Avian Influenza: A Ticking Time Bomb?
"Maybe more than 100 million deaths in a few weeks worldwide."

This worst-case scenario was brought up in one of our medical school microbiology lessons covering viral infections and the dangers of flu (influenza). All the students were suddenly very quiet. The professor's statement also peaked my interest in one of the most important global challenges of the 21st century.

On March 12, 2004, the World Health Organization (WHO) in accord with representatives from different countries and the pharmaceutical industry underlined the urgent need for the development of a vaccine against dangerous variations of the flu virus.

There is a "unique window of opportunity" to avoid a horrific pandemic, explained Dr. Klaus Stöhr, director of the WHO's global influenza program. He said it would be costly, but there are no alternatives.

A cruel lesson ahead for mankind

Since the early days of global air travel, scientists have warned that one day humankind will face a remorseless enemy. They say this enemy will be an aggressive and highly infectious virus, which, due to modern air traffic, will spread all over the world within days.

Some scientists are afraid that mankind will not consider preventative measures as necessary until it is too late.

As we have seen, the Ebola virus frequently kills many in Central Africa, and movies like "Outbreak" (1995) and "Twelve Monkeys" (1996) have infected cinema visitors worldwide. But as usual, it takes more than alarming movies or so-called "Third World" tragedies for governments to open their coffers and fund essential scientific investigations.

Naturally, before the Hong Kong outbreak of 1997, mankind tended to think of global pandemics as being scourges of the past. But the bird flu (avian influenza) pathogen H5N1, which was believed to only affect bird species, ended up infecting 16 people and killed four. Since this occurred next to an international airport, concerns were raised whether H5N1 could be the beginning of a deadly global pandemic.

With every year that passed, the virus continued to spread over East Asia. It forced national governments in China, Vietnam, Thailand, Indonesia, Japan and South Korea to kill millions of potentially infected poultry. The virus killed about 70 persons worldwide and at least 13 already in 2005.

But how can a virus that kills less than 100 people over a period of four years incite governments, the pharmaceutical industry and the food industry to institute the necessary, expensive measures and intensified research?

The answer is that back in September 2004 in Thailand, H5N1 has already been transmitted from human to human. Such vectors cannot be ruled out anymore and the virus may someday become a primarily human affliction.

The danger: An H5N1/H3N2-mutant

Around 16,000 people annually die of the common flu in Germany. One of the most important of these human-afflicting subtypes of the influenza virus is the pathogen type H3N2. Many of these deaths, often referred to as pneumonia, could be avoided.

A Swedish study conducted from 1996 to 1999, including 100,242 people over 65, demonstrated that annual vaccinations were able to reduce influenza-related hospital treatment by 46 percent and serious cases of influenza by 29 percent. The numbers of deaths were reduced by 57 percent.

When the power of the human immune system weakens from the age of 35 onward, the risk of infections rises. So those most at risk are unvaccinated people over the age of 65 and those with a weak immune system like HIV patients, people undergoing chemotherapy or who have an otherwise compromised immune system and children.

In contrast to the common flu, the bird flu seems to have the potential to more readily afflict people with a normal immune system. Moreover, H5N1 more often leads to death than H3N2.

There remains no vaccination for bird flu. Flu vaccines are produced when eggs are infected with the common flu viruses. The procedure takes four months on average. This fact alone demonstrated that current health care systems are unable to adequately react to a possible outbreak.

The major problem, however, is that the virus does not only kill birds (and humans), but also destroys the eggs of hens needed for industrial vaccine production.

If H5N1 ever succeeds in combining with H3N2 -- and if this hybrid does not lose its deadly effect -- the then "former bird flu" will spread like the common flu. This kind of nightmare hybrid may appear when a person is simultaneously infected with both virus types. Such a scenario underlines the necessity of vaccinating older people against the common flu, in the interest of the individual and the general population.

There is another possibility for hybrid creation, too: pigs. Both the bird flu virus, H5N1, and the common flu virus, H3N2, manage to survive in pigs. Naturally, within the pig's body an H5N1/H3N2-mutant can be formed.

The American Centers for Disease Control (CDC) high-security labs in the city of Atlanta are trying to artificially combine both types. The scientists' intention is to determine whether a hybrid form can be created and if it will harbor its deadly attributes.

Strategies to avoid the worst-case scenario

In order to avoid a scenario that eclipses the Spanish Flu Pandemic of 1918, important steps have to be taken by national governments and individuals.

One is to end mass animal-husbandry. Too many individuals are kept in too little space, exposing them to massive social stress in which diseases find a perfect environment to develop. The same argument is valid for slums and refugee camps. Ending poverty helps contain infectious diseases.

Furthermore, pigs and poultry must be kept separate on these massive agricultural plots.

Another important step is to inoculate the population, especially older citizens, with the (completely safe) flu vaccines, not only to rule out recombination of H5N1 and H3N2 genes in the human body, but to effectively determine whether a person suffers from the common flu or the bird flu.

In addition, new strategies to create vaccines that can be produced within a few days, independent from the eggs of hens, must be investigated. Several pharmaceutical companies are actually working to find new ways to produce such flu vaccines.

Maybe the most important measurement is to check every passenger before he or she departs on an international flight. We should not just worry about people carrying knives onboard, but ensure that he or she is not ill. If a global pandemic starts, like during the days of SARS, international air traffic must be reduced to a bare minimum.

Last, but not least, new medications have to be developed to treat persons suffering from the flu. At the moment there are only so-called "neuraminidase inhibitors" to which virus types can rapidly adapt

http://english.ohmynews.com/articleview/ar...1&isPrint=print

Avian influenza – situation in Cambodia - update 15

12 April 2005

The Ministry of Health in Cambodia confirmed that an 8-year-old girl from Kampot province who died on 7 April, was the country’s third case of avian influenza.

The girl became ill with a fever on the 29th March. Her condition deteriorated rapidly on 7 April, when she was taken to a district referral hospital and then transferred to Kuntha Bopha Hospital in Phnom Penh, where she died. Samples from the girl tested positive for avian influenza H5N1 virus at the Pasteur Institute, Phnom Penh.

A field investigation was conducted immediately, with team members from the Ministry of Health, Ministry of Agriculture, WHO, Pasteur Institute and FAO. Poultry deaths occurred in this village in February, but no poultry deaths occurred in the two weeks prior to the girl’s onset of symptoms. Human-to-human transmission as a source of the girl’s infection appears unlikely, as none of her known contacts were sick with similar symptoms before she became ill. Investigations as to the source of the girl’s infection are continuing.

Samples were collected from four close contacts who cared for her at the village and nine medical contacts from Kampot and Phnom Penh. All have tested negative for the H5N1 virus.

The public education campaign in Banteay Meas and neighbouring districts is continuing. The recent funding from international donors will be crucial in helping Cambodia control this disease.

Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) since 28 January 2004

http://www.who.int/csr/don/2005_04_12/en/

Bird Flu Adds New Danger to Bloody Game
Cockfighting Among Asian Customs That Put Humans at Risk
By Alan Sipress
Washington Post Foreign Service
Thursday, April 14, 2005; Page A16


CHIANG RAI, Thailand -- As the pair of fighting cocks lunged at each other through the air, spectators surged against the edge of the ring with anticipation.

Feathers flew. Blood oozed from wounded eyes and throats.

Phapart Thieuviharn, a lifelong cock breeder with intense brown eyes and black hair speckled with gray, shifted anxiously on the edge of his seat in the concrete bleachers, clutching the notepad on which he had scribbled his bets. Within moments, when one of the roosters surrendered to its injuries and retreated, hundreds and perhaps thousands of dollars would change hands in the arena, located down a dirt track deep in the rice paddies of northern Thailand.

But Phapart and 125 other spectators were wagering more than banknotes. According to international health experts, they were gambling with their lives.

Cockfighting, popular in many parts of Southeast Asia, is suspected of spreading the highly lethal bird flu virus from poultry to humans through contact with blood, feces and droplets of fluid. It is one of several cultural practices, including the eating of raw duck blood and the raising of chickens in back yards, that are threatening to help spark a global pandemic that the World Health Organization warns could kill tens of millions of people.

For centuries, these practices posed no human threat. But a dramatic increase in poultry farming in the region in the past 15 years has allowed avian influenza to become entrenched in the bird population. Now, these cultural routines represent a potential springboard for a human epidemic.

"There will be opportunities for the virus to take advantage of these practices," said Klaus Stohr, director of WHO's global influenza program. "They didn't cause trouble before, but now they do."

So far, the virus has killed 71 people in Southeast Asia. Though it remains difficult for a person to catch the disease from someone else, each human case presents a chance for the virus to mutate genetically, making it far easier to spread that way and spawn an epidemic.

Vietnamese have traditionally eaten a dish called tiet canh vit, prepared from duck blood, stomach and intestines, to mark the anniversary of a death in the family and other special occasions. Health investigators suspect that as many as five people from two families near Hanoi contracted bird flu this year after dining on this pudding.

Markets in several countries, including Vietnam and Cambodia, have long sold live chickens and ducks, but health experts now warn that the virus can be spread by sick birds to other poultry and to people who buy and sell them, especially if they do not wear protective gear. At Phnom Penh's cavernous Orussey Market, for instance, live chickens and ducks are hawked on muddy floors, where they are crammed together, legs bound. In the warren of aisles, peddlers with bare hands butcher, pluck and wash them.

