Body To Be Exhumed For Bird Flu Clues

[george]

Body to Be Exhumed for Bird Flu Clues

A victim of the world’s worst epidemic is due to be exhumed to help scientists trying to avert the spread of bird flu, it was revealed today.

Scientists plan to remove lung samples from the body of 20-year-old Phyllis Burn, who was buried in London 85 years ago.

The Army officer’s daughter, from Strawberry Hill, south west London, was one of 50 million people killed by a devastating strain of influenza that swept across the world in 1918.

Evidence points to the 1918 virus being a type of bird flu similar to the one now claiming human lives in Asia.

Scientists are desperate to know more about what caused the pandemic in order to avoid another disaster on the same scale.

Investigation leader Professor John Oxford, from Queen Mary’s School of Medicine in London, said: “The big question is was there something special about this virus that enabled it to kill 50 million people, was there something special about the people that led them to die so quickly, or was it a combination of the two?

“No-one expects the 1918 virus to come back again, but there is the possibility of a new virus arising in the same way today.”

Miss Burn was buried in a lead coffin, which, if properly sealed, would have been virtually airtight.

Prof Oxford hopes that even after more than 80 years her internal organs will be sufficiently preserved to allow tissue samples to be taken from her lungs.

The scientists are looking for a “genetic footprint” – fragments of RNA – left by the 1918 virus that could yield important clues.

Professor Oxford said although he did not believe there was any way the virus could come back to life, his team was taking no chances.

The researchers would wear special containment suits as they extracted tissue samples from the body in situ.

They would work within a tent erected over the grave, and the body itself would not be moved from the cemetery in Twickenham.

Back at the laboratory the first job would be to screen the samples for any sign of dangerous virus.

“I don’t think there is any chance of finding an infectious virus, but you never know,” said Prof Oxford. “We are treading into the unknown a little bit.”

Only a handful of samples from the 1918 pandemic exist in Britain and the United States. They consist of small lung “blocks” about half the size of a sugar cube.

Scientists have already managed to identify half a dozen of the virus’s genes. The clues point to an avian, or bird, virus – but not the same strain as the one currently worrying health officials in Vietnam and Thailand.

The 1918 virus was an H1 strain, whereas the virus responsible for the new outbreaks is categorised as H5.

In Vietnam at least six people have been killed by the infection and two other cases have been confirmed.

The World Health Organisation said yesterday that two other deaths being investigated in Vietnam had been prematurely blamed on the virus.

Thailand says the virus has been detected in about a third of its 76 provinces, including Bangkok, and China is halting exports of poultry from regions suspected of being affected.

At present the virus does not seem capable of passing from person to person, as happened in 1918.

The greatest fear of experts is that it will genetically combine with normal human flu to produce an infection that can sweep through populations.

“That’s the Armageddon scenario – that the two will mix together,” said Prof Oxford.

A key question scientists want answered is whether such a combination triggered the 1918 pandemic.

Prof Oxford has spent a year clearing obstacles in the way of the exhumation, but believes he is now “95% there”.

First, permission had to be obtained from the relatives, who had to be traced. The Home Office, Health and Safety Executive, and the ethics committee that vets research at St Mary’s also had to approve the move.

Finally, consent had to be sought from the church authorities in charge of the cemetery. This is still continuing.

Prof Oxford admitted that the exercise was a “long shot”. Success depended on the coffin being sealed and airtight. But he said if Miss Burn failed to yield any useful samples there were nine other bodies buried in lead coffins in south London that could be examined.

The investigation will be featured in a BBC Radio 4 programme, “Flu: A Medical Mystery” to be broadcast on Monday.

--P A News/Scotsman.com

[george]

Bird-flu blueprint sees up to 58,000 deaths

Health Canada's preparedness document says pandemic would hit children, elderly

CANADA: If avian flu becomes pandemic, as many public-health officials fear, it could kill as many as 58,000 people in Canada alone, according to Health Canada.

As part of a detailed pandemic preparedness plan, epidemiologists estimate that a new strain of influenza, such as one that jumps from birds to humans, could kill 11,000 to 58,000 Canadians in a matter of weeks.

Those hardest hit would likely be young children and the old, whose immune systems are least able to fight off infection.

The disease could also put 35,000 to 138,000 people in hospital and leave between 4.5 million and 10.6 million others too sick to work, which could have a devastating economic impact.

"Obviously, our goal is to minimize death, serious illness and social disruption, which is why we have developed a pandemic preparedness plan," said Arlene King, director of the immunization and respiratory diseases division of Health Canada.

In a normal year, influenza kills 4,500 to 9,000 Canadians, and more than 500,000 people worldwide. New flu strains develop each year, but vaccines are available and many people have at least partial protection because they have been exposed to flu in the past.

The danger of a pandemic arises only when an entirely new form of influenza emerges. A strain of avian flu, H5N1, is spreading among birds in Asia. With the deaths yesterday of two sisters in Vietnam, it has killed 10 people.

