BEIJING, Nov. 4 (AP) - China and Vietnam reported new bird flu outbreaks in poultry on Friday, while Japan prepared to destroy 180,000 birds to stop a suspected outbreak and Thailand announced plans to distribute its own generic antiviral drug.
Adding to the concerns, ministers from 17 African nations meeting in Kigali, Rwanda, warned that migratory birds from Europe and Asia could carry the virus to their shores and distribute it throughout the continent.
"The first birds should hit the continent in two to three weeks," said Aberra Deressa, Ethiopia's agriculture minister. "We cannot move separately. We have to move together or we will fail."
Africa is of particular concern, experts say, because its overtaxed public health system will not be able to efficiently report and manage outbreaks of the disease.
The virulent H5N1 strain of bird flu has devastated Asia's poultry flocks and killed at least 62 people since 2003.
Most of the human deaths from bird flu have been linked to close contact with infected birds, but experts fear the virus could mutate into a form easily spread from person to person and start a worldwide pandemic.
China's latest outbreak, its fourth in the last three weeks, killed 8,940 chickens on Oct. 26 in Badaohao village in Liaoning Province east of Beijing, the government said. The outbreak prompted the authorities to destroy 369,900 other birds in the region and came despite efforts to tighten controls on China's 5.2 billion chickens, ducks and other poultry.
Hong Kong immediately banned poultry imports from Liaoning.
No human cases have been reported in China, but the authorities warn that one is inevitable if the government cannot stop repeated outbreaks in poultry.
In Vietnam, where most of the human deaths have occurred, more than 3,000 birds died or were slaughtered this week in three villages in Bac Giang Province, 35 miles northeast of Hanoi, said the provincial vice chairman, Nguyen Dang Khoa.
Transporting poultry in or out of the three villages was banned, and the area has been disinfected and remaining poultry vaccinated, he said. In one village, Van Trung, a dozen local officials went from house to house on Friday, beating to death any poultry they found.
"We expect more outbreaks, not just in Bac Giang, but also in other provinces," said Hoang Van Nam, deputy director of the Animal Health Department. "Cooler weather now makes it easier for the virus to spread."
In Japan, the authorities said they had found that 80 chickens on a farm in Ibaraki Prefecture had been exposed to an H5 virus, a type of virus of which the H5N1 strain is a variety, but had survived. Nevertheless, hundreds of thousands of birds at the farm will be killed as a precaution, officials said.
In Thailand, the head of the state drug production company said Friday that as early as February, the country could begin distributing its generic version of oseltamivir, considered to be one of the most effective antiviral drugs for bird flu.
The Swiss pharmaceutical company Roche developed oseltamivir, known by the trademarked name Tamiflu, but cannot keep up with demand.
Roche confirmed that Tamiflu was not patented in Thailand, so the country could make it without compensating the company. It also offered Thailand its expertise in making the drug, saying it was "interested in ensuring the best possible global preparedness for a potential pandemic threat."
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AP, BEIJING - China and Vietnam yesterday each confirmed new bird flu outbreaks, while Japanese authorities said 180,000 chickens would be killed after signs of the virus were found at a farm.
Adding to global jitters about bird flu, the Asian Development Bank warned in a report that a flu pandemic could kill up to 3 million people in Asia, cost the region billions and plunge the world into recession.
China's latest outbreak -- the fourth in the past three weeks in the world's most populous country -- killed almost 9,000 chickens on Oct. 26 in Badaohao village in Liaoning Province east of Beijing, the official Xinhua News Agency reported yesterday, citing the Agriculture Ministry.
The outbreak prompted authorities to destroy 369,900 other birds in the region, Xinhua said, and came despite efforts to tighten controls on China's 5.2 billion chickens, ducks and other poultry. Hong Kong immediately banned poultry imports from Liaoning, reflecting growing concern that China is becoming a potential bird flu flashpoint.
Beijing created an anti-flu task force this week and a 2 billion yuan (US$250 million) fund to pay for anti-disease work. In the latest anti-bird flu measure, Beijing ordered hospitals to report data on flu cases daily to the government, Xinhua said.
No human cases have been reported in China, but authorities warn it is inevitable if the government can't stop repeated outbreaks in poultry.
In Vietnam, more than 3,000 birds died or were culled this week in three villages in Bac Giang Province, about 60km northeast of Hanoi, provincial vice chairman Nguyen Dang said.
In Japan, authorities said antibody testing had found that chickens at a farm in Ibaraki state had been exposed to a virus of the H5 strain, and that 180,000 birds would be culled. About 1.5 million birds have already been killed in the state after finding signs of the disease at other farms.
In a report released on Thursday, the Asian Development Bank outlined a number of scenarios -- some catastrophic -- that could face Asian nations in the event of a global flu outbreak.
In a worst-case scenario, in which the psychological impact of a pandemic lasts a year, the bank said Asia could lose almost US$282.7 billion -- or 6.5 percent of its GDP -- in consumption, trade and investment and another US$14.2 billion due to workers' incapacity and death.
The report said that "growth in Asia would virtually stop," and the economic impact would likely force the world into a recession. That scenario assumes about 20 percent of Asia's population would fall ill, and 0.5 percent would die.
In a less pessimistic forecast, the bank said that if the psychological impact of an outbreak lasted six months, the cost to Asia in lost consumption, trade and investment would be about US$99 billion.
A separate report by the World Bank said a human pandemic triggered by bird flu could cost the world economy as much as US$800 billion.
AP, HANOI - Thinking about giving your pet parrot a kiss? It's not advised in Hong Kong. And officials in Vietnam say duck blood pudding -- a delicacy for some -- should be off the menu.
The warnings are among the more unusual pronouncements by officials in Asian nations as bird flu fears spread faster than the virus itself.
"Bird owners should not kiss their pets," Hong Kong's Agriculture, Fisheries and Conservation Department said in a statement outlining precautions people should take when handling their feathered friends.