Millions of villagers across the region, meanwhile, raise chickens in their back yards and even inside their homes. When the birds fall sick, villagers are more likely to eat them than dispose of their bodies, U.N. agriculture officials say.

Often, the home-raised birds are fighting cocks. In Thailand alone, estimates put their number in the millions. According to WHO and local news reports, infected fighting cocks may have caused at least eight confirmed human cases of avian influenza in Thailand and Vietnam since the beginning of 2004.

In September, the virus killed an 18-year-old Thai man who raised fighting cocks outside Bangkok. Thai health officials said he had the habit of sucking mucus and blood from the beaks of his injured roosters and sometimes even slept with his birds. Earlier last year, a 13-year-old boy who frequented cockfights in Vietnam's Ho Chi Minh City and often held the birds before the bouts also succumbed to the disease.

Phapart, 47, recalled learning to raise cocks from his father and grandfather. As a boy, he refused to go to the barbershop unless he could take along his favorite rooster. As a teenager, he rose hours before school began to train his cocks and then pitted them against those of his teacher.

"When you raise fighting cocks, you see them from the moment you open your eyes in the morning. You can even recognize the way each one coos," Phapart said, wearing a green work shirt and chomping on an ever-present piece of gum. "You have a very close relationship with your fighting cocks, and the closer you are, the more confident you are about their health. You know their condition."

Emphasizing each word somewhat defensively, he added, "That is why I am not afraid."

On a recent Sunday, Phapart pulled up at the cockfighting arena as the dirt parking lot was beginning to fill with pickup trucks. Spectators, mostly men from surrounding provinces, crowded three rows of concrete bleachers below a corrugated metal roof.

As the elegant, long-legged roosters began to stalk each other, cries rose from the crowd. Many people barked out wagers. Most pressed closer, in some cases leaning into the ring.

It is this proximity to the blood and breath of the frenetic fighters that can make cockfighting so hazardous to humans. But the intimacy of the owners and trainers with their birds also poses a profound danger.

Between the 20-minute rounds, the owners scrubbed the blood off their birds with bare hands, wringing out the rags on the ground. Then, with ordinary thread, they stitched the wounds around their eyes and fed them painkillers. Sometimes, Phapart recounted as he watched the hurried surgery, the injuries are so severe that owners relieve the swelling by sucking out the blood by mouth.

A day earlier, Phapart had made the rounds in his home town of Phayao, where he is admired as one of the most accomplished breeders, and offered advice to other owners. Not a word was uttered about bird flu.

At his first stop, a farmhouse on the edge of town, two trainers were teaching young cocks to feint and dart by thrusting more seasoned roosters toward them. The men clasped the birds in their bare hands, and their forearms were scarred and swollen from the errant attacks of their pupils.

"Train harder," Phapart told them. "They're not really strong enough."

At the next stop, a large exercise facility where several roosters had just completed their morning sparring, the trainer was bathing them with a hot, moist towel, scrubbing each feather individually and massaging their muscles. Then, with his fingertips, he fed them a special dish made from the minced flesh of a river fish famed for its brawny nature, mixed with honey and herbs.

Fighting cocks represent a lavish investment. A proven winner can sell for as much as $2,500, Phapart said.

That is why some owners hid their roosters when Thai officials ordered the mass culling of poultry to contain the bird flu epidemic. Others have smuggled cocks across provincial lines, potentially spreading the disease. Officials in Malaysia blamed the outbreak in the north of their country in September on fighting cocks illegally transported from Thailand.

Thai officials have imposed a system of fighting cock passports that requires owners to get a veterinarian's stamp before taking their birds into another district. Though Phapart said he obeyed these rules, he acknowledged that many villagers did not.

But Phapart dismissed the government's worries about bird flu as overblown and its proposals as unworkable. "The decision-makers analyze the situation just on paper," he said, growing agitated. "Their feet aren't on the ground. They don't really know how we treat the cocks and don't really share our feelings."

He urged that the owners of fighting cocks be left to police themselves because, in his view, they have the most to lose if the virus spreads among the birds. "We care more for the fighting cocks than the health officers do," he argued.

Last summer, roosters on Phapart's family farm in Chiang Mai province developed flu symptoms. Instead of informing the government, he said, he slaughtered all 600 and burned their bodies. For good measure, he gave away 10 others he was keeping in bamboo cages behind his house for fear they might catch the virus.

He has already restocked. The new birds are still young, he said, cradling one in his arms, but he likes their looks. They may even grow to be champions like his beloved rooster Lucky, who died undefeated and whose framed photograph hangs in Phapart's living room.

Phapart leaned forward intently and vowed, "They'll never be able to stop us from doing cockfighting."

http://www.washingtonpost.com/ac2/wp-dyn/A...anguage=printer

Flu error prompts promise of controls Boston Globe

US Seeks Cause of Flu Virus Mix-up Forbes

ABC Nightline did a program last night on the mixup about the flu virus getting out and the Avian flu.

Flu Viruses made prior to 1969 if out in public would cause epidemics because most people have not been vaccinated against that strain of flu. About 4000 samples were sent out by mistake this week. The labs were told to destroy them, but the government has no security systems to ensure it.

Commentary

Efficient Transmission of H5N1 in Northeast Vietnam

Recombinomics Commentary
April 7, 2005

>> I know that many of you have dedicated your careers to this field. In the short time that I have been Secretary of Health and Human Services, I have become acutely aware of the disastrous public health impact that an influenza pandemic could have throughout the world. This is one of the most urgent health challenges we face, and I've made it a top HHS priority. Recently, I increased my briefing frequency on the flu to daily......

In order to increase our readiness against a pandemic strain of influenza, last Friday, on my recommendation, President Bush added pandemic influenza to the list of quarantinable events. This gives HHS the authority to take steps to prevent people with a new or reemerging influenza virus from infecting others by stopping them at our borders. <<

The above remarks by US Health and Human Services Secretary Mike Leavitt, support the comment that an H5N1 infection of a 34 year-old physician at Vietnam-Sweden hospital in Quang Ninh led to the executive order of April 1, allowing the US to quarantine bird flu cases.

The monitoring of the outbreak in the US has been elevated to a daily briefing, which almost certainly includes additional notifications of unusual events. Therefore, when the physician developed Acute Respiratory Distress Syndrome (ARDS) on Friday, April 1, in Vietnam (Thursday night in the US), he was probably tested with a quick test for H5N1. When he tested positive, an alert was issued.

This alert then went to HHS in the US, which resulted in the recommendation for the executive order, which was signed on April 1.

It is unclear if the three suspect bird flu cases at the hospital were patients who were recently admitted because of bird flu symptoms, or were patients who were tested because there was a concern about further H5N1 transmission within the hospital.

In either event, ARDS, followed by death on Sunday without a known source, has provided yet another signal that the flu pandemic of 2005 has begun. H5N1 that is efficiently transmitted to humans appears to be generating a range of outcomes. The family of five in Haiphong appears to be on the way to recovery. Results on their neighbors, admitted on or about March 25, have not been released. The family of five was H5N1 positive, clearly showing efficient transmission.

Although there has been minimal or no reporting of H5N1 in poultry in Thai Binh, Haiphong, and Quang Ninh provinces, the three adjacent provinces each have set a record related to efficient transmission (longest transmission chain, largest cluster admitted on the same day, first fatal infection of a health care worker - from an unknown source).

Thus, H5N1 is clearly transmitting efficiently in northeastern Vietnam. However, since many of the cases are mild, most of this transmission is not being detected and/or reported. The time between this efficient transmission in northeast Vietnam, and a pandemic resulting in millions of fatalities may be weeks or months, but the efficient transmission is the missing requirement for the start of the pandemic, and that requirement has now been met.

http://www.recombinomics.com/News/04070501...NE_Vietnam.html

Commentary

Thai Binh Haiphong and Quang Ninh H5N1 Clusters

Recombinomics Commentary
April 6, 2005

The clusters of bird flu in northern Vietnam have merged and now cover the northeastern coastline of Vietnam adjacent to Haiphong Harbor.

The three provinces, Thai Binh, Haiphong, and Quang Ninh have the three largest clusters in terms of members admitted on the same day (Haiphong), longest transmission chain including two health care workers (Thai Binh), and first heath care worker fatality (Quang Ninh).

There is clear human-to-human transmission going on in this region, which led to the executive order on April 1 in the US authorizing bird flu quarantine.

Quang Ninh is adjacent to China, and the four cases at the Vietnam-Sweden hospital are ringing alarm bells loudly.

The flu pandemic of 2005 has clearly begun.

http://www.recombinomics.com/News/04060504...m_Clusters.html

Commentary

Dearth of Data from Vietnam is Deafening

Recombinomics Commentary
April 10, 2005

The dearth of data from Vietnam has been deafening. There are three clusters of cases where samples have been sent to the Institute of Hygiene and Tropical Diseases in Hanoi and the results from these samples have not been reported. Most, if not all, are expected to be H5N1 positive for the cases in the central highlands province of Quang Binh, and the northern provinces of Haiphong and Quang Ninh, which are adjacent to each other in the northeast corner of Vietnam. Quang Ninh borders mainland China.

The suspect cases in Quang Binh were initially identified in media reports. There had been a report of a familial cluster. The index case, a 13 year-old girl, had died and her 5 year-old brother had symptoms. His samples were sent to Hanoi and tested positive for H5N1. Media reports indicated that 195 others in the commune had flu-like symptoms. More recent reports suggested that they were infected with H5N1 from meals using dead poultry. An investigative team found 37 people who still had symptoms and samples were collected from patients, poultry, and environmental swipes. The samples were sent to Hanoi on March 25. Results have not been reported.

