic. The international community would look to the United States, Canada, Japan, and Europe for answers, vaccines, cures, cash, and hope. How these wealthy governments responded, and how radically the death rates differed along worldwide fault lines of poverty, would resonate for years thereafter.

WHAT ONCE WAS LOST

Nearly half of all deaths in the United States in 1918 were flu related. Some 675,000 Americans — about 0.6 percent of the population of 105 million and the equivalent of 2 million American deaths today — perished from the Spanish flu. The average life expectancy for Americans born in 1918 was just 37 years, down from 55 in 1917. Although doctors then lacked the technology to test people’s blood for flu infections, scientists reckon that the Spanish flu had a mortality rate of just less than one percent of those who took ill in the United States. It would have been much worse had there not been milder flu epidemics in the 1850s and in 1889, caused by similar but less virulent viruses, which made most elderly Americans immune to the 1918-19 strain. The highest death tolls were among young adults, ages 20-35.

The Spanish flu got its name because Spain suffered from an early and acute outbreak, but it did not originate there. Its actual origin remains uncertain. The first strain was mild enough to prompt most World War I military forces to dismiss it as a pesky ailment. When the second strain hit North America in the summer of 1918, however, the virus caused a surge of deaths. First hit was Camp Funston, an army base in Kansas, where young soldiers were preparing for deployment to Europe. The virus then spread swiftly to other camps and on troop ships crossing the Atlantic, killing 43,000 U.S. military personnel in about three months. Despite the entreaties of the military’s surgeons general, President Woodrow Wilson ordered continued shipments of troops aboard crowded naval transports, which soldiers came to call “death ships.” By late September 1918, so overwhelmed was the War Department by influenza that the military could not assist in controlling civic disorder at home, including riots caused by epidemic hysteria. Worse, so many doctors, scientists, and lab technicians had been drafted into military service that civilian operations were hamstrung.

Under these conditions, influenza swept from the most populous U.S. cities to extraordinarily remote rural areas. Explorers discovered empty Inuit villages in what are now Alaska and the Yukon Territory, their entire populations having succumbed to the flu. Many deaths were never included in the pandemic’s official death toll — such as the majority of victims in Africa, Latin America, Indonesia, the Pacific Islands, and Russia (then still in the throes of revolution). What is known about the toll in these regions is staggering. For example, influenza killed 5 percent of the population of Ghana in only two months, and nearly 20 percent of the people of Western Samoa died. The official estimate of 40-50 million total deaths is believed to be a conservative extrapolation of European and American records. In fact, many historians and biologists believe that nearly a third of all humans suffered from influenza in 1918-19 — and that of these, 100 million died.

In the last years of the nineteenth century and the early years of the twentieth, a series of important scientific discoveries spawned a revolution in biology and medicine and led pioneers such as Hermann Biggs, a New York City doctor, to create entire legal and health systems based on the identification and control of germs. By 1917, the United States and much of Europe had become enthralled by the hygiene movement. Impressive new public health infrastructures had been built in many cities, tens of thousands of tuberculosis victims were isolated in sanatoriums, the incidences of child-killing diseases such as diphtheria and typhoid fever had plummeted, and cholera epidemics had become rare events in the industrialized world. There was great optimism that modern science held the key to perfect health.

Influenza’s arrival shattered the hope; scientists still had virtually no understanding of viruses generally, and of influenza in particular. The hygienic precautions and quarantines that had proved so effective in holding back the tide of bacterial diseases in the United States proved useless, even harmful, in the face of the Spanish flu. As the epidemic spread, top physicians and scientists claimed its cause was everything from tiny plants to old dusty books to something called “cosmic influence.” It was not until 1933 that a British research team finally isolated and identified the influenza virus.

Most strains of the flu do not kill people directly; rather, death is caused by bacteria, which surge into the embattled lungs of the victim. But the Spanish flu that circulated in 1918-19 was a direct killer. Victims suffered from acute cyanosis, a blue discoloration of the skin and mucous membranes. They vomited and coughed up blood, which also poured uncontrollably from their noses and, in the case of women, from their genitals. The highest death toll occurred among pregnant women: as many as 71 percent of those infected died. If the woman survived, the fetus invariably did not. Many young people suffered from encephalitis, as the virus chewed away at their brains and spinal cords. And millions experienced acute respiratory distress syndrome, an immunological condition in which disease-fighting cells so overwhelm the lungs in their battle against the invaders that the lung cells themselves become collateral damage, and the victims suffocate. Had antibiotics existed, they may not have been much help.

OOPS

In January 1976, 18-year-old Private David Lewis staggered his way through a forced march during basic training in a brutal New Jersey winter. By the time his unit returned to base at Fort Dix, Lewis was dying. He collapsed and did not respond to his sergeant’s attempts at mouth-to-mouth resuscitation.

In subsequent weeks, U.S. Army and CDC scientists discovered that the virus that had killed Lewis was swine flu. Although no other soldiers at Fort Dix died, health officials panicked. F. David Matthews, then secretary of health, education, and welfare, promptly declared, “There is evidence there will be a major flu epidemic this coming fall. The indication is that we will see a return of the 1918 flu virus that is the most virulent form of flu. In 1918, a half million people died [in the United States]. The projections are that this virus will kill one million Americans in 1976.”

At the time, it was widely believed that influenza appeared in cycles, with especially lethal forms surfacing at relatively predictable intervals. Since 1918-19, the United States had suffered through influenza pandemics in 1957-58 and 1968-69; the first caused 70,000 deaths and the second 34,000. In 1976, scientists believed the world was overdue for a more lethal cycle, and the apparent emergence of swine flu at Fort Dix seemed to signal that another wave had come. The leaders of the CDC and the Department of Health, Education, and Welfare (HEW) warned the White House that there was a reasonably high probability that a catastrophic flu pandemic was about to hit. But opinion was hardly unanimous, and many European and Australian health authorities scoffed at the Americans’ concern. Unsure of how to gauge the threat, President Gerald Ford summoned the polio-fighting heroes Jonas Salk and Albert Sabin to Washington and found the long-time adversaries in remarkable accord: a flu pandemic might truly be on the way.

On March 24, 1976, Ford went on national television. “I have just concluded a meeting on a subject of vast importance to all Americans,” he announced. “I have been advised that there is a very real possibility that unless we take effective counteractions, there could be an epidemic of this dangerous disease next fall and winter here in the United States. … I am asking Congress to appropriate $135 million, prior to the April recess, for the production of sufficient vaccine to inoculate every man, woman, and child in the United States.”

Vaccine producers immediately complained that they could not manufacture sufficient doses of vaccine in such haste without special liability protection. Congress responded, passing a law in April that made the government responsible for the companies’ liability. When the campaign to vaccinate the U.S. population started four months later, there were almost immediate claims of side effects, including the neurologically debilitating Guillain Barré Syndrome. Most of the lawsuits — with claims totaling $3.2 billion — were settled or dismissed, but the U.S. government still ended up paying claimants around $90 million.

Swine flu, however, never appeared. The head of the CDC was asked to resign, and Congress never again considered assuming the liability of pharmaceutical companies during a potential epidemic. The experience weakened U.S. credibility in public health and helped undermine the stature of President Ford. Subsequently, an official assessment of what went wrong was performed for HEW by Dr. Harvey Fineberg, a Harvard professor who is currently president of the Institute of Medicine.

Fineberg concluded:”In this case the consequences of being wrong about an epidemic were so devastating in people’s minds that it wasn’t possible to focus properly on the issue of likelihood. Nobody could really estimate likelihood then, or now. The challenge in such circumstances is to be able to distinguish things so you can rationally talk about it. In 1976, some policymakers were simply overwhelmed by the consequences of being wrong. And at a higher level [in the White House] the two — likelihood and consequence — got meshed.”