On Tuesday, Vietnam banned the sale of duck blood pudding -- a specialty appetizer that aficionados say is too much of a tradition to give up, although it's been blamed for passing bird flu to people.
"I still eat it. Not everyday, but three or four times a week," restaurant owner Pham Van Vinh said. He sold up to 300 bowls of the cold, congealed treat before recent warnings scared some customers away. "I'm not afraid."
Made from the raw blood of freshly slaughtered ducks or geese and mixed with boiled organs, the dish was linked to at least one bird flu death last year.
But Vietnam, which has been hardest hit by the H5N1 virus with more than 40 deaths, has also offered citizens and tourists a bit of comfort. Anyone infected by the virus in the communist country will be treated at hospitals -- free of charge.
The Philippines and China's largest city, Shanghai, have also announced strict new policies to try to remain bird-flu free.
Shanghai officials say they will disinfect the shoe soles of all travelers arriving by land, sea or air, according to the official Xinhua News Agency. The report was unclear how the sterilization would be done or how authorities planned to enforce such precautions on the millions of people entering the city by road each day.
In the Philippines, officials announced that all athletes from bird flu-affected countries coming to Manila for the 23rd Southeast Asian Games this month will be banned from visiting aviaries and poultry farms -- just in case that was on their itinerary. Health officials have expressed concern the virus could be carried into the archipelago on clothing or shoes.
In addition, a northern Philippine mountain town canceled a bird hunting tradition that draws scores of tourists each year. Visitors will be banned this year from going to Sagada to trap migratory birds at night with nets.
Wild birds have been blamed for spreading bird flu across Asia and into Europe. The disease has ravaged Asian poultry stocks and killed at least 62 people in Southeast Asia. Health experts fear the virus will mutate into a form easily spread from person to person, possibly igniting a global outbreak that kills millions. So far, most human cases have been traced to contact with birds.
Many Asian countries have already declared bans on poultry imports from affected countries and increased surveillance, including screening passengers at airports for fever or other flu-like symptoms.
Some, like New Zealand, have announced plans to seal off all borders if human-to-human transmission is reported.
And last Friday, a Hong Kong lawmaker proposed a solution for stopping bird flu altogether.
"Perhaps what we should do is give each person a gun, and when we see a migrant bird, we can just shoot it," he said.
LONDON Britain will stage a surprise exercise involving 28 European countries to test their ability to cope with a possible avian flu pandemic among humans, the project's director said Friday.
The two-day drill will take place before the end of the year, but health services will not know the precise dates in advance in order to make it as realistic as possible.
Dr. John Simpson, deputy director of emergency preparedness at the Health Protection Agency of Britain, said the event had been planned since January, long before the H5N1 avian virus spread from Southeast Asia to birds in Turkey, Romania and Croatia, heightening fears of a global pandemic.
"It's a command post exercise," he said. "All the countries and organizations have teams playing and it is coordinated from a central operations room in the U.K."
Empowered by the European Commission, the Health Protection Agency has led similar exercises into scenarios including a bioterrorism attack.
The bird flu exercise will include members of the European Union as well as nonmember countries, like Switzerland.
Bird flu continued to spread in Asia on Friday. China reported its fourth bird flu outbreak in three weeks, saying that 8,940 chickens died in a northeastern village despite a nationwide effort to contain the virus. The discovery prompted the authorities to destroy about 370,000 birds.
The Japanese authorities have detected signs of bird flu at a northern farm and plan to kill 180,000 chickens after they discovered antibodies in some for the H5 family of bird flu virus. The deadly H5N1 strain of bird flu, which is the only one that has spread to humans, has not yet been detected in Japan, but the less virulent H5N2 strain hit the country last year.
The Japanese Agriculture Ministry said that it had ordered 30 farms in eight prefectures across the country to undergo testing because previous tests at these farms had been carried out by private veterinarians. This called the results into question, said a ministry spokesman, Hirofumi Kugita.
Vietnam also confirmed bird flu outbreaks in three northern villages, despite stepped up efforts to fight the disease. More than 3,000 poultry died or were killed this week in Bac Giang Province, said Nguyen Dang Khoa, vice chairman of the People's Committee of the province.
In the European exercise, hundreds of officials at health departments in Europe, experts in other areas and business partners will help assess how well countries are prepared and what gaps need to be filled if a pandemic emerges.
Although Simpson, a communicable disease epidemiologist, could not reveal details, he said the scenario would probably be a pandemic strain emerging in Southeast Asia and spreading to Europe.
A deadly outbreak is more likely to begin in Asia because of the closer proximity between humans and animals. But where it happens does not affect the planning. If it does emerge in Asia it would give Europe about two weeks to prepare, according to Simpson.
The European exercise will examine the role of countermeasures including antiviral drugs and any vaccine, assess containment measures and examine the role of the European Commission during a pandemic.
In the 1918 Spanish flu pandemic, between 20 million and 40 million people worldwide died. There was about a 2 percent mortality rate. In subsequent pandemics in 1957 and 1968, which killed far fewer people, it was about 0.45 percent, Simpson said.
"We know at some point there will be a pandemic, so it is an important thing to have preparedness for," he added.
In Asian reaction to the spread of the disease, the government of Hong Kong said Friday that it was banning the import of live chickens and poultry meat from the bird flu-affected northern Chinese province of Liaoning.
Health experts are warning a flu pandemic is imminent - with attention being focussed
on the deadly H5N1 strain of bird flu which has emerged in South East Asia.
The UK government has put together a plan for what it would do if a pandemic reached the UK.
BBC News, London,
4 November, 2005.
Here, the BBC's 'Panorama' programme looks at the dilemmas it poses.
THE PROBLEM
The UK first began planning for a flu pandemic earlier this year, putting it ahead of the vast majority of countries in the world who have no plans in place at all for a pandemic.
But flu is not an easy thing to prepare for.
People will not have immunity to a pandemic flu because it will be a new type, and many will die. Others will spread it unknowingly.
