Avian Flu Watch

Study: Poultry most likely to bring H5N1 to Americas

2006-12-24T21:34:00.000-05:00

Study: Poultry most likely to bring H5N1 to Americas

Maryn McKenna * Contributing Writer

Dec 5, 2006 (CIDRAP News) – Poultry infected with H5N1 avian influenza pose the greatest risk of bringing the disease to the Americas, according to a new study by British and US researchers that challenges US efforts to detect flu in migratory birds.

Once on this continent, avian flu is likely to spread to migratory birds that will cross US borders—but the greatest risk will be birds from Central and South America that are not sampled in current wild-bird testing, the researchers said.

The study, to be published in Proceedings of the National Academy of Sciences, employs a complex analytical method that compares the migratory routes of wild bird species thought to be the main reservoirs of avian flu with data on legal trade in poultry and wild birds and avian-flu gene sequences deposited in the public database GenBank.

Plotting those pieces of data against each other allowed the researchers to hypothesize whether migratory birds, wild bird trade, or poultry were responsible for H5N1 influenza's past spread across the globe, as well as to model its possible future paths.

Heading their conclusions: The combination of poultry trade and bird migrations allowed the virus to spread much farther than either would have allowed on its own.

Heading their predictions: The greatest threat to the continental United States will be the arrival of avian flu in Central and South America—where poultry trade is less restricted than in North America—via live poultry imports from countries where avian flu has affected either domesticated or wild birds. Strict regulation of poultry trade across US borders will not be adequate protection, they concluded.

"The question is not just who you trade with, but who your neighbors trade with," A. Marm Kilpatrick, PhD, a senior research scientist with the Consortium for Conservation Medicine and the lead author of the study, told CIDRAP News.

The Consortium is a New York-based non-profit supported by six institutions: the Cummings School of Veterinary Medicine at Tufts University, the Johns Hopkins University School of Public Health, the U.S. Geological Survey's National Wildlife Health Center, the University of Pittsburgh School of Public Health, the University of Wisconsin-Madison Nelson Institute for Environmental Studies, and the Wildlife Trust. Other authors came from the Royal Society for Protection of Birds and the Smithsonian Institution.

Kilpatrick said the researchers' analytical method allowed them to theorize about which population—poultry, migratory birds such as ducks and swans, or traded wild birds such as parrots and birds of prey—was responsible for the spread of H5N1 influenza across Asia and into Europe.

Poultry played a greater role than wild birds in distributing H5N1 through Asia, they found, but migratory birds that picked up the virus from poultry carried it westward, introducing it to 20 of the 23 European countries where it has been found. In Africa, they suggested, both poultry and wild birds played a role, along with poultry products such as chicken droppings bought for fertilizer and fish feed.

The findings challenge previous conclusions on the routes by which some countries were infected. For instance, plotting genetic sequences from H5N1 isolates against migratory routes revealed that bird flu arrived in Turkey, the first European-region country to be affected, not through previously blamed poultry imports from Thailand but via migratory birds winging from Russia.

The researchers' method—which combined estimates of "infectious bird days" (the product of the number of birds entering a country, the prevalence of infection in those populations, and the number of days birds are likely to shed virus) with data on trade and migration from U.S. and international agencies—does not consider the possible influence of the illegal trade in poultry and wild birds, an omission that Kilpatrick acknowledged is a weakness.

But the analysis points so strongly to the influence of legal trade in spreading the pathogen that it argues for implementing trade controls, he said.

"Although the risk of H5N1 introduction into the mainland United States by any single pathway is relatively low, the risk of introduction by poultry to other countries in the Americas, particularly Canada, Mexico and Brazil, is substantial unless all imported poultry are tested for H5N1 or trade restrictions on imports from the old world are imposed," the report says.

The argument over the relative roles played by poultry and migratory birds in spreading H5N1 has been bitter, with agricultural interests defending poultry and conservation groups contending that wild birds are victims rather than disease vectors. The researchers' conclusions are likely to find favor with conservation groups, and appear to accord with past observations by avian virologists that migratory-bird importation to the United States is unlikely because flyways and feeding grounds allow relatively little overlap for viral exchange.

But the research implicitly challenges the focus of the $29 million migratory-bird testing effort being conducted in the United States by the departments of Interior and Agriculture. Since April that effort has tested more than 21,000 samples from wild birds in the United States, primarily in Alaska, without finding any high-pathogenic avian flu.

Because the wild birds sampled to date have shown such low prevalence of all avian flu strains—2.6% among Alaskan isolates, according to the National Wildlife Health Center in Madison, Wis.—surveillance should refocus on dead birds, the researchers said.

But scientists at the National Wildlife Health Center—which leads the US sampling effort but is also a coalition partner of the Consortium for Conservation Medicine—said Monday's study lacks enough data to persuade them to shift their efforts. In particular, they said a decision by the authors to exclude shorebirds from their analysis leaves out important information, because shorebirds congregate in large groups that facilitate viral exchange more than individual encounters do.

"A model is only as good as the assumptions you make and the data you put into it," said Leslie Dierauf, VMD, the center's director. "There may be better data we can obtain on trade in domestic fowl. There is certainly in my mind at this point not good enough data for migratory birds."

Nevertheless, Dierauf, who reviewed the paper a year ago when it was in draft form, said the analysis raises questions that are vital for successful avian flu prevention and control.

"I am not certain [the paper] makes a significant advance in knowledge, but I do know it sets a number of scientific matters on the table that we all need to look at, no matter whether we are looking from the wild-bird perspective or the poultry perspective or the trade perspective," she said. "That is very good."

Kilpatrick AM, Chmura AA, Gibbons DW, et al. Predicting the global spread of H5N1 avian influenza. Proc Nat Acad Sci 2006 (published online Dec 7) [Abstract]

See also:

Olsen B, Munster VJ, Wallensten A, et al. Global patterns of influenza A virus in wild birds. Science 2006 Apr 21;313(5772):384-8 [Full text]

Center for Infectious Disease Research & Policy
Academic Health Center -- University of Minnesota
Copyright © 2006 Regents of the University of Minnesota

Bird flu virus 'still smoldering,' U.S. expert says

2006-12-24T21:30:00.000-05:00

Bird flu virus 'still smoldering,' U.S. expert says
By Caleb Hellerman
CNN

A year ago, headlines were screaming about a looming disaster: the rapid spread of bird flu across two-thirds of the globe. The H5N1 strain of the virus was killing more than half its human victims. Experts were urging the government to stockpile medicine and experimental vaccines.

Dr. Robert Webster, whose vaccine the U.S. government plans to use in case of an outbreak, told CNN at the time, "If this virus learns to transmit human to human and maintains that level of killing, we've got a global catastrophe."

That worldwide pandemic hasn't yet materialized, and bird flu has been out of the headlines for a while. But we may be in for another round of news.

Last week South Korea announced two new outbreaks in poultry. And Dr. Timothy Uyeki of the U.S. Centers for Disease Control and Prevention said he's bracing for another surge in human infections. "When the temperature drops and the humidity drops, that's when you start seeing more poultry outbreaks. And when you see poultry outbreaks, that's when you see human cases."

"It's still smoldering," said Dr. Anthony Fauci, who heads U.S. scientific efforts to combat bird flu. "What it hasn't done, much to our relief, is to become more virulent or better able to transmit from person to person."
New research

Three recent papers in the New England Journal of Medicine illustrate serious roadblocks to understanding and controlling the virus. The first describes three clusters of cases within families in Indonesia, eight patients in all. In two of the clusters, the authors said it's quite possible one person caught the disease, then passed it to family members.

One of those families was profiled in "Killer Flu," a CNN program last December. Rini Dina, a 37-year-old woman in a Jakarta suburb, died of an H5N1 infection, and her 8-year-old nephew, Firdaus, was hospitalized with fever for 10 days. Indonesian health officials said Rini was probably infected by tainted fertilizer in her garden. Firdaus had no direct contact with birds or the garden, but cuddled with his aunt on a couch while she lay shivering with fever. According to medical detectives, that's probably how he got sick.

"We can't prove it, but it probably happened," said Dr. Uyeki, who helped an Indonesian team with the investigations. Worldwide, about a third of all cases involve family clusters and there are a handful of cases where the virus likely passed from person to person, he said.

As a clinician, Uyeki has also helped to examine bird flu patients in Indonesia and Vietnam, the only U.S. doctor to do so. As the virus evolves, he said, its symptoms are evolving as well. "The clinical features in 1997 were different than what they are now. We're seeing less diarrhea, and in Indonesia, it's been much more fatal." Other, more common symptoms are hard to distinguish from other infections -- fever, aches and coughing, and shortness of breath and pneumonia as the illness progresses.

Simply making a diagnosis can be difficult. A second NEJM paper describes eight human patients in Turkey, all of whom initially tested negative for H5N1. The first samples were taken by swabbing the patients' nasal passages. That's standard for most influenza tests, but Uyeki says the H5N1 virus embeds itself deeper in the throat and lungs.

In Turkey, all the patients had been in contact with sick birds, so doctors were looking for H5N1. But in less-suspicious cases, a delay could be fatal. The only known treatment is the drug oseltamivir, sold as Tamiflu. While data are scarce because of the small number of human cases, most experts believe Tamiflu can lessen the symptoms of bird flu -- as it does with typical influenza - but only if taken in the first two days after symptoms appear.

In a commentary published with the two articles, Webster and another prominent flu expert said efforts to eradicate the virus, through killing infected chicken flocks or by vaccinating poultry, have largely failed. Worse, they said, many vaccines used in Asia are of poor quality and are pushing the virus to mutate faster, in potentially more dangerous directions.

So far, H5N1 hasn't gained the ability to easily infect humans, but eyebrows went up during an outbreak in May, on the Indonesian island of Sumatra. Bird flu infected eight people in a single family, killing seven of them. The World Health Organization concluded the illness had spread among the victims, but said genetic testing did not show major changes in the virus. Fauci said the H5N1 virus is indeed "a moving target," but that the existing vaccine provides at least some protection against the different strains. Work on more advanced vaccines is ongoing, he said. "Our capability is getting better and better, but it's not going to happen overnight."

"It's been a really rare human disease to date," Uyeki cautions, but "who can predict what's going to happen? We better continue to monitor and plan. To ignore this would be insane."

Caleb Hellerman is a producer with CNN Medical News.

Find this article at:
http://www.cnn.com/2006/HEALTH/12/06/bird.flu

Scientists to Review Fight Against Bird Flu at Mali Conference

2006-12-24T21:27:00.000-05:00

Scientists to Review Fight Against Bird Flu at Mali Conference
By Phuong Tran
Dakar
05 December 2006

Representatives from more than 100 countries are preparing to attend the fourth international conference on avian influenza, Wednesday in Bamako, Mali. Scientists fear that the rapid spread of this highly contagious virus, combined with the lack of preparation in vulnerable countries, can lead to added economic and human losses. Phuong Tran reports from Dakar.

The participants will include donors, health professionals and representatives from the livestock industry. They will discuss ways to contain the highly contagious H5N1 virus, also known as bird flu.

A conference report prepared by the World Bank says that some of the most rapid promulgation in the past year has happened in Africa, where several countries have reported the avian flu in both poultry and humans.

Vendor prepares chickens for sale in Garki market in Abuja, Nigeria (File photo)
Vendor prepares chickens for sale in Garki market in Abuja, Nigeria (File photo)
This report suggests Africa needs close to a half billion dollars to fight the avian flu. A veterinary consultant to the conference, Faouzi Kechrid, explains Africa's vulnerability.

Kechrid believes that the virus poses a big problem for Africa, given the nature of cattle breeding, the lack of well-developed veterinarian services and what he says is the lack of proper information for people working on non-commercial family farms.

Alex Thiermann is president of the standards committee at the Paris-based World Organization for Animal Health. The committee develops the World Trade Organization's standards for the trade of animals and animal products. Thiermann's concern is that the most vulnerable countries for the spread of avian flu are also the ones that do not have the tools to control the virus.

"The concern that we have is countries that do not have the necessary infrastructure to do an early detection, take rapid action and notify international authorities," he said. " In Africa, we have problems because either the message does not get to the farmer or the message gets to the farmer and the farmer is afraid to report it, because he or she may lose the poultry, and [they think] it may be better to move them to a neighboring village or a neighboring country."

Thiermann and Kechrid identify two conditions for a successful containment strategy. First, Thiermann points to Southeast Asia, where there was an outbreak of the virus in poultry in 2003. He thinks this region's strong veterinary infrastructure helped contain the virus.

Second, Kechrid explains how a compensation system can help encourage farmers to take early action.

Kechrid explains that the ideal situation would be that when a farmer suspects an animal of carrying the virus, he kills it. But this can seriously damage the farm's earnings. Kechrid says that is why a compensation system is needed to ease farmers' losses from killing poultry.

Since 2003, the World Bank reports that avian influenza has killed or forced the killing of 250 million poultry birds, which translates to direct economic losses for people connected to the livestock industry. According to the World Health Organization, most cases have occurred in rural households, where small flocks of poultry are kept.

The World Bank conference report says the international community needs to raise an additional $1.5 billion to control the virus. Some of this money would go to a compensation system for farmers.

Thiermann of the World Organization for Animal Health says that a similar compensation system for livestock farmers in Thailand and Vietnam contributed toward those countries' success in controlling the spread of avian flu.

Thiermann's focus goes beyond the conference, to long-term structural change.

"Tomorrow, we are going to be fighting another emerging disease. We cannot target just avian flu. We need to strengthen each country's infrastructure. Otherwise, not only those countries, but the rest of the world is going to be at risk for these new emerging diseases."

According to the World Health Organization, since the discovery of the virus in a human in 1997, there have been close to 250 laboratory confirmed human cases of avian flu, leading to more than 150 deaths. Health experts have been monitoring the H5N1 strain for almost eight years, aware that there is a chance the virus can cross over to humans and spread rapidly.

New Research Predicts U.S. Entry of H5N1 Avian Influenza

2006-12-24T21:25:00.000-05:00

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December 05, 2006 08:00 AM Eastern Time
New Research Predicts U.S. Entry of H5N1 Avian Influenza

Scientists Uncover Disease Pathways and Causes

NEW YORK--(BUSINESS WIRE)--Scientists at the Consortium for Conservation Medicine (CCM), Royal Society for the Protection of Birds, and Smithsonian Institution’s National Zoo report H5N1 avian influenza is most likely to be introduced to countries in the Western Hemisphere through infected poultry trade.

Following initial outbreaks of H5N1 avian influenza in Hong Kong, scientists and government officials worldwide have debated exactly how the virus was being spread and what could be done to stop it.

Dr. Marm Kilpatrick, senior research scientist with CCM, led the team in their efforts to predict the most likely method of introduction to the U.S. Dr. Kilpatrick and colleagues predict that bird flu will most likely be introduced to countries in the Western Hemisphere through infected poultry trade rather than from migrating birds from eastern Siberia, as previously thought. The subsequent movement of infected migrating birds from countries south of the U.S. would be a likely pathway for H5N1 avian influenza to reach the USA.

Avian influenza has reached more than 50 countries, and millions of chickens have been either infected and/or culled to prevent its spread to other poultry farms. Estimated financial losses are in the tens of billions of dollars. In addition, 258 people have been infected and 153 human deaths have occurred, with most cases in Vietnam, Indonesia, Thailand, and China.

This new research set out to identify the pathways for individual H5N1 introductions as the virus spread through Asia, Europe and Africa. The predictive modeling approach used offers substantial promise for understanding past introductions, the pathway for new introductions, and ways to prevent future spread of the deadly virus.

The researchers analyzed the risk of introduction by three different pathways: poultry, wild bird trade, and movement of migratory birds. “To determine the pathway of introduction we gathered global data on country-to-country trade in poultry and wild birds and mapped out the migratory routes of every species of duck, goose, or swan. We then compared our analyses based on these data to the relationships between virus isolates from the different countries,” said Kilpatrick. Dr. Robert Fleischer, a Smithsonian Institution scientist noted, “The rate of genetic change of the virus is extremely fast, which means we can use genetic analysis to trace the geographic and evolutionary pathways the virus has taken.”

The findings showed that migratory bird movements were likely responsible for three introductions in Asia, 20 in Europe, and three in Africa. Dr. David Gibbons, Head of Conservation Science with UK's Royal Society for the Protection of Birds said, “Much of the spread of H5N1 around Europe followed an unusually cold period of weather in central and eastern Europe in January and February 2006, with wild birds moving west through Europe in search of more clement conditions, some carrying H5N1 with them. As part of the UK Government's AI surveillance strategy, RSPB staff will be looking for sick or dead ducks, geese and swans this winter.”

Peter Marra, an avian ecologist with the Smithsonian’s Migratory Bird Center at the National Zoo commented, “In almost all cases in which we have detected H5N1 in wild birds, it has been found in dead birds. It’s critical that dead bird surveillance mechanisms be developed for early detection of H5N1 and other diseases.” In comparison, poultry trade was responsible for two introductions to countries in Africa and nine important introductions in Asia where the disease is still infecting humans and poultry. “The synergistic combination of poultry trade and migratory bird movements spread H5N1 much further than it would have gone by either of these pathways alone,” said Dr. Kilpatrick.

Dr. Peter Daszak, Executive Director of CCM stated, “This study shows how trade between continents opens the door for pathogens to move effortlessly along those routes.” Daszak added, “The study of Conservation Medicine strives to understand how human activities drive disease spread and proposes critical action steps on preventing future pandemics.” Donald Burke, Dean of the University of Pittsburgh Graduate School of Public Health, and an advisor to the group said, “This report shows how we can move beyond the conventional surveillance and response mode to one of prediction and prevention.” Dr. Mary Pearl, President of Wildlife Trust and co-founder of CCM noted, “Fully three-quarters of new diseases have an animal origin. By researching the links among wildlife, livestock, and humans, we can preempt the movement of many new disease-causing agents to people.” Dr. Leslie A. Dierauf, Director of USGS National Wildlife Health Center, a Federal laboratory that conducts influenza surveillance, commented, “This research is integral to our preparedness for the anticipated arrival of HPAI in North America.”

About The Consortium for Conservation Medicine

The Consortium for Conservation Medicine is a coalition of six scientific organizations that enables scientists from multiple disciplines to collaborate on key issues of human, animal, and environmental health and conservation. The CCM is a think-tank for the origin, prediction, and prevention of emerging diseases. www.conservationmedicine.org
Contacts

For The Consortium for Conservation Medicine
Anthony Ramos, 212-380-4469
ramos@wildlifetrust.org

Bird Flu Outbreak Detected Again

2006-11-29T00:13:00.000-05:00

Bird Flu Outbreak Detected Again

By Park Chung-a
Staff Reporter

Another case of the highly virulent H5N1 avian influenza has been discovered at a poultry farm located about 3 kilometers from the first reported outbreak in Iksan, North Cholla Province, the Agriculture Ministry said Tuesday.

The latest discovery of avian influenza has raised fears that the virus has already spread beyond the high risk zone set by the government and the crisis will last longer than originally expected, despite the government's massive quarantine measures.

The owner of the farm requested a virus test on his farm on late Monday as 206 of 12,000 chickens in the farm died in just two days from Sunday to Monday. Another 400 chickens in the farm were reportedly found dead yesterday morning.

The National Veterinary Research & Quarantine Service, the state laboratory, announced that their analysis of samples from the farm confirmed that the chickens were infected with the highly pathogenic bird flu.

Since Sunday, quarantine officials have been destroying all poultry within a 500-meter radius of the initially infected farm, about 250 kilometers south of Seoul. Yesterday alone, they destroyed 46,000 chickens and 300 pigs.

Owing to the second outbreak of the highly pathogenic virus, it is highly likely that a special surveillance zone will be expanded, and that poultry within the 3-kilometer radius quarantine zone will be slaughtered.

Meanwhile, the death of a large number of chickens in Sosan, South Chungchong Province last week was found to be unrelated to the bird flu virus, according to the ministry.

The chicken farm operators at Sosan, just north of the site of a bird flu outbreak in Iksan, 230 kilometers south of Seoul, had requested an investigation after more than 1,000 chickens died since Nov. 20 without a clear reason.

The ministry said that according to the investigation, the deaths were highly likely to have been caused by common poultry infections.

The ministry has been on alert since Nov. 18 when avian influenza was first detected. The ministry has destroyed nearly 100,000 chickens, pigs, cats and eggs in areas near the outbreak site.

No South Koreans have ever fallen ill from bird flu.

michelle@koreatimes.co.kr
11-28-2006 17:16

Flu Viruses May Be Preserved in Ice for Millennia

2006-11-29T00:07:00.000-05:00

Flu Viruses May Be Preserved in Ice for Millennia (Update1)

By Jason Gale

Nov. 28 (Bloomberg) -- Influenza viruses may be preserved in glaciers and Arctic ice for thousands of years and released into the environment when the frozen water is thawed, potentially touching off lethal pandemics, researchers said.

Global warming may speed the release of the microbes, increasing the frequency of outbreaks, according to a study in the December issue of the Journal of Virology. The study is based on tests of water and ice from three lakes in Siberia, where large populations of migratory waterfowl breed before traveling to North America, southern Asia, Europe and Africa.

The finding may help explain the constant emergence of influenza A-type viruses that cause seasonal epidemics and occasionally set off pandemics capable of killing millions of people. Disease trackers are monitoring flu viruses amid an outbreak of the H5N1 strain, known to have infected 258 people in 10 countries in the past three years, killing 153 of them.

``One expectation in relation to this phenomenon would be an increased rate of release of these microbes during times of global, or local, warming events and a decrease during cooler periods,'' said the authors, led by Gang Zhang from Ohio's Bowling Green State University.

Last year was the warmest in more than a century, according to the National Aeronautics and Space Administration's Goddard Institute for Space Studies in New York. Climatologists there monitoring global annual average surface temperatures found that the four previous hottest years since the 1890s were 1998, 2002, 2003 and 2004.

Pandemic Threat

The spread of H5N1 in late 2003 has put the world closer to another pandemic than at any time since 1968, when the last of the previous century's three major outbreaks occurred, according to the World Health Organization.

The H5N1 virus killed about 200 chickens at a South Korean farm, the second outbreak in three days, fueling concerns that the disease may be spreading in the country again after three years. The farm, in the southwestern city of Iksan, is about 3 kilometers (1.9 miles) from a property where H5N1 was confirmed Nov. 25, said Kim Yang Il, an agriculture ministry spokesman.

In Indonesia, the country with the most H5N1 fatalities, the virus killed a 35-year-old woman in a Jakarta hospital early today. The woman from Banten province was most likely infected by diseased poultry, said Joko Suyono, an official at the health ministry.

Bird Contact

Almost all human H5N1 cases have been linked to close contact with sick or dead birds, such as children playing with them or adults butchering them or plucking feathers.

A pandemic can start when a novel influenza A-type virus, to which almost no one is naturally immune, emerges and begins spreading. Experts believe that a pandemic in 1918, which may have killed as many as 50 million people, began when an avian flu virus jumped to people from birds.

Aquatic birds, such as ducks and geese, are the primary host of all influenza viruses. The virus is shed in feces and frequently deposited in rivers and lakes.

Many species of aquatic birds flock to Siberia and other areas near the Arctic Circle for breeding during the Northern Hemisphere's summer before flying south during the fall.

As the birds visit lakes along their paths they shed viruses into the water and onto any ice present, and drink water containing viruses discharged by other birds or released from the ice by thawing, the authors said in the study.

140,000 Years

In previous studies, the authors, who include researchers from Israel's Bar-Illan University and the Russian Academy of Sciences, documented the preservation of viruses, bacteria, and fungi in glacial ice for as long as 140,000 years.

Surveillance of Arctic lakes may help disease trackers predict which flu strains will cause future outbreaks and shape long-term vaccination strategies, the researchers said.

Ice, ice-covered lakes and glaciers have ``the potential for being major sources of viruses that cause pandemics and epizootics in birds and other animals,'' they wrote.

Until refreezing takes place, viruses of both present and past strains may be contracted by the waterfowl, allowing old and new viruses to continually recombine, the study said.

``Conceivably, such ongoing perpetual mechanisms have been operating cyclically throughout the virus's evolution, enabling recurrent emergence of past genes,'' according to the authors.

The same pattern of evolution probably occurs in other diseases as well, the authors said, adding that ``this awaits thorough examination.''

It may explain why some influenza virus strains have appeared, disappeared, and then re-emerged decades later virtually unchanged, they said. A Russian H1N1 influenza virus that caused an epidemic in 1977 was almost identical to the H1N1 strain that caused an epidemic in 1950. Other strains, most notably variants of H2N2 and H3N2 and several H1 varieties, have made similar returns, the researchers said.

To contact the reporter on this story: Jason Gale in Singapore at j.gale@bloomberg.net
Last Updated: November 28, 2006 04:36 EST

Va. hunters' game tested for avian flu

2006-11-28T00:53:00.000-05:00

Nov. 27, 2006, 4:48PM
Va. hunters' game tested for avian flu

© 2006 The Associated Press

RICHMOND, Va. — Waterfowl hunters in Virginia are being enlisted in the fight against avian flu.

Along eastern Virginia's waterways, the Department of Game and Inland Fisheries is scouting out hunters at wildlife management areas, popular hunting spots and boat ramps. There, some of them are being asked to allow a swab of their bagged game to test for the highly pathogenic version of H5N1 avian flu, according to Bob Ellis, assistant director of the department's wildlife division.

Species being sampled include tundra swan, mute swan, snow goose, Atlantic brant and mallards.

People are also encouraged to report to game officials unusual sickness or death they observe in waterfowl or shorebirds. Hunters should refrain from picking up the birds but note their location and contact game officials.

Since 2003, the H5N1 virus has killed more than 100 people and millions of birds worldwide, sparking fears that the virus could mutate into a pandemic influenza.

Officials know of no U.S. bird infected by this highly pathogenic avian influenza.

Low-pathogenic viruses common among waterfowl and shorebirds cause little illness among birds and don't threaten human health.

This summer, federal officials began monitoring Alaska and the Pacific Northwest as the likeliest entry point of infected birds from Asia. The Atlantic Flyway, which includes Virginia, stretches from Greenland to Canada and south to Florida and Puerto Rico.

American birds summering in Greenland mix with those migrating from Africa and Europe, where avian flu already exists.

In Virginia, Game and Inland Fisheries has tested about 190 mute swans and about 90 mallards, Jonathan Sleeman, a state wildlife veterinarian, told the Richmond Times-Dispatch.

Game officials have checked on Tangier Sound, Virginia Beach, the Potomac River, the Beaverdam reservoir, Hog Island and Chickahominy River, according to Sleeman.

Tests on a couple of mallards that died suddenly in Portsmouth came back negative for the H5N1 virus, he said.

The surveillance will continue through the winter as the last of the birds migrating south come through Virginia, Sleeman said.

___

Information from: Richmond Times-Dispatch, http://www.timesdispatch.com

Awaiting Lengthy Lab Confirmation of Bird Flu Risks Treatment Delays, Studies Find

2006-11-28T00:41:00.000-05:00

November 26, 2006
Awaiting Lengthy Lab Confirmation of Bird Flu Risks Treatment Delays, Studies Find
By DONALD G. McNEIL Jr.

Because detecting Avian flu with standard tests is so difficult and time-consuming, waiting for laboratory confirmation of an outbreak would cause dangerous treatment delays, according to new studies of two flu outbreaks.

The studies, published Thursday in The New England Journal of Medicine, were of family clusters of flu cases in Turkey and Indonesia.

Rapid tests on nose and throat swabs failed every time, and in Turkey, so did all follow-up tests known as Elisas. The only tests that consistently worked were polymerase chain reaction tests, or PCRs, which can be done only in advanced laboratories and take several hours.

