BEIJING, Oct. 31 -- Local authorities across the nation stepped up the war against avian influenza after three outbreaks and the death of a girl who had pneumonia-like symptoms in a bird flu-hit area this month.
Increased surveillance on migratory birds has become a priority in many areas and local officials are setting up checkpoints to keep questionable poultry away from markets.
In Harbin, capital of Northeast China's Heilongjiang Province, a pigeon race was cancelled for fears that the birds might transmit the virus even though an organizer said homing pigeons could not fly as far as Inner Mongolia, Anhui or Hunan where outbreaks were reported.
In Shanghai, medical staff are being trained to handle an emergency; vaccine research has become a key focus; and emergency materials, such as disinfectant and protective outerwear, are being stockpiled.
In Shenzhen of South China's Guangdong Province, health workers are distributing brochures which explain the differences between regular and bird flu and give tips on hygiene.
The Hong Kong government will conduct a drill next month in case of a flu outbreak. Residential communities, hospitals and even Chief Executive Donald Tsang will participate, Xinhua News Agency reported.
The three bird flu-stricken areas in Central China's Hunan Province, East China's Anhui Province and the Inner Mongolia Autonomous Region of North China remain closed to outsiders.
Health authorities had confirmed the death of a 12-year-old girl this month in Hunan after she ate a disease-stricken chicken and caught pneumonia.
The Ministry of Health reported the girl's death to the World Health Organization on Friday evening.
Tamiflu production
Swiss drug maker Roche Holding AG reiterated yesterday that it is looking for outside producers for its Tamiflu drug, amid skyrocketing demand and concerns about a possible pandemic caused by bird flu.
"We are currently assessing which organizations and countries have the ability to supplement our own capability," Roche Chairman Franz Humer said on the sidelines of an event in Shanghai, Reuters reported.
Demand has soared in recent weeks for Tamiflu, an antiviral drug approved for use as a treatment but not a cure for seasonal flu, amid mounting concerns of a potential flu pandemic that could be caused by the H5N1 strain of bird flu.
Countries, companies and individuals have been stockpiling the prescription drug, prompting Roche to suspend deliveries in the United States last week to prevent a run on stocks by consumers and companies.
The spike in demand led Roche to say it would enter into discussions with other companies, primarily makers of generic or copycat drugs, and with governments in developing countries over whether they can help produce the drug in part of as a whole.
The company also previously said it would not let patents stand in the way of getting Tamiflu to patients in case of a bird flu pandemic.
Some countries, such as Argentina, have said they will produce their own version of Tamiflu.
Humer said the decision whether or not countries should stockpile the drug was up to individual nations.
"Countries need to make up their own mind what they intend to do," he said.
(Source: China Daily)
Of the sum, VND13 trillion would be used to equip and upgrade treatment facilities, while the rest would be spent for prevention activities, Nguyen Kinh Quoc told the press in Hanoi.
The press briefing came at the end of a monthly government meeting, which focused on plans to tackle bird flu.
At the meeting, PM Phan Van Khai told the Ministry of Agriculture and Rural Development to ensure bird flu did not break out on a large scale among poultry.
If the epidemic jumped to humans, full responsibility would shift to the Ministry of Health, Quoc quoted Khai as saying.
It was very likely that Vietnam would ban raising, slaughter, and trade in poultry in all cities and major towns, Quoc said.
Agriculture minister Cao Duc Phat signed last Friday a decision to halt import of fowls from November 1 to March 31 next year.
Meanwhile, AFP quoted a Vietnamese medical official as saying Saturday that two people died this week in the central region showing symptoms similar to bird flu but that it could not be confirmed due to concern over the quality of the samples.
In the Mekong delta’s Dong Thap and Bac Lieu provinces, there were two outbreaks of bird flu October, director of the Animal Health Department, Bui Quang Anh, said. Tests confirmed that ducks were infected with the deadly H5N1 strain.
Vietnam has imported over 140 million doses of bird flu vaccine and has distributed half of them to provinces for a mass poultry vaccination program, according to local media.
Animal Health Department statistics show that 10 provinces have completed the vaccination program while 22 other provinces and cities have completed the first round of immunization.
(Source: Thanh Nien, Tuoi Tre, AFP)
BANGKOK, Thailand (AP) -- A woman in a northern suburb of the Thai capital of Bangkok has been diagnosed with bird flu, Deputy Public Health Minister Anutin Charnvirakul said Monday.
The 50-year-old woman, who is recovering in Bangkok's Siriraj Hospital, is the country's 20th human victim of the disease since 2003, and the third this year. Thirteen of those infected by the virus died.
The woman fell ill a day after helping clean excrement from a chicken coop in Nonthaburi province's Buathong district, said Thawat Suntarajarn, director-general of Thailand's Department of Communicable Disease Control. Laboratory results a week later confirmed that she had the virulent H5N1 strain of bird flu, he told The Associated Press.
Thailand's first human cases this year were reported in October in the western province of Kanchanaburi. One was a 48-year-old man who died after handling his neighbors' sick chickens, and the other was his 7-year-old son, who also contracted the disease after handling the birds, but is recovering after being teated with anti-viral medicine.
The human cases arose as fresh outbreaks of the disease among poultry have been reported from several areas around the country.
Bird flu has killed or forced the cull of more than 100 million poultry in Asia since it surfaced in Vietnam in late 2003.
Up through October 24, the World Health Organization listed 121 confirmed cases of bird flu in humans, 62 of them fatal. It listed 41 deaths in Vietnam, 13 in Thailand, four in Indonesia and four in Cambodia.
So far, most human cases have been traced to direct contact with sick birds, but health authorities fear that the virus could mutate into a form that is easily transmissible between humans, possibly causing a global pandemic.
Thai health authorities said earlier Monday they are stepping up their guard against the smuggling into the country of bird flu vaccine for poultry.
Dr. Manit Arunakun, deputy chief of the Food and Drug Administration, said the use of bird flu vaccine was not approved because it might keep the birds from dying but still allow them to carry the virus, increasing the potential for its spread.
Deputy Public Health Minister Anutin Anutin said that six smuggling arrests had been made at a border checkpoint in the northern province of Chiang Rai this year, with 1,500 bottles of bird flu vaccine from China confiscated. With one bottle containing enough vaccine for 650 birds, the total seized would have been enough for almost 1 million doses.