The biggest unknown is how bad it is all going to be. The government is working with a range of outcomes from under 20,000 deaths up to 750,000.
Plans which might work to ameliorate suffering and panic at the lower end of this scale, will look completely inadequate at the other end.
The UK's plan will come into operation when the World Health Organization reports that a new variant of flu is transmitting from human to human.
How the UK acts will depend on how the virus behaves, what age groups it targets, where the flu comes from and how fast it transmits.
But the proposals lead to a number of dilemmas.
SHOULD THE GOVERNMENT SHUT SCHOOLS?
Schools, where large groups of people gather and mingle, are central to the spread of any infectious disease.
Children may be stopped from going to school in a flu outbreak
When children catch flu, the period of time during which they could pass it on to other people, is longer than for adults who have caught the same bug.
So it makes sense to shut schools to curb the spread of disease.
But that would mean parents having to be at home to look after the children - including nurses, doctors, police and local government officials, who would all be needed to cope with the pandemic.
It would also remove a large proportion of people from the workforce, affecting business.
And it's not clear that closing schools will actually stop children socialising with each other.
How long would parents be willing to quarantine their children for? If they are out on the street playing football with the neighbours then they may as well be in school.
Local education authorities would take the responsibility for deciding if schools should be closed, but a situation where one area chooses to shut schools while another keeps them open is probably not tenable.
Local authorities have asked for more guidance from the government.
It is a tight call, and for now the government has decided that making the decision will have to wait until a pandemic strain emerges.
If it is clear that it affects the young in particular, schools will be shut.
If not, if the virus kills the elderly as the seasonal flu tends to, they will probably remain open.
SHOULD THE GOVERNMENT RESTRICT AIR TRAVEL?
If, as is most likely, a pandemic starts in South East Asia, the way it will arrive in Britain is on an aeroplane, carried by a human.
Given this knowledge, it would seem to make sense simply to stop flights coming into the country.
But if air travel was stopped as soon as a pandemic was identified, thousands of UK citizens would be stranded abroad.
During the SARS outbreak, travellers in the affected area were checked
Even shutting routes into the UK from one country in South East Asia would result in abandoning travellers, business people and diplomatic staff to the flu.
It would also be hugely detrimental to the affected area, potentially stopping the flow of aid and medical supplies.
And if you cannot stop 100% of flights, it's not really worth stopping any.
Modelling work has shown that if you even let in 1% of normal flights you have merely slowed the spread of flu by a few days or weeks, at vast cost to the economy.
Australia has said it will screen all passengers for flu on entrance to the country when a pandemic starts elsewhere.
But some might develop symptoms during the flight, and still others might carry the flu without ever appearing ill.
UK scientists warn people can have flu, and be able to spread it without having any symptoms, so airport screening catches only a very few cases.
The differing strategies of governments is likely to cause some confusion and there is chance that, even in Britain, politicians will respond to public demand to 'do something'.
Potentially, you could quarantine people in the same way that live animals are quarantined today, but this is an extreme measure which may not be popular or possible.
ANTI-VIRAL STRATEGY
Anti-virals are drugs which can be used to treat flu, and are potentially life saving.
The government has currently ordered enough Tamiflu to treat 25% of the population from its manufacturer Roche.
The government is stockpiling millions of courses of the drug
The stockpile of 14.6m doses will be in place by September 2006.
When a pandemic strain emerges, doctors will see which groups are most at risk, and allocate the stockpile accordingly.
The elderly, and people with weakened immune systems are likely to be among those at the top of the list.
People need to be given the drug within 48 hours of developing flu symptoms for it to be effective.
How the NHS gets the drug to people in this timeframe is still being worked out.
It may be that there are 'flu centres' where you go to pick up the drug or that it is actually delivered to your door by a health professional.
Tamiflu can also be given to prevent people getting flu - but this only works if they are taking the drug when they are exposed to the virus.
So using the drug this way would mean a stockpile would be reduced very quickly.
But it may be useful to use Tamiflu as a preventive drug in some cases in a bid to stop the spread of the virus.
However, using the drug in this way would mean obtaining more of it, and demand for Tamiflu greatly exceeds supply.
In addition, these drugs have not been tested in a pandemic situation, so no one is certain they will work.
CONTAINMENT
If the human to human transmission of flu was spotted quickly, anti-virals could be given at the point of outbreak in a bid to wipe the virus out by giving it no human hosts to spread to.
Roche has offered to provide the World Health Organization with a stockpile of 3m doses of the drug which would be shipped to the scene of the outbreak when it was discovered.
But come a pandemic, the biggest stockpiles will be held by governments like our own.
Would it be better to send this stockpile to the country where the pandemic occurs, or keep it and wait for the flu to come?
Again this is not an easy call. If the containment strategy doesn't work then the government would have used up part of a stockpile which could have been used for treating sick people at home.
If a pandemic were to start closer to home in say Romania, Turkey or another European country, the decision is likely to be harder.
We might feel more responsibility to closer neighbours, and our economic ties with these countries are stronger.
Even some of our essential services, such as domestic gas, are dependent on European suppliers.
Across Europe, stockpiles of anti-virals are nowhere near WHO recommended levels.
The EU, as part of its co-ordination of pandemic plans - which will be discussed later this month, is considering creating its own 'solidarity fund' in order to pay for anti-virals and other measures if a relatively unprepared country is affected first.
VACCINE STRATEGY
Perhaps the most contentious questions of all concern vaccines.
A vaccine against the pandemic strain cannot be made until it appears
No vaccine would be available until four to six months into a pandemic - because scientists have to see the flu strain before they can develop a vaccine.
People will then have to wait their turn for immunisation. Priority groups like healthcare workers will be vaccinated first.
But the government is building up a contingency stockpile of 2m-3m doses of H5N1 vaccine which can be manufactured now.
This is not yet a pandemic strain. The vaccine might offer some protection against the strain which does emerge - but nobody can be certain about this in advance.