Fineberg’s warnings are well worth remembering today, as scientists nervously consider H5N1 avian influenza in Asia. The consequences of a form of this virus that is transmittable from human to human, particularly if it retains its unprecedented virulence, would be disastrous. But what is the likelihood that such a virus will appear?

DEVOLUTION

Understanding the risks requires understanding the nature of H5N1 avian flu specifically and influenza in general. Influenza originates with aquatic birds and is normally carried by migratory ducks, geese, and herons, usually without harm to them. As the birds migrate, they can pass the viruses on to domesticated birds — chickens, for example — via feces or during competitions over food, territory, and water. Throughout history, this connection between birds and the flu has spawned epidemics in Asia, especially southern China. Aquatic flu viruses are more likely to pass into domestic animals — and then into humans — in China than anywhere else in the world. Dense concentrations of humans and livestock have left little of China’s original migratory route for birds intact. Birds that annually travel from Indonesia to Siberia and back are forced to land and search for sustenance in farms, city parks, and industrial sites. For centuries, Chinese farmers have raised chickens, ducks, and pigs together, in miniscule pens surrounding their homes, greatly increasing the chance of contamination: influenza can spread from migrating to domestic birds and then to swine, mutating and eventually infecting human beings.

Ominously, as China’s GDP grows, so do the expensive appetites of the country’s 1.3 billion people, more of whom can afford to eat chicken regularly. Today, China annually raises about 13 billion chickens, 60 percent of them on small farms. Chicken farming is quickly morphing into a major industry, with some commercial poultry plants rivaling those in Arkansas and Georgia in scale — but lagging behind in hygienic standards. These factors favor rapid influenza evolution. By the close of the twentieth century, at least two new types of human-to-human flu spread around the world every year.

Influenza viruses contain eight genes, composed of RNA and packaged loosely in protective proteins. Like most RNA viruses, influenza reproduces sloppily: its genes readily fall apart, and it can absorb different genetic material and get mixed up in a process called reassortment. When influenza successfully infects a new species — say, pigs — it can reassort, and may switch from being an avian virus to a mammalian one. When that occurs, a human epidemic can result. The transmission cycles and the constant evolution are key to influenza’s continued survival, for were it to remain identical year after year, most animals would develop immunity, and the flu would die out. This changing form explains why influenza is a seasonal disease. Vaccines made one year are generally useless the following.

Among the eight influenza genes there are two, dubbed H and N, that provide the code for proteins recognized by the human immune system. Scientists have numbered the many types of H and N proteins and use this system to classify a virus. A different viral combination of H and N proteins will trigger a different human immune response. For example, if a strain of H2N3 influenza circulates one year, followed by a different variety of H2N3 the next year, most people will be at least partially immune to the second strain. But if an H2N3 season is followed by an outbreak of H3N5 influenza, few people will have any immunity to the second virus, and the epidemic could be enormous. But a widespread epidemic need not be a severe or particularly deadly one: a virus’ virulence depends on genes other than the two that control the H and N proteins.

Scientists first started saving flu virus samples in the early twentieth century. Since that time, an H5N1 influenza has never spread among human beings. According to the World Health Organization (WHO), “No virus of the H5 subtype has probably ever circulated among humans, and certainly not within the lifetime of today’s world population. Population vulnerability to an H5N1-like pandemic virus would be universal.” As for virulence, within about 48 hours of infection, H5N1 avian influenza kills 100 percent of infected chickens — although the virulence of a potential human-to-human transmissible H5N1 is impossible to predict.

A team of Chinese scientists has been tracking the H5N1 virus since it first emerged in Hong Kong in 1997, killing 6 people and sickening 18 others. The strain came out of southern China’s Guangdong Province, where it apparently was carried by ducks, and hit Hong Kong’s chicken population hard. After authorities there killed 1.5 million chickens — almost every single one in Hong Kong — the outbreak seemed to stop. But the virus had not disappeared; rather, it had retreated to China’s Guangdong, Hunan, and Yunnan provinces, spreading once again to aquatic birds.

From 1998 to 2001 the virus went through multiple reassortments and moved back to domestic birds, spreading almost unnoticed in Chinese chicken flocks. It continued to evolve at high speed: 17 more reassortments occurred, and in January 2003 the “Z” virus emerged, a mutant powerhouse that had become tougher, capable of withstanding a wider range of environmental challenges. The Z virus spread to Vietnam and Thailand, where it evolved further, becoming resistant to one of the two classes of antiflu drugs, known as amantadines, or M2-inhibitors.

In early 2004, it became supervirulent and capable of killing a broad range of species, including rodents and humans. That permutation of the virus was dubbed “Z+.” In the first three weeks of January 2004, Z+ killed 11 million chickens in Vietnam and Thailand. By April 2004, 120 million chickens in Asia had died of flu or been exterminated to slow the influenza brushfire. The avian epidemic stopped for a while, but in July another 1 million chickens died from the disease. The Z+ virus was causing massive internal bleeding in the birds. By the beginning of 2005, with chickens dying and customers shying away from what remained, the Asian poultry industry had lost nearly $15 billion.

By April 2005, the H5N1 virus had also moved to pigs. Scientists isolated the disease from swine in a part of Indonesia where pigs are raised underneath elevated wood-slatted platforms that house chickens. Less rigorous investigations had previously indicated that pigs in China and Vietnam may also have been infected by H5N1 influenza. The discovery in Indonesia provided disturbing evidence that the virus was infecting mammals, although it was not yet known how widely the swine disease had spread or how lethal it was for the animals.

HARD TO KILL

Over the course of this brief but rapid evolution, the H5N1 virus developed in ways unprecedented in influenza research. It is not only incredibly deadly but also incredibly difficult to contain. The virus apparently now has the ability to survive in chicken feces and the meat of dead animals, despite the lack of blood flow and living cells; raw chicken meat fed to tigers in Thailand zoos resulted in the deaths of 147 out of a total of 418. The virus has also found ways to vastly increase the range of species it can infect and kill. Most strains of influenza are not lethal in lab mice, but Z+ is lethal in 100 percent of them. It even kills the very types of wild migratory birds that normally host influenza strains harmlessly. Yet domestic ducks, for unknown reasons, carry the virus without a problem, which may explain where Z+ hides between outbreaks among chickens.

Traditional Asian methods of buying, slaughtering, and cooking meat make it hard to track the spread of an influenza virus — and tracking it is critical to preventing the disease from spreading. In Asia, consumers prefer to buy live chickens and other live animals at the market, slaughtering them in home kitchens. Asians thus have a high level of exposure to potentially disease-carrying animals, both in their homes and as they pass through the markets that line the streets of densely packed urban centers. For someone trying to trace a disease, Asia is a nightmare: with people daily exposed to live chickens in so many different environments, how can a sleuth tell whether an ailing flu victim was infected by a chicken, a duck, a migratory heron — or another human being?

Although most of the 109 known human H5N1 infections have been ascribed to some type of contact with chickens, mysteries abound, and many cases remain unsolved. “The virus is no longer causing large and highly conspicuous outbreaks on commercial farms,” a 2005 WHO summary of the human Z+ cases states. “Nor have poultry workers or cullers turned out to be an important risk group that could be targeted for protection. Instead, the virus has become stealthier: human cases are now occurring with no discernible exposure to H5N1 through contact with diseased or dead birds.”

