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A Tourism Mecca, Hawaii Braces for Flu
[Are there quick and easy ways to distinguish H5N1 virus from the common cold? And where can they quarantine a planeload of passengers at or near a Hawaii airport on short notice? (and how will they make the passengers comply?
Plus, if a bird with bird flu arrives in Hawaii, it could devastate the local bird population.]
By AUDREY McAVOY, Associated Press WriterFri Apr 14, 8:51 AM ET
Hawaii, both tourist mecca and western gateway to the nation, is ahead of many states in preparing for a possible global flu epidemic.
With thousands of tourists arriving daily, many from Asia, officials here were first to start an airport flu monitoring program. Experts say the state is "in the vanguard" when it comes to preparedness.
And no wonder. Hawaii's early history is filled with the ravages of disease after Captain James Cook arrived in 1778. Cook's crew and the Europeans who followed brought smallpox, measles and syphilis — devastating to the islanders.
Today the fear is over the potential for a deadly flu epidemic if the bird flu in Asia mutates into a form that is more dangerous to people.
"We are very concerned in Hawaii about the fact we are the western doorway to the United States," said Dr. Chiyome Fukino, director of the state Department of Health. "We see a large number of visitors ... and a good proportion of them are from the Far East where we know a good number of emerging diseases are originating."
The Honolulu airport's program to examine incoming passengers on a voluntary basis was announced in November, making Hawaii the first state to monitor airports for signs of bird flu or other flu viruses.
Officials also have plans for limited quarantines and amassed a supply of protective gear for doctors and nurses. Next month, the state will hold a seminar to help employers learn how a pandemic might affect their workers and businesses.
Dr. Gregory Poland, director of the Mayo Vaccine Research Group at the Mayo Clinic in Rochester, Minn., said Hawaii authorities understand the danger posed by the disease.
"Very definitely you guys are in the vanguard, in the lead of state level and local level preparations," Poland said on the sidelines of a Waikiki conference convened to educate island nurses, doctors, police and others about pandemic flu. "I think you've crossed the biggest hurdle which I said is imaginability. People here seem to get it."
No one knows if there will be a global flu epidemic. But scientists and public health officials are worried about a deadly form of H5N1 flu that has killed millions of birds from Asia to Europe to Africa. Although it is not easily spread to people, about half of the nearly 200 who have caught it since 2003 have died.
If it mutates into a form more easily spread among people, it could unleash a deadly new type of flu.
In Hawaii, which has 1.3 million residents, there are an average of 171,000 travelers at any given time. About 20,000 people fly in each day.
Hawaii's airport plan calls for a nurse to take a swab from a potentially infected passenger on any plane, at the gate, or inside the airport. If tests show the traveler has the H5N1 variety, authorities are prepared to quarantine the entire jet. Officials are also ready to cordon off a gate or other section of the airport to isolate people exposed to the passenger.
Still, officials know they won't be able to fully block the virus even with this approach because some people won't immediately show symptoms and won't be singled out for testing.
Instead, the state expects the screening to alert officials to the presence of the illness so they can contain it as much as possible, said Dr. Sarah Park, deputy chief of the Health Department's disease outbreak and control division.
"You can't guarantee a 100 percent barrier. You need to think more in terms of how do we detect it and once it's detected, how do we control it," Park said.
During an outbreak, Hawaii expects to test 6,000 samples per day. That's enough for more than a third of Hawaii's population over eight weeks — roughly the length of time experts estimate each outbreak will last before petering out.
If the next pandemic proves to be as virulent and deadly as the 1918 Spanish flu, the federal government estimates 90 million people will contract the disease and 1.9 million people will die from it nationwide.
Even if Hawaii is not the first state to suffer heavy losses, experts say it's vital that the islands be prepared.
Robert Kim-Farley, a professor at the University of California at Los Angeles School of Public Health, said Hawaii is right to get an early start because all 50 states will be too busy dealing with their own outbreaks to help anyone else if the disease strikes.
"A pandemic is a local emergency happening worldwide. It's something that has to be handled and dealt with on a local level," Kim-Farley said. "We will never be blamed for preparing too far in advance. We will be blamed, however, if we prepare too late."
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On the Net:
Hawaii State Department of Health: http://www.hawaii.gov/health/
U.S. Department of Health and Human Services flu site: http://www.pandemicflu.gov/
New bird flu tests prove negative
Matt Weaver and agencies
Friday April 7, 2006
Guardian Unlimited
Tests on nine birds checked for bird flu in the wake of the first UK case of the deadly H5N1 virus proved negative, the Scottish Executive announced today.
It followed reassurances that bird flu still posed minimal risk to the British public despite confirmation that a dead swan found in the coastal village of Cellardyke, in Fife, had tested positive for H5N1.
The Scottish Executive yesterday said the remains of another 14 birds found in Scotland were being tested for the disease.
Today, a spokeswoman said she could not confirm how many birds were still being tested and whether the number had risen or fallen since yesterday.
"No further positive results have been received," she said. "Nine negative results have come back, but we are unable to provide a running commentary on every test result."
The Scottish Executive has set up a 2,500km sq wild bird risk area in which farmers have been told to keep poultry indoors. Bird gatherings such as pigeon races have been banned, and the surveillance of wild birds will be stepped up.
The area encompasses 175 registered poultry farms containing more than 3m birds, including 260,000 free range poultry.
The swan infected with H5N1 was discovered more eight days ago in Cellardyke, which is around nine miles from St Andrews.
Local poultry farmers and the Scottish National party criticised the time it had taken to confirm the swan had died of the virulent strain of avian influenza.
The Cabinet Office's civil contingencies committee, Cobra, held a second meeting with Scottish Executive officials to discuss the situation today.
Meanwhile, the Northern Ireland Department of Agriculture and Rural Development also announced that tests on six dead swans found in the province had proved negative.
Four carcasses recovered in Portglenone, Co Antrim, and two found in Moira, Co Down, were checked for H5N1 and given the all-clear.
"So far this year, DARD has tested 23 swans, all of which have been negative for highly pathogenic avian influenza," the chief veterinary officer for Northern Ireland, Bert Houston, said. "We will continue to undertake such testing as necessary."
Earlier today, the government's chief scientific adviser, Sir David King, insisted that Britain was better prepared than any other country to cope with bird flu.
He told BBC Radio Four's Today programme that one case of a bird with the H5N1 strain - which can pass to humans - did not constitute a crisis.
The current outbreaks of pathogenic avian flu began in south-east Asia in mid-2003. There have been 191 confirmed human cases of the H5N1 strain of bird flu reported to the World Health Organisation to date, and 108 human deaths.
http://www.guardian.co.uk/birdflu/story/0,,1749268,00.html
Courtesy of Fiercebiotech.com
400 Chinese students hospitalized with unknown flu
Sun Apr 2, 8:36 AM ET
Over 400 students at a university in central China's Henan province were hospitalized with high fevers linked to an unknown flu virus, state press and a school official have said.
The outbreak began on March 26 when 22 students were hospitalized with high fevers, Xinhua news agency said.
The next day the number of sick students at the Henan University of Science and Technology in Luoyang city rose to 88, and on March 28 there were 208 sick students in the university's infirmary, it said.
"There were over 400 students that became feverish with the flu," a university official who declined to be named told AFP when contacted by phone.
He refused to detail what type of flu it was or how the outbreak had succeeded in infecting so many students.
Local health officials were currently trying to identify the flu strain, Xinhua said.
The temperatures of some of the students reached 39.6 degrees celsius (103.3 degrees Fahrenheit), it said.
The sick students were quarantined while school officials, under directions from provincial health authorities, cancelled classes and began disinfecting the university's 2,000 dormitory rooms, dining halls and classrooms, it said.
Most students were only hospitalized for about three days and released, the report said, adding that only several dozen students remained hospitalized as of Sunday.
http://news.yahoo.com/s/afp/20060402/hl_afp/healthchinaflu_060402123620
Glaxo starts trials of H5N1 pandemic flu vaccine
http://yahoo.reuters.com/stocks/QuoteCompanyNewsArticle.aspx?storyID=urn:newsml:reuters.com:20060330...
>>
LONDON, March 30 (Reuters) - GlaxoSmithKline Plc <GSK.L> said on Thursday it had started clinical trials of two pandemic vaccines against the H5N1 strain of bird flu in humans and reiterated plans to have a shot in production by the year end.
One trial in Germany is testing a flu vaccine made with a classic adjuvant, or additive, while the second study in Belgium involves a novel adjuvant, which Glaxo believes could help stretch supplies of vaccine in the event of a pandemic.
A total of 800 healthy volunteers have been enrolled in the two trials.
A key challenge in the race to develop a potential pandemic flu vaccine is how to make the maximum number of shots from the minimum amount of antigen, or active ingredient.
"The second vaccine may offer governments a preferred option to proactively stockpile and begin vaccination before the onset of a pandemic, significantly increasing the speed of a public health response in the event of an outbreak," Glaxo head of vaccines Jean Stephenne said.
The British-based company has already submitted a "mock-up" dossier to European healthcare regulators seeking outline clearance to market a vaccine against pandemic flu, the first manufacturer to do so under new EU rules designed to fast-track approval.
Should a pandemic flu strain emerge, a variation to the dossier would allow rapid European registration and production.
Experts fear the H5N1 strain of virus now circulating in birds will mutate enough to allow it to pass easily from person to person. If it does, it could cause a catastrophic pandemic, killing tens of millions of people, because humans lack immunity to it.
No one knows how well human H5N1 vaccines will match a future pandemic strain but they might "prime" a person's immune system.
"We believe that vaccinating populations with the appropriate H5N1 vaccine will help educate the body's immune system and reduce expected morbidity and mortality associated with a pandemic," Glaxo flu operations head Emmanuel Hanon said.
"This means that if the current bird flu virus mutates to allow human-to-human transmission, a vaccinated person will be better prepared to combat the H5N1 pandemic flu virus."
Glaxo is one of several companies, including Sanofi-Aventis SA <SASY.PA> and Chiron Corp <CHIR.O>, working to develop a vaccine against the H5N1 strain of virus.
The normal seasonal flu vaccine provides no protection against pandemic disease.
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“Researchers say the bird flu vaccine may be less effective because hardly anyone in the United States has been exposed to the A(H5N1) virus. People have no resistance to it, and so it takes a lot of vaccine to jump-start the immune system.”
An alternate explanation is that perhaps H5N1 is not all that immunogenic, and this could be the reason it is so deadly in those who do get infected.
More on the same story:
http://www.nytimes.com/2006/03/30/health/30vaccine.html
>>
Doubt Cast on Stockpile of a Vaccine for Bird Flu
March 30, 2006
By DENISE GRADY
A bird flu vaccine being stockpiled by the government in preparation for a possible pandemic protects only about half the people who receive it, scientists are reporting. In addition, it must be given in such high doses that if a pandemic were to start soon, manufacturers could not begin to make enough vaccine for all who would need it.
A dose 12 times the amount used in a standard flu shot protected 54 percent of the people in a study being described today in The New England Journal of Medicine. That level of effectiveness is "poor to moderate at best," said Dr. Gregory A. Poland of the Mayo Clinic, who wrote an editorial accompanying the report.
But Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Disease, which paid for the development and testing of the vaccine, called the results "muted good news."
"We have a long way to go," Dr. Fauci said, but he said the research was a step in the right direction, adding, "You have to go through these early steps."
The new report is the first to include results on all the participants, 451 adults ages 18 to 64 who were inoculated at three medical centers in the United States. They received two shots a month apart. No serious side effects occurred, though some got sore arms from the shots.
Dr. Fauci and Dr. John Treanor of the University of Rochester, the lead investigator of the study, discussed the results on Tuesday in a telephone news conference.
The vaccine, developed by government and other researchers, is being made by Sanofi Pasteur under a government contract. It is designed to prevent the disease caused by the A(H5N1) virus, which has been spreading rapidly through Asia, Europe and Africa. The disease has not reached the Americas.
The virus attacks mainly birds, but some humans have been infected, almost all of them through contact with birds, and half have died. Some health officials are concerned that the virus could mutate in a way that would make it more contagious in people and start a lethal pandemic.
Vaccines work by activating a patient's immune system. Standard flu shots, even with their smaller doses, are more effective than the new bird-flu vaccine: they protect 75 percent to 90 percent of people under 65, and 50 percent to 60 percent of those who are older, Dr. Fauci said.
The standard shots probably work better because the viruses they protect against have been around for a long time, and most adults have some immunity to them. The vaccine acts like a booster shot to enhance an immunity that is already there.
Researchers say the bird flu vaccine may be less effective because hardly anyone in the United States has been exposed to the A(H5N1) virus. People have no resistance to it, and so it takes a lot of vaccine to jump-start the immune system.
The study used blood tests, which measured immunity to the virus, and researchers set the bar fairly high. Dr. Treanor said he thought that the vaccine might actually work better than it appeared from the study.
A next step in the research is to try adding a substance called an adjuvant to the vaccine, to try to make it work better and at lower doses. Adjuvants stir up the immune system. Alum is a common one.
The government has stored a "modest" amount of the Sanofi vaccine, Dr. Fauci said, about seven million to eight million doses. He said that such a small amount would not be of much help to the public, but he described it as stopgap.
If the disease emerged, he said, the main purpose of the supply would be to inoculate health care workers and people involved in the rush to make a vaccine specific for the virus strain causing the outbreak.
Currently, the United States does not have the production capacity to make bird flu vaccine and the usual vaccines for seasonal flu.
The bird flu vaccine can be made only between runs of the seasonal vaccines, which have to take priority because those types of flu occur every year, and bird flu is a theoretical threat.
Dr. Fauci said the government was spending several hundred million dollars to increase the nation's ability to make flu vaccine.
Another company, Chiron, also has a government contract to make millions of doses of bird flu vaccine. But Chiron, which has a history of manufacturing problems, has produced only 70 percent of the amount it promised the government it would provide by now, and it will not begin making the rest until this fall.
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I consider these results more disappointing than promising (#msg-10428652).
Bird flu vaccine promising in humans
The NIH and HHS are releasing data on 30 different vaccines in the next 6 -12 months?
http://news.yahoo.com/s/nm/20060330/hl_nm/bird_flu_vaccine_promising_humans_dc_2
By Karla Gale Wed Mar 29, 9:29 PM ET
NEW YORK (Reuters Health) - Tests in humans of an experimental vaccine against H5N1 avian influenza (bird flu) show that the vaccine is safe and spurs the immune response needed to protect against the deadly illness. The achievement is reported in The
New England Journal of Medicine this week.
Dr. John J. Treanor, from the University of Rochester Medical Center in New York, and his associates developed the vaccine, in part, by using the hemagglutinin protein, the "H" in the virus designation, and the neuraminidase protein, the "N" in the virus designation, taken from an avian flu virus that killed a boy in Vietnam in 2004. The vaccine also contains genes derived from a lab flu strain commonly used for seasonal influenza vaccines.
According to Treanor's team, tests conducted on 451 healthy adults showed that the vaccine was generally well tolerated and produced an immune response that the researchers think may protect against exposure to avian flu.
Roughly half of the volunteers who got the vaccine and a booster shot of the highest dosage of the vaccine developed infection-fighting antibodies that current data suggest would neutralize the virus.
The primary value of this vaccine, noted Dr. Anthony S. Fauci, Director of the National Institute of Allergy and Infectious Diseases, is that the federal government can begin stockpiling a small amount of the vaccine before any human pandemic ever occurs.
If the virus evolves so that human-to-human transmission becomes possible, Fauci continued, "it's likely to be different from the H5N1 strain that Dr. Treanor's team tested, but not completely different."
Therefore, the researchers still expect some degree of protection from the current vaccine, and by having a stockpile available, first responders could "hit the ground running" and spur on the development of a vaccine against the evolved virus.
In a related editorial subtitled "A Race against Time," Dr. Gregory A. Poland, from the Mayo Clinic in Rochester, Minnesota, notes that the US
Department of Health and Human Services and the
National Institutes of Health have funded studies of more than 30 candidate vaccines, the efficacy of which should be reported within the next 6 to 12 months.
In addition to the development and manufacture of candidate vaccines, he lists other strategies to prevent a pandemic, including "synchronization among countries of regulatory approaches; the resolution of issues concerning liability and intellectual property; ensuring the efficiency of clinical trials, and the use of methods to stockpile and rapidly deploy these vaccines."
Bird flu found at Maale HaHamisha
Kibbutz Maale HaHamisha near Jerusalem, is the eighth farm in which the disease has been found.
Gadi Golan 29 Mar 06 19:44
The Ministry of Agriculture and Rural Development and the Ministry's department of veterinary services and animal health today demarcated a 10 km. quarantine perimeter around Kibbutz Maale HaHamisha, near Jerusalem. The shut-down was carried out following a decision to cull 30,000 fowl from the poultry house where avian flu was found.
Including Maale HaHamisha, this is the eighth farm in which the disease has broken out. The Ministry stated that in order to prevent the disease from spreading, although there are no other poultry houses within a three kilometer radius of the infected one, it had made the decision to destroy all poultry in neighboring farms. In addition, the veterinary services decided to carry out a more in-depth examination of the affected area, so as to stop the disease from spreading.
At Sunday's cabinet meeting, Minister of Agriculture Ze'ev Boim announced that the veterinary services had succeeded in containing the bird flu outbreak. Boim noted, however, that there was a chance the disease would be discovered in other poultry houses, and that his ministry was prepared for such an event.
Avian flu first broke out at Hofit and Ein Hashlosha in the western Negev. After that, the disease spread to Moshav Sde Moshe and Gat in the Lachish region. Later, it was discovered at Moshav Bekaot in the Jordan Valley.
Published by Globes [online], Israel business news - www.globes.co.il - on March 29, 2006
Dubi
“The ratio of meetings to patients is probably 10 to 1”
http://www.nytimes.com/2006/03/28/health/28skep.html
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The Skeptic: A Pandemic Is
Worrisome but 'Unlikely'
March 28, 2006
By ELISABETH ROSENTHAL
OXFORD, England — The Hospital for Tropical Diseases in Ho Chi Minh City, where Dr. Jeremy Farrar works, has treated about two dozen people with avian influenza in the last three years.
With that tiny number, Dr. Farrar and his Vietnamese colleagues probably have more clinical experience than any other doctors with the A(H5N1) virus — the dreaded germ that international health officials fear may ignite the next flu pandemic.
Yet, Dr. Farrar notes, this trickle of humans infected with bird flu — 186 in all since 2003 — has provoked a flood of scientific meetings on pandemics, accelerating in recent months.
"The ratio of meetings to patients is probably 10 to 1: Hawaii tomorrow. Geneva and Singapore next week," said Dr. Farrar, in jeans and carrying a red backpack, on a break from a conference where he was — naturally — speaking on the topic.
"The interest is phenomenal," he said, clicking at his popular PowerPoint presentation.
Still, Dr. Farrar is not sure that this intensity is entirely rational:
Having observed A(H5N1) for many years in Asia, he thinks it is unlikely that the virus is poised to jump species, becoming readily transmissible to humans or among them. Nor does he believe the mantra that a horrific influenza pandemic is inevitable or long overdue. He points out that the only prior pandemic with a devastating death toll was in 1918, and he says that may have been "a unique biological event."
"For years, they have been telling us it's going to happen — and it hasn't," said Dr. Farrar, director of the Oxford University Clinical Research Unit at the hospital in Vietnam. "Billions of chickens in Asia have been infected and millions of people lived with them — we in Asia are intimate with our poultry — and less than 200 people have gotten infected. That tells you that the constraints on the virus are considerable," he continued. "It must be hard for this virus to jump."
Still, a part of Dr. Farrar is terrified of A(H5N1) — "a very nasty virus," he calls it — which he has watched kill healthy young people, devouring their lungs.
In the last year, the virus has extended its range in birds from Eastern China to Western Africa. Over time, it has expanded the variety of species it can infect, including ferrets and cats.
"That is alarming," he acknowledges in the understated British way.
Like all responsible scientists, Dr. Farrar believes the world should prepare. But schooled in places where people die of real and present diseases like malaria and tuberculosis, he finds the "doomsday" predictions sketched out by some international officials unhelpful, more fantasy than fact.
And even if these officials' dire forecasts were to come true, he says, many of their elaborate pandemic preparedness plans are unworkable in developing countries, which do not have the resources or medical facilities to comply.
"I think you have to say we really don't know the odds of pandemic, and people are not comfortable with that," Dr. Farrar said. "It could fizzle out and kill 98 people — one more than the number dead today. Or it could be something like 200 million," closer to an estimate once made by Dr. David Nabarro, chief avian flu coordinator for the United Nations.
"It's terrifying if it happens, but it is very, very unlikely, I think — and it is difficult to balance those facts."
At the Tropical Disease Hospital in Vietnam, doctors have been doing just that, bracing for a pandemic that may never come, since long before it became fashionable in the West.
Before Vietnam began vaccinating poultry in mid-2005, the disease was rampant among birds there. Of the world's 186 confirmed human cases, 93 are from Vietnam. There have been no new cases this year.
But in the Tropical Diseases Hospital, doctors and nurses still don full bio-protective gear when they evaluate suspected cases, because "you don't know if the next one will mark the start of human to human transmission," Dr. Farrar said.
With each new patient, they assiduously try to follow international scientific recommendations. But their on-the-ground experience reveals holes in the neat strategies coming from United Nations experts in Geneva and Rome.
The World Health Organization suggests that it might be possible to contain a pandemic by quickly diagnosing index cases, identifying contacts, prescribing all antiviral drugs, and quarantining, for example.