The UK government is also tendering for a "sleeping contract" so that a vaccine manufacturer can be primed to produce enough vaccine for the UK population - 120m doses - as soon as the pandemic strain is identified.
In the last three years we have been through the Severe Acute Respiratory Syndrome (Sars) health crisis and are battling our third outbreak of bird flu. With so much experience, we should be confident in our ability to handle medical emergencies and have quarantine and control honed to a fine art. And perhaps all of us would have this confidence, were it not for those alarmists fanning the flames of hysteria with their predictions of a pandemic of biblical proportions. The agent of our destruction, they say, will be the H5N1 avian flu virus which, at present, is simply not capable of human to human transmission. In the future, who knows? This is a formidable enemy but there is no need for the scaremongers to whip up a mass frenzy. There are no records of anyone seeing the ``black death'' coming nor did anyone predict the 1918 global flu outbreak which took the lives of over 50 million people. The experts failed to see the implications of ``mad cow disease''in Britain and did not even sound the alarm when the first cases of HIV/Aids emerged. These purveyors of gloom did predict Y2K, though, and the crippling millennium bug that wasn't. To put it mildly, the track record of these doomsayers is not very good.
Yes, we should do everything in our power to control this latest threat and people are right to be scared of it. We must, and are, taking it seriously. But, no, there is no reason to panic or smuggle in illicit tubes of vaccine from China to secretly immunise birds, avoid cooked chicken, refuse to eat eggs or head for the hills. Nor should anyone listen to unscrupulous entrepreneurs, purveyors of spam and snake-oil salesmen cashing in on people's fears by selling them drugs purporting to be the anti-viral Tamiflu treatment or various other ``immune-system boosters'' over the internet along with `magic' potions fraudulently claimed to protect against the virus. These human parasites turn fear into fortunes. Remember the anthrax scare?
While genuine Tamiflu can lessen the severity of the symptoms of the current strain of avian flu, it cannot protect against it. If abused, though, and taken by the wrong people for the wrong reasons, it could create resistant bugs and become useless in the event of a real emergency. This could be disastrous because Tamiflu is regarded as a first line of defence in combating human infection. Fortunately, the Health Ministry has imposed strict controls on stocks and limited the ability to write prescriptions to infectious disease specialists. The stuff circulating at high prices in the black market is almost certainly fake.
So far this week we have had one case of bird flu and two scares over deaths which were unrelated. The death toll in the eight years the disease has been known to exist stands at 13 in Thailand and 62 worldwide. Scientifically, this is insignificant -- far more have died from food allergies -- and if the sole method of transmission remains from bird to human then we are safe from any threatened great plague.
If, though, it crosses over, mutates and becomes a human-to-human strain then, and only then, are we in danger of an epidemic which could spiral into a pandemic if a vaccine could not be synthesised and distributed in time. Even so, it could get watered down in making the jump to humans and turn out to be nothing more than a really nasty flu. And such a jump, if it ever happened, could take years. Medical technology, in the meantime, is moving fast to combat such threats. After all, this is not 1918, when health services were rather primitive.
So let's calm down, stop hyping this up and scaring ourselves half to death, and start making sensible contingency plans. We are already one of the best-prepared and equipped countries in the region in terms of being able to tackle a large-scale and fast-developing public health emergency. Disease containment is nothing new. Sars was the trial run and was successfully stopped in its tracks. Then there is the matter of cooperation. All countries have to ensure resources are in place within the region most likely to be the source of any pandemic, which, in all likelihood if it ever happened, would be us. The challenges would be great but not insurmountable so long as we kept our collective fingers and thumbs away from the panic button.
HONOLULU -- It sounds a bit off the wall, but some people believe eating kimchee could ward off the avian bird flu.
"I'm a believer in kimchee," said Ray Fretias. "I really think it keeps you healthy."
A report out of Seoul, Korea, points to how infected birds recovered from the flu after being fed an extract of kimchee.
"Maybe it does help some with bird's immune system, but it's a big extrapolation to think it would help a human's immune system if in fact, it really does do that," said human nutrition and animal science specialist Alan Titchenal.
Titchenal has his doubts how the bacteria produced by the spicy fermented cabbage would help tackle the virus, but one local business is looking at how the publicity about the avian flu may help its sales.
Halm Enterprises is Hawaii's largest kimchee company. It's already been approached to develop a new product line.
"We have been approached by a gentleman that has interest in producing a natural organic kimchee with the thought, as he has found it, has some value to help in avian flu problem," said Gary Ishimoto, of Halm Enterprises.
Ishimoto isn't so sure eating kimchee will help ward off avian flu, but he just might eat extra before he heads off to China and Vietnam this month.
© 2005 by TheHawaiiChannel.com
WESTWOOD - As many as 180,000 Californians could die -- and millions more hospitalized -- if bird flu becomes contagious among humans and reaches California, health officials warned Friday.
"There's no reason to believe it's not going to reach North America," said Dr. Scott Layne during a hearing on California's preparations for a possible pandemic.
Assemblyman Hector De La Torre, D-South Gate, hosted Friday's hearing at UCLA. State and local health officials, university professors and health advocates outlined the state's level of preparedness in the event of an Avian Influenza outbreak.
De La Torre said he convened the hearing after working on bio-terrorism preparedness this summer.
"I became convinced these issues aren't that different," he said. "We need to be prepared."
Alaska will likely be the first place in North America hit by bird flu, and if that happens, it will be only a matter of weeks before the disease spreads to California, officials said.
Avian flu will most likely be brought to Alaska by migrating birds, Layne said.
"Pandemic flu is coming our way," Layne said. "It's going to, I think with very high probability, get into the animals in the state of California."
"Whether or not its going to turn into a human pathogen is unknown," he said.
During the hearing, Layne painted a grim picture on what bird flu could do to California.
There is a 90 to 100 percent chance Americans will be affected by the disease, which could potentially infect 9 million Californians, of which 180,000 could die, Layne said. Millions more would be hospitalized, he added.