Manit said the number of checkpoints manned by food and drug specialists would be increased to 61 from the current 25.
The sale of such vaccine is illegal and those violating the law could face a maximum penalty of five years imprisonment.
Because my grandfather was one of the victims of the flu epidemic of 1918-19, I've always been diligent about getting my flu shots. But this year, as last year, regular flu shots are not available to everyone who wants them. One reason given is that companies that produce the vaccine risk losing millions when supply outpaces demand for the shots.
Now I read that many physicians are refusing requests for Tamiflu from people who want to protect themselves and their families in case of a pandemic of bird flu [front page, Oct. 22].
Our government is not purchasing anywhere near the amount of Tamiflu doses that would be needed if a pandemic occurred. Why not let individuals create additional demand for Tamiflu by getting prescriptions from their physicians? Such increased demand would motivate pharmaceutical companies to work with manufacturer Roche Pharmaceuticals to produce more Tamiflu.
Similarly, why not set up a subscription system for regular annual flu shots? Such a system would ensure companies producing vaccine of a base demand for their product. A surcharge for subscriptions could cover administration and also increase the availability of vaccine to those who couldn't afford to subscribe a year in advance.
TOM HOLLIDAY,
Annandale.
President Bush recently raised the idea of deploying the National Guard in the event he needed to quarantine a region or multiple states because of a bird flu outbreak ["Troops Might Be Used to 'Effect a Quarantine,' Bush Says," news story, Oct. 5].
This is strange because he already has the uniformed Public Health Service, which is empowered to quarantine people under the Public Health Service Act. Its members would be assisted in quarantine duty by federal law enforcement agencies, including the U.S. Marshals Service and the FBI. The Public Health Service could ask for local assistance, but if a state is cordoned off, any National Guard troops who reside there would be included in the quarantine.
At the same time, Congress, presumably with the blessing of the president, was contemplating budget cuts at the federal level to help pay for the rebuilding of the Gulf Coast states. One of the cuts contemplated was to the budget of the Centers
for Disease Control and Prevention, our first line of defense against any outbreak or epidemic.
Based on the above, I do not believe the administration knows how to manage a major disease outbreak or epidemic.
DENISE D. DION,
Gaithersburg.
The writer is a regulatory consultant and formerly worked as an investigator for the Food and Drug Administration.
Oct 31 (Reuters) - A suspected outbreak of bird flu in poultry on the Greek Aegean island of Chios has proved negative after a second series of tests, the European Commission said on Monday.
Greece had reported on October 17 that H5 bird flu -- which is not necessarily a deadly form of the lethal H5N1 -- was thought to have been detected on the Aegean island of Chios.
Turkey also ended its quarantine of an area in northwest Turkey where an outbreak of bird flu was identified three weeks ago.
Here is a chronology of bird flu developments:
Dec 15, 2003 - South Korea confirms a highly contagious type of bird flu at a chicken farm near Seoul and begins a mass cull of poultry when the virus rapidly spreads across the country.
Jan 8, 2004 - Vietnam says bird flu found on poultry farms.
March 16 - China declares it has stamped out bird flu.
Sept 27 - Thailand says it has found a case where one human probably infected another with bird flu. It said this was an isolated incident posing little risk to the population.
Oct 10, 2005 - The European Commission announces a ban on imports of live birds and feathers from Turkey to the 25-nation EU. This was in response to Turkey reporting its first case of bird flu two days earlier. It was later confirmed as the type dangerous to humans, the H5N1 strain.
Oct 15 - British tests identify H5N1 in three ducks found dead in Ceamurlia de Jos in Romania, the first incidence in mainland Europe of H5N1.
Oct 21 - Hungary says a vaccine against the deadly strain of bird flu has proven effective. Scientists also detect the H5 avian flu virus in wild swans found dead in eastern Croatia.
Oct 23 - Britain says that a parrot that died in quarantine in Britain has been found to have the deadly H5N1 strain.
Oct 25 - Indonesia reports the death of a man from bird flu which, according to the World Health Organisation, brings the human death toll throughout Asia to 62, comprising 41 in Vietnam, 13 in Thailand, four in Indonesia and four in Cambodia.
Oct 29 - A hospital in the central Vietnamese province of Quang Binh says two patients who showed symptoms of bird flu infection had died in the past week.
Oct 30 - Turkey ends its quarantine of an area in northwest Turkey near the Aegean Sea where the outbreak of bird flu was identified three weeks ago. No other incidence has been identified in any other part of the country since then.
Japanese officials planned on Monday to slaughter 82,000 more chickens after signs of bird flu were detected at a farm northeast of Tokyo.
Hong Kong said it would shut down farms and kill all poultry in the territory if the virus is found on more than one farm.
Meanwhile, Pacific rim disaster experts met in Australia to discuss how to respond to a possible pandemic.
The latest Japanese outbreak occurred on a farm in Ibaraki, just northeast of Tokyo, officials said. The farm was inside a quarantined area where authorities had already found signs of the disease and culled around 1.5 million birds, prefectural livestock farming chief Taro Imai said.
Antibody tests showed the chickens had been exposed to a bird flu virus from the H5 family but survived, Ibaraki officials said in a statement. No active bird flu viruses were found, Imai said.
Bird flu hit Japan last year for the first time in decades. Officials say the strain that hit the country, H5N2, is less virulent than the H5N1 variety that has ravaged Southeast Asia since 2003 and killed at least 62 people there.
tMost human cases have been traced to direct contact with sick birds, but health officials fear the H5N1 virus could mutate into a form that is easily transmissible among humans, possibly sparking a deadly pandemic.
Eddy Chan, Hong Kong's deputy secretary for health, welfare and food, said the government would kill all poultry in the territory if the H5N1 bird flu strain was found in chickens at two separate farms.
"If infections happen at a second farm, it shows that the virus is already spreading. So we can't wait for it to happen in a third farm before taking action," Chan told lawmakers at a legislative meeting.
Chan added that all of Hong Kong's 2260 poultry farms would likely be closed for good under the plan.
Hong Kong reported the world's first outbreak of bird flu in humans in 1997 and the illness killed six people there.