If proximity to infected animals is the key, why have there been no deaths among chicken handlers, poultry workers, or live-chicken dealers? The majority of the infected have been young adults and children. And there has been one documented case of human-to-human transmission of the Z+ strain of the H5N1 virus — in late 2004, in Thailand. Several more such cases are suspected but cannot be confirmed. According to the WHO, there is “no scientific explanation for the unusual disease pattern.”

Assessing and understanding H5N1’s virulence in humans has also proved elusive. When it first appeared in Hong Kong in 1997, the virus killed 35 percent of those it was known to have infected. (Less severe cases may not have been reported.) The Z strain of the disease, which emerged in early 2003, killed 68 percent of those known to have been infected. In H5N1 cases since December 2004, however, the mortality has been 36 percent. How can the fluctuation over time be explained? One disturbing possibility is that H5N1 has begun adapting to its human hosts, becoming less deadly but easier to spread. In the spring of 2005, in fact, H5N1 infected 17 people throughout Vietnam, resulting in only three deaths. Leading flu experts argue that this sort of phenomenon has in the past been a prelude to human influenza epidemics.

The medical histories of those who have died from H5N1 influenza are disturbingly similar to accounts of sufferers of the Spanish flu in 1918-19. Otherwise healthy people are completely overcome by the virus, developing all of the classic flu symptoms: coughing, headache, muscle pain, nausea, dizziness, diarrhea, high fever, depression, and loss of appetite. But these are just some of the effects. Victims also suffer from pneumonia, encephalitis, meningitis, acute respiratory distress, and internal bleeding and hemorrhaging. An autopsy of a child who died of the disease in Thailand last year revealed that the youth’s lungs had been torn apart in the all-out war between disease-fighting cells and the virus.

BAD MEDICINE

According to test-tube studies, Z+ ought to be vulnerable to the antiflu drug oseltamivir, which the Roche pharmaceuticals company markets in the United States under the brand name Tamiflu. Yet Tamiflu was given to many of those who ultimately succumbed to the virus; it is believed that medical complications induced by the virus, including acute respiratory distress syndrome, may have prevented the drug from helping. It is also difficult to tell whether the drug contributed to the survival of those who took it and lived, although higher doses and more prolonged treatment may have a greater impact in fighting the disease. A team of Thai clinicians recently concluded that “the optimal treatment for case-patients with suspected H5 infection is not known.” Lacking any better options, the WHO has recommended that countries stockpile Tamiflu to the best of their ability. The U.S. Department of Health and Human Services is doing so, but supplies of the drug are limited and it is hard to manufacture.

What about developing a Z+ vaccine? Unfortunately, there is only more gloom in the forecast. The total number of companies willing to produce influenza vaccines has plummeted in recent years, from more than two dozen in 1980 to just a handful in 2004. There are many reasons for the decline in vaccine producers. A spate of corporate mergers in the 1990s, for example, reduced the number of major international pharmaceutical companies. The financial risk of investing in vaccines is also a key factor. In 2003, the entire market for all vaccines — from polio to measles to hepatitis to influenza — amounted to just $5.4 billion. Although that sum may seem considerable, it is less than two percent of the global pharmaceutical market of $337.3 billion. Unlike chemical compounds, vaccines and most other biological products are difficult to make and can easily become contaminated. There is also a large and litigious antivaccine constituency — some people believe that vaccines cause harmful side effects such as Alzheimer’s disease and autism — adding considerable liability costs to manufacturers’ bottom lines.

The production of influenza vaccines holds particular drawbacks for companies. Flu vaccines must be made rapidly, increasing the risk of contamination or other errors. Because of the seasonal nature of the flu, a new batch of influenza vaccines must be produced each year. Should sales in a given year prove disappointing, flu vaccines cannot be stockpiled for sale in a subsequent season because by then the viruses will have evolved. In addition, the manufacturing process of flu vaccines is uniquely complex: pharmaceutical companies must grow viral samples on live chicken eggs, which must be reared under rigorous hygienic conditions. Research is under way on reverse genetics and cellular-level production techniques that might prove cheaper, faster, and less contamination-prone than using eggs, but for the foreseeable future manufacturers are stuck with the current laborious method. After cultivation, samples of the viruses must be harvested, the H and N characteristics must be shown to produce antibodies in test animals and human volunteers, and tests must prove that the vaccine is not contaminated. Only then can mass production commence.

The H5N1 strain of avian flu poses an additional problem: the virus is 100 percent lethal to chickens — and that includes chicken eggs. It took researchers five years of hard work to devise a way to grow the 1997 version of the H5N1 virus on eggs without killing them; although there have been technological improvements since then, there is no guarantee that an emerging pandemic strain could be cultivated fast enough.

In the current system, all influenza vaccines must be quickly made following a WHO meeting of flu experts held every February. At that gathering, scientists scrutinize all available information on the flu strains known to be circulating in the world. They then try to predict which strains are most likely to spread across every continent in the next six to nine months. (This year the WHO committee chose three human flu strains, of types H3N2 and H1N1, to be the basis of the next vaccine.) Samples of the chosen strains are delivered to pharmaceutical companies around the world for vaccine production, and the vaccines are hopefully available to the public by September or October — a few months after influenza typically strikes Asia, in the early summer. Europe and the Americas are usually hit shortly after, in September. Because viruses constantly change themselves, the process cannot be executed earlier in the year.

Although new technology may allow an increase in production capacity, manufacturers have never made more than 300 million doses of flu vaccine in a single year. The slow pace of production means that in the event of an H5N1 flu pandemic millions of people would likely be infected well before vaccines could be distributed.

GLOBAL REACH

The scarcity of flu vaccine, although a serious problem, is actually of little relevance to most of the world. Even if pharmaceutical companies managed to produce enough effective vaccine in time to save some privileged lives in Europe, North America, Japan, and a few other wealthy nations, more than six billion people in developing countries would go unvaccinated. Stockpiles of Tamiflu and other anti-influenza drugs would also do nothing for those six billion, at least 30 percent of whom — and possibly half — would likely get infected in such a pandemic.

Resources are so scarce that both wealthy and poor countries would be foolish to count on the generosity of their neighbors during a global outbreak. Were the United States to miraculously overcome its vaccine production problems and produce ample supplies for U.S. citizens, Washington would probably deny the vaccine to neighbors such as Mexico, since governments tend to reserve vaccine supplies for their own citizens during emergencies. Were the United States to falter, it would probably not be able to rely on Canadian or European generosity, as it did just last year. When the United Kingdom suspended the license for the Chiron Corporation’s U.K. production facility for flu vaccine due to contamination problems, Canada and Germany bailed the United States out, supplying additional doses until the French company Sanofi Pasteur could manufacture more. Even with this assistance, however, the United States’ vaccine needs were not fully met until February 2005 — the tail end of the flu season.

In the event of a deadly influenza pandemic, it is doubtful that any of the world’s wealthy nations would be able to meet the needs of their own citizenry — much less those of other countries. Domestic vaccine purchasing and distribution schemes currently assume that only the very young, the elderly, and the immunocompromised are at serious risk of dying from the flu. That assumption would have led health leaders in 1918 to vaccinate all of the wrong people. Then, the young and the old fared relatively well, while those aged 20 to 35 — today typically the lowest priority for vaccination — suffered the most deaths from the Spanish flu. And so far, H5N1 influenza looks like it could have a similar effect: its human victims have all fallen into age groups that would not be on national vaccine priority lists, and because H5N1 has never circulated among humans before, it is highly conceivable that all ages could be susceptible. Every year, trusting that the flu will kill only the usual risk groups, the United States plans for 185 million vaccine doses. If that guess were wrong — if all Americans were at risk — the nation would need at least 300 million doses. That is what the entire world typically produces each year.