In response, Dr. Farrar shows a picture of the home of a patient: a hut on stilts by the Mekong River. When that patient fell ill, he took a boat to the local health station, and was transferred to the district hospital, Dr. Farrar says. Later, an ambulance took him to Ho Chi Minh City, where genetic analysis showed that he had avian influenza, instead of typical pneumonia. If bird flu ever gained the ability to spread easily among humans, that patient would have infected thousands before diagnosis.
"You've got to act quickly, but the process now takes many days," Dr. Farrar said, suggesting that more money for clinics, labs and experts should be flowing to developing nations.
"Then you're supposed to go back to the village and saturate it with oseltamivir?" he asks, using the generic name for the antiviral drug Tamiflu. "What do the villagers do when they hear the man has bird flu? They don't sit still; they get on buses and flee and stay with relatives in other villages," potentially spreading it there.
For doctors in Vietnam, human cases of avian influenza have been a frightening reality for more than three years, and Dr. Farrar vividly remembers the initial terror of the devoted hospital staff, unsure if they could catch bird flu from patients.
"Look at this lung — there's nothing there," he said pulling up the X-ray of a patient who is back at the university, but whose left chest shows a vast empty cavern. Studies from the hospital have taught the world much about A(H5N1): humans took longer to clear this virus than normal influenza, for example, and Tamiflu can quickly breed resistant strains.
But, to Dr. Farrar's chagrin, the treatment options have not really improved.
Flu vaccines are still manufactured by an "ancient strategy" that involves injecting eggs with virus, he complained, even as other vaccines rely on more sophisticated methods. As a result, flu vaccines — including experimental versions aimed at A(H5N1) — are cumbersome to produce, and target just one strain.
"What we need is a vaccine that is effective across strains because the virus can be different each year," he said. "My mom in the U.K. can get a shot every year, but that is not realistic in rural Asia."
More remarkable still, he said, Tamiflu is still the only drug useful against avian influenza, "and we all know that one drug is not adequate to treat any viral disease," he said, noting that multiple drugs are used in AIDS.
Patients at Dr. Farrar's Hospital are given Tamiflu, and it appears to help some. "It's all that we have," he said. "So if I was sick, I'd certainly want to get it."
But, he rues the lack of international research and coordination to tackle a disease that has been in Asia for nearly 10 years. For example, he said, although Vietnam has greatly reduced the number of bird flu outbreaks by vaccinating poultry, no one knows if the vaccine puts pressure on A(H5N1) to mutate to develop resistance to the shot, which could cause a rebound of disease in the coming years.
Personally, Dr. Farrar remains optimistic, believing a pandemic will not come. If A(H5N1) changed so that it readily infected people, it would probably become less deadly, he said.
But if disaster happens, he says: "People will look back and say: 'This was a nasty virus that you knew could sometimes infect other species. Why didn't you do something? All you had was a single effective drug and no vaccine?' "
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Bird flu program on Charlie Rose show:
http://video.google.com/videoplay?docid=2343414988689203314&q=tvshow%3ACharlie_Rose
>>
3/22/2006
ANALYZING THE AVIAN FLU THREAT WITH:
SIR PAUL NURSE, President, Rockefeller University
MICHAEL LEAVITT, Secretary of Health & Human Services
DR. JULIE GERBERDING, Director, Centers for Disease Control
DR. HARVEY FINEBERG, President, Institute of Medicine
DR. PETER PALESE, Mount Sinai School of Medicine
DR. DAVID NABARRO, Coordinator, U.N. Response to Avian Flu
LAURIE GARRETT, Author / Council on Foreign Relations
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http://www.charlierose.com/
[Thanks to pompart2000 on the NSTK ymb for the heads up.]
Source of (possibly hyped) info on bird-flu developments:
http://www.recombinomics.com/in_the_news.html
Yet another take on same story:
Studies Suggest Avian Flu
Pandemic Isn't Imminent
http://www.nytimes.com/2006/03/23/science/23flu.html
>>
March 23, 2006
By NICHOLAS WADE
Two groups of researchers, in Japan and in Holland, say they have discovered why the avian flu virus is rarely if ever transmitted from one person to another.
The reason, the researchers propose, is that the cells bearing the type of receptor the avian virus is known to favor are clustered in the deepest branches of the human respiratory tract, keeping it from spreading by coughs and sneezes. Human flu viruses typically infect cells in the upper respiratory tract.
The avian virus would need to accumulate many mutations in its genetic material before it could become a pandemic strain, said Yoshihiro Kawaoka, a virologist at the University of Tokyo and the University of Wisconsin.
According to a University of Wisconsin news release approved by Dr. Kawaoka, "The finding suggests that scientists and public health agencies worldwide may have more time to prepare for an eventual pandemic."
Dr. Kawaoka's finding is published in today's issue of Nature, and a similar finding, by Thijs Kuiken and colleagues at the Erasmus Medical Center in Rotterdam, appears in this week's Science.
Flu experts already knew that people who contract the current avian flu virus, a type known as A(H5N1) or H5 for short, are infected in the lower lung.
Paul A. Offit, a virologist at the Children's Hospital of Philadelphia, said the new reports helped explain why the H5 virus, though it can infect people, does not easily spread from one person to another.
Virologists agree that a flu pandemic will happen sooner or later as one of the 16 types of flu virus in the animal world, probably one that infects birds, will manage to switch hosts, and grow and spread in humans. But they differ over whether H5 is the likeliest candidate to make such a switch. Previous pandemics have been caused only by H1- (the 1918 pandemic), H2- (the 1957 Asian flu) or H3-type viruses (the Hong Kong flu of 1968).
The H5 strain of avian flu has so far failed to develop a pandemic form. Some virologists fear it may need only better transmissibility. The new findings suggest that the virus could acquire such a property by switching its preference from the cell receptor found in the lower lung, known as alpha 2-3, to the receptor found on cells in the upper airways, known as alpha 2-6.
A team of scientists at the Scripps Research Institute reported in Science last week that only a couple of mutations might be needed to enable the H5 virus to make this switch to the alpha 2-6 receptor. This is the about same number of mutations made by the H1, H2 and H3 viruses when they adapted to infect people. Since viruses mutate fast, a two-mutation step is not such a big hurdle.
Because the H5 virus has killed about half of the 187 people it has infected, "a lot of its genes are already optimized for virulence," said James C. Paulson, a member of the Scripps team. For H5 to become pandemic, "the key gene that needs to be mutated is the HA gene," he said, referring to the hemagglutinin gene that makes the protein probe used by the virus to latch onto a cell's receptor sites.
Though H5 may seem only a couple of steps from transmissibility among people, many virologists believe mutations in several other genes would be necessary as well, even though those changes are not yet well understood.
Viruses find it difficult to switch hosts, and though they may quite often cause outbreaks in just a few individuals, "viruses that produce a self-sustaining chain of transmission in the new host appear rare," Dr. Kawaoka writes in the current Annual Review of Microbiology. "Most of these transfers are dead ends," he said.
The H5 virus has been present in the human population since the late 1950's, said Dr. Offit of Children's Hospital, but has never acquired the full set of mutations needed to set off a pandemic. Such epidemiological evidence "should make us feel safe that there's a substantial barrier," he said, noting the small number of people who have been infected.
Dr. Offit said it was a good thing to worry about the next flu pandemic, given that about three can be expected every century. "What's not good is to try to sell the public on their fear of pandemic flu being this particular bird flu, since if it's not, crying wolf will lose you credibility," he said.
Peter Palese, a virologist at the Mount Sinai School of Medicine, said he did not believe the H5 virus could infect people except when they were exposed to large doses, for example, by sleeping in the same room as chickens. "I feel strongly that H5 has been around in humans for a long time and never caused a pandemic, suggesting that this is not the virus which is likely to be the next pandemic," he said.
But like Dr. Offit, Dr. Palese said he fully supported plans for better preparations for the next flu pandemic, whatever its source. "People have to understand we are not really prepared should it come," he said.
<<
More on the same topic:
Studies Spot Obstacle to
Human Transmission of Bird Flu
http://www.forbes.com/lifestyle/health/feeds/hscout/2006/03/22/hscout531699.html
>>
WEDNESDAY, March 22 (HealthDay News) -- Two new studies help explain why human-to-human transmission of the bird flu virus has so far not happened -- and might not happen in the future.
Both reports found the H5N1 virus prefers to settle in cells deep within the lungs, rather than in the upper respiratory tract, as happens with human flu strains.
That's important because "most of the coughing and sneezing that transmits flu is going to be from the upper respiratory tract, and not way down in the lower respiratory tract," explained Dr. Arnold S. Monto, a professor of epidemiology at the University of Michigan School of Public Health. "So, unless you have relatively close contact, you're not going to have much [bird flu] virus get out."
The findings may also explain why bird flu has proven so lethal whenever it has managed to get a foothold in humans, the experts added.
Since 2003, the H5N1 virus has been found in Asia, Europe, Africa and the Middle East, and has led to the slaughter of tens of millions of domestic fowl. While infection has primarily been limited to birds, the virus has killed 103 people via bird-to-human transmission. Scientists worry, however, that the germ could mutate into a form that would make human-to-human transmission far easier, raising the specter of a pandemic that could kill millions of people.
One of two studies published this week that looked at that possibility was conducted by researchers working at the University of Wisconsin and the University of Tokyo. They reported their findings in the March 23 issue of Nature.
The team focused on two variants of a receptor molecule lying on the surface of cells that line the nasal/bronchial passages and the lungs. These receptors, called SAalpha2,3Gal and SAalpha2,6Gal (2,3 and 2,6, for short), are the biochemical "hook" flu viruses use to latch onto cells.
Scientists long ago determined that H5N1 strongly prefers the 2,3 form of the molecule. "What this paper was doing was identifying where the locus of these 2,3 receptors are in humans," Monto explained.
The Japanese-American team found that, as expected, H5N1 avian flu is drawn to the 2,3 receptors. Luckily for humans, they also found that 2,3 is most abundant on cells within the alveoli, the most remote, microscopic branches of the lungs' "respiratory tree."
H5N1 was much less likely to bind to cells in the upper respiratory tract.
In contrast, common human flu strains prefer to bind with the 2,6 receptor, which is found in plentiful numbers on upper respiratory tract cells. That makes sense, experts say, because every time humans cough or sneeze, droplets from this area are easily expelled into the air, making human-to-human transmission of ordinary seasonal flu possible.
H5N1 colonizes a much deeper, tough-to-access region of the lung -- making infection more difficult to spread and treat in humans, the researchers said.
The finding also helps explain another phenomenon: The fact that many people have tested positive for exposure to H5N1, but have never developed actual infection or illness.
"They didn't have bird flu, but they made antibodies to it," explained Dr. Marc Siegel, a clinical associate professor of medicine at New York University School of Medicine and author of Bird Flu: Everything You Need to Know About the Next Pandemic.
According to Siegel, it appears that these people may have encountered H5N1, but because the virus failed to reach the lower lung, it never gained a "foothold" for infection.
How, then, to explain the more than 200 documented human cases where people did develop full-blown bird flu?
"I've always assumed it's due to [the patient's] high viral load," Siegel said. In other words, these patients -- most of whom worked every day in close proximity to infected birds -- were so surrounded by H5N1 that it eventually managed to colonize the lower reaches of their lungs.
Once the virus does lodge and flourish in the lower lung, it can quickly prove deadly, Monto said. "It causes pneumonia, a whiting out of the lungs," he said. "In fact, a lower respiratory pathology fits very well with what we are finding" in human cases.
The Japanese/American findings were echoed in another paper, scheduled for release in the March 24 issue of Science but published early to coincide with the Nature study.
In that study, Dutch researchers at the University of Rotterdam again found that avian flu preferred receptors on cells deep in the lungs, and shunned binding with cells in the upper respiratory tract.
All of this means that human-to-human transmission of H5N1 is highly unlikely, at least for now, experts say. However, any mutation or series of mutations that caused H5N1 to switch its preference from the 2,3 receptor to the 2,6 receptor could change all that.
Could such genetic changes occur, as experts believe may have happened in the 1918 Spanish flu pandemic?
"That's the $64,000 question," Monto said. "We're all concerned about mutations or any re-assortment that might change the virus."
But Siegel believes the virus would have to undergo a number of complex genetic mutations to move up the respiratory tract. "And even if it does, that's still not an assumption that it's going to cause a severe pandemic," he said.
Still, he and other experts agree that as the virus circulates in millions of migrating birds, vigilance will be key.
"All of this argues for intensified surveillance and attempting to contain, if possible, the disease in poultry," Monto said
<<
A Clue Is Found on Why Bird Flu
Is Slow to Spread Among Humans
[This is the first reassuring article on bird flu in quite a while.]
http://online.wsj.com/article/SB114301270715304989.html
>>
By ANTONIO REGALADO
March 23, 2006
Scientists have a new clue why the feared H5N1 strain of the avian-influenza virus hasn't spread easily among people.
According to research published this week by teams in the U.S. and the Netherlands, the bird virus primarily infects cells deep in the human lung, possibly making it difficult for the germ to spread.
The H5N1 avian-flu virus was first detected in Hong Kong in 1997, and has since claimed millions of birds and more than 100 human lives. The virus has continued to spread across the globe and has been detected in birds in both Europe and Africa, although not yet in the U.S.
Humans have very limited immunity to such avian viruses, and health authorities say that if the bird-flu virus begins to spread between people, it could spark a global outbreak of deadly respiratory disease. That hasn't happened, and the new findings may help explain why.
Using tissues from human cadavers, researchers at the Erasmus Medical Center in Rotterdam studied which cells the bird virus would become attached to. According to Thijs Kuiken, a veterinary pathologist who directed the research, H5N1 attached to cells deep in the lung, but not cells in the throat, where human-flu viruses multiply. The study appears in the journal Science.
Dr. Kuiken called the finding a possible explanation for why the avian virus doesn't jump easily between people. "It must reach the lower respiratory tract to replicate, and it's harder to spread by coughing and sneezing," he said.
Other doctors questioned that conclusion, saying that patients with such infections were likely to cough more heavily. "I don't think it directly affects the transmissibility just because it's in the lower respiratory tract," said Nikki Shindo, an influenza expert at the World Health Organization who has studied human cases, most recently in Turkey.
Dr. Shindo said that if the virus has to reach deep into the lung before causing an infection, that could make it harder to catch.
In a separate study released yesterday by the journal Nature, a research group headed by Yoshihiro Kawaoka of the University of Wisconsin-Madison reached similar conclusions after analyzing the specific molecules on human cells to which influenza viruses attach.
They found that molecules preferred by H5N1 are expressed mostly by cells deep in the lung. To spread between humans, the virus would need to adapt in a way that enabled it to attach to a different type of molecule present in cells higher in the respiratory tract.
"This restriction may contribute to the inefficient human-to-human transmission of H5N1 viruses seen to date," Dr. Kawaoka wrote in his report.
<<
TA University expert develops early-warning system for bird flu
By MATTHEW KALMAN
In a nondescript corner of an anonymous administration building on the campus of Tel Aviv University, Yossi Leshem has been using the latest satellite technology to track the movements of a couple code-named Princess and Jonas.
For nearly a year, Israeli experts were able to track the pair as they left their adopted home in Germany and set out on their travels. Jonas traversed Europe to southern Spain, where he spent several months before rejoining his partner back in Germany. Princess journeyed east across Turkey and Lebanon, passing through Israel, the Palestinian territories and Egypt before making a long stopover in Sudan. She then continued on to South Africa, returning to rendezvous with Jonas in Germany 235 days later.
For more than five years, Leshem has been tracking the travels of Princess and Jonas and dozens like them. He worries that their apparently benign wanderings could inflict death and devastation across the world, at a cost of untold numbers of human lives.
Princess and Jonas are white storks, the long-legged waterfowl that nest in Europe during the summer and migrate south for the winter. Princess is among an estimated half a billion fowl that fly over Israel twice a year on their way to and from their nesting grounds.
Until now, the spectacular arrival of vast flocks of birds in the Hula Valley in northern Israel had been regarded as a nuisance for the farmers whose seed they feed on - and a beautiful twice-yearly attraction for thousands of bird-watchers from around the world who flock to Israel to see the storks, pelicans, vultures, even eagles.
But with outbreaks of deadly avian flu in East and Southeast Asia, Africa, Europe, and closer countries such as Turkey and Egypt, Leshem says the fascinating journeys of birds like Princess and Jonas could be the key to understanding how avian flu might spread around the globe. Every autumn, birds from Northern Europe and Northeast Asia fly south, soaring past the eastern Mediterranean region before fanning out across Africa and the Arabian Peninsula, then fly the same route in reverse every spring. The resulting crush creates an avian air-traffic jam above Israel twice a year.
"Birds infected with avian flu originating in the Far East are funneled through the Israeli 'bottleneck' as the birds migrate, and the virus can be passed through the air," said Leshem, an air force colonel. "If a flock of migrating geese land near a chicken farm, the virus can spread like fire."
"The biggest threat is a mutation of the virus and its transfer to people," said Leshem. "We know that birds are disease carriers. It could be a worldwide disaster."
To date, the H5N1 flu virus has killed 95 people out of 175 confirmed human cases worldwide. Those deaths have occurred in a swath from China to Turkey, according to the World Health Organization.
Perched on a hillside near the Latrun junction, about 800 feet above sea level in the foothills of the West Bank, Gen. Leonid Dinevich recalls the days when he commanded 40 Soviet air bases, 500 warplanes and silos containing thousands of ballistic missiles.
Back then, he occupied a spacious office at the top of a 14-story tower at a base in Kishinev in what is now Moldova. Today, Dinevich, 64, spends nine hours a day in an MMR-5 radar station, a camouflaged hut on wheels with a 15-foot antenna circling slowly in a huge sphere mounted on the roof. The cramped interior is alive with blinking lights, computer screens and buzzing equipment.
"Once a general, always a general," said Dinevich. "Today I am the general of millions of birds, defending against the new enemy of avian flu."
Dinevich and Leshem established the Latrun radar to track migration patterns and warn aircraft of birds in their flight path to avoid collisions. Now they hope that the data collected at Latrun will be developed into an early-warning system to help halt the spread of disease.
"We want to create a network with radar stations here in Israel, in Russia, in Bulgaria, in Turkey, in Jordan - and many more," said Dinevich. "We have to unify them into a single system. On the screen you can see millions of birds on their way to Turkey. We can warn our friends in Turkey that tomorrow the birds will reach there, and they must cover up their poultry and other domestic birds. Then Turkey needs to warn Russia, and so on."
In keeping with the international nature of the threat, the Israeli experts have been working closely with regional colleagues.
Imad Atrash, director of the Palestine Wildlife Society, said the avian flu threat has brought together Israeli and Palestinian officials at a time when cooperation between the two governments on many other issues has come almost to a standstill.
"There is full cooperation," said Atrash. "We are all aware that the disease will make no distinction between Israeli, Palestinian, Christian, Muslim or Jew. We all face the same problem. It will affect everyone. Disease knows no boundaries."
http://www.jpost.com/servlet/Satellite?apage=2&cid=1139395644010&pagename=JPost%2FJPArticle%...
Dubi
Clues to the Virulence of H5N1 Viruses in Humans
Science 17 March 2006:
Vol. 311. no. 5767, pp. 1562 - 1563
DOI: 10.1126/science.1125998
Perspectives
VIROLOGY:
Clues to the Virulence of H5N1 Viruses in Humans
Robert M. Krug*
H5N1 strains of avian influenza A virus have already caused the deaths of more than 90 people since the outbreak of infection in Southeast Asia in 1997, corresponding to a death rate of ~50% for known infections. These viruses, which have now spread from Asia to Europe and Africa, are strong candidates for causing the next flu pandemic if they acquire the ability for efficient human-to-human transmission. A major research goal has been to identify the molecular basis of the virulence of H5N1 viruses in humans (1, 2). Several virus-encoded proteins will likely contribute to virulence in humans, because previous studies have shown that the virulence of influenza A virus of different organisms is caused by multiple genes (2). The study by Obenauer et al. (3) on page 1576 of this issue, presents evidence suggesting that the virulence of H5N1 viruses may be caused at least in part by the function of a previously unnoticed amino acid sequence motif in the virus-encoded nonstructural protein called NS1 (see the figure).
The NS1 protein is synthesized in infected cells but not incorporated into virus particles. Rather, this small, multifunctional protein participates in both protein-RNA and protein-protein interactions during infection. Its amino-terminal RNA-binding domain binds to double-stranded RNA (dsRNA) with low affinity (4), but the significance of this activity during viral infection is controversial (5, 6). The NS1 protein also binds and inhibits the function of two cellular proteins that are required for the modification of the 3' ends of cellular messenger RNAs (mRNAs) (6). Consequently, the production of a key component of the host antiviral response, interferon- mRNA, is substantially reduced, although not eliminated (7). The NS1 sequences that participate in binding to either these two cellular proteins or dsRNA are not part of the putative new virulence determinant in NS1.
Ten other proteins are encoded by influenza A virus, whose genome consists of eight single-stranded RNAs (8). Three proteins (PB1, PB2, and PA) comprise the polymerase that is associated with each of the viral genomic RNAs in the virus particle. The polymerase copies these genomic RNAs into viral mRNAs and also catalyzes the replication of the genomic RNAs in infected cells. Investigators have identified the amino acid sequences of the PB1, PB2, and PA proteins that function in specific steps of virus-specific RNA synthesis or in mediating interactions between the three proteins (2). The amino acid at position 627 in PB2, which has been implicated in human virulence of H5N1 viruses, does not participate in these known functions. H5N1 viruses that are virulent in mice encode lysine at this position in PB2, whereas H5N1 viruses that are not virulent in mice, as well as other avian influenza A virus strains, encode glutamic acid at this position (9). It is thought that this change from glutamic acid to lysine represents an adaptation of H5N1 viruses for efficient replication in mammalian cells (10).