Meanwhile, Swiss drug company Roche Holding AG was reportedly in talks with Chinese officials about jointly producing its anti-viral medication Tamiflu, considered one of the few drugs likely to be effective in an outbreak of bird flu in humans.
Countries around the world have rushed to stockpile the drug.
"We are talking with a number of Chinese authorities to see what is the best way to address the issue at this point," the Hong Kong newspaper South China Morning Post quoted Roche's chairman and chief executive officer, Franz Humer, as saying while attending a weekend conference of business and city leaders in Shanghai.
Roche Holding AG has been inundated with requests from other pharmaceutical companies for licences to produce Tamiflu and is doing "everything to increase its supply," the company said in a statement.
Roche's office in Shanghai refused to comment by telephone and did not immediately respond to a written inquiry on on Monday.
China has reported three bird flu outbreaks in poultry over the past month. No human cases have been reported, but authorities warned on Friday that one was inevitable if the country was not able to prevent outbreaks in chickens and ducks.
In Australia, disaster and pandemic coordinators from the 21-member Asia-Pacific Economic Cooperation forum, along with health, animal and quarantine officials, were meeting behind closed doors in Brisbane to determine the best ways to deal with various threat levels posed by diseases such as bird flu.
Speaking on the sidelines of the meeting, Vietnamese Vice Minister of Agriculture Bui Ba Bong said the country needed $US50 million ($66 million) and help building up its stockpile of bird flu drugs as it struggles to keep a lid on the virus.
Vietnam has been hardest hit by bird flu, which has killed more than 40 people in the country and prompted authorities to destroy tens of millions of poultry.
MOSCOW, October 31 (RIA Novosti) - Suspected cases of avian influenza have now been confirmed in ten rural communities across Russia and are being verified in 19 others, the Agriculture Ministry said in a press release Monday. The confirmed outbreak sites are in the central regions of Tula and Tambov, as well as in the Urals province of Chelyabinsk and in Omsk and Altai, in Siberia.
Russia's Kurgan region is the worst affected, with three confirmed outbreak sites and three suspected. In the Novosibirsk province, 16 communities are currently under suspicion.
NOVOSIBIRSK, October 31 (RIA Novosti, Yana Ryabinskaya) - A total of 38 domestic fowl died in a Siberian village in Russia's Altai Territory raising fears of a bird flu outbreak in the region, amid similar reports from two other villages, a spokesman for the local emergency situations ministry said Monday.
The spokesman said specific antibodies to the virus were found in the dead birds and specimens had been submitted to the Novosibirsk regional medical center for analysis.
He said regional medical centers were also examining similar specimens obtained from the two other villages in Altai, where more than 100 fowl have died.
Migrating birds can carry the infection anywhere. The death of a girl in Hunan is still the subject of debate. Beijing stands accused of "excessive use" of an antiviral drug which has led to resistance of the virus. New cases are reported in Japan and South-east Asia.
Beijing (AsiaNews/Agencies) - Alarm bells are ringing loudly in China because of migrating birds which can take bird flu anywhere. Meanwhile the World Health Organisation (WHO) is asking for more information about the death of He Yin, a 12-year-old girl from Wantang in Hunan.
On Saturday, Jia Youling, chief veterinary officer within the Agriculture Ministry, defined the situation as "extremely serious". Said Jia: "The movements of migrating birds are frequent and the virus they carry is highly pathogenic. In April, 6,345 birds died near Lake Qinghai. A total of 138,323 chickens were culled in the last three cases of infection in Mongolia Interior, Anhui and Hunan and the spread of infection was contained. "But it is unrealistic to believe that the country can absolutely eliminate the virus.”
Meanwhile, a polemic between the Chinese health authorities and WHO continues. Chen Xinyi, vice director of the Health Ministry's department of disease control, insists that China did not have any cases of human infection in 2005 and that He Yin died of "pneumonia". However, he added that the disease, which also struck the deceased’s brother, He Junlong - still in hospital - was "caused by unknown factors and we have sent experts on site to undertake better research".
Observers said those who were in close contact with the two children in Wantang were "placed in isolation" and that police were watching the house of the family and forbidding any contact. The epidemic among chickens in the village started more than 15 days ago, however it was declared only on 25 October. Thousands of hens and ducks were slaughtered.
Aphaluck Bhatiasevi, WHO spokeswoman in Beijing said once again that "we do not have indications in the Health Ministry report about which tests were carried out, which samples taken for testing and when they were undertaken". She added that the WHO wanted more information about the case and was offering its help in carrying out laboratory testing. The girl was cremated and there are doubts about whether all necessary tests were done beforehand to ascertain the cause of death.
China has 14.2 billion farmed poultry, which amounts to 20.8% of the global total; its boast is that it has only 1.5% of cases of infection.
Meanwhile scientists have confirmed that the H5N1 virus in Vietnam and Thailand is resistant to Amantadine, one of the two antiviral drugs useful for protecting human beings. They said an excessive use of the drug to vaccinate chickens has led to the development of resistant strains of the virus. China stands accused of having made indiscriminate use of the drug to vaccinate poultry and of having given it to neighbouring countries too. The other drug, Oseltamivir used for Tamiflu, is much more expensive. Jia admitted that Beijing used the drug but never "after the 2004 epidemic" as it has a less expensive vaccine. Experts say the drug is not readily available to other states in the area and that the mutation of the virus points to its extensive use.
Japan. In a large breeding farm in Ibaraki, 100km north of Tokyo, hens have presented anti-bodies to bird flu. It was not possible to ascertain the type of virus. Around 82,000 hens were culled. Japan was struck by the less devastating H5N2 virus in 2004.
Thailand. A new breeding ground of infection among poultry is found in the north-east province of Kalasin.
Indonesia. Anton Apriyantono, Agriculture Minister warned that the situation is "critical, because the virus has infected pigeons" which fly everywhere. The first sick pigeon was found last week in Belasi, a short distance away from the capital Jakarta. Results are expected to ascertain if the virus came from Padang Sambian, a village in Bali, so far immune.
Russia. The infection of many chickens has been verified in the districts of Novicikha, Bavevsky and Gryaznovo, in the Siberian region of Altai bordering Kazakhstan. (PB)
BEIJING -- Organizers canceled a pigeon race and authorities were watching migratory birds for the bird flu virus as China stepped up efforts to prevent a new outbreak, a news report said Monday.