There would thus be a global scramble for vaccine. Some governments might well block foreign access to supplies produced on their soil and bar vaccine export. Since little vaccine is actually made in the United States, this could prove a problem for Americans in particular. Facing such limited supplies, the U.S., European, and Japanese governments might give priority to vaccinating heads of state around the world in hopes of limiting social chaos. But who among the elite would be eligible? Would their families be included? How could such a global triage be executed justly?

A similar calculus might be necessary for countries engaged in significant military operations. Troop movements would certainly help spread the disease, just as World War I aided the growth of the 1918-19 Spanish flu. Back then, the flu wreaked havoc on combatant nations. In the summer of 1918, influenza killed far more soldiers than did bombs, bullets, or mustard gas. By October, some 46 percent of the French army was off the field of battle — ailing, dying, or caring for flu victims. Influenza death tolls among the various military forces generally ranged from 5 to 10 percent, but some segments fared even worse: historian John Barry has reported that 22 percent of the Indian members of the British military died.

In the event of a modern pandemic, the U.S. Department of Defense, with the lessons of World War I in mind, would undoubtedly insist that U.S. troops in Iraq and Afghanistan be given top access to vaccines and antiflu drugs. About 170,000 U.S. forces are currently stationed in Iraq and Afghanistan, while 200,000 more are permanently based elsewhere overseas. All of them would potentially be in danger: in late March, for example, North Korea conceded it was suffering a large-scale H7N1 outbreak — taking place within miles of some 41,000 U.S. military forces. It is impossible to predict how such a pandemic influenza would affect U.S. operations in Iraq, Afghanistan, Colombia, or any other place.

Armed forces throughout the world would face similar issues. Most would no doubt pressure their governments for preferential access to vaccine and medications. In addition, more than a quarter of some African armies and police forces are HIV positive, perhaps making them especially vulnerable to influenza’s lethal impact. Social instability resulting from troop and police losses there would likely be particularly acute.

Such a devastating disease would clearly have profound implications for international relations and the global economy. With death tolls rising, vaccines and drugs in short supply, and the potential for the virus to spread further, governments would feel obliged to take drastic measures that could inhibit travel, limit worldwide trade, and alienate their neighbors. In fact, the Z+ virus has already demonstrated its disruptive potential on a limited scale. In July 2004, for example, when the Z+ strain reemerged in Vietnam after a three-month hiatus, officials in the northern province of Bac Giang charged that Chinese smugglers were selling old and sickly birds in Vietnamese markets — where more than ten tons of chickens are smuggled daily. Chinese authorities in charge of policing their side of the porous border, more than 1,000 kilometers long, countered that it was impossible to inspect all the shipments. Such conflicts are now limited to the movement of livestock, but if a pandemic develops they could well escalate to a ban on trade and human movement.

Although there is little evidence that isolation measures have ever slowed the spread of influenza — it is just too contagious — most governments would likely resort to quarantines in a pandemic crisis. Indeed, on April 1, 2005, President George W. Bush issued an executive order authorizing the use of quarantines inside the United States and permitting the isolation of international visitors suspected of carrying influenza. If one country implements such orders, others will follow suit, bringing legal international travel to a standstill. The SARS (severe acute respiratory syndrome) virus, which was less dangerous than a pandemic flu by several orders of magnitude, virtually shut down Asian travel for three months.

As great as they would be, the economic consequences of travel restrictions, quarantines, and medical care would be well outstripped by productivity losses. In a typical flu season, productivity costs are ten times greater than all other flu-related costs combined. The decline in productivity is usually due directly to worker illness and absenteeism. During a pandemic, productivity losses would be even more disproportionate because entire workplaces — schools, theaters, and public facilities — would be shut down to limit human-to-human spread of the virus. Workers’ illnesses also would likely be even more severe and last even longer than normal. Frankly, no models of social response to such a pandemic have managed to factor in fully the potential effect on human productivity. It is therefore impossible to reckon accurately the potential global economic impact.

AILING

The potential for a pandemic comes at a time when the world’s public health systems are severely taxed and have long been in decline. This is true in both rich and poor countries.

The Bush administration recognized this weakness following the anthrax scare of 2001, which underscored the poor ability of federal and local health agencies to respond to bioterrorism or epidemic threats. Since that year, Congress has approved $3.7 billion to strengthen the nation’s public health infrastructure. In 2003, the White House also took several steps to improve the nation’s capacity to respond to a flu pandemic: it increased funding for the CDC’s flu program by 242 percent, to $41.6 million in 2004; gave the National Institutes of Health an additional 320 percent in funds for flu-related research and development, for a total of $65.9 million; increased spending on the Food and Drug Administration’s licensing capacity for flu vaccines and drugs by 173 percent, to $2.6 million; and spent an additional $80 million to create new stockpiles of Tamiflu and other anti-influenza drugs. On August 4, 2004, the Department of Health and Human Services also issued its pandemic flu plan, detailing further steps that would be taken by federal and state agencies in the event of a pandemic. Several other countries have released similar plans of action.

But despite all this, a recent event underscored the United States’ tremendous vulnerability. In October 2004, the American College of Pathologists mailed a collection of mystery microbes prepared by a private lab to almost 5,000 labs in 18 countries for them to test as part their recertification. The mailing should have been routine procedure; instead, in March 2005 a Canadian lab discovered that the test kits included a sample of H2N2 flu — a strain that had killed four million people worldwide in 1957. H2N2 has not been in circulation since 1968, meaning that hundreds of millions of people lack immunity to it. Had any of the samples leaked or been exposed to the environment, the results could have been devastating. On learning of the error, the WHO called for the immediate destruction of all the test kits. Miraculously, none of the virus managed to escape any of the labs.

But the snafu raises serious questions: If billions have been spent to improve laboratory capabilities since 2001, why did nobody notice the H2N2 flu until about six months after the kits had been shipped? Why did a private company possess samples of the virulent flu? Why was the sample included in the kits? In the aftermath of the September 11, 2001, attacks and the anthrax scare, many countries reclassified 1957-58 and 1968-69 influenza strains as Level 3 pathogens, requiring extreme care in their handling, distribution, and storage — why did the United States still consider H2N2 to be a mere Level 2 pathogen, a type frequently mailed and studied? Finally, around the world, what other labs — public and private — currently possess samples of such lethal influenza viruses? The official CDC answer to these questions is, “We don’t know.”

Even with all of these gaps, probably the greatest weakness that each nation must individually address is the inability of their hospitals to cope with a sudden surge of new patients. Medical cost cutting has resulted in a tremendous reduction in the numbers of staffed hospital beds in the wealthy world, especially in the United States. Even during a normal flu season, hospitals located in popular retirement areas have great difficulty meeting the demand. In a pandemic, it is doubtful that any nation would have adequate medical facilities and personnel to meet the extra need.

National policymakers would be wise to plan now for worst-case scenarios involving quarantines, weakened armed services, and dwindling hospital space and vaccine supplies. But at the end of the day, effectively combating influenza will require multilateral and global mechanisms. Chief among them, of course, is the WHO, which since 1947 has maintained a worldwide network that conducts influenza surveillance. The WHO system oversees laboratories all over the world, chases (and sometimes refutes) rumors of pandemics, pushes for government transparency regarding human and avian flu cases, and acts as an arbiter in negotiations over vaccine production, trade embargoes, and border disputes. Its companion UN agency, the Food and Agriculture Organization (FAO), working closely with the World Organization for Animal Health, monitors flu outbreaks in animal populations and advises governments on culling flocks and herds, cross-border animal trade, animal husbandry and slaughter, and livestock quarantine and vaccination. All of these organizations have published lengthy guidelines on how to respond to a pandemic flu, lists of answers to commonly asked questions, and descriptions of their research priorities — most of which have been posted on their Web sites.