While that number is modest, the widespread infection of chickens and other poultry in at least 10 Asian countries and the growing number of cases in humans has public-health officials fearing the worst. The worry is that H5N1 could swap genes with a human influenza virus, creating a dangerous strain that could spread from person to person.

It is that possibility that public-health officials are girding for worldwide. They met yesterday in Bangkok for an emergency conference to co-ordinate the response to a potentially deadly outbreak. The emphasis now is on culling and quarantining birds, but surveillance has been stepped up and laboratory work on developing a vaccine is under way.

The World Health Organization estimates that a pandemic flu could spread around the world in about six months, posing a "serious global threat to human health."

While the WHO has not released detailed mortality estimates, officials say an avian influenza outbreak could rival the Spanish flu pandemic, which killed up to 40 million people in 1918-19. Two other pandemics occurred in the past century: so-called Asian influenza in 1957 and Hong Kong influenza in 1968.

Since then, vaccines were developed to protect against influenza.

According to the WHO, it would take about one month after a pandemic strain is identified to produce a "seed flu strain." After that, it would take manufacturers four to six months to develop a vaccine to protect humans against avian influenza.

But Dr. King said Canada is so well prepared that it could produce a vaccine from the seed strain within 48 days: Canada is the only country that has a contract that ensures a secure domestic supply of vaccine. The government signed the deal with Shire Pharmaceuticals Group PLC of Laval, Que. It has a plant that is able to manufacture six million doses a month.

(An influenza vaccine cannot be produced instantaneously because the key component needs to be grown in chicken eggs. With the avian flu, there is an added technical problem: Exposure to H5N1 could kill the chickens that lay the eggs. But Dr. King said that problem could be overcome using a method known as reverse genetics, in which vaccines are made in cell culture instead of eggs, although it is much more expensive.)

The pandemic preparedness plan, to be published in about two weeks, is designed to guide the actions of government and health officials. It spells out priority lists for immunization, plans for minimizing exposure and even "recovery plans" for health-care facilities after a pandemic.

--Guardian

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Potential for bird flu pandemic is real

The illness began with a headache like the blow of a sledgehammer. The victims shook with chills and burned with fever, and they whispered of agonizing muscle aches. They fought for breath as their lungs filled with fluid; as their bodies were starved of oxygen, their skin turned the deep gray of roofing slates. Within days -- sometimes within hours -- they died.

The first cases showed up in Boston, but the infection raced across the country on every road and railroad. In two weeks, Florida. In a month, California. In a single week, 2,000 people died in Chicago, 3,000 in Philadelphia, and more than 5,000 in New York.

Buffalo ran out of coffins. Philadelphia ran out of gravediggers. In Atlanta, every public gathering was banned.

The year was 1918. The disease was influenza. A common virus had produced a brand-new strain, one never seen before. Within 11 months it killed 675,000 Americans, and as many as 50 million people around the world.

Today, world health authorities are anxiously watching Southeast Asia, where a new strain of flu virus has spread to at least nine countries, infecting an unknown number of people and killing at least 10.

When they imagine the possible forms the unfolding epidemic could take, 1918 is what they see.

"I feel totally powerless," said Dr. Arnold Monto, a flu authority at the University of Michigan, "to do something about what I think is a potentially dangerous situation."

Born among birds

Influenza is a constant winter companion for humans. Every year it sickens 10 percent to 20 percent of the U.S. population with fever, aches and cough. Most recover, though in an average year flu kills up to 36,000 Americans, many of them elderly.

Roughly every 30 years, though, influenza gets dramatically worse and causes what is known as a pandemic: large outbreaks in widely separated parts of the world at roughly the same time. The last three pandemics occurred in 1968, when 700,000 died worldwide; 1957, when 100,000 died; and 1918.

In every case, science discovered afterward that the influenza virus had undergone a sudden and dramatic genetic shift. People whose immune systems had gotten used to the currently circulating flu viruses, and had evolved some defense against them, had no protection against the new strain. It struck with extraordinary force.

The virus causing the Southeast Asian "bird flu" -- influenza A H5N1 -- is as new to humans as possible: It is a disease of waterfowl and poultry, according to analyses done in Hong Kong and at the Centers for Disease Control and Prevention in Atlanta.

Recent genetic sequencing has shown that the viruses in the three previous pandemics had at some point crossed over from birds as well.

At the moment, every confirmed human victim in Asia is believed to have been infected by a bird: The virus made one jump, between species, but then ran out of steam. Scientists are bracing for the possibility that, at some point, the chain of transmission will not stop, but continue from person to person.

Virologists agree that for the bird flu to pass from person to person, it would have to shift genetically, acquiring the infectiousness that human flu already possesses. That could happen if a person already infected with common human flu -- this year, the strain H3N2 -- also acquired the bird flu virus; within that person's body, the two viruses could swap genes.

Experts say the swap becomes more likely as the bird flu spreads and more people are exposed. Already it has spread from Japan to Indonesia and as far west as Thailand.