“It’ll be a disaster if we have to use PCRs for everybody,” said Dr. Anne Moscona, a professor of pediatrics and immunology at Weill Cornell Medical College. “It just isn’t available at a whole lot of places.”

If the A(H5N1) flu mutates into a pandemic strain, rapid tests “will be really key,” she said.

The studies followed clusters in three families in Indonesia in 2005 and in what appears to have been one extended family near Dogubayazit, in eastern Turkey, in January. Case clusters particularly worry public health authorities because they raise the possibility that the flu is mutating to spread faster between people.

In the Indonesian cases, the authors, from Indonesia, the World Health Organization and the Centers for Disease Control and Prevention in Atlanta, concluded that human-to-human transmission had probably taken place in two of the three family clusters. In one case, a 38-year-old government auditor appeared to have caught the flu from his 8-year-old daughter or her 1-year-old sister. All three died; his wife and two sons did not get sick. No one in the family had any known contact with poultry, wild birds, animals or sick people, so the source was a mystery.

“But you can’t always tell what a young child has done,” said Dr. Tim Uyeki, a Centers for Disease Control flu specialist and an author of the study. “There’s no magical test, and you don’t always get a perfect explanation.”

The Dogubayazit cluster was a cause célèbre for some Internet flu-watchers following Turkish news reports in January. They contended that widespread human-to-human transmission seemed to be taking place, and that it may have begun at a banquet attended in late December by members of two related families named Ozcan and Kocyigit. The Turkish government and the World Health Organization did not link the cases or families and tentatively blamed birds for all transmission.

The studies showed how wide a net was cast: 290 people were tested at one hospital because they either had flu symptoms or contact with dying birds, or both. All were given the antiviral drug oseltamivir, which is also sold as Tamiflu, and about half were hospitalized. That accorded with health organization recommendations: widespread testing and use of antivirals, both to save lives and to snuff out any suspected outbreak of a mutant strain.

Only 10 came up positive on PCR tests, and 8 of those were confirmed by a World Health Organization laboratory. All were children; four died. The studies confirmed suspicions that the families were linked; 7 of the 8 children were related or lived near each other. The December banquet was not mentioned.

It was impossible to tell whether the other argument made by the Internet flu-watchers was correct: that poor testing and the oseltamivir had disguised the extent of the outbreak. But the lead author, Dr. Ahmet Faik Oner, a professor of medicine at Yuzuncu Yil University in Turkey, said in a telephone interview that he believed that there had been no human-to-human transmission because all the children had been in close contact with poultry within seven or fewer days before they fell ill and none of their parents or the hospital staff members that treated them had become sick.

Dr. Uyeki declined to comment on the Turkey outbreak, but said both studies lent support to the theory that some people were genetically more susceptible to the flu.

Junk medicine: pandemic flu

2006-11-28T00:37:00.000-05:00

The Times

November 25, 2006

Body&Soul

Junk medicine: pandemic flu
Mark Henderson
Take risks to save lives

The H5N1 bird flu virus is changing. It emerged last week that it has acquired two mutations that suit it better to infecting human cells. It has not triggered a pandemic yet, and may never do, but these are the sort of developments we would see if the worst- case scenario were unfolding.

Britain is among the countries that are best prepared for this. The Government’s contingency plans have won international praise, and the decision to stockpile 14.6 million doses of the antiviral agent Tamiflu means that a first line of defence is in place.

The lack of room for complacency, though, was highlighted by this week’s report from the Royal Society and the Academy of Medical Sciences. It found that while the Tamiflu order is a necessary measure, it is not sufficient. There is a good case for buying a lot more, so it can be used preventively. And supplies of a second antiviral, Relenza, are also needed, as there are signs that H5N1 could become resistant to Tamiflu. An alternative weapon is essential.

Another way of protecting against a pandemic, of course, is vaccination. But as the report cautioned, this is fraught with difficulty. Production capacity is limited by demand for seasonal flu jabs, currently about 350 million a year. It would be difficult to cover more than a small fraction of the world’s 6.5 billion people.

On top of that, an effective vaccine can be designed only once the precise pandemic strain is known. Safety testing, regulatory approval and manufacturing mean a delay of seven to nine months before anyone can be immunised. Millions would be dead before the first injection is given.

The first problem will probably be impossible to solve. It is impractical for industry or governments to build vaccine factories and mothball them. The priority should be research into adjuvants, additives that get more response from vaccines at lower doses.

The second issue also looks intractable. But as Professor Nick White, a flu specialist at the Wellcome Trust, pointed out in the Natural History Museum’s annual science lecture, that is true only up to a point. Some manufacturing delays are inevitable, but weeks or even months might be saved by cutting corners on research.

Under normal circumstances, it is right and proper that vaccines are assessed rigorously and produced to the highest standards to prevent side effects. A pandemic, though, is not a normal circumstance. Professor White argued persuasively that trading off a little more risk for speed might be a bargain worth making. “Have we become too risk-averse to move quickly?” he asked. “We need to think as a society about underwriting scientists to run risks.” A saving of a month would not allow a vaccine to be used in the first phase of a pandemic, but it might make all the difference against its second wave. The vaccine might itself cause deaths, but this must be set against lives saved by speed. The balance of risks and benefits is not yet clear, but this is certainly a debate worth having.

It is not one that has much engaged the Government so far. As Professor White said, it would get fuller consideration if ministers were to accept another of the Royal Society’s recommendations: the appointment of an expert scientist as “flu czar”.

The Chief Medical Officer and the Chief Scientific Adviser have done fine work on pandemic preparedness, but both have significant other responsibilities. They cannot be expected either to be influenza specialists or to give the issue the time it warrants. The UK is fortunate in that many of the world’s leading authorities on pandemic flu are based here: Professor Neil Ferguson of Imperial College London and Sir John Skehel of the National Institute for Medical Research are two of them.

It is critical that their voices are heard at the highest level. Mark Henderson is Science Editor of The Times

Copyright 2006 Times Newspapers Ltd.

Three years into H5N1 outbreak, new research highlights how little is known

2006-11-24T02:06:00.000-05:00

Three years into H5N1 outbreak, new research highlights how little is known
Published: Wednesday, November 22, 2006 | 8:14 PM ET
Canadian Press: HELEN BRANSWELL

(CP) - Three years into the outbreak of the H5N1 avian flu virus, two international teams of researchers scored major scientific credibility points Wednesday when the New England Journal of Medicine published their articles on the diagnosis and treatment of a mere 16 H5N1 patients.

With the official World Health Organization case count hovering near 260 human cases and 153 deaths from 10 countries, it might seem that the problems Turkish doctors experienced diagnosing eight patients in January or the investigation of three clusters of Indonesian patients last year wouldn't rate publication in the world's most prestigious medical journal.

But in fact, there is so little clinical and epidemiological information about H5N1 disease in the scientific literature that experts are eagerly welcoming the addition.

"Boy, it would just be nice to have more of this information out there," Dr. Keiji Fukuda, who heads the WHO's global influenza program, said in an interview from Geneva.

"It's tough. It's not easy getting this information."

A deputy editor of the journal agreed the information charting the virus in people is sparse.

"The number of documented human cases of H5N1 and the number of deaths attributed to it - well-characterized - is still a relatively small number," Dr. Lindsey Baden explained.

"We as a scientific and public health community need to have well-characterized the known human cases so that appropriate lessons can be learned."

Potential lessons from these papers include the observation by the Turkish researchers - from Yuzuncu Yil University in Van - that laboratories inexperienced with testing for H5N1 may have trouble confirming infections. They urged doctors in areas where there are H5N1 outbreaks in poultry to repeat sample taking and testing if initial tests come up negative for patients manifesting an H5N1-like disease.

The Indonesian paper points to the need to follow up with contacts of H5N1 patients. Three of the eight patients reported in the article experienced only mild disease and only came to light when investigators looked for illness in hospitalized cases.

The article noted limited human-to-human transmission may have occurred in two of the three clusters.

Both papers noted that diarrhea was rare among their H5N1 patients - a departure from the case description already in the medical literature. That may be due to the fact that the Turkish and Indonesian cases were caused by a different subgroup of viruses (called a clade) than cases outlined in earlier reports. But one of the authors of the Indonesia paper cautioned against drawing too many conclusions on too few patients.

"It would be interesting to look at clade 2 (infections) versus clade 1 (cases)," said Dr. Tim Uyeki of the U.S. Centers for Disease Control.

"But right now, it's not quite fair to do that. . . . There's a need for more epidemiological and clinical data on H5N1 patients."

The WHO is hoping to fill those knowledge gaps more efficiently in the future.

Scientists working with Fukuda are devising a checklist of basic information they hope attending doctors will collect for each future case of H5N1 infection - recording when people got sick, what symptoms they experienced, what their blood testing showed, which drugs they received and when, how patients responded, and which survived.

"Because there's no place that's having - fortunately - large numbers of cases, the only way to try to do this in a meaningful way is to collect as many of the cases from the different countries as possible," Dr. Frederick Hayden, a WHO scientist involved in the project, explained in a recent interview.

Collecting and sharing standardized information is the only way to start teasing out answers to the myriad questions that continue to puzzle scientists. With so many people exposed to this virus, why do so few get sick? Why do so many clusters of cases among blood relatives occur? Why do children make up such a disproportionate number of the total cases?

When considering the slow accumulation of H5N1 data, it's tempting to contrast it against the world's most recent emerging infectious disease experience - SARS.

But Dr. Malik Peiris - a leading SARS and influenza expert from the University of Hong Kong and an author of the Indonesian paper - cautioned that the analogy isn't a good one.

SARS exploded, triggering major outbreaks in places like Hong Kong, Taiwan, Hanoi and Toronto. The large volume of cases in teaching hospitals steeped in a tradition of research led to the rapid unravelling of an impressive number of SARS mysteries.

By comparison, H5N1 cases have occurred in random fashion in remote locales - villages in Cambodia, Indonesia, Vietnam, Azerbaijan, even war-torn Iraq.

"Here the cases are so dispersed," Peiris said. "There are so many clinicians involved, so many people involved, I think it makes it very difficult to pull these cases together from many different hospitals into one single analysis."

An infectious diseases expert not involved with the papers noted that it's not surprising so many questions remain about H5N1, given the enormous number of mysteries that remain unanswered about seasonal influenza.

"There are many, many questions with regard to influenza that have really only been recognized as important issues over the past 36 months," said Dr. Michael Osterholm, director of the University of Minnesota's Center for Infectious Diseases Research and Policy.

"We want to basically have this breadth of information (about H5N1) that's far and wide, and how do you do it when you're dealing with a disease that's only had 250-some cases documented from beginning to end right now?"

Even with a standardized form for data collection, accumulating information about the disease will remain challenging if cases continue to occur here and there in remote parts of the globe.

"Those very painstakingly developed studies and systems require people to come in - and that's a complete haphazard thing," Fukuda said.

© The Canadian Press, 2006

Severe Flu Pandemic May Cost U.S. $623 Billion, World Bank Says

2006-11-24T02:04:00.000-05:00

Severe Flu Pandemic May Cost U.S. $623 Billion, World Bank Says

By Jason Gale

Nov. 23 (Bloomberg) -- A severe influenza pandemic would cost the U.S. $623 billion, or about 60 times more than an average flu season, and ``constitute a major global recession,'' the World Bank said.

Economists at the Washington-based World Bank estimated a contagion capable of killing more than 1 percent of people worldwide could cause losses of $1.5 trillion to $1.8 trillion globally. The spread of the H5N1 avian influenza strain has put the world closer to another pandemic than at any time since 1968, when the last of the previous century's three major outbreaks occurred, according to the World Health Organization.

The Bank, which funds projects to alleviate poverty, is working with countries to improve hospitals and laboratories to bolster disease surveillance and management of avian flu. Human fatalities from the H5N1 strain of the virus this year have surpassed the previous two years combined, providing more chances for the virus to mutate into a lethal pandemic form.

``Even with such efforts, an eventual human pandemic at some unknown point in the future is virtually inevitable,'' the Bank said in an e-mailed report today. ``Because such a pandemic would spread very quickly, substantial efforts need to be put into place to develop effective strategies and contingency plans that could be enacted at short notice.''

The H5N1 virus is known to have infected 258 people in 10 countries in the past three years, killing 153 of them, the WHO said on Nov. 13. Millions could die if H5N1 becomes as easily transmissible between people as season flu.

Seasonal flu causes the deaths of as many as 500,000 people annually. In the U.S., the disease results in about 36,000 deaths and more than 200,000 hospitalizations each year, costing more than $10 billion, the White House said in a statement last year.

Egyptian Patient

Egypt reported a suspected new human case in the central city of Sohag, the Al-Ghomhuria newspaper reported today, without saying where it got the information. A 25-year-old woman was transferred to the hospital for treatment, the newspaper said.

A pandemic can start when a novel influenza A-type virus, to which almost no one has natural immunity, emerges and begins spreading. Experts believe that a pandemic in 1918, which may have killed as many as 50 million people, began when an avian flu virus jumped to people from birds.

Disease trackers are monitoring for signs the virus is becoming adept at infecting humans, not just birds. The H5N1 strain was first detected in a farmed goose a decade ago in Guangdong, the same province of China where severe acute respiratory syndrome, or SARS, was reported in 2003.

SARS Experience

During SARS, air travel to Hong Kong plunged by as much as 75 percent during the worst four months of the epidemic and retail sales fell by an average of 9 percent, the World Bank said in its report, ``Evaluating the Economic Consequences of Avian Influenza,'' by Andrew Burns, Dominique van der Mensbrugghe and Hans Timmer.

The World Bank's economic modeling for a flu pandemic assumed a 20 percent decline on an annualized basis in air travel and other mass transportation, as well as in services such as restaurant dining, tourism and non-essential retail shopping. Pandemics are typically experienced in at least two waves, with infections peaking in winter, the authors said.

That could cause the world economy to shrink by 3.1 percent, while gross domestic product could be cut by as much as 4.4 percent in Latin America and the Caribbean, the study said.

``Developing countries would be hardest hit because higher population densities and poverty accentuate the economic impacts in some countries,'' the authors said.

The world economy may contract by 4.8 percent during the first year of a ``severe'' pandemic, 2 percent in a ``moderate'' outbreak and less than 1 percent in the event of a ``mild'' pandemic.

`Purely Illustrative'

``Given the tremendous uncertainties surrounding the possibility and eventual nature of a pandemic inflation, these simulations must be viewed as purely illustrative,'' the World Bank said. ``They provide a sense of the overall magnitude of potential costs. Actual costs, both in terms of human lives and economic losses, are likely to be very different.''

Poultry farmers in infected countries have already suffered because of outbreaks. The World Bank in January estimated the cost at $10 billion in Asia alone. The virus has since been found in wild birds and domestic poultry in at least 38 countries in Asia, Africa, the Middle East and Europe.

South Korean health inspectors are testing poultry for H5N1 on a farm where 6,000 birds died this week in the southwest of the Korean peninsula, the agricultural ministry said in a briefing today.

In Somalia, dozens of bird carcasses have been found in Elbaraf, 55 kilometers (34 miles) north of the town of Johwar, raising fears of an H5N1 outbreak in the Horn of Africa, Reuters reported today, citing Ali Hamud, a local veterinarian.

To contact the reporter on this story: Jason Gale in Singapore at j.gale@bloomberg.net
Last Updated: November 23, 2006 08:14 EST

Outbreaks Show Bird Flu Virus Is Changing

2006-11-23T02:49:00.000-05:00

Outbreaks Show Bird Flu Virus Is Changing
11.22.06, 12:00 AM ET

WEDNESDAY, Nov. 22 (HealthDay News) -- Detailed data on clustered human cases of avian flu have experts agreeing that the H5N1 virus is evolving -- but in what direction?

"The virus is always changing, and the mutations that make it more compatible with human transmission may occur at any time," warn Drs. Robert Webster and Elena Govorkova, both virologists at St Jude's Children's Research Hospital in Memphis, Tenn.

Their commentary accompanies reports from Indonesia and Turkey, both published in the Nov. 23 issue of the New England Journal of Medicine.

However, another expert believes that, so far, H5N1 has given no indication it is mutating toward human-to-human transmission.

"It's far from a certainty," said 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. "The virus could move closer to human-to-human transmission, and it could move farther away. I don't think that you can conclude from these articles in the NEJM that the thing is becoming easier to transmit."

The two studies' most basic data is not new. They focus on three clusters of H5N1 infection in Indonesia in mid-to-late 2005, involving four deaths, and an eight-patient cluster treated in the first weeks of 2006 at a hospital in far-eastern Turkey. Four of the Turkish patients died.

Details published in the journal do point to some intriguing trends, however.

As noted in other cases, almost all infections were linked to close handling of domestic fowl. More troubling was the fact that the Turkish group, led by Dr. Ahmet Oner, of Yuzuncu Yil University, in Van, found it very difficult to diagnose H5N1 in humans at its earliest stages.

Two standard tests turned up negative for the virus, and only a high-tech "polymerase-chain-reaction assay" confirmed H5N1 as the culprit. Infection also "causes a wide spectrum of illnesses in humans," the study authors wrote, with symptoms varying widely among patients.

In the Indonesian report, led by epidemiologist Dr. Timothy Uyeki of the U.S. Centers for Disease Control and Prevention, researchers found that H5N1 affected some patients more severely than others, suggesting that there are genetic factors influencing patient vulnerability. They also noted that certain drugs, such as oseltamivir (Tamiflu), could help fight the predominant Indonesian strain, but these drugs are only effective when given a day or two after infection. That's probably too early for most patients, however.

"In the countries that have reported human H5N1 cases, patients generally do not seek medical care early in their illness," Uyeki explained. "They usually present for medical care when their illness is advanced, e.g., they have pneumonia, and therefore they are not able to receive early oseltamivir treatment."

In their commentary, Webster and Govorkova noted that the number of documented human cases of H5N1 infection is rising worldwide. A total of 251 cases have been recorded globally since 1997, they said, and "by mid-August, 97 humans had been infected in 2006 -- the same number as in all of 2005."

No definite case of human-to-human transmission has yet been reported, suggesting that "the current H5N1 virus is apparently not well 'fitted' to replication in humans," the two experts wrote. However, "the intermittent spread to humans will continue, and the virus will continue to evolve," they added. "Clearly, we must prepare for the possibility of an influenza epidemic."

Siegel believes this kind of language can be misleading.

"We don't know enough about H5N1, and the science hasn't evolved to the point where we can predict when an epizoonotic problem -- a disease that has killed a lot of birds -- is going to start killing a lot of humans," he said.

And, while reports do suggest a rise in human cases over time, Siegel noted that, prior to 1997, no one was keeping close tabs on the epidemiology of H5N1. "I think there may have been previous clusters that might have gone unreported because of a lack of attention -- they may have been misdiagnosed as other kinds of flu," he explained.

Underreporting of prior outbreaks means it also impossible to say that the avian flu is mutating in any one direction, Siegel said. "There's just no way of telling from these clusters that this virus is evolving in the direction of easier transmission -- we can't tell if these clusters are anything new, or if there was a precedent for them," he said.

Finally, he said, H5N1's genetic "leap" to human-to-human transmission -- if it ever happens -- will be much tougher than media reports have let on.

"I've talked to a top expert at the U.S. National Institutes of Health," Siegel said. "He has tried [in the lab] to manipulate H5N1 to make it transmit more easily human-to-human, and he hasn't been able to do it. He's tried different mutations, including using proteins from the 1918 Spanish flu."

While that doesn't mean the right combination of random mutations won't happen in the natural world, it suggests that a bird flu pandemic is a possibility -- but not a certainty. "There's no sense of 'imminence' here," Siegel said.

All of the experts agreed that more needs to be done to curb the spread of the virus among birds, however.

"H5N1 viruses are a 'moving target' and are evolving globally," Uyeki said. "Therefore, what is needed is ongoing, expanded surveillance of highly pathogenic avian influenza A (H5N1) viruses in animals (including poultry and wild birds) and humans in many countries."

Webster and Govorkova noted that countries that have implemented tough, bird-focused interventions did reduce the threat. But with winter approaching, they worry that H5N1 will finally make its way from Eurasia to the Americas via migrating flocks.

However, Siegel said, vaccinating every bird in the United States does not make sense right now. That's because the virus would simply go "underground," infecting fowl but not producing outward symptoms.

"You want to vaccinate susceptible populations, and then control outbreaks by killing affected birds," Siegel said.

But he also stressed that, "here, in the U.S., we as yet have no birds that have this virus. We don't even have a problem yet, except for fear."

More information

There's more on bird flu at the U.S. Centers for Disease Control and Prevention.

UNH gets $1.55M for avian flu study

2006-11-23T02:45:00.000-05:00

11-23-2006

UNH gets $1.55M for avian flu study

DURHAM -- An international, interdisciplinary team of researchers led by professor Xiangming Xiao of the University of New Hampshire is taking a scientific approach in an attempt to understand the ecology of the avian influenza, develop better methods of predicting its spread and provide an accurate early warning system.

Xiao and colleagues were recently awarded $1.55 million for a four-year project funded by the U.S. National Institutes for Health as part of the Ecology of Infectious Diseases Program jointly sponsored with the U.S. National Science Foundation. The EID program supports research projects that develop quantitative analysis and modeling capacity for better understanding the relationship between manmade environmental change and the transmission of infectious agents.

The UNH project will use environmental remote sensing data from Earth-observing satellites in combination with research in epidemiology, ornithology and agriculture to provide a better picture of how the Highly Pathogenic Avian Influenza survives and gets transmitted among poultry and wild birds. The work focuses on China, where outbreaks of the virus have been prominent.

Xiao, of the UNH Institute for the Study of Earth, Oceans and Space Complex Systems Research Center, is the principal investigator for a team that includes scientists from the United Nations Food and Agriculture Organization and research institutes in Belgium and China. Research scientist Rob Braswell is a co-investigator.

The ecology of the avian influenza involves a complex web of factors, including environmental settings, agricultural practices of rice production and harvesting, poultry production involving huge populations of free-grazing ducks and the migratory behavior of wild bird populations. Depending on how all of these risk factors intermingle over time, the virus can be spread through the environment by infected wild birds or domestic poultry.

"The strength of our group, and of this proposal, is that over the last few years we've been able to pull a lot of information out of satellite observations that can help unravel the complex risk factors involved in avian flu ecology," said Xiao.

For example, using imagery from satellites, the team can map and track the times when crops are planted and harvested and monitor activity in wetlands. Used in conjunction with other data of the environment, bird migration and poultry production, dynamic maps of "hot spots" and "hot times" for viral transmission can be developed and will aid the public, researchers, business and decision-makers in preparing for a potential pandemic crisis.

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What is bird flu?

2006-11-21T23:46:00.000-05:00

What is bird flu?

Last Updated: 12:01am GMT 21/11/2006

What is bird flu?

Avian influenza or 'bird flu' is a contagious disease of birds, caused by influenza A viruses that can cause a range of symptoms, from mild illness and low mortality to a highly contagious disease with a near 100% fatality rate. The bird flu virus currently affecting poultry and some people in Asia and other areas is the highly pathogenic H5N1 strain of the virus.

How is it spread?

As the virus can remain viable in contaminated droppings for long periods, it can be spread among birds, and from birds to other animals, through ingestion or inhalation. All bird species are thought to be susceptible to avian influenza. Migratory birds such as wild ducks and geese can carry the viruses, often without any symptoms, and show the greatest resistance to infection. Domestic poultry flocks, however, are particularly vulnerable to epidemics of a rapid, severe and fatal form of the disease.

What kind of virus is it?

There are many different subtypes of influenza A virus. The most virulent are called highly pathogenic avian influenza and can reach epidemic levels among birds. Of these, subtype H5, and more particularly subtype H5N1, pose the greatest concern for human health. According to the World Health Organization (WHO), there is mounting evidence that the H5N1 strain has a unique capacity to jump the species barrier and cause severe disease, with high mortality, in people.

How did the current outbreak start?

The outbreak of avian influenza of most concern - H5N1 - began in poultry in South Korea in mid-December 2003, and has affected birds in many countries in Asia, Europe, Middle East and Africa. It involves a variant of the same virus subtype as that associated with the 1997 Hong Kong outbreak.

How can bird flu infect people?

H5N1 is able to infect people although it does not do this easily. In human populations, where domestic pigs and wild and domestic birds live in close proximity with people, the mingling and exchange of human and animal viruses can more easily occur. Those who have become infected have had close direct contact with infected birds.

What symptoms does it cause?

Human infection with avian influenza viruses usually causes conjunctivitis (eye infection) and mild flu-like symptoms, with one notable exception, the highly pathogenic H5N1 virus which can be deadly. The first documented cases in people appeared in Hong Kong in 1997, when 18 people infected with an H5N1 virus strain were admitted to hospital, six of whom died. As of 15 November 2006, 258 reported cases of H5N1 infection in people have occurred in ten countries, Thailand, Vietnam, Cambodia, Indonesia, China, Turkey, Iraq, Azerbaijan, Egypt, and Djibouti. One hundred and fifty-three of these have been fatal.

Risk of a human influenza pandemic

"We do not know what the virus is that will cause pandemic 'flu. What we do know is that Mother Nature has the recipe book and its just a matter of time before she starts cooking,." said Sir Liam Donaldson, Chief Medical Officer. "Wherever in the world a flu pandemic starts, perhaps with its epicentre in the Far East, we must assume we will be unable to prevent it reaching the UK. When it does, its impact will be severe in the number of illnesses and the disruption to everyday life."

What is a pandemic, and what causes it?

We are used to epidemics of 'ordinary' flu, which occur seasonally, every year, around the world. An epidemic is a widespread outbreak of disease occurring in a single community, population or region. A pandemic, on the other hand, occurs on a much greater scale, spreading around the world and affecting many hundreds of thousands of people across many countries.

Three influenza pandemics occurred in the last century - 1918 to 1919 (Spanish flu), 1957 to 1958 (Asian flu) and 1968 to 1969 (Hong Kong flu). All affected large numbers of the population, causing many deaths and huge economic and social disruption. In the case of the 1918 outbreak, around 50 million people are thought to have died.

What are the most important signals that a pandemic is about to start?

The most important warning signal comes when clusters of patients with clinical symptoms of a new influenza, closely related in time and place, are detected, as this suggests human-to-human transmission is taking place. For similar reasons, the detection of cases in health workers caring for H5N1 patients would suggest human-to-human transmission.

Why are they worried about H5N1?

The H5N1 virus is one of 16 different known subtypes of influenza virus. Experts fear that the H5N1 subtype could trigger the next pandemic for several reasons. Firstly, it has already demonstrated an ability to infect people and kill - one of the key characteristics of a pandemic strain. Secondly, the virus has the ability to mutate and acquire genes from viruses infecting other species. Experts are concerned that the virus could either: adapt, giving it greater affinity for humans, or; exchange genes with a human flu virus, thereby producing a completely new virus strain capable of spreading easily between people, and causing a pandemic. Alternatively the pandemic could arise from a strain of influenza A unrelated to H5N1.

Why is this influenza virus called H5N1?

Subtypes of influenza virus are named according to two specific proteins, hemagglutinin and neuraminidase, on the surface of the virus. Hemagglutinin allows the virus to "stick" to a cell and initiate infection, while neuraminidase enables newly formed viruses to exit the host cell. Currently, there are 16 known variants of hemagglutinin protein and 9 known variants of neuraminidase proteins. This particular subtype of influenza virus has hemagglutinin type 5 and neuraminidase type 1, so it is known as H5N1.

If there was a flu pandemic, what could I do?

You can reduce, but not eliminate, the risk of catching or spreading influenza during a pandemic by: covering your nose and mouth when coughing or sneezing, using a tissue when possible; disposing of dirty tissues promptly and carefully – bag and bin them; avoiding non-essential travel and large crowds whenever possible; maintaining good basic hygiene, for example washing your hands frequently with soap and water to reduce the spread of the virus from your hands to your face, or to other people; cleaning hard surfaces (e.g. kitchen worktops, door handles) frequently, using a normal cleaning product; making sure your children follow this advice.