Another virulence determinant for the H5N1 virus in mammals has previously been identified in the hemagglutinin, the major surface protein of the virus (8). Hemagglutinin, which binds to sialic acid-containing receptors on host cells, is the protein against which neutralizing antibodies are produced. Because the H5 type of hemagglutinin in avian influenza A viruses has not been found in previously circulating human influenza A virus strains, humans are potentially susceptible to infection by these viruses. Cleavage of hemagglutinin into two disulfide-linked sub-units is a prerequisite for initiating infection (8). H5N1 viruses that are highly pathogenic in mice contain a stretch of basic residues adjacent to the hemagglutinin cleavage site, enabling these hemagglutinins to be cleaved by ubiquitous intracellular proteases, including furin. Recombinant H5N1 viruses lacking these basic amino acids are no longer virulent in mice (9), demonstrating that the presence of these amino acids, and the consequent cleavage by intracellular proteases, are required for the virulence of these viruses.
To further understand the molecular basis of virulence, Obenauer et al. first sequenced the genes of a large number of H5N1 viruses isolated from wild birds and poultry, providing an invaluable resource for many investigators. This analysis revealed not only the expected variability in the sequences of the two major surface proteins of the virus, hemagglutinin and neuraminidase, but also variability in the sequence of the NS1 protein. Despite variability in the latter, it was noted that the carboxyl terminus of the NS1 proteins of the vast majority of avian H5N1 viruses contains a sequence motif, Glu-Ser-Glu-Val (ESEV). These residues are predicted to mediate binding to proteins bearing a region called a PDZ domain. The multitude of human proteins that contain a PDZ domain function in diverse cellular signaling pathways including those that regulate protein traffic within the cell and those that maintain cell morphology and organization. Another PDZ-binding sequence, Glu-Pro-Glu-Val (EPEV), was identified at the carboxyl terminus of the NS1 proteins of all the virulent H5N1 viruses isolated from humans. In contrast, the carboxyl terminus of the NS1 proteins of low-virulence human influenza A usually contains a different sequence, Arg-Ser-Lys-Val (RSKV), which is not a PDZbinding motif. Further, Obenauer et al. verified that the carboxyl-terminal ESEV and EPEV sequences indeed bind to PDZ domains. Consequently, the presence of a functional carboxyl-terminal PDZ-binding domain in the NS1 protein of H5N1 viruses correlates with human virulence. This supports the authors' hypothesis that the carboxyl-terminal domain of the NS1 proteins of avian H5N1 viruses acts as a virulence factor by binding cellular PDZ-containing proteins and disrupting their participation in important cellular processes.
This is an intriguing hypothesis that, however, needs to be evaluated in animal experiments with H5N1 viruses that have been altered to express a NS1 protein lacking the carboxyl-terminal ESEV/EPEV sequence. Such experiments are critical because it has already been established that this carboxyl-terminal sequence is not required for the virulence of previously isolated H5N1 viruses in ferrets (11). An analysis of the virulence of H5N1 viruses isolated in 2004 identified the human isolate A/Vietnam/1203/04 as the most pathogenic isolate. The NS1 protein encoded by this virus is truncated and consequently lacks the suspect carboxyl-terminal ESEV/EPEV motif. Future experiments will establish whether eliminating the carboxyl-terminal ESEV/EPEV sequence of the NS1 protein of other H5N1 viruses has any effect on their virulence in animal models. In addition, the search for other molecular determinants of the virulence of H5N1 viruses in humans will undoubtedly continue.
References
T. Horimoto, Y. Kawaoka, Nat. Rev. Microbiol. 3, 591 (2005). [Medline]
D. L. Noah, R. M. Krug, in Advances in Virus Research, K. Maramorsch, A. J. Shatkin, Eds. (Elsevier, Amsterdam, 2005), vol. 65, pp. 121-145. [Medline]
J. C. Obenauer et al., Science 311, 1576 (2006); published onlne 26 January 2006 (10.1126/science.1121586).
C. Y. Chien et al., Biochemistry 43, 1950 (2004). [Medline]
A. Garcia-Sastre, Virology 279, 375 (2001). [Medline]
R. M. Krug, W. Yuan, D. L. Noah, A. G. Latham, Virology 309, 181 (2003). [Medline]
D. L. Noah, K. Y. Twu, R. M. Krug, Virology 307, 386 (2003). [Medline]
R. A. Lamb, R. M. Krug, in Fields Virology, D. M. Knipe, P. M. Howley, Eds. (Lippincott, Williams, and Wilkins, Philadephia, 2001), vol. 1, pp. 1487-1531.
M. Hatta, P. Gao, P. Halfmann, Y. Kawaoka, Science 293, 1840 (2001). [1840]
K. Shinya et al., Virology 320, 258 (2004). [Medline]
E. A. Govorkova et al., J. Virol. 79, 2191 (2005). [Medline]
10.1126/science.1125998
The author is at the Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA. E-mail: rkrug@mail.utexas.edu
Figure caption:
Variation locations. Strains of the H5N1 influenza A virus that are virulent in mammals, including mice and humans, have alterations in the sequences of any of three viral proteins hemagglutinin (HA), the viral polymerase protein PB2, and the nonstructural protein NS1. Influenza A virus has 8 genomic RNA strands and 10 proteins, as shown.
CREDIT: P. HUEY/SCIENCE
Bird flu kills five young people in Azerbaijan
Reuters
GENEVA - Bird flu has killed five young people in Azerbaijan, the World Health Organization said on Tuesday, adding it was investigating whether some of the victims could have been infected collecting feathers from dead swans. Confirmation of the five deaths takes the WHO toll from the virus to 103 since late 2003. Egypt reported its fourth suspected human case over the past week.
Confirmation of the five deaths takes the WHO toll from the virus to 103 since late 2003.
Egypt reported its fourth suspected human case over the past week. The Egyptian authorities have said that one of the patients died of bird flu last Friday, but that has not been confirmed by the WHO.
Pakistan on Tuesday became the latest country to confirm bird flu in poultry, saying the virus found in two poultry flocks late last month was the highly pathogenic H5N1 strain.
Bird flu has spread with alarming speed in recent weeks as it marches deeper into Africa, Europe and Asia. The United States says it is likely to arrive on its shores before the end of the year.
Fears are growing the H5N1 flu virus will mutate and pass easily from one person to another but for the moment it remains hard for people to catch it from infected birds.
"We don't see any human-to-human transmission (in Azerbaijan). The exact source of exposure to the deadly virus is under investigation, which is focusing on defeathering of birds," WHO spokesman Dick Thompson said.
Four of those who died came from a settlement of around 800 homes in the Salyan region in the southeast of the country, while the fifth victim came from Tarter in the west. Azerbaijan lies at the crossroads between Europe and Asia.
The WHO said an investigation in Salyan had found some evidence that carcasses of swans, dead for some weeks, may have been collected by residents as a source of feathers.
Adolescent women and young girls usually pluck birds in the affected community, the WHO said.
Four of the victims in Azerbaijan were women aged between 17 and 21, while the other was the 16-year-old brother of one of the dead women.
EGYPT
Egypt reported a fourth suspected case of bird flu in humans on Tuesday, in a 17-year-old boy whose father had an outbreak of the disease on his chicken farm in the Nile Delta on Saturday and Sunday.
Health Minister Hatem el-Gabali, quoted by the state new agency MENA, said the boy was taken to hospital in the town of Tanta on Sunday and was being treated with Tamiflu, the drug used to fight bird flu in humans. His condition was "good and stable," he added.
The boy was the fourth Egyptian suspected of contracting the disease from infected birds. Of the first three, one has died, one has recovered and the third is receiving treatment.
The Palestinian Authority declared a state of emergency on Tuesday in the hope of preventing the spread of H5N1 which struck Israel last week. Israel has poisoned hundreds of thousands of turkeys and chickens in a bid to curb its outbreak.
PAKISTAN POULTRY
In Pakistan, Livestock Commissioner Muhammad Afzal said there had been no other cases of bird flu since the outbreak was first reported on February 27 at farms in the North West Frontier Province.
Samples from two farms were sent to a laboratory in Britain, and the flocks -- totaling around 23,000 birds -- were culled.
"I can only confirm that the H5N1 type of virus was found in chickens from both the farms," Agriculture Ministry official Mohammad Akhlaque told Reuters.
"We have conducted tests on the people who worked on both the farms and they are healthy. There is no sign of any bird flu in those people. We have already culled all chickens so there is not much more we can do," he told Reuters.
(Additional reporting by Mohammed Abbas in Cairo, Simon Cameron Moore in Islambad)
http://news.yahoo.com/s/nm/20060321/ts_nm/birdflu_dc_11;_ylt=AqfTxRK1HEy53qFiFgOoMMyTvyIi;_ylu=X3oDM...
CDC Reports H5N1 Has Split Into Two Different Forms
Pakistan Reports First Cases of H5N1
A WALL STREET JOURNAL ONLINE NEWS ROUNDUP
March 21, 2006 9:46 a.m.
The H5N1 virus responsible for the global bird-flu outbreak has evolved into two genetically different strains, U.S. scientists reported, raising concerns of an increased risk to humans.
Researchers from the Centers for Disease Control and Prevention reported their findings at the International Conference on Emerging Infectious Diseases being held in Atlanta.
CDC FINDINGS
Read the CDC news release1 and read more about the ICEID conference2.
"As the virus continues its geographic expansion, it is also undergoing genetic diversity expansion," Rebecca Garten, a researcher on the study, said in a news release.
Up until now, there was only one form of H5N1, and scientists feared that could pose a risk to humans. But now that it has split into two genetically distinct forms, scientists are even more concerned that it will evolve into a form easily transmissible between humans, which could spark a pandemic. So far, the only human cases have been from direct contact with infected poultry, and most have been poultry farmers, worked in the industry or lived in close proximity to poultry.
The CDC researchers studied over 300 H5N1 virus samples taken from both avian and human sources from 2003 through the summer of 2005. The scientists found that, in 2005, a second strain of H5N1 was affecting humans in Indonesia. They concluded that the strain belonged to different subgroup of the virus that was previously not known to cause the disease in humans. The strains are similar, but different enough that the scientists likened the two strains to cousins.
H5N1 Detected in Chickens in Pakistan
Pakistan reported its first cases of H5N1 -- in chickens. The H5 type of avian influenza was detected in chickens at two farms in northwestern Pakistan last month. Tests conducted in Britain confirmed the subtype to be H5N1.
Pakistan's Agriculture Ministry said it had taken all necessary measures to stop it spreading further in the country but urged farmers to vigilant. "We are continuously watching to see whether there is another outbreak elsewhere" in Pakistan, ministry spokesman Mohammed Afzal told Geo television.
Neighboring India, Iran and mostly recently, Afghanistan, have already reported H5N1 outbreaks, but officials confirmed this was the first case in Pakistan.
Pakistan's two cases were detected at a commercial farm in Charsadda, near Peshawar, the capital of North West Frontier Province, and at a small breeder farm in the hill-resort city of Abbottabad. The ministry said the farms were quarantined, thousands of chickens slaughtered and farm workers given medical checkups and found to be free of infection.
"So far no new farm or bird has been found to be affected with the disease anywhere in the country," a ministry statement said. It urged all poultry farmers to increase the level of "bio-security" at their farms and immediately report any abnormal or high mortality among poultry.
In 2003, between three million and four million chickens were killed in Pakistan after an outbreak of the less dangerous H7N3 strain of bird flu.
U.S. Completes New Surveillance System
On Monday, U.S. Department of Agriculture Secretary Mike Johanns and Secretary of Interior Gale Norton announced the completion of a new early warning system to detect highly pathogenic avian flu in wild migratory birds in the U.S. The interagency plan outlines five specific strategies for early detection, including: investigating disease-outbreak events in wild birds; expanding monitoring of live wild birds; monitoring hunter-killed birds; use of sentinel animals, such as backyard poultry flocks; and environmental sampling of water and bird feces.
"By intensifying our monitoring of migratory-bird populations, we increase the likelihood of early detection, which is key to controlling the spread of the virus, particularly in our domestic poultry," Mr. Johanns said in a release.
The H5N1 strain of bird flu has killed or forced the slaughter of tens of millions of chickens and ducks across Asia since 2003, and recently spread to Europe, Africa and the Middle East. Bush administration officials have increasingly warned that H5N1 could turn up in the U.S. by the end of this year.
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This is the official PR from the FDA prohibiting use of AV drugs for poultry.
http://www.fda.gov/bbs/topics/NEWS/2006/NEW01339.html
FDA Prohibits Use of Antiviral Drugs in Poultry to Help Keep Drugs Effective for Humans
The Food and Drug Administration today published a proposed final rule to prohibit the extralabel use in poultry of two classes of approved human antiviral drugs in treating influenza. FDA is taking this measure to help preserve the effectiveness of these drugs for treating or preventing influenza infections in humans.
Specifically, the order prohibits the extralabel use by veterinarians of anti-influenza adamantane (amantadine and rimantadine) and neuraminidase inhibitor (oseltamivir and zanamivir) drugs in chickens, turkeys, and ducks. Extralabel use is the actual use or intended use of a drug in an animal in a manner that is not in accordance with the approved labeling.
"Today's action is a preventive measure designed to protect the public health and illustrates FDA's high level of commitment and key role in preparing for a possible influenza pandemic, which is a top priority for our nation" said Acting FDA Commissioner Dr. Andrew von Eschenbach.
Currently, no drugs are approved for the treatment or prevention of influenza A in animals. However, two classes of antiviral drugs are approved in the United States for the treatment or prevention of influenza A in humans. Under the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA) veterinarians can legally prescribe these human antiviral drugs to protect animals from influenza (www.fda.gov/cvm/amducatoc.htm.)
Under AMDUCA and its implementing regulations, FDA can issue an order prohibiting certain extralabel uses in animals if such extralabel use presents a risk to the public health. FDA has considered all available information and has concluded that the extralabel use of anti-influenza adamantane and neuraminidase inhibitor drugs in chickens, turkeys, and ducks presents a risk to public health. FDA may add other animal species to the prohibited list as new data becomes available.
Thus far, there have been no reported cases of avian influenza H5N1 in the U.S. Nor is FDA aware that there is ongoing extralabel use of these antiviral drugs in the U.S. by poultry producers. However, concerns have been raised by a number of public health organizations, such as the World Health Organization, Food and Agriculture Organization, and the World Animal Health Organization, that the extralabel use of these drugs in poultry could lead to the emergence of resistant strains of type A influenza. This is of particular concern if the avian influenza H5N1 (commonly known as bird flu) that has been identified in other countries were to emerge in the U.S.
Influenza viruses mutate frequently. Some mutations confer drug resistance to influenza viruses. Repeated and improper use of anti-influenza drugs could allow resistant influenza viruses to flourish.
Interested parties may submit comments on this final rule by May 22, 2006. Comments may be submitted electronically through the Federal eRulemaking Portal: www.regulations.gov or to the Agency Web site: www.fda.gov/dockets/ecomments. Written comments may be faxed to 301-827-6870, or delivered by mail or hand to: Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852. All comments must be identified by Docket No: 2006N-0106. The order of prohibition will become effective June 20, 2006, unless FDA revokes the order, modifies it, or extends the comment period.
Additional information on the final rule may be found in the March 22, 2006 Federal Register or by contacting Kim Young, Center for Veterinary Medicine (HFV-230), Food and Drug Administration, 7519 Standish Place, Rockville, MD 20855, 240-276-9207, e-mail: kim.young@fda.hhs.gov
Information about the pandemic flu may be found at: www.pandemicflu.gov.
The FDA wants to ban the use of Tamiflu, Relenza and the older drugs in fear of Avian mutating.
US proposes banning human flu drugs in poultry
Mon Mar 20, 2006 12:34 PM ET
WASHINGTON, March 20 (Reuters) - U.S. regulators on Monday proposed banning the use of two types of human flu-fighting drugs in poultry in order to preserve their effectiveness for people in case of a bird flu pandemic.
The proposal would prohibit use of neuraminidase inhibitors, Roche's Tamiflu (ROG.VX: Quote, Profile, Research) and GlaxoSmithKline Plc's (GSK.L: Quote, Profile, Research) (GSK.N: Quote, Profile, Research) Relenza, and the older drugs rimantadine and amantadine in chickens, turkeys and ducks, the Food and Drug Administration said.
The drugs are not approved to treat or prevent influenza in animals, but veterinarians can still legally prescribe them.
Officials worry that repeated use of the drugs could allow a deadly flu strain to mutate and resist the treatments when they are needed for people.
Concern is growing as the H5N1 flu strain spreads among birds in Europe, Africa and Asia. Experts say it could change to a form that moves easily between people, causing a worldwide flu pandemic.
Bird flu threatens 40% of Israel's poultry sector, warns Dun & Bradstreet
19.3.06 | 08:53 By Amiram Cohen and Orna Livne
More than 40 percent of the businesses in the poultry, egg and meat sectors could collapse as avian flu depresses sales, Dun and Bradstreet warns.
Companies in danger of bankruptcy include farmers, slaughterhouses, meat processing plants, hatcheries and food companies and businesses that use eggs in baked products.
This means an almost doubling of the potential number of businesses likely to go under - which Dun and Bradstreet said stood at only 24% before the avian influenza struck Israel.
(#msg-10235305)
Dubi
Renowned Bird Flu Expert Warns: Be Prepared
http://abcnews.go.com/WNT/print?id=1724801
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There Are "About Even Odds" That the Virus Could Mutate to an Easily Transmitted Form, He Tells 'World News Tonight'
By JIM AVILA and MEREDITH RAMSEY
March 14, 2006 — - Robert G. Webster is one of the few bird flu experts confident enough to answer the key question: Will the avian flu switch from posing a terrible hazard to birds to becoming a real threat to humans?
There are "about even odds at this time for the virus to learn how to transmit human to human," he told ABC's "World News Tonight." Webster, the Rosemary Thomas Chair at St. Jude Children's Research Hospital in Memphis, Tenn., is credited with being the first scientist to find the link between human flu and bird flu.
Webster and his team of scientists are working to find a way to beat the virus if it morphs. He has even been dubbed the Flu Hunter.
Right now, H5N1, a type of avian influenza virus, has confined itself to birds. It can be transmitted from bird to human but only by direct contact with the droppings and excretions of infected birds.
But viruses mutate, and the big fear among the world's scientists is that the bird flu virus will join the human flu virus, change its genetic code and emerge as a new and deadly flu that can spread through the air from human to human.
If the virus does mutate, it does not necessarily mean it will be as deadly to people as it is to birds. But experts such as Webster say they must prepare for the worst.
"I personally believe it will happen and make personal preparations," said Webster, who has stored a three-month supply of food and water at his home in case of an outbreak.
Frightening Warning
"Society just can't accept the idea that 50 percent of the population could die. And I think we have to face that possibility," Webster said. "I'm sorry if I'm making people a little frightened, but I feel it's my role."
Most scientists won't put it that bluntly, but many acknowledge that Webster could be right about the flu becoming transmissible among humans, even though they believe the 50 percent figure could be too high.
Researcher Dr. Anne Moscona at New York Weill Cornell Medical Center said that a human form may not mutate this year or next -- or ever -- but it would be foolish to ignore the dire consequences if it did.
"If bird flu becomes not bird flu but mutates into a form that can be transmitted between humans, we could then have a spread like wildfire across the globe," Moscona said.
No one knows how long or how many mutation changes it would take for bird flu to become a direct threat to humans.
"It may not do it. There may just be too many changes. The virus may not be able to be a human virus," Moscona said.
But that hasn't stopped Moscona from searching for new types of anti-viral treatments that both prevent and slow the spread of bird flu.
"I don't think that once we have human-to-human transmission, it's going to be possible to contain it," she said.
That is why nearly every viral scientist in America, perhaps the world, is waiting and watching the avian flu virus to see if it remains just a threat to birds or changes its genetic code and becomes a deadly threat to humans as well.
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Study finds mutations needed for bird flu pandemic
http://news.yahoo.com/s/nm/20060316/hl_nm/birdflu_mutation_dc
>>
By Maggie Fox, Health and Science Correspondent
Mar 16, 2006
Scientists said on Thursday they had identified some of the mutations the H5N1 avian influenza virus needs to gain a permanent foothold in the human population, causing a greatly feared pandemic.
They said the test they used, called a glycan microarray, might be useful in monitoring the virus in birds and as it infects people, to see if it is mutating into a form that would allow it to pass easily from person to person.
H5N1 has moved steadily across Asia and into Europe since it reappeared in 2003, and has picked up speed in recent weeks. It has killed just over 100 people but remains mostly a virus of birds.
No one can predict when, or even if, it will evolve into a form that transmits easily from one person to another, but fears are that it will. Scientists have been examining the virus when they can get samples and trying to predict just which changes are needed to make it change from a bird-specific to a human-specific form.
Ian Wilson and a team at The Scripps Research Institute in La Jolla, California looked at a structure on the surface of all influenza viruses called hemagglutinin. It is the "H" in H5N1 and there are 16 known types of hemagglutinin.
Only three -- H1, H2 and H3 -- have been known to cause human disease and they caused the last three great influenza pandemics, in 1918, 1957 and 1968.
"When pandemics start, we really don't know, with the first virus that enters the human population, how well it is adapted to humans," Wilson said in a telephone interview.
Working with flu experts Terence Tumpey of the Centers for Disease Control and Prevention in Atlanta and Jeffery Taubenberger of the Armed Forces Institute of Pathology in Rockville, Maryland, Wilson's team dissected and imaged a sample of influenza virus that killed a 10-year-old Vietnamese boy in 2004.