"It will overwhelm us -- it will simply overwhelm us," he said.
Up-to-date information is the best way for Californians to prepare, officials said.
Sandra Shewry, director of the state Department of Health Services, said her agency is tracking statewide cases of pneumonia, flu and respiratory problems.
"Early detection will help," Shewry said.
More staff and better equipment, however, is needed to prepare medical personnel to treat the disease, Shewry said.
There are about 300 million doses worldwide of the only known vaccine for Avian flu, Layne said.
It takes about six months to make that much vaccine, he said.
Like most vaccines, it won't stop people from catching the disease, but they might not get as sick, or die, he said.
Spread by migrating waterfowl, bird flu appeared in Southeast Asia two years ago and has killed about 70 people who had direct contact with infected birds.
There have been about 140 reported cases in four Asian countries, Layne said. No cases of bird flu cases have been reported in the United States, but birds recently have tested positive for the disease in Turkey, Romania, Greece and Russia.
There is no overwhelming evidence that the bird flu virus has mutated into a form allowing for human-to-human contagion, although U.N. and U.S. officials have cited a handful of suspected cases of such transmission since the late 1990s in Hong Kong, Thailand, Cambodia, Thailand, Vietnam, Indonesia and -- in 2003 -- the Netherlands.
The possibility of the virus mutating into a form that can pass from human to human is behind fears of a pandemic.
If a bird flu pandemic breaks out, the world's ability to fight back may come down to an ancient Chinese cooking spice - or the perseverance of people like Professor Frost.
The Chinese spice, star anise, provides the starting material for the manufacture of the anti-influenza drug Tamiflu, which is expected to be the first line of defense in a pandemic.
But there is probably not enough star anise in China or anywhere else to meet the rapidly growing global demand for Tamiflu. That could mean that Tamiflu production cannot be ramped up, even if the maker, Roche, bows to pressure to allow other companies to manufacture the drug.
The professor is John W. Frost, a chemist at Michigan State University who developed a technique for making the starting material, shikimic acid, without the coveted star anise. Roche has used Professor Frost's method in recent years, in fact, but he says he heard the company had cut back. Undeterred, Professor Frost is starting a company that he says could produce huge quantities of the material.
"I'm just completely astonished about the gnashing of teeth and the wringing of hands about the shikimic acid," Professor Frost said. "The bottleneck should not be shikimic acid availability."
Professor Frost is one of many entrepreneurs seeking to help ramp up production of Tamiflu, perhaps the most sought-after drug in the world right now. Roche says it has received licensing inquiries from more than 100 companies. And some countries and companies say they might produce Tamiflu, also known as oseltamivir, even without Roche's permission.
But a debate is raging on how easy that would be to do.
Roche has said the manufacturing process requires 10 steps that take six to eight months once the raw materials are in hand. It also says that some steps in production are potentially hazardous because they involve the use of sodium azide, the chemical that makes automobile air bags inflate in an explosive rush. The company says it would take a newcomer two to three years to be able to start production.
Roche has never said how much Tamiflu it can make, only that by next year it will be making 8 to 10 times the amount it did in 2003. Roche would not discuss its manufacturing for this article, saying it would do so at a presentation Wednesday at its headquarters in Basel, Switzerland.
But others insist that the manufacturing process, while more challenging than for some drugs, is not extremely difficult.
"I don't think the chemistry is such a big issue," said Yusuf K. Hamied, chairman of Cipla, a generic drug company in India that has announced it will produce oseltamivir, the generic name for Tamiflu. He said Cipla already uses sodium azide, the air bag chemical, to produce the AIDS drug AZT and an anti-epilepsy drug.
Part of the disagreement about the difficulty might stem from the difference between making small quantities in the laboratory, which can be done quite easily, and producing large amounts commercially. Ernie Prisbe, vice president for chemical development at Gilead Sciences, which invented Tamiflu and licensed it to Roche, said an industry rule of thumb is that each step, even if well defined, takes one month to six weeks to put into practice. Tamiflu manufacturing, by his count, involves 12 steps.
The National Health Research Institutes of Taiwan took only 18 days to produce a small quantity of Tamiflu, with guidance from published papers and patents. But producing large quantities is "another story" said K. S. Shia, who headed the project. Officials in Taiwan would not say how long it would take to achieve larger production.
Even if companies can make the drug, they might not have enough shikimic acid. That ingredient is extracted from the fruit of star anise trees, which grow in Southern China. Most of the star anise is now used for Roche's production, but it is also an Asian cooking spice and is used in herbal medicines and in the production of the liqueur pastis.
Since demand for Tamiflu started growing recently, the price of shikimic acid from China has soared to more than $400 a kilogram, from $40.
"We managed to corner a few tons but it won't go very far," said Mr. Hamied of Cipla. The company hopes by March to have produced enough oseltamivir to treat 100,000 to 200,000 people, he said.
Last week, the Taiwan government said it had signed an agreement with an unidentified supplier for three metric tons of shikimic acid, which could conceivably provide enough drug to treat 2.3 million people.
According to a presentation at a conference last year by a Roche chemist, it takes 13 grams of star anise to make 1.3 grams of shikimic acid, which in turn can be made into 10 Tamiflu capsules - enough to treat one person. By that reckoning, one ton of shikimic acid would be enough for 770,000 people.
But Mr. Hamied, a chemist, disputed that, saying one ton of shikimic acid would yield enough for only 300,000 people at most. And newcomers are not likely to have the same production efficiency as Roche, he said.
The alternative method of producing shikimic acid developed by Professor Frost involves fermentation using vats of genetically engineered bacteria. He said people he knew at Roche told him the company has curtailed the fermentation of shikimic acid to devote fermenting equipment to more valuable products. If so, that would increase the pressure on star anise supplies.
In the fiscal year that ended in June, Michigan State received $113,000 in royalties from Roche, according to Paul Hunt, the university's associate vice president for research and graduate studies. Roche pays $1.85 for each kilogram of shikimic acid it makes using the process, indicating it made about 60 metric tons in that year.