The efforts of these agencies should be bolstered, both with expertise and dollars. The WHO, for example, has an annual core budget of just $400 million, a tiny increment of which is spent on influenza- and epidemic-response programs. (In comparison, the annual budget of New York City’s health department exceeds $1.2 billion.) An unpublished internal study estimates that the agency would require at least another $600 million for its flu program were a pandemic to erupt. It is in every government’s interest to give the WHO and the FAO the authority to act as impartial voices during a pandemic, able (theoretically) to assess objectively the epidemic’s progress and rapidly evaluate research claims. The WHO in particular must have adequate funding and personnel to serve as an accurate clearinghouse of information about the disease, thereby preventing the spread of false rumors and global panic. No nation can erect a fortress against influenza — not even the world’s wealthiest country.

Few members of the U.S. Congress or its legislative counterparts around the world were alive when the great Spanish flu swept the planet. There may be some who lost parents, aunts, or uncles to the 1918-19 pandemic, and perhaps even more have heard the horror stories that were passed down. But politics breeds shortsightedness, and for decades the threat of an influenza pandemic has been easily forgotten, and therefore ignored at budget time. Politicians and health leaders made many serious errors in 1918-19; some historians say that President Wilson sent 43,000 soldiers to their deaths by forcing them aboard crowded ships to join a war he had already won. But in those days, human beings had no understanding of their influenza foe.

In 1971, the great American public health leader Alexander Langmuir likened flu forecasting to trying to predict the weather, arguing that “as with hurricanes, pandemics can be identified and their probable course projected so that warnings can be issued. Epidemics, however, are more variable [than hurricanes], and the best that can be done is to estimate probabilities.”

Since Langmuir’s time a quarter of a century ago, weather forecasting has gained a stunning level of precision. And although scientists cannot tell political leaders when an influenza pandemic will occur, researchers today are able to guide policymakers with information and analysis exponentially richer than that which informed the decisions of President Ford and the 1976 Congress. Whether or not this particular H5N1 influenza mutates into a human-to-human pandemic form, the scientific evidence points to the potential that such an event will take place, perhaps soon. Those responsible for foreign policy and national security, the world over, cannot afford to ignore the warning.

www.foreignaffairs.org is copyright 2002–2005 by the Council on Foreign Relations. All rights reserved.

Preparing for the Next Pandemic by Michael T. Osterholm

Given so many other significant infectious diseases, why does another influenza pandemic merit unique and urgent attention? First, of the more than 1,500 microbes known to cause disease in humans, influenza continues to be the king in terms of overall mortality. Even in a year when only the garden-variety strains circulate, an estimated 1-1.5 million people worldwide die from influenza infections or related complications. In a pandemic lasting 12 to 36 months, the number of cases and deaths would rise dramatically.

Recent clinical, epidemiological, and laboratory evidence suggests that the impact of a pandemic caused by the current H5N1 strain would be similar to that of the 1918-19 pandemic. More than half of the people killed in that pandemic were 18 to 40 years old and largely healthy. If 1918-19 mortality data are extrapolated to the current U.S. population, 1.7 million people could die, half of them between the ages of 18 and 40. Globally, those same estimates yield 180-360 million deaths, more than five times the cumulative number of documented AIDS deaths. In 1918-19, most deaths were caused by a virus-induced response of the victim’s immune system — a cytokine storm — which led to acute respiratory distress syndrome (ARDS). In other words, in the process of fighting the disease, a person’s immune system severely damaged the lungs, resulting in death. Victims of H5N1 have also suffered from cytokine storms, and the world is not much better prepared to treat millions of cases of ARDS today than it was 85 years ago. In the 1957-58 and 1968-69 pandemics, the primary cause of death was secondary bacterial pneumonias that infected lungs weakened by influenza. Although such bacterial infections can often be treated by antibiotics, these drugs would be either unavailable or in short supply for much of the global population during a pandemic.

……..Vaccine would have no impact on the course of the virus in the first months and would likely play an extremely limited role worldwide during the following 12 to 18 months of the pandemic. Despite major innovations in the production of most other vaccines, international production of influenza vaccine is based on a fragile and limited system that utilizes technology from the 1950s. Currently, annual production of influenza vaccine is limited to about 300 million trivalent doses — which protect against three different influenza strains in one dose — or less than one billion monovalent doses. To counter a new strain of pandemic influenza that has never circulated throughout the population, each person would likely need two doses for adequate protection. With today’s limited production capacity, that means that less than 500 million people — about 14 percent of the world’s population — would be vaccinated within a year of the pandemic. In addition, because the structure of the virus changes so rapidly, vaccine development could only start once the pandemic began, as manufacturers would have to obtain the new pandemic strain. It would then be at least another six months before mass production of the vaccine.

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Foreign Affairs

Preparing for the Next Pandemic

By Michael T. Osterholm

From Foreign Affairs, July/August 2005

Summary: If an influenza pandemic struck today, borders would close, the global economy would shut down, international vaccine supplies and health-care systems would be overwhelmed, and panic would reign. To limit the fallout, the industrialized world must create a detailed response strategy involving the public and private sectors.

Michael T. Osterholm is Director of the Center for Infectious Disease Research and Policy, Associate Director of the Department of Homeland Security’s National Center for Food Protection and Defense, and Professor at the University of Minnesota’s School of Public Health.

FEAR ITSELF

Dating back to antiquity, influenza pandemics have posed the greatest threat of a worldwide calamity caused by infectious disease. Over the past 300 years, ten influenza pandemics have occurred among humans. The most recent came in 1957-58 and 1968-69, and although several tens of thousands of Americans died in each one, these were considered mild compared to others. The 1918-19 pandemic was not. According to recent analysis, it killed 50 to 100 million people globally. Today, with a population of 6.5 billion, more than three times that of 1918, even a “mild” pandemic could kill many millions of people.

A number of recent events and factors have significantly heightened concern that a specific near-term pandemic may be imminent. It could be caused by H5N1, the avian influenza strain currently circulating in Asia. At this juncture scientists cannot be certain. Nor can they know exactly when a pandemic will hit, or whether it will rival the experience of 1918-19 or be more muted like 1957-58 and 1968-69. The reality of a coming pandemic, however, cannot be avoided. Only its impact can be lessened. Some important preparatory efforts are under way, but much more needs to be done by institutions at many levels of society.

THE BACKDROP

Of the three types of influenza virus, influenza type A infects and kills the greatest number of people each year and is the only type that causes pandemics. It originates in wild aquatic birds. The virus does not cause illness in these birds, and although it is widely transmitted among them, it does not undergo any significant genetic change.

Direct transmission from the birds to humans has not been demonstrated, but when a virus is transmitted from wild birds to domesticated birds such as chickens, it undergoes changes that allow it to infect humans, pigs, and potentially other mammals. Once in the lung cells of a mammalian host, the virus can “reassort,” or mix genes, with human influenza viruses that are also present. This process can lead to an entirely new viral strain, capable of sustained human-to-human transmission. If such a virus has not circulated in humans before, the entire population will be susceptible. If the virus has not circulated in the human population for a number of years, most people will lack residual immunity from previous infection.

Once the novel strain better adapts to humans and is easily transmitted from person to person, it is capable of causing a new pandemic. As the virus passes repeatedly from one human to the next, it eventually becomes less virulent and joins the other influenza viruses that circulate the globe each year. This cycle continues until another new influenza virus emerges from wild birds and the process begins again.