China has reported three bird flu outbreaks in poultry over the past month. No human cases have been reported, but authorities warned Friday that one was inevitable if the country couldn't prevent outbreaks in its huge flocks of chickens and ducks.
In Harbin, a city in the northeast, organizers canceled a homing pigeon race for fears the birds might spread the virus, the China Daily newspaper said.
In Shanghai, medical workers were receiving emergency training and authorities were stockpiling protective clothing, disinfectant and other supplies, the report said.
"Increased surveillance on migratory birds has become a priority in many areas and local officials are setting up checkpoints to keep questionable poultry away from markets," the China Daily said.
In the southern city of Shenzhen, which borders Hong Kong, health workers handed out brochures with hygiene information, the China Daily said.
China has reported bird flu outbreaks on farms in the northern region of Inner Mongolia and the provinces of Anhui in the east and Hunan in central China. Authorities destroyed tens of thousands of birds in order to stop the outbreaks and have quarantined the farms.(AP)
A US delegate at a major avian influenza forum in Brisbane concedes that a human pandemic is likely.
Disaster management experts from Asia-Pacific Economic Cooperation group (APEC) are attending the two-day meeting, which is examining ways to prevent an outbreak of the deadly H5N1 strain of bird flu.
Infectious diseases adviser Dr John MacArthur says he would not be surprised by a global outbreak.
"I think that it's certainly likely," Dr MacArthur said.
"It's happened three times in the past 100 years and we very well expect it to happen again.
"Whether it happens with H5N1 or whether it's another human influenza virus that comes in the future, we'd do very well to expect that a pandemic will occur."
The International Red Cross also warns the risk of a pandemic is real.
"There appears to be a development in the virus where it is becoming easier for the virus to infect humans," Dr Grete Budsted said.
"Most authorities are pretty certain this will happen."
'Do not panic'
Despite the predictions, doctors groups are calling for calm.
The Australian Medical Association's (AMA) president, Dr Mukesh Haikerwal, says the meeting must deliver a clear message to the public.
"What we need to do is reassure the public that we are planning for this, that we are aware of this," he said.
"Reassure the public that they are in no immediate danger so that they don't get too concerned about rushing off getting immunisations that don't exist and rushing off getting tablets and sprays against influenza that may not work."
The AMA's Queensland spokesman for infectious diseases, Dr Michael Whitby, says the deadly severe acute respiratory syndrome (SARS) in China three years ago has taught world medical leaders valuable lessons about possible bird flu pandemics.
The initial outbreak in China's southern Guangdong province killed 349 people.
Dr Whitby says the medical profession is a step ahead after the SARS experience.
"We learnt quite a lot the global initiatives, the cooperation between various countries showed that we can control people crossing borders, we can put in place surveillance and all of those lessons we learnt from SARS are very important," he said.
The APEC delegates will consider issues such as border control and how to keep businesses operating tomorrow.
STAUNTON - Influenza is an unwelcome guest anytime, anywhere. The avian variety periodically sets the poultry-rich Shenandoah Valley on edge; it can - and has - wiped out entire flocks.
A relatively new strain of the type-A avian flu, called H5N1, is playing chicken with the rest of us. Within its rapidly mutating DNA lurks the potential for a sweeping, human-to-human transmission.
Responses to this recent flu renegade range from hysteria to media-overloaded resignation.
In China’s Jilin province, where Augusta County native Timothy Shell manages a livestock farm, the news is likewise mixed.
The English-language edition of the China Daily (newspaper) has "a plethora of articles," Shell wrote in a recent e-mail.
But he sees no change in Chinese farming practices.
"No one here seems too concerned about (avian flu), at least not concerned enough to make any real changes in the root problems that creates (the) bird flu threat," he added.
"Pig/human/poultry pathogen recycling and confinement poultry production models" create the greatest risk to human health, Shell wrote. Human contact with poultry feces is widely thought to be the primary infection route from birds to people.
The ability of the H5N1 strain of the avian flu virus to kill humans makes it a likely candidate for a global disease outbreak, or pandemic. Humans have not yet developed a natural immunity to the new strain, health experts say.
Shell is among those taking precautions.
"I pursue an aggressive immune-building program for the family as the primary strategy for dealing with such risks," he said. "We continually invest time and energy in making diet and lifestyle changes."
A pastured poultry system, such as the one on his farm in China, help interrupt pathogen cycles, Shell wrote.
"Health is always much less expensive than disease," he wrote. "Nature always bats last."
So far, no vaccine has been developed for H5N1.
The World Health Organization Web site acknowledges that certain anti-viral drugs would probably reduce the severity of an infection by the H5N1 flu. But it warns that those drugs (the best known being Tamiflu) would only be effective if administered within 48 hours of an onset of the symptoms.
Furthermore, the WHO Web site states that the drugs’ high cost and slow production would severely hamper its distribution - thus its ability to slow a pandemic.
BAGHDAD, Oct. 29 (UPI) -- Iraqi medical sources reported Saturday the first case of bird flu found in the northern Iraqi Kurdish city of Erbil.
The head of the central veterinary laboratory in Erbil, Ilham Butros, said in a statement made available to United Press International that a chicken was found to have been infected with the strain.
She said a sample was taken from a sick bird in a poultry farm in the city and sent for tests in a reputable Cairo lab because Erbil has no advanced laboratories to detect such viruses.
Butros said the tests in the Egyptian capital confirmed the chicken was infected with the bird flu.
Iraqi medical and veterinary officials have repeatedly said Iraq was free of bird flu and the government has taken strict measures to prevent the entry and import of birds, live and slaughtered chicken and all poultry products.
The report, which could not be confirmed from other sources, makes Iraq the first country in the Middle East to report the strain.
It comes two weeks after Turkey, which borders northern Iraq, reported a case of the pandemic.
AS new cases of bird flu get nearer and nearer, the appearance of streams of migrating birds in our autumn skies must fill us with a sense of foreboding.
Over flight paths that extend across thousands of miles, several billion migrating birds inhale and recycle large volumes of air at a height of around a kilometre above the ground.
If the birds are incubating the dreaded H5N1 virus, it is possible that vast numbers of viral particles will be discharged into the atmosphere, some of which would serve to nucleate raindrops, others would rise in updrafts into the stratosphere and be carried around the world.