Roche has given conflicting statements about its use of fermentation. In an e-mail message, Daniel Piller, a spokesman for Roche, said the company got about a third of its shikimic acid from fermentation and planned to increase that over time.
In a conference call with securities analysts two weeks ago, William M. Burns, the head of Roche's pharmaceutical business, said fermentation was part of the company's plan for the medium term. But for now, he said, the use of star anise was the only process approved by regulators.
Professor Frost, some industry consultants and Gilead, though, said that government manufacturing regulations did not cover the production of shikimic acid.
In any case, Roche is apparently looking to farm out fermentation to others, according to Professor Frost. He is starting a company, Draths Industries, in hopes of supplying it to Roche and other companies.
Professor Frost, working with MBI International, a fermentation company in Lansing, Mich., near the university, said he hoped to raise $1 million and had lined up a big fermentation company in Asia that would be able to produce 100 tons of shikimic acid a year.
Gilead initially chose quinic acid over shikimic acid as a starting material. Quinic acid, from the bark of the tropical cinchona tree, was available in much greater supply and at lower prices, even though using it required more steps than using shikimic acid, Mr. Prisbe said.
But political upheaval in Zaire, the source of its material, raised doubts about future supplies, forcing Gilead to scramble. "Roche was saying if you guys don't come up with a starting material you don't have a deal with us," Mr. Prisbe said.
Gilead began looking at extracting shikimic acid from gingko trees and even found a scientific paper discussing the extraction from needles of giant sequoias. A gingko products company in Beijing offered to supply the material but suggested star anise would be a better source.
Still, quinic acid could be a potential alternative starting material and there might be other sources of shikimic acid besides star anise. Virtually all plants produce some shikimic acid, which they use in making certain amino acids. The herbicide Roundup, in fact, works by interfering with this process.
To make Tamiflu, shikimic acid is turned into an intermediate called an epoxide through a series of about five steps that are not considered out of the ordinary. But then the ring-shaped epoxide molecule must be opened up and some atoms substituted for other atoms.
That is where the air bag chemical, sodium azide, comes in. Chemists say it is used because it can produce a sharp, clean reaction that leaves few impurities. Although the reaction used to produce Tamiflu does not involve explosions, the azides, as a class, can be explosive. But sodium azide is not dangerously so, some experts say, or it would not be used inside cars.
"It's a wimpy explosive," said Thomas Archibald, a chemical consultant in the Virgin Islands. He and some others say that drug companies have a needless aversion to azide chemistry - a fear that K. Barry Sharpless, a Nobel Prize-winning chemist at the Scripps Research Institute, has referred to as "azidophobia."
Many drug companies, including Roche, farm out azide processing steps to companies that specialize in what the industry calls "energetic" chemistry. Such contractors, presumably, would be available to companies besides Roche that want to make Tamiflu.
Many of the companies started doing work on explosives for the military or other uses. Aerojet Fine Chemicals, which did the initial azide processing for Gilead, is part of a company that builds rocket motors outside of Sacramento.
"This is our version of turning swords into plowshares," said Joseph Carleone, Aerojet's president. "We took our ability to handle explosives and propellants and applied it to pharmaceuticals."
Mr. Carleone would not say whether his company was doing Tamiflu work for Roche, citing customer confidentiality. Roche has recently said that it has set up manufacturing in the United States at the behest of the federal government, which was worried about reliance on foreign supplies of a vital drug.
Among those looking at Tamiflu manufacturing is Gilead, which wants to regain control of the drug from Roche. It accuses Roche of not doing an adequate job in manufacturing and marketing. Roche denies that, and the dispute is in arbitration.
Whether for Gilead or for others, when it comes to making Tamiflu "on a scale of 1 to 10 in difficulty, this is maybe a 7 or so,"' Mr. Prisbe said, "There's nothing that overwhelming in this kind of synthesis, or that formidable, that someone couldn't do it."
Keith Bradsher contributed reporting for this article.
Vietnam will continue talks with Swiss pharmaceutical company Roche for permission to produce the anti-viral drug Tamiflu but will go ahead and produce the drug anyway if it fails to get permission Tamiflu is the main drug used to treat bird flu.
On November 7, the Ministry of Health would meet with Roche to discuss conditions and procedures for the right to produce the drug in Vietnam, Cao Minh Quang, head of the ministry’s Drug Administration Department, said.
If Roche consented, Quang told Tuoi Tre newspaper, local production of Tamiflu would begin in the first quarter of 2006 at the latest.
“If Roche disagrees, the country will go ahead and produce the drug for non-commercial purposes since Roche was unable to satisfy its orders,” Quang said.
He was referring to an earlier ministry plan to place an order with Roche for eight million Tamiflu tablets in phase one and 25 million tablets in the next phase.
Roche had, however, said it could not meet the order completely. The drug giant said delivery would be made in early 2007 if Vietnam placed order right now.
Locally-made Tamiflu would be sold for US$1.5 per tablet, Quang added.
Soaring price
Quang said the health ministry had stockpiled large quantities of Tamiflu as a precaution against a bird flu pandemic.
Le Truong Giang, deputy director of the HCMC Health Department, assured the city had enough drugs to fight the pandemic up to a certain level.
The health ministry had promised to supply more if a pandemic did break out.
However, local authorities and hospitals have rushed to purchase the drug, creating an impression that demand far outstripped supply.
HCMC-based Pharmaceutical Import-Export Co. (Yteco), one of the companies permitted to import Tamiflu, had received orders for 2,000-3,000 boxes, a company official said.
People even contacted Yteco for the drug which could only be used upon doctors’ prescription, he said.
“It is not true to say that Tamiflu is scarce in Vietnam,” said Nguyen Tien Hung, director of Vimedimex, Roche’s distributor in Vietnam.
Hung said his company had 10,000 boxes containing 100,000 tablets in stock.
But, Vimedimex has decided to halt further sales of the drug after many local pharmacies began gouging consumers.