Are drugs effective in treating avian influenza in humans?

The recently circulating H5N1 strains are susceptible to two antiviral drugs —oseltamivir (sold as Tamiflu) and zanamivir (sold as Relenza). However, these medicines need to be started early enough—usually within the first two days of infection—to be effective. Many of the recently circulating H5N1 influenza viruses have been shown to be resistant to two older, inexpensive antiviral drugs, rimantadine and amantadine. Scientists are studying how the H5N1 viruses became resistant to these older drugs and watching for any signs of resistance to the newer drugs.

What is the status of vaccine development and production?

Vaccines effective against a pandemic virus are not yet available. Vaccines are produced each year for seasonal influenza but will not protect against pandemic influenza. Although a vaccine against the H5N1 virus is under development in several countries, no vaccine is ready for commercial production and no vaccines are expected to be widely available until several months after the start of a pandemic.

Some clinical trials are now under way to test whether experimental vaccines will be fully protective and to determine whether different formulations can economize on the amount of antigen required, thus boosting production capacity. Because the vaccine needs to closely match the pandemic virus, large-scale commercial production will not start until the new virus has emerged and a pandemic has been declared. Current global production capacity falls far short of the demand expected during a pandemic.

Is the world adequately prepared?

No. Despite the advance warning the world is ill-prepared to defend itself during a pandemic. The World Health Organisation has urged all countries to develop preparedness plans, but only around 40 have done so. WHO has further urged countries with adequate resources to stockpile antiviral drugs nationally for use at the start of a pandemic. Around 30 countries are purchasing large quantities of these drugs, but the manufacturer has no capacity to fill these orders immediately. On present trends, most developing countries will have no access to vaccines and antiviral drugs throughout the duration of a pandemic.

Sources: Department of Health, National Institutes of Health, World Health Organisation

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Britain vulnerable to drug-resistant bird flu

2006-11-21T02:11:00.000-05:00

Britain vulnerable to drug-resistant bird flu

By Roger Highfield, Science Editor
Last Updated: 2:07am GMT 21/11/2006

# The report: Pandemic influenza: science to policy
# Q&A: What is bird flu?

The nation has been left vulnerable to a global bird flu pandemic because the stockpile of anti virus drugs is deficient, leading doctors and scientists have warned.

Only a few days after MPs criticised the way politicians abused scientific research, a report warns that the Government is not making best and timely use of independent scientific advice in preparing for an influenza pandemic, when an avian strain of influenza develops the means to spread among people and kill millions worldwide.

The report by the Royal Society and the Academy of Medical Sciences, published today, recommends that the Department of Health urgently revisits its decision to stockpile only one antiviral drug – Tamiflu – in light of emerging scientific evidence that the avian flu virus known as H5N1, can develop resistance to this drug.

The Government has ordered 14.6 million courses of Tamiflu, which could cover one quarter of the population.

Leaving aside issues of how to use Tamiflu effectively, how much drug will be required to treat infections, and whether it should also be used to prevent infections, Prof Neil Ferguson, from Imperial College London, said that the emergence of a Tamiflu-resistant pandemic strain is a "nightmare scenario" for which the UK needs to be prepared.

Stocking the alternative - inhaled - antiviral Relenza, alongside Tamiflu, which is taken in tablet form, could provide an important second line of defence in the event of a pandemic, as in other countries, because "not all viruses that are resistant to Tamiflu are resistant to Relenza," said Sir John Skehel, chair of the report's working group.

"The Government was right to order Tamiflu in early 2005," he said. "However, we are concerned that it is not updating its plans as the landscape of what we know about influenza changes.

This shortcoming illustrates how "we are concerned that decisions are being made, as the UK prepares for a possible pandemic, that fail to take account of expert advice," he said.

The Department of Health ordered two pandemic vaccines on the basis of preliminary data and no human or animal trial data, according to the report, which calls on samples to be made available to scientists for testing as soon as possible and for more openness: "The working group found difficulty in penetrating the barrier of confidentiality that surrounds the industry and its relationship with the Department of Health."

The report recommends the appointment of a leading influenza specialist as a high-level independent adviser to government, a Flu Czar, to feed the latest scientific information from academic researchers, industry and government departments into the ministerial committee which is responsible for preparing for a pandemic.

The report also calls on the Department of Health to bring together academic researchers and those in pharmaceutical companies to develop and improve vaccines – which will be a fundamental tool to control the scale of an influenza pandemic.

The report highlights that it would not be possible to manufacture enough influenza vaccines globally in a pandemic. However, limited supplies can "go-further" if combined with compounds known as "adjuvants" which increase vaccine effectiveness.

Improving vaccine performance with these compounds will help overcome the challenges of producing sufficient H5N1 vaccine against the particular virus that may hit the UK. "Encouraging researchers and drug manufacturers to share information would speed up the development of adjuvants and vaccines to make the UK more responsive during a pandemic," the report says.

And it says that the Government should consider "population priming" where, even without an exact match in virus strain, it may be possible to provide broad immunity by vaccinating with a pre-pandemic influenza vaccine.

So far this year, there have been 75 deaths caused by the H5N1 virus, compared with 42 last year, and there are still widespread concerns that it could mutate or combine to make a superflu capable of causing a global pandemic.

Prof Lindsey Davies, the Department of Health's Director of Pandemic Influenza Preparedness, said: "We are already addressing many of the report's recommendations in our ongoing pandemic preparedness planning."

Information appearing on telegraph.co.uk is the copyright of Telegraph Media Group Limited and must not be reproduced in any medium without licence. For the full copyright statement see Copyright

Bird Flu Vaccine Has Short Shelf Life

2006-11-18T21:30:00.000-05:00

NOVEMBER 18, 2006 | SAN DIEGO, CA
KFMB STATIONS: News 8 | 100.7 JACK FM | 760 KFMB

Bird Flu Vaccine Has Short Shelf Life

Last Updated:
11-18-06 at 2:24PM

WASHINGTON -- Some of the first doses of bird flu vaccine in the nation's stockpile are growing weaker with age. If the shots are needed anytime soon, there will be enough for a million fewer people than previously thought.

More up-to-date vaccine is being brewed to supplement the supply, which today has enough full-strength shots to vaccinate about 3 million people, according to an update issued this week by Health and Human Services Secretary Mike Leavitt.

Last summer, HHS officials were estimating that the stockpile had enough vaccine for 4 million people.

All vaccines lose potency if they spend enough time sitting on the shelf unused. Sure enough, routine testing uncovered that that has begun to happen with some of the first-brewed vaccine against the deadly Asian bird flu known as H5N1, HHS spokesman Bill Hall said Friday.

The government is stockpiling antiflu medications and a small amount of H5N1 vaccine in case the bird flu or some other super-strain sparks the next influenza pandemic. Here's the rub: If such a super-flu began circulating, it would take several months to begin brewing vaccine that was an exact genetic match. But the hope is that if H5N1 were the culprit, health workers and certain other people at high risk might get some protection from shots made against earlier strains of that virus.

The first batches in the nation's stockpile were brewed using an H5N1 strain that circulated in 2004. Now, manufacturers are brewing vaccine using a newer strain that circulated in Indonesia last year. With that updated version, HHS expects to have enough shots for another 5 million people sometime next year.

Meanwhile, the older shots' loss of strength is gradual, raising the question of whether some subpotent doses might be able to be used if absolutely necessary, Hall noted. "It doesn't go from 100 percent to zero," he said.

Copyright © 2006 Midwest Television

OSHA Updates Avian Flu Guidance

2006-11-18T21:21:00.000-05:00

OSHA Updates Avian Flu Guidance
November, 16 2006
Updated guidance from OSHA for occupational exposure to the H5N1 virus – avian flu – focuses on good hygiene, including use of gloves and hand washing, as well as respiratory protection for those who work with infected animals or individuals.

By Josh Cable

"We encourage employers and employees who are most likely to be exposed to avian flu to take the appropriate precautions," OSHA Administrator Ed Foulke Jr. said. "This guidance offers them practical tips, such as hand washing and the use of proper protective equipment, for preventing illness."

The new document – OSHA Guidance Update on Protecting Employees from Avian Flu Viruses – updates guidance on avian flu issued by OSHA in 2004.

The update provides separate recommendations for poultry employees and those who handle other animals, and for laboratory employees, health care personnel, food handlers, travelers and U.S. employees stationed abroad.

The guidance also includes links to helpful Web sites with additional information, and a list of technical articles and resources, including a history on flu pandemics, symptoms and outcomes of various strains of the avian flu, a summary of the bird importation regulations and details on the transmission of the virus.

Avian Flu Could Be the Next Flu Pandemic

Wild birds, particularly waterfowl, are natural hosts of avian flu viruses and often show no symptoms; however, some of the viruses can cause high mortality in poultry, including the H5N1 virus.

Some strains of avian flu viruses carried by these wild birds can infect domestic fowl and in turn can infect humans, causing fever, cough, sore throat, eye infections and muscle pain. Avian flu can also lead to pneumonia, acute respiratory distress, and other severe and life-threatening complications. The most common route of transmission to humans is by contact with contaminated poultry.

The federal government is providing funding, advice, support and up-to-date information to help Americans prepare for and prevent the spread of avian flu in this country. The world's public health community is concerned that a new avian flu subtype may acquire the capability of human-to-human transmission, and become an agent for the next flu pandemic.

Increasing concern over the possibility of a pandemic has led the World Health Organization to develop a Global Influenza Preparedness Plan, and the White House to issue its National Strategy for Pandemic Influenza.

OSHA Guidance Available on Agency's Web site

OSHA Guidance Update on Protecting Employees from Avian Flu Viruses, as well as other important information on the topic, is available in English and Spanish by visiting the In Focus section on the home page of OSHA's Web site or by clicking here.

For more information on federal activities on avian flu and pandemic flu, visit http://www.pandemicflu.gov.

Occupational Hazards | Copyright © 2006 Penton Media, Inc. All Rights Reserved.

International Avian Flu Meeting To Be Held in Bamako, Mali

2006-11-18T21:15:00.000-05:00

17 November 2006

International Avian Flu Meeting To Be Held in Bamako, Mali

U.S. co-sponsors conference organized by African Union, Mali, European Union

By Cheryl Pellerin
USINFO Staff Writer

Washington -- Health and agriculture ministers from many countries around the world will gather in Bamako, Mali, December 6-8 to address issues of growing concern involving avian and pandemic influenza and international response and preparedness.

The African Union, the government of Mali and the European Union are co-organizing the conference, and the U.S. State Department is a co-sponsor.

The meeting will be the fourth since September 2005, when President Bush announced before the United Nations General Assembly a new International Partnership on Avian and Pandemic Influenza that would bring together key nations and international organizations to bolster global readiness ahead of the growing threat.

Members of the international partnership met in Washington in October 2005 and in Vienna, Austria, in June 2006, and donors from the global community met in Beijing in January 2006, pledging $1.9 billion to fight avian and pandemic influenza.

Of that total, the U.S. contribution has been $334 million. In September, the total U.S. contribution rose to $392 million.

"Avian influenza is expanding across the globe and remains a serious concern for all of us, including countries that are not yet affected, such as those in the Western Hemisphere," said Ambassador John Lange, special representative for avian and pandemic influenza at the State Department, at a press briefing November 16.

The United States is working with many other countries, Lange added, including African nations, "because avian influenza spread to Africa in 2006 and continues to be a concern."

PREPAREDNESS IN AFRICA

The 4th International Conference on Avian Influenza in Bamako aims to give new insights into avian influenza disease development worldwide and offer the latest information on strategies, vaccination and forms of compensation to citizens for poultry deaths. The assembled ministers also will work to foster integrated national strategies coordinated at regional and global levels.

"Given the urgency and the seriousness of the situation," said African Union Chairman Alpha Konaré of Mali in a statement on the conference Web site, "I therefore invite all our partners and stakeholders to leave no stone unturned in working towards our goal of minimizing HPAI [highly pathogenic avian influenza] impact in livestock and public health domains in Africa."

The United States is concerned about the possible decimation of the poultry population in Africa if bird flu spreads beyond the eight currently affected countries.

"If [avian influenza] continues to spread in Africa," Lange said, "then separate from the infections that take place in humans who are very close to the chickens, you may have a loss of a primary protein source [for human diets] in some countries."

For those interested in the economic and social development of Africa, he added, "that is a serious concern.”

The virus now is considered endemic, or prevalent, in poultry populations in large parts of Asia, according to the World Health Organization (WHO), and time frames for controlling the disease are being measured in years.

"We hope to avoid that in Africa," Lange said. "That's one of the reasons we're so excited about the event coming up in Bamako, to focus at the ministerial level, in African countries and other countries around the world, attention on avian and pandemic influenza" and on the importance of engaging in pandemic preparedness.

ENHANCING THE ASIA-PACIFIC REPONSE

The focus on preparedness is also intensifying in Asia.

The two-day 18th Asia-Pacific Economic Cooperation (APEC) Ministerial Meeting concluded November 16 in Vietnam with a joint statement by representatives from 21 member economies that included a section on enhancing avian and human pandemic influenza preparedness and response.

The ministers renewed their commitment to communicate outbreaks transparently and share samples for research to improve preparedness, and urged continued efforts to develop, integrate and practice avian and pandemic influenza preparedness plans to mitigate human suffering and major effects on commerce, trade and security.

APEC economic ministers also agreed to continue to collaborate with the International Partnership on Avian and Pandemic Influenza and to maintain cooperation with international organizations such as the WHO, the United Nations Food and Agriculture Organization and the World Organization for Animal Health.

"As one of the core principles of the International Partnership," Lange said, “we are stressing to country after country the importance of transparency and sample sharing in dealing with avian influenza."

The sooner the world knows about each outbreak, he added, "the more able we are to help a country try to control the outbreaks and to deal with what could someday be a pandemic.”

The next meeting of the international partnership will be held in New Delhi in 2007.

More information about the conference is available on an African Union Web site.

For more information on U.S. and international efforts to combat avian influenza, see Bird Flu (Avian Influenza).

(USINFO is produced by the Bureau of International Information Programs, U.S. Department of State. Web site: http://usinfo.state.gov)

This page printed from: http://usinfo.state.gov/xarchives/display.html?p=washfile-english&y=2006&m=November&x=20061117171159lcnirellep0.3019983

Inexpensive Test Detects H5N1 Infections Quickly and Accurately

2006-11-18T21:11:00.000-05:00

Inexpensive Test Detects H5N1 Infections Quickly and Accurately
Posted on: 11/14/2006

Scientists from the University of Colorado at Boulder and the Centers for Disease Control and Prevention (CDC) have developed an inexpensive “gene chip” test based on a single influenza virus gene that could allow scientists to quickly identify flu viruses, including avian influenza H5N1. The researchers used the MChip to detect H5N1 in samples collected over a three-year period from people and animals in geographically diverse locales. In tests on 24 H5N1 viral isolates, the chip provided complete information about virus type and subtype in 21 cases and gave no false positive results, report the scientists. They say the MChip could provide a significant advantage over available tests because it is based on a single gene segment that mutates less often than the flu genes typically used in diagnostic tests. As a result, the MChip may not need to be updated as frequently to keep up with the changing virus.

The research was led by University of Colorado scientist Kathy L. Rowlen, Ph.D., and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. A paper describing the work, now available online, is scheduled to appear in the December 15 issue of the American Chemical Society’s journal Analytical Chemistry.

“Concerns about a possible influenza pandemic make it imperative that we continue to devise reliable and easy-to-use diagnostic tests for H5N1 that can be employed on-site where outbreaks are suspected,” says NIAID director Anthony S. Fauci, MD. “The MChip developed by Rowlen and her colleagues performed extremely well in initial tests and has the potential to be a valuable tool in global influenza surveillance efforts.”

The MChip has several advantages over the FluChip, a flu diagnostic previously developed by the same research team, says Rowlen. While the FluChip is based on three influenza genes — hemagglutinin (HA), neuraminidase (NA) and matrix (M) — the MChip is based on one gene segment. Unlike HA and NA, which mutate constantly and thus are technically difficult to use to develop gene chip diagnostic tests, the M gene segment mutates much less rapidly, Rowlen explains. “The M gene segment is much less of a moving target than the HA or NA gene. We believe that a test based on this relatively unchanging gene segment will be more robust because it will continue to provide accurate results even as the HA and NA genes mutate over time. The work summarized in our paper strongly supports that idea,” she says.

Another potential advantage is that the MChip would, for the first time, create a way to simultaneously screen large numbers of flu samples to learn both the type and subtype of virus present. Current real-time tests provide information about the type of virus (type A or B) in a sample, but additional tests must be run to determine the virus subtype (for example, H5N1 subtype.)

Working in biosafety-level-3-enhanced labs in Atlanta, CDC scientists, including Catherine B. Smith, MS, extracted H5N1 genetic material from virus samples derived from human, feline and multiple avian hosts, including geese, chickens and ducks. The samples represented infections that had occurred between 2003 and 2006 over a vast geographic area, including Vietnam, Nigeria, Indonesia and Kazakhstan. Six of the human viral isolates were taken from an Indonesian family in which human-to-human H5N1 virus transmission was suspected. The virus diversity in the samples is important, explains Rowlen, because any diagnostic tool designed for eventual use on a rapidly changing virus, such as H5N1, must be able to detect as many variants as possible.

Rowlen and her colleagues tested the ability of the MChip to correctly identify 24 different H5N1 viral isolates, and distinguish those from seven non-H5N1 isolates. The MChip accurately identified and gave complete subtype information (identifying the samples as H5N1) for the 21 out of 24 strains of H5N1. Importantly, notes Rowlen, the test gave no false positives, meaning that the chip never indicated the presence of H5N1 when none was present. Following exposure to a viral isolate, the MChip displays results as a pattern of fluorescent spots. To automate the process of interpreting this pattern — thus eliminating the possibility of human error — the researchers developed an artificial neural network trained to recognize the distinctive pattern indicative of H5N1. Automating the interpretation of MChip results could allow it to be used more readily by health workers at the site of possible flu outbreaks, notes Rowlen.

“This new technology, once manufactured and distributed, could have the potential to revolutionize the way laboratories test for influenza,” says Nancy J. Cox, PhD, director of the CDC’s influenza division. “The MChip could enable more scientists and physicians, possibly even those working in remote places, to more quickly test for H5N1 and to accurately identify the specific strain and its features. This would greatly increase our ability to learn more about the viruses causing illness and take the best steps to respond.”

The raw materials for the MChip cost less than 10 dollars, Rowlen says, and discussions are under way to commercialize its manufacture.

References:

Dawson, E.D., et al. Identification of A/H5N1 influenza viruses using a single gene diagnostic microarrray. Analytical Chemistry. 2006.

Dawson E.D., et al. MChip: A new tool for influenza surveillance. Analytical Chemistry. 2006.

Source: National Institutes of Health

Clues to pandemic bird flu found

2006-11-16T20:06:00.000-05:00

BBC NEWS
Clues to pandemic bird flu found
International scientists believe they have identified some of the key steps needed for bird flu to develop into the deadly pandemic strain of the disease.

The team pinpoints two genetic mutations that would need to occur to the H5N1 virus for it to potentially spread readily between humans.

Writing in the journal Nature, the scientists said the findings would help them to detect pandemic strains.

At present, H5N1 can pass only from bird-to-bird or, rarely, bird-to-human.

This work shows that at least two changes... are needed for H5N1 to transform to strain that could infect humans
Dr Wendy Barclay, Reading University

So far, there have been a total of 258 cases of H5N1 in humans, causing 153 deaths, according to figures from the World Health Organization.

But flu viruses mutate and evolve quickly, and scientists believe the virus could acquire the ability to pass between humans.

They fear this could trigger a repeat of the devastation of the 1918 flu pandemic, which is thought to have killed 50 million people.

Docking station

To investigate how the virus might do this, the researchers looked at samples of H5N1 that had been taken from birds and also from infected humans.

In a small number of the human samples, they found the virus had acquired small changes to a protein called haemaggluttinin, which sits on the surface of the H5N1 molecule.

This protein helps the flu virus to spread by binding to the receptors on cells, which are like docking stations, allowing the virus to invade and infect the cells.

While the haemaggluttinin in most of the samples could only bind to bird cell-receptors, the researchers discovered that in some of the human samples, the haemaggluttinin had acquired the ability to bind to both bird and human cell-receptors.

It is thought this is a key step needed for H5N1 to be able to spread from human to human.

Further analysis revealed two separate mutations at different positions on the protein had enabled H5N1 to recognise human receptors.

The researchers said the discovery of the location of the mutations would help identify H5N1 strains that might be on the way to developing pandemic potential.

Pandemic pathway

Lead researcher Yoshihiro Kawaoka, a virologist at the University of Wisconsin-Madison School of Veterinary Medicine, US, said more mutations would be required for the virus to fully adapt to humans, but it is not known how many mutations are needed for such a change.

The team thought these changes were most likely to occur when a human influenza virus mingled with H5N1, particularly if it could already bind to human receptors.

Dr Wendy Barclay, a molecular virologist from Reading University, UK, said: "This work shows that at least two changes in the haemaggluttinin protein are needed for H5N1 to transform to strain that could infect humans, and knowing what these are will help to inform surveillance."

But, she said, the fact these mutations had already been seen in viruses isolated from human H5N1 cases, and a pandemic had not yet struck, suggested a number of other steps might be needed for the virus to be able to pass from human to human.

Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/1/hi/health/6151638.stm

Published: 2006/11/16 00:49:27 GMT

© BBC MMVI

Experts identify key mutations in bird flu virus

2006-11-15T19:54:00.000-05:00

Experts identify key mutations in bird flu virus
15 Nov 2006 18:00:26 GMT
Source: Reuters

HONG KONG, Nov 16 (Reuters) - A group of scientists has discovered two spots on the H5N1 bird flu virus that need to mutate for the virus to infect people more easily.

The virus has surface proteins that bind more easily to "receptors" lining respiratory tracts of birds, rather than receptors in humans. This means it easily causes disease in animals such as poultry but is much harder for humans to be infected.

But experts fear the H5N1 virus will infect more humans and trigger a pandemic killing millions of people if it mutates to attach easily to human receptors.

In the latest issue of Nature, scientists in Japan, Britain and the United States say they have discovered two specific spots on the genes of the virus that appear to determine if it attaches more easily to bird or human receptors.

This discovery will help scientists determine if any strain of H5N1 has the potential to cause a human pandemic. There are a number of strains now circulating across large areas of the globe.

"The bottomline is that the changes (on the two spots) can be used as molecular markers to identify the potential of the viruses that may grow well in humans," said Yoshihiro Kawaoka of the Institute of Medical Science at the University of Tokyo.

Using 21 samples of the H5N1 virus taken from human victims in Indonesia and Vietnam, the team of scientists found that three of them bound especially easily to human receptors.

"We found many mutations and we tried to identify which mutations were important ... two appeared to be very important (in the virus infecting a human)," Kawaoka told Reuters by telephone from the United States.

He warned against any over-emphasis on these two spots.

"It is very important that we shouldn't only focus on these two. The virus can become human-like by many mutations, these two are important but they are not the only ones," he said.

"But these two will give indication when a virus has changed receptor specificity," he said.

© 1998-2006 Reuters Limited. All rights reserved.

A flu pandemic: Could it happen again?

2006-11-15T19:31:00.000-05:00

A flu pandemic: Could it happen again?

BY DELTHIA RICKS
Newsday Staff Writer

November 13, 2006, 7:30 PM EST

An extraordinarily contagious form of influenza that circumnavigated the globe toward the close of World War I holds the distinction of triggering the most lethal single event in the history of humankind.

Nothing quite like it has occurred since.

As scientists confirmed only last year, the pandemic was caused by a bird flu virus that jumped species.

Now, experts say, the world is overdue for a similar killer strain.

An estimated 50 million people died during the terrifying winter of 1918-1919, the deadliest flu season in the history of the world. More U.S. soldiers succumbed to influenza than died in the war. Indeed, more people died from that illness than lost their lives during the Middle Ages to bubonic plague, a rat-borne bacterial infection that swept unremittingly across Europe between 1348 and 1354.

From a more modern perspective: The AIDS epidemic has killed 25 million people worldwide in 25 years. The great flu pandemic -- known also as the Spanish flu -- killed twice that number in only a matter of months.

Could such a flu season flare again?

"Certainly another pandemic can occur," said Dr. John Oxford, a virologist at Queen Mary's School of Medicine in London and one of the world's leading influenza experts.

"The World Health Organization and the United Nations are both in agreement with that. All of the conditions exist for a virus like H5N1 to take off," Oxford said, referring to the current flu strain responsible for avian influenza.

Dr. Michael Greger, director of public health and animal agriculture at the Humane Society of the United States, also believes the makings of a pandemic already are here.

"Bird flu has gone from snowflake to avalanche. This used to be a very rare disease," Greger said of the infection among birds. "This is not a disease that anyone can miss, because it wipes out entire flocks."

Oxford sees many parallels between the 1918 flu and current avian influenza, which has become a global pandemic among birds. A growing number of human infections have cropped up in Southeast Asia, mostly as a consequence of direct contact with birds. And scattered cases of human illness have emerged in other parts of the world where H5N1 has infected birds.

Gene swap feared

The conditions exist for the disease to become highly contagious, Oxford said. It is possible, Oxford and other scientists theorize, for H5N1 to exchange genes with a common form of flu that routinely infects people. Should this happen, the H5N1 virus could acquire the basic genetic blueprint for spreading quickly -- and explosively -- through human populations. Scientists believe a similar exchange of genetic material occurred prior to 1918.

Because it would be a new virus in humans, it might very well carry a high fatality rate, just like the 1918 flu, Oxford said.

A study reported in August by scientists at the U.S. Centers for Disease Control and Prevention involving ferrets suggested that the "mixing bowl" theory of viral gene exchange didn't seem likely. But they have not ruled it out. Experiments, they say, do not always replicate conditions that occur accidentally in nature.

CDC scientists took genetic material from a common human A-strain of flu and introduced it into the H5N1 strain, and vice versa. Ferrets were used in the experiment because they catch and transmit the flu almost identically to humans, spreading it to each other by coughing and sneezing. The animals emerged from the experiments somewhat weakened but not devastated. To the scientists' surprise, they had not developed a more contagious form of flu.

French roots?

Two years before the 1918 outbreak, cases of a new and unusual respiratory illness were smoldering without much notice among British soldiers assigned to a military base in Etaples, France, Oxford said.

Digging through old medical journals trying to find the beginnings of the 1918 flu pandemic, Oxford and his colleagues ran across a copy of The Lancet from 1916 in which British military physicians described in great detail a series of illnesses diagnosed at the Etaples encampment. Although Oxford's theory differs from that of many American researchers who believe the 1918 flu started at a military base in Kansas, Oxford said the most convincing data suggests the pandemic's roots can be found in France. (Virtually all agree that "Spanish flu" is a misnomer.)

Up to 40,000 men had been processed through the French base on their way to the front lines where the British and their allies were fighting the Germans.

But it seems, at least from what Oxford can discern, that the men were fighting an even more vicious enemy in the camp. In a 145-case sampling documented in the journal report, 50 percent of the soldiers died of their infections. British doctors called the illness infectious bronchitis, something that probably threw off Americans when they read the report.

Soon the French would call it la grippe. Americans would dub it the "great flu," even though it would take until the 1930s for the actual culprit -- a virus -- to be found.

Strikingly, Oxford said, statistics from the 90-year-old medical report are uncannily like those involving human cases of bird flu today.

"To date, the World Health Organization estimates there have been 151 cases [of bird flu] in humans, with a case fatality rate of about 50 percent," Oxford said.