There is a wealth of information to be gleaned concerning the 1917-19 influenza pandemic, if one has the patience to leaf through tomes of yellowing papers in the dusty archives of libraries.
This is precisely the task that the late Sir Fred Hoyle and I undertook in 1978, examining sources that included The Times, Times of India, The Lancet and US Senate Committee reports to name but a few. Our researches led to a stark, yet inescapable conclusion: at the very least some component of the infective agent responsible for the 1918-1919 outbreaks of a lethal brand of influenza fell directly through the skies.
Long before the viral cause of influenza was established, physicians in the late 19th century had confidently asserted that epidemic influenza spreads so rapidly across the country that it defies explanation on the basis of person-to-person spread alone.
The distinguished English physician Charles Creighton described its spread as a miasma descending over the land. The viral nature of the causative agent does not preclude a reservoir being established in the atmosphere, for instance through the agency of high flying birds.
While we await the prospect of another influenza pandemic with apprehension, various estimates of the economic cost of such a major disaster are being aired. One such estimate gives a worldwide death toll of 7.4 million, a cost to GDP in Britain alone of £95m, and close to a billion job losses across the world as companies go bankrupt.
Whether or not one accepts these forecasts, it is clear that any measures to reduce influenza attack rates by even a few per cent would have huge economic benefits. In the absence of a full knowledge of how pandemic influenza arises and spreads, lessons from history are worth looking at more carefully than they have been done so far.
Particularly so as the bird flu virus currently in circulation in the avian population has been discovered to be very similar in its gene structure to the virus recovered from victims of the great pandemic of 1918-19.
If we had even the slightest clue pointing to pandemic flu being carried though the air, for instance in fog and mist, it would surely be foolish to dismiss this possibility out of hand. There are indeed tantalising hints from the historical record that such a process might have occurred for the lethal second wave of the pandemic that ripped across the world in 1918, taking a huge toll of life.
Estimates of the death toll in 1918 vary from a minimum of 30 million to about twice that number. There are some estimates that suggest that 20 million deaths occurred in India alone. In parts of Alaska and in the Pacific Islands over half the total population in some villages and cities had perished.
The rapid spread of influenza across the frozen wasteland of Alaska in November/December 1918 remains a mystery on the basis of person-to-person transmission. With a population of 50,000 people very thinly spread over an area the size of Europe, and with ground transportation virtually impossible, the only route of viral transfer must have been through the air.
There were three waves of pandemic influenza occurring in less than 12 months. In the first wave, which occurred in the spring of 1918, the attack rate was 50%, but the mortality rate was not high. The second wave, which came in the autumn, was also characterised by high attack rates but very high mortality rates. The peak death rates from this lethal second wave happened to be in the 20-40 year age group, precisely the age group that would presumably have spent more time breathing the external virus-laden air in the course of their hectic social activities and working habits.
The overall scale of the disaster caused by the pandemic is difficult to imagine. Populations in many cities and villages were decimated in a matter of weeks. In the state of Punjab in India, streets were reported to have been strewn with corpses of victims, and at railway stations carriages had to be continually cleared of dead or dying passengers.
On the other hand, some places miraculously escaped from the pandemic. St Helena, an island in the mid-Atlantic, is known to have definitely escaped, despite all the shipping that had called there.
Then there was a puzzling long delay before the pandemic reached the shores of Australia. This country seems to have been quite remarkably free of the disease until early in 1919, despite all the ships that called there from infected ports, and despite the well-attested attacks that occurred in mid-ocean.
The first influenza death in Australia occurred at Sydney on February, 10 1919, and was reported in The Times of London of February 20, 1919.
Again there was an enormous variability in the way ships at sea were affected. Passenger liners arriving in Australia during the pandemic recorded attack rates that ranged between 4% and 43%. And there were similar differences in the attack rates on crews of ships in the British Navy.
The erratic behaviour of the influenza virus, particularly in the lethal second wave of 1918, is described graphically in an article by Dr Louis Weinstein.
He said, "The lethal second wave, which started at Ford Devens in Ayer, Massachusetts, on September 12, 1918, involved almost the entire world over a very short time. Its epidemiologic behaviour, was most unusual. Although person-to-person spread occurred in local areas, the disease appeared on the same day in widely separated parts of the world on the one hand, but on the other took days to weeks to spread relatively short distances.
"It was detected in Boston and Bombay on the same day, but took three weeks before it reached New York City, despite the fact that there was considerable travel between the two cities. It was present for the first time in Joliet in the State of Illinois four weeks after it was first detected in Chicago, the distance between those areas being only 38 miles."
The lethal second wave also provided striking evidence of local patchiness from one American city to another. Death rates from respiratory disease recorded in the late months of 1918 varied dramatically between different cities.
A striking contrast came from Pittsburgh and Toledo, neighbouring cities with normally almost identical death-rates and with populations engaged in similar daily occupations. The late 1918 death-rate from respiratory diseases in Pittsburgh exceeded that in Toledo, not by a few per cent or a few tens of per cent, but by an enormous 400%.
The only reasonable inference to be drawn is that the virus was airborne with an incidence at ground level that was temporally erratic and spatially very patchy. It would be unwise to dismiss the historical evidence that leads to this conclusion as being flawed and inadmissible.
It is true that we have no detailed record of all the causative agents that might have been involved in the 1918 disaster, but the indications are that a pure avian virus, ominously related to the present H5N1 bird flu, was implicated.
Evidence that the human cases of bird flu recorded over the past two years did not show person- to-person infectivity but had a 50% fatality rate, taken together with similar historical evidence from 1918, should make us approach an impending pandemic with a measure of caution as well as humility.
Despite the great strides of progress achieved in the past few years in the understanding of viruses, the complex patterns of genetic variability found in isolates of the H5N1 virus is admitted by experts to defy complete understanding.
An external reservoir of the virus in the high atmosphere, amplified by the exudations of billions of high-flying migratory birds, cannot be ignored, no matter how unlikely it might sound. Winter downdrafts could bring down the amplified virus as nuclei of mist that can directly enter the respiratory tracts of susceptible humans. A heavy fallout in any location could give a semblance of high infectivity which would then be an illusion.
In these circumstances, it would make sense if contingency plans for the next pandemic include measures to minimise unprotected exposure to mist and weather, as soon as cases are detected in any locality.