Both Vimedimex and Yteco sell Tamiflu to pharmacies at VND403,000 a box but the market price has soared to VND600,000-700,000.
Immediate check
To address the pricing problem, Quang said the ministry had asked local health departments to check Tamiflu sales at pharmacies.
Stores found to have arbitrarily raised prices would be severely punished, he said.
Source: Tuoi Tre - Compiled by T.H.
UNTOLD numbers of sufferers will be confined to their own homes in the event of a flu pandemic taking grip in Britain, The Times has learnt.
Patients with serious breathing problems will be treated in hospital but the Government’s strategy for the vast majority of the sick is enforced home quarantine.
In a further drastic measure, anyone caught exposing others to the risk of infection will face summary prosecution under emergency regulations in the Public Health Act.
Armed troops would be used on the streets only as a last resort as ministers have made clear that they do not want afflicted communities treated in the same way as the 17th-century villages gripped by the Great Plague.
Police, however, would have a key public order role and would guard supplies of anti-viral drugs and vaccines.
Once a vaccine has been developed, walk-in vaccination centres have been planned but they will be subject to strict queueing rules to minimise the risk of turning them into contamination zones. Scientific experts have said that a minimum two-metre gap is required between individuals to prevent the spread of the virus through droplets.
Schools would be kept open unless there was a particular threat to the young, because the country would need working parents to keep the emergency services running.
A leaflet giving key facts about the virus and advice on self-help would be given to every household, and a television advertising campaign would be run during the emergency. Healthy people, however, would be expected to carry on with their day-to-day lives.
Details of how the country would cope with a flu pandemic emerged as scientists and public health experts prepared to gather in Geneva next week for a three-day World Health Organisation summit on dealing with the deadly avian flu virus H5N1 and its possible human form.
Despite claims from the Conservatives that Britain is lagging behind in preparations, officials have spent more than a year fine-tuning emergency arrangements.
Some controls are already in place. Airline companies have been called in by the Department of Transport (DoT) and told not to carry sick passengers, particularly from South-East Asia, where the H5N1 virus has killed 68 human beings and 125 million birds.
Air companies have the legal right to withhold travel from any passenger, and a number of British people have already been turned away until their health has recovered.
However, the flu virus takes 24 to 48 hours to incubate so unless airline staff spot obvious symptoms they are unlikely to identify sufferers. Port health authority staff have been told to look out for travellers feeling sick on arrival in the UK. New posters are also planned for airports to remind passengers not to travel if they are feeling ill.
The DoT has also reconvened an airline committee set up to deal with the threat of severe acute respiratory syndrome (Sars) to monitor the threat of avian flu.
In China the authorities have already ordered passengers to be screened to check whether they have flu. GPs are also on alert to identify unusual and extreme flu symptoms in their patients. A handful of people with acute respiratory problems are already in hospital under surveillance.
Vets, too, have been asked to monitor cases of the usual seasonal avian flu in dead birds.
At present six tests from birds killed by low pathogenic avian flu are being analysed by the Veterinary Laboratory Agency in Weybridge.
The Government has been in touch with leading banks and food, water, gas and electricity companies to ensure that vital services can continue even if as many as a quarter of staff are off sick.
Gas and electricity companies are keeping retired engineers and maintenance workers on standby to help out in an emergency, while many companies are training extra staff to cope with computer problems.
BANGKOK , Nov 4 (IPS) - Suddenly, in the face of a possible global pandemic of bird flu, the World Bank is developing signs of cold feet. It is choosing to distance itself from the role it has carved out over decades as an advocate of policies to ''help'' developing countries.
The bird flu test that revealed the Bank in this new light is the position it has taken regarding Tamiflu, the only known drug capable of protecting people from the deadly H5N1 strain of the avian flu virus.
The Bank has decided that it is not in keeping with its mission to get involved in the emerging global debate on the Tamilfu patent held by the Swiss pharmaceutical giant Roche and that stands to be broken under the 'compulsory licencing' rules of the World Trade Organisation (WTO).
When pressed on the Bank's position on compulsory licencing and the hope it holds out to protect people in the developing world, a senior Bank official revealed this week that the Washington-based entity is not in the business of ''advocating'' or ''taking positions'' on issues under ''negotiation''.
''We do not take positions and advocate what should be happening in any of the trade negotiations,'' Homi Kharas, the Bank's chief economist for the East Asia and Pacific region said Thursday, during a teleconference between Bank officials and journalists in four cities, Washington, Bangkok, Phnom Penh and Hanoi.
''When there are concrete proposals on the table, we are asked how they might affect our member countries, the developing countries, and then we offer (our) analysis,'' he added. ''We will be doing the same kind of analysis with compulsory licencing as well.''
The debate over compulsory licencing has heated up after it became evident that Roche was unable to meet the international demand for Tamiflu.
Joining the fray and calling on Roche to give up its right to the patent to save lives are ranking officials from the United Nations and a member of the U.S. Senate, Chuck Schumer.
By late October, the Swiss company had caved in and agreed to give four manufacturers of generic drugs the licence to produce Tamiflu.
Under compulsory licencing, countries have a right to break the patent of a brand-name drug if it is an available remedy to save lives from public health emergencies. For years, developed countries like the United States, Canada and Australia have resorted to this measure when faced by public health crises, according to a U.N. study.
Yet, developing countries have been prevented from pursuing such measures, even after a breakthrough at the WTO ministerial meeting in Doha, Qatar, in November 2001.
Pressure by the developed world to protect the profit margins of the pharmaceutical giants has been the main reason in denying the developing world an opportunity to make the commitments at the WTO meeting in Doha a reality. It was agreed by trade negotiators at that gathering that developing nations, under the special provisions of the Trade-related Intellectual Property Rights (TRIPS), can either produce or buy cheaper generic drugs to deal with pandemics, such as HIV/AIDS.