Because the fatality rate in the 1916 sampling was also 50 percent, Oxford sees a parallel that "carries a very strong warning."

Eighty-eight years ago, influenza caught everyone off guard, sweeping ferociously from one corner of the globe to another. Few places were left unscathed.

In 1918, everybody had a flu story if they were lucky enough to live to tell it. The disease was especially devastating among people between the ages of 18 and 40.

Worldwide, people were ordered to wear face masks. If you tried to board a streetcar without one, you could be hauled off to jail. Quarantine was the order of the day. On Long Island, homes became makeshift hospitals.

Symptoms from the 1918 flu included dry cough, high fever and extreme muscle aches. The way that particular flu ravaged the human body mirrors the effects physicians have found in autopsies of people infected with bird flu. Oxford said the body responds in a "cytokine storm" that causes internal bleeding, the result of an immune system gone haywire.

Scientists today are well aware of the 1918 pathogen's virulence because it was reconstructed last year by teams of scientists nationwide, including researchers at Mt. Sinai School of Medicine in Manhattan

A few who lived through the pandemic recorded their horror.

Pulitzer Prize-winning author Katherine Anne Porter, who in 1918 had just begun working as a reporter for the Rocky Mountain News in Colorado, came down with the crippling infection. She would later write about the experience in a trilogy called "Pale Horse, Pale Rider."

This was no simple influenza.

For Porter, who died at the age of 90 in 1980, the memory of it was haunting and indelible, a life-altering experience that pushed her within a whisper of death -- then freed her to tell the story.

Bodies piled like bricks

Throughout the winter of 1918, people were dying so fast a coffin shortage quickly occurred. Even when coffins could be found, there was a shortage of people to bury the dead. Bodies were piled like bricks on streets. Everyone, it seemed, was sick, dying or dead.

But this was 88 years ago. Surely -- certainly -- nothing of this magnitude could surface again?

"Ten years ago there wasn't a single known human infection with bird flu, but now there are several strains of bird flu viruses that have infected people from Hong Kong to Turkey," notes Greger, author of the book "Bird Flu: A Virus of Our Own Hatching."

Bird flu in humans was first diagnosed in 1997 in Hong Kong, and though health officials there ordered the slaughter of millions of birds to stop the virus in its tracks, it cropped up in 2003 in Vietnam in both birds and people.

Last week, Dr. Bu Zhigao and colleagues at the Harbin Veterinary Research Institute in China discovered the gene that makes some strains of the avian infection highly virulent. This knowledge could be used in the development of vaccines to benefit birds, and ultimately humans, scientists say.

Still, Greger says, a single chicken can harbor numerous strains of H5N1. "It takes only a single mutation for a single virus to turn deadly."

Greger estimates that in mainland China alone there are 13 billion chickens. At the time of the last flu pandemic in 1968, he said, there were only 13 million chickens in that country. Presuming 10 percent might be infected now, he believes a staggering number of viruses are probably mutating in the birds.

"We've got to stop encouraging the Western model of poultry production elsewhere in the world," Greger said. "It's a very powerful industry that has grown tremendously in recent years."

With the potential for the emergence of a pandemic strain, Greger said, "people may start questioning whether it's worth risking the lives of millions of people for the sake of cheaper chicken."

Oxford said he believes modern vaccines and antiviral medications, especially those known as neuraminadase inhibitors, such as Tamiflu, will help physicians effectively fight the disease, should a pandemic occur.

"Your government has thrown more cash at this virus than any other flu virus in history," Oxford said of U.S. health officials' ongoing tests of new vaccines and antiviral medications to fight bird flu. "We have two classes of drugs in the medicine cupboard. We could use a few more."

Copyright 2006 Newsday Inc.

EGYPT: Winter may bring more bird flu, health ministry says

2006-11-15T19:12:00.000-05:00

EGYPT: Winter may bring more bird flu, health ministry says
13 Nov 2006 14:58:56 GMT
Source: IRIN

CAIRO, 13 November (IRIN) - With the onset of winter, there may be an increase in cases of the potentially lethal avian flu virus H5N1 among fowl and humans in Egypt, according to health ministry officials.

"In Egypt, as in the rest of the world, although we have all the necessary precautions well in place, there might be a new surge," Sayyid al-Abbasi Egyptian health ministry official, said.

He added that the danger was renewed with each season of migration for birds, and as Egypt is on a major migratory route, it is particularly affected.

On 11 November, the health ministry said a new bird flu location was discovered in Luxor, 720 km south of the capital, Cairo. According to the health ministry, the area of Najaa Al-Abyada has now been quarantined, after domestic birds there were tested and found to be carrying the virus. Birds in the vicinity were being culled, Egypt's official news agency MENA reported.

There has been no new human infections, said al-Abbasi. To date, the majority of cases among humans have been linked to domestic breeding, which remains very common. Bird flu can not be caught from cooked chicken.

While a ban on the practice in urban areas was imposed soon after the virus was first detected, domestic breeding in the rural areas has remained rife as the government did not feel it would be productive to impose a similar ban there.

"A ban would lead many to conceal their birds, heightening the danger rather than quelling it," Abdel Rahman Shahine, health ministry spokesperson, said.

Instead, the authorities tried to focus on raising awareness across the country as well as training health and social workers on how to deal with bird flu.

Out of 15 people infected with bird flu since March 2006, seven have died. The most recent death occurred on 30 October.

Ever since bird flu was first detected among fowl in Egypt in February this year, more than 30 million birds have been culled under government supervision, mostly in poultry farms.

as/ar/ed

IRIN news

© 1998-2006 Reuters Limited. All rights reserved

Influenza Pandemic "Inevitable"

2006-11-15T19:04:00.000-05:00

Monday, November 13, 2006
Influenza Pandemic "Inevitable"

Influenza pandemics are considered inevitable, and the expected worldwide mortality from a severe pandemic is 45 million people, according to Dr David Bradt, from the Department of Emergency Medicine at Royal Melbourne Hospital and the Centre for Refugee and the Disaster Response at Johns Hopkins Medical Institutions in the United States, and Dr Christina Drummond, from the Infectious Diseases Unit at Monash Medical Centre.

Melbourne, Australia - infoZine - Writing in the October/December issue of Emergency Medicine Australasia, the journal of the Australasian College for Emergency Medicine, they say that despite mathematical models suggesting that an emerging pandemic could be contained at its source, this conclusion is not entirely accepted by public health experts.

"Consequences of a pandemic have been widely predicted in the biomedical literature to include overwhelmed healthcare systems, interrupted logistics chains, collapse of economies and destabilized governments," the authors say.

According to Dr Bradt and Dr Drummond, of the 58 countries with animal disease from H5 virus, most are in developing areas.

"In effect the very countries that are the most epidemiologically burdened by avian influenza are also the most developmentally challenged to manage it."

Control strategies such as culling generally result in financial loss to the owner of the birds, which creates an economic disincentive to report bird illness or flock death, the authors say.

They urge governments and health authorities to stay abreast of rapidly evolving technical guidance.

"Personal protective equipment kits, decontamination kits and specimen collection kits in lightweight, portable packages are becoming standardized."

However, air transport border control measures purporting to delay importation and spread of human avian influenza "are scientifically controversial", they say.

"Prehospital care, triage and acute care all require additional professional standardization for the high patient volumes anticipated in a pandemic."

Writing in the same issue of Emergency Medicine Australasia, Mr Alan Hampson, from the Australian Influenza Specialist Group in Melbourne, says that although there is no certainty an avian influenza (H5N1) pandemic will occur, history suggests that there will be future influenza pandemics.

Although such a pandemic is beyond our control, we can try to minimize its impact through planning and research, he suggests.

Recent widespread outbreaks of avian influenza and, associated with these, a growing number of human infections with a high mortality rate have raised concerns that this might be the prelude to a severe pandemic of human influenza, he says.

Recent improvements in scientific testing have revealed that influenza viruses have evolved in an avian host, probably waterfowl.

According to Mr Hampson, there is now little doubt that migratory birds have contributed to the global spread of avian influenza, although it appears that in some areas spread might have been by trade in domestic poultry.

Dr Peter Ritchie, Chair of the Public Health committee of the Australasian College for Emergency Medicine, said preparation for influenza outbreaks is an important public health issue, and emergency physicians are involved in such preparation both within their own emergency departments and at state and federal health department level...

"In the hospital setting, simple measures of infection control including hand-washing, use of appropriate surgical masks, not using nebulisers in patients with suspected influenza-like illness, and simple isolation of these patients are most important," he said.

"In some circumstances the use of more elaborate personal protective equipment and negative pressure room isolation may be required."

This study is published in the October/ December 2006 issue of Emergency Medicine Australasia.

Bird flu expert to lead WHO

2006-11-13T02:19:00.000-05:00

Bird flu expert to lead WHO

GENEVA, Switzerland (AP) -- Dr. Margaret Chan, who spearheaded the World Health Organization's fight against bird flu, was chosen Wednesday to head the agency and lead the international assault on polio, AIDS and other global scourges, becoming the first Chinese to win such a high-profile United Nations post.

Chan, 59, was Hong Kong's health director when the city reported the world's first known human outbreak of the H5N1 bird flu virus in 1997. Six people died, but Chan was credited with heading off a major human health crisis by ordering the slaughter of Hong Kong's entire poultry population -- about 1.5 million birds -- in three days.

She also received international praise for organizing Hong Kong's response to a 2003 outbreak of SARS -- or severe acute respiratory syndrome -- which killed several hundred people.

Her nomination is a victory for China and indicated the communist nation's interest in playing a bigger role in global affairs.

"I will work tirelessly with my eyes on the goal we agreed on together, my ears open for the voices of all and my heart committed to the populations of your countries," Chan told the 34-member WHO executive board after her nomination.

Chan will officially be appointed the next director-general if she gains a two-thirds majority at a special session Thursday of the agency's governing World Health Assembly, comprising all 193 member countries. The assembly has never rejected an executive board nominee.

She joined the WHO in 2003, after the SARS outbreak, and took over as the agency's flu pandemic chief in 2005. As an assistant director-general, she has led efforts to fight communicable diseases and prepare for a possible pandemic should bird flu mutate into a strain easily transmitted among humans.

"This was not an election about countries," U.S. Assistant Secretary for Health John O. Agwunobi told The Associated Press. "This was an election about individuals ... Margaret will be a servant of the entire world."

Dr. Richard Horton, editor of the British medical journal The Lancet, was more reserved.

"Although Margaret Chan has strong abilities in some areas, like epidemic diseases, she is very much untested in other areas," Horton told the AP. "She has never run a really big organization like WHO."

Horton said it would be imperative that Chan "build a strong team that fills the gaps in her own expertise."

The board set Chan's term to start January 4 and to last until through June 2012.

China -- which has recently been criticized for dragging its feet in reporting outbreaks of bird flu to WHO and supplying virus samples for analysis -- expressed satisfaction.

"We look forward to the approval and support of Dr. Chan by the member states," a statement from the Chinese Foreign Ministry said.

Chan was chosen over four other candidates on the shortlist in a tight race to fill the post vacated by the death in May of Dr. Lee Jong-wook. In the final round of voting, she easily defeated Mexico's health minister, Dr. Julio Frenk, 24-10.

Copyright 2006 The Associated Press. All rights reserved.This material may not be published, broadcast, rewritten, or redistributed.

Find this article at:
http://edition.cnn.com/2006/HEALTH/conditions/11/08/who.elections.ap

China shares bird flu samples with global researchers

2006-11-11T00:03:00.000-05:00

Posted on Fri, Nov. 10, 2006

China shares bird flu samples with global researchers

By TIM JOHNSON
McClatchy Newspapers

BEIJING — After more than a year of international pressure, China acquiesced Friday to demands that it share samples of avian influenza virus with global health authorities but rejected a report that a new vaccine-resistant strain of the disease is spreading.

China provided samples from bird flu outbreaks in 2004 and 2005 but didn't offer samples from outbreaks this year, when the variant reportedly has flourished. The nation's chief veterinarian, Jia Youling, said 20 samples had been delivered to the Atlanta-based U.S. Centers for Disease Control and Prevention, a research partner with the World Health Organization.

At a news conference, Jia, a lead spokesman for China on bird flu issues, made little effort to assuage tensions between his nation's scientists and global health experts.

He heaped scorn on a Hong Kong researcher who alleged last month that a new variant of the deadly H5N1 virus had emerged in Fujian province and spread to Southeast Asia, and labeled as "irresponsible" an earlier CDC proposal for ending a deadlock over providing the virus samples.

"There is no such new `Fujian-like' variant at all. It is utterly groundless to assert that the outbreak of bird flu in Southeast Asia was caused by avian influenza in China," Jia said.

The harsh words reflected resentment in China at what it contends is a lack of acknowledgement of its successful efforts to identify earlier strains of the virus.

They also underscored tensions over whether China conceals information about outbreaks that could threaten the globe. In late 2002, China initially covered up an epidemic of severe acute respiratory syndrome, which eventually killed more than 770 people worldwide.

The World Health Organization's China representative, Henk Bekedam, said he was "very encouraged" that China had offered the bird-flu virus samples, and would "follow up instantly" to press for samples isolated this year.

"Viruses do change, and we need to monitor the change," Bekedam said.

Global health workers require updated virus samples to prepare effective vaccines as new strains of disease emerge.

Pressure on China mounted last week when the journal U.S. Proceedings of the National Academy of Sciences published a study by scientists in Hong Kong and the United States reporting that a new bird-flu variant was detected in March 2005, then spread across six Chinese provinces and regions and to Hong Kong, Laos, Malaysia and Thailand.

The journal says current vaccines aren't as effective against the new strain.

Chen Hualan, the head of China's bird-flu reference laboratory, said the charge wasn't true and that existing vaccines continued to contain the disease.

Bird flu largely has fallen out of the headlines because it hasn't mutated into a strain that passes easily among humans. U.N. experts said last year that bird flu threatened to become a global pandemic that could kill millions of people.

Deaths from avian flu remain contained. It's killed 74 people worldwide so far this year, up from 42 in 2005 and 32 in 2004.

Frictions between China and foreign researchers soared after two past cases in which foreign scientists received Chinese viral samples and later published articles failing to acknowledge that China was the first to isolate and identify the viruses.

China and the CDC sparred over a different issue earlier this year: how to transport virus samples. Jia said U.S. scientists had suggested that samples of bird flu viruses be labeled as "samples for testing" rather than "highly virulent" material, which requires stiffer precautions.

"We deem it irresponsible either for China or for other countries to say those viruses are not highly virulent," Jia said.

The CDC couldn't be reached immediately for comment.

--------------------------------------------------------------------------------

© 2006 McClatchy Washington Bureau and wire service sources. All Rights Reserved.
http://www.mercurynews.com

Chinese scientists identify deadly gene in H5N1

2006-11-10T23:58:00.000-05:00

Chinese scientists identify deadly gene in H5N1
Reuters
HONG KONG - Chinese scientists have identified a gene in the H5N1 bird flu virus which they say is responsible for its virulence in poultry, opening the way for new vaccines.

There are many different strains of H5N1, some of which kill more than half the people they infect, while others do little or no harm.

"We can now understand how this virus becomes lethal and the molecular basis for its pathogenicity," Bu Zhigao at the Harbin Veterinary Research Institute told Reuters.

The Chinese researchers zeroed in on the virulent gene after analyzing two closely related strains of the H5N1 obtained from infected geese in southern Guangdong province in 1996 -- one highly pathogenic in chickens and the other harmless.

Differences between the two strains were located in four genes, they found.

The scientists designed four genetically modified viruses each containing one of the four genes in question and tested them on laboratory chickens.

Only chickens infected with the modified virus containing the highly pathogenic gene died. The other chickens had no signs of disease, the scientists wrote in the November issue of the Journal of Virology.

"Now that we know the special role of the (highly pathogenic) NS1 gene, we can think about developing a vaccine," Bu said, adding that a vaccine which neutralizes the gene known as NS1 could be quickly designed.

"Technically, that can happen very soon, but it is the tests and other procedures that will take a long time."

The scientists are from the Ministry of Agriculture's Animal Influenza Laboratory, the National Key Laboratory of Veterinary Biotechnology, Chinese Academy of Agricultural Sciences, and the Harbin Veterinary Research Institute.

H5N1 remains largely a disease in birds although it has killed over 150 people, mostly in Asia, since 2003. Experts fear that it can spark a pandemic and kill millions of people if it begins to transmit efficiently among humans.

Copyright 2006 Reuters News Service. All rights reserved.
Copyright © 2006 ABC News Internet Ventures

IBM Races H5N1

2006-09-20T11:45:00.000-05:00

IBM Races H5N1
By John Russell
Sept. 18, 2006 | Sometimes it’s good to be Goliath. Unlike most (perhaps all) of its IT brethren, IBM has the size and breadth of technology expertise to make waves in basic research beyond IT and to tackle global projects that enable Big Blue to do well by doing good. The Global Pandemic Initiative (GPI) formally launched in May is a perfect example of that capacity.

“[It’s] an attempt to do a group of projects we believe will basically help the world get ready for the possibility of a 1918-like influenza pandemic,” says Joseph Jasinski, program director, healthcare and life sciences, at IBM Thomas Watson Research Center, Hawthorne, N.Y. “The economic impact would be more devastating, we believe, than in 1918 when the world was a relatively isolated place.”

That’s a tall order but reflective of Big Blue ambition. IBM Research is the technology engine underpinning many of IBM’s eye-catching projects, and the Watson Lab, with its abundance of technological exotica and supercomputing resources, is the soul of IBM Research.

Consider the scope of the GPI. IBM assembled and advisory board of world health organizations, NGOs, and universities and “basically asked them what they thought IT could do or a company like IBM could do that wasn’t currently being done in helping to get the world ready,” says Jasinski. What emerged are three projects currently under way:

• Checkmate is an effort to computationally model the influenza virus family and to “anticipate” problematic mutations in flu virus

• STEM (spatio temporal epidemiological monitor) is a nearly finished open-source modeling framework intended to help health officials worldwide build better predictive models and play more what-if games in terms of public planning scenarios

• Work with MECIDS (Middle East Consortium for Infectious Disease Surveillance) hopes to create an interoperability framework to share food- and waterborne disease information in real time.

Clearly, IBM hopes to leverage the resulting technology and public goodwill to create future business opportunities (and why not), but the projects also have clear public benefit and collectively represent a scale of undertaking that would deter smaller companies.

“[Checkmate is] a project between the Scripps Institute in Florida and IBM Research using their experimental biology and our Blue Gene supercomputer in the Watson lab, which is the second fastest machine in the world currently,” says Jasinski. “The name Checkmate comes from playing chess with the virus and ultimately figuring our where its going before it gets there.”

“We are looking at the phylogeny of all influenza viruses, H5N1, being a particularly nasty one,” says Ajay Royyuru, senior manager, computational biology center. “What if we could understand all the potential mutations that are available to influenza viruses and figure out ways in which we can recognize new variation, particularly harmful ones, before the viruses has chance to get into those evolutionary niches?”

Moving Target
Traditional approaches, says Royyuru, are often too slow: “You look at what exists today in bird and human populations; you characterize that strain; and you develop vaccines or antibodies or therapeutics against that particular known strain. I’m not dismissing that strategy. It’s quite useful, but there is a hit-or-miss attribute to this reactive strategy, and the problem is you do not get enough time to react.”

“What if the target is actually moving faster than the time it takes for you to react? Then you’re basically caught without an appropriate response strategy if the virus is evolving very fast. Which is the case when you have widespread infection in either animal or human population. The selection pressure on the virus is enormous at that point, and you will have a lot of escaped mutants occurring quite rapidly,” he says.

Large-scale computing is the key to tackling projects such as Checkmate, and Royyuru divides it into two branches: data driven and compute intensive.

“We get quantities of data that were unimaginable just a decade or 15 years ago. Data-driven computing is basically allowing you to take more data and make sense of it. And it’s not a huge amount of computing. It’s not a huge amount of flops. It’s just being able to put a lot of data together and draw arrows between points of data to conceptualize what the connectivity is and integrate the data,” he says.

The problem is, he says, you don’t really know “what happens when you throw the switch on. So it’s the dynamics and the interactions between the entities which you are trying to probe, not just the presence or absence of the entity or just the relationships between them.” Modeling and simulation is the compute-intensive part of large-scale computing and Blue Gene’s strength.

Checkmate requires both large data set handling and simulation horsepower. Other GPI projects, such as STEM, are less compute intensive but consume lots of data and will be only effective if many users can access it and contribute data — an ideal application for grid computing such as the World Community Grid developed by IBM.

STEM is currently available free for use for nonprofits on IBM’s alpha site, as a standalone application will soon be passed to an open-source community, Eclipse, run by the Open Healthcare Framework. The idea is to build an open-source modeling community of experts around the world who might contribute their unique data sets. Large chunks of geographic and infrastructure data are already included.

“We have a few pieces to fill in [from less developed regions]. But hopefully if we can get enough interest from the community, you might find somebody for example who’s an expert in migratory bird pathways and has the world’s best data set on where birds go, particularly relevant in H5N1. From the poultry industry or university research on poultry you might get data sets on where all the chicken in the worlds are,” says Jasinski.

IBM envisions health organizations creating specific models for their particular use. “You know, 14 people showed up sick in NYC in Queens with this particular disease on Monday. How many cases will there be by Tuesday? What are the next cities to be impacted and so forth? If you can do that at a reasonably accurate level then you can start to try to develop rational response strategies, for example, should I close the airports? Will that do any good in this day and age? Where should I position antiviral drugs or vaccines?”

There could even be commercial applications, says Jasinski. “We can imagine it being used as the front end to other commercial products. If I wanted to understand how my business would fare depending on where my locations are and what kind business I’m in and what my cash flows are like and that kind of stuff. You can imagine using the epidemiological model as an input to that kind of an analysis.”

The MECIDS project is still in planning. Its membership consist of the ministries of health of Israel, Jordan, and the Palestinian Authority, and since the United States has embargoed Hamas, IBM is required us to get an additional license, which it’s now doing.

One question is whether there is a shortage of biologists sufficiently comfortable with high-end computing to use tools such as Blue Gene to attack complex problems. Says Royyuru, “I think there is a small gap that still needs to be bridged between folks who do computation, computational biologists included, versus biology as field or discipline as a whole. We’re beginning to make some progress and getting people to talk to each other and understand each other more, but a lot more needs to be done.”

Ever the optimist, Royyuru adds, “Do we have enough compute capability to answer all the complexity that we know exists in biology? Certainly not. [But] I think for simple molecular processes we are beginning to approach that point.”

Email John Russell at john_russell@bio-itworld.com.

WHO Chief: Bird Flu Funds Still Needed

2006-09-20T11:18:00.000-05:00

WHO Chief: Bird Flu Funds Still Needed

By MARGIE MASON
The Associated Press
Tuesday, September 19, 2006; 3:41 PM

AUCKLAND, New Zealand -- The World Health Organization still lacks half the funds it needs to help countries fight bird flu as more human cases are expected in the coming months, the acting director-general said Tuesday.

WHO needs $90 million to $100 million over a two-year period, but has only received about half that amount, Anders Nordstrom told The Associated Press.

"We have still not been able to fill the gap. There's still a shortfall," Nordstrom said. "We still are able to respond when there are outbreaks, but to be able to really work with countries to build up good surveillance systems and information systems, we do need more resources."

He said individual countries also need to come up with more funding to help strengthen surveillance and rapid-response systems within their borders.

International donors in January pledged $1.9 billion in Beijing to help fight bird flu and prepare for a pandemic, but only a portion of that money has been disbursed.

Nordstrom spoke on the sidelines of the weeklong annual WHO Western Pacific regional meeting in Auckland, New Zealand, which brings together health officials from across the Asia-Pacific to set the organization's strategic agenda for coming years.

Bird flu has remained a top item on the meeting's agenda for the third straight year. Experts fear the H5N1 virus will mutate into a form that spreads easily among people, potentially sparking a pandemic. So far, most human cases have been linked to contact with infected birds.

As the cooler months approach, Nordstrom said another spate of poultry outbreaks and human infections will likely emerge, but added that many countries have made great strides to combat the virus.

"I think we will see the same pattern," he said. "If we look back three years, we have had a peak starting in January and February, and what has changed over the last three years is that we have seen cases in more and more countries, both in birds and in human beings."

Representatives from nearly 20 countries pledged their support and vowed to continue working together to prepare for a worst-case scenario, with several Pacific island nations requesting help in monitoring migratory birds.

Singapore Health Minister Khaw Boon Wan said his city-state has already held two practice drills and he encouraged more countries to set up mock events.

"I think almost certainly if there were to be a crisis, very likely it would originate from our part of the world," he said. "So our region should really be exemplary in showing the rest of the world how you can avoid this crisis and should it happen, how to minimize it."

The H5N1 virus has killed at least 144 people since it began ravaging Asian poultry stocks in late 2003.

On Tuesday, delegates also tackled the topic of chronic ailments such as heart disease, diabetes and cancer, which are the world's No. 1 killers, causing 35 million deaths a year _ 60 percent of all deaths worldwide. Globally, 1 billion people are overweight or obese, according to the WHO.

"What we have before us is an overwhelming pandemic of chronic diseases," said Robert Beaglehole, director of the WHO's Geneva-based chronic diseases department. "It used to be thought that these were conditions of rich people and rich countries, but now we know in fact that 80 percent of all deaths from chronic disease occur in low- and middle-income countries."

Just as countries taxed tobacco and decreased advertising, governments can do the same for sugary drinks and fatty foods, he said. Children and teenagers also can be offered healthy foods in school and be encouraged to exercise.

At the meeting, top health officials demonstrated their commitment to fighting obesity and chronic disease by working out to an exercise video played on the conference-room screen.

Non-communicable diseases are blamed for seven out of every 10 deaths among the Western Pacific region's 1.8 billion people.

"It is crucial that we not just talk about this issue _ that we walk the talk," said Australian Health Secretary Jane Halton. "We are the department of health, and we should practice what we preach."

© 2006 The Associated Press

Bird Flu Fight Will Cost More Than $1.9 Billion, UN Envoy Says

2006-09-17T22:18:00.000-05:00

Bird Flu Fight Will Cost More Than $1.9 Billion, UN Envoy Says

By Jason Gale and Damien Ryan

Sept. 18 (Bloomberg) -- The global effort to fight bird flu and prepare for a threatened pandemic will cost more than the $1.9 billion already pledged, and more support is needed in Indonesia, which is ``seriously affected'' by the virus, a United Nations envoy said.

David Nabarro, the UN's senior coordinator for avian and pandemic flu, said the money promised by donor countries and organizations at a conference in Beijing in January won't be enough to sustain programs aimed at identifying and controlling the virus in poultry, and upgrading laboratories and hospitals.

``We are just at the beginning,'' Nabarro, 57, said yesterday in an interview in Singapore, where he was attending the annual meetings of the Washington-based International Monetary Fund and the World Bank. ``We are going to need to have a pipeline of funding for further work in the next few years both in the animal sector and also in the human sector.''

Human fatalities from the H5N1 avian influenza strain have almost tripled this year, providing more chances for the virus to mutate into a lethal pandemic form. A severe pandemic similar to the one that killed 50 million people in 1918 may cause global economic losses of as much as $2 trillion, Jim Adams, head of the World Bank's avian flu taskforce, told reporters in Singapore yesterday.

The H5N1 virus is known to have infected 246 people in 10 countries, killing 144, since 2003, the World Health Organization said on Sept. 14. Millions could die if it becomes easily transmissible between people, causing a global outbreak.

``We cannot predict how it will happen, and so we encourage communities, governments, and private entities to get prepared for a pandemic that might start anytime,'' Nabarro told reporters in Singapore yesterday.