Some pandemics result in much higher rates of infection and death than others. Scientists now understand that this variation is a result of the genetic makeup of each specific virus and the presence of certain virulence factors. That is why the 1918-19 pandemic killed many more people than either the 1957-58 or the 1968-69 pandemic.

A CRITICAL DIFFERENCE

Infectious diseases remain the number one killer of humans worldwide. Currently, more than 39 million people live with HIV, and last year about 2.9 million people died of AIDS, bringing the cumulative total of deaths from AIDS to approximately 25 million. Tuberculosis (TB) and malaria also remain major causes of death. In 2003, about 8.8 million people became infected with TB, and the disease killed more than 2 million. Each year, malaria causes more than 1 million deaths and close to 5 billion episodes of clinical illness. In addition, newly emerging infections, diarrheal and other vector-borne diseases, and agents resistant to antibiotics pose a serious and growing public health concern.

Given so many other significant infectious diseases, why does another influenza pandemic merit unique and urgent attention? First, of the more than 1,500 microbes known to cause disease in humans, influenza continues to be the king in terms of overall mortality. Even in a year when only the garden-variety strains circulate, an estimated 1-1.5 million people worldwide die from influenza infections or related complications. In a pandemic lasting 12 to 36 months, the number of cases and deaths would rise dramatically.

Recent clinical, epidemiological, and laboratory evidence suggests that the impact of a pandemic caused by the current H5N1 strain would be similar to that of the 1918-19 pandemic. More than half of the people killed in that pandemic were 18 to 40 years old and largely healthy. If 1918-19 mortality data are extrapolated to the current U.S. population, 1.7 million people could die, half of them between the ages of 18 and 40. Globally, those same estimates yield 180-360 million deaths, more than five times the cumulative number of documented AIDS deaths. In 1918-19, most deaths were caused by a virus-induced response of the victim’s immune system — a cytokine storm — which led to acute respiratory distress syndrome (ARDS). In other words, in the process of fighting the disease, a person’s immune system severely damaged the lungs, resulting in death. Victims of H5N1 have also suffered from cytokine storms, and the world is not much better prepared to treat millions of cases of ARDS today than it was 85 years ago. In the 1957-58 and 1968-69 pandemics, the primary cause of death was secondary bacterial pneumonias that infected lungs weakened by influenza. Although such bacterial infections can often be treated by antibiotics, these drugs would be either unavailable or in short supply for much of the global population during a pandemic.

The arrival of a pandemic influenza would trigger a reaction that would change the world overnight. A vaccine would not be available for a number of months after the pandemic started, and there are very limited stockpiles of antiviral drugs. Plus, only a few privileged areas of the world have access to vaccine-production facilities. Foreign trade and travel would be reduced or even ended in an attempt to stop the virus from entering new countries — even though such efforts would probably fail given the infectiousness of influenza and the volume of illegal crossings that occur at most borders. It is likely that transportation would also be significantly curtailed domestically, as smaller communities sought to keep the disease contained. The world relies on the speedy distribution of products such as food and replacement parts for equipment. Global, regional, and national economies would come to an abrupt halt — something that has never happened due to HIV, malaria, or TB despite their dramatic impact on the developing world.

The closest the world has come to this scenario in modern times was the SARS (severe acute respiratory syndrome) crisis of 2003. Over a period of five months, about 8,000 people were infected by a novel human coronavirus. About ten percent of them died. The virus apparently spread to humans when infected animals were sold and slaughtered in unsanitary and crowded markets in China’s Guangdong Province. Although the transmission rate of SARS paled in comparison to that of influenza, it demonstrated how quickly such an infectious agent can circle the globe, given the ease and frequency of international travel. Once SARS emerged in rural China, it spread to five countries within 24 hours and to 30 countries on six continents within several months.

The SARS experience teaches a critical lesson about the potential global response to a pandemic influenza. Even with the relatively low number of deaths it caused compared to other infectious diseases, SARS had a powerful negative psychological impact on the populations of many countries. In a recent analysis of the epidemic, the National Academy of Science’s Institute of Medicine concluded: “The relatively high case-fatality rate, the identification of super-spreaders, the newness of the disease, the speed of its global spread, and public uncertainty about the ability to control its spread may have contributed to the public’s alarm. This alarm, in turn, may have led to the behavior that exacerbated the economic blows to the travel and tourism industries of the countries with the highest number of cases.”

SARS provided a taste of the impact a killer influenza pandemic would have on the global economy. Jong-Wha Lee, of Korea University, and Warwick McKibbin, of the Australian National University, estimated the economic impact of the six-month SARS epidemic on the Asia-Pacific region at about $40 billion. In Canada, 438 people were infected and 43 died after an infected person traveled from Hong Kong to Toronto, and the Canadian Tourism Commission estimated that the epidemic cost the nation’s economy $419 million. The Ontario health minister estimated that SARS cost the province’s health-care system about $763 million, money that was spent, in part, on special SARS clinics and supplies to protect health-care workers. The SARS outbreak also had a substantial impact on the global airline industry. After the disease hit in 2003, flights in the Asia-Pacific area decreased by 45 percent from the year before. During the outbreak, the number of flights between Hong Kong and the United States fell 69 percent. And this impact would pale in comparison to that of a 12- to 36-month worldwide influenza pandemic.

The SARS epidemic also raises questions about how prepared governments are to address a prolonged infectious-disease crisis — particularly governments that are already unstable. Seton Hall University’s Yanzhong Huang concluded that the SARS epidemic created the most severe social or political crisis encountered by China’s leadership since the 1989 Tiananmen crackdown. China’s problems probably resulted less from SARS’ public health impact than from the government’s failed effort to allay panic by withholding information about the disease from the Chinese people. The effort backfired. During the crisis, Chinese Premier Wen Jiabao pointed out in a cabinet meeting on the epidemic that “the health and security of the people, overall state of reform, development, and stability, and China’s national interest and image are at stake.” But Huang believes that “a fatal period of hesitation regarding information-sharing and action spawned anxiety, panic, and rumor-mongering across the country and undermined the government’s efforts to create a milder image of itself in the international arena.”

Widespread infection and economic collapse can destabilize a government; blame for failing to deal effectively with a pandemic can cripple a government. This holds even more for an influenza pandemic. In the event of a pandemic influenza, the level of panic witnessed during the SARS crisis could spiral out of control as illnesses and deaths continued to mount over months and months. Unfortunately, the public is often indifferent to initial warnings about impending infectious-disease crises — as with HIV, for example. Indifference becomes fear only after the catastrophe hits, when it is already too late to implement preventive or control measures.

READY FOR THE WORST

What should the industrialized world be doing to prepare for the next pandemic? The simple answer: far more. So far, the World Health Organization and several countries have finalized or drafted useful but overly general plans. The U.S. Department of Health and Human Services has increased research on influenza-vaccine production and availability. These efforts are commendable, but what is needed is a detailed operational blueprint for how to get a population through one to three years of a pandemic. Such a plan must involve all the key components of society. In the private sector, the plan must coordinate the responses of the medical community, medical suppliers, food providers, and the transportation system. In the government sector, the plan should take into account officials from public health, law enforcement, and emergency management at the international, federal, state, and local levels.

At the same time, it must be acknowledged that such master blueprints may have their drawbacks, too. Berkeley’s Aaron Wildavsky persuasively argued that resilience is the real key to crisis management — overly rigid plans can do more harm than good. Still, planning is enormously useful. It gives government officials, private-sector partners, and the community the opportunity to meet, think through potential dilemmas, purchase necessary equipment, and set up organizational structures for a 12- to 36-month response. A blueprint forces leaders to rehearse their response to a crisis, preparing emotionally and intellectually so that when disaster strikes the community can face it.