RESEMBLING A PANDEMIC VIRUS
They found its hemagglutinin looked very similar to the virus that caused the 1918 pandemic, which killed anywhere between 50 million and 100 million people. It looked less similar to H5N1 taken from a duck in Singapore.
"Of the H5N1 viral isolates studied to date, A/Vietnam/1203/2004 (Viet04) is among the most pathogenic in mammalian models, such as ferrets and mice," the researchers wrote in their report, published in the journal Science.
Hemagglutinin allows the virus to attach to the cells it infects, and it has to be able to grapple a structure called sialic acid, which is slightly different in different animal species.
So to pass from birds to humans, the virus must mutate enough to allow it to bind to, for instance, both a human lung cell and a chicken's intestinal cell.
Wilson's team identified a structure that, in the human configuration, is called an alpha 2-6 receptor and in birds an alpha 2-3 receptor. It must change from the bird to human configuration, they found, to cause human epidemics.
This "critical step ... appears to be one of the reasons why most avian influenza viruses, including current avian H5 strains, are not easily transmitted from human-to-human following avian to human infection," they wrote.
Earlier studies had shown it took only two changes to make the 1918 virus look just like a purely avian virus. That may suggest it may not take much mutation to change a bird virus into a human pandemic strain.
The test may help monitor for these changes, Wilson said.
"This test that you can do for receptor testing specificity, this glycan array, is something you could possibly think about using in the field," Wilson said.
So if the virus has not mutated yet, why does it ever infect people? "It's not an all or nothing," Wilson said.
"It's a preference. At higher doses, doses that normally you and I wouldn't pass the virus on to one another... you can overcome this (species) barrier."
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Deadly bird flu strain may have reached Israel
By JUDY SIEGEL-ITZKOVITCH AND AP
The Health Ministry voiced caution and urged the public not to panic after the Agriculture Ministry announced on Thursday night that turkeys in two Negev farms were "suspected" of having died from the H5N1 strain of avian flu.
Associate director-general Dr. Boaz Lev said that there is no danger to the general public, as avian flu directly among poultry and wild birds and can spread only to people in direct contact with live birds whose droppings contain the virus. There is no danger eating poultry, even if the food supply is affected by the virus, as it is destroyed by the heat of cooking and does not pass to humans who touch raw processed poultry.
"It's a problem for the turkey and the chickens, but not for humans at this point," said Prof. Manfred Green, director of the Israel Center for Disease Control. "If it is bird flu, poultry will be isolated and killed in the affected area within a radius of three kilometers.
"Agriculture workers who have been directly in contact with them could be given anti-virals as a prophylactic measure and on an individual basis," he added. "We are waiting for confirmation. So far, it seems to be the H5 strain, but we are not sure that it is H5N1, which is more infectious."
Israel has had sporadic cases of avian flu in wild birds, but not of the specific strain H5N1.
Agriculture Minister Zeev Boim said Thursday that the widespread death of turkeys at the two western Negev communities of Kibbiutz Ein Hashlosha and Holit could have been caused by the deadly H5N1 strain of bird flu.
"Tonight, we will likely find out if indeed we are talking about bird flu," Boim told Israel TV. "In the meantime, it is a suspicion."
The Agriculture Ministry said that they may know Friday morning if it is an outbreak of avian flu, and that there's a 50-50 chance.
"We have imposed a quarantine in a radius of 7 kilometers around the area, and we are prepared, in case our suspicions are confirmed, to prepare for a widescale destruction of the flocks in a radius of 3 kilometers," he said.
Boim stressed that Israelis should remain calm until the tests have been completed.
There have periodically been such bird flu cases in wild birds and even domestic ones in recent years, the most recently about three years ago.
The Israeli Veterinary Service said that initial results indicated that the birds had died from avian flu, though it had not yet been determined if they were infected with the feared H5N1 strain of the virus.
Many Israeli agricultural communities are largely dependant on the poultry industry.
The H5N1 virus was detected in neighboring Egypt last month, and Boim said the death of the birds in southern Israel might indicate that the disease could have entered the country from Egypt.
The H5N1 strain has killed or forced the slaughter of tens of millions of chickens and ducks across Asia since 2003, and recently spread to Europe, Africa and the Middle East.
Health officials fear H5N1 could evolve into a virus that can be transmitted easily between people and become a global pandemic, but there has been no confirmation of this happening yet.
http://www.jpost.com/servlet/Satellite?cid=1139395620139&pagename=JPost/JPArticle/ShowFull
Dubi
Bird Flu Puts An Element Of Peril Into Buddhist Rite
Animal Experts Warning Against Traditional Release
By Alan Sipress
Washington Post Foreign Service
Thursday, March 16, 2006; A15
PHNOM PENH, Cambodia -- Over the centuries, Buddhists in Cambodia and elsewhere in Asia have released the sorrows born of sickness, hunger and war through the simple, cathartic act of buying caged birds and setting them free, sometimes with a kiss.
In front of the shimmering gold pagoda of Wat Phnom, built on the grassy hill that lent the capital its name, Cambodians reach inside the metal and wire mesh cages, draw out sparrows, swallows, munias and weavers, often in pairs, then raise them in cupped palms to their lips. The devotees mumble a prayer and then set them free into the warm, still air.
But the tradition, in which devotees seek blessings for this life and the next, could now prove to be a curse. Animal health experts warn that the practice of capturing wild birds, holding them in confined quarters and then turning them over to human hands could spread avian flu among birds, across species and on to people.
So far, avian influenza has not been diagnosed in any of the birds released at the temples of Buddhist Asia, from Thailand to Taiwan. But that is only because so few have been tested, according to Martin Gilbert, a field veterinarian with the U.S.-based Wildlife Conservation Society. The virus, which has killed people in at least seven countries, including Cambodia, and infected birds on three continents, has been discovered in some of the same species that are sold in front of Buddhist shrines.
Gilbert said that the threat is comparable to the danger posed by live poultry markets blamed for several Asian outbreaks of the highly lethal H5N1 strain of bird flu, including one in Phnom Penh this month.
"H5N1 is out there and we have to be cognizant of the risks in acting this way," Gilbert cautioned.
On a recent morning, Kong Phalla, a young, slight woman wearing a red knit cap, stood under a tree at the base of Wat Phnom, clasping lotus stems in one hand and a metal cage crammed with scores of birds in the other. She said that the birds had been shipped into the city overnight by boat and that she had sold nearly three dozen to worshipers by the morning.
"They want to free their depression, free their sadness and illness with the birds," Kong Phalla, 23, explained, resting the cage beside a table of incense sticks.
She flashed a thin smile, saying she had brought five cages to the temple and was confident that nearly all 1,000 birds would be gone by nightfall. Bird flu was of no concern, she continued, patting the cage. It is only the foreign tourists who fret, often paying her to release the birds herself so they do not have to touch them.
"Bird flu has never happened to me," Kong Phalla boasted reassuringly.
Spotting a Cambodian man approaching the temple, she abandoned her thought and gave chase, following him up the long brick staircase, past the statues of lions and balustrades of mythical serpents, beseeching him at each step to purchase a few of her birds.
At another pagoda in the Cambodian capital, Khy Sovanratana sat cross-legged on a thin cushion, his orange monk's robe draped over his left shoulder. He recounted the legend of how the Buddha, before attaining enlightenment, had found a swan wounded by an arrow, nursed the creature back to health then set it free.
"Giving life is very much extolled in Buddhism," the monk explained softly. "People here hope that by releasing a bird, they will give life to another being, and they will also be free from illness, trauma and depression."
Moreover, the monk continued, the act of liberating a living creature can also earn devotees religious merit toward reincarnation into a better life.
But, setting aside the sublime, he added: "There's no point if you don't get benefits but instead catch a virus. Monks should be given this kind of awareness and pass it on to devotees when preaching."
Though the ritual of releasing birds is practiced in several Asian countries with Buddhist populations, the tradition in Cambodia is intertwined not only with religion but national identity. The king frees doves, pigeons and other wild fowl about four times a month -- in especially generous numbers to mark royal birthdays -- and this has complicated efforts to curb the practice.
Its adherents rarely remark on the apparent contradiction of trapping birds only to set them free -- an irony compounded by the attempts of some boys to catch fowl moments after their release so they can be sold yet again.
Gilbert's team has run into resistance from peddlers when trying to take fecal swabs from the birds to test for the disease. So in recent weeks, he enlisted a former Cambodian monk, a young man who swapped the monastery for work as a wildlife researcher, to delicately negotiate with the sellers.
Another U.S.-based group, WildAid, previously tried to curtail the practice of selling birds for the tradition on the grounds that the exchange represented improper trade in wildlife. The group established a rapid-response unit that included Cambodian military police and forestry officials and carried out several raids on bird peddlers. The campaign culminated last June in the confiscation of birds sold at Wat Phnom and elsewhere, according to Nick Marx, who coordinated the effort. But because of religious and political sensitivities, the government postponed further raids.
"We were requested at least temporarily to stop doing this until the government decides what to do about the matter," Marx said. "It's a difficult issue."
Not long after Kong Phalla vanished up the steps of Wat Phnom, a Cambodian family approached another, smaller shrine along the city's Tonle Sap River across from the ornate royal palace. The family briefly haggled with a peddler, then purchased an entire cage of birds, about a hundred of them with frenetic, flapping wings.
Two by two, the family pulled the birds from behind the mesh and, with the occasional whisper of a prayer, set them loose until all of them had disappeared along the banks.
"I have no concern about getting sick with bird flu, and the buyers have no concern," said Srey Leap, a 21-year-old bird merchant, who watched from the shade of a nearby umbrella. "They never worry about this. It is our Cambodian tradition."
http://www.washingtonpost.com/wp-dyn/content/article/2006/03/15/AR2006031502198.html
After Fighting A Cattle Disease, Vet Turns to Birds
http://online.wsj.com/article/SB114246885425899518.html
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Dr. Roeder Advocated Targeting
Animal Vaccines in Africa;
Finding 'Viral Reservoirs'
By NICHOLAS ZAMISKA
March 16, 2006
MALANG, Indonesia -- For centuries, a virus called rinderpest destroyed the world's cattle and the livelihood of people who depend on them.
Now, animal-health workers have corralled this disease onto a relatively small stretch of desert in Africa, where it appears on the verge of extinction. If so, it would mark a rare case in which humans have wiped an animal virus off the face of the Earth.
Among those involved in the most recent assault on rinderpest is a 60-year-old British veterinarian named Peter Roeder, who has spent decades fighting the disease in Africa and Asia. Dr. Roeder, fresh from his battle against one animal virus, has recently been in Indonesia, helping lead the charge against another -- the deadly avian influenza virus known as H5N1, or bird flu.
He believes bird flu may eventually be halted by a lesson learned in the fight against rinderpest: that mass vaccinations don't always work as well as narrowly targeted attacks on the disease. "There are a lot of similarities," between the two diseases, says Dr. Roeder, secretary of the United Nations' Food and Agriculture Organization's Global Rinderpest Eradication Program.
But unlike rinderpest, which never spread to humans, bird flu has crossed the species barrier, killing at least 98 people since late 2003, mostly in Asia. If the disease mutates into a form that spreads easily among humans, scientists fear it could cause a pandemic killing millions. Eliminating H5N1's threat to humans means eradicating it from the birds that harbor the virus.
Many factors went into bringing rinderpest to its knees, including an effective vaccine that worked with one dose and a centralized disease-control program that had authority to operate within countries. In the case of bird flu, neither exists. And bird epidemics, carried by flocks, can move more quickly.
For decades, veterinary authorities embraced one basic approach to attacking rinderpest: mass vaccination. That helped rid many countries of the disease. But Dr. Roeder says the approach sometimes failed in places where there simply weren't enough veterinarians or vaccine supplies to guarantee thorough coverage, leaving pockets of unprotected animals that could harbor the virus. In Ethiopia, for instance, veterinary officers repeatedly trekked through the desert in an attempt to inoculate every cow in the country. But the virus remained firmly entrenched in the east African nation.
"Why try to vaccinate the whole of Ethiopia?" Dr. Roeder says. "You could never do that."
The key to rinderpest's defeat, he says, lay in being selective. It was better to leave certain areas altogether unprotected, he says, if that allowed a blitzkrieg attack with all available resources on stubborn strongholds of the disease -- so-called viral reservoirs. These reservoirs were often in remote areas, far from veterinary services and vaccines, with a high density of animals in which the virus thrived.
The idea has begun to resonate with some bird-flu experts. China last year announced an ambitious plan to vaccinate its billions of birds. But last month, a group of nearly 30 scientists from around the world argued in a paper published in the Proceedings of the National Academy of Sciences that southern China in particular has been a breeding ground for avian influenza viruses for at least a decade, allowing the virus to fester and spread from there. Eliminating the virus at its source, in Guangdong province, they argue, could go a long way to eliminating the disease.
"A lot of people don't understand it," Dr. Roeder says. "They just think it's vaccination, vaccination, vaccination, but they don't realize that you can vaccinate for 30 years and still have the disease right under your nose." But he adds, "unless you understand this, you don't have a hope in hell with a disease-control program. And that's the same with avian influenza."
To be sure, the strategy of targeted vaccination may likely be most effective with bird flu later in the battle against the disease, if the virus becomes much less widespread. The U.N.'s Food and Agriculture Organization currently recommends that Nigeria and Vietnam, for instance, vaccinate "as much as they can," says Juan Lubroth, a senior officer with the FAO's animal-health service in Rome.
Dr. Lubroth acknowledges the advantages of a targeted approach, if there were more veterinarians available on the ground to figure out which places to target. "We need a competent veterinary authority that knows where these hot spots are."
Rinderpest, which means "cattle plague" in German, dates back at least two millennia. Some historians believe the fall of the Roman Empire may have been hastened by a rinderpest-induced famine.
As understanding of the disease, and of viruses in general, advanced, rinderpest began gradually to be beaten back. By 1928, outbreaks in Europe had ceased, but the virus still ran rampant through much of Africa and Asia. As recently as the 1980s, rinderpest swept across Africa, decimating herds.
After graduating from the Royal Veterinary College in London, Dr. Roeder wound up in Africa. In the 1970s, while working for the British Overseas Development Administration in Ethiopia, he saw his first field case of the deadly rinderpest virus, which produces a fever in cows, covers their nostrils and eyes in mucus and can kill them within a week. In villages, cattle carcasses littered the ground between the mud huts, he recalls. Emaciated cows walked aimlessly.
Dr. Roeder spent years in Africa researching the virus and plotting how to contain it. The turning point came in 1992.
After hours driving along the Rift Valley in Ethiopia looking for pockets of infected cattle, Dr. Roeder sat at a bar with two veterinary colleagues. As they talked, he says he realized Ethiopia's constant efforts to vaccinate its cattle en masse failed because the country had too many cows and too few people to vaccinate them.
Only a limited portion of the total cattle population could be protected at any one time. He says they understood then that defeating the disease would mean leaving some areas of Ethiopia unvaccinated, so resources were available to blanket the trouble spots, the viral reservoirs.
Dr. Roeder and his two colleagues began scribbling a map of the country on a piece of paper, plotting their attack. They chose to target several reservoirs of the virus, including the herds of the Afar people, who keep cattle for milk. Grazing in the lowlands, those cattle likely became infected in the 1970s, then spread the disease to other areas while never being vaccinated themselves.
Gijs van't Klooster, a Dutch veterinarian who worked with Dr. Roeder at the time and still lives in Addis Ababa, the Ethiopian capital, quips that the country had a " 'pillow' vaccination instead of 'blanket' vaccination." After he studied vaccination records, "it became very clear that with the resources available at that time, a blanket vaccination coverage could never be achieved."
Still, the idea of targeted vaccination met stiff resistance. In 1993, one of Dr. Roeder's colleagues presented it to a meeting of international health experts and country officials in Cairo, Egypt, only to be "shouted down by people" who considered the plan far-fetched and dangerous, Dr. Roeder says.
Their fear: Unvaccinated areas would allow the virus to spread unchecked, undoing decades of hard-won progress. If outbreaks occurred in areas where veterinary officers had stopped vaccinating, Dr. Roeder says, "their heads would be on the block."
Among those who opposed the idea was Martyn Jeggo, who spent some 15 years working on rinderpest in Africa and is currently director of the Australian Animal Health Laboratory. "I don't think this will work," Dr. Jeggo remembers telling Dr. Roeder.
But slowly, the idea won adherents. The U.N.'s Food and Agriculture Organization endorsed the plan by Dr. Roeder and his colleagues to target the reservoirs of the virus, including the Afar people's cattle -- while leaving the rest of Ethiopia's herds almost untouched.
For about five years now, no confirmed case of rinderpest has appeared anywhere in the world, a sign that the battle against the disease could soon be declared over.
"Peter and his colleagues were the first people to emphasize that blanket vaccination was not the best way to eradicate the disease," says Walter Plowright, a British veterinary researcher who developed the vaccine that proved decisive in crippling the disease. "I don't think he's had enough credit."
The targeted approach wasn't new, having been used sporadically with rinderpest in places such as Tanzania in the 1960s, the inner delta of Niger river in Mali and Mauritania in the early 1980s, says Paul Rossiter. He was the regional epidemiologist in Nairobi, Kenya, to the Pan African Rinderpest Campaign, an effort to stamp out the disease in the 1990s. "What Peter and his close team have done is to champion the targeted approach when it appeared to have been forgotten or was neglected in favor of widespread mass vaccination," he says.
Australia's Dr. Jeggo now says he was "proved wrong" and calls the targeted approach in Africa "incredibly successful. It showed there was a different way to do vaccination." While he says mass vaccinations work in areas where there is enough money and manpower to vaccinate all animals, "the targeted approach for rinderpest is going to be the right way forward with avian influenza."
Last fall, as bird-flu deaths were rising in Indonesia, Dr. Roeder says his boss asked him to go there. Within a week, he left his home in Rome for Jakarta.
It is crucial to figure out how the disease moves from place to place, Dr. Roeder says. So he and colleagues have been visiting Indonesia's poultry markets, as well as the homes of farmers.
One colleague is Christine Jost, an assistant professor at Tufts University. She, too, has worked with rinderpest. In Uganda years ago, she trained villagers to administer vaccines, to reduce reliance on the country's patchy veterinary service. That taught her the importance of targeted vaccination in a country with limited resources, she says.
"If you can achieve 90% to 95% vaccination, then you should vaccinate," Dr. Jost says. Anything less, she says, makes it impossible to know whether an area is free of the disease.
Indonesia, like other countries, has been trying to vaccinate as many birds as possible, and now provides vaccines free to smaller farmers. But there are obstacles.
"It is not easy to motivate people to get their birds or free-range chickens vaccinated," says Sudjono, a veterinary official at the Ministry of Agriculture in Malang, a city in Java. Like many Indonesians, he goes by one name. "Besides, we are short of people in the office." There are only two veterinarians and two volunteers for each subdistrict, which can include 15 villages, he says. "If we had more people and enough funds, I believe that 90% of the vaccination program will be successful."
Some resistance is cultural. Suryanto, a local religious teacher, says his chickens started dying last September. Of a flock of 50, four survived. "I think the time has come for them," he says. "That has been written by Allah up there. I also have three canaries. They're healthy. I will not give any vaccine to the birds or to the chickens. If they will have to die, it will be their fate. You and I, we will die, too."
Susetiyowati, another local resident, says when her chickens fall ill, she feeds them a concoction of soybeans, ketchup and coffee. When that doesn't work, she says she buries them in the yard. But she says families in Malang sometimes sell birds that get sick, to chicken traders who come by in the morning on motorcycles. The going rate for a healthy chicken is 20,000 to 40,000 rupiah, or about $2 to $4, depending on weight; a sick chicken fetches around 13,000 to 15,000 rupiah, she says.
Dr. Roeder thinks traders like these may be a reason the virus suddenly shows up in a place that has never had an outbreak. It is crucial, he says, to target the sources, or reservoirs, of the disease. "What we're doing now in Indonesia is essentially what we did in Ethiopia in 1992," he says, "to work out the reservoirs of the virus and eliminate them."
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Roche aims for 400 mln Tamiflu doses by end 2006
Thu Mar 16, 2006 4:25 AM ET
The Basel-based firm said it hoped to have the capacity to produce 400 million treatments of the drug by the end of 2006, a welcome boost in output as governments around the world build stocks of the medicine to ward off a bird flu outbreak.
Bowing to pressure to increase capacity, Roche has struck deals with a total of more than 15 external contractors in nine different countries. These firms will produce parts or all of the drug in order to help speed up production.
Roche also said it was stepping up its research drive through a range of new studies to understand how Tamiflu can be best used as the virus evolves.
"Roche has in place a number of research initiatives to answer questions raised on the use of Tamiflu against the evolving H5N1 avian virus," David Reddy, Roche's executive in charge of bulk sales of the drug, said in a statement.
Roche also said it was in the final stage of negotiations for a production sublicense with a company in China and said it was also looking at sharing know-how to help start up production in Africa.
This was in addition to sub-licenses for the complete production of oseltamivir, as the drug is known generically, that were granted to Hetero and Shanghai Pharmaceuticals (600849.SS: Quote, Profile, Research) last year.
Roche has received and fulfilled pandemic orders for Tamiflu from more than 65 countries worldwide, it said.
The drug, a neuraminidase inhibitor, is seen as the best defence against a human form of the bird flu pandemic which has been found in wild birds across Asia and Europe.
The highly pathogenic H5N1 strain of bird flu has killed about 100 people and experts fear a pandemic if the disease develops to a point where it can be transmitted between humans.