Virus Hotbed

More than half the 66 fatalities reported this year have occurred in Indonesia, where the virus is reported to have infected at least two people a month during the past year.

Indonesian authorities have intensified efforts to control the virus during the past few months, Nabarro said. ``I am very impressed with the progress that I have seen, but I want to see greater investment not only by government but also by the international community in Indonesia.''

The World Bank is finalizing an agreement with the Indonesian government on a $15 million grant, Adams said. About $1.2 billion of the $1.9 billion promised in January has been committed, he said. At least part of the $700 million that's not yet committed may be directed at programs in Africa.

Representatives of about 100 countries will meet in Mali's capital, Bamako, later this year to discuss funding needs.

Funds for Africa

``There will be on the table a request for some increases in dedicated funds to Africa,'' Adams said in an interview. ``What we will be looking for from Bamako are some incremental commitments from donors, either from unallocated or additional funds, to fund the specific African programs that are going to emerge.''

In Africa, where H5N1 was first reported in Nigeria in February, the virus has spread to Niger, Egypt, Cameroon, Burkina Faso, Ivory Coast and Djibouti.

The continent will require $760 million over the next three years to help prevent avian flu, according to a report released in June by a coalition of international governmental organizations known as the ALive initiative.

Avian flu in Africa could spread rapidly because of insufficient financial and logistical resources, weak veterinary services, lax border controls and government conflicts, the coalition said in its report.

``There is a shortage of funds in some of the countries that really are fighting an uphill struggle to control avian influenza and also to prepare for the pandemic,'' Nabarro said. ``Please make sure that Africa, that Indonesia, and that countries with great needs do manage to access the resources they require.''

To contact the reporters on this story: Jason Gale in Singapore at j.gale@bloomberg.net ; Damien Ryan in Singapore at dryan3@bloomberg.net .

Last Updated: September 17, 2006 20:29 EDT

Scientists reveal how H5N1 kills

2006-09-17T22:12:00.000-05:00

Scientists reveal how H5N1 kills

Scientists have discovered a potential reason to explain why the H5N1 strain of bird flu is so much more deadly to people than standard human flus.

A team in Vietnam compared people infected with the different flus.

The Nature Medicine research found that the bird flu virus triggers a massive inflammatory response, which often proved fatal.

A UK expert said the study provided vital information about how best to treat people infected with the virus.

There have been 241 cases of people being infected with H5N1 since the outbreak started in 2003. Over half died from the disease.

The team from the Oxford University Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, looked at 18 people who had had H5N1 and eight who had had normal human flu.

They looked at the level of the viral load - the concentration of the relevant virus in a person's blood, and at how the person's immune system had responded to infection.

Blood cells

It was found that the patients infected with H5N1 had much higher viral loads in the throat than those patients infected with the human flu virus.

And the markers of viral load were highest in the H5N1 patients who had died.

Virus could also frequently be detected in the blood of H5N1 patients, but only in those who died.

The researchers noted that the presence of high levels of H5N1 virus triggered a release of proteins called cytokines which should control a body's response to infection.

The highest levels of cytokines were seen in those with the highest viral loads- who were those who had died.

In these cases there was also an associated loss of lymphocytes (types of white blood cell) in the peripheral blood.

The team suggests it is these factors which lead to lung damage and, on many occasions, death.

Dr Menno de Jong and his colleagues wrote in Nature Medicine: "The focus of clinical management should be on preventing this intense cytokine response, by early diagnosis and effective antiviral treatment."

Professor John Oxford, a virus expert based at Barts and The London NHS Trust in the UK, said: "This clearly puts the emphasis on the level of virus a person has.

"The higher it is, the higher the chance of death."

He said it showed people infected with H5N1 should be treated with antiviral drugs - Tamiflu, Relenza or amantadine - in order to reduce the amount of virus in their systems.

Professor Oxford said the information would also help if the virus mixed with a human flu and mutated into a form which was easily transmitted between people.

He added: "We are lucky this is happening now. If it had been the 1970s or 80s, we would not have had these antiviral drugs to turn to."

Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/5327204.stm

Published: 2006/09/11 06:44:03 GMT

© BBC MMVI

Human-to-human transmission possible in Indonesia's 65th avian flu case

2006-09-17T22:06:00.000-05:00

Human-to-human transmission possible in Indonesia's 65th avian flu case
Sep 14, 2006 (CIDRAP News) –

The World Health Organization (WHO) today recognized two cases of H5N1 avian influenza in Indonesia, including one from March that was first reported yesterday by a WHO official and one from May involving a man who may have become infected after exposure to an ill family member.

In both instances, the WHO has retroactively confirmed the cases on the basis of its new criteria for laboratory confirmation. The boy's case put Indonesia's count at 64 cases with 49 deaths, and the man, who recovered, represents the country's 65th officially confirmed case.

The 5-year-old boy from East Bekasi in West Java province became ill on Mar 4, was hospitalized 2 days later, and died on Mar 19. The WHO said test results using two different assays revealed high antibody titer for H5N1 on serum samples taken on days 11 and 15 of his illness. Field investigators had determined that the boy had been exposed to sick poultry near his home, where some birds had tested positive for the H5 virus subtype.

Investigators identified the second case, in a 27-year-old man from Solok in West Sumatra province, when they traced contacts of the man's 15-year-old sister who had a confirmed H5N1 infection in May. Her brother spent 6 days caring for her during her hospitalization. On May 28 he experienced mild cough and abdominal discomfort but no fever. His symptoms improved and he recovered in a few days.

Despite his mild and atypical symptoms, the brother was tested as part of the health ministry's contract tracing and management program. He was given a 5-day course of oseltamivir beginning Jun 1 and was placed in voluntary isolation during his recovery.

Initial samples were negative for H5N1 infection; however, in August, follow-up testing of paired-serum samples found a fourfold rise in neutralization antibody titer for H5N1, a result that meets WHO's new criteria for laboratory confirmation.

The man reported no contact with diseased or dead poultry before he became ill. Investigators determined that human-to-human transmission resulting from exposure to his sister could not be ruled out.

The WHO issued a report confirming his sister's H5N1 infection on May 29. It said she remained hospitalized, but no details were available on the outcome of her illness.

In other developments in Indonesia, the director of the country's main treatment center for avian flu told participants attending a scientific conference in Jakarta yesterday that avian flu will continue to circulate among the country's poultry flocks because of shortfalls in vaccination and biosecurity measures, according to an article today in The Jakarta Post.

Santoso Soeroso, director of Sulianti Saroso Hospital, said improper vaccination of ducks and chickens may be contributing to the spread of the H5N1 virus. He said authorities are using substandard vaccines and are unable to evaluate the effectiveness of the programs because they lack an unvaccinated control group.

Soeroso said recent research in Bali province revealed a vaccine failure rate of 39% and that 60% of the area's ducks had avian flu.

Indonesian agriculture minister Bagoes Poermadjaja told the group that only 60% of the country's 300 million chickens and ducks had been vaccinated. He said the country lacked resources of early detection and is not adequately compensating citizens for slaughtered birds.

He said biosecurity measures are also deficient, and he noted that most cases of avian flu in humans had occurred in provinces where transport of poultry is constant. Poermadjaja also said weak coordination between central government and regional administration hinders the coordination of avian flu prevention and management.

See also:

Sep 14 WHO statement
http://www.who.int/csr/don/2006_09_14/en/index.html

May 29 WHO statement
http://www.who.int/csr/don/2006_05_29/en/index.html

Center for Infectious Disease Research & Policy
Academic Health Center -- University of Minnesota
Copyright © 2006 Regents of the University of Minnesota

Chinese report results for whole-virus H5N1 vaccine

2006-09-11T00:25:00.000-05:00

Chinese report results for whole-virus H5N1 vaccine
Sept 7, 2006 (CIDRAP News) – In a human trial in China, a whole-virus H5N1 avian influenza vaccine generated an immune response with a relatively low dose of antigen, suggesting that it could be used to immunize more people than may be possible with some other vaccines under development.

The study, published online today in The Lancet, showed an adequate immune response in 78% of volunteers after two 10-microgram (mcg) doses of the vaccine plus an aluminum hydroxide (alum) adjuvant. That exceeds the European Union's requirement of an acceptable response (a hemagglutinin-inhibition titer of 40 or more) in 70% of volunteers.

The vaccine is made by Sinovac Biotech in Beijing, China, from an inactivated strain of H5N1 known as Vietnam/1194/2004. The report says that Sinovac was involved in designing and monitoring the study but played no role in collecting the data or writing the report.

The randomized, placebo-controlled, double-blind study involved 120 adults (aged 18 to 60). They were divided into five groups of 24, with each group receiving either a placebo or 1.25, 2.5, 5, or 10 mcg of the vaccine.

Each volunteer received the vaccine on the first day of the study and 28 days later. Serum samples were assessed for evidence of an immune response on days 0, 14, 28, 42, and 56.

An antibody response was seen after the first injection at all dose levels. The highest response (78% seropositivity) was seen in the 10-mcg group after two doses.

The investigators reported that all four doses were well tolerated, even though whole-virion vaccines are generally thought to cause more reactions than split-virion vaccines. No serious reactions were reported, and most local and systemic reactions were mild and brief. Three people dropped out of the study, and one person was excluded from the final analysis.

The authors concluded that the dose required to reach an acceptable immune response was much lower than for vaccines reported in previous studies. Two reports published earlier this year described trials of a split-virus H5N1 vaccine developed by Sanofi Pasteur. The reports said two 90-mcg doses of nonadjuvanted vaccine or two 30-mcg doses of adjuvanted vaccine were required to produce the desired immune response.

(In July, GlaxoSmithKline reported a good immune response in 80% of volunteers who received a dose of only 3.8 mcg of the company's adjuvanted H5N1 vaccine. However, a full report of those findings has not yet been published.)

"The manufacturing capacity for an H5N1 vaccine would increase if a whole-virion vaccine is used, because 20% to 30% of vaccine antigen is expected to be lost during the disruption process in the preparation of split-virion vaccines, according to our experience with seasonal influenza vaccine," the Chinese researchers write.

In an accompanying commentary, Iain Stephenson, MD, of the Infectious Diseases Unit at Leicester Royal Infirmary in Leicester, England, writes that the findings point up of "a potential dose-sparing approach that could be crucial for a global supply of pandemic vaccine."

He says that trial results for split-virion H5N1 vaccines have been disappointing, because within current manufacturing constraints, the two such vaccines under development would yield only enough to vaccinate 75 million to 225 million people.

Though whole-virion vaccines generally produce a better immune response than split or subunit vaccines, development of whole-virion H5N1 vaccines has been delayed, Stephenson writes. He says it is difficult for manufacturers that produce split seasonal vaccines to switch production approaches and processing methods.

Stephenson cautions that whole-virion vaccines have been associated with febrile reactions in children and emphasizes that careful investigation is needed before such vaccines can be widely used.

It remains to be seen whether whole-virion vaccines can induce the broad cross-reactive response that would be needed to treat a variety of H5N1 viruses, Stephenson writes.

Lin J, Zhang J, Dong X, et al. Safety and immunogenicity of an inactivated adjuvanted whole-virion influenza A (H5N1) vaccine: a phase 1 randomised controlled trial. Lancet 2006 (early online publication, Sep 7) [Abstract (registration required)]

Stephenson I. H5N1 vaccines: how prepared are we for a pandemic? (Commentary). Lancet 2006 (early online publication, Sep 7)

See also:

May 12 CIDRAP News story "Sanofi reports results for H5N1 vaccine with adjuvant"

Jul 26 CIDRAP News story "Glaxo says its H5N1 vaccine works at low dose"

Center for Infectious Disease Research & Policy
Academic Health Center -- University of Minnesota
Copyright © 2006 Regents of the University of Minnesota

Advice on treating bird flu: Hit it hard and early

2006-09-11T00:23:00.000-05:00

Advice on treating bird flu: Hit it hard and early
By Donald McNeil The New York Times
SUNDAY, SEPTEMBER 10, 2006

Avian flu kills in much the same way the 1918 flu did, by drowning victims in fluid produced in their own lungs, a new study has found.

The study also suggests that immediate treatment with antiviral drugs is crucial, because the H5N1 virus reproduces so quickly that, if not suppressed within the first 48 hours, it tends to push victims into a rapid decline to death.

"The paradigm 'hit hard and hit early' probably is very true for H5N1 influenza," said Menno de Jong, an Oxford University virologist and the study's lead author.

However, he added, because the body's own immune response does part of the damage, doctors should consider giving anti-inflammatory drugs along with antivirals like Tamiflu.

Although the results of the relatively small study are precisely what flu experts had predicted from laboratory work, Anne Moscona, a professor of pediatrics and immunology at the Weill Medical College of Cornell University, called it a "major advance" because so little clinical information had previously been gleaned from the 241 known cases of the disease.

Many of those cases have been in rural villages in Asia, where victims get the virus from backyard chickens and are buried before the virus that killed them is even identified. Provincial hospitals have done few autopsies and little genetic analysis.

This study, which appears in the October issue of Nature Medicine, was led by an Oxford research team in Ho Chi Minh City, Vietnam, and compared 18 people with the H5N1 avian flu in 2004 and 2005 to eight people infected with seasonal human flus.

It found that bird flu patients, and particularly the 13 who died from it, had unusually high levels of virus in their bodies. Consequently, they also had high levels of the chemicals, known as cytokines and chemokines, that trigger the immune system's inflammatory response.

Those chemicals, some of which are produced in cells lining the narrowest passages in the lungs, draw in white blood cells to attack invaders. But doing so too vigorously can flood the lungs, causing deadly pneumonia.

The effect, known as the "cytokine storm" is the leading theory as to why so many young, previously healthy people died in the 1918-19 pandemic, known as the Spanish flu. Young adults have stronger immune systems, and accounts of the deaths of recruits in World War I military camps describe whole rows of men turning blue-black as they struggled for breath.

The virus was also found in the blood of most patients who died. It probably leaked in from their lungs, de Jong said, which showed that the disease has the same potential to reach and destroy other organs in humans as it does in birds.

It was easier to detect in throat swabs than in nasal swabs, de Jong said, which is the opposite of seasonal flu and useful for doctors doing flu tests. And it was found in rectal swabs, which is important for hospitals to know because it means diarrhea, common among flu patients, can also spread the disease.

Flu experts were surprised that such high viral loads were found in nose and throat swabs. Earlier studies had suggested that the avian flu is not easily transmitted between humans because, unlike seasonal flu, it primarily attaches to receptors found deep in the lungs.

De Jong said there could be several explanations: The throat swabs could have picked up virus coughed up from the lungs. Different receptors are spread up and down the breathing tract.

It is also possible, although unproven, that some people might simply be born with receptors more amenable to the virus. That theory has been offered before by epidemiologists noting that, even in villages where all the chickens are sick, human outbreaks tend to cluster in families.

The study also showed that some of the flu strains isolated in Vietnam had particular genetic changes that virologists have been watching for, fearing they would make them more lethal.

One, known as an E627K substitution on the PB2 gene, has been much discussed on Web sites devoted to the flu because, in laboratory tests, it lets the virus reproduce 20 times faster at the lower temperatures found in mammals' cool noses as compared to those found in birds' hot intestines.

But those changes appeared in only some patients, and in patients who died and those who lived "so I wouldn't make too much of it," Moscona said.

Copyright © 2006 The International Herald Tribune | www.iht.com

Bird flu triggers high and sustained virus buildup, cause of severe disease

2006-09-11T00:20:00.000-05:00

Bird flu triggers high and sustained virus buildup, cause of severe disease
15:13:05 EDT Sep 10, 2006
Canadian Press: HELEN BRANSWELL

(CP) - The severe disease that H5N1 avian flu provokes in people appears to be caused by the virus's ability to replicate at unusually high levels for a prolonged period - an overwhelming assault that triggers a massive and devastating immune system response, a new scientific paper suggests.

Interrupting that process before it reaches the tipping point is critical, say the authors of the article, who based their observations on detailed study of 18 H5N1 patients in Vietnam.

But experts unrelated to the research wonder whether the current anti-flu arsenal - mainly neuraminidase inhibitors such as Tamiflu - is equipped to do that job.

"The question I worry about is whether treating patients now with neuraminidase inhibitors may be very much like shutting the barn door after the horse is already out," said Dr. Michael Osterholm, director of the Center for Infectious Diseases Research and Policy at the University of Minnesota.

"I don't know that. But we've got to find that out."

The World Health Organization is in the process of setting up a research network across countries afflicted with H5N1, in the hopes that joint studies will answer questions like the one Osterholm poses.

Dr. Frederick Hayden, an antiviral expert who heads the effort, said the first task will be to investigate whether different dosing regimes for Tamiflu might achieve better results.

As well, the group hopes to look at whether a flu drug that could be administered intravenously would be more effective at combating H5N1 infection. Injectable forms of two drugs - peramivir and zanamivir - are in development.

"A potent parenteral (injectable) agent ... is really needed and will give us the ability, I hope, to more rapidly control replication in patients with these kinds of severe infections," Hayden said.

The paper, to be published Monday in the journal Nature Medicine, is the first detailed record of the disease process or pathogenesis of H5N1 in humans. The observations are based on 18 H5N1 patients who were treated in Vietnam during 2004 and 2005. Thirteen of them died.

The researchers charted the way H5N1 replicated in those cases and how their immune systems responded. The massive amounts of virus generated triggered production of excessive levels of some chemokines and cytokines, chemicals used to attract white blood cells - the body's cleanup crew - to the site of infection.

This hyperactive immune response - called a cytokine storm - actually does more damage than it sets out to fix. And scientists aren't clear on how to suppress the damaging parts of that process without disabling the immune system's ability to fight the virus.

Lead author Dr. Menno de Jong suggested the key is early treatment with antivirals, perhaps combined with drugs that modify the immune response.

"The paradigm 'Hit hard and hit early' which has been used for treatment of HIV-AIDS in the past may well be very true for the treatment of avian flu," said de Jong, a physician and virologist with Oxford University's Clinical Research Unit at the Hospital for Tropical Diseases in Ho Chi Minh City.

"Considering the likely role of the immune response in causing damage during the later stages of infection, it obviously makes sense to think about the use of anti-inflammatory or immune-modulatory treatment," he said in an e-mail interview.

"However, we still know relatively little about which part of the immunological cascade is best targeted and how to target this."

The director of the U.S. National Institutes of Allergy and Infectious Diseases said more needs to be known about the way the virus interacts with a human host. That could shed light on when antiviral drugs would have maximum impact on replication and the cytokine storm phenomenon, Dr. Anthony Fauci said in an interview.

But finding that optimal point may not be easy, he suggested, because influenza replication typically peaks as people are becoming symptomatic and the immune response is already kicking into gear.

"To me that's almost a catch-22," Fauci said.

"Because if you know the person is infected and has virus replication only when they become symptomatic, then depending on how long that peak lasts, will you or will you not be able to have a substantial impact on it by (administering) antivirals?"

Osterholm for one is pessimistic on that count, suggesting neuraminidase inhibitors like Tamiflu may be better suited to preventing H5N1 infection rather than treating the ensuing disease once it's apparent someone is infected.

If that's true, he advocates stockpiling the drugs to protect health-care workers and keep hospitals operational during a pandemic rather than using the drugs for treatment, as the pandemic plans of many countries - including Canada - currently stress.

De Jong's paper also clearly underscores the differences between the disease provoked by H5N1 and that caused by human flu strains.

It notes, for instance, that swabbing the pharynx to look for virus is a more effective way to diagnose H5N1 than taking a nasal swab. With human flu strains, the reverse is true.

The researchers also found traces of the virus in the blood and rectum of critically ill patients. While that could be a hint the virus replicates in organs outside the respiratory tract and the lungs, it isn't proof positive, de Jong said.

Autopsies of H5N1 patients would needed to determine that, he and others said. But because of cultural objections, autopsies have been performed on fewer than a handful of the 143 people known to have died of H5N1 so far.

© The Canadian Press, 2006

Satellites Track Migratory Birds in Fight Against Avian Influenza

2006-09-10T14:02:00.000-05:00

Satellites Track Migratory Birds in Fight Against Avian Influenza
--------------------------------------------------------------------------------

Posted on: 09/07/2006

Wearing light solar-powered GPS satellite transmitters, wild swans from Mongolia are winging their way across Eurasia, while land-bound scientists tracking the birds’ journeys on computers say that these unique studies will shed light on how wild birds may be involved in the spread of avian influenza.

In August, a team of international scientists from the United Nations Food and Agriculture Organization (FAO) and the U. S. Geological Survey (USGS) joined the Wildlife Conservation Society (WCS) and MongolianAcademy of Sciences (MAS) in the surveillance project, which is part of the Wild Bird Global Avian Influenza Network for Surveillance (GAINS) program funded by USAID. The team attached the GPS transmitters to wild whooper swans in an effort to track the birds to their wintering grounds.

Such research is providing information on migration routes and informs governments about potential threats from diseases such as highly pathogenic avian influenza (HPAI). The HPAI strain known as H5N1 is highly lethal for a variety of species, especially poultry and some waterfowl species. When transmitted to people through close contact with infected birds, the virus can be deadly. Leaders across the world are concerned about a potential pandemic threat should the virus become transmissible among humans.

“We are working to understand the role wild birds may play in the spread of H5N1,” said Dr. Scott Newman, international wildlife coordinator for avian influenza for the FAO, seconded from Wildlife Conservation Society, and based in Rome, Italy. “Although poultry and bird trade are probably the primary routes of movement, migratory birds are likely involved in some areas.”

The whooper swans drew increased attention after large numbers perished in Mongolia in 2005 and in western China in 2005 and 2006 in areas where few poultry are present. Subsequent sampling of the dead swans by WCS scientists Drs. Martin Gilbert and William Karesh, verified that some of the swans were infected with HPAI. This discovery suggested that HPAI may be moving through the region and potentially spreads from it, prompting the study to identify where these migratory bird populations fly in the winter.

“Although we are sampling wild birds for avian influenza in the field, we will not be able to fully understand their role in this disease unless we better understand their movements,” said Karesh, who is WCS’s director of the Field Veterinary Program in New York and coordinator of the GAINS system. “WCS samples birds in East Asia under the GAINS program, but when we find infected birds, we need to know where they are going.”

Many migratory species nest thousands of miles from where they spend the winter, and it is difficult to determine which groups come from which areas, said Dr. John Takekawa, one of the wild swan study scientists, who is with the USGSWesternEcologicalResearchCenter in California. “We are marking swans with very small GPS transmitters that are similar to navigation systems on cars, but that also transmit the data through weather satellites so we can track their movements.”

The whooper swan locations are being updated twice weekly on a project webpage that also includes access to the data in Google Earth format. A comprehensive database of information on international wild bird avian influenza surveillance and migratory bird activity is available on the WCS website at http://www.gains.org.

Whooper swans were captured by the international team in early August on the grassland steppe of far eastern Mongolia, near the borders of Russian and China. Each year, swans molt their feathers after the breeding season, and during that flightless period, the birds were captured by biologists in boats and on-foot. Small, 70-gram (2.3 ounces or the weight of a dozen quarters) solar-powered transmitters were affixed on 10 of the 8-kilogram (18-pound) large swans with backpack harnesses. The harnesses are made of Teflon ribbon that deteriorates and falls off of the birds within a few years.

Takekawa noted that satellite tracking data will provide information that will not only help scientists better understand and document links between wild birds and the spread of avian influenza, but that will also help enhance conservation efforts through determining the non-breeding ranges of birds and the mechanisms involved in long-distance migration.

The GPS transmitters are made by a wildlife specialty company; it is only in the last 5 years that they were reduced to a size suitable for migratory birds. Their accurate locations, often better than 30 feet, provide a wealth of information on migrating birds and use of their habitats that was not available before. The locations are recorded every 2 hours and stored in the transmitter memory before being sent to the research team by email through weather satellites every two days.

Recommendations from the FAO-OIE International Scientific Conference on Avian Influenza and Wild Birds in Rome include improving our understanding of wild bird behavior, precise migratory strategies, locations of aggregation and convergence, and interactions between wildlife and domestic species. “The whooper swan project in Mongolia demonstrates the importance that FAO places on understanding the relationship between agricultural, wildlife, and human health,” Newman said.

The USGS serves the nation by providing reliable scientific information to: describe and understand the Earth; minimize loss of life and property from natural disasters; manage water, biological, energy, and mineral resources; and enhance and protect our quality of life.

The Wildlife Conservation Society (WCS) saves wildlife and wild lands. WCS does so through careful science, international conservation, education, and the management of the world's largest system of urban wildlife parks, led by the flagship Bronx Zoo. Together, these activities change individual attitudes toward nature and help people imagine wildlife and humans living in sustainable interaction on both a local and a global scale.

Source: Food and Agricultural Organization of the United Nations

Could blood from H5N1 flu survivors help others?

2006-09-10T13:50:00.000-05:00

Could blood from H5N1 flu survivors help others?
Robert Roos News Editor

Sep 8, 2006 (CIDRAP News) – A recent report about the use of blood products to treat patients in the Spanish influenza pandemic of 1918 has sparked interest among those concerned about the threat of the next pandemic, but experts say it's far from clear whether the approach would be practicable in a pandemic today.

In a report published last week, US military researchers said blood products obtained from recovering influenza patients apparently helped save the lives of some patients in the 1918 pandemic, and the same approach should be considered today in the face of another pandemic threat.

Combing the medical literature from the Spanish flu era, the researchers found six controlled studies in which the use of blood plasma, serum, or whole blood from recovering flu patients reduced mortality in seriously ill patients. The authors hypothesize that antibodies in the blood products blunted the effects of the flu virus.

"Patients with Spanish influenza pneumonia who received transfusion with influenza-convalescent human blood products may have experienced a clinically important reduction in the risk for death," say Thomas C. Luke, of the Navy Bureau of Medicine and Surgery, and colleagues. Their report was published online by Annals of Internal Medicine.

Luke and colleagues write that borrowed antibodies in blood products have been used to prevent and treat a number of infectious diseases, including rabies, measles, hepatitis B, cytomegalovirus, and respiratory syncytial virus.

Six studies showed benefit
The authors searched eight major medical journals for controlled trials of the use of blood products from recovering flu patients to treat a minimum of 10 severely ill patients. They found eight studies that met their criteria, ranging in size from 43 to 551 patients, with a total of 1,703. None of the trials was blinded or randomized, and the methods were rated as poor by today's standards. Most of the patients were men between the ages of 17 and 45.

Six of the eight studies showed that the treatment improved survival. The overall case-fatality rate for treated patients was 16% (54 of 336), versus 37% among the controls (452 of 1,219). In addition, all eight reports said that patients showed clinical improvement after treatment. Moderate to serious transfusion-related adverse events occurred in 4% (9 of 235) of patients in studies that included such data.

The timing of treatment made a difference. On the basis of data from four studies, patients treated within 4 days of the onset of pneumonia had an overall case-fatality rate of 19% (28 of 148), whereas those treated later had a fatality rate of 59% (49 of 83).

Acknowledged limitations of the analysis include the small size of the studies, the lack of blinding, and the lack of placebo treatment. The authors also say they can't exclude the possibility that other studies yielded negative findings but went unpublished. Therefore they couldn't reach a firm conclusion about the effectiveness of the treatment.

Nonetheless, they recommend that a committee of experts be set up to consider using plasma treatment for H5N1 patients and to recommend a research strategy.

In an editorial accompanying the report, John J. Treanor, MD, an infectious disease expert at the University of Rochester, says the strategy deserves consideration, but he also raises some caveats.

Passive immunotherapy for flu viruses, including H5N1, has worked in lab mice, Treanor writes. Such treatment prevents many viral diseases in humans, but little recent evidence supports using this approach to treat sick patients, he says. Also, obtaining and using blood products for treatment in the midst of an outbreak would involve "formidable logistical hurdles."