The use of face masks could possibly reduce attack rates, as well as a general reduction of non-essential travel. It might also be profitable to explore the feasibility of deploying modern techniques of molecular biology to identify viruses in the environment (air and rainwater samples), with a view to preparing vaccines ahead of major infective outbreaks. Such measures should of course to be considered in addition to the other precautions currently in train.
Accepting the possibility of a vertical atmospheric incidence of the pandemic virus, to the extent of taking cost-effective measures such as I have discussed, is fully consistent with the currently accepted Rio declaration of a "precautionary principle" for dealing with serious threats to the environment and to human health.
The Rio declaration of 1992 states that "in order to protect the environment, the precautionary approach shall be widely applied by States according to their capability. Where there are threats of serious or irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost-effective measures to prevent environmental degradation".
The price to be paid for neglecting this principle could be too high.
Chandra Wickramasinghe is Professor of Applied Mathematics and Astronomy and Director of the Cardiff Centre for Astrobiology at Cardiff University
If bird flu erupts into a pandemic, the world will need a lot of vaccine in a hurry. That would be virtually impossible with the current flu-vaccine manufacturing method, which is little changed since the 1940s.
Several companies have bird flu vaccines in development, though none is yet commercially available. Chiron Corp. of Emeryville, Calif., and Paris-based Sanofi-Aventis have begun clinical trials with vaccines that could be ready next year.
But flu vaccines traditionally are grown in millions of fertilized chicken eggs, a process that takes at least six months. The lengthy production cycle makes it hard for drug makers to keep up with mutating flu strains and limits the amount of vaccine they can produce quickly.
The egg-based method is particularly problematic for bird-flu vaccines because the disease threatens chickens, which provide the essential raw material.
So pharmaceutical companies are developing two methods - using cell cultures and DNA cloning - that could speed things up. But each faces hurdles in gaining official approval.
The best-known alternative is to grow vaccines in cell cultures, a decades-old technology already used for vaccines against chicken pox, hepatitis A and polio. Partly by removing the step of procuring huge stores of specially prepared eggs, it makes on-demand manufacturing possible.
Culturing flu vaccine strains using human, monkey or canine cells within sealed vats "can cut the production cycle to about four months, perhaps a little better," while vastly increasing yield, said Lei Zhong, an analyst with Banc of America Securities who holds a doctoral degree in immunology.
Annual flu vaccine preparations begin in February and shots are ready in October. Cell culture vaccines could be available by July, and if a new flu strain suddenly emerged, an updated vaccine could be produced before the flu season peaked.
Chiron, Sanofi-Aventis and other companies have produced experimental cell-culture flu vaccines, and a European product may hit the market as early as next year, Zhong said.
But analysts said a U.S. product was still at least three years away because of more-demanding regulations.
Other vaccine makers and experts are putting faith in a second alternative to egg-based vaccines, one that involves a radical shift into genetic engineering.
Peter Dunnill, chairman of biochemical engineering at University College London, said DNA vaccine production, a technique invented a decade ago, eventually could yield 500 million doses of flu vaccine from a single lab in as little as three weeks and could cut the entire production cycle to three months.
PowderMed Ltd., a biotech in Oxford, England, and San Diego-based Vical Inc. have shown that DNA vaccines hold promise for fighting flu outbreaks.
DNA vaccines are far from proven, said Dr. Stanley Plotkin, an emeritus professor of pediatrics and microbiology at the University of Pennsylvania and consultant to Sanofi Pasteur, the vaccine unit of Sanofi Aventis. But animal studies show intriguing potential for stronger immunity and the prospect that one vaccine could confer a degree of immunity to a range of flu viruses.
PowderMed clones the gene for hemagglutinin, a protein on the surface of flu viruses, within the common lab bacterium E. coli. The flu DNA is purified, dried and coated onto microscopic specks of gold, forming a powder.
In clinical trials of an experimental vaccine for common flu with 36 subjects, the company's vaccine worked well, with no serious side effects. The company said it would soon test a vaccine for H5N1, a bird flu strain.
Vical received a federal grant to develop a bird flu vaccine last month and hopes to advance to human trials with an experimental vaccine within two years.
The company plans to target the virus' surface proteins as well as "conserved core proteins" - internal parts of the virus that are less changeable, said company spokesman Alan Engbring.
The approach could produce a vaccine that would still have some benefit as the flu virus mutated, or allow faster development of a new vaccine if H5N1 evolved into a pandemic strain, he said.
If large-scale trials succeed, the DNA method could offer some of the same advantages as the cell-culture method - with cost savings.
"The expense associated with DNA vaccines is much lower than with the other methods," said Eric Schmid of SG Cowen Securities in New York.
The DNA and cell culture methods are also easier to keep clean than a factory full of eggs.
PowderMed knows the issue firsthand. In May 2003, Chiron Corp. agreed to buy British vaccine maker PowderJect Pharmaceuticals for about $878 million. A month later, PowderJect's plant in Liverpool, England, was cited by regulators for contamination. It was the start of problems that led to the plant's temporary closure last year and sparked a crisis in the U.S. flu vaccine supply.
Chiron spun off PowderMed last year, including executives and researchers at the original PowderJect, as a privately held company dedicated to producing powder-based vaccines. PowderMed has 36 employees and has raised $35 million in venture capital.
Another advantage of DNA vaccines is that they can be given without a needle. PowderMed uses a painless "gene gun" - much like the device used by Dr. McCoy on the TV series "Star Trek." A high-speed puff of compressed helium implants the gold powder into the skin. The devices are so easy to use that the company plans to train grocery clerks to give vaccines.
Nevertheless, DNA vaccines are running well behind cell-culture methods in the competition to replace egg-based methods of flu vaccine production, said Aaron Geist, an analyst with Robert W. Baird & Co. who has a doctorate in microbiology and virology.
"The standard manufacturing capacity of cell culture has been proven in the biotechnology market," Geist said. "We have yet to see the feasibility of DNA vaccines in scientific studies to determine if or when they will hit the commercial market."
Dr. Gary Nabel, director of vaccine research for the National Institute of Allergy and Infectious Diseases, compared egg-based manufacturing to the traditional QWERTY typing keyboard layout - awkward and inefficient, yet so widely used that moving to a new method would be staggeringly hard.