U.S. bird flu budget focuses on future vaccines
Mon Mar 13, 2006 5:43 PM ET
By Maggie Fox, Health and Science Correspondent
WASHINGTON, March 13 (Reuters) - More than half the U.S. bird flu budget will go to developing new vaccines, Health and Human Services Secretary Michael Leavitt said on Monday, but he stressed that companies, schools and local officials would have to do most of the work of preparing for a pandemic.
Another big part of the $3.3 billion allocated by Congress for this year would go to stockpiling drugs that fight influenza, Leavitt told reporters.
"The bulk of our money -- $1.781 billion of the money -- is directed at a vaccine," Leavitt said.
In the meantime, he said, state and local officials, companies, schools and individuals should be preparing for the economic and social disruption that would come with any pandemic.
The H5N1 avian influenza virus has spread across Europe, taken hold in Africa and flared anew in Asia in recent weeks. While it remains mostly a disease of poultry, it can occasionally infect people and has sickened 176, killing 98 of them, according to the World Health Organization.
That does not include three people reported by Azerbaijan's Health Ministry on Monday as having died from the virus.
Leavitt and other experts say it is only a matter of time, perhaps just a few months, before the virus spreads to birds in the United States. No one can say if or when the virus would mutate into a form spread easily from person to person, thus setting off a pandemic.
Last year, U.S. President George W. Bush asked Congress for $7.1 billion to prepare for a pandemic. Congress approved just half of that and Leavitt on Monday released the details of how it would be spent.
His report said $731 million would be spent on drugs such as Roche's (ROG.VX: Quote, Profile, Research) and Gilead Sciences' (GILD.O: Quote, Profile, Research) Tamiflu and GlaxoSmithKline's (GSK.L: Quote, Profile, Research) Relenza. Leavitt said he hoped the federal government would have 26 million courses of the antivirals by the end of the year.
BUYING MASKS AND VENTILATORS
"In addition to stockpiling antivirals, $162 million will be used to procure essential medical supplies for a pandemic. Planned purchases this year include 6,000 ventilators, 50 million surgical masks, 50 million N95 respirators (face masks), and face shields, gloves and gowns," the report reads.
Last week, Leavitt's office authorized the development of a second vaccine formulation using one of the new strains of H5N1 that has emerged as it spreads from birds to people.
Companies are already developing and testing vaccines based on the strain that infected people in Vietnam in 2004, but at least two substrains have since emerged that are different enough to justify making a new formulation.
"We are within a matter of weeks before we will put ... out contracts to major manufacturers," Leavitt said.
He said HHS would also be looking for proposals from companies to make vaccines using new technologies that do not rely on eggs, as current influenza vaccines do, and perhaps using boosters known as adjuvants to stretch the vaccine supply.
Leavitt has been traveling across the United States holding pandemic "summits" where he hears concerns and urges local leaders to get busy preparing for a pandemic. He issues checklists and signs a "contract" with each state on what it plans to do.
He has seen much that worries him -- a lack of hospital space, few ideas for when and how to close schools and difficulties surrounding the distribution of drugs and vaccines.
"I am seeing many states exercise their plans and when they exercise their plans, weaknesses are revealed," Leavitt said. "And when weaknesses are revealed, things get better."
© Reuters 2006. All Rights Reserved.
How Can We Protect Patients With Weakened Immune Systems From Influenza?
Monday March 13, 12:53 pm ET
-- Biodefense Grant Will Study Vaccine Responses to Common Flu, with Implications for Potential Avian Form or Terror Weapon --
PHILADELPHIA, March 13 /PRNewswire/ -- The flu is bad enough for healthy people, but the disease can place a special burden on those with weakened immune systems, such as patients on chemotherapy. A five-year, $10.7 million federal grant to The Children's Hospital of Philadelphia will support research to determine how adults and children with impaired immune systems may be uniquely vulnerable to influenza, and will seek better ways to protect them.
Because patients with compromised immune systems may be contagious longer than people with healthier immune systems, they may be a reservoir for the disease. In addition to the yearly toll of ordinary influenza (as many as 36,000 annual fatalities in the U.S.), added concerns over potential threats - an avian flu pandemic or the use of flu as a weapon of biological warfare - put anti-flu measures into the category of biodefense.
Under a biodefense program mandated by Congress, the National Institute of Allergy and Infectious Diseases, in conjunction with the Department of Defense, has awarded the grant to researchers at The Children's Hospital of Philadelphia and the University of Pennsylvania, led by pediatric immunologist Kathleen Sullivan, M.D., Ph.D., chief of Allergy and Immunology at Children's Hospital.
"Our research focuses on the basic question of who benefits most from influenza vaccine," said Dr. Sullivan. "This question becomes paramount if influenza reaches epidemic proportions and supplies of vaccine are limited. We want to offer protection to these special populations of immunocompromised patients, but not to vaccinate them needlessly."
Patients on chemotherapy, on immunosuppressive drugs, or with diseases that weaken the immune system may be especially vulnerable to influenza, whether the ordinary annual variety or deadlier types. The researchers will study how such patients' vaccine responses change over time: "Some patients may not benefit from flu vaccine at one point in time, but they may benefit just two or three weeks later," said Dr. Sullivan.
The research teams will measure T cell and B cell counts in the targeted patients. Both types of cells play important roles in the immune system. T cells that recognize and fight influenza may help predict whether a patient will produce protective antibodies after vaccination. Producing those antibodies is the job of B cells. "We hope to be able to use a simple blood test to help determine which immunocompromised patients will benefit from an influenza vaccine," added Dr. Sullivan.
The full grant encompasses six projects, each of which focuses on particular immunocompromised subpopulations. Ultimately, the researchers expect to have customized treatment recommendations for each group.
Half of the projects cover children at The Children's Hospital of Philadelphia. One project will study immune responses in children receiving different intensities of chemotherapy for solid tumors and two types of leukemia. Another project is dedicated to children with neuroblastoma, a solid tumor of the peripheral nervous system, who are treated with a novel type of stem cell transplant. Both chemotherapy and stem cell transplants involve suppressing the patients' immune defenses. A third group of patients has chromosome 22q.11.2 deletion syndrome, a congenital multisystem disorder that impairs the immune system. Children's Hospital is a world leader in studying and treating this syndrome.
Three projects involving adults are led by researchers in the University of Pennsylvania Health System. Two projects involve cancer patients: those receiving stem cell transplants for multiple myeloma (a cancer originating in bone marrow) and patients with ovarian cancer receiving an experimental treatment - an anti-cancer vaccine made from dendritic cells. Carl June, M.D., director of translational research at Penn's Abramson Cancer Center, leads both projects.
A third group of adult patients suffers from autoimmune diseases, those in which an abnormal immune system turns on itself: systemic lupus erythematosus and Sjogren's syndrome.
Core research facilities will assist all the projects in systematically measuring T cell and B cell counts and developing specialized assays. The researchers will begin enrolling patients this fall under the five-year program.
"A major reason to study influenza is the quick-changing nature of the influenza virus," said Dr. Sullivan. The virus mutates its outer coating from year to year, a process called viral drift, which is why new flu vaccines are developed each year. The potential threat of avian flu is that mutations in the avian virus could allow it to easily pass from person to person. An epidemic with a completely new type of virus such as this represents viral shift, and is usually far deadlier because there is no pre-existing immunity in the population.
Furthermore, although it has never been known to have been developed as a bioterror weapon, the influenza virus may be relatively easy to manipulate for such purposes in a laboratory - which is why the federal government is funding medical research to improve defenses against flu.
Dr. Sullivan looks to broader and longer-term benefits of her funded program. "Even if the worst-case scenarios of flu pandemic or weaponized flu attack do not occur in the next few years, we will have greater understanding of how to protect vulnerable patients."
The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking second in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.
Contact: John Ascenzi
Phone: (267) 426-6055
Ascenzi@email.chop.edu
http://biz.yahoo.com/prnews/060313/phm028.html?.v=43
Bird flu targeting the young
http://www.thestar.com/NASApp/cs/ContentServer?pagename=thestar/Layout/Article_Type1&c=Article&a...
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As death toll nears 100, scientists scramble to explain why H5N1 virus is killing healthy people under 40
Mar 11, 2006.
By RITA DALY
With the World Health Organization set to announce the 100th death from bird flu any day now, data compiled by the Toronto Star lead to one particularly compelling question: Why does the H5N1 virus attack the young?
The Star's analysis shows that all but six of the 97 people who have died globally so far from bird flu were under 40.
People, in other words, with the strongest immune systems and not, as one might expect, the elderly and those already sick. The median age was 19, and a quarter of them were under age 12.
Children, teenagers and young adults are the unfortunate victims of the deadly H5N1 bird flu sweeping through poultry farms in Asia, Africa and now Europe.
Hooked up to breathing tubes and dialysis machines in local hospital beds, bodies soaked in sweat, and blood oozing from their nostrils and mouth, they have a mere 50 per cent chance of pulling through. The rest die in a matter of days.
Any day now the World Health Organization will announce the 100th death from the bird flu that re-emerged in late 2003.
Yesterday, health officials confirmed a 4-year-old Indonesian boy died last month, bringing the number of confirmed cases to 176 and the world death toll to 97. Another three deaths in Azerbaijan are under investigation.
Although human cases are uncommon, it is now apparent the H5N1 will eventually reach North American shores, possibly via migratory birds in Alaska within six to 12 months. So what health experts know about how and whom it strikes is crucial.
So far, they know nearly everyone who died of the respiratory disease was in close contact with infected domestic birds, and most were young and previously healthy. Yet scientists still aren't sure why they fell ill, while others equally exposed to H5N1-infected chickens and ducks were spared.
"There are still a lot of unanswered questions and that's one of them," Sonja Olsen, an epidemiologist for the Atlanta-based U.S. Centers for Disease Control, said in an interview from Thailand where she is studying human cases of the H5N1.
There are other unanswered questions, like why is it some family members become infected and others not? Why aren't health-care workers in hospitals or unprotected agricultural workers slaughtering chickens also getting sick?
Originally surfacing in Hong Kong in 1997, killing six, then again in early 2003, killing one, the bird flu re-emerged later with a vengeance, decimating poultry stocks and infecting more people in areas of Southeast Asia.
The 97 deaths in the third wave are now spread across seven countries — Vietnam, Cambodia, Indonesia, China, Thailand, Turkey and Iraq. The infection rate is already double this year over last, with more than three human cases a week as infected birds spread the virus further afield.
"A lot of the human cases of bird flu have occurred in people under 25 and we're still not exactly sure why that is," said the WHO's Maria Cheng.
"They may have different behaviour patterns, they may be exposed to the virus in closer ways, they may be more susceptible to it. But there's such a small number of cases that it's difficult to draw any conclusions about how it's transmitted in target populations."
WHO officials stress the number of deaths from H5N1 bird flu is extremely low compared to the 250,000 to 500,000 who die annually from seasonal human flu, or the nearly 800 people who died during the SARS epidemic in 2003, 44 of them in Toronto. But health experts also warn no bird flu has ever sickened and killed so many people as H5N1.
The virus has only a limited ability to infect people, but experts fear it could mutate and spread easily among humans, sparking a pandemic that could kill millions within months.
Canadian officials have devised an emergency plan in the event of a pandemic, but say as long as H5N1 remains bird flu there is little cause for alarm in a country where people and poultry live separate lives.
In the past century we've had three human flu pandemics: in 1918, 1957 and 1968. The most lethal — the 1918 Spanish flu — also targeted the young and healthy, killing 20 million to 50 million worldwide.
In a study published in the online medical journal Respiratory Research in November, Hong Kong scientists noted the H5N1 was creating what's called a "cytokine storm" in its healthy victims, causing their immune system to overreact to the virus, flood the lungs with an overabundance of antibodies and cause extensive lung damage, eventually shutting them down. It's the same response scientists believe caused so many deaths during the Spanish flu.
The H5N1 virus has already earned the notorious reputation of being the worst flu in birds. An unprecedented 200 million have died or been slaughtered. It is so highly pathogenic, infected chickens drop dead in 48 hours. This month, the virus showed up in several domestic cats and a weasel-like animal called a stone marten in Germany and Austria, creating fear in the European Union that it might easily be infecting other species.
Earl Brown, an avian flu expert and professor of immunology and virology at the University of Ottawa, said the behaviour of small children playing among infected fowl could logically account for the high infection rate among the young.
A recent news report saw 15 Iraqi children running through an area where thousands of culled chickens were dumped, tying them to sticks and waving them in the air.
A 14-year-old Turkish boy and his two sisters, 15 and 11, died in January after playing with the head of an infected chicken the family slaughtered and ate. And an 8-year-old Turkish girl died after kissing and hugging her dying pet chicken.
But each person's immunity, even genetic factors, may also play a part in determining who falls ill and dies, Brown said.
"On average, you'll get influenza once every five or 10 years, so kids are less likely to have antibodies from prior exposure," he said. "Adults will have had experiences with different influenza viruses."
It still doesn't explain the disproportionate number of people in their 20s and 30s who have succumbed to the disease. One theory is that some people have immunity to the N1 antigen of the bird flu virus developed from the H1N1 Spanish flu. That virus was still circulating in a milder form until 1957 and also re-emerged as a milder strain in 1977.
Each time there is a suspected case, WHO officials quickly send a team of field experts to investigate.
Swab samples are sent to the organization's reference labs for further tests and to determine whether the virus has changed genetically in a way that might allow it to transmit more easily between people.
So far, they have found most confirmed cases involve people with backyard poultry farms who had close contact with infected or dying birds — in some cases slaughtering, defeathering and preparing them for dinner.
"When the chickens get sick and die, they get plucked, eviscerated and put into a pot, so maybe it's the mother and kids that are exposed at this point," Brown said.
Virologists know infection occurs through contact with blood, feces and other body fluids, and WHO officials recently reiterated the flu virus is also airborne, posing even a greater threat than AIDS.
If the virus were to start spreading easily among people, the first warning signal of a possible pandemic will be more and more clusters of people getting sick.
The CDC's Olsen and a team of researchers looked for this while examining 15 family clusters of infected cases in Vietnam, Thailand, Cambodia and Indonesia between Jan. 2004 and July 2005 — a mother and child; siblings; cousins; a niece and aunt; a teenager, her older brother and grandfather.
They found no increase over time.
But Olsen said most had not been investigated thoroughly enough to say for certain there was no person-to-person transmission.
"There was only one where you could clearly say there was person-to-person transmission and the others left you sort of wondering," she said.
WHO officials said this week there are three confirmed cases of suspected person-to-person transmission:
In January 2004, Ngo Le Hung, a 31-year-old Vietnamese schoolteacher, became infected and died from a chicken he bought for his wedding, and his two sisters also died.
In September 2004 a dying 11-year-old Sakuntala Premphasri infected her mother Pranee, 26, in Thailand and both died. And in July 2005 a 38-year-old father is believed to have infected his two daughters, aged one and eight — all three died.
Cheng said there may be other cases in which people became infected through human-to-human transmission, but there isn't enough evidence to prove it. There may also be many less severely ill people going unnoticed.
"But we haven't seen any substantial change in the virus and that is really the trigger we're watching for."
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Scientist Rebels Against WHO Over Bird Flu
http://online.wsj.com/article/SB114221407089396217.html
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By NICHOLAS ZAMISKA
March 13, 2006
Scientists around the world, racing to discover how avian influenza is spreading and whether it is evolving toward a pandemic strain, face a dilemma: Should they share their interim findings widely, show them only to a select set of peers, or keep them to themselves until they can publish papers, often critical to their careers?
Even as the World Health Organization presses China and other countries to share bird-flu data for the public good, the WHO itself runs a database limited to a select group of scientists and containing a massive trove of data -- some 2,300 genetic sequences of the virus, around a third of the world's known sequences, according to two people familiar with the database's contents. Any one of those sequences could hold clues to an effective human vaccine or drugs that could kill the virus, or help scientists determine how great a threat it poses.
Now, a lone Italian researcher has cast a harsh spotlight on the WHO's system, suggesting that it places academic pride over public health -- and snubbing it by posting prized bird-flu data in plain view.
Ilaria Capua, a 39-year-old Italian veterinarian working on avian influenza in a government lab, last month received a sample of the virus in the mail from Nigerian health authorities. The virus had just attacked birds in Nigeria, the first confirmed case of the disease in Africa. The sample was something of a prize, a chance to study a specimen and explore how it spread from its stronghold in Asia.
Within days of isolating the virus, Dr. Capua says, she got an offer from a senior scientist at the WHO in Geneva, whom she declined to name, to enter her finding in the closed system. She could submit the virus's genetic information, or sequence, to the database. In exchange, she would be given the password to the WHO's massive stash of data. A spokesman for the WHO confirmed that the offer was made.
Instead, Dr. Capua posted the gene sequence in a public database accessible on the Internet. She also sent a letter on Feb. 16 to around 50 of her colleagues urging them to do the same with their bird-flu samples.
"If I had agreed" to the WHO's request, she said in an interview, "it would have been another secret sequence."
The WHO, normally an outspoken advocate of transparency, says it limits access to the database so scientists and governments will share bird-flu data they might otherwise hoard to further their own research. Scientists with access to the system can collaborate with each other but must agree not to publish results without prior consultation. Michael Perdue, a leading scientist at the WHO in Geneva, says the system has proven to be a useful compromise, because some sharing is better than none.
Critics of the closed system argue that if the data were made public, other researchers could be making breakthroughs that the select group may be missing. They say that to complete the bird-flu puzzle, all the pieces are needed.
The lethal form of bird flu known as H5N1, which occasionally passes from birds to humans, has recently spread beyond Asia into Africa and Europe, though there have been fewer than 100 confirmed deaths since late 2003. Scientists worry that the virus could mutate into a pandemic strain readily transmissible between people that could take millions of lives. That nightmare scenario is fueling the rush to learn how the virus is evolving.
When a bird or human falls ill with avian influenza and researchers are able to isolate a sample of the virus in a test tube, they will often send that virus to a lab so that scientists can run tests to determine the virus's genetic code. Researchers have been poring over those genetic sequences looking for patterns between viruses found in different parts of the world in an effort to determine which viral strains are related and how they are evolving. Scientists are also sifting through the viral sequences to see which ones may make good candidates for a vaccine.
Dr. Capua's letter, reported in the journal Science on March 3, has touched a nerve in the scientific community. Scientists and agriculture officials from Switzerland, Croatia, Slovenia, the United Kingdom, Iran and Niger have written Dr. Capua giving her permission to make public viral sequences made from samples they submitted to her lab, or have done so themselves in a show of solidarity, she says. Nancy Cox, chief of the influenza branch at the Centers for Disease Control and Prevention in Atlanta, replied to the letter with a personal note saying, "I applaud your decision," according to Dr. Capua.
Dr. Perdue, of the WHO, goes still further, saying the exclusive-access system should change and adding that his sentiment is shared by others within the organization who have privately congratulated Dr. Capua on her effort.
But both Drs. Cox and Perdue say the problem isn't so much getting WHO-affiliated scientists to share their data as it is getting permission from their countries to release the genetic sequences from the viruses found on their soil. "I am hopeful that other countries will note and follow this example" set by Nigeria, Dr. Cox says.
Dr. Capua challenges the assertion that countries are the culprits. "I believe this story about obtaining permission is a scapegoat," she said, pointing to the countries that have given their consent to make their sequences public.
In shunning the system, Dr. Capua instead submitted genetic sequences of her virus sample to GenBank, a publicly accessible database for DNA sequences run by the National Center for Biotechnology Information in Bethesda, Md., which is part of the National Institutes of Health.
In less than two weeks, the Nigerian data and another sequence Dr. Capua deposited have been downloaded more than 1,000 times, according to David Lipman, director of the center that runs GenBank. Researchers can choose whether GenBank releases their sequences immediately or keeps them private until they have had a chance to publish a paper. Even though many, if not most, researchers opt to keep their data private until publishing, the system allows scientists to share information immediately if they chose, as Dr. Capua did.
There are signs that Dr. Capua's letter has spurred the WHO to seriously rethink its closed system, although change could still take some time. Dr. Perdue says that he thinks scientists should no longer be sitting on sequences of H5N1 viruses, given how pressing the threat is, and that most of the labs with special access to the data now agree. "It takes time to change," he says.
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Avian found in cats, now weasels, another mammal has been infected...
Bird Flu Found in Weasel-Like Animal
BERLIN - A German lab has found the H5N1 bird flu virus in a weasel-like animal called a stone marten, officials said Thursday, marking the disease's spread to another mammal species beyond cats.
The marten, sick and apparently already dying, was found on the north German island of Ruegen, where Germany's bird flu outbreak first appeared earlier this year.
The animal came from near the Wittow Ferry area of the island, the same location where three cats and dozens of wild birds have been found with the disease, according to a statement from the agriculture ministry of the state of Mecklenburg-Western Pomerania.
Stone martens look like weasels and have brown fur with a white chest patch.
A veterinarian put down the animal and sent its corpse for further testing. The virus was confirmed by the government's Friedrich-Loeffler Institute laboratory.
The rapid spread of the virus in birds throughout Europe, the Middle East, Africa and Asia has been accompanied by fears it will mutate into a form easily transmissible between humans and cause a worldwide flu pandemic that could disrupt travel and commerce and kill large numbers of people.
"The presence of an H5N1 infection in a second mammalian species is not surprising," Till Backhaus, the regional minister for agriculture, said in a statement, adding martens and cats eat similar prey.
Cats are believed to have caught the virus by eating infected birds. Ulrich Arnold, a scientist at the University of Marburg's Institute for Medical Microbiology, said the discovery was "no new situation for Germany."
He pointed out that during the winter months hungry martens will eat carrion such as dead birds.