Proving the concept of "serotherapy" for H5N1 would require running controlled trials in regions where human H5N1 cases are occurring, Treanor asserts. He believes the effort would be worthwhile: "We can, should, and must explore these issues about serotherapy now, in advance of the pandemic."

Serotherapy called impractical
Other experts who were asked about using this approach in the next pandemic expressed views ranging from guarded interest to dismissive skepticism.

Michael T. Osterholm, PhD, MPH, didn't question the scientific plausibility of the idea, but argued that it wouldn't be practical in a pandemic. Osterholm is director of the University of Minnesota Center for Infectious Disease Research and Policy, publisher of the CIDRAP Web site.

"We won't have the capacity to do much plasmapheresis [harvesting of plasma] of recovered patients because the system—healthcare workers and equipment—will collapse," Osterholm told CIDRAP News. "And with today's safety regulation, you couldn't do it like you did in 1918."

He said supplies and equipment needed for blood transfusions and processing are likely to run out. "The entire healthcare system is a just-in-time delivery system for virtually everything. . . . You couldn't do it if you wanted to, because you just won't have the equipment. Blood banks don't have months and months of inventory on hand. The bags, tubing, needles, and reagents are made offshore."

"Transfusion medicine is going to be severely challenged during a pandemic," Osterholm said. "Just transfusing the blood we need [will be difficult], let alone doing this kind of thing."

Blood-bank official sees logistical problems
Louis Katz, MD, chair of an American Association of Blood Banks task force on pandemic flu and the blood supply, acknowledged that supplies are likely to be a problem but said that using plasma from recovered patients could be helpful in a pandemic.

The idea "is something we're trying to think about, but it hasn't made it into the first edition of our pandemic flu planning guidelines," said Katz, who is executive vice president of the Mississippi Valley Regional Blood Center in Davenport, Iowa.

He said blood banks are likely to run short of both personnel and supplies in a pandemic, but supplies are the bigger worry.

"We take delivery twice a month on critical lab reagents and once or twice a month on pheresis kits, so the maximum [inventory on hand] is a month," Katz said.

His center doesn't have space to store 8 to 12 weeks' worth of supplies, and even if it did, suppliers might not be able to ramp up deliveries to permit stockpiling, he said. "The just-in-time economy has its advantages in terms of efficiency, but in a crunch there are serious problems," he added.

Further, few recovered flu patients would be available to donate plasma in the early stage of a pandemic, Katz said. "I think there are substantial barriers to providing a lot of it during the first wave." He predicted the task would be "substantially easier" in the second wave of a pandemic.

Katz thinks blood banks could get recovered patients to donate plasma, but not until weeks into the pandemic. "I think they'd come in, but whether we could process enough [blood products] to treat meaningful number of patients, I don't know," he said.

If the pandemic resembled those in 1957 and 1968, in which "business operations weren't horribly disrupted, we probably could ramp up and make immune plasma fairly quickly," Katz said. "It totally depends on what happens."

Another question is whether the Food and Drug Administration (FDA) would approve the use of blood plasma to treat flu patients. "It's complicated, but it becomes an issue of labeling," Katz said. "As long as I didn't label it 'hyperimmune influenza plasma,' I think they'd be fairly permissive." Before allowing such a label, the FDA would require clinical trials and other steps to certify the safety, purity, and potency of the product, he said.

Summing up his thoughts on the topic, Katz said, "While theoretically it's a great idea, the logistics are going to be difficult."

Dr. Jed Gorlin, medical director of Memorial Blood Centers in St. Paul, said the concept of using plasma to treat flu patients has been under discussion in blood-bank circles for a while.

Gorlin said blood banks are worried about shortages of blood donors and of staff to collect blood in a pandemic. But he was more optimistic than Katz on the question of supplies and equipment.

The 1918 flu pandemic lasted about 2 months in most places, he said, adding, "For things like bags and so on we easily have a month and often 2 months, so that part we're not particularly concerned about." On the other hand, other supplies, such as N95 breathing masks, may well run out, he said.

"Blood centers are ahead of most hospitals in that we already have lists of critical reagents and equipment," Gorlin said. "We're already sensitive to our supply chain and in some cases we have alternative suppliers."

Transfusion specialist interested
Robert J. Bowman, MD, a transfusion medicine specialist at the University of Minnesota Medical School in Minneapolis, called the proposal "very interesting," at least theoretically.

"I am unsure of the relative success of immunoglobulin preparations in treating viral illness but given the paucity of treatment options the strategy ought to be tried," he commented by e-mail.

Criteria for acceptance of plasma donors would have to be developed, he said. Plasma could be tested for antibodies and used directly, or many units could be pooled and used to make a standardized intravenous immunoglobulin preparation (IVIG), he suggested.

"Not only do I think this is possible, I think the idea should be tried with standardized IVIG preparations," Bowman wrote. If the treatment worked, its applicability would depend on collection agencies having enough staff and enough money to pay for the IVIG, he added.

Bowman predicted that safety and other regulatory issues would be "manageable," but he acknowledged that supply interruptions could be a problem.

He also said he was uncertain how much IVIG would cost or how long it would take to prepare. "We're not talking about days, we're talking weeks or months," he said. "It takes some time to pool it, then you have to fractionate it, and then there's testing. So it's a big deal. But all the technology is there."

Luke TC, Kilbane EM, Jackson JL, et al. Meta-analysis: convalescent blood products for Spanish influenza: a future H5N1 treatment? Ann Intern Med 2006 Oct 17;145(8) (early online publication) [Full text]

Treanor JJ. Avian influenza: exploring all the avenues. (Editorial) Ann Intern Med 2006 Oct 17; 145(8) (early online publication) [Full text]

Center for Infectious Disease Research & Policy
Academic Health Center -- University of Minnesota
Copyright © 2006 Regents of the University of Minnesota

Blood Plasma From Bird Flu Survivors May Fight Virus

2006-09-09T01:04:00.000-05:00

Blood Plasma From Bird Flu Survivors May Fight Virus (Update2)

By Jason Gale and Vesna Poljak

Sept. 5 (Bloomberg) -- An infusion of blood products from bird flu survivors may help fight the virus, according to doctors who studied such treatments used during the 1918 Spanish influenza pandemic that killed 50 million people.

Treating patients in 1918 with blood, plasma or serum obtained from people who recovered from Spanish flu cut mortality of seriously ill patients by 50 percent, the doctors said a report in the online edition of next month's Annals of Internal Medicine. The finding is based on an analysis of studies conducted more than 86 years ago.

Disease trackers are searching for ways to treat the H5N1 avian flue strain, which has infected at least 241 people in 10 countries, killing 141 of them, since 2003. The virus may kill millions if it sparks a global outbreak, especially since vaccines and antiviral drugs won't be widely available in the first months.

``Passively delivered anti-influenza antibodies in convalescent human plasma obtained from H5N1 survivors may offer a novel treatment approach and possible solution to these problems,'' said authors Edward Kilbane, Jeffrey Jackson and Thomas Luke, from the Uniformed Services University in Bethesda, Maryland, and retired Navy physician, Stephen Hoffman.

Scientists are seeking clues from the 1918 outbreak, the deadliest of the 20th century's three major pandemics, about how to treat H5N1 patients and how to prepare for a new contagion. Similar disease patterns and a tendency to kill younger people have been observed in both Spanish flu and H5N1.

CSL's Plans

CSL Ltd., the world's second-largest maker of blood plasma products, hasn't considered bringing on new treatments for avian and pandemic flu beyond a candidate vaccine that it's developing, Mark Dehring, a spokesman for the Melbourne-based company said in a telephone interview today.

``It's probably something we'd have a look at more so at the end of this year,'' when clinical trials on the vaccine are concluded, he said.

Producing blood products for flu is ``well within our capabilities,'' Dehring said. ``We're certainly keeping our eye on it.''

Antibody infusions have been used to prevent and treat diseases such as rabies, measles, hepatitis B, cytomegalovirus, and respiratory syncytial virus, and human plasma may be effective in the treatment of severe acute respiratory syndrome, or SARS, the authors said.

Blood collection centers at many hospitals produce large volumes of plasma for treating blood-clotting disorders and other conditions. The same infrastructure, personnel, and regulatory framework could produce plasma for the treatment of H5N1 influenza, they said.

`Immediately Effective'

``A single H5N1 convalescent donor could provide a weekly volume of plasma sufficient to treat multiple patients with H5N1,'' the authors said. Locally produced plasma from survivors or early vaccine recipients ``could be immediately effective,'' they said. Blood products could also be processed into a frozen form and shipped to other regions for use during a pandemic.

``While these may be interesting ideas, and they may have biologic plausibility, they have very little supply chain and logistic possibility,'' said Michael Osterholm, head of the University of Minnesota's Center for Infectious Disease Research and Policy in Minneapolis.

Needles, syringes, reagents and other equipment needed for blood collection and screening might be difficult to source, as supply chains ``around the world will quickly collapse during a pandemic,'' Osterholm said in a telephone interview today.

`Formidable' Hurdles

``Formidable logistical hurdles would complicate the ability to obtain, characterize, and prepare these materials for use in the midst of an outbreak,'' John Treanor, professor of medicine at the University of Rochester Medical Center in Rochester, New York, wrote in a review of the study, also appearing in October's Annals of Internal Medicine.

``We lack sufficient understanding of the immune response to H5N1 infection in humans,'' including whether patients who recover from infection develop high levels of antibody, Treanor said. ``We don't know the level of antibody that needs to be achieved to confer protection or the appropriate dose of serum needed to achieve useful antibody levels in recipients.''

`Extremely Expensive'

The volume of plasma from recovered H5N1 patients that has been screened for diseases such as HIV and hepatitis would be ``miniscule'' and ``extremely expensive'' to collect, said Donald Kaye, a professor of medicine at Drexel University, in Gladwyne, Pennsylvania.

Collecting plasma from people immunized against the pandemic flu strain would also be difficult because there will be inadequate supplies of vaccine, Kaye said in an e-mail.

``It probably would be effective if given early or prophylactically, but again this is impractical as huge amounts would be necessary,'' he said. ``If given once severe disease occurs, it remains to be seen if it would be effective.''

The concept is important and it should be explored further, especially given the lack of proven interventions to prevent or treat illness due to H5N1 influenza, Treanor said.

``We can, should, and must explore these issues'' in advance of the pandemic, he said. ``Although many logistical hurdles exist, controlled clinical studies done now will probably pay a considerable dividend when the pandemic begins.''

To contact the reporters on this story: Jason Gale in Singapore at at j.gale@bloomberg.net ; Vesna Poljak in Sydney at vpoljak@bloomberg.net
Last Updated: September 5, 2006 04:49 EDT

Researchers Find Validity in 1918 Treatment for Avian Influenza

2006-09-09T00:33:00.000-05:00

Source: Uniformed Services University of the Health Sciences (USU) Released: Sun 03-Sep-2006, 21:30 ET
Researchers Find Validity in 1918 Treatment for Avian Influenza

USU faculty have discovered that a treatment for the Spanish Influenza pandemic may also be effective for current Avian Influenza patients. Navy Capt. Edward Kilbane, Army Col. Jeffrey Jackson and Navy Lt. Cmdr. Thomas Luke, are all alumni and faculty of the Uniformed Services University of the Health Sciences. They, along with retired Navy physician, Capt. Stephen Hoffman, published their research Tuesday, Aug. 29.

Newswise — USU faculty have discovered that a treatment for the Spanish Influenza pandemic may also be effective for current Avian Influenza patients. Navy Capt. Edward Kilbane, Army Col. Jeffrey Jackson and Navy Lt. Cmdr. Thomas Luke, are all alumni and faculty of the Uniformed Services University of the Health Sciences (USU). They, along with retired Navy physician, Capt. Stephen Hoffman, published their research Tuesday, Aug. 29, in the online edition of the Annals of Internal Medicine.

The four researchers analyzed medical literature reported during the Spanish Flu pandemic of 1918 to 1920. They found that transfusions with blood products from Spanish Flu survivors may have reduced the risk of death in seriously ill Spanish Flu patients.

The meta-analysis of these data show that treatment of patients in 1918 with convalescent whole blood, plasma or serum obtained from humans who had recovered from Spanish Influenza resulted in a reduced mortality of seriously ill patients by 50 percent.

The next steps would be a study to determine if treatment of patients with convalescent plasma containing anti-H5N1 antibodies from recovered from patients could lead to similar results for patients with Avian Influenza.

“Plasma is produced in local hospitals worldwide and transfusions might be useful in treating bird flu patients during outbreaks and pandemics, especially in light of the limitations of existing treatment options,” Commander Luke said. “A single recovered bird-flu patient could donate a weekly volume of plasma sufficient to treat many patients with H5N1 influenza.”

Their article titled, “Convalescent Blood Products for Spanish Influenza Pneumonia: A Future H5N1 Treatment?” will be published in the Oct. 17 print edition of Annals of Internal Medicine.

Established by the U.S. Congress in 1972, the Uniformed Services University of the Health Sciences (www.usuhs.mil) is located on the campus of the National Naval Medical Center in Bethesda, Md., and is the nation’s only federal school of medicine and graduate school of nursing.

© 2006 Newswise. All Rights Reserved.

CDC announces test distinguishing bird flu

2006-09-09T00:17:00.000-05:00

USA TODAY

CDC announces test distinguishing bird flu
Posted 8/28/2006 9:06 PM ET
ATLANTA (AP) — Scientists have developed a biological microchip test designed to help laboratories better identify if a person has bird flu.

The Flu Chip test was developed by the University of Colorado and the U.S. Centers for Disease Control and Prevention. It is detailed in the current issue of a scientific publication, the Journal of Clinical Microbiology.

Earlier this year, federal officials announced a lab test that within four hours can evaluate whether a person has the type of bird flu circulating in Asia.

But the test doesn't say much beyond positive or negative. The new test, which takes about 12 hours, can identify the specific subtype of the disease and name the virus's geographic origin.

"This test provides a lot more information," said Kathy Rowlen, a University of Colorado scientist who led the research.

It should help national and international diseases investigators, "who want to track all subtypes of influenza that are infecting people," she added.

In the Flu Chip test, a robotic arm drops spots of various flu viruses' genetic material onto a microscope slide. The 55 spots are each one-hundredth of an inch in diameter. The slide is immersed in a liquid containing flu gene fragments from an infected person. Scientists watch to see if genetic material from the infected person binds to any of the material on the slide, indicating a match.

The Flu Chip allowed users to obtain correct information about both type and subtype — which is considered a full characterization of a strain — from 72% of the samples, according to an evaluation of the test.

The test can help identify emerging viruses, and can be designed to distinguish between the genetic groups — or "clades" — of bird flu, said Dr. Nancy Cox, director of the CDC's Influenza Division.
Copyright 2006 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

New Web tool tracks H5N1 testing of US wild birds

2006-09-09T00:15:00.000-05:00

New Web tool tracks H5N1 testing of US wild birds

Aug 25, 2006 (CIDRAP News) – The US government announced yesterday the launch of a Web site that allows the public to view current information about testing of wild birds for H5N1 avian influenza.

The site, available at http://wildlifedisease.nbii.gov/ai/, is part of a database and Web application housed at the US Geological Survey (USGS) National Wildlife Health Center in Madison, Wis., according to a press release yesterday from the USGS. The Web application, called HEDDS (Highly Pathogenic Avian Influenza Early Detection Data System), allows scientists to share information on sample collection sites, bird species sampled, and test results.

"HEDDS provides a critical comprehensive view of national sampling efforts at a time when the demand for this type of information is increasing, along with the growing interest in HPAI surveillance efforts in wild birds," said project leader Joshua Dein, VMD, MS, of the USGS Wildlife Health Center.

The national wild-bird surveillance plan, released in March 2006, is part of US efforts to prepare for a potential flu pandemic. The plan includes five strategies for early detection of highly pathogenic avian influenza. Sample numbers from three of these will be available on HEDDS: live wild birds, subsistence hunter-killed birds, and investigations of sick and dead wild birds. The other two strategies involve domestic bird testing and environmental sampling of water and wild-bird droppings.

Agencies, organizations, and policymakers involved in avian flu monitoring and response can access the database. Scientists can use the data to assess risk and refine monitoring strategies if H5N1 avian flu is detected in the United States. Public access is more limited but includes a map showing the number of samples collected in each state.

The 2006 surveillance year runs from April 1, 2006, to March 31, 2007. So far this year, 9,590 wild-bird samples have been entered into HEDDS. No cases of H5N1 have been detected. Most of the samples are from Alaska because it is the first US stopover for birds from Asia and other continents where the H5N1 virus is present. Federal officials announced on Aug 9 that surveillance efforts had expanded to the lower 48 states, Hawaii, and other Pacific islands.

A map on the new USGS site shows that 9,327 birds from Alaska have been tested so far this year, with only a few from most other states. Last year officials tested just 721 birds from Alaska and none from most other states, another map shows.

The goal of the surveillance program for 2006 is to collect 75,000 to 100,000 samples from wild birds and 50,000 environmental samples, officials have said.

HEDDS was produced by the National Biological Information Infrastructure Wildlife Disease Information Node, part of the USGS National Wildlife Center. Several agencies are financially supporting the system, including the US Fish and Wildlife Service, the USGS, and the US Department of Agriculture's Animal and Plant Health Inspection Service. Participants include state wildlife agencies, universities, and nongovernmental organizations.

See also:

Aug 24 USGS press release on Web site tracking H5N1 testing of wild birds
http://wildlifedisease.nbii.gov/ai/index.jsp

Aug 9 CIDRAP News story "US's wild bird H5N1 monitoring expands beyond Alaska"

Center for Infectious Disease Research & Policy
Academic Health Center -- University of Minnesota
Copyright © 2006 Regents of the University of Minnesota

Scientists launch effort to share avian flu data

2006-09-09T00:09:00.000-05:00

Scientists launch effort to share avian flu data

Robert Roos * News Editor

Aug 25, 2006 (CIDRAP News) – Leading medical researchers yesterday announced the formation of a consortium to unlock genetic and other data on avian influenza in the hope of improving the understanding of how viruses such as H5N1 spread and evolve.

A letter published online yesterday by Nature, signed by 70 scientists and health officials, announced the launch of the Global Initiative on Sharing Avian Influenza Data (GISAID). Authors of the letter include Dr. Nancy Cox, head of the Influenza Division at the US Centers for Disease Control and Prevention (CDC), and Ilaria Capua, an Italian veterinary virologist who is a leading advocate of greater sharing of H5N1 genetic data.

"The Initiative is coming together to work around restrictions which have previously prevented influenza information sharing, with the hope that more shared information will help researchers understand how viruses spread, evolve, and potentially become pandemic," states a news release on the GISAID Web site.

The consortium "is open to all scientists, provided they agree to share their own data, credit the use of others' data, analyze findings jointly, and publish results collaboratively," the release says. The Nature letter says that data will be published in three public databases "as soon as possible after analysis and validation, with a maximum delay of six months."

Details are still being worked out, but the participants have agreed to deposit genetic data into secure sections—not yet set up—of existing public databases, according to a Nature news article published yesterday. The data will initially be accessible only to the consortium researchers, but will be opened to public access within 6 months.

The consortium said it will use the three databases participating in the International Nucleotide Sequence Database Collaboration: EBML in the United Kingdom, DDBJ in Japan, and GenBank in the United States.

Yesterday's announcement is the second major development this week affecting the availability of genetic data on flu viruses. Two days ago the CDC said it was depositing the blueprints for 650 human flu virus genes in GenBank, a public database, and would release data on several hundred more flu viruses each year henceforth. The data are from viruses collected in the United States.

Scientists have complained in recent months about the withholding of genetic sequences of flu viruses, especially H5N1. The World Health Organization (WHO) obtains such data as its affiliated laboratories analyze viruses, but the WHO releases the data only with permission from the country of origin. Some countries battling H5N1 have refused to allow release of the information. Indonesia, an H5N1 hot spot, had long refused to authorize release of data on its viruses, but earlier this month the government changed its stance.

In a telephone interview, Cox said the goal of GISAID is to share clinical and epidemiologic information as well as genetic data on avian flu cases.

"The aim is that eventually the data will be linked together so there will be not only the sequence data but also the clinical and epidemiologic data," she told CIDRAP News. "The sequences become much more meaningful with other data linked to them."

Clinical information would include such things as the patient's age, whether he or she survived the illness, how long the illness lasted, and what part of the body a specimen was taken from, she said.

"All of this information is very useful when you're trying to understand the evolution of the virus," Cox said, adding that data would be stripped of personal identifiers.

Public genetic databases aren't necessarily set up to accommodate additional information beyond the bare sequence data, and some work will be required to remedy that, Cox said. For example, a database should have fields for such information as whether the virus came directly from a clinical specimen or from an isolate obtained by amplifying the original specimen, she explained.

"All of these details are potentially very important because they can have an impact on the sequence itself," she said.

GISAID will include experts in animal and human virology, epidemiology, bioinformatics, and intellectual property issues, according to the Nature letter.

A concern of developing countries battling the H5N1 virus is that they won't benefit from releasing data derived from samples they collect, because any resulting drugs or vaccines will be too expensive. Because of this, Cox said, "There really is going to be a lot of effort put into the intellectual property rights issue to assure proper acknowledgment of the origin of the sequences and recognize the scientists and the public health workers in the country of origin of the virus."

A group within the consortium will focus on intellectual property issues, Cox said. They will work to credit the scientists who are on the front lines in affected countries and also "to determine if there are ways the consortium could help facilitate benefits for those countries that are hardest hit by avian flu."

The equity issue has been discussed a lot, she added. "We don’t have the solutions yet, but it's an area that needs to be tackled."

Cox said scientists working for pharmaceutical companies could participate in the consortium. "Pharmaceutical manufacturers would be able to look at the data, and, for example, if they 're trying to design new antiviral drugs for H5N1 or other flu viruses, they'd be able to use the data to do that," she said.

The director of GISAID is Peter Bogner, chief executive of the Bogner Organization, Santa Monica, Calif. He is an author of the Nature letter, along with Cox; Capua, who chairs the scientific committee of the joint avian flu expert panel of the World Organization for Animal Health (OIE) and the United Nations Food and Agriculture Organization; and David J. Lipman, director of the US National Center for Biotechnology Information.

According to the Nature news article, Capua started something of a rebellion against the hoarding of avian flu virus data last March, when she put her own H5N1 sequence data into GenBank instead of in the protected database used by WHO-linked labs, and challenged others to do the same.

Capua then collaborated with Bogner, who talked with many scientists and policymakers about the issue, according to the article. Subsequently, the OIE-FAO avian flu expert panel (OFFLU) endorsed the consortium idea.

The 70 signers of the Nature letter include researchers and health officials from countries around the world, including those hard-hit by H5N1 avian flu, such as Thailand, Indonesia, Vietnam, China, Cambodia, Egypt, and Turkey, as well as countries not yet affected.

Cox said the consortium is "really at a very formative stage right now. There's a lot of groundswell of support for it. There's a lot of enthusiasm, but it's just the beginning."

See also:

GISAID letter to Nature
http://www.nature.com/nature/journal/vaop/ncurrent/full/442981a.html

GISAID news release
http://gisaid.org/press_releases.html

Nature news story
http://www.nature.com/news/2006/060821/full/060821-10.html

Center for Infectious Disease Research & Policy
Academic Health Center -- University of Minnesota
Copyright © 2006 Regents of the University of Minnesota

Experts worry that antivirals may mask avian influenza

2006-09-08T23:57:00.000-05:00

Experts worry that antivirals may mask avian influenza

Aug 24, 2006 (CIDRAP News) – Avian flu experts in two of the countries with the most human H5N1 avian influenza cases to date—Vietnam and Thailand—are warning that the antiviral drug oseltamivir may mask the infection and complicate laboratory detection.

Menno de Jong, a virologist at an Oxford University clinical research unit in Ho Chi Minh City, Vietnam, told Bloomberg News this week that avian influenza may go undetected in patients who take the drug days before testing. An incorrect diagnosis is problematic because it may hamper early detection of disease spread.

Some countries are responding to local human H5N1 avian influenza outbreaks by distributing oseltamivir to local citizens. For example, the Jakarta Post reported this week that Indonesia's health ministry had distributed the drug to 2,100 villagers in Garut, a district in West Java, Indonesia, where three recent cases have been documented and authorities are investigating the possibility of human-to-human transmission.

Antiviral drugs such as oseltamivir are designed to reduce the duration of viral replication and should be taken within 48 hours of symptom onset, according to World Health Organization (WHO) recommendations. However, De Jong's team, which observed 18 cases in Vietnam, found that analysis of nasal and throat swabs taken from patients 48 to 72 hours after beginning oseltamivir treatment was unable to detect the virus.

A study of Vietnamese H5N1 cases in a September 2005 issue of The New England Journal of Medicine found that genetic evidence of the H5N1 virus could not be detected in throat swab samples until between 2 and 15 days (median 5.5 days) after illness onset.

"If a patient is on oseltamivir for 3 days before the first swab is taken for diagnostic testing, it's possible the result will be negative, but the patient could be infected," he told Bloomberg News.

To prevent the drug from masking a possible H5N1 virus infection, he advises that patients undergo testing before or soon after taking oseltamivir. Obtaining a swab sample from the patient takes only seconds and should not delay the patient's treatment, de Jong said.

Meanwhile, a public health official in Thailand expressed the same concerns about possible false-negative testing results for the H5N1 virus in patients who take oseltamivir. In an article that appeared in The Nation, a Thai daily newspaper, Paijit Warachit, director-general of the Department of Medical Sciences, said that initial laboratory tests did not detect the H5N1 virus in the country's two most recent cases.

Warachit said the disease progression may be becoming more complicated in humans, or the use of oseltamivir could be complicating the patients' lab results. He noted that the drug is able only to prevent the virus from replicating, not destroy it, and that little of the virus was in the patients' respiratory tract for testing.

With the last two Thai cases, the avian influenza virus was found to be deeper in the respiratory tract than is typically found with other influenza viruses. Warachit said the medical staff has been told to probe deeper to obtain a complete testing specimen.

Since 2004 Thailand's health ministry has tested more than 4,000 people for the H5N1 avian influenza virus, with a 3% failure rate. However, Warachit said the failure rate has risen to 20% this year. "We need to continue our studies to see whether the virus will become more and more difficult [to detect] in the future," he noted.

See also:

Sep 29, 2005, New England Journal of Medicine article on avian influenza in humans
http://content.nejm.org/cgi/content/full/353/13/1374

Center for Infectious Disease Research & Policy
Academic Health Center -- University of Minnesota
Copyright © 2006 Regents of the University of Minnesota

Flu Roundup: Fear of human spread lessens

2006-09-08T23:54:00.000-05:00

From Monsters and Critics.com

Health News
Flu Roundup: Fear of human spread lessens
By Kate Walker
Aug 23, 2006, 19:00 GMT

OXFORD, England (UPI) -- Despite a number of recent deaths and infections in Indonesia that looked as though they may have been an infection cluster, the World Health Organization has confirmed that there is no evidence that bird flu has gained human-to-human transmissibility.

The Cikelet region of Indonesia`s West Java province is remote, accessible only by motorbike or horse. News travels there slowly, and is often the result of Chinese whispers. So when a number of locals died of flu-like symptoms in a short space of time and WHO investigators arrived, they were unsurprised to discover that a lack of information had led to unsafe practices.

'As the population had no experience with this disease, high-risk behaviors commonly occurred during the disposal of carcasses or the preparation of sick or dead birds for consumption,' WHO said in a statement.

'Though some of the undiagnosed deaths occurred in family members of confirmed cases, the investigation has found no evidence of human-to-human transmission and no evidence that the virus is spreading more easily from birds to humans.'

Birds in the area began to die in large numbers after birds purchased outside Cikelet were incorporated into flocks in July.