Influenza-vaccine production deserves special attention. An initiative to provide vaccine for the entire world must be developed, with a well-defined schedule to ensure progress. It is laudable that countries such as the United States and Vietnam are pursuing programs with long-term goals to develop and produce H5N1 vaccine for their respective populations. But if the rest of the world lacks supplies, even the vaccinated will be devastated when the global economy comes to an abrupt halt. Pandemic-influenza preparedness is by nature an international issue. No one can truly be isolated from a pandemic.

The pandemic-related collapse of worldwide trade and its ripple effect throughout industrialized and developing countries would represent the first real test of the resiliency of the modern global delivery system. Given the extent to which modern commerce relies on the precise and readily available international trade of goods and services, a shutdown of the global economic system would dramatically harm the world’s ability to meet the surging demand for essential commodities such as food and medicine during a crisis. The business community can no longer afford to play a minor role in planning the response to a pandemic. For the world to have critical goods and services during a pandemic, industry heads must stockpile raw materials for production and preplan distribution and transportation support. Every company’s senior managers need to be ready to respond rapidly to changes in the availability, production, distribution, and inventory management of their products. There is no model for how to revive the current global economy were it to be devastated.

To truly be complete, all planning on international, regional, national, and local levels must consider three different scenarios: What if the pandemic begins tonight? What if it starts one year from now? What if the world is so fortunate as to have an entire decade to prepare? All are possible, but none is certain.

STARTING TONIGHT

What would happen today in the office of every nation’s leader if several cities in Vietnam suffered from major outbreaks of H5N1 infection, with a five percent mortality rate? First, there would be an immediate effort to try to sort out disparate disease-surveillance data from a variety of government and public health sources to determine which countries might have pandemic-related cases. Then, the decision would likely be made to close most international and even some state or provincial borders — without any predetermined criteria for how or when those borders might be reopened. Border security would be made a priority, especially to protect potential supplies of pandemic-specific vaccines from nearby desperate countries. Military leaders would have to develop strategies to defend the country and also protect against domestic insurgency with armed forces that would likely be compromised by the disease. Even in unaffected countries, fear, panic, and chaos would spread as international media reported the daily advance of the disease around the world.

In short order, the global economy would shut down. The commodities and services countries would need to “survive” the next 12 to 36 months would have to be identified. Currently, most businesses’ continuity plans account for only a localized disruption — a single plant closure, for instance — and have not planned for extensive, long-term outages. The private and public sectors would have to develop emergency plans to sustain critical domestic supply chains and manufacturing and agricultural production and distribution. The labor force would be severely affected when it was most needed. Over the course of the year, up to 50 percent of affected populations could become ill; as many as five percent could die. The disease would hit senior management as hard as the rest of the work force. There would be major shortages in all countries of a wide range of commodities, including food, soap, paper, light bulbs, gasoline, parts for repairing military equipment and municipal water pumps, and medicines, including vaccines unrelated to the pandemic. Many industries not critical to survival — electronics, automobile, and clothing, for example — would suffer or even close. Activities that require close human contact — school, seeing movies in theaters, or eating at restaurants — would be avoided, maybe even banned.

Vaccine would have no impact on the course of the virus in the first months and would likely play an extremely limited role worldwide during the following 12 to 18 months of the pandemic. Despite major innovations in the production of most other vaccines, international production of influenza vaccine is based on a fragile and limited system that utilizes technology from the 1950s. Currently, annual production of influenza vaccine is limited to about 300 million trivalent doses — which protect against three different influenza strains in one dose — or less than one billion monovalent doses. To counter a new strain of pandemic influenza that has never circulated throughout the population, each person would likely need two doses for adequate protection. With today’s limited production capacity, that means that less than 500 million people — about 14 percent of the world’s population — would be vaccinated within a year of the pandemic. In addition, because the structure of the virus changes so rapidly, vaccine development could only start once the pandemic began, as manufacturers would have to obtain the new pandemic strain. It would then be at least another six months before mass production of the vaccine.

Even if the system functions to the best of its ability, influenza vaccine is produced commercially in just nine countries: Australia, Canada, France, Germany, Italy, Japan, the Netherlands, the United Kingdom, and the United States. These countries contain only 12 percent of the world’s population. In the event of an influenza pandemic, they would probably nationalize their domestic production facilities, as occurred in 1976, when the United States, anticipating a pandemic of swine influenza (H1N1), refused to share its vaccine.

If a pandemic struck the world today, there would be another possible weapon against influenza: antiviral medicine. When taken daily during the time of exposure to influenza, antivirals have prevented individuals from becoming ill. They have also reduced the severity of illness and subsequent complications when taken within 48 hours of onset. Although there is no data for H5N1, it is assumed antivirals would also prevent H5N1 infection if taken before exposure. There is no evidence, however, that current antiviral influenza drugs would help if the patient developed the kind of cytokine storm that has characterized recent H5N1 infections. But barring this complication, H5N1 should be treatable with Tamiflu (oseltamivir phosphate), which is manufactured by the Roche pharmaceuticals company in a single plant in Switzerland.

In responding to a pandemic, Tamiflu could have a measurable impact in the limited number of countries with sizable stockpiles, but for most of the world it would not be available. Although the company plans on opening another facility in the United States this year, annual production would still cover only a small percentage of the world’s population. To date, at least 14 countries have ordered Tamiflu, but the amount of these orders is enough to treat only 40 million people. The orders take considerable time to be processed and delivered — manufacturing can take up to a year — and in an emergency the company’s ability to produce more would be limited. As with vaccines, countries would probably nationalize their antiviral supplies during a pandemic. Even if the medicine were available, most countries could not afford to buy it. Critical antibiotics, for treatment of secondary bacterial infections, would also be in short supply during a pandemic. Even now, supplies of eight different anti-infective agents are limited in the United States due to manufacturing problems.

Aside from medication, many countries would not have the ability to meet the surge in the demand for health-care supplies and services that are normally taken for granted. In the United States, for example, there are 105,000 mechanical ventilators, 75,000 to 80,000 of which are in use at any given time for everyday medical care. During a routine influenza season, the number of ventilators being used shoots up to 100,000. In an influenza pandemic, the United States may need as many as several hundred thousand additional ventilators.

A similar situation exists in all developed countries. Virtually every piece of medical equipment or protective gear would be in short supply within days of the recognition of a pandemic. Throughout the crisis, many of these necessities would simply be unavailable for most health-care institutions. Currently, two U.S.-based companies supply most of the respiratory protection masks for health-care workers around the world. Neither company would be able to meet the jump in demand, in part because the component parts for the masks come from multiple suppliers in multiple countries. With travel and transportation restricted, masks may not even be produced at all.

Health-care providers and managed-care organizations are also unprepared for an outbreak of pandemic influenza today. There would be a tremendous demand for skilled health professionals. New “hospitals” in high school gymnasiums and community centers would have to be staffed for one to three years. Health-care workers would probably get sick and die at the same rate as the general public — perhaps at an even higher rate, particularly if they lack access to protective equipment. If they lack such fundamental supplies, it is unclear how many professionals would continue to place themselves in high-risk situations by caring for the infected. Volunteers who are naturally immune as a result of having survived influenza infection would thus have to be found and employed. That means that the medical community’s strong resistance to using lay volunteers, which is grounded in both liability concerns and professional hubris, would need to be addressed.

Other unpleasant issues would also need to be tackled. Who would have priority access to the extremely limited antiviral supplies? The public would consider any ad hoc prioritization unfair, creating further dissent and disruption during a pandemic. In addition, there would not even be detailed plans for handling the massive number of dead bodies that would soon outstrip the ability to process them. Clearly, an influenza pandemic that struck today would demand an unprecedented medical and nonmedical response. This requires planning well beyond anything devised thus far by any of the world’s countries and organizations.