On that same day, at least one neighbor of a family of five was hospitalized in Haiphong, in northern Vietnam. The family of five had been hospitalized three days earlier and subsequently tested positive for H5N1. Media reports indicate that 1 or 2 adults and one child were admitted on or about Match 25. Samples were collected and sent to Hanoi. Results have not been reported.

A week later, on Apri1 in Quang Ninh, a province adjacent to Haiphong, a 34 year-old physician developed acute respiratory distress syndrome (ARDS). That day President Bush signed an executive order making bird flu a quarantinable disease in the United States. The physician died 2 days later and samples were collected for SARS and H5N1 testing. Monday it was disclosed that at the same hospital, Vietnam Sweden, there were two H5N1 confirmed and one H5N1 suspect cases on another ward. Samples were sent to Hanoi. Results were to be made public by Friday, April 5. Results have not been reported.

Each of the above clusters would create a record on H5N1 clusters in Vietnam and would strongly point toward efficient transmission of H5N1 to humans.

Vietnam's failure to report the bird flu results speaks loud and clear. The dearth of data is deafening.

http://www.recombinomics.com/News/04100502...ata_Dearth.html

Experts still baffled by bird flu

April 18 2005 at 04:21PM

By Ho Binh Minh

Hanoi - The bird flu virus which has killed 36 people in Vietnam may not be contained until 2007 because the way it is spreading still baffles experts, officials said on Monday.

The government aimed to contain the H5N1 virus by next year or 2007 and eliminate it by 2010, Deputy Agriculture Minister Bui Ba Bong told a conference reviewing the fight against bird flu in Vietnam, the country hit hardest by the epidemic.

Other senior officials said current knowledge about the virus, which has been at its worst during the cool season between December and March in each of the last two years, meant the fight would be a tough one.

'There are cases where a healthy person carries the virus without showing clinical symptoms'
"This is a new, extremely dangerous disease which contemporary knowledge in our country and internationally has not been able to explain properly," Deputy Prime Minister Nguyen Tan Dung said.

He told health, agriculture officials and foreign experts it was still not known for sure how the virus was transmitted from water fowl, which can carry it without getting sick, to poultry and then to people.

"There are cases where a healthy person carries the virus without showing clinical symptoms, which has made the risk of spreading the virus in the community greater," Deputy Health Minister Tran Chi Liem said.

What Vietnam knows for sure is that H5N1 has killed 36 of the 71 people known to have contracted the virus since it swept across much of Asia in late 2003.

What the World Health Organisation (Who) fears is that the virus will mutate into a form which can pass easily between people and millions will die in a global pandemic.

"If the virus changes, it will be the biggest global health crisis," said Hans Troedsson, the Who representative in Vietnam, predicting "50 to 100 million deaths in the worst situation".

"We are facing a serious situation not only in Vietnam, but in the region of avian influenza," he said. "There is an extremely short window to contain the virus if the virus changes."

If the virus mutated, the first 20 people with it could infect 800 others in 10 days and a pandemic would have to be stifled within that brief period, he said.

"SARS will be nothing compared to the avian influenza pandemic. Let's work together," said Who's Troedsson, referring to the Severe Acute Respiratory Syndrome outbreaks in 2003 which killed nearly 800 people worldwide, five of them in Vietnam.

Bird flu has killed 51 people in Asia - 36 Vietnamese, including 15 since December, 12 Thais and three Cambodians - since arriving in Asia in late 2003, brought probably by migrating wild fowl.

A ban on hatching and raising water fowl until June 30 would be extended until the end of the year, Bong said.

Given the bird flu is likely to recur between December and March, south-east Asia's cool season, the ban should be extended to February 2006 at least, a senior provincial official said.

"The extended ban will be supported by farmers, and we will enforce the rule anyway," said Nguyen Duy Long, head of the animal health department of Long An province in the Mekong Delta, where the virus erupted again in December.

The one-day conference in Hanoi was expected to decide if all water fowl carrying the H5 component of the bird flu virus in the Mekong Delta would be slaughtered.

But the government left it open to scientists to decide if all ducks carrying H5 viruses should be killed, an agriculture ministry spokesperson said.


http://www.iol.co.za/index.php?set_id=14&c...13822361510B216

Vietnam extends bird flu controls
From correspondents in Hanoi
April 19, 2005
From: Agence France-Presse
A BAN on poultry farming in Vietnam's urban areas was being extended to 15 cities and provinces as part of efforts to combat bird flu, the agriculture ministry said today.

The measures were revealed following a government meeting attended by Deputy Prime Minister Nguyen Tan Dung yesterday on the ministry's strategy to wipe out the H5N1 virus.
"Although we are still in difficulties, we are determined to ensure safety for the community, no matter how much it will cost," state media quoted Deputy Prime Minister Nguyen Tan Dung as saying.

"The government is determined to apply (the) toughest measures to prevent the recurrence of bird flu," he said.

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Earlier, the ban was only imposed on the southern business capital, Ho Chi Minh City. But now, several other cities and provinces including Hanoi, the central cities of Hue and Danang, the northeastern coastal province of Quang Ninh, and the Mekong Delta province of Can Tho have been included in the ban.

Small markets dealing in live poultry in urban areas will be closed and replaced by big slaughterhouses and a complete ban will be imposed on the free-range breeding of water fowls, according to the ministry's decision.

The compulsory vaccination of poultry is to start in August and expanded to all high-risk areas in early October, with 100 per cent of the cost to be paid by the state. The cost is estimated to be about $US6.3 million ($A8.21 million) a year for the 2005-06 period.

The country had set itself the target of preventing the epidemic from periodically breaking out in the way that it had for the past two years, said agriculture officials at the meeting.

"Our objective is to prevent the recurrence of bird flu this year, aiming at eliminating the epidemic," said Minister of Agriculture Cao Duc Phat.

Official figures showed that bird flu epidemics have forced Vietnam to cull almost 46 million birds since late December 2003, with financial losses mounting $US220 million ($A286.53 million). The crisis in early 2004 led to a reduction of 0.5 per cent in the gross domestic product growth (GDP).

Thirty-five of Vietnam's 64 provinces and cities have been hit by the virus this year. According to an official report, all but one is now clear of the disease.

However, the disease is continuing to claim human casualties at regular intervals, even though it has apparently been waning in poultry.

Health experts have warned the H5N1 virus strain could lead to a pandemic if it mutated into a form which could be easily transmitted between humans.

http://www.news.com.au/story/0,10117,15019840-23109,00.html

Commentary

Fifth Bird Flu Fatality in Kampot Cambodia

Recombinomics Commentary
April 20, 2005

>> Dom said Cambodians often crossed the border to seek medical care at the hospital, which provides better treatment than hospitals in their country.

Health authorities in Cambodia said they had no independent information on the case, but were investigating.

"The first thing we're going to do is to try and verify the rumour and get our network to find out if she does actually test positive for bird flu," said Megge Miller, an epidemiologist working with the World Health Organisation in Cambodia.

Experts have said the virus is now endemic in many parts of the region. <<

The investigations in Cambodia have failed to halt the steady increase in H5N1 deaths in Cambodia. The death of the 20 year-old female is now the fifth reported fatality from Cambodia. It is the second reported death of a Cambodian who died in Kien Giang, after crossing from Cambodia to Viet Nam seeking better medical care.

All five fatalities have been from Kampot, and a recent OIE report indicated H5N1 had been detected in Kia Thavong Le in Banteay Meas district from an outbreak that had begun on March 24 in backyard chickens, but the number of fatal cases continues to increase.

This season all reported cases in Cambodia and all confirmed cases in southern Vietnam, have been fatal.

http://www.recombinomics.com/News/04200502...1_Kampot_5.html

In Vietnam, A Dark Side To Good News On Bird Flu

By Alan Sipress
Washington Post Foreign Service
Saturday, April 23, 2005; Page A01


HANOI -- Nguyen Sy Tuan can barely talk. His wasted frame is tucked beneath a thin white sheet on the hospital cot. His cheeks are sunken and his bulging eyes stare blankly at the ceiling. But the young man has begun to eat rice again and can finally breathe without a mechanical ventilator, a dramatic turnaround for a bird flu patient whom doctors had assumed would die.

More than a year after avian influenza emerged in East Asia, killing more than two-thirds of the people with confirmed cases, Vietnamese doctors are reporting that the mortality rate in their country has dropped substantially.

But while this is good news for survivors, it could mean the outbreak of bird flu in Southeast Asia is taking an ominous turn. If a disease quickly kills almost everyone it infects, it has little chance of spreading very far, according to international health experts. The less lethal bird flu becomes, they say, the more likely it is to develop into the global pandemic they fear, potentially killing tens of millions of people.

"The virus could be adapting to humans," said Peter Horby, an epidemiologist with the World Health Organization in Hanoi, the Vietnamese capital. "There's a number of indications it could be moving toward a more dangerous virus."

The mortality rate for bird flu in Vietnam this year is about 35 percent, almost exactly half that of last year, according to Health Ministry statistics. The mortality rate of the 1918 Spanish flu pandemic, by comparison, was less than 5 percent, but the outbreak killed an estimated 40 million people worldwide.