Indonesian authorities have begun to test all those who were in contact with the bird flu victims and sufferers; so far all have been returned negative. To prevent further outbreaks of the disease, 2,400 people in the area have been provided with Tamiflu, and 2,500 chickens have been culled.

Meanwhile:

-- Thai authorities are using a team of 800,000 health volunteers to educate the public about avian influenza and means of preventing it.

The volunteers will go door-to-door throughout 30 provinces which have been affected by bird flu, and will present householders with posters and leaflets with simple language and easy-to-understand cartoons.

In announcing the initiative Wednesday Thai Health Minister Pinij Jarusombat said: 'They will give information to people about what they should do to be seriously safe from bird flu.'

The education drive begins Wednesday and will continue for nine days.

Previous efforts to educate the Thai populace about methods of bird flu prevention have included similar education drives organized by the Agriculture Ministry and television advertising.

-- As the autumnal migration of wild birds begins, governments along migratory routes are warning their citizens that further avian influenza outbreaks are possible, and that care and diligence should be taken when dealing with dead birds.

The latest country to issue such a warning was Turkey, where domestic bird keepers have been told they should reprise the precautionary measures put into place last year. These include keeping domestic birds penned and avoiding all contact with wild birds.

Some have called for the widespread vaccination of all domestic birds, but no such plan is yet in place.

Turkey first saw an avian influenza outbreak in October 2005. Between December 2005 and February 2006, more than one-third of Turkish provinces saw outbreaks of avian flu in birds. At least six people died.

-- The Dutch Agriculture Ministry this week ordered farmers to begin keeping their poultry flocks indoors from Sept. 1 to guard against avian influenza outbreaks caused by migrating birds.

In a statement released Tuesday, the ministry advised farmers: 'During the forthcoming migration period, there is a risk that migratory birds can spread bird flu. For this reason all holders of chickens, geese and other birds should keep them indoors.'

In lieu of keeping the birds indoors, the ministry added, farmers could instead construct pens and enclosures which would prevent the poultry flocks from coming into contact with migrating birds.

The Netherlands, which is one of the world`s largest exporters of poultry and Europe`s second-largest poultry producer, has yet to identify any incidence of H5N1 infection in commercial poultry.

Earlier this month two suspected cases of avian influenza infection were reported in owls in a zoo in Rotterdam. Initial tests ruled out H5N1 infection as a cause of illness, but the conclusive result is expected this week.

Copyright 2006 by United Press International

© Copyright 2003 - 2005 by monstersandcritics.com.
This notice cannot be removed without permission.

Winged Disaster Business continuity planning should already be in place in preparation for avian flu (or other) pandemics

2006-09-08T23:49:00.000-05:00

Canadian Underwriter, August 2006

Winged Disaster

Business continuity planning should already be in place in preparation for avian flu (or other) pandemics

This article is a condensed version of "Avian Flu: Preparing for a Pandemic," with a contribution from Paul Allen, Managing Director, Marsh Canada Ltd.

With increasing urgency over the past year, a variety of governments, non-governmental organizations, industry groups, and media outlets have trumpeted the potential dangers of avian influenza, commonly called "bird flu."

Suddenly, the word "pandemic" is on the tongues of world leaders, references to the catastrophic 1918 Spanish flu are common, and many businesses are nervously looking for gaps in their business continuity plans. Human deaths from the bird flu have been reported in seven countries. Thus far, the spread of the virus to humans has largely been through contact with infected birds, although a few possible cases of human-to-human transmission are under investigation. The possibility the virus will mutate allowing sustained human-to-human transmission has health authorities on high alert.

"It is only a matter of time before an avian flu virus - most likely H5N1 - acquires the ability to be transmitted from human-to-human, sparking the outbreak of human pandemic influenza," Lee Jong-wook, director-general of the World Health Organization (WHO), said during a late 2005 gathering of health experts from more than 100 countries. "We don't know when this will happen. But we do know that it will happen."

GLOBAL THREAT

A human influenza pandemic represents the extreme end of what risk managers call low-frequency, high-severity events. Just as the risk of a hurricane, tsunami or earthquake is known, so to is the risk of pandemic. And as with natural catastrophes, we can't measure the severity of pandemic until it is over. But a pandemic will not limit its damage to one or a few countries, or even a single geographic region. The global consequences of a pandemic could include:

* more than 7 million deaths from even a mild pandemic, according to the WHO (death estimates vary wildly - some top 350 million - and will ultimately depend on the virulence of a pandemic strain);

* 25% or more of the world's workers needing to take between five and 20 days of sick leave, according to the United Kingdom Department of Health;

* US$800 billion global economic damage, according to The World Bank; and

* major disruptions to every industry, particularly those with strong ties to travel, tourism, sports and entertainment, lodging, and health care.

The hardest hit companies in any industry are likely to be those with worldwide operations, global supply chains, and/or international customers. Already, some local, state, and national governments are setting in place plans to curtail travel, close schools, quarantine individuals and communities, and ban public gatherings. Such steps were taken during the epidemic of SARS (Severe Acute Respiratory Syndrome) in 2003 - especially in Asia, where the disease was most prevalent. Such measures, although necessary to help slow the spread of the disease and allow time for an increase in medical efforts, impede commerce. Even a relatively mild pandemic could "slow or halt economic growth in Asia and lead to a significant reduction in trade, particularly of services," according to analysis by the Asian Development Bank.

CORPORATE PREPAREDNESS

Many businesses, particularly large multinational corporations, have established avian flu/pandemic planning committees. According to media reports, some companies have created task forces that combine strategic planning, operations continuity procedures, human resources, and health services to adopt event-specific measures in anticipation of an avian flu pandemic. Others, primarily those sectors of the food industry that use poultry, are preparing marketing campaigns aimed at allaying fears about the use of their products - and thus protecting their brands - should an avian flu pandemic occur.

It's also likely that many companies are not making any special preparations in advance of what they see as the slim likelihood of an avian flu pandemic. Instead, they are operating with the belief that should a pandemic occur, either it will not affect them or they will respond as the need arises. An outbreak of avian flu will severely test even the best business continuity plans; businesses are well advised to review and revise their plans in light of this threat.

In theory, business continuity management (BCM) should already be in place to identify, respond to and recover from a broad range of potential interruptions. Pandemic influenza, however, isn't a "normal" business risk. Some of a pandemic's unique characteristics include:

* an international impact with no demarcation by culture, industry, or geography;

* the potential to escalate quickly and last for many months;

* a projected infection rate of 25% or more of the world's population, according to many public health experts;

* extreme taxation of health care facilities, public health agencies, and their workforces; and

* a macro impact on regional and global economies that could result in a significant shift in the way companies conduct businesses and their ability to continue operations.

Companies should be taking a number of steps and considering a number of issues before, during and after an outbreak. If avian flu does not emerge, the time spent on planning and preparation will not have been wasted. After all, avian flu is a good proxy for other potential pandemics. Pandemics are a good proxy for potential bio-terrorism, and bio-terrorism is a good proxy for other forms of terrorism. Corporate preparedness is a transferable skill, even if the risk emerges from a totally different direction or source than anticipated.

BEFORE AN OUTBREAK

Before an outbreak, risk managers and other executives with risk management responsibilities should understand the nature of the disease and the means by which it could affect their operations, resources, reputations, and financial fitness. They should review, revise and test existing corporate preparedness plans, procedures and policies; review and/or develop employee health procedures; and ensure that senior managers have the skills to handle an event before it becomes a crisis.

UPON OUTBREAK

During a pandemic, an organization's ability to identify problems and respond quickly and effectively will make a significant difference to the success or failure of protecting staff, profits, reputation and, ultimately, the company's survival. Companies should consider structuring their corporate preparedness plans for a pandemic crisis into four to six thresholds for escalating action.

Such a plan would provide information in advance and allow individual facilities, regions and businesses to detect an emerging event and respond appropriately at each escalated threshold. Tiered planning should provide applicable guidance in areas including allocation of resources, health and safety issues, operations responses, security measures and more.

Companies should review their existing preparedness plans and consider how - and if - they will be able to respond to the following areas during an outbreak:

* Information and communication concerns;

* Human resources/benefits concerns;

* Operational concerns; and

* Risk communication concerns.

DURING AN ESCALATING PANDEMIC

Businesses looking to ensure continued operations during the pandemic and in its immediate aftermath may find it critical to closely monitor areas including the business recovery team's operations; integration of continuity strategies for various processes; supply-chain issues; and transportation links.

The timing and severity of a pandemic, the nature of a particular business or industry and other variables will all come into play during an actual incident and subsequently as the spread of the disease progresses. For example, at what point should a college or university with a large number of students living on campus decide to cancel classes and/or shut down the campus?

In that situation, a balance will need to be struck between acting too soon, which could mean canceling school unnecessarily, and acting too late, which could force students to attempt travel in a time of major transportation disruptions.

Likewise, a professional services company may have a significant number of employees traveling overseas. At what point should it curtail overseas travel? How much of its resources should it dedicate to increasing its ability to conduct business through teleconferencing?

It is not clear that the H5N1 avian flu will mutate into a human-to-human disease this season, or ever. However, it is widely believed that in the near term, the global population will have to face a pandemic.

It is incumbent on corporate officers to make sure their companies have evaluated the risks and implemented the appropriate steps to mitigate those risks.

INSURANCE COVERAGE

In the event of a pandemic, businesses around the world could suffer severe economic damage, the extent of which will depend on the severity of the outbreak. Whenever businesses suffer a loss, owners naturally look to their insurance policies for help. As was the case with the SARS virus, many claims stemming from a flu pandemic are likely to lead to disputes. Although the outcome of any claim is dependent on its facts and the legal rules in the applicable jurisdiction, some generalizations can be drawn.

Understanding some of the underlying issues and potential responses may assist in planning and preparation. Some of the lines of coverage likely to come into play should a pandemic occur are:

General liability

The standard general liability policy typically responds to bodily injury, sickness, or death allegedly caused by the insured. Insurers are therefore likely to scrutinize closely the alleged causal connection between a claimed infection or exposure and the actions of the insured. Because insurers take the position that the policy extends only to actual injuries, they are also likely to look closely at the nature of injuries alleged by third parties and may reject claims based on fear of exposure, exposure without actual symptoms, or other mental or emotional injuries. However, under the "bodily injury" and/or the "personal injury" language of some policies and the law of some jurisdictions, such emotional injuries may be covered, so careful review is necessary.

Workers compensation

Workers' compensation coverage in Canada will undoubtedly be an issue in the event of an avian flu pandemic. Entitlement to benefits will be among the most difficult issues for the Canadian Workers' Compensation Boards (WCB) to consider. The WCBs will need to determine whether or not the exposure to Avian Flu "arose out of and in the course of employment." The recent SARS (Severe Acute Respiratory Syndrome) outbreak in Toronto, Ontario served as an example of how this type of issue may be handled. The Ontario Workplace Safety and Insurance Board allowed claims for benefits only where a definite link could be shown between SARS and the workplace (e.g. hospital workers exposed to the patients with SARS).

Exposure to avian flu ay result from work duties in:

1. Canada (regular duties with employer)

2. Outside of Canada (short-term or long-term assignment outside of Canada).

If an employee alleges a workplace exposure to avian flu, the employer should report the incident to the provincial Workers' Compensation Board (WCB) and cooperate in any investigation. Compensability of each case must be determined on the merits of the situation and the law of the province or territory.

Property

Real property may be contaminated in an avian flu outbreak. Governments may close or quarantine a building or an entire neighborhood. This could produce claims under an insured's first-party property coverage. Insurers begin every analysis of a claim under a property policy, whether for direct damage or time-element loss, by asking whether the insured property (or property of the type insured) has sustained physical loss or damage from an insured event or peril. Generally, unless the insured's policy provides specific time-element coverages for "infectious disease outbreaks," coverage is unlikely to be triggered. In regard to avian flu, the two most likely scenarios resulting in a time-element loss are:

* fear the virus may exist in or near the insured's property, thereby leading to employee absences and diminished customer traffic to the site; and

* actual contamination of the site by the virus, resulting in governmental or voluntary closure.

Although it is unlikely any insurer will immediately acknowledge coverage under a standard property policy for avian flu scenarios, it is important that all such potential claims be reviewed. Where the insured can demonstrate that a public authority has closed or quarantined its premises as a result of an actual - provable - contamination by avian flu, the potential claim should be reported to its property insurers for review.

CONCLUSION

The question on the tip of everyone's tongue is: "Just how worried should we be about an avian flu pandemic?" The answer is not simple. Just as residents of San Francisco and Tokyo live with the knowledge they reside in an active earthquake zone, the entire world is becoming aware that we all live in a potential pandemic zone. Even if the H5N1 avian flu strain fails to mutate into a form easily transmissible among humans, it has raised awareness that pandemics are a natural part of the world.

Every corporate leader must now consider this issue. Coupled with this emerging awareness is the reality that it's impossible to predict just how severe an outbreak will be. Beyond fears over the possible loss of life, avian flu has raised concerns about the preparedness of governments and businesses to deal with a crisis of enormous scale. However, there is still time to prepare for the contingency. Now is the time to check your company's preparedness for handling a pandemic crisis.
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Human Bird Flu Cases Found This Year Equal 2005 Level

2006-09-08T01:47:00.000-05:00

Human Bird Flu Cases Found This Year Equal 2005 Level (Update2)

By Jason Gale and Karima Anjani

Aug. 21 (Bloomberg) -- Bird flu killed a 35-year-old woman in Indonesia, raising the number of cases worldwide this year to 95, the same number reported in the whole of 2005, as health authorities study whether the virus is spreading between humans.

Tests on the woman were positive for the H5N1 strain of avian influenza, I Nyoman Kandun, a director general at the Ministry of Health, said late yesterday. Indonesia, with the most H5N1 deaths, confirmed two other cases from the village where the woman lived. No signs of human-to-human transmission have been found, health officials said today.

``The cases have occurred in a remote, mountainous area where there are a lot of other diseases,'' Georg Petersen, the World Health Organization's Indonesia representative, said in a telephone interview today. ``It's important to identify illnesses caused by bird flu and illnesses caused by the other diseases.''

The death toll from H5N1 has tripled this year as the virus spread in wild birds and domestic poultry to at least 38 countries. It may kill millions of people should it change into a pandemic form and spread easily among people.

An average of three new human cases a week have been reported this year as the virus became entrenched in Indonesia and China, and infected people for the first time in Turkey, Iraq, Azerbaijan, Egypt and Djibouti. It claimed more lives in Thailand and Cambodia, where fresh outbreaks killed fowl in the past month.

Death Tally

Since 2003, H5N1 is known to have infected 240 people in 10 countries, killing 141 of them, the WHO said today. The virus has killed 64 people this year, compared with 22 in the first eight months of 2005.

The spread of the virus is slowing worldwide as efforts to contain the illness partially succeed, the Food and Agriculture Organization of the United Nations said. Among the areas where migratory birds and poultry remain at risk are Asia, including Indonesia where 46 people have died; some African countries such as the Ivory Coast; and the southern Balkan and Caucasus regions in Europe, the organization said.

Almost all human H5N1 cases have been linked to close contact with sick or dead birds, such as children playing with them or adults butchering them, according to the WHO.

Doctors from the Geneva-based health agency joined a team of local medical and veterinary officials last week to identify the cause of the cases in West Java's Garut district, where the 35- year-old woman lived. Deaths from established infectious diseases are common in the area and public-health resources are minimal, the WHO said today.

Human-To-Human Transmission

While deaths from respiratory disease are known to have occurred there in late July and early August, no samples were taken, the United Nations health agency said on its Web site.

``Though some of these undiagnosed deaths occurred in family members of confirmed cases, the investigation has found no evidence of human-to-human transmission and no evidence that the virus is spreading more easily from birds to humans,'' the agency said in the statement.

Large numbers of poultry began dying in Garut after live chickens were purchased from outside the area in late June and integrated into local flocks, WHO said. Many chicken carcasses were eaten without proper preparation or were incorrectly disposed of, the agency said.

``These exposures are, at present, thought to be the source of infection for most confirmed or suspected cases,'' the agency said.

Testing

Samples have been sent for testing and some patients and their close contacts are taking antiviral drugs. Residents are cooperating with the investigation and treatment efforts, the WHO said.

At least 16 other people are undergoing testing for the virus, Agence France-Presse reported yesterday. Clusters of cases may signal the virus is becoming more adept at infecting humans, not just birds.

A pandemic can start when a novel influenza A-type virus, to which almost no one has natural immunity, emerges and begins spreading. Experts believe that a pandemic in 1918, which may have killed as many as 50 million people, began when an avian flu virus jumped to people from birds.

A flu outbreak killing 70 million people worldwide may cause global economic losses of as much as $2 trillion, Milan Brahmbhatt, a World Bank lead adviser in the East Asia region, said in June.

Indonesia, the world's fourth-most-populous country, attracted international attention in May when seven members of a family from the island of Sumatra contracted H5N1, six of them fatally. The cases represented the largest reported cluster of infections and the first laboratory-proven instance of human-to- human transmission.

To contact the reporters on this story: Jason Gale in Singapore at j.gale@bloomberg.net ; Karima Anjani in Jakarta at kanjani@bloomberg.net
Last Updated: August 21, 2006 14:18 EDT

Bird flu viruses diversifying, making vaccine target harder to pick: WHO

2006-08-26T01:25:00.000-05:00

Bird flu viruses diversifying, making vaccine target harder to pick: WHO
19:23:04 EDT Aug 18, 2006
Canadian Press: HELEN BRANSWELL, The Canadian Press

(CP) - The World Health Organization urged influenza vaccine makers Friday to use newer strains of virus when making vaccine to protect against H5N1 avian flu, saying the evolution of the microbe has led to increased variety in circulating strains.

While the diversity creates challenges for vaccine manufacturers - and potentially additional costs for the governments paying them to make and test vaccine against H5N1 - it does not mean the worrisome virus has moved closer to being able to spark a human flu pandemic, a senior official of the World Health Organization said.

"I don't think it's possible to interpret these kinds of changes in terms of whether the virus is moving closer to developing greater transmissibility properties among people," said Dr. Keiji Fukuda, co-ordinator of the WHO's global influenza program.

"I think what it simply reflects is that influenza viruses have evolutionary pressures on them and they evolve. They change. And that's what we're seeing."

Experts who have studied numerous samples of the virus have suggested nothing in them points to the development of mutations that would increase H5N1's ability to infect people and spread among them.

But an infectious diseases expert at the University of Minnesota questioned whether the scientific community knows enough about how influenza viruses adapt to a human host to be sure it would recognize it if H5N1 were on that path.

"What does it mean for an influenza strain today to be more adapted towards human-to-human transmission?" Dr. Michael Osterholm, director of the Center for Infectious Disease Research and Policy, wondered.

He said he was not suggesting the virus is becoming more transmissible, only that the patterns that would lead to that end aren't defined.

With the spread of the virus to many different countries, sublineages of H5N1have emerged, each with distinct genetic properties. It's been known for at least a year that the viruses break down roughly into two families or "clades."

Clade 1 viruses have circulated in Cambodia, Thailand and Vietnam and caused human infections in those countries during 2004 and 2005. Clade 2 viruses circulated in birds in China and Indonesia in 2003 and 2004 and have since spread westward through the Middle East, Russia, Europe and Africa.

It is the clade 2 viruses that have caused most of the human H5N1 cases that have occurred since last 2005. And it is with representative samples from these viral strains that the WHO is now recommending vaccine makers work.

The Geneva-based agency isn't recommending work on vaccines made with the earlier strain - a virus isolated in Vietnam in early 2004 - be abandoned. At least a dozen companies are working on vaccine based on that seed strain.

Fukuda said there is an upside to working with additional virus types. The more practice manufacterers have working with the virus, the better placed they will be to move quickly to make a vaccine should H5N1 become a pandemic strain.

"To be able to work with more than one strain of H5 vaccine just gives the manufacturers that much of a leg up in terms of the experience that they may need later on," he said.

Since the current outbreak of H5N1 flu erupted in late 2003, at least 239 people have been infected with it and 140 of them have died.

© The Canadian Press, 2006

New Weakness in Avian Flu Virus Found

2006-08-26T01:11:00.000-05:00

New Weakness in Avian Flu Virus Found
08.16.06, 12:00 AM ET

WEDNESDAY, Aug. 16 (HealthDay News) -- British researchers have identified a feature of the avian flu virus that could be a target for new drugs.

"This points the way to the development, in the future, of other types of drugs," said Dr. Pascal James Imperato, distinguished service professor and chairman of the department of preventive medicine and community health at State University of New York Downstate Medical Center in New York City. "The results of the research do not nullify the effectiveness of current drugs, but simply show that there may be a possibility of developing new ones in the future."

Imperato was not involved in the research, which was published online Aug. 16 in Nature.

Any new drug development is not going to happen right away, however.

"Given the long time period that it takes in research and development of such drugs, and then FDA approval, I don't see that occurring probably for several years," Imperato added. "There's no immediate benefit."

On the other hand, once drugs are developed, they could be applied to other viruses as well.

Health officials across the globe have worried that the bird flu virus that has infected 238 people and killed 139 worldwide might mutate, possibly in tandem with a more common flu virus, unleashing a new type of flu virus that could prove even more deadly because people's immune systems would not be able to fend off the disease.

Different nations have been stockpiling the drugs oseltamivir (Tamiflu) and zanamivir (Relenza) should the current H5N1 bird flu mutate and become able to infect humans.

Both drugs inhibit the enzyme neuraminidase (the "N" in "H5N1"), found on the surface of the avian flu virus, but they only block the N2 and N9 versions.

"Those drugs were designed using the structure from one group of neuraminidases and, it turns out, genetically, there's another group," said John Skehel, senior author of the study and director of the National Institute of Medical Research in London. "The first group contains five neuraminidases, and the second group contains four."

"What we've done is determine the structure of three of those four, which hadn't been done before and, it turns out, they show some structural differences from the group that was used to develop Tamiflu and Relenza," he continued. "The major difference is the presence of a cavity next to the active site of the enzyme. In this group, the cavity is a constant feature."

This suggests that it may be possible to design or identify other compounds that would block neuraminidase activity.

"Relenza and Tamiflu work, so the idea is that this difference in structure might be used to develop new drugs which would block the neuraminidase just in this group," Skehel explained. "It may also well be that they block activity in both groups."

And it may block activity in viruses as well.

Skehel's group is currently working with pharmaceutical interests to find or develop new drugs. It's possible that new drugs might work in tandem with Tamiflu and Relenza to overcome resistance to those agents. "It would be a combination therapy like you have in HIV," Skehel explained.

Few would deny the need for new weapons against avian flu, but a human pandemic may not loom quite as large as it once appeared.

When government researchers recently tried to combine the deadly H5N1 strain of bird flu with a common strain of flu that infects humans, they were unable to produce a strain that could be transmitted easily. This indicates that the road to easily transmissible bird flu is more complicated than once thought.

Also, Bloomberg News recently reported that two Michigan swans infected with bird flu don't have the lethal form spreading elsewhere.

More information

Visit the U.S. Centers for Disease Control and Prevention for more on bird flu.

Bird flu vaccination can ‘worsen spread’

2006-08-26T01:06:00.000-05:00

Bird flu vaccination can ‘worsen spread’
JAMES MORGAN

August 17 2006
Vaccinating poultry flocks against bird flu could make the spread of deadly strains such as H5N1 worse, Scottish scientists have found.

An Edinburgh University study concluded that, even though the available vaccines are effective on individual birds, the disease is likely to spread unless more than 95% of a flock has been protected.

The paper, published in the journal Nature, is the first to quantify how incomplete vaccination of flocks can contribute to the undetected spread of the disease.
In Vietnam, where 42 people have died of bird flu, mass vaccination of poultry has been successful in checking the spread of H5N1.

The Netherlands has already started unrolling a vaccination programme even though it has not yet been hit by H5N1.

But despite the Cellardyke swan, the UK authorities have ruled out a vaccination programme, on the grounds that it would disguise the spread of a much larger outbreak of H5N1.

"Silent spread" occurs because immunised birds can still catch and pass on avian flu, but without presenting any symptoms.

Therefore, as protection levels rise in a vaccinated flock, it becomes ever harder to detect the spread of avian flu, simply because fewer birds die. The result is increasing amounts of bird flu virus contaminating the birds' surroundings without farmers realising it.

The UK government's fears appear to be borne out by the new study, led by Dr Nick Savill, of the university's centre for infectious diseases.

Using computer modelling, Dr Savill found that, in practice, it is very hard to protect more than about of 90% of the birds in any given flock, and protection levels are usually much lower.

New Bird Flu Drugs Possible, Study Says

2006-08-26T00:15:00.000-05:00

ABC News
New Bird Flu Drugs Possible, Study Says
New Bird Flu Drugs Possible, Study Using Advanced X-Ray Technology Discovers
By MARIA CHENG
The Associated Press

LONDON - Advanced X-ray technology has helped scientists spot a new target that drug designers might use to attack the dreaded bird flu virus.

Though a new drug would still be years off, the new research being published Thursday offers hope of a fresh way to fight a disease that health experts fear could one day evolve into a deadly human flu pandemic.

"This gives us a new target that we didn't know we had before," said Dr. Michael Perdue, a flu expert at the World Health Organization, who had no role in the study.

Researchers used advanced X-ray technology to provide an "atomic picture" of the atoms and molecules that comprise one of the two surface proteins in the H5N1 virus.

Neuraminidase the "N" in H5N1 is the protein in bird flu that allows the virus to spread to other cells in the body. Drugs currently used to treat bird flu are based on other neuraminidase models that are not specific to H5N1.

By identifying H5N1's unique blueprint, researchers may one day be able to use drugs that home in on the strain that has killed 139 people in the past three years.

New drugs targeting H5N1 could potentially be used in combination with the current leading bird flu medication Tamiflu to reduce the risk of the virus mutating into a resistant form, said John Skehel, lead author of the paper appearing in the journal Nature.

Drug combinations can reduce the risk of a virus becoming resistant to one drug, a lesson learned in the fight against AIDS, noted Skehel, director of the National Institute for Medical Research in London.

Research into new flu drugs has traditionally focused on the neuraminidase protein because flu's other surface protein hemagglutinin, the "H" in H5N1 has proven harder to attack.

To date, Tamiflu, which was developed to treat human flu, is the only drug shown in lab studies to be somewhat effective against H5N1. However, there have been isolated instances of strains resistant to Tamiflu.

Experts agree on the importance of having more drugs in the arsenal to fight bird flu.

"Right now, our options are really quite limited," said Dr. Fred Hayden, an antivirals and influenza expert at the WHO. "We're really down to Tamiflu and Relenza, so there is a need for an alternative."

Though the timeline for producing a new drug usually takes between three to five years, it could potentially be shortened as countries accelerate their pandemic preparedness plans.

"Since drug companies have already attacked neuraminidase before, they should already have a lot of information on how to build compounds that would work in attacking it," said Perdue, who cautioned that the process of conducting clinical trials in humans could still take years.

Copyright 2006 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

Copyright © 2006 ABC News Internet Ventures

AVIAN INFLUENZA Low Pathogenic H5N1 vs. Highly Pathogenic H5N1

2006-08-26T00:04:00.000-05:00

Release No. 0296.06
Contact:
USDA Press Office (202) 720-4623

AVIAN INFLUENZA Low Pathogenic H5N1 vs. Highly Pathogenic H5N1
Latest UPDATE August 17, 2006

There are two types of avian influenza (AI) that are identified as H5N1. A difference exists in the virus classification; one is low pathogenic (LPAI) and the other is highly pathogenic (HPAI). Pathogenicity refers to the ability of the virus to produce disease.

HPAI H5N1, often referred to as the "Asian" H5N1, is the type causing worldwide concern. LPAI H5N1, often referred to as the "North American" H5N1, is of less concern. Following is an explanation of the differences between them.