German officials have asked that cats be kept indoors and dogs on leashes in areas where bird flu has been found.
Dick Thompson, spokesman for the
World Health Organization, said it was too soon to say whether the stone marten infection poses a new threat to humans.
"Further investigation is needed to determine whether evidence of the infection in a new mammalian species has any significant risk for humans," Thompson told the AP.
Erwin Reisinger, the director of the Department of Tropical Medicine at the University of Rostock, said the marten case did not show the virus altering its means of transmission and did not therefore indicate increased risk for people.
But he said the case suggested that the disease could be expected to spread to still further species. He said it could be transmitted to rats, mice and swine, as shown by naturally occurring cases in Southeast Asia or in the laboratory.
According to the World Health Organization tigers and snow leopards in a zoo in Thailand died of H5N1 after being fed infected chicken carcasses in 2003 and 2004.
In addition to the large cats infected in Thailand, three house cats near Bangkok were infected with the virus in February 2004. Officials said one cat ate a dead chicken on a farm where there was a bird flu outbreak, and the virus apparently spread to the others.
WHO said tests on three civets that died in captivity last June in Vietnam also detected H5N1. The source of that infection was unknown.
The organization says that cat populations are not known to be reservoirs of the virus and that cat infections have so far all spread from birds.
With avian flu spreading, U.S. to expand its testing
http://www.usatoday.com/news/health/2006-03-07-bird-migration_x.htm
By Anita Manning, USA TODAY
The U.S. government, bracing for the possibility that migrating birds could carry a deadly strain of bird flu to North America, plans to test nearly eight times as many wild birds this year as have been tested in the past decade.
The U.S. Geological Survey is testing live migratory birds and those killed by hunters. The U.S. Geological Survey is testing live migratory birds and those killed by hunters.
By David Silverman, Getty Images
Starting in April, samples from 75,000 to 100,000 birds will be tested for the virus, mainly in Alaska, as part of a joint effort of the departments of Agriculture and Interior, along with state Fish & Wildlife agencies. That's a jump from the 12,000 birds tested since 1996, the USDA's Angela Harless says.
The expanded program, which will include birds in the Pacific islands and on the West Coast, reflects growing concern that the virus, highly pathogenic A (H5N1), which has spread across Asia and Europe, could arrive in North America as soon as this spring and be carried into the western continental USA by fall.
"I would expect" the virus to arrive in North America, USDA Secretary Mike Johanns says. It could enter in other ways, he says, including smuggling of infected pet birds or fighting cocks, but the chance that it could be carried in with the spring migration "is definitely a possibility."
A disease of birds, not humans
If tests find the virus in birds in North America, it would not signal the start of a human pandemic, because it still primarily is a disease of birds, he says. The virus was first found in birds in China in 1996. It moved into people for the first time in Hong Kong a year later and now has turned up in 39 countries.
Since December 2003, at least 175 people have been infected, and 95 have died, most of them after having close contact with infected chickens but not wild birds. Scientists say the virus hasn't developed the ability to spread easily from person to person. If that happens, it could start a pandemic.
Of four major bird migratory patterns, or flyways, in North America — the Pacific, Central, Mississippi and Atlantic — the Pacific flyway is of greatest interest now, says Frank Quimby of the U.S. Department of the Interior. "The Pacific flyway is the most likely route, because birds that winter in Asia migrate in spring to Alaska." Alaska, with its wetlands and coastal areas, is a kind of Grand Central Station for bird species.
"Alaska is the crossroad of bird migration pathways," says Rick Kearney, wildlife program coordinator for the U.S. Geological Survey. "With the coming of the spring migration season, we are increasing surveillance" in partnership with federal, state and local agencies. "We shall be collecting samples from live migratory birds and samples from hunters."
Birds on the Asian flyway could arrive in Alaska in April and May, says Nicholas Throckmorton of the U.S. Fish & Wildlife Service. "That could be the moment when wild birds bring Asian bird flu to Alaska. As those birds spend the summer breeding in Alaska, they could pass it to birds that migrate south in the fall," he says. He added that if the virus arrives in Alaska, the agency doesn't expect it to move south until sometime between August and November.
To test the birds, scientists capture them in nets, take swabs from the throat or cloaca (posterior opening) and send the samples to the U.S. Geological Survey's National Wildlife Center in Madison, Wis. If any test positive for H5N1, confirmatory testing will be done at the USDA's National Veterinary Services Laboratories in Ames, Iowa. USDA spokeswoman Angela Harless says as many as 18,000 samples a day can be tested. Tests also will be made on birds killed by hunters in Alaska this spring, and in Oregon, Washington and California during the fall, Throckmorton says.
To bird experts, avian flu is nothing new. There are at least 144 types of bird flu viruses, most of which don't kill the birds. Only two types, H7 and H5, have become highly pathogenic, killing three out of five chickens infected, Throckmorton says. In Asia, the H5N1 virus "went from wild birds to domestic poultry, evolved in poultry and reinfected wild birds," he says. Now more lethal than it was, it kills some wild birds, but not all. "It's proven wild birds can carry this virus and not have illness."
What if it is found in the USA?
If the virus is detected in wild birds in North America, there will be no massive killing of them to contain it, because experts, including those from the World Health Organization, the World Organisation for Animal Health and the USDA, agree that destroying birds is not an effective control method. What would happen, Kearney says, is health experts and people involved in agriculture would be put on alert and warned to make sure poultry are separated from wild birds.
Some scientists say the focus on wild birds is misplaced. "Migratory birds are probably the least likely way avian flu is going to enter the Western hemisphere," says Peter Marra, a bird ecologist at the Smithsonian Institution in Washington, D.C.
The more likely route into the USA, he says, is through the pet trade and the movement of poultry, legally or illegally. "Migratory birds are innocent bystanders," Marra says. "I don't doubt (they're) moving the virus. I just don't think they're the primary movers."
Poultry industry on guard
The USDA has banned importation of live birds or bird products from countries where the virus has spread. Birds that are legally brought into the country are tested for H5N1 and other bugs, and they're held in quarantine for 30 days. But experts warn that illegal trade in birds and the smuggling of wild birds or fighting cocks could provide an entry.
Richard Lobb of the National Chicken Council says poultry farmers have been warned that "if you have hired help, make sure they don't have fighting birds at home. That is the only way it would get into commercial poultry."
If it spread into domestic poultry, it could threaten the USA's $43-billion-a-year broiler industry, but Lobb says there are precautions in place, from routine testing of every flock to extensive farm bio-security measures. An outbreak on a farm would be quickly detected, contained and extinguished, he says.
"We're not complacent by any means," he says. "It is the No. 1 issue in the industry."
Bird Flu Could Appear in U.S. in Months
By LARA JAKES JORDAN, Associated Press Writer Thu Mar 9, 12:36 PM ET
WASHINGTON - A deadly strain of bird flu could appear in the United States in the next few months as wild birds migrate from infected nations,
Homeland Security Chertoff said "there will be a reasonable possibility of a domestic fowl outbreak" as migrating birds mix with ducks, chickens and other birds in the U.S. But he cautioned against panic, noting that the Agriculture Department has dealt with other strains of bird flu for years.
"If we get a wild bird or even a domestic chicken that gets infected with avian flu, we're going to be able to deal with it, because we've got a lot of experience with that," Chertoff said, speaking to newspaper editors and publishers.
"I can't predict, but I certainly have to say that we should be prepared for the possibility that at some point in the next few months, a wild fowl will come over the migratory pathway and will be infected with H5N1," he said.
The H5N1 strain has killed at least 95 people since 2003, mostly in Asia, according to the
World Health Organization, and has devastated poultry stocks. Scientists are concerned that the virus could mutate into a form easily spread among people, sparking a pandemic.
Hemophiliacs have traditionally been in the fast lane for blood borne diseases.
Let's hear it for biotech!
Zoos Make Plans To Detect Spread Of Bird Flu in U.S.
http://online.wsj.com/article/SB114187447776793387.html
>>
By STEVEN GRAY
March 9, 2006
Anticipating the eventual arrival of bird flu in the U.S., American zoos are racing to make contingency plans and to develop a national surveillance system for the protection of both their wildlife collections and their human customers.
The zoos' efforts could help U.S. officials detect the arrival and track the movement of the lethal virus, which recently has spread from Asia into Europe and the Mideast. Containment and protection efforts could result in quarantines of birds and other animals, and limit the viewing experiences of visitors, although mass zoo shutdowns don't seem likely at this point, zoo officials say.
Government officials have said the deadly H5N1 strain of avian-flu virus probably will show up in the U.S. sooner or later. The virus is likely to be carried by migratory birds, which frequently find sanctuary in open-air zoos and could infect other wildlife. Bird flu has killed at least 91 people in Asia and Turkey since 2003; most victims had close contact with sick birds. There is no evidence the disease can pass easily between humans, but experts fear the virus could mutate into a form that will.
If the virus is detected near a U.S. zoo, some zoos are expected to close walk-through aviaries to minimize contact between humans and birds. Indoor quarantines of susceptible animals such as birds, tigers and lions are possible, and visitors might not be able to view them as easily.
In the event of bird flu on U.S. shores, New York's Bronx Zoo is considering having visitors dip the bottoms of shoes in liquid disinfectant before entering the park, says John Calvelli, spokesman for the Wildlife Conservation Society, which manages the zoo. "This is a very exhaustive internal review right now, and our experts are grappling with issues because we want to make sure we make the right decisions."
"We are very worried about the health of our animals, and there's no reason to think they're not vulnerable," says Dominic Travis, an epidemiologist at Chicago's Lincoln Park Zoo. Mr. Travis is leading an effort among zoo officials, as well as federal, state and local authorities, to develop a surveillance system to detect a range of diseases, particularly H5N1.
The plan draws on zoos' experiences in dealing with the mosquito-borne West Nile virus in recent years. As envisioned, zoos would send blood and tissue samples of waterfowl, for instance, to regional labs such as one at the University of Minnesota. A screening that is positive for H5N1 or other serious diseases would be sent to a federal lab for confirmation.
Zoos are seeking up to $2 million in federal funding that would pay for a database and testing of blood and tissue samples, Mr. Travis says. The zoos are working with the Centers for Disease Control and Prevention, the U.S. Agriculture Department and the U.S. Fish and Wildlife Service.
Saint Louis Zoo officials say that if H5N1 is found nearby, they will consider vaccinating birds. Generally, though, zoos are wary of vaccinating wildlife because that makes it difficult to detect disease in animals infected before vaccination. Guidelines developed by the American Zoo and Aquarium Association, a trade group, urge zoos to consider vaccination only under "substantial threat" of an H5N1 outbreak in the zoo's region.
At the Zoological Society of San Diego, whose two parks, including the San Diego Zoo, boast one of the nation's largest wildlife collections, officials say that if the virus were detected nearby, they would drain ponds to discourage wild birds from lingering, move scores of animals indoors, and build additional indoor facilities. Some will present special challenges. Flamingos, for instance, are "not used to being confined, and they need to live in water," says Donald L. Janssen, the park's associate director for veterinarian services. They live outside, so the zoo would have to build or find indoor shelter, he says. Moving flamingos is risky because their legs and necks are delicate, officials say.
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Hospital Link Could Catch Outbreaks Early
http://online.wsj.com/article/SB114186869834793251.html
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By BETSY MCKAY
March 9, 2006
Epidemiologists in North Carolina spent two weeks in 2001 sifting by hand through more than 5,000 medical charts and 700 laboratory reports to rule out the possibility that Bob Stevens, the first person to die in the anthrax attacks that year, fell ill on a family visit to their state.
That search today probably would take minutes. Within a few weeks, 113 hospitals in North Carolina are expected to be linked to an electronic database that state officials scour at least twice a day for warning signs of infectious-disease outbreaks. The system, already up and running in 72 hospitals, recently helped health officials diagnose an illness at a college sorority as a food-borne infection rather than a stomach virus about 12 hours after the first students sought medical care.
Now, the Centers for Disease Control and Prevention is developing a similar -- but national -- electronic surveillance system called BioSense that is designed to help health officials spot an outbreak soon after infected people show up at emergency rooms. By the end of the year, BioSense is expected to link 250 hospitals in more than 30 cities to servers at the CDC's Atlanta headquarters. CDC officials will look at disease patterns in several major metropolitan areas at once. State and local health officials will be able to tap into the system to review data collected on symptoms and diagnoses of illnesses in their area.
At least 100 local or state disease-surveillance programs in the U.S. already crunch data daily on everything from school absenteeism to pharmacy sales of diarrhea medication to the incidence of flu and other common illnesses, according to the CDC. These programs are generally run by state and local health departments, and they won't be a part of BioSense.
With the growing pace at which avian flu is spreading globally, health officials are looking to make bigger strides in the rapid detection of infectious outbreaks. Since the beginning of February, the H5N1 avian flu virus has spread in animals to several more countries in Europe, the Middle East, and Africa, raising the specter of more human infections.
In the event of a bioterrorism attack, or if the bird flu breaks out in the U.S., "we would have broad, rich data that would show us how big it is, where it's spreading, how fast," says Blake Caldwell, a senior adviser to the CDC who is leading the development of BioSense. The system could also help evaluate whether the public-health response is working. The federal government spent $50 million in 2005 on BioSense, and the CDC says it expects to receive another $50 million this year.
But sifting through all the data that pour in from hospitals can be daunting, even electronically. And some electronic databases aren't connected to doctors' offices, often the first stop for patients, so those infected by diseases with the highest threat to overall public health still could slip through the safety net. Public-health officials also acknowledge that computers aren't necessarily going to outsmart doctors, since symptoms such as fever and cough could indicate a variety of problems ranging from a routine, 24-hour bug to avian flu.
Despite the limitations, real-time electronic monitoring of symptoms seen by emergency-room doctors is a huge leap forward. For decades, doctors mailed handwritten reports that were used by federal officials to track diseases. Paper surveillance systems were becoming inefficient, but the Sept. 11, 2001, terrorist attacks and rapid spread of bird flu and SARS, or severe acute respiratory syndrome, made them obsolete.
New York, which has one of the earliest electronic monitoring systems, hasn't limited itself to emergency room data. Collecting information from ambulance dispatches starting in 1998 gave New York City Department of Health and Mental Hygiene officials a "one- to two-week earlier indication of community-wide influenza than we could get from providers and labs," says Farzad Mostashari, an assistant commissioner who helped create the city's system. The program now collects data from 50 hospitals that account for 90% of emergency-room visits in New York City, he says.
Considered one of the most advanced disease-detection programs in the U.S., the North Carolina Hospital Emergency Surveillance System was started by state public-health officials and a trade group of North Carolina hospitals. A rudimentary version collected data from only six hospitals. But the anthrax attacks made health officials realize they needed a more sophisticated system.
Mr. Stevens had visited about eight counties in the state, and officials handchecked medical files to see if any people in the places he visited had reported symptoms of inhalation anthrax. "We were waking people up in the middle of the night," for information, says Leah Devlin, director of the North Carolina Department of Health and Human Services. (It turned out that the anthrax that killed him was mailed to the supermarket-tabloid office in Boca Raton, Fla., where Mr. Stevens worked.)
The North Carolina system secured $3.4 million in federal funding earmarked for bioterrorism defense after Sept. 11, to expand into a statewide, 24-hour public health radar-like system. The new system allowed them to monitor symptoms, and technology from a Durham, N.C., company, MercuryMD Inc., made it possible for them to pull up and review patient records if they needed more information.
Participating hospitals were given $5,000 each toward the personnel and technology costs of linking their computers and the state network. Meanwhile, public-health officials persuaded the North Carolina legislature to pass a law that took effect last year requiring hospitals that keep patient information in electronic form to report 22 "data elements" -- such as age, sex, body temperature and symptoms -- at least once every 24 hours -- to the state public-health department.
The electronic-surveillance systems have raised questions about potential intrusion on patient privacy, but some officials say existing public health laws already give them access to the same data in a public-health investigation. "We didn't have to expand our public-health authority," says Steve Cline, chief of epidemiology for North Carolina's division of public health.
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Israel sends bird flu aid to Nigeria
Nigerian government asks for aid following discovery of virus in country; Israeli Foreign Ministry responds
Roee Nahmias
Israel joins fight against bird flue: The Foreign Ministry sent medical equipment and protective, anti-contagion gear to Nigeria. The equipment arrived Tuesday at the capital Abuja to be distributed to other locations around the country.
Following the bird flu outbreak in Nigeria and fear of it spreading throughout the most populated country in Africa, the Nigerian government turned to the international community for aid.
Israeli Ambassador in Nigeria Noam Katz even received a personal request from senior Nigerian officials, and the Israeli Foreign Ministry decided to respond.
"Signs of the bird flu were discovered in several areas in Nigeria, especially in the capital Abuja, and the central and northern regions. For now, it hasn't been diagnosed in humans, but the fear it will be transmitted to humans is there", Amir Lati, head of the African department in the Foreign Ministry, explained to Ynet.
"The Nigerian government is afraid that the outbreak would reach other countries in Africa. Some neighboring countries have already prohibited importing poultry from Nigeria," he said.
'Nigeria personally asked for Israel's help'
"The first discovery of bird flu was in Niger, Nigeria's neighboring country in the north," he added.
Lati said that "the Nigerians distributed a list of the equipment they need and personally asked for aid from Israel."
"We got the request list 10 days ago, and with the help of the Foreign Ministry's international coordinator stationed in Nairobi, who happens to be a medical doctor, we managed to quickly put together all the equipment. It arrived at the capital Abuja on Tuesday. We also sent, among other things, safety goggles, safety suites, and overshoes," he added.
The Nigerian ministers of information and foreign affairs, as well as Nigeria's ambassador to Israel, thanked Israel for its readiness to help fight the outbreak.
"We have good relations", Lati explained. "We see it as a testimony to the close relations between the countries".
(03.07.06, 20:48)
http://www.ynetnews.com/articles/0,7340,L-3225083,00.html
Dubi
For hemophiliacs and others in need of
transfusions, one less thing to worry about…
http://yahoo.reuters.com/news/articlehybrid.aspx?type=comktNews&storyid=urn:newsml:reuters.com:2...
>>
Baxter said plasma treatment kills bird flu virus
LOS ANGELES, March 6 (Reuters) - Baxter Healthcare Corp. ( BAX ) said on Monday that a study has verified the successful inactivation of the bird flu virus during processes routinely used in the production of its plasma-derived therapeutics.
The study showed that the bird flu virus is inactivated through proven processes such as pasteurization, vapor heating, low pH and solvent detergent treatment methods.
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“It's easy to blame migrating birds,
because then no one is responsible…”
http://www.nytimes.com/2006/03/06/international/europe/06flu.html
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Recent Spread of Bird Flu Confounds Experts
March 6, 2006
By ELISABETH ROSENTHAL
OZZANO EMILIA, Italy — As new outbreaks of bird flu have peppered Europe and Africa in recent weeks, experts are realizing that they still have much to learn about how migrating birds spread the A(H5N1) virus, leaving the continents vulnerable to unexpected outbreaks.
After new scientific research published in February clarified the role of wild birds in spreading the disease from its original territory in southern China, the virus promptly moved into dozens of locations in Europe and Africa, following no apparent pattern and upsetting many scientific assumptions about the virus and its course around the world. In fact, knowledge of how the virus is spreading in Europe and Africa is so rudimentary that experts say there is no way of predicting where it will strike next, although they are now certain that it will, again and again.
"We know next to nothing about this virus; we have only anecdotal information about where it exists and what birds it infects," said Vittorio Guberti, head veterinarian at the Italian National Institute for Wildlife here in a rural corner of northeastern Italy. He has been studying influenza in wild birds for more than 10 years.
"We don't even know where to focus. We have to sit and wait for the big epidemic to occur, and in the meantime there will probably be small outbreaks all the time."
Scientists do not know, for example, which species are the major carriers of A(H5N1). While they suspect that there may be a few areas at the fringes of Europe that are perpetually infected with the virus, they are not sure exactly where. And while they are convinced that the virus can be carried on trucks, on soles of shoes and in fertilizer, they are not sure how significant those routes are.
"Think about this," Mr. Guberti said in his cluttered laboratory here. "Two million ducks from Nigeria, where there is a big problem, will arrive in Italy. And we don't know a thing about them."
Outbreaks in Nigeria have occurred in commercial poultry, but there is no information about whether the disease is in wild birds. Samples from African birds have been shipped to Italy for analysis, but the laboratory has been overwhelmed by samples from Europe, a United Nations official confirmed.
If they are infected, North American birds may be vulnerable, too, since some wading birds from Africa will fly as far north as Canada and the United States in the months to come, experts said.
While A(H5N1) does not now readily infect humans or spread from person to person, scientists are worried that it could acquire that ability, setting off a worldwide human pandemic. Until this year, Europe's small fraternity of wild bird researchers was severely underfinanced, its warnings about bird flu unheeded. Now the researchers are racing to fill gaps in knowledge and answer crucial questions.
In February, new research provided clues about how the A(H5N1) virus broke out of its original stalking grounds in Southeast Asia, moving to western China and on to the edges of Europe late last year.
Dr. Guan Yi and his colleagues at the University of Hong Kong reported in the Proceedings of the National Academy of Sciences that some birds infected with A(H5N1) could survive for a week, and so were capable of spreading the disease over vast areas — to China's remote west and to Mongolia, for example. Previously, scientists thought that infected birds would be too sick to cover such distances.
From there, A(H5N1) predictably moved on to Russia, Ukraine, Turkey, Romania and the Balkans. But the recent pattern of spread, into European and African nations, has been far more confusing.
"For a couple of weeks, it was raining dead swans all over Europe, which left everyone scratching their heads," said Jan Slingenberg, a senior veterinary official at the United Nations Food and Agriculture Organization in Rome.