Officials said the drop in the bird flu mortality rate was more marked in northern Vietnam than in the south. While the virus in southern Vietnam is still killing at the same pace as last year, the rate in the area around Hanoi and elsewhere in the north has dropped from that level to as low as 20 percent. Vietnamese health experts said their suspicion that the disease is shifting is further supported by preliminary research showing a genetic change in the virus in the north resulting in the production of a protein with one less amino acid than in the south.

Health researchers believe that nearly all the 52 people known to have died of bird flu in Southeast Asia caught the virus from infected poultry. But with more clusters of cases among families reported in Vietnam this year -- including that of Tuan, his sister and their grandfather -- experts say they are growing increasingly suspicious that the disease has begun passing from one human to another.

Also worrying is the discovery of at least five cases, including that of Tuan's grandfather, in which people tested positive for bird flu but showed no symptoms. This could make it more difficult to contain an epidemic because people could transmit the disease without anyone realizing it.

Last year, U.S. researchers reported that ducks in Southeast Asia had begun carrying the bird flu virus without showing symptoms. Now, scientists in Vietnam have found numerous asymptomatic cases in the country's vast chicken population, according to Nguyen Tran Hien, director of the National Institute of Hygiene and Epidemiology.

"It seems that the virus may adapt in humans and in poultry a little bit. Therefore, the symptoms are not as severe as before," Hien said. "Also, the transmission may be faster and easier."

Moreover, the existing virus strain is not the only threat. Each human case also presents a chance for the bird flu virus to swap genetic material with an ordinary flu bug -- if the person becomes infected with both strains at the same time -- potentially creating a new hybrid that is highly lethal and even easier to catch.

"We are concerned that if the virus is changing, maybe a new virus is coming in the future," Hien said.

Two Survivors


Tuan, 21, left his home among the glistening paddies of northern Vietnam's rice-growing region more than a year ago for Haiphong, on the coast, where he worked harvesting seaweed for use in local cuisine. In early February, he returned to his family's simple brick house to celebrate the Tet New Year holiday.

According to his doctors, Tuan slaughtered a chicken for a festival meal, cutting its neck while his 14-year-old sister clutched the wings and legs. The bird was likely infected, and soon the siblings were, too.

Tuan started running a high fever about four days later, his wizened father recounted between puffs on a traditional bowl pipe in the family's one-room home.

When Tuan started coughing and had trouble breathing, he was taken to the local health center in Thai Thuy district. X-rays showed a white smudge on his left lung. Tuan was transferred after less than a day to a larger hospital in the provincial capital. There, the doctors concluded he had contracted the H5N1 strain of avian influenza and immediately rushed him to the tropical disease institute at Hanoi's Bach Mai Hospital.

By the time he arrived, X-rays showed, the white smudge had clouded the entire lung. Soon it took over the other one as well. "From one day to the next day, it spread very quickly," recalled Nguyen Thi Tuong Van, deputy director of the Bach Mai intensive care unit.

After 10 days, with his breathing failing, the doctors inserted a tube in Tuan's throat and put him on a ventilator. The infection spread to his kidneys and liver.

"We thought it was very likely the bird flu would kill him," Van said. "Then, when it seemed the situation couldn't get much worse, it started to get better. Two weeks later, when he didn't die, I thought maybe we could cure him."

Tuan's sister, Nguyen Thi Ngoan, a tall, mischievous 14-year-old with large black eyes, fell sick several days after her brother and also recovered.

At the district health center, X-rays revealed her lungs were clear, but a subsequent blood test was positive for bird flu. She was transferred to the Hanoi hospital, where she lay in the cot beside her brother and her temperature soared to 105 degrees.

But the fever broke after four days and returned to normal within two weeks, her doctors said. Ngoan went back to school in late March as a local celebrity, teased by her peers as "Miss H5."

A Vital Question


Vietnamese and international health officials say they are confident that the mortality rate has dropped but are not sure by how much. Better screening and wider public awareness of bird flu could mean health workers are catching and recovering from milder cases that would have gone unreported a year ago. WHO officials have complained, however, that Vietnam is reluctant to provide detailed information about human cases. Senior Health Ministry officials respond that reports are provided in accord with national regulations.

The question now is whether bird flu in Vietnam has begun passing among humans.

If it has, Nguyen Duc Tinh, a nurse who treated Tuan at the Thai Thuy district health center and fell sick with bird flu soon after, would be a likely case. Tinh, 26, said he had no contact with poultry for a month beforehand despite government accounts attributing his illness to infected chickens.

Tinh said he was the hospital staff member who had the closest contact with Tuan during his brief stay at the health center, taking his blood pressure and temperature, giving him injections and helping him walk. Within a week, Tinh had developed muscle aches and a high fever, symptoms of what he believed was a common flu. But when the fever subsided and then returned two days later, he grew alarmed.

"Then I suspected I had bird flu," he recalled, his brown eyes widening. "I was really, really afraid of dying."

But just two weeks after joining Tuan in the Hanoi hospital, Tinh was discharged and went back to his village.

"I had lost hope when the fever came a second time," he said. "When I returned to my home town, I felt as if I were born again."

http://www.washingtonpost.com/ac2/wp-dyn/A...anguage=printer

Bird Flu Outbreak in North Korea Contained (but not in Viet Nam & Cambodia)

ROME, Italy, April 25, 2005 (ENS) - An outbreak of avian influenza in North Korea has been contained, the United Nations said today, assuring the world and at the same time urging the country to continue surveillance on the affected farms and elsewhere to ensure that no residual infection remains.

An H7 strain of the bird flu virus had been detected recently on three poultry farms near the capital Pyongyang, said the UN Food and Agriculture Organization (FAO). Although this virus caused severe disease in thousands of chickens, it is not directly related to the H5N1 avian influenza virus circulating in other parts of Asia.

"The virus appears to have been eliminated from the three infected farms by combining culling of around 218,000 infected chickens, vaccination of unaffected birds in unaffected poultry houses and strict biosecurity measures," said FAO consultant Les Sims, who travelled to Pyongyang to advise the North Korean veterinary authorities on bird flu control.

North Korea has acted promptly and appropriately and has provided essential information in a timely manner, Sims said, and the official declaration to the World Organization for Animal Health (OIE) was done in due time.


Chickens are susceptible to the 15 strains of avian influenza that are known to exist. (Photo by Ian Douglas courtesy FAO)
The FAO sent three experts to the country to assist national authorities in diagnosis and disease management. This was done through the East Asian Regional Network on Avian Influenza set up by the FAO.
The government of North Korea formally appealed to the international community for help to fight avian influenza at an international conference in Paris earlier this month, according to the World Organisation for Animal Health (OIE) and the FAO.

Some 300 key veterinary experts and scientists met to discuss the current scientific information on bird flu and to address different aspects of disease surveillance and control strategies at the conference jointly organized by OIE/FAO, in collaboration with the World Health Organization.

North Korea asked FAO and OIE to provide diagnostic tools and technical assistance for disease control strategies, including vaccination.

The two international agencies welcomed North Korea's request as a sign of improved transparency and international cooperation on the part of the reclusive government.

Public health experts reacted quickly to North Korea's request for help because of fears that the H5N1 strain of the virus might mutate into a form that is easily spread from one human to another, setting off a global pandemic.

FAO officials urged North Korea to continue bird flu surveillance throughout the country. "Reagents and laboratory tools provided by FAO will assist in continuing the battle against the virus, but additional strengthening of veterinary diagnostic and surveillance capacity is seen as a priority to ensure that this work is completed," said Joseph Domenech, FAO's Chief Veterinary Officer.

North Korea received help in fighting the flu from its neighbor to the south on Friday. In a rare contact between the two countries, a team of South Korean officials travelled to the North Korean city of Kaesong, Unification Ministry officials said. The team included agricultural, veterinary and unification officials.

Poultry production is one of the few economic sectors that is growing in North Korea, the FAO says. The number of poultry is estimated at some 25.5 million in 2004, about double that in 1997.

The supply of animal protein has been very limited in North Korea, and the FAO says the poultry sector could contribute to improve the nutrition of the country's population of around 22.5 million people by adding a valuable source of animal protein to their diets.


North Korea is one of the poorest countries in the world, and the UN's World Food Programme (WFP) says millions of people need food assistance.
Tony Banbury, WFP's Director for Asia, warned earlier this month that many people in North Korea who desperately need WFP food will suffer even more if the agency does not receive additional contributions quickly. “We’re doing our best to mobilize support, but we need more help from the authorities in Pyongyang,” he said.

The spread of the disease into North Korea underlines the need for close regional cooperation, the FAO said. North Korea is already benefiting from a regional FAO project on avian influenza, shared with China, Mongolia and South Korea. The project assists in improving and upgrading veterinary laboratories as well as creating a network for the sharing of epidemiological information, and provision of equipment to control and prevent avian flu.

A national workshop on bird flu will be held soon in North Korea to improve awareness of the disease, and provide information on control methods, laboratory diagnosis and good farming practices. The workshop will be jointly organised by the government and FAO.

It is essential to fight the bird flu virus in poultry, free-range chickens and ducks, in order to reduce the risk of a human flu pandemic, the UN agency said.

Since the most recent emergence of the H5N1 avian flu virus in December 2003 in China, hundreds of millions of birds have been killed in eight Asian countries. The countries subject to infection are now on high alert to keep the disease in check.

Vietnam announced plans on Tuesday to bring the disease under control by 2006 or 2007, and eliminate it by 2010, the local newspaper "Viet Nam News" reported.