So for the time being manufacturers will try to increase egg-based vaccine efficiency with "adjuvants" - chemical additives that boost immune response so that a lower dose has the same benefit. Chiron reported positive results Friday for early trials of an experimental adjuvant vaccine for H9N2, another common bird flu virus that can infect humans.
"We like DNA vaccines because they are so simple," Nabel said, noting that his agency funds more than $30 million in DNA vaccine research for several diseases. "But it's not quite ready for prime time."
Nabel also cautioned against being seduced by what seemed at first like a miracle solution.
In 1976, swine flu virus was mistakenly seen as a pandemic strain. The government rushed a vaccine into circulation that was later believed to have caused hundreds of cases of Guillain-Barre syndrome, a rare paralytic disorder.
"The ghost of swine flu is out there," Nabel said. "We're trying to balance the risk of the pandemic, the risk of the vaccine not working, the risk of side effects."
Such cases led to stringent regulations that increase safety but delay promising strategies. Given low profit margins in the vaccine business, few drug companies can justify the long-term risk.
"You're talking about a billion-dollar project for not a very high-profit product," said Dr. Paul Offit, a vaccine expert at Children's Hospital of Philadelphia.
Despite the obstacles, one fact remains: With egg-based manufacturing methods, if pandemic flu strikes, the supply of vaccine would run out virtually overnight.
Offit and others have called for urgent action on all fronts.
Nabel endorsed the concept.
"In three to five years we'll say we finally stared this problem in the face and found the solution," he said. "DNA would be part of it."
A faster way?
A new DNA technology may produce more flu vaccine more quickly than the traditional method, which uses chicken eggs.
Traditional method
Samples of flu strains are injected into millions of eggs, where the viruses multiply. The viruses are harvested from the egg whites and killed to produce flu shots. The production process takes at least six months.
DNA vaccines
1. A tiny section of the genetic material of the flu virus is patched into a circular piece of DNA called a plasmid.
2. The plasmid is cloned within bacteria, creating many copies of the viral DNA.
3. The flu DNA is purified, dried and coated onto microscopic gold particles, forming a powder.
4. A "gene gun" uses compressed helium to painlessly implant the vaccine powder into the skin.
The production process would take about three months.
Sources: PowderMed, Times reporting
Of the many worries raised by the H5N1 bird flu, nothing can top modern medicine's reliance on a rickety system that makes influenza vaccine from chicken eggs and has repeatedly failed in the annual bouts against ordinary strains.
Fearing that a pandemic capable of killing millions of people could spring from the avian flu, researchers are studying a range of choices aimed at stretching vaccine supplies, finding new ways to make traditional shots or leaping to new methods of immunization only now being tested in humans.
"Our main weapon in the armamentarium against influenza is a vaccine," said Dr. Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases. "The fragility of the influenza enterprise is real, and we must address it."
The Department of Health and Human Services is investing $165 million to build a stockpile of 20 million doses of an experimental H5N1 vaccine, but there is no certainty the egg-based serum will work. Bird flu won't spread easily among people unless it mutates. Those same genetic changes could render the stockpiled vaccine a mismatch -- triggering a mad race to make a new one.
The fate of millions may rest in the daily work of an army of laying hens, enlisted to deliver billions of eggs to vaccine factories around the globe. But if that same virus also sweeps through the world's henhouses, there may not be enough chickens left to lay the eggs.
In this milieu of unknown risks and extraordinarily high stakes, both government researchers and private industry are mulling over vaccine alternatives.
Fifteen years ago, Dr. Stephen Johnston, now a professor at Arizona State University, developed what he called a "gene gun." With a burst of compressed helium gas, the gun blasts a microscopic dose of gold particles into the upper layers of skin tissue, which are rich in disease-fighting white blood cells.
Piggybacked onto each speck of gold are segments of DNA -- the genetic blueprints of living things -- that once inside these cells cause them to make proteins that rev up the immune system.
Today, a group of British entrepreneurs backed by venture capitalists are testing a version of Johnston's gene gun. The device by PowderMed Ltd. of Oxford can deliver a DNA vaccine that carries the blueprints for protein found on the outer surface of the flu virus. The vaccine can be formulated to mimic the surface proteins -- known as hemagglutinin antigens -- of any flu virus.
Just like the antigens harvested and purified from vaccine strains grown in eggs, these proteins stimulate antibodies that will destroy any similar appearing flu virus that enters the bloodstream.
In a small study last year, PowderMed's gold-borne vaccine raised protective antibodies against a common flu in 12 volunteers. A larger trial of the technology is slated for next year. In August, PowderMed announced that it also had developed a DNA vaccine against the H5N1 strain -- ready only for testing in animals. The first human tests of that vaccine may begin in mid-2006.
PowderMed's prowess in following through with its technology is yet to be proven. The management team had previously owned the troubled egg-based vaccine facility in Liverpool that was sold to Chiron Corp. in 2003. The plant was subsequently shut down last year because of persistent contamination, but Chiron has solved those problems and will be making H5N1 vaccine at the same facility.
Should PowderMed's new technology prove effective, the company claims its vaccine would hold an extraordinary advantage over egg-based serums -- only 2.6 pounds of DNA would be needed to immunize the entire U.S. population. Using standard biotechnology industry processes, it all could be manufactured in three months -- compared with a year for making 80 million doses of vaccine from eggs.
The rush to develop a vaccine for the H5N1 strain is driven by the chilling theory that the bird flu now spreading throughout the avian world could mutate into one that reprises the 1918 Spanish influenza, which killed an estimated 50 million people.
"We really do need an entirely new approach to vaccine manufacturing," said PowderMed chief medical officer Dr. John Beadle. "The 1918 pandemic killed most people in the first six months. An egg-based vaccine won't even be produced in time to make an impact."
If tests prove the DNA vaccine works, the trickier part of this technology would be in making enough of the disposable plastic gene guns. PowderMed's planned factory capacity would yield in three months only enough for 75 million two-dose immunizations. The handheld guns -- each with a tiny reservoir of pressurized helium -- are also inherently more costly than a standard syringe. However, because the DNA vaccine itself would be much cheaper than an egg-based product, PowderMed executives contend that the overall cost would be competitive.