Wetlands International, a Dutch nonprofit organization that has sent teams to several African nations to sample wild birds, has made a list of 17 species it believes are particularly likely to spread A(H5N1) in Europe. There is no list for Africa or Asia. Some species, like pigeons, which have provoked angst in European cities, are not particularly susceptible, so there is little point in directing vigilance there, officials said.
Mr. Guberti and others say they suspect that there are now permanent reservoirs of the disease on Europe's doorstep, so that birds like the mute swan may pick up the disease every time they enter the Continent. Suspects include the Black Sea and the lower Volga River, areas that have suffered previous outbreaks of A(H5N1), and where mute swans often winter.
Nations must identify such reservoirs, Mr. Guberti said, so that scientists can see which birds live there and where they migrate, creating a kind of early warning system.
The dead ducks that have been found in various corners of Europe, from Geneva to central Italy and the suburbs of Lyon, have proved even more disquieting to scientists.
"It's hard to explain," said Alex Kaat, spokesman for Wetlands International, noting that scientists have no idea whether the ducks got the virus from infected poultry nearby, from mute swans, from another species that is spreading the disease undetected in Europe — or if they are birds making an early migration from infected parts of Africa.
While ornithologists think that most of the cases in Europe are tied to migration, they are also quick to note that wild birds are sometimes unfairly blamed, as in Turkey and Nigeria. "It's easy to blame migrating birds, because then no one is responsible," said Juan Lubroth, a senior veterinary health officer at the Food and Agriculture Organization.
In Croatia, for example, Mr. Kaat said, fertilizer made of manure from infected poultry probably spread A(H5N1). The manure is commonly used to fertilize fish ponds, which are frequent stopover points for migrating birds that probably contracted the virus there, he said. The virus persists in water for weeks.
In Nigeria, the first huge outbreak occurred in January in hens in the north, a dry area far from the wetlands that are home to the country's migratory birds.
"The outbreaks were in the wrong place and at the wrong time of year," Mr. Kaat said.
Instead, he and others believe, Nigeria's problem was probably caused by the transport of sick birds or bird products infected with A(H5N1) from another country in Africa or even Asia.
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Avian Influenza
In Europe, birds and a cat have died from avian flu; governments are responding
Patricia Short
Governments in Europe are building stockpiles of vaccine to protect people from the avian influenza virus, known as H5N1, following its spread into Europe and Africa from Asia.
The virus has been identified in scores of dead wild birds, particularly swans and ducks, across Europe; in domesticated turkeys in France; and in a dead cat thought to have eaten infected wild birds on the Baltic Coast of Germany. To date, no occurrence of bird flu in humans in the region has been reported. But public health officials are taking no chances.
The U.K. government recently said it will spend a total of nearly $60 million on 3.5 million doses of the vaccine from Chiron and 2 million doses of the vaccine from Baxter International for stockpiles. Chiron has already netted a contract to build a stockpile of bulk H5N1 vaccine for the U.S. Department of Health & Human Services.
Sanofi Pasteur said it had supplied the Italian government with a stock of bulk H5N1 vaccine that could be formulated into 185,000 doses. Sanofi notes that it earlier reached supply agreements with the U.S., Australian, and French governments.
Meanwhile, vaccination of domestic poultry has begun in France. Akzo Nobel subsidiary Intervet is supplying the French Ministry of Agriculture with vaccine for domestic poultry in regions at risk from migrating birds. Additionally, Intervet will supply at least 30 million doses of vaccine against the virus strain known as H5N2, which the company says is closely enough related to the avian flu virus to induce protection in vaccinated poultry.
Chemical & Engineering News
ISSN 0009-2347
Copyright © 2006 American Chemical Society
http://pubs.acs.org/cen/news/84/i10/8410notw5.html
The FDA published new guidelines today for accelerated approval for pandemic flu.
http://www.fda.gov/bbs/topics/NEWS/2006/NEW01330.html
FDA Initiative Helps Expedite Development of Seasonal and Pandemic Flu Vaccines
The Food and Drug Administration (FDA) today issued recommendations to aid manufacturers in developing seasonal and pandemic influenza vaccines. FDA's goal is to expedite the development and availability of safe and effective vaccines needed to protect against influenza.
"This action illustrates FDA's high level of commitment and key role in preparing for influenza pandemic, which is a top priority for our nation" said Acting FDA Commissioner Dr. Andrew von Eschenbach.
In two guidance documents released today, one for seasonal, and the other for pandemic influenza vaccines, the FDA provides manufacturers with clear guidance on developing and submitting clinical data to show safety and effectiveness for new vaccines. Consistent with the aims of FDA's Critical Path Initiative to get products to market more quickly and to advance the development and use of new technologies, these documents outline specific approaches that vaccine developers may follow.
For licensed vaccines, they describe the process for changing rapidly from the currently-licensed seasonal vaccine to a new pandemic vaccine by supplementing the existing license. For new vaccines, they describe defined pathways for both traditional and accelerated approval approaches. Accelerated approval allows for evaluation based on biological indicators (e.g., the immune response to the vaccine) likely to demonstrate effectiveness.
Because these guidances will assist manufacturers in the development and evaluation of seasonal and pandemic influenza, the direction that they provide to new manufacturers, in turn, helps address the increased demand for influenza vaccine. The guidance also helps support and defines steps needed for development and evaluation of vaccines using new technologies (such as cell culture and recombinant manufacturing) and potential approaches to stretching limited pandemic vaccine supplies (such as with the use of ingredients added to a vaccine to improve the immune response it produces, known as adjuvants and different vaccine delivery methods).
The accelerated approval pathway was critical in allowing last year's rapid approval of a new influenza vaccine, Fluarix, and broke new ground in that it was the first vaccine approved using that approval process.
In issuing this advice, FDA aims to facilitate manufacturers in increasing the number of doses to ensure that enough influenza vaccine is available to vaccinate each person in the at-risk population. Having additional diversity in our vaccine supply helps enhance the capacity to produce more doses of influenza vaccine and contributes to the nation's pandemic preparedness.
"These guidance documents provide important advice for manufacturers on how to develop needed vaccines more quickly," said Dr. Jesse Goodman, Director of the Center for Biologics Evaluation and Research, FDA. "FDA is committed to helping companies develop safe and effective vaccines to prevent influenza, including pandemic influenza, and is very engaged with product developers."
The release of these guidances is part of the comprehensive effort that FDA is undertaking to work with manufacturers to facilitate the development of vaccines. Other examples include a recent CBER advisory committee meeting to discuss novel approaches to develop influenza vaccine such as using cell technology rather than eggs, frequent interactions with vaccine manufacturers to provide both scientific and regulatory guidance, as well as CBER's preparation of material for testing the potency of new vaccines, which are made available to manufacturers.
A copy of the guidance, "Draft Guidance for Industry, Clinical Data Needed to Support the Licensure of Trivalent Inactivated Influenza Vaccines," is available at: http://www.fda.gov/cber/gdlns/trifluvac.pdf.
A copy of the guidance, "Draft Guidance for Industry, Clinical Data Needed to Support the Licensure of Pandemic Influenza Vaccines," is available at: http://www.fda.gov/cber/gdlns/panfluvac.pdf.
The public has 90 days to comment on the drafts. When finalized, the guidances will represent the FDA's current thinking on these topics.
katie....
>>“The only economic question we’ve been asked until now was, ‘If bird flu comes to Israel, and there’s not enough medicine for everyone, who should get priority in treatment?’ We replied, ‘Every effort must be made to ensure enough medicine for everyone. If we reach a situation in which we have to use triage, that would be an ethical disaster.’ In any case, we said patients and the most vulnerable should be treated first. It turns out that this isn’t a trivial matter. In the UK, it was said that caretakers should have priority, and in the US, it was said priority should be given to those producing the treatment.” >>
(#msg-9944763)
Dubi
France Fights Panic From Bird Flu Outbreak
Another large outbreak in France now, just reiterates how infectious this virus has become....I got a chuckle out of Chirac's comment eating succulent chicken....only the French!
By ELAINE GANLEY, Associated Press Writer Sun Feb 26, 12:45 AM ET
PARIS - French
President Jacques Chirac urged consumers not to panic Saturday, hours after the government announced the
European Union's first outbreak of deadly bird flu in commercial poultry.
Chirac said chickens and eggs remained safe to eat as he munched a piece of the famously succulent chicken from the Ain region, where the lethal virus was confirmed in turkeys.
Panic among consumers is "totally unjustified," Chirac said during a visit to open the annual Paris Agriculture Fair. "The virus in question ... is automatically destroyed by cooking. So there is absolutely no danger."
Yet fear already was setting in, raising worries for a multibillion-dollar industry that makes France the premier poultry producer among the EU's 25 nations.
Japan's decision Friday to suspend imports of French poultry and poultry products, including foie gras, signaled the potential impact even before the confirmation that the deadly H5N1 virus had decimated a farm of more than 11,000 turkeys at Versailleux in southeastern France.
Hong Kong also has temporarily suspended imports of French poultry, Brenda Chan, a spokeswoman of Hong Kong's Food and Environmental Hygiene Department, said Sunday.
In France itself, there has been a drop of up to 30 percent in poultry purchases in recent weeks. Chirac noted the "economic and social consequences" of panic and said the French must not fall into such a trap.
The lethal strain has spread from Asia to at least 10 European countries and Africa, and scientists fear it could mutate into a form that is easily transmitted between humans, sparking a pandemic. The disease has killed at least 92 people, mostly in Southeast Asia, according to the
World Health Organization.
China on Sunday warned the public of a possible "massive" bird flu, and said two more people had contracted H5N1. The official Xinhua News Agency also quoted Agriculture Minister Du Qinglin as saying there was another new bird flu outbreak in eastern China.
Indonesia recorded its 20th human death from bird flu Saturday and India said two poultry farms in western Gujarat state had been contaminated by the virus in that nation's second known outbreak.
No human cases of bird flu have been reported in the EU.
French authorities sealed off the infected turkey farm Thursday. The farm's veterinarian said nearly all the 11,000 birds there were sick and hundreds had died. Surviving birds were slaughtered.
The farmer's family was quarantined and vehicles passing through a protection zone around the farm were required to ride through a 100-foot-long trough of disinfectant.
News that bird flu had spread to farm stocks was particularly bitter for France, which has been working for months to prevent and prepare for an outbreak.
France has some 200,000 farms that raise 900 million birds each year. In 2004, the latest year for which figures are available, the French poultry sector generated more than $3.6 billion in revenues — more than 20 percent of the EU's total poultry production.
The head of France's powerful farm union, Jean-Michel Lemetayer, asked Chirac to demand financial aid from the EU.
Agriculture Minister Dominique Bussereau said Friday that authorities were perplexed about how the virus appeared in commercial poultry despite precautionary measures.
The farm is located in a protection zone set up after two wild ducks died and were confirmed infected with H5N1. There was speculation the outbreak may have been caused by duck droppings on straw placed in the turkey pens, France's Poultry Industry Association said.
Claude Lassus, the veterinarian for the Versailleux farm, told France-Info radio Friday that he believed the straw theory was the only explanation for the infection.
Authorities in the eastern German state of Brandenburg said Saturday that two wild birds had tested positive for the H5N1 strain of bird flu, the first cases in that part of Germany.
The state's Agriculture Ministry said the two dead birds — a swan and a duck — were found around the town of Schwedt, northeast of Berlin and close to the border with Poland.
How Academic Flap Hurt World
Effort On Chinese Bird Flu
http://online.wsj.com/article/SB114072620677781658.html
>>
Country's Scientists Demand
Bigger Role in Research;
A Setback for Vaccine?
Dead Geese at a Remote Lake
By NICHOLAS ZAMISKA
February 24, 2006
BEIJING -- China's efforts to maintain control over samples of avian flu taken on its soil, as well as the research done on them, have put it at odds with international health officials trying to defeat the disease.
The standoff pits a high-ranking veterinarian in China's Ministry of Agriculture named Jia Youling against international health authorities leading the fight against bird flu. Their conflict surfaced after wild birds began dying by the thousands last spring in a remote region of western China. At the ministry's headquarters in Beijing, officials from the World Health Organization and the United Nations' Food and Agriculture Organization asked Dr. Jia to share with them the samples of bird flu that scientists under his ministry had collected from the birds.
He didn't provide them. Instead, Dr. Jia -- a professorial-looking 58-year-old who had risen steadily through the ministry's ranks since he joined it in 1979 -- began to talk about a recent research paper he had noticed on avian flu. According to Julie Hall, the WHO's top communicable-disease expert in Beijing and a participant at the meeting, he had a complaint: Months earlier, a team led by American scientists published a paper in an academic journal using China's samples, but without crediting or consulting their Chinese counterparts. The occasion, Dr. Hall says, "was used to express their deeper concern about ensuring that Chinese scientists were duly recognized." Dr. Jia declined to comment, saying, "I don't want to mention those things because they are all in the past."
Since that meeting, China hasn't provided a single sample from its infected flocks, despite repeated requests by WHO amid the roughly 30 outbreaks the country has reported in the past 12 months.
In another field, a dispute like this might seem like typical academic back-biting. But as the lethal form of bird flu known as H5N1 spreads beyond Asia into Africa and Europe, the stakes are rising fast. Since late 2003, at least 92 people in five Asian countries, as well as Turkey and Iraq, have died from avian flu, which has devastated flocks of birds across Asia. Disease experts fear human casualties could soar into the millions if the virus mutates to allow rapid transmission between people.
The genetic information contained in China's samples could help develop a more effective vaccine that could save countless lives. Currently, a human bird-flu vaccine produced by a unit of Sanofi-Aventis SA, Paris, is finishing clinical trials. Like many rival vaccines, it is based on an older strain of H5N1 taken from Vietnamese samples in 2004 and is endorsed by WHO. The Bush administration last fall asked Congress to spend $162.5 million on bird-flu vaccines, $100 million of which will be spent on Sanofi's vaccine.
But if the virus from China has changed significantly since then, scientists making the vaccine might never know, and Americans could be spending millions of dollars buying an antidote that is a year or more out of date.
"We think it's very important that [China] share viruses with the WHO as soon as they can, so we can test the vaccine efficacy," says Michael L. Perdue, an avian-flu expert with WHO at its headquarters in Geneva. "When people start hoarding" samples of bird flu, he says, "it limits our capability to develop the optimal vaccine."
Chinese officials have told WHO and FAO officials that they will begin sharing their samples again soon. A person familiar with China's position says it has taken time to negotiate a new agreement to ensure that Chinese researchers are involved in, and properly credited for, research on Chinese viruses. This person noted that other countries don't share their viruses with China.
"All the scientists should collaborate, but there's still a lot of competition," adds Shu Yuelong, the director of China's national influenza laboratory in Beijing. "Scientists are human."
Other countries from Indonesia to Turkey and Nigeria have provided international health authorities with samples of the virus from stricken birds.
China is widely considered to be a key laboratory for research. Scientists say the close proximity of poultry, people and pigs in southern China has spawned past influenza pandemics, including the Asian flu of 1957 and the Hong Kong flu of 1968.
For now, the more than 100 virus isolates Chinese veterinarians have collected from bird-flu outbreaks across China sit in refrigerators at China's National Influenza Research Center in Harbin, a city best known for its winter ice-carving festivals. The center employs around 500 scientists, at least 50 of whom are working on avian influenza and report to Dr. Jia's ministry.
One researcher worried that the Chinese lab would lose its competitive edge and would have less work to do if it was too generous in sharing their viruses.
"If we get the virus, and we send it out right away," a Chinese scientist says, we "don't need those people."
The Harbin scientists are proceeding with their own research. They have tested H5N1's virulence in mice, chickens, ducks and geese. The lab published six papers last year and three have been accepted this year, according to one scientist. The scientific journal Virology published a paper, written by a group of 10 researchers from China, in October. The paper used samples collected from China's outbreaks in 2004 to test an avian-flu vaccine made in China for use with birds.
When it comes to not sharing, China isn't alone. All over the world, competitive pressures can drive scientists to hoard data that might lead to ground-breaking research.
U.S. researchers have drawn flak. This past September, complaints over the failure of the Centers for Disease Control and Prevention in Atlanta to share the genetic sequences of flu viruses with outside researchers prompted the prominent scientific journal Nature to print an article titled, "Flu researchers slam US agency for hoarding data." In the article, a CDC official said the need for openness "must be balanced against the needs for maintaining high standards for data quality and for protecting sensitive information when the situation warrants."
"There is a world-wide tendency to bash China for everything it does," says Juan Lubroth, a senior officer of the animal-health service for the FAO. "I think it's important that countries hold a mirror up to themselves."
China's handling of disease outbreaks has come under intense scrutiny from the international community before. In early 2003, Chinese government officials defied efforts by world health officials to investigate outbreaks of severe acute respiratory disease. SARS eventually killed at least 349 people in mainland China, more than in any other country.
By the next year, official attitudes in Beijing appeared to have changed somewhat. Bird flu began breaking out across the country early that year, killing flocks of chickens, ducks, geese and doves. Local officials shipped some of the dead birds to researchers in Harbin.
WHO officials asked China's Ministry of Agriculture if they could obtain specimens to share abroad. After months of talks over issues such as how to transport the samples, the ministry agreed to hand over around half a dozen isolates.
In other areas as well, international health officials say, China has been helpful and cooperative. The country's Ministry of Health recently shared two of the seven virus samples it has collected from its human cases, according to Dr. Hall. The Ministry of Agriculture also has shared genetic sequences of viruses it has collected.
By last summer, things had changed. On the shores of China's largest saltwater lake, in a remote corner of the Tibetan plateau, at least 5,000 geese, gulls and other wild birds had died from avian flu. It was the first report of the disease attacking birds other than domestic poultry in such large numbers. Chinese researchers traveled to obtain samples of the virus from the dead birds. At their meeting with the agriculture ministry in Beijing, officials from WHO and FAO asked for the samples.
Instead, Mr. Jia told them about the paper that appeared several months earlier in the Journal of Virology. His point: China's permission to use its samples was never sought, his scientists were excluded from the research and their names were noticeably missing from the list of 14 scientists who contributed to the study.
"That's when it surfaced in all of its entirety," says WHO's Dr. Hall.
The paper, whose lead author was Elena A. Govorkova, a Russian researcher at St. Jude Children's Research Hospital in Memphis, Tenn., seemed innocuous enough. The study concluded that some of the latest strains of the H5N1 virus killing birds in Asia were lethal to ferrets as well and still posed a serious threat to humans. It used two samples from China and 11 others from elsewhere in Asia.
Dr. Govorkova's use of the Chinese samples, however, was news to Chen Hualan, the director of the Harbin research center who isolated them.
Nobody had asked Dr. Chen's permission before using her samples, a violation of WHO guidelines. Dr. Chen, 36 years old, the daughter of rice farmers and a rising star in China's scientific ranks, first heard about the study when she received a call early last year from a young official with the Chinese Ministry of Agriculture, according to a person familiar with the situation. The official had been scanning the latest research articles on bird flu and came across Dr. Govorkova's study. He noticed the paper from Memphis seemed to reference samples that could have come only from Dr. Chen's lab. "I've been burned," Dr. Chen told an international health official who spoke with her after she heard about the Memphis paper.
The Chinese researcher tried to clarify what happened with Dr. Govorkova's supervisor at St. Jude, an influenza specialist named Robert Webster. Dr. Webster quickly replied with an apology for what he described as a mix-up.
Dr. Govorkova also sent Dr. Chen a note, apologizing for the oversight. "I feel that this was an honest mistake," Dr. Govorkova says. "We apologized almost immediately." For her part, Dr. Chen says: "I really don't want to talk about that. It's something that happened a long time ago. Dr. Webster already apologized." She added that her laboratory will share the samples soon.
Both Drs. Webster and Govorkova say they believe China's Ministry of Agriculture is less concerned about this particular incident than in ensuring Chinese researchers have exclusive access to the country's viral samples.
"This has been used by the authorities as a crutch," Dr. Webster says. "They want all the credit themselves, which is reasonable," he adds. "They will eventually release them once they have a major publication." He points out that he has collaborated with Chinese scientists, including Dr. Chen, since the incident. Dr. Webster also points out that such oversights aren't unknown when so many researchers are involved, as is often the case, and at least one other similar incident happened in which the Chinese weren't properly credited for their work last year.
Dr. Govorkova says authorities "are making an excuse" and notes that even before the incident over her paper, "it was very difficult to obtain samples" from the Chinese. She says she has received an email from the Journal of Virology inquiring about the crediting of Dr. Chen's work and has replied suggesting a correction.
At another meeting in Beijing this fall, several WHO officials met with the Ministry of Agriculture again to try and coax China into sharing its samples. Dr. Jia again brought up the issue of the paper, according to two people who were in the room.
While the Ministry of Agriculture still hasn't shared any samples, it and WHO have been hammering out a new agreement for months that has been referred to as the "Seven Steps" plan, according to a person familiar with the talks. It is aimed at ensuring Chinese scientists are credited and involved in the work that comes from strains collected on Chinese soil.
"It's like a marriage," Dr. Hall says. "You have to keep working at it."
<<
In Pile of Waste, Md. Scientists Dig Up a Response to Bird Flu
Making Compost of Infected Flocks May Curb Spread
By William Wan
Washington Post Staff Writer
Monday, February 20, 2006; B01
The problem is one local farmers hope to avoid. The solution is a simple, if gruesome, one. When avian flu is detected in a single chicken on a farm, the entire flock -- often tens of thousands of chickens -- must be killed. So, what to do with all those dead birds?
Enter the humble compost heap.