The country will ban raising poultry in some inner cities and urban areas, including Hanoi capital city, Ho Chi Minh city, Hai Phong northern city, and Hue central city, and isolate fowl production establishments from residential areas, Vietnamese deputy minister of agriculture and rural development Bui Ba Bong said at a conference reviewing bird flu prevention on last Monday.

Vietnam will extend an existing ban on hatching and raising waterfowl to the end of this year, and local farmers will not be allowed breed waterfowl in fields. In addition, the country will use bird flu vaccines on chicken flocks and waterfowl in southern Tien Giang province and northern Nam Dinh province on a trial basis this year.

Bird flu has infected 71 Vietnamese people and killed 36 of them since December 2003, according to the Health Ministry. Meanwhile, the disease has killed or led to the forced culling of some 46 million fowl in Vietnam.

http://www.ens-newswire.com/ens/apr2005/2005-04-25-05.asp

Swiss get ready for human flu pandemic

swissinfo April 27, 2005 2:19 PM



The Swiss government is preparing itself for an expected influenza epidemic by issuing new guidelines.

The announcement comes at a time when the authorities are revamping their emergency health services. The closure of hospitals and fewer medical personnel means that new ways of responding to threats have to be found.


With restricted finances and changes to their mission, civilian and military specialists will be expected to cooperate more closely in the future.

The government has pledged to draw up an action plan, which will be regularly adapted to the World Health Organization’s (WHO) recommendations.

The international body is warning that a human flu pandemic is on the cards in the not-so-distant future.

Actions

In the event of an outbreak on Swiss soil, the cabinet will keep the upper hand on operations dealing with an outbreak.

The government will announce the beginning and the official end to an epidemic and will be advised by a team of specialists.

The action plan will determine who receives medical treatment first.

Healthcare personnel, people working in essential services such as transport or the army, and those with a high risk of mortality should be among the first recipients of medications.

The plan will also contain recommendations on how to prevent the spread of the disease, to disseminate important information, to run a vaccination campaign and guarantee medical supplies.

The Federal Health Office is also expected to take measures to ensure proper supply of medications and vaccines. Cantons could also force hospitals to stock these.

The government can also place restrictions on – or even ban – exports of some products. The federal authorities will pay for the purchase of vaccines but cantons will have to foot the bill for distribution costs.

Worst scenario

Switzerland fell victim to the last major worldwide pandemic in 1918.

The Spanish flu pandemic - the biggest pandemic known to man so far with up to 50 million deaths around the world – killed 25,000 Swiss and a quarter of the population fell ill.

If this were to happen again, the Health Office estimated recently that there could be 42,000 deaths in a "worst-case scenario." In addition, there would be two million medical consultations and 14,000 cases of hospitalisation.

Currently, strains of avian flu are believed to present the biggest threat to mankind.

The WHO has warned that the recent outbreaks in Southeast Asia showed a more deadly strain of bird flu than the one originally detected in Hong Kong in 1997.

Experts say though that the virus could kill even more people if it mutates into a form easily transmitted among humans.

swissinfo with agencies

http://www.swissinfo.org/sen/swissinfo.htm...y=1114599309000

EU makes plans to fight avian flu


By Donna Borak
UNITED PRESS INTERNATIONAL


Washington, DC, Apr. 29 (UPI) -- The European Commission announced plans this week to update efforts among EU member nations to help prevent outbreaks of avian and human influenza.

The H5N1 strain of avian flu is sweeping through poultry in Asia and has spread in some instances to the human population, causing fatalities. Health officials fear the virus could become more infectious to people and cause a devastating global pandemic.

"Beyond the known impact on animal health and welfare, there is a real fear that a mutant strain of avian flu could cause a human influenza pandemic," Markos Kyprianou, the EU's commissioner for health and consumer protection, told reporters in Brussels on Thursday.

Until now, the EU has not adopted measures to monitor the virus, but as a result of the recent outbreak in Southeast Asia, and previous poultry cases reported in Europe, Canada and the United States, health commission officials said they have been prompted to install a continental surveillance plan.

Under the new proposal, the 25 member states would be required to boost their veterinary surveillance of the poultry population to try to detect low-pathogen forms of the virus -- which generally are not dangerous to humans-- and prevent them from mutating into potentially deadly high-pathogenic forms.

The commission recommended each member nation watch for risk factors, such as possible contact of domestic poultry with wild birds, spread of infection among different poultry species and the density of poultry farms.

Commission officials said in a statement the cost of the programs could run from 3 million to 8 million euros ($3.8 million to $10.2 million) per year, adding they were confident the laws would pay for themselves by helping to safeguard the continent's agricultural sector.

"The current situation in Asia and recent outbreaks of avian flu in the EU has shown us how devastating the social and economic consequences of this disease can be," Kyprianou said.

Europe has seen sporadic avian flu outbreaks, beginning in Italy in 1999-2000, with other cases reported in the Netherlands, Belgium, and Germany. So far, Europe has experienced only one human death as a result of avian flu -- in 2003 in the Netherlands.

As a result of the outbreak, however, Dutch authorities worked with the health commission to cull 33 million birds, including one-day old chicks, costing 150 million euros ($192 million).

"This proposal aims to set up the best possible system to prevent new outbreaks of avian flu in the EU, to swiftly manage those that do occur and to minimize their negative impact," Kyprianou added.

In January 2004, the World Health Organization activated its influenza pandemic-preparedness plan after individuals infected with H5N1 died in Vietnam and Thailand.

Since then, the WHO has reported a series of outbreaks in six South Asian countries, including Cambodia, China, Indonesia, Thailand and Vietnam and the Republic of Korea.

A report by WHO officials issued April 12 said there have been 80 confirmed human cases of avian flu, 50 of which were fatal, since Jan. 28. Of those, Cambodia reported three cases, all of which were fatal -- including an 8-year old girl from Kampot. Thailand had 17 cases, 12 of which were fatal. Vietnam was hardest hit, with 60 human cases in 18 cities and provinces and 35 dead.

Humans become infected by the avian strain through the air, after inhaling the dried and pulverized feces of birds. Symptoms are similar to other types of flu, including fever, malaise, sore throat and cough. Some victims even develop conjunctivitis.

A WHO report earlier this year concluded that surveillance and reporting systems for both the human and animal variations of the disease have been weak.

"Assessment of the risk to humans need to be based on a risk assessment of the disease situation in poultry that considers the prevalence of highly pathogenic avian influenza and the adequacy of the surveillance system," the report said. "A reliable system of review and verification is needed to ascertain that poultry are disease-free in an area or country. Equally important is a robust surveillance system for human respiratory illnesses that might signal transmission of avian H5N1 infection to humans."

--

Donna Borak is a UPI Business Correspondent. E-mail: sciencemail@upi.com
http://washingtontimes.com/upi-breaking/20...20712-1879r.htm

Thailand says its avian flu battle is over

May 5, 2005 (CIDRAP News) – After an arduous 10-month battle against the H5N1 avian influenza virus, Thailand has declared itself free of the disease, the Bangkok Post reported today.

The country hasn't identified a human case of H5N1 infection since the death last October of a 14-year-old girl in Sukhothai province, but poultry outbreaks had continued. Yesterday marked the end of a 3-week surveillance period at a farm in Lop Buri, the last place to have reported an H5N1 outbreak, the newspaper said.

This is the first time Thailand has been free of avian flu since the disease re-emerged last July, officials told the Post. The Ministry of Agriculture and Cooperatives will continue to watch for any re-emergence of the virus, said ministry assistant Charal Trinvuthipong. Officials will continue to conduct bi-weekly checks for avian flu.

In addition, the ministry has recruited more than 600 temporary workers to watch for avian flu. They will work in nine northern and central provinces where H5N1 kept reappearing: Ang Thong, Lop Buri, Kampheng Phet, Nakhon Sawan, Phichit, Phitsanulok, Sukhothai, Suphan Buri, and Uttaradit, the Post reported.

Along with the surveillance, officials will seek closed-system poultry-raising methods for small-scale farms, said Sudarat Keyuraphan, agriculture and cooperatives minister.

The end of the outbreaks is good news for Thailand's poultry industry. Chicken exports are expected to reach a target of 300,000 tons this year, Anan Sirimongkolkasem, president of the Thai Broiler Processing Exporters Association, told the Post in a separate story today. That's nearly a 40% increase over the previous year.

Thailand is chiefly shipping cooked products because raw poultry remains banned in major export markets, he said.

http://www.cidrap.umn.edu/cidrap/content/i...y0505avflu.html

Avian flu virus changing
By HELEN BRANSWELL

Canadian Press

Sunday, May 01, 2005

Toronto — Ominous changes in the behaviour and the makeup of the H5N1 avian influenza virus in northern Vietnam has the flu world worried the virus may be getting better at infecting humans.

In recent months the virus has sparked increasing numbers of small clusters of cases, suggesting more frequent occurrences of limited person-to-person spread.

http://www.theglobeandmail.com/servlet/Pag...orce_login=true

Cambodia's fourth reported case of Avian Flu, 20 year old woman
06 May 2005


The Ministry of Health in Cambodia confirmed today that a 20-year-old woman from Kampot province who died on 19 April in a hospital in Viet Nam, was the country's fourth reported case of avian influenza.

The woman, a secondary school student, was from Kompong Trach district in Kampot province, the same district as the first case reported from Cambodia in February. Samples taken from the woman tested positive for avian influenza A/H5 virus by the Pasteur Institute in Ho Chi Minh City, Viet Nam.