A different approach to DNA vaccines is being pursued by Vical Inc., a small San Diego company run by former executives of Merck & Co. Here, there is no reliance on unorthodox gold beads and helium-powered guns -- the vaccine is injected into the muscle by hypodermic needle.
The vaccine itself contains three components of a flu virus -- the surface antigen, as well as two proteins found in the influenza virus core.
One advantage of including core proteins, according to Vical Chief Executive Vijay Samant, is that they do not mutate as quickly as surface antigens, so a vaccine against one strain of influenza might work against others.
Although the surface antigens raise protective antibodies, core proteins stimulate a second line of antiviral defense known as cellular immunity. Specialized white blood cells detect and destroy the body's own tissues that have been infected by a virus -- preventing them from churning out copies of the unwelcome invader.
A vaccine that stimulates both antibodies and cellular immunity would in theory provide broader and more long-lasting protection against flu viruses. Vical has secured a $2.9 million grant from the National Institutes of Health to develop flu vaccines using the technology, which is also being used to develop immunizations against the Ebola virus and HIV, the virus that causes
AIDS.
Dr. Gary Nabel, director of the NIH's Vaccine Research Center, said DNA flu vaccines hold real promise, but need at least three to five years to prove their safety and effectiveness. "We'd better start now, because if we don't, we'll find ourselves in the future wishing that we had," he said.
Another vaccine alternative is to grow the flu virus in a culture of mammal cells, instead of in eggs. Chiron Corp., the Emeryville biotech company that ran into trouble last year with its egg-based flu vaccine plant in England, on Tuesday announced it has begun testing on human volunteers in the United States a cell culture vaccine against common influenza.
Nabel said cell-culture has been an obvious alternative for many years, but the Food and Drug Administration has been cautious because of safety concerns. The mammal cell lines used to brew vaccines are cancerous -- either dog or monkey kidney cells that replicate continuously.
"They are a wonderful source of cells for production, because almost all tumor cell lines grow forever," Nabel said. The theoretical concern is that a cancer-causing factor in the production cells could migrate into a vaccine. So the FDA has required lengthy "oncogenicity testing" -- for example, injecting in immune-compromised mice to see if they develop cancer -- to be certain the risk is minuscule. "With vaccines, we have to set a very high bar for safety," Nabel said.
Although Chiron's test of the cell culture vaccine in the United States will involve a small number of volunteers, the company completed a large-scale trial of a similar vaccine in Europe last year and has just launched a second one.
Chiron declined to predict when the American vaccine might be ready for marketing approval, but chief executive Howard Pien said he anticipated the company would seek a license in the European Union next year.
Another strategy for stopping a pandemic influenza is to use a live but greatly weakened strain of bird flu in a nasal vaccine. Although the nasal vaccine made by MedImmune Inc. of Rockville, Md., has not proven popular against ordinary influenza, studies have consistently shown that such vaccines offer broader "cross-immunity" protection against strains that have mutated from the original target.
That is a quality that may prove particularly valuable against a pandemic strain.
Last month, the company announced a cooperative research agreement with the National Institutes of Health to develop attenuated strains against all 16 different families of bird flu. The vaccines would serve as seed stock should a pandemic spring from any of these bird flu families. The H5N1 strain comes from only one of those families. Other avian flu strains thought to have a high potential for causing a pandemic include H9N2 and H7N7, which are not as lethal but have shown they can infect humans in close contact with birds.
MedImmune has developed a vaccine strain against H5N1, tested only in animals. "There is a theoretical possibility that it is more immunogenic, would work quicker and would require one shot," said Dr. Harry Greenberg, Stanford's associate dean for research, who helped develop the original nasal vaccine.
Nasal vaccines have the same disadvantage of traditional flu shots, however, in that they are grown in eggs -- a serious drawback against a bird flu that has proven especially lethal to chickens.
The experimental H5N1 vaccine now being stockpiled had to be developed by modifying the surface protein -- in a process known as reverse genetics -- so it would not kill the chicken embryos inside the fertilized eggs used to grow it.
That modification may explain why it takes two 90 microgram doses of the vaccine to build up a protective level of antibodies. "That is a boatload of antigen," said Greenberg. Ordinary flu shots require only 15 micrograms to raise immunity.
Doris Bucher, a flu vaccine expert at New York Medical College in Valhalla, N.Y., said it would take four fertilized chicken eggs to grow two 90 microgram doses of flu vaccine.
At that rate, it would take 1.2 billion eggs to make enough vaccine for the U.S. population -- an enormous demand for chickens themselves at risk from the lethal bird flu. Bucher warned that vaccinating the birds wouldn't help. Their own protective antibodies would prevent the vaccine strain from growing in their eggs. "This could be a major complication," she said.
That leaves pandemic planners with few options in the near term other than to build up stocks of H5N1 vaccine in advance of an outbreak, hope that the vaccine is a match and find ways to stretch existing supplies.
One strategy of "dose sparing" is to inject flu vaccine just under the surface of the skin, rather than into muscle. The technique was employed by doctors in 1957, when the Asian flu pandemic struck. The National Institutes of Health has been conducting high-priority experiments to see if the technique will work again against bird flu.
The reason this may work is that the skin is rich in those specialized blood cells that respond most vigorously to vaccines -- the same immune system cells targeted by the gold-beaded DNA vaccine of PowderMed.
Last year, researchers found that ordinary flu vaccine was effective in as low as one-fifth the normal dosage if slipped under the skin of healthy adults. The effect was less impressive among the elderly test subjects.
Another way to stretch thin vaccine supplies is to combine the vaccine with immune system stimulants called adjuvants. Vaccine-makers often include aluminum hydroxide as an adjuvant to boost potency. Chiron has used a proprietary adjuvant mixture in its European flu vaccines that has shown promise for reducing by 92 percent the amount of H5N1 vaccine required.
During a recent visit to San Francisco, Dr. Klaus Stohr, head of the World Health Organization's influenza program, said the avian flu has spotlighted the need for a more efficient way to combat seasonal influenza, which kills tens of thousands of people around the world every year.
"Radical long-term solutions need to be pursued," he said.
An outbreak of avian influenza in the northeastern province of Kalasin is the first case outside the Central region's poultry zone since the third wave of infections in July. It has raised fears among bird flu fighters about the spread of the disease, and prompted warnings t