The brown pile of recyclable waste is one of the latest tactics in the global effort against avian flu. A deadly strain in Asia and Turkey has killed millions of chickens and dozens of people, sparking fears of a worldwide pandemic.
Federal officials have held emergency drills in the District. Health agencies have created stockpiles of antiviral drugs. And through it all, two Eastern Shore scientists have been traveling the country on a mission of their own: to show farmers what to do if they wind up with thousands of chicken carcasses.
After trying to burn the bodies (too expensive), burying them (an environmental hazard) and trucking them to rendering plants (risking further spread of the disease), poultry experts believe that the safest means of disposal might be to roll the dead birds into a small hill and let the blistering heat of decomposition burn away the disease inside.
"It's as much of an art as science," said Nathaniel Tablante, associate professor of poultry health at the University of Maryland.
Tablante has spent the past three years studying the possibilities of recycling chickens. His office in College Park is overflowing with chicken paraphernalia: clocks, paintings, cartoons, even a little chicken statue made by his daughter after she learned about his job. But Tablante said he has no sentimental feelings for chickens. After all, he explained, he mostly deals with dead ones.
The idea of composting flu-contaminated chickens came to him and his colleagues while they were tracking a 2002 outbreak of avian flu in Virginia. The virus, a less-deadly strain than the one in Asia, cost Virginia's poultry industry an estimated $130 million and caused the deaths of 4.7 million birds -- a logistical nightmare.
On the first farms infected, poultry experts buried the chickens on-site, prompting a flood of complaints from residents worried about water contamination and property values. The state quickly stopped issuing burial permits. So scientists tried burning the bodies instead, but they couldn't keep up with the rising cost of fuel. Ultimately, most of the birds were taken to landfills, but in the two weeks it took to negotiate with landfill companies, the virus had spread to 35 more flocks.
Watching it all with equal measures of fascination and dread, Tablante and others started to wonder: What would they do if the virus reached the chicken houses of Maryland and Delaware?
At least one infected flock in Virginia was composted, officials said, but the option was largely ignored. Although the idea of poultry composting had been around since the mid-1980s, applying it to such large-scale mortalities was still experimental.
And so, a year after the Virginia outbreak, University of Maryland researchers -- along with Bud Malone, a University of Delaware poultry expert -- began their experiment, funded by a $36,000 industry grant.
They called it "in-house composting" and believed that if they could kill and dispose of the birds where they lived, they could stop the virus from spreading. After their first year of research at a vacant poultry house in Laurel, the team was forced to test its efficiency in a real-life situation: In 2004, avian flu was detected on three farms on the Eastern Shore.
First, the scientists had to kill all the birds, or "depopulate," as it is called in the poultry industry. Wary of animal rights groups, the researchers are reluctant to discuss details, but the process involves plastic sheets, large tanks of carbon dioxide and the transformation of live birds into dead ones.
"I'm going to get letters from PETA about this, but, yes, essentially we create a gas chamber," Tablante said.
Afterward, emergency workers used a bulldozer-like machine to scoop up the dead chickens and the chicken litter beneath them. Mixing both, they formed a long, narrow heap along the middle of each chicken house and capped it with a layer of litter and sawdust.
The litter provides carbon and microbes. The carcass contains moisture and serves as "food." And the ensuing microbial action can produce temperatures as high as 145 degrees, hot enough to kill avian flu. The end result, vast hills of organically rich dirt, can safely be used to fertilize farm fields.
The outbreak on the Eastern Shore was contained to the three farms and resulted in the destruction of about 525,000 birds -- a fraction of the mortalities in other areas.
"It did the job," said Malone, who has since begun a second experiment involving the use of firefighting foam to kill the birds faster and more humanely, with the added benefit of moisturizing the compost heap.
Since their work on the Eastern Shore outbreak, Malone and Tablante have been traveling across the country on a federal grant, spreading the gospel of composting after large-scale bird deaths. Lately, requests for talks have increased as the more deadly strain continues to spread abroad.
Locally, the two experts have visited composting classes that the Maryland Cooperative Extension uses to teach farmers how to recycle carcasses from routine chicken deaths.
For their most recent class in Princess Anne, Md., the room was packed. Farmers had come from as far as Pennsylvania for the day-long seminar, which included composting recipes, diagrams, lunch (deli sandwiches, no chicken) and some helpful, albeit gruesome, pictures.
Most of the farmers, however, seemed unfazed by the gore, even when instructor Gary Felton stuck a pitchfork into a compost heap and pulled out a half-decomposed bird.
"I've smelled worse," said Joseph Paul, 63, a third-generation farmer from Reliance, Md. "I can be picking up a dead chicken one minute and eat breakfast the next. It don't bother me."
For most farmers, Paul said, the truly frightening part was Tablante and Malone's slideshow of avian flu-infected farms, swarming with scientists in white suits.
Just the idea of killing millions of dollars' worth of poultry and throwing it into a compost heap made him cringe, he said. "That's what I consider a real nightmare."
http://www.washingtonpost.com/wp-dyn/content/article/2006/02/19/AR2006021901145.html
Avian Influenza: Significance of Mutations in the H5N1 Virus
http://biz.yahoo.com/prnews/060221/cntu001.html?.v=3
>>
Source: World Health Organization
GENEVA, Feb. 21 /Xinhua-PRNewswire/ -- Several recent media reports have included speculations about the significance of mutations in H5N1 avian influenza viruses. Some reports have suggested that the likelihood of another pandemic may have increased as a result of changes in the virus.
Since 1997, when the first human infections with the H5N1 avian influenza virus were documented, the virus has undergone a number of changes.
These changes have affected patterns of virus transmission and spread among domestic and wild birds. They have not, however, had any discernible impact on the disease in humans, including its modes of transmission. Human infections remain a rare event. The virus does not spread easily from birds to humans or readily from person to person.
Influenza viruses are inherently unstable. As these viruses lack a genetic proof-reading mechanism, small errors that occur when the virus copies itself go undetected and uncorrected. Specific mutations and evolution in influenza viruses cannot be predicted, making it difficult if not impossible to know if or when a virus such as H5N1 might acquire the properties needed to spread easily and sustainably among humans. This difficulty is increased by the present lack of understanding concerning which specific mutations would lead to increased transmissibility of the virus among humans.
Animal viruses
Virtually all the known subtypes of influenza A viruses circulate in some wild birds, most notably wild waterfowl. In these birds, different viruses constantly mingle with each other and frequently exchange genetic material, resulting in a huge pool of constantly changing viruses. Mutations and reassortment events are commonly observed in the affected bird populations.
In animals, some recent evolutionary changes in the H5N1 virus appear to have made control efforts more difficult and further international spread of the virus in birds more likely. Such changes are fully understandable, particularly in view of the exceptionally large number of birds that have been infected with the H5N1 virus and the frequent interactions between infected free-ranging poultry and wild waterfowl.
Studies have shown that H5N1 viruses from the current outbreaks, when compared with viruses from 1997 and 2003, have become progressively more lethal in experimentally infected chickens and mice, and are also hardier, surviving several days longer in the environment. Other studies have shown that the virus is not yet fully adapted to poultry and is continuing to evolve.
Domestic ducks have acquired an ability to resist the disease caused by some strains, and are now capable of excreting large quantities of highly pathogenic virus without showing the warning signs of illness. In endemic countries, this altered role of domestic ducks is now thought to contribute to perpetuation of the transmission cycle. Research conducted in South-east Asia has recently shown that multiple distinct lineages of H5N1 virus have become established in poultry in different geographical regions, indicating the long- term endemicity of the virus in parts of Asia. That research also detected highly pathogenic H5N1 virus in apparently healthy migratory birds.
In birds, one important recent finding has been the remarkable similarity of viruses from recent outbreaks to those isolated from migratory birds that began dying at the Qinghai Lake nature reserve in central China in late April 2005. Evidence is mounting that this event, which resulted in the deaths of more than 6,000 wild birds, signalled an important change in the way the virus interacts with its natural reservoir host.
Unlike the case with mutations of human viruses (some of which have been transient), it appears that some changes have become fixed in viruses circulating in at least some species of wild birds.
Prior to the Qinghai Lake event, the highly pathogenic H5N1 virus was known to cause occasional sporadic deaths in migratory waterfowl, but not to kill them in large numbers or be carried by them over long distances.
Viruses from Qinghai Lake showed a distinctive mutation at one site experimentally associated with greater lethality in birds and mice. Viruses from the most recent outbreaks, in Nigeria, Iraq, and Turkey, as well as from earlier outbreaks in Russia, Kazakhstan, and Mongolia, are virtually identical to Qinghai Lake viruses.
It is considered unusual for an avian influenza virus causing outbreaks in birds to remain this genetically stable over so many months. This finding raises the possibility that the virus -- in its highly pathogenic form -- has now adapted to at least some species of migratory waterfowl and is co-existing with these birds in evolutionary equilibrium, causing no apparent harm, and travelling with these birds along their migratory routes.
If further research verifies this hypothesis, re-introduction of the virus or spread to new geographical areas can be anticipated when migratory birds begin returning to their breeding areas.
The recent appearance of the virus in birds in a rapidly growing number of countries is of public health concern, as it expands opportunities for human exposures and infections to occur. These opportunities increase when the virus spreads from wild to domestic birds, especially when these birds are kept as backyard flocks in close proximity to humans.
To date, no human cases have been linked to exposure to wild birds. Close contact with infected poultry and other domestic birds remains the most important source of human infections.
Human viruses
Some mutations have been detected in human viruses isolated in 2005 and, most recently, in one virus isolated from a fatal case in the January 2006 outbreak in Turkey. Although these mutations were found at the receptor- binding site and involved the substitution of more mammalian-like amino acids, the effect of these changes on transmissibility of the virus, either from birds to humans or from one person to another, is not fully understood. Moreover, recent studies show that these mutations were transient and did not become fixed in the circulating viruses.
Scientists do not presently know which specific mutations are needed to make the H5N1 virus easily and sustainably transmissible among humans. For example, it is not known whether the absence of a specific receptor in humans for this purely avian virus is responsible for the present lack of efficient human-to-human transmission. For this reason, virological evidence of mutational changes must be assessed together with epidemiological information about transmission patterns actually occurring in human populations. This necessity further underscores the importance of close surveillance and thorough investigation during every outbreak involving human cases.
Assessments of the outbreak in Turkey, conducted by WHO investigative teams, have produced no convincing evidence that mutations have altered the epidemiology of the disease in humans, which was similar to the pattern consistently seen in affected parts of Asia. There is no evidence, at present, from any outbreak site that the virus has increased its ability to spread easily from one person to another.
http://www.who.int/csr/2006_02_20/en/print.html
Cumulative Number of Confirmed Human Cases of Avian
Influenza A/(H5N1) Reported to WHO
20 February 2006
Country 2003 2004 2005 2006 Total
cases deaths cases deaths cases deaths cases deaths cases deaths
Cambodia 0 0 0 0 4 4 0 0 4 4
China 0 0 0 0 8 5 4 3 12 8
Indonesia 0 0 0 0 17 11 9 8 26 19
Iraq 0 0 0 0 0 0 1 1 1 1
Thailand 0 0 17 12 5 2 0 0 22 14
Turkey 0 0 0 0 0 0 12 4 12 4
Viet Nam 3 3 29 20 61 19 0 0 93 42
Total 3 3 46 32 95 41 26 16 170 92
Total number of cases includes number of deaths.
WHO reports only laboratory-confirmed cases. http://www.who.int/csr/disease/avian_influenza/country/cases_table_2006_02_20/ en/print.html
<<
Health Experts Surprised at Rapid Spread of Bird Flu
http://www.nytimes.com/2006/02/20/health/20flu.html
>>
February 20, 2006
By HARI KUMAR and ELISABETH ROSENTHAL
NEW DELHI, Feb. 19 — The first reports of bird flu that cropped up in recent days in widely separated countries — India, Egypt and France — highlighted the disease's accelerating spread to new territories.
International health experts have been predicting widespread dissemination of the disease for about half a year, since they concluded that it could be spread by migrating birds. But the recent acceleration has perplexed many experts, who had watched the A(H5N1) virus stick to its native ground in Asia for nearly five years.
The most alarming of the current outbreaks, if only for sheer size, were the two widely separated episodes of avian flu in India, one of which has killed 50,000 birds in poultry flocks in the last few days. The Indian government, which has long been on alert for the virus because that country is on many migration paths in Asia, began killing half a million birds in the hopes of quashing the outbreaks, officials announced Sunday.
But the most perplexing report involved the single case in France — a wild duck found dead in the suburbs of Lyon — because migratory birds from Asia that carry the virus do not normally travel there at this time of year.
"After several years in one place, why is it now moving so rapidly?" asked Dr. Samuel Jutzi, director of the Animal Production and Health Division at the United Nations Food and Agriculture Organization in Rome. "There is a lot about this that we just don't know."
The dead duck in France, he said, was "very odd, very difficult to explain." But he added, "What is known is that the width of flyways are very broad, and there may have been a swarm that went farther westward than normal."
In Western Europe, the disease has been confined to wild migratory birds, and authorities across the Continent were taking severe measures to protect domestic poultry. Many countries are now requiring that all poultry be kept indoors to prevent mixing with potentially infected wild birds.
In recent days, a wild duck in central Italy was also found dead from the virus, the first time it had been found so far north in that country.
On the German island of Rügen in the Baltic Sea, 18 wild birds were confirmed to have the disease, bringing the total of infected birds there to 59 in the past week, mostly swans and hawks. The German chancellor, Angela Merkel, visited the island on Sunday, a sign of how seriously European governments are taking the disease.
Germany is preparing to kill at least some of the 400,000 domestic birds on the island to make sure the virus does not spread into poultry flocks, local authorities said. When bird flu is detected in an area, the most effective way to control an outbreak is to kill all the birds in a surrounding area to isolate the highly infectious virus, and to ban movement of poultry in and out of the area.
But in India the disease is already in farm birds, raising more complicated issues, and the possibility that there will be human infections. Although the dreaded virus does not now readily infect humans or spread among them, more than 160 people have caught the disease worldwide, all of them people who had close contact with sick birds.
Experts are worried that A(H5N1) could acquire the ability to spread from human to human through natural processes, setting off a worldwide influenza pandemic.
Government officials in a rural district of western India on Sunday began to slaughter and inoculate roughly a million chickens, and dozens of people from the same area were dispatched to be tested, a day after test results confirmed the first outbreak of avian flu in this country.
Officials in New Delhi took pains to dismiss earlier press reports of a poultry farmer's death from suspected bird flu. The central government ordered state governments to step up surveillance efforts, urged the public to "maintain proper hygiene and sanitation," and announced that it was taking steps to increase the availability of bird flu treatment in India.
If it is not swiftly contained, bird flu could be disastrous in this country, where the population density and a feeble public health system, especially in the countryside, make it particularly vulnerable to a pandemic of this sort. India is the world's sixth-largest poultry producer, according to the United States Department of Agriculture.
The poultry deaths took place in a district called Nandurbar, near the northern border of Maharashtra State. State health officials said by telephone that 68 people were being tested for the virus. Workers in the 16 poultry farms in the area, which until two days ago had exported poultry to neighboring states, had tested negative for the virus.
The home minister of India, Shivraj Patil, announced Sunday that chickens within a two-mile radius of the outbreak would be killed while others within six miles would be inoculated. A statement issued late Saturday by the central government information bureau said that the situation was "under control."
News reports on Saturday suggested that a 27-year-old poultry farmer, also in the Nandurbar area, had died of bird flu. On Sunday, the Indian government announced that "preliminary" test results had been negative.
About 50,000 poultry are reported to have died from the infection in recent days in the western state of Maharashtra. Officials were also testing for the A(H5N1) strain in India's most populous state, Uttar Pradesh, after 1,400 birds died at a farm there.
United Nations health officials have long urged the governments of India and Egypt to be on high alert for bird flu.
But Dr. Jutzi, the United Nations health official, and other international experts added that the extent of the problem was still unclear in those two countries.
"How extensive the problem is in India is still not known," said Juan Lubroth, a senior veterinary official at the Food and Agricultural Organization, who said the United Nations first received an alert about the outbreak on Friday, and reports from India's states were still coming in.
<<
Bird flu could be major problem for Africa
By Laurie Goering
[Chicago] Tribune foreign correspondent
February 16, 2006, 6:30 PM CST
JOHANNESBURG -- Bird flu has spread to Africa, and experts fear that containing it will be a major problem on a continent where backyard chickens are the norm, health infrastructure is weak and many governments have little in the way of funding or plans to deal with an avian flu outbreak.
In northern Nigeria, where a deadly strain of bird flu began killing chickens this month, cheap chicken has flooded local meat markets, local media report. Poultry farm workers, faced with thousands of dead birds, are working without protective gear to toss them onto open fires. Farmers, not yet certain what government compensation they will receive, remain reluctant to report dying birds.
"If the situation in Nigeria gets out of control, it will have a devastating impact on the poultry population in the region, it will seriously damage the livelihoods of millions of people and it will increase the exposure of humans to the virus," warned Samuel Jutzi, director of the United Nations' Food and Agriculture Organization, which has rushed experts to Nigeria to try to contain the outbreak there.
Nigeria's new cases "prove that no country is risk-free and that we are facing a serious international crisis," he said.
International experts confirmed this week that the H5N1 strain of bird flu had been identified on at least four poultry farms in three states of northern and central Nigeria. What is unclear is whether the deadly virus—also recently discovered in Germany, Austria, Greece and Iran—reached the West African nation through migrating wild birds, in poultry imports or by some other method.
What worries international flu experts, who have poured into Nigeria, is that Africa could prove an ideal place for the disease, which is now deadly to birds but only rarely passed to human beings, to mutate into a form capable of infecting and killing large numbers of people.
So far, the disease has killed just over 90 people, primarily in Asia and the Middle East. But earlier flu pandemics that made the jump to human beings—like the Spanish flu of 1918-19—have killed tens of millions worldwide.
Across Africa, as in Asia, "there's very close interaction between farmers and their birds," many of whom run free in and around homes, said Duncan Mwangi, an immunologist with the International Livestock Research Institute in Kenya. "African governments now have a huge task of trying to educate the public about the dangers. Without that, a lot of people will be exposed to the disease."
Africa has in recent months rushed to prepare to combat bird flu. South Africa and Morocco have been testing migratory birds on their lakes and wetlands for the disease, and Malawi recently determined that a die-off of wild birds there was due to bad weather rather than avian flu. More than 40 of the continent's governments sent representatives to a World Health Organization meeting on the problem last month in Central Africa.
But preparedness remains the exception on the continent. As of the end of November, only a third of the continent's countries had begun any planning process for dealing with avian flu, according to the World Health Organization's regional Africa office.
Planning for a large-scale human outbreak is even further behind. Almost no African countries have stocks of Tamiflu, a drug considered the most effective in treating the disease, and continental leaders like South Africa have yet to license the drug. Weak health infrastructure on the continent—already strained by widespread HIV/AIDS, malaria, tuberculosis and other killer diseases—means any human outbreak would be hard to treat or contain.
"The poor health infrastructure in Africa and the non-availability of vaccines or drugs ... means that millions of people would be at high risk if a pandemic influenza emerges," Dr. Luis Gomes Sambo, the regional WHO director for Africa, warned in a speech last month.
Another problem is that "no one has any idea yet what impact avian influenza will have on a population that's severely immune-compromised" as a result of widespread AIDS, said F. Gray Handley, a representative of the U.S. Department of Health and Human Services stationed in South Africa. In Turkey, also recently affected by the virus, avian flu has killed few of the people who have contracted it, but health officials fear the opposite result in Africa.
Africa's widespread poverty may keep it from adopting some of the preventative measures being undertaken elsewhere. In Europe, for instance, poultry farmers are moving their flocks inside to avoid contact with migrating wild birds.
But in Africa "how many people can make chicken houses when people themselves do not even have good housing?" Mwangi said.
The good news for Africa—though a worry for other parts of the world—is that while the continent lies along major migratory flight paths to Europe and the Middle East, wild birds are now heading north rather than south. That means African countries south of Nigeria probably face a risk of exposure in coming months only from transported domestic birds rather than migrating wild ones.
To avoid that, Nigeria and its neighbors are stepping up protective measures, banning imports of poultry, putting out educational radio announcements and offering compensation to farmers who report bird die-offs and face the culling of their flocks. In Niger, soldiers are patrolling the border with Nigeria to prevent birds being carried across, and voodoo priests in Benin have been warned of the dangers of sacrificing chickens with their bare hands or teeth.
"Poultry is not essential to us. Saving human lives is," Mohamed Ben Omar, a Nigerian government spokesman, said in a national television broadcast recently urging farmers to report sick birds.
International bodies, including the U.S. Centers for Disease Control, U.S. Department of Agriculture and U.S. Office of Foreign Disaster Assistance, are rushing experts, testing equipment and protective clothing to Nigeria to try to contain the outbreak.
In Kenya, one of the African nations best prepared to deal with any outbreak of bird flu, worries about the disease have sent chicken sales plunging 40 percent since November as people turn to alternatives such as mutton and beef.
But across much of Africa, where many families already face a variety of killer diseases and are preoccupied simply with getting food on the table each day, raising, slaughtering and eating chickens remains a daily party of life and bird flu a rather abstract worry. That may make identifying outbreaks difficult, particularly if farmers are reluctant to come forward or simply don't recognize the disease, experts say.
"You never know what's going on out in the bush," Handley said. "We just have to watch and wait and do all we can to prepare" for more outbreaks, something, he said, that "everyone feels is a likely event."
http://www.chicagotribune.com/news/local/chi-060216birdflu,1,4618492.story?coll=chi-news-hed
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