A YEAR FROM NOW

Even if an H5N1 pandemic is a year away, the world must plan for the same problems with the same fervor. Major campaigns must be initiated to prepare the nonmedical and medical sectors. Pandemic planning must be on the agenda of every school board, manufacturing plant, investment firm, mortuary, state legislature, and food distributor in the United States and beyond. There is an urgent need to reassess the vulnerability of the global economy to ensure that surges in demand can be met. Critical heath-care and consumer products and commodities must be stockpiled. Health professionals must learn how to better communicate risk and must be able to both provide the facts and acknowledge the unknowns to a frightened or panicked population.

If there is a year of lead-time before an H5N1 pandemic, vaccine could play a more central role in the global response. Although the world would still have a limited capacity to manufacture influenza vaccine, techniques that could allow scientists to get multiple doses from a current single dose may increase the supply. In addition to further research on this issue, efforts are needed to ensure the availability of syringes and equipment for delivering vaccine. There must also be an international plan for how the vaccine would be allocated. It is far better to struggle with the ethical issues involved in determining such priorities now, in a public forum, rather than to wait until the crisis occurs.

Prevention must also be improved. Priority should be placed on early intervention and risk assessment. And an aggressive and comprehensive research agenda must be launched immediately to study the ecology and biology of the influenza virus and the epidemiologic role of various animal and bird species.

TEN YEARS LATER

If developed countries begin to transform radically the current system of influenza-vaccine production, an influenza pandemic ten years from now could have a much less devastating outcome. The industrialized world must initiate an international project to develop the ability to produce a vaccine for the entire global population within several months of the start of a pandemic. The initiative must be a top priority of the group of seven industrialized nations plus Russia (G-8), because almost nothing could inflict more death and disruption than a pandemic influenza.

The current BioShield law and additional legislation recently submitted to Congress will act to enhance the availability of vaccines in the United States. This aim is laudable, but it does little to address international needs. The ultimate goal must be to develop a new cell-culture vaccine or comparable vaccine technology that works on all influenza subtypes and that can be made available on short notice to all the people of the world.

WHAT COURSE TO TAKE?

The world must form a better understanding of the potential for the emergence of a pandemic influenza strain. A pandemic is coming. It could be caused by H5N1 or by another novel strain. It could happen tonight, next year, or even ten years from now.

The signs are alarming: the number of human and animal H5N1 infections has been increasing; small clusters of cases have been documented, suggesting that the virus may have come close to sustained human-to-human transmission; and H5N1 continues to evolve in the virtual genetic reassortment laboratory provided by the unprecedented number of people, pigs, and poultry in Asia. The population explosion in China and other Asian countries has created an incredible mixing vessel for the virus. Consider this sobering information: the most recent influenza pandemic, of 1968-69, emerged in China, when its population was 790 million; today it is 1.3 billion. In 1968, the number of pigs in China was 5.2 million; today it is 508 million. The number of poultry in China in 1968 was 12.3 million; today it is 13 billion. Changes in other Asian countries are similar. Given these developments, as well as the exponential growth in foreign travel over the past 50 years, an influenza pandemic could be more devastating than ever before.

Can disaster be avoided? The answer is a qualified yes. Although a coming pandemic cannot be avoided, its impact can be considerably lessened. It depends on how the leaders of the world — from the heads of the G-8 to local officials — decide to respond. They must recognize the economic, security, and health threat that the next influenza pandemic poses and invest accordingly. Each leader must realize that even if a country has enough vaccine to protect its citizens, the economic impact of a worldwide pandemic will inflict substantial pain on everyone. The resources required to prepare adequately will be extensive. But they must be considered in light of the cost of failing to invest: a global world economy that remains in a shambles for several years.

This is a critical point in history. Time is running out to prepare for the next pandemic. We must act now with decisiveness and purpose. Someday, after the next pandemic has come and gone, a commission much like the 9/11 Commission will be charged with determining how well government, business, and public health leaders prepared the world for the catastrophe when they had clear warning. What will be the verdict?

www.foreignaffairs.org is copyright 2002–2005 by the Council on Foreign Relations. All rights reserved.

2 Responses to “‘Avion Flu’: Bush and the Senate mark the Year of the Rooster”

  1. Marcel Says:

    Truthseeker, this “Bird Flu” bullshit is much more cynical than you imagine. Has anyone even proved that the 100 or so people claimed to have died from bird flu really died from it? No, they just find the virus in them and assume that’s what killed them.Has this virus even been isolated by strict isolation protocol?This thing is so transparently phony I don’t know why people don’t just laugh these WHO stooges off the world stage. It’s perfectly clear what all the fuss is about. The idea is to give the taxpayers’ money to Roche and the rest of the “public health” establishment. And to do that you have to invent a “crisis.” Inventing crises seems to be the number one preoccupation with the power elite these days. The WHO and FAO and most UN agencies are now essentially “public-private partnerships,” with massive funding coming from corporations. Their job is to provide the scaremongering that gives justification for making massive welfare payments to these corporations, disguised as “essential public health measures.”And I trust you know that the Council on Foreign Relations is David Rockefeller’s baby, and has been providing the intellectual pretexts for the Rockefellers’ financial interests for around 80 years if I’m not mistaken.The second major reason for “bird flu” is to end backyard chicken and duck farming, which is omnipresent in the Third World, so that agribusiness can have a monopoly on all poultry raising. Since backyard bird farming is the way millions of 3rd world people make ends meet, you can expect more poverty after this happens. And the power elite are indeed calling for this small scale farming to end.The third major reason for “bird flu” is just to frighten people out of their wits so they will permit the elite to continue to accelerate the globalization process, which will eventually produce total centralized world dictatorship. Globalization, not surprisingly, is the major preoccupation of the Council on Foreign Relations.There is absolutely no proof that the 1918 “flu epidemic” was caused by any virus. What seems more likely is that, first of all, estimated numbers of deaths are wildly exaggerated in order to terrify people and make them submit to the Public Health gang’s will. Secondly, deaths from all sorts of causes were lumped together and called “flu.” Thirdly, a great deal of evidence suggests that it was widespread vaccinations, not any virus, that caused most of the deaths.We are in the era of total corruption. This is freedom’s endgame I’m afraid.

  2. Truthseeker Says:

    Marcel, thank you for your comment but I do believe you are carrying an admirable habit of skepticism too far into cynicism. I completely agree with inspecting carefully what the authorities tell us, but in this case it seems to me that now they have sequenced the virus, they have pretty much nailed it.On the other hand I realize that my opinion is worthless until I have read much more about the 1918 flu and the current situation to see if the story is convincingly supported against the kind of alternative narrative you suggest.Unfortunately that kind of reading which so few people have time for these days is the only route to confirming this kind of narrative. Even those in authority are very often unable to do it themselves, as AIDS has shown so clearly.In the great new mega-information era, we seem to be as much at a loss as ever in knowing whether to trust scientific and medical paradigms, or conventional wisdom of any kind, without looking into it ourrselves. If anything, the early years of thge Internet have served to expose more reasons to doubt than to confirm conventional wisdoms. That’s why we need trustworthy and informed critics in science and medicine who can help sort it all out for us, which is the aim of this site. How many informed critics can there be, however, unless they are well funded? The tendency of paranoia to run free seems likely only to grow in the short run. Buit in the long run, I believe, it will all be sorted out.But that is why we try in this blog to be responsible in our claims, rather than give our suspicions full rein in the absence of full information.

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