Staff from the Ministry of Health, Cambodia conducted active case finding in the village where the woman attended school and also provided education sessions to the students at the school. The Ministry of Agriculture are conducting an investigation into poultry deaths in the area of the school.

http://www.who.int

Thousands infected in flu outbreak in southern Chinese city: report


Canadian Press


Sunday, May 08, 2005

HONG KONG (AP) - More than 10,000 people, mostly children, suffered from flu symptoms during an outbreak in southern China during the weeklong Labour Day holiday, a Hong Kong newspaper reported Sunday.

The victims had symptoms including runny noses, cough and fever, Ming Pao Daily News newspaper reported.

More than one-half of the 10,000 people who contracted the virus were children, the report said, adding a hospital in Shenzhen had to set up temporary beds to accommodate nearly 700 children admitted daily during last week's holiday.

A man surnamed Shen who answered the phone at Shenzhen's health department said he didn't have information on the outbreak.

Asian countries are vigilant about flu outbreaks amid warnings that avian flu could mutate and become easily transmissible among humans, sparking a pandemic that could kill millions.

Avian flu has killed 52 people in Vietnam, Thailand and Cambodia since it began ravaging poultry farms across Asia in late 2003 but there have been no signs of human-to-human transmission so far.

© The Canadian Press 2005

http://www.canada.com/health/story.html?id...88-03b482ac3dc3

Politicians bury their heads in the sand while global avian flu threat mounts
06 May 2005


Governments around the world must stop burying their heads in the sand over the growing threat of a global epidemic of avian flu, argues a GP in this week's BMJ.

Disasters like the Asian Tsunami “pale into insignificance” compared to the human cost of an influenza pandemic, says Dr Higson, which will wipe out “hundreds of millions” of lives if it is not prevented.

A recent report in the BMJ showed that avian flu (called H5N1) is beginning to jump from human to human - as opposed to transmission from bird to human only, as happened initially. This vastly increases the potential for spreading the virus across the population, as infection no longer depends on direct contact with diseased birds.

Governments must fund the rapid development of vaccines against H5N1, and build up sufficient stocks of anti-viral drugs such as zanamivir or olsetamivir, the best treatment for anyone infected, says Dr Higson.

Pharmaceutical companies should also expand the manufacture and supply of relevant drugs, he argues, and GPs and other prescribing practitioners must prepare for the practicalities of dealing with an epidemic or pandemic of influenza.

Avian flu is now a true threat to the world's population, Dr Higson concludes. Planning from world leaders to prevent it and deal with its consequences is now vital.

Letter - Sit up and take notice about avian flu BMJ Volume 330, pp 1087

Click here to view full letter (p4 of pdf):
press.psprings.co.uk/bmj/may/ltr1084.pdf

http://www.medicalnewstoday.com/medicalnews.php?newsid=23960

9 May 2005
Warning On Avian Flu Complacency

A UK doctor writing in the British Medical Journal has warned that governments around the world must stop burying their heads in the sand over the growing threat of a global epidemic of avian flu. Dr. Nigel Higson writes that disasters like the Asian Tsunami will "pale into insignificance" when compared to the human cost of an influenza pandemic which has the potential to wipe out "hundreds of millions" of lives.

Higson says the catalyst for government action should have been the discovery earlier in the year that avian flu (known as strain H5N1) is now spreading via human to human transmission. "Development of vaccines against H5N1 needs government pump priming, as will the stockpiling of euraminidase inhibitors, which should be effective against avian flu," writes Higson. "It is many years since a pandemic struck, and people have become complacent in that time. For governments to bury their heads in the sand may have some benefits in many political areas but it will be disastrous in terms of pandemic planning."

Now that human to transmission has been confirmed, Higson believes that doctors should prepare themselves for the practicalities of treating epidemic or pandemic influenza as well as encouraging increased pharmaceutical company capacity.

http://www.scienceagogo.com/news/200504082...trunc_sys.shtml

On Front Lines Of Asian Battle Against Bird Flu

By Alan Sipress
Washington Post Foreign Service
Sunday, May 22, 2005; A01



HANOI -- Behind high gray double doors, Professor Nguyen Thu Van, a simply dressed woman with black hair held back by a barrette, has been laboring tirelessly with her team of researchers in a race to avert a pandemic.

Her white-coated co-workers scurried about one recent day in their small, second-floor laboratory in an elegant French colonial building in the Vietnamese capital. Engaged in a drive to perfect a human vaccine against avian influenza, Van, 50, has produced an experimental version and conducted successful tests on monkeys. She and her researchers have volunteered to be the first subjects in human trials, which she hopes will begin this summer despite warnings from the World Health Organization.

Van is at the forefront of a campaign in Southeast Asia to halt the progress of bird flu. International health specialists say they fear the virus could undergo genetic changes suddenly and become the most deadly disease to strike humanity in modern times. Almost 200 million chickens, ducks and other birds throughout Southeast Asia have died from the virus or been slaughtered to contain it in the last two years.

So far, bird flu has killed 53 people, mostly as a result of close contact with infected poultry. But international health experts say they suspect the virus has also begun to spread among humans.

With bird flu endemic among birds in the Asian countryside, the disease could pose a threat to humans for years. And in an age of global travel, health experts predict that an easily transmitted human strain could move beyond Asia in a matter of weeks and infect tens of millions of people worldwide.

When bird flu began spreading in Southeast Asia, governments in the region initially denied its presence. But a Thai doctor, Prasert Thongcharoen, sounded the alarm, issuing blunt declarations that forced Thailand to acknowledge early last year that the disease was decimating bird populations and beginning to infect people.

In Indonesia, the government has campaigned to vaccinate poultry across the vast archipelago, but tens of thousands of doses sit unused in government refrigerators while farmers leave their birds unprotected. A veterinarian named Suparno patrols the country's most populous island in an ambitious endeavor to prevent the virus from spreading.

Van's eyes gleamed with enthusiasm as she predicted that Vietnam could become the first country to develop a human vaccine against the lethal H5N1 strain of bird flu endemic among poultry in Southeast Asia. But WHO officials charge that Van's team has flouted international guidelines, saying that material used to develop the vaccine is potentially contaminated and that the planned human tests involve imprudent shortcuts.

"We cannot wait," Van responded.

A Warning in Thailand

Prasert, 71, one of his country's most eminent virologists, literally wrote the book on influenza in Thailand, published seven years ago.

He was a physician fresh out of school when the 1957 Asian influenza pandemic swept through Thailand, flooding his hospital with patients. Later, when an outbreak of Hong Kong flu reached Bangkok in 1968, Prasert was already emerging as a leading researcher.

In the fall of 2003, he learned that tens of thousands of chickens had begun dying in Thailand, he said during an interview in his research office in Bangkok. The government was insisting that the birds had contracted fowl cholera, a common affliction. As the world's fourth-largest poultry exporter, Thailand would suffer an economic blow if other countries learned its flocks were infected with bird flu.

Prasert decided to obtain more information. He visited a Bangkok market, where farmers confided they believed it was something worse.

"They said it wasn't like fowl cholera," Prasert recounted. "If they have chickens that are sick with that, they give them tetracycline and they get better. But these chickens, by the next morning, they're all dead."

Prasert's suspicions mounted in early December when friends who usually bring him six or a dozen eggs when they visit their farm east of Bangkok came back empty-handed. "They told me the farm is usually full of chickens," he recalled, "but the chickens all died."

In mid-December, researchers privately showed Prasert results of tests done on chickens revealing that they had influenza. Prasert warned officials that urgent action was needed.

"I told them it is a public health concern and I would not close my mouth. I will talk even louder," Prasert said.

Senior ministers continued to deny the presence of bird flu throughout much of January 2004, according to Thai and international officials.

But in the first week of January, a 6-year-old boy from a province west of the capital developed a high fever, followed a week later by symptoms of severe pneumonia. The boy was admitted to Prasert's hospital, and tests on Jan. 22 came back positive for bird flu. He died three days later.

Prasert told the Health Ministry that it was too late for a coverup, he recounted with an ironic smile and narrowed eyes. The strain had reached humans.

On Jan. 23, the health and agriculture ministers announced that bird flu had arrived in Thailand.

Late Response in Indonesia

Suparno, the Indonesian government veterinarian, crouched in the cramped backyard of a farmhouse in a Central Java village, clad in a tan uniform. He slowly drew the bird flu vaccine from a plastic container into a syringe. Then his fellow animal health officers brought five black hens, one by one, from a barn. Suparno inoculated each one.

There were 20 more chickens running around the farm, but they escaped the needle.

"Too hard to catch," Suparno explained before driving off.

But by leaving most of the flock unprotected, the exercise was pointless. The remaining chickens could catch avian flu, and sick birds, in turn, could infect even those that had been immunized. Vaccinated birds can still become carriers of the disease and transmit it to humans.

Several governments in Southeast Asia are considering following Indonesia's lead in making poultry vaccination central to efforts to contain bird flu.

But interviews with livestock officials and farmers in three districts of Central Java, the Indonesian province hardest hit by bird flu, suggest that the immunization campaign sputtered from the start and has now all but stalled.

Tri Satya Putri Naipospos, national director of animal health, said Indonesia turned to vaccination because it was too costly to carry out widespread culling of flocks as Vietnam and Thailand were doing. By the time Indonesian officials acknowledged the presence of the virus, it had already infected much of Java, Bali and the Sumatra islands.

"The announcement of the government came very late," Naipospos admitted. "Our laboratory people knew it already." She said senior Indonesian officials delayed acknowledging the disease after the outbreak in August 2003 because of intense pressure from the poultry industry, which was afraid it would hurt sales.