And epidemiologists say the location of the epidemic sharpens the odds. Southeast Asia, particularly southern China, is the historic home of new flu strains -- millions of rural people there keep a pig and a few chickens or ducks, putting them in constant contact with the species that harbor nonhuman flu.

On Friday, the official Chinese news agency Xinhua confirmed that H5N1 now is suspected in three more Chinese provinces, added to the three where it already has been found.

"This is the perfect storm," said Michael Osterholm, who heads the Center for Infectious Disease Research and Policy at the University of Minnesota. "The only question now is: Will this set of circumstances be sufficient to push the microbial genetics over the edge and create a new strain of influenza virus that rivals past pandemic strains?"

Several risk factors

When health authorities select which disease threats to focus on, they tick off a mental list of danger signs. A disease is considered troublesome if it spreads rapidly, cannot be stopped by isolating victims, and has severe consequences. Avian influenza passes all those tests and more.

"Add to that the fact that a vaccine is not presently in hand and may be hard to make," said Dr. Jeffrey Koplan, the CDC's former director, who is now vice president for academic health affairs at Emory University. "And there is no way to treat it when people get it -- or at least we are not sure that we can treat it well."

Even in an average flu year, flu vaccine is a challenge. Flu viruses have the genetic quirk of making many small errors when they reproduce. The result, from the point of view of the immune system, is a virus slightly different from the previous flu season, but different enough that last year's flu shot cannot protect against it. Thus flu vaccines must be reformulated each year.

When everything goes well, the six-month process produces just enough vaccine just in time for the start of flu season. When it goes badly, as it did this winter -- because the A/Fujian strain of human flu emerged last spring, too late to be included in the vaccine formula -- flu cases and flu-related deaths rise.

If avian influenza became human-adapted, the process would be more complicated, virologists say. The H5N1 virus is so dangerous to chickens that only labs possessing high levels of biosafety protection, such as those at the CDC, are allowed to handle it. For the virus to be released to vaccine manufacturers, it must first be reverse-engineered to remove the lethal portion. That step is necessary whether the vaccine is to be produced the old way, in chicken embryos -- which the unaltered virus would kill -- or via the new technology of cell culture.

Reverse engineering takes at least a month. Three labs -- at the CDC, St. Jude's Children's Research Hospital in Memphis, and the National Institute for Biological Standards and Control in London -- began the viral tinkering last week.

Once a pandemic is identified, "it will still take four to six months before a significant amount of vaccine can be produced," Dr. Klaus Stohr, project leader for influenza surveillance in the World Health Organization's H5N1 Outbreak Response Group, said last week.

Eleven pharmaceutical companies have expressed interest in manufacturing a vaccine once the virus is reverse-engineered, Stohr said, though they could not begin immediately because they currently are making flu vaccine for the upcoming flu season in the Southern Hemisphere, where autumn arrives in June.

Stohr acknowledged that flu could spread faster than any vaccine could be produced.

"If a pandemic virus would emerge, then we would presume -- these are estimates based on historical data -- that this virus might travel around the world in a relatively short period of time," he said.

And a recent CDC computer model projects the worst-case scenario: If pandemic influenza came to the United States, it would cause 20 million to 47 million cases of illness and 89,000 to 207,000 deaths.

There is some hope, health authorities say.

If infection with avian influenza cannot be prevented by vaccination, it might be slowed down by other drugs. There are two classes of antiviral drugs -- adamantanes and neuraminadase inhibitors -- that can slow down the process by which flu takes hold in the body, reducing the severity of the symptoms and the risk of death.

But WHO analysis of the H5N1 strain recovered from recent victims in Vietnam shows that it is unaffected by adamantanes. That leaves only two neuraminadase inhibitors -- oseltamivir and zanimivir, known in the United States as Tamiflu and Relenza -- to blunt the impact of a pandemic if one develops.

Defenses are weak

WHO recommended Friday that countries stockpile anti-virals. But both drugs are new, and supplies are limited. Last week, the CDC, WHO and the Canadian government all said separately that they were discussing buying the drugs from their manufacturers. However, neither drug exists in sufficient quantity to fill all those orders.

It is unclear how rapidly the two manufacturers -- Tamiflu's Roche Pharmaceuticals and Relenza's GlaxoSmithKline -- could spool up production. Late last week, Roche said it had enough Tamiflu in reserve to dose the thousands of workers engaged in the preventive slaughter of chickens and ducks in Southeast Asia. Giving Tamiflu to the slaughterers would suppress any human flu virus in their bodies, preventing it from combining with avian viruses shed by the dying birds.

As the flu spread last week, a reluctant consensus emerged among health authorities: Despite years of warnings and a clear advance understanding of the risks, there are no mechanisms in place that could adequately brake a worldwide outbreak of avian-to-human flu.

"If we are lucky and dodge this bullet, we should remember that we are not prepared for pandemics," Monto said. "And you cannot prepare for a pandemic once it rears its ugly head."

--Atlanta Journal/AP 2004-02-01