This week's revelation by a senior economist at the Bank comes at a time when it, together with other financial institutions like the Manila-based Asian Development Bank (AsDB), have expressed worry about the dismal picture that lies ahead if bird flu triggers a pandemic.
Yet, when it comes to the obvious life-saving solution, the Bank is trying to present itself as a powerless and passive entity, preferring to observe events from the sidelines of global policy debates.
Such a position, however, is far from the case when it comes to strengthening opportunities for multinational companies to profit through the onward march of the global free-trade agenda.
A typical example of such advocacy is the paper prepared by Bank officials to pressure developing countries to embrace the neo-liberal trade policies at the forthcoming WTO ministerial meeting in Hong Kong.
''Openness to trade has been a central element of successful growth strategies: in all countries that have sustained growth, the share of trade in GDP (gross domestic product) has increased and trade barriers have reduced,'' argued this paper, prepared in August by the Bank, 'Trade Progress Report: Doha Development Agenda and Aid for Trade'.
Little wonder why critics of the Bank are surprised at the excuse offered by it in its attempt side-step the issue of compulsory licencing. '' The World Bank has been producing advocacy documents and pushing its stance on public policy issues for decades. It is no secret,'' Shalmali Guttal, senior researcher at the Focus on the Global South, a Bangkok-based think tank, told IPS.
She argued that the Bank ''should not remain non-committal'' about the debate over Tamiflu and compulsory licencing . ''Even if past health crises did not jog the Bank's sense of ethics, at least the impending threats of pandemics from viruses such as bird flu, should be enough to catalyse it to immediately call for a halt to TRIPS (Trade Related Intellectual Property Rights) and patent regimes.''
Asia Russell, director of international policy at the U.S.-based advocacy group, Health GAP (Global Access Project), argues along the same lines. ''The World Bank should advocate, as part of its efforts to combat poverty, for countries to use their WTO legal rights to issue compulsory licences and take other measures to ensure access to medicines for all,'' she said in an e-mail interview.
So far, 62 people have died out of 121 human cases of bird flu in four South-east Asian countries, Cambodia, Indonesia, Thailand and Vietnam. But public health authorities fear that the virus could mutate to one easily transmitted among humans, triggering a global pandemic that could kill millions.
With a vaccine to prevent this pandemic years away, hope lies in Tamiflu, for the human immune system lacks the strength to fight infections caused by the H5N1 strain of the avian flu virus.
Yet, the global institution that claims to ''help'' the developing world has, quite contrary to its usual character, chosen not to throw its weight behind.
The Bank's convenient silence over compulsory licencing of Tamiflu reveals where its loyalties lie-- with the profits of a pharmaceutical giant rather than vulnerable populations in the developing countries across this region.
''I suppose it will remain non-committal until it is pushed in one direction or the other way by the U.S., or its silence becomes untenable,'' said Guttal.
An official sprays disinfectant around a house in tambon Phimonrat of Nonthaburi's Bang Bua Thong district yesterday to combat bird flu. — TAWATCHAI KEMGUMNERD
The country's 20th bird flu patient, a 50-year-old woman, was probably infected with the H5N1 virus from cooking and eating wild birds at her home in Nonthaburi province, a local health officer said yesterday. His opinion was based on a lengthy interview with the patient, whose name is being withheld, and her husband.
It was at odds with Deputy Health Minister Anuthin Charnveerakul's assertion the woman caught the virus while cleaning out chicken droppings at her husband's fighting cock farm in Bang Bua Thong district.
The husband told the officer that last week he and his wife killed and cooked wild doves for dinner. After returning to Bangkok, his wife became sick and went to Siriraj Hospital on Oct 29.
He said he had been raising more than 30 roosters in his backyard farm for six years. He also caught wild birds for sale and for food. His cocks became sick and died last month after he placed several wild birds in a cage close to their pen.
Dr Ruengpung Sutthent, who is in charge of the sick women's treatment, said her condition was improving because she had been prescribed the anti-viral drug oseltamivir, sold as Tamiflu, at an early stage of her illness.
''When the patient came to the hospital the first time, she told us right away that she might be infected with the avian flu virus. We immediately checked her lungs and found traces of bird flu infection. ''This shows that the patient has a good knowledge of avian flu's symptoms, which eventually helped saved her life,'' Dr Ruengpung said.
The woman is the third victim of H5N1 avian flu since the current outbreak started in July and the 20th overall.
Livestock Development Department chief Yukol Limlamthong said the cause of the woman's infection was unclear. Livestock and health officers were working against the clock to identify it.
Poultry movements in the affected area had been banned to prevent the virus spreading. Doctors were closely monitoring the health of relatives and the husband had been treated with Tamiflu.
Medical Sciences Department chief Paijit Warachit said that the public had become more alert to disease judging by the increasing number of samples sent in for testing _ up from 66 in the first half of last month to almost 400 over the past two weeks.
Bang Bua Thong district chief Surapong Maiyawong said local residents were still at risk of infection as there were up to 100,000 free-range ducks in the district, although they were kept in contained areas.
Officers had been unable to destroy some ducks due to protests from owners.
Agriculture and Cooperatives Minister Sudarat Keyuraphan confirmed fresh outbreaks in three poultry farms in Sam Chuk district of Suphan Buri province, bringing the total number of infected areas to 14 in six provinces _ Chachoengsao, Kalasin, Kamphaeng Phet, Kanchanaburi, Nonthaburi and Suphan Buri.
New Public Health Minister Phinij Jarusombat said he would call a meeting tomorrow of doctors and health workers from 33 provinces where avian flu had recurred to discuss strengthening the bird flu control operation.
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President Bush has announced this week a $7.1 billion plan to prepare the United States for a possible influenza pandemic. As the country heads into another flu season, the highly infectious strain of avian influenza now reported in Asia and Europe - and the danger it could mutate into a quick-spreading human flu - has Americans concerned that the virus could soon reach their shores.
During one week last month the Centers for Disease Control and Prevention logged 500,000 hits on its avian flu webpage. The United