Central government officials said they distributed 150 million doses of free vaccine to inoculate poultry nationwide at small and mid-size farms and that 98 percent of those earmarked for Central Java had been used.

But local officials and farmers countered that immunization was spotty at best. "Maybe the farmers get the vaccine," said Widodo Sumantri, chief livestock officer in Karanganyar district. "The percentage of those who use it is small."

In the neighboring Sragen district, Sri Harjono, a farmer who runs a cooperative that has 23,000 broiler chickens, said he lost more than half of his flock after the initial bird flu outbreak in 2003. He restocked and began vaccinating in October, Harjono recalled, standing outside a cavernous coop on stilts fashioned from bamboo and screens.

But no longer. "It's too much hassle," he said, stroking a baby chick. "You have to go one by one. Can you imagine vaccinating 23,000 chickens over and over?"

Hope, Hazards in Vietnam

Educated partly in the Soviet Union, Van, the Hanoi scientist, later trained at the Centers for Disease Control in Atlanta, where she developed an interest in working on hepatitis. Her efforts to develop a hepatitis B vaccine in Vietnam helped her win appointment as general director of Vietnam's Vaccine and Biological Production Company No. 1.

As the number of human cases in Vietnam grew last year, a senior colleague suggested that Van try to reprise her success with hepatitis B by developing an avian influenza vaccine.

"It was difficult at the beginning because we did not have the experience," she said, but added that Vietnam could not afford to wait for vaccines being developed in the West, which she also feared would be exorbitantly expensive.

Vietnam publicly acknowledged the presence of the disease in January 2004, although Trinh Quan Huan, director general of preventive medicine, said the Health Ministry knew of it five months earlier. Hospitals in the Hanoi area had already admitted 13 children and an adult with symptoms associated with bird flu, according to WHO. Twelve people had died.

Vietnam's current strategy of poultry control measures has not tamed the outbreak. The government recently extended a ban on hatching ducks and other waterfowl, but enforcement has been erratic. The raising of all poultry in cities was recently prohibited. But in Ho Chi Minh City, where such a ban was already in effect last year, chickens are still a common sight in back lanes.

After a study last month discovered that more than 70 percent of ducks and geese sampled in the Mekong Delta tested positive for influenza, the government ordered the slaughter of 1.5 million waterfowl, according to state media. But experts with the U.N. Food and Agriculture Organization predicted that as long as farmers were offered only a fraction of the birds' value in compensation, they would refuse to cooperate.

Last year, Van's researchers developed the virus strain for the vaccine. The self-administered clinical tests are due to begin as early as August. If they are successful, Van says, she hopes Vietnam can produce about half a million doses by January.

WHO experts visited Hanoi earlier this year and warned that the material used to grow the virus strain in Van's laboratory was not approved by international health agencies. It could be contaminated and was grown in cancer cells, according to Michael L. Perdue, a WHO influenza expert. Perdue's team also told the Vietnamese that testing the vaccine on researchers rather than on true volunteers would be unethical.

Van's worry is that by the time the vaccine is ready, it will no longer be effective against an influenza virus that easily mutates. If the vaccine cannot be updated, she cautioned, Vietnam would be left vulnerable in the face of a mass killer.

"I'm confident it will work," she said, adding, "I'm 80 percent confident we will succeed."

Special correspondent Yayu Yuniar in Jakarta contributed to this report.

http://www.washingtonpost.com/wp-dyn/conte...2100908_pf.html

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.

http://www.nytimes.com/2005/10/06/health/0...agewanted=print

Changes Cited in Bird Flu Virus
Deadly Strain Acquiring Mutations Similar to Those in Reconstructed 1918 Virus

By David Brown
Washington Post Staff Writer
Thursday, October 6, 2005; A03



The strain of avian influenza virus that has led to the deaths of 140 million birds and 60 people in Asia in the past two years appears to be slowly acquiring genetic changes typical of the "Spanish flu" virus that killed 50 million people nearly a century ago, researchers said yesterday.

How far "bird flu" virus has traveled down the evolutionary path to becoming a pandemic virus is unknown. Nor is it certain that the much-feared strain, designated as influenza A/H5N1, will ever acquire all the genetic features necessary for rapid, worldwide spread.

Nevertheless, the similarities between the Spanish flu virus of 1918 and the H5N1 strain slowly spreading through Asia provide unusually concrete evidence of how dangerous the newer virus is. At least four of its eight genes now contain mutations seen in the deadly strain that circled the globe during and after World War I.

"These H5N1 viruses might be acquiring the ability to adapt to humans, increasing their pandemic risk . . . there is a suggestion there may be some parallel evolution going on," said Jeffery K. Taubenberger, a molecular pathologist at the Armed Forces Institute of Pathology in Rockville.

The comparison of the old and new flu viruses is the first practical use of a science-fiction-like scenario that concluded yesterday with the release of two papers, one by the journal Science and the other by its chief competitor, Nature.

After 10 years of work, Taubenberger and his team succeeded in reconstructing the Spanish flu virus, which was responsible for the deadliest epidemic since the Black Death of the Middle Ages. Reborn in mid-August at a high-security laboratory at the Centers for Disease Control and Prevention in Atlanta, the pathogen appears in animal experiments to be as lethal as it was in humans 87 years ago.

The report came as the United States, many other countries and the World Health Organization are making increasingly urgent preparations for a new flu pandemic.

The Department of Health and Human Services is stockpiling antiviral drugs and is buying enough experimental bird flu vaccine to inoculate 20 million people. President Bush said in a news conference this week that he is considering the use of the military to enforce quarantines, if necessary, and that the government's long-awaited pandemic plan will be released soon.

What makes the accomplishment reported yesterday so remarkable is that no intact samples of the Spanish flu virus exist.

When the pandemic occurred in 1918 and early 1919 -- only American Samoa and parts of Iceland appear to have been spared -- microbiologists did not know for certain what caused it. (The influenza virus was not identified until 1933.) Although biologists were later able to deduce the broad family of influenza viruses the 1918 strain came from, its genetic identity was lost.

Taubenberger and his colleagues were able to piece together the 1918 virus's genes from two unconventional sources. One was fingernail-size pieces of lung tissue, preserved in wax after the autopsies of two soldiers who were among the pandemic's 675,000 American victims. The other source was the frozen body of an Inuit woman who died of influenza in November 1918 and was buried in the permafrost.

The virus's eight "gene segments" -- strands of RNA that are the equivalent of DNA and chromosomes in cells -- were in pieces, like a shelf of ancient vases tipped onto a stone floor. But with gene sequencing and polymerase chain reaction -- the magnifying glass and glue of molecular genetics -- the team reassembled the infamous microbe.

"It is an amazing feat," said Edwin D. Kilbourne, 85, one of the country's leading influenza virologists and a retired professor from Mount Sinai School of Medicine and New York Medical College. "It's a tribute to imagination, perseverance and a great deal of very hard work."

The reconstruction of the 1918 virus is expected to provide immediately useful insights to epidemiologists studying the kind of flu viruses that are being passed among dozens of species of birds and mammals worldwide.

"I think we have been able to unmask the 1918 virus, and it is revealing some of the secrets that will help us prepare for the next pandemic," said Julie L. Gerberding, director of the CDC.

By identifying how the 1918 virus differs genetically from related viruses that do not infect people, researchers hope to pinpoint the mutations an animal flu virus needs to acquire to adapt to human beings. Taubenberger estimates, as a rough guess, that 25 mutations may be essential.

"It could theoretically provide a checklist for surveillance," he said. "You might be able to say: This strain has six of these changes; it's a worrisome virus we need to keep our eye on. Or this one has none."

It will be especially useful to compare the 1918 gene sequence to those of the two flu viruses that have caused pandemics since then -- the "Asian flu" of 1957 and the "Hong Kong flu" of 1968. Hybrid viruses containing genetic features of each can then be constructed and studied in the laboratory.

"We are trying to elucidate the general rules of human adaptation. How does a bird virus become a human virus? Generically put, that is what we're trying to answer," Taubenberger said.

In their paper, Taubenberger, Ann. H. Reid, Thomas G. Fanning and other colleagues at the AFIP describe three genes that make up more than half the 1918 virus's genetic material. Previous papers had described the reconstruction of the virus's five other genes.

Analysis of all eight genes strongly suggests that the Spanish flu virus descended directly from a bird virus and moved into human hosts after slowly accumulating the necessary mutations. It does not appear to have combined with a pig or human flu virus in a process called "reassortment" and to have become a human virus in a sudden step. The 1957 and the 1968 pandemic strains arose through reassortment.

This insight hints that H5N1 might also be capable of adapting to human beings through gradual evolution. In fact, there is evidence the process is already underway.

The polymerase genes described in the new paper produce three proteins that together allow the virus to replicate in cells. Of the 2,232 amino acids in those proteins, 10 are consistently different in the 1918 virus and in other human flu viruses, compared with the proteins in avian flu viruses. The researchers believe the 10 changes may be keys to enabling avian viruses to replicate easily in people. In the past two years, scientists have isolated H5N1 viruses in Asia that have two of the 10 changes.

Similarly, the researchers believe adaptation to humans requires six changes in another gene, called nucleoprotein. H5N1 strains have been found carrying one. In yet another gene -- for a protein called matrix -- four changes appear necessary. Surveillance has turned up H5N1 strains carrying two of the four.

Altogether, the changes suggest that though H5N1 is still a bird virus, it is partway along a path to becoming a human virus.

In a second paper to be published tomorrow in Science, Terrence M. Tumpey of the CDC and Adolfo Garcia-Sastre of Mount Sinai describe experiments with the live, reassembled virus.

They found that mice infected with the microbe died in three days -- unusually fast -- and that unlike most flu viruses, the 1918 strain replicated deep in the lung, not just in the throat and bronchi. That fits the observation that many victims of Spanish flu died when blood or fluid flooded their lungs, often after only a day or two of illness.

The gene sequence of the 1918 virus is now public, which theoretically means it could be reconstructed by others. Publication of the new papers was approved by the federal body that reviews research that could have bioterrorism uses, the National Science Advisory Board for Biosecurity.

Many scientists, however, doubt that Spanish flu could cause a pandemic today if it got out of the laboratory. That is because virtually everyone on Earth has been exposed to many of its descendants in the H1N1 flu virus family -- and consequently are at least partly immune to it.

http://www.washingtonpost.com/wp-dyn/conte...0501098_pf.html

October 7, 2005
After Delay, U.S. Faces Line for Flu Drug
By GARDINER HARRIS
As concern about a flu pandemic sweeps official Washington, Congress and the Bush administration are considering spending billions to buy the influenza drug Tamiflu. But after months of delay, the United States will now have to wait in line to get the pills.

Had the administration placed a large order just a few months ago, Roche, Tamiflu's maker, could have delivered much of the supply by next year, according to sources close to the negotiations in both government and industry.

As the months passed, however, other countries placed orders that largely exhausted Roche's production capacity this year and next.

Democrats on Capitol Hill are complaining that the delay has put Americans in jeopardy. "The administration has just drug its feet through this whole process," said Senator Tom Harkin, Democrat of Iowa, who has pressed for legislation to buy more courses of Tamiflu. A course includes enough pills for a full treatment.

Senator Barack Obama, Democrat of Illinois, said in an interview that Michael O. Leavitt, the secretary of health and human services, told senators in a closed-door briefing last week that the administration would soon place an order to raise the government's Tamiflu stockpile to 81 million courses - up from 12 million to 13 million courses expected by the end of 2006. Mr. Obama has long been urging the government to buy more Tamiflu.

"Secretary Leavitt admitted that they are currently in negotiations with Roche to try to rapidly build up those stockpiles," Mr. Obama said. "But we're behind countries like Great Britain, France and Japan, and it's probably going to cost us a lot more money than it would have to catch up."

In an interview on Tuesday, Mr. Leavitt said that the government would buy more Tamiflu although he did not specify how much.

"But it's not a surrogate for preparation," he said. "It's like saying that if we could get everyone in America to wear seat belts, we would solve auto accidents. It's part of a comprehensive solution."

Christina Pearson, a spokeswoman for Mr. Leavitt, said she could not confirm whether the Bush administration had a new goal of buying the 81 million courses.

Mr. Leavitt said the Bush administration planned to prepare for a possible influenza pandemic by strengthening both international and domestic disease surveillance programs, buying drugs like Tamiflu and investing in research to develop alternative methods of making flu vaccines.

Preparing the vaccines usually takes nine months and involves the eggs of thousands of chickens. Because chickens themselves could be wiped out in a pandemic, the present system of manufacturing vaccines is highly vulnerable.

Introduced in 1999, Tamiflu for years had disappointing sales and received little attention. But just as Bayer's antibiotic Cipro became wildly popular in the wake of the 2001 anthrax attacks, Tamiflu has become the drug of choice for those worried about pandemic flu because it is one of the only medicines proven to reduce the duration and severity of the potentially deadly disease if taken within 48 hours of infection.

Dr. Irwin Redlener, director of the National Center for Disaster Preparedness at Columbia University, is among those who have been insisting for months that the government buy more Tamiflu. But he said the Bush administration largely ignored his and others' warnings.

"And now that they're finally worked up about it, the store is closed," Dr. Redlener said, referring to Roche's supply problems. "The U.S. is now in line behind much of the rest of the world."

Terence Hurley, a Roche spokesman, said that 40 countries had ordered Tamiflu to fill medical stockpiles in case of a pandemic. Many countries in Europe - including France, Britain, Finland, Norway and Switzerland - have ordered enough to treat 20 percent to 40 percent of their populations. The American stockpile would treat less than 2 percent of the population.

Mr. Hurley said that Roche would be able to deliver all the courses that the United States government has currently ordered, including at least two million courses ordered this year.

Asked how soon the company could produce 68 million more courses if the United States placed such an order, Mr. Hurley refused to say. "We're just going to have to see what their demands are," Mr. Hurley said. The suggested 81 million courses would cover more than a quarter of the population.

The government and industry officials, however, said that Roche had committed to delivering seven million courses to the United States next year and would not be able to deliver substantially more until 2007.

Since 1997, avian flu strains have killed millions of birds in nearly a dozen countries. But so far, nearly all of the people infected - more than 100 so far, including some 60 who died - got the sickness directly from birds. Until the virus passes easily among humans, it is unlikely to cause a pandemic that could kill millions.

An outbreak, therefore, may still be years away or may never occur. But news this week that the 1918 flu virus, which killed at least 50 million worldwide, was also a form of avian flu raised concerns further.

On Thursday, Senator Hillary Rodham Clinton, Democrat of New York, and Senator Pat Roberts, Republican of Kansas, introduced a bill that would bolster defenses against the flu.

http://www.nytimes.com/2005/10/07/politics...agewanted=print

October 8, 2005
Bush Plan Shows U.S. Is Not Ready for Deadly Flu
By GARDINER HARRIS
WASHINGTON, Oct. 7 - A plan developed by the Bush administration to deal with any possible outbreak of pandemic flu shows that the United States is woefully unprepared for what could become the worst disaster in the nation's history.

A draft of the final plan, which has been years in the making and is expected to be released later this month, says that a large outbreak that began in Asia was likely, because of modern travel patterns, to reach the United States within "a few months or even weeks."

If such an outbreak occurred, hospitals would become overwhelmed; riots would engulf vaccination clinics; and even power and food would be in short supply, according to the plan, which was obtained by The New York Times.

The 381-page plan calls for quarantine and travel restrictions but concedes that such measures "are unlikely to delay introduction of pandemic disease into the U.S. by more than a month or two."

The plan's 10 supplements suggest specific ways that local and state governments should prepare now for an eventual pandemic by, for instance, drafting legal documents that would justify quarantines. Written by health officials, the plan does yet address responses by the military or other governmental departments.

The plan outlines a worst-case scenario in which more than 1.9 million Americans would die and 8.5 million would be hospitalized with costs exceeding $450 billion.

It also calls for a domestic vaccine production capacity of 600 million doses within six months, more than 10 times the present capacity.

On Friday, President Bush asked the leaders of the nation's top six vaccine producers to the White House to cajole them into increasing their domestic vaccine capacity, and the flu plan demonstrates just how monumental a task these companies have before them.

In the wake of Hurricane Katrina, the Bush administration's efforts to plan for a possible pandemic flu have become controversial, with many Democrats in Congress charging that the administration has not done enough. Many have pointed to the lengthy writing process of the flu plan as evidence of this.

But while the administration's flu plan, officially called the Pandemic Influenza Strategic Plan, closely outlines how the Health and Human Services Department may react during a pandemic, it skirts many essential decisions, like how the military may be deployed.

"The real shortcoming of the plan is that it doesn't say who's in charge," said a top health official who provided the plan to The Times. "We don't want to have a FEMA-like response, where it's not clear who's running what."

Still, the official, who asked for anonymity because the plan was not supposed to be distributed, called the plan a "major milestone" that was "very comprehensive" and sorely needed.

The draft provided to The Times is dated Sept. 30, and is stamped "for internal H.H.S. use only." The plan asks government officials to clear it by Oct. 6.

Christina Pearson, a spokeswoman for Health and Human Services Secretary Michael O. Leavitt, responded, "We recognize that the H.H.S. plan will be a foundation for a governmentwide plan, and that process has already begun."

Ms. Pearson said that Mr. Leavitt has already had one-on-one meetings with other cabinet secretaries to begin the coordination process across the federal government. But she emphasized that the plan given to The Times was a draft and had not been finalized.

Mr. Leavitt is leaving Saturday for a 10-day trip to at least four Asian nations, where he will meet with health and agriculture officials to discuss planning for a pandemic flu. He said at a briefing Friday that the administration's flu plan would be officially released soon. He was not aware at the briefing that The Times had a copy of the plan. And he emphasized that the chances that the virus now killing birds in Asia would become a human pandemic were unknown but probably low. A pandemic is global epidemic of disease.

"It may be a while longer, but pandemic will likely occur in the future," he said.

And he said that flu planning would soon become a national exercise.

"It will require school districts to have a plan on how they will deal with school opening and closing," he said. "It will require the mayor to have a plan on whether or not they're going to ask the theaters not to have a movie."

"Over the next couple of months you will see a great deal of activity asking metropolitan areas, 'Are you ready?' If not, here is what must be done," he said.

A key point of contention if an epidemic strikes is who will get vaccines first. The administration's plan suggests a triage distribution for these essential medicines. Groups like the military, national guard and other national security groups were left out.

Beyond the military, however, the first in line for essential medicines are workers in plants making the vaccines and drugs as well as medical personnel working directly with those sickened by the disease. Next are the elderly and severely ill. T