LPAI H5N1 ("North American" H5N1)

LPAI, or "low path" AI, commonly occurs in wild birds. In most cases, it causes minor sickness or no noticeable signs of disease. It is rarely fatal in birds. LPAI strains are not a human health concern. This includes LPAI H5N1.

Evidence of LPAI H5N1 has been found in wild birds in the United States in recent years and is not closely related to the more severe HPAI H5N1 circulating overseas. Examples of historical reports of LPAI H5N1 received by USDA include:

1975 – LPAI H5N1 was detected in a wild mallard duck and a wild blue goose in Wisconsin as part of routine sampling, not as a result of noticeable illness in the birds

1981 and 1985 – the University of Minnesota conducted a sampling procedure in which sentinel ducks were monitored in cages placed in the wild for a short period of time and LPAI H5N1 was detected in those ducks in both years.

1983 – LPAI H5N1 was detected in ring-billed gulls in Pennsylvania.

1986 - LPAI H5N1 was detected in a wild mallard duck in Ohio as part of routine sampling, not as a result of noticeable illness in the birds.

2002 – LPAI H5N1 antibodies were detected in turkeys in Michigan but the virus could not be isolated; therefore this detection could not be confirmed.

2005 LPAI H5N1 was detected in ducks in Manitoba, Canada.

In the past, there was no requirement for reporting or tracking LPAI H5 or H7 detections in wild birds so states and universities tested wild bird samples independently of USDA. Because of this, the above list of previous detections might not be all inclusive of past LPAI H5N1 detections. However, the World Organization for Animal Health (OIE) recently changed its requirement of reporting detections of avian influenza. Effective in 2006, all confirmed LPAI H5 and H7 AI subtypes must be reported to the OIE because of their potential to mutate into highly pathogenic strains. Therefore, USDA now tracks these detections in wild birds, backyard flocks, commercial flocks and live bird markets.

HPAI H5N1 ("Asian" H5N1)

HPAI, or "high path" AI, spreads rapidly and is often fatal to chickens and turkeys. This includes HPAI H5N1. Millions of birds have died in countries where HPAI H5N1 has been detected. This virus has also infected people, most of whom have had direct contact with infected birds.

HPAI H5N1 has not been detected in the United States. However, other strains of HPAI have been detected and eradicated three times in the United States: in 1924, 1983 and 2004. No significant human illness resulted from these outbreaks.

The 1924 HPAI H7 outbreak was contained and eradicated in East Coast live bird markets.

The 1983-84 HPAI H5N2 outbreak resulted in humanely euthanizing approximately 17 million chickens, turkeys and guinea fowl in Pennsylvania and Virginia to contain and eradicate the disease.

In 2004, USDA confirmed an HPAI H5N2 outbreak in chickens in Texas. The disease was quickly eradicated thanks to close coordination and cooperation between USDA and State, local, and industry leaders.

TERMINOLOGY

Avian influenza (AI)--the bird flu--is a virus that infects wild birds (such as ducks, gulls, and shorebirds) and domestic poultry (such as chickens, turkeys, ducks, and geese). There is flu for birds just as there is for humans and, as with people, some forms of the flu in birds are worse than others.

AI viruses are classified by a combination of two groups of proteins: the hemagglutinin or H proteins, of which there are 16 (H1-H16), and neuraminidase or N proteins, of which there are 9 (N1-N9).

Pathogenicity: the ability of the virus to produce disease. AI strains also are divided into two groups based upon the ability of the virus to produce disease: low pathogenic (LP) and highly pathogenic (HP).

Low Pathogenic or "low path" avian influenza (LPAI): LPAI occurs naturally in wild birds and can spread to domestic birds. In most cases it causes no signs of infection or only minor symptoms in birds. These strains of the disease pose little significant threat to human health. These strains are common in the U.S. and around the world.

Highly Pathogenic or "high path" avian influenza (HPAI): HPAI is often fatal in chickens and turkeys. HPAI spreads rapidly and has a high death rate in birds than LPAI. HPAI has been detected and eradicated three times in U.S. domestic poultry. HPAI H5N1 is the subtype rapidly spreading in some parts of the world.

#

Out of obscurity step our best hope for bird-flu vaccine

2006-08-26T00:03:00.000-05:00

Out of obscurity step our best hope for bird-flu vaccine
Sunday, August 13, 2006
BY KITTA MacPHERSON AND ED SILVERMAN
Star-Ledger Staff

For years, the world's vaccine companies have labored in the shadows of the pharmaceutical industry, vilified by parent groups who claim childhood vaccines can cause neurological disorders like autism.

Now, almost overnight, these same companies have been thrust to the forefront of a massive campaign to produce a vaccine against pandemic flu. Not since Jonas Salk's work to find a cure for polio in the 1950s have vaccine scientists been so squarely in the vanguard of medicine.

The challenges are vast. The unanswered questions surrounding the influenza virus are profoundly difficult, the process for producing vaccines is slow and unwieldy, and the infrastructure needed to make major advances quickly has suffered from decades of neglect.

"I can't emphasize enough how daunting the task is to go about creating the industrial infrastructure to make hundreds of millions of doses in periods of months using technology that is on the drawing board," said Bruce Innis, vice president of clinical research and development for GlaxoSmithKline Biologicals in North Carolina.

But with avian flu spreading through flocks in Asia, Europe and Africa, raising the specter of a global pandemic, it's no longer a matter of choice.

The race is on.

INSUFFICIENT STOCKPILES
The influenza virus is one of nature's most talented chameleons. Its genetic matter allows for a constant reshuffling of genes.

This process, known as antigenic drift, alters the shape of its surface proteins in a way that can fool antibodies generated by the body to seek and destroy older versions of the flu virus.

Flu also is what scientists describe as a "superspreader." Its animal and human carriers are highly infectious before they even realize they are ill.

The bird flu virus known as H5N1 is a particularly lethal variant. Beyond wiping out millions of chickens and other birds, the virus has killed more than 130 people around the globe. Humans have no natural immunity.

The pathogen has not yet mutated to allow easy transmission between people, but government and industry scientists agree that society's defense system against such a threat is inadequate.

For starters, there is no surefire vaccine against the H5N1 virus. Even if there were, the ability to produce it quickly on a large scale is limited.

Officials at the federal Centers for Disease Control and Prevention have stockpiled new batches of H5N1 vaccine in an undisclosed location for safekeeping. But there is evidence the bird flu virus in circulation has mutated enough so that the vaccine supply may no longer provide protection, according to many scientists.

"We need a better vaccine -- clearly, one that works against multiple strains," said Anthony Fauci, director of the National Institute of Allergy and Infectious Disease. The agency, lead actor in the federal government's vaccine effort, funds research into bioterrorism countermeasures and treatments for diseases such as flu, AIDS and immune disorders.

The existing vaccine stockpile is also much too small to protect the general population. Of the 4 million doses available, one-third would be given to the military and the rest would be severely rationed.

"No matter how you slice that one, we don't have a large enough stockpile," Fauci said.

Traditionally, flu vaccines are grown in millions of fertilized chicken eggs, a process that can take six to nine months. Such a lengthy production cycle gets in the way of responding quickly to mutating flu strains.

Science and technology are not the only factors that have held back the field.

For many years, the inventions produced by vaccine companies were not viewed by the pharmaceutical industry as life-saving instruments, but as unprofitable commodities. Unlike treatments for chronic illnesses, which can reap billions for drug companies, vaccines could block an illness with a single shot.

Industry mergers and corporate decisions to leave the business because of low profits ended up reducing the size of the specialized, century-old field. Controversies, such as concerns over side effects and additives such as thimerosal -- which is at the center of the debate over childhood autism -- pushed the industry further to the margins.

Now, nearly overnight, the ground has shifted.

A BOOM IN THE MAKING
The global vaccine business is surging, according to a report by Richard Bernstein, chief investment strategist at Merrill Lynch. He forecasts double-digit growth rates over the next decade.

There are several reasons: New research techniques have created fresh opportunities for manufacturers; the demand for protection against bioterrorism has increased; developing nations have sought to raise immunization rates; and there has been a new emphasis on vaccines to treat, not just prevent, disease.

But clearly the biggest factor has been the avian flu outbreak.

The U.S. National Institutes of Health is pouring tens of millions of dollars into basic research on flu vaccines in both private industry -- mainly biotechs -- and academia. The effort has not been dampened by a report issued earlier this month by federal scientists that found it would not be so easy for the virus, genetically speaking, to mutate and spread among humans.

That report "provides meaningful information," said José Galarza, a vaccine scientist at TechnoVax Inc. in Tarrytown, N.Y. But scientists can't rule out the possibility that the right mutation could produce a true pandemic form, he said, and it's "necessary that we maintain surveillance."

The NIH's parent agency, the Department of Health and Human Services, is funneling more than $1 billion to major drug firms such as Novartis, GlaxoSmithKline and Sanofi-Aventis to enhance manufacturing capacity, support new construction and speed the conversion from egg-based vaccine creation to a process known as rapid cell-culture. This technique allows for the proliferation of animal cells infected with flu virus, nimbly producing the key content of vaccines.

Developing new kinds of weapons against pandemic flu requires massive investment and a sturdy infrastructure -- acres of property, huge plants and highly trained personnel.

Faced with this task of creating this arsenal, scientists, engineers and production experts are under unprecedented pressure to reinvent and scale up their most basic manufacturing processes -- and to stretch their thinking beyond available technologies.

There have been some promising developments already:

Breakthroughs in fundamental genetic science. The flu has been well-studied, from X-ray images of the virus in crystalline form to wholesale genetic sequencing. Such techniques have revealed secrets such as the virus' detailed surface structure and chemical patterns responsible for many of its key features. "We now have better technologies to make better vaccines both for the regular influenza vaccine and also against pandemics," said Peter Palese, a pioneering vaccine researcher at the Mount Sinai School of Medicine in New York.

"Broad" vaccines: An inoculation that provides a degree of immunity to a range of flu viruses is being developed by several biotech companies, including Novavax of Malvern, Pa.; Vical in San Diego; Protein Sciences in Meriden, Conn.; and PowderMed in Oxford, England. And some scientists even hold out hope for a "universal vaccine," a drug that in theory could protect a person against almost any pathogen it recognizes. Though years away, such a product is scientifically feasible, according to experts like Gary Nabel, director of vaccine research for the National Institute of Allergy and Infectious Diseases.

Improved boosters: Molecules known as adjuvants, which normally boost the body's immune response when added to a vaccine mix, are showing some promise in protecting humans against different versions of the flu virus. Glaxo last month reported its adjuvant-enhanced pandemic flu vaccine is more effective than any other vaccine to date.

Revitalized cell-culture technology: Scientists are taking a technique already used to produce other kinds of vaccines and tweaking it. Using cells taken from monkey or dog organs and growing them in lab dishes, scientists are infecting them with bird flu virus and growing those in huge vats laced with growth media. All the major pharma companies are experimenting with the technique.

Enlarged capacity: Sanofi is building a new cell-culture plant at its Swiftwater, Pa., facility; Novartis also is expanding, building a new facility in Europe and another one in Holly Springs, N.C.; and Glaxo will be tripling the capacity of its Quebec vaccine plant and doubling that of a European factory. With more capacity and a faster manufacturing process, these companies are hoping to dramatically improve their ability to respond to a pandemic.

ON A MISSION
Some industry analysts speculate that big pharma and smaller biotech firms eventually may form strategic alliances for vaccine discovery and invention to capitalize on collective strengths.

"They could become knights in shining armor," said Mark Ravera, an industry analyst with Strategic Pharma in Chatham. "Because, if bird flu shows up, the general public would probably be grateful these companies had the foresight and made the investment to fight this disease."

Those who have stayed with the science are feeling a sense of mission. "I feel honored to be part of this effort and I'm excited that I can do something important," said Norbert Klein, a vaccine manufacturing executive with Novartis in Marburg, Germany. "What we are coming up with is a much more robust technology. It has very distinct advantages for future developments."

The prize, for the public and the companies who will profit, will be, if not a universal treatment, then at least broader protection against a killer that can mutate with abandon, rendering custom-tailored vaccines useless. And the technologies developed for new types of seasonal and pandemic flu vaccines could be used to fight other diseases, opening up potentially lucrative markets.

"It's a foot race all right, with everyone out there toe-to-toe waiting for the big break," said Richard Bright, vice president for vaccine development for Novavax, one of several fledgling biotechs in the hunt. "And someone is going to get it."

© 2006 The Star Ledger
© 2006 NJ.com All Rights Reserved.

Threat of avian flu prompts crisis plans

2006-08-25T23:48:00.000-05:00

Threat of avian flu prompts crisis plans
Seminar for health care workers and area residents underscores need to prepare for pandemic

By AMBER VAN NATTEN, Special to the Times Union
First published: Friday, August 11, 2006

Messages like "Keep your germs to yourself. STAY HOME!" or "Did you ask about masks?" greeted Kathy Beers and Tina VanDerwerken on a recent visit to Glen Sanders Mansion in Scotia.

The women -- Beers of Schenectady and VanDerwerken of Scotia -- attended a Schenectady County seminar on pandemic flu preparedness. And they weren't alone, more than 200 health care workers, volunteers and concerned citizens participated in the day-long sessions that covered everything from explaining what bird flu is to explaining how families can protect themselves.

"According to the World Health Organization and the Department of Health, we're overdue for a pandemic," said Glynnis Hunt, health education coordinator for the Schenectady County Health Department. "We feel it is a real concern and we're preparing for that."

Besides the seminar at Glen Sanders, the New York State Department of Health and the New York State Emergency Management Office also held a recent flu planning forum. In a separate event, Hometown Health Center in Schenectady brought experts and workers together to talk about worst-case scenarios and strategies to deal with them. And hospitals across the region have been running drills to test their plans and taking part in these county- and state-wide efforts.

"We feel that the more prepared people are now, the less chaotic the situation will be in the event of a pandemic," said Hunt.

The trigger of a pandemic anytime soon would most likely be avian influenza, or bird flu, which had claimed 134 lives worldwide by the end of July, according to health experts. According to the World Health Organization, a U.N. specialized health agency, more than half those that contract the disease die from it.

"I've been following the flu pandemic since it came out," said VanDerwerken, a stay-at-home mom. "I'm very interested personally in this. I'm very prepared though. I have enough food and water for six months."

Beers, a school nurse at Ballston Spa High School, said she, too, is concerned.

"People need to be informed. I feel very strongly about this," said Beers. "People are going to start to see things happen in the community a lot sooner than they might think."

In fact, the state has 60,000 flu treatments stockpiled and is purchasing more than a million anti-virals for recently infected people, according to Robert Kenny, the state health department's public affairs director. Of $29 million in the state budget for pandemic flu planning, most of it -- $23 million -- will go to medications. The rest goes to planning, equipment and supplies.

At the Glen Sanders planning session, three training seminars took place: one for health care professionals, one for volunteers and one for the community.

"We're only scraping the surface," said Dr. Russell Fricke, Schenectady County's public health commissioner. "There needs to be a broader discussion in this country."

Fricke specifically worried about broad-based financial planning.

"Businesses will have to interact with the government because what will parents or single parents do if they can't come to work for extended periods of time?" he said. "Will they still receive an income if they can't come to work because they're sick or their family is sick?"

That's partly where volunteers will come in. Health care agencies, like the county department, will need volunteers to help with child care, translation, inventory and delivering medicines quickly.

"We need a reserve of medical and non-medical volunteers to help," said Shelly Glock, Schenectady County's volunteer coordinator. "We want people to be trained, organized and ready in case of an emergency."

Anyone interested in volunteering can sign up online at http://www.schenectadycounty.com or by phone at 386-2810.

"If a large amount of people become ill, the system will become overwhelmed," said Glock. "People may need to care for their family, their co-workers and their neighborhoods and we want to train them to do that before it happens."

At the planning sessions hosted by the state, media representatives were asked to talk through how vital and possibly life-saving information in the event of a pandemic would be disseminated.

"We want to plan ahead how the Department of Health will get information to the media and how the media should take that information and present it to the public," said Rachel Smith, a state environmental scientist.

While news outlets would still be relied on to pass along accurate and timely information, they would be facing similar problems with staff shortages and a lack of resources.

"If your delivery guy sneezes on a newspaper and then drops it on your front step, that could be a problem. Does he have bird flu? Do you have it now? Is that going to make you stop reading the paper?" said Mike Spain, the Times Union's deputy managing editor, who attended the forum. "As far as covering stories, our people are going to be on the front lines if anything happens, and that could mean exposure to the virus. These are things we have to think about."

At Hometown Health Center, which serves mostly low-income residents, center workers and experts ran a planning session, called a tabletop drill to strengthen plans and check weaknesses in its system.

Besides expressing concern over possible language barriers among the center's employees and its multilingual community, the staff noted it would need backup in case workers grew ill. If nothing else, they noted, patients with chronic conditions like diabetes or AIDS would need to keep their appointments.

"There's a lot of holes between what's on paper and what we really have to do," said John Silva, the center's CEO.

Organizing and leading the center's drill was Dr. Jonathan Weinstein, emergency preparedness director for the Community Health Care Association of New York State, a nonprofit public advocacy association.

Weinstein suggested the center establish an extra fund for emergencies. In a pandemic, patients without health care or resources still would need to be treated. That and overtime worked by staff members would create a financial burden that health centers would need to prepare for.

Other than those issues, the staff said it felt reassured by the session.

"We've attended several flu presentations and we have an excellent clinical staff. I think we would be more ready than most places," said Angella Timothy, the center's executive vice president.

As for hospitals in the Capital Region, they have participated in such county- and state-wide sessions and continue with other efforts.

"Disasters affect more than just one hospital," said Scott Heller, director of the regional resource center for emergency and disaster preparedness in Albany. He works out of Albany Medical Center Hospital. "It's not just an Albany Med issue or a St. Peter's Hospital issue. It will be a problem for every health care facility in the region."

According to Paul Segovis, emergency preparedness coordinator at Ellis Hospital in Schenectady, his hospital has coordinated efforts with the county, and staff recently participated in a drill to test their emergency plan.

"Will things go perfectly? No. We can't anticipate every scenario, but we have the requirements in place to respond to any emergency that comes our way," said Segovis. "We're keeping an eye on avian flu and being aware of it, but we're also going to be ready. At this point we hope it never happens, but if it does, we'll be ready."

No plan could ever be final, as every organization tweaks its effort with new information and discussions, but Heller said, "As a whole I think we're a lot better than we were three or five years ago. Our plans are constantly changing and evolving anytime something occurs with the potential to affect us locally. We've really come a long way."

Amber Van Natten, a Times Union intern, is a SUNY Purchase sophomore. She can be reached at 454-5420 or by e-mail at avannatten@timesunion.com.

How to be prepared

Dr. Jonathan Weinstein, emergency preparedness director for the Community Health Care Association of New York State, offered these tips for how people can prepare themselves and their families before an emergency:

Have a family emergency plan. If you work and have young children, arrange now for them to stay with a neighbor, friend or family member in case of an emergency. Discuss with your family what you would do and how you would contact each other in different emergency situations.

Have basic supplies in your home to last for several days such as water (one gallon per person per day); nonperishable food; a battery-operated radio; a flashlight; blankets and a first aid kit containing over-the-counter medications for fever, pain and minor stomach problems; anti-bacterial ointments; and an extra supply of any prescription medication especially insulin or asthma inhalers.

Practice hand hygiene and respiratory etiquette. Wash your hands frequently with hot water and anti-bacterial soap. Wash hands after coughing, sneezing or blowing your nose. Cover your mouth and nose with a tissue when sneezing or coughing or cough and sneeze into the crook of your arm to avoid spreading germs. If you have flu-like symptoms or are in contact with someone with flu-like symptoms, wear a mask.

Go Online to the American Red Cross (http://www.redcross.org) or the Centers for Disease Control (http://www.bt.cdc.gov) to get more information on how you can prepare your family for an emergency.

All Times Union materials copyright 1996-2006, Capital Newspapers Division of The Hearst Corporation, Albany, N.Y.

Bird Flu Monitoring Goes Nationwide

2006-08-10T23:42:00.000-05:00

--------------------------------------------------------------------------------

Bird Flu Monitoring Goes Nationwide

WASHINGTON, Aug. 10, 2006
--------------------------------------------------------------------------------
(CBS/AP) Monitoring of wild migratory birds to prevent a deadly bird flu virus is expanding to cover the entire nation and U.S. territories in the Pacific.

The stepped-up testing will be done by scientists in the lower 48 states, Hawaii and other Pacific islands. They will begin keeping an eye out for the deadly H5N1 strain of the avian flu that has killed more than 100 people, mostly in Asia.

In Alaska, where the first migratory birds began arriving, monitoring started just before summer.

"This move to test thousands more wild birds throughout the country will help us to quickly identify, respond and control the virus if it arrives in the United States," Agriculture Secretary Mike Johanns said Wednesday. "Because we cannot control wild birds, our best protection is an early warning system."

Interior Secretary Dirk Kempthorne said more coordinated monitoring by federal agencies, states and universities "will be important this fall as birds now nesting in Alaska and Canada begin their migration south through the continental United States."

The Agriculture and Interior departments are providing $4 million to state agencies to collect samples from specific species of migratory birds winging along four major U.S. migratory bird flyways. Congress budgeted $29 million for monitoring for the highly pathogenic strain of bird flu.

Feces or tissue samples from 75,000 to 100,000 wild birds will be collected, along with 50,000 samples of the water and ground that birds come into contact with. Locations where the samples will be collected will vary depending on weather and habitat conditions.

Likely sites include national and state wildlife refuges and parks, city ponds and parks, and private lands where owners have given approval.

While the much-talked-about H5N1 avian flu virus has yet to make an appearance on American soil, restaurants and other companies that rely on poultry sales are preparing for it, and for the impact it could have on their business.

Boston Market Corp. is developing and testing alternative menu items at its Golden headquarters.

Officials at Red Robin Gourmet Burgers Inc. are prepared to substitute pictures of burgers for those of chicken sandwiches on the company's menus and signs.

Executives at Red Bird Farms Co. in Englewood have drafted a nine-point plan for communicating the safety of their product.

Since 2003, the virus has infected at least 231 people in 10 countries in Asia and the Middle East, killing 133. All have contracted the virus from direct contact with infected birds and not from the food supply.

Experts say the virus cannot survive in poultry that has been cooked to 165 degrees and that infected birds are exterminated before they even make it into the food supply.

Nonetheless, a survey of 1,043 adults released this year by the Harvard School of Public Health found that nearly half the respondents who eat chicken or other poultry said they would stop doing so if an outbreak occurred among U.S. flocks.

A similar crisis hit the U.S. beef industry in 2003, when bovine spongiform encephalopathy — better known as mad cow disease — was discovered in a cow in Washington.

©MMVI CBS Broadcasting Inc. All Rights Reserved. This material may not be published, broadcast, rewritten, or redistributed. The Associated Press contributed to this report.

Release of Indonesian avian, human H5N1 viruses may offer insights on spread

2006-08-10T23:32:00.000-05:00

Release of Indonesian avian, human H5N1 viruses may offer insights on spread
18:21:18 EDT Aug 10, 2006
Canadian Press: HELEN BRANSWELL, The Canadian Press
(CP) - The scientific community may soon have a clearer picture of what is going on with the H5N1 avian flu virus in Indonesia, the country which most concerns many experts following the worrisome virus.

After hoarding for months the genetic blueprints of the viruses isolated from both poultry and people, Indonesian officials have done an about-face and are sharing a large number of both avian and human viral isolates.

A scientist with the UN's Food and Agriculture Organization confirmed Thursday that Indonesia recently sent 91 avian viruses to the Geelong Laboratory in Australia, a reference lab for the FAO.

"We managed to get 91 isolates out to Geelong about two weeks ago. Took us months to get it to happen. But they arrived I think about 10 days ago or something like that - in good condition," Dr. Peter Roeder, an animal health officer with the Rome-based FAO, said in an interview.

"It will make a tremendous difference in the interpretation of the sequence data of the human viruses."

Last week the country's health minister, Siti Fadilah Supari, announced that Indonesia wanted the genetic sequences of all the viruses isolated from human cases in Indonesia to be put into open access databases where any scientist could study them.

The ability to compare the viruses spreading through bird populations to the ones that have jumped into people should provide badly needed insight into the H5N1 situation in Indonesia, where investigators have often been stumped trying to determine how people contracted the virus. A number of investigations have shown few if any links between human cases and infected birds.

The Geelong lab has been working to sequence the avian viruses and should have some initial results any day now, Roeder said. That information will be placed in the public domain, he added.

"As soon as the sequence data become available to the government of Indonesia we have an agreement with them that they'll make it available to the international community."

Sequence data for viruses isolated from about 40 human cases has in recent days been placed in public access databases. When the World Health Organization learned Indonesia was willing to share the data, it asked the two laboratories that had sequenced the viruses for Indonesia to put the information into the public domain. Up until then the data had been stored in a password-protected database accessible only to scientists working for the WHO or for laboratories that do this type of work for the organization.

The two labs quickly complied with the WHO request.

Last Friday, scientists at the U.S. Centers for Disease Control in Atlanta transferred the data into the open access database housed by the U.S. Department of Energy's Los Alamos National Laboratory, whose computers also host the password protected databank. The CDC was also in the process of logging the material into a second public access database, Genbank, the director of the agency's influenza division, Dr. Nancy Cox, said earlier this week.

The second laboratory, at the University of Hong Kong, is run by noted influenza expert Dr. Malik Peiris. In an interview Thursday, he confirmed that his team put the data into the Los Alamos database last Saturday.

Dr. Ilaria Capua, an Italian veterinary virologist who has spearheaded a campaign to put sequence data for all H5N1 viruses in the public domain, said Indonesia's move may be part of a trend to greater openness.

"There is a growing consensus on this data sharing," Capua, who runs an avian influenza reference laboratory for the International Organization for Animal Health, said from Rome.

"I would applaud Indonesia and then invite all the other health ministers (of affected countries) to follow that example. And then the veterinary isolates will come."

As for the human isolates, Peiris said there is a lot of overlap between the viruses his lab sequenced and the work done by the CDC.

Peiris said the viruses isolated from human cases showed no evidence of having swapped genes - the process is called reassortment - with flu viruses from humans, pigs or other mammals. Reassortment is one of the ways an avian flu virus could acquire the ability to spread easily to and among people, a development that would lead to a flu pandemic.

"There isn't anything (evident in the human isolates) that rings particular alarm bells as such," Peiris said.

But he suggested the viruses that infected people in Indonesia are only one part of the picture of what is going on there.

"It is probably important to have more avian virus sequences from the same geographical areas where the human cases are coming from," he said from Hong Kong.

Experts tracking the dangerous and economically devastating H5N1 virus have been concerned about Indonesia, where inadequate control methods have led to widespread outbreaks across the vast and densely populated archipelago.

Indonesia trailed other affected Asian countries in developing human cases, marking its first in July 2005. But since then cases in Indonesia have cropped up at a rate unparalleled elsewhere. And the country's H5N1 death toll recently surpassed that of Vietnam to make Indonesia the country that has lost the most lives to the virus.

Indonesia has logged 56 confirmed human cases, 44 of which have been fatal. Globally 236 cases of H5N1 infection have been confirmed in 10 countries since late 2003 and 138 of those people have died.

© The Canadian Press, 2006

Indonesia, Worst Affected by Bird Flu, Denies Lax Control

2006-08-10T23:30:00.000-05:00

Indonesia, Worst Affected by Bird Flu, Denies Lax Control
Aug. 9 (Bloomberg) -- Indonesia, which has the most number of human deaths from avian influenza, said it hasn't been lax in controlling the spread of the virus.

``It's untrue that Indonesia is hesitant to act, one that suggests we're hesitant to use our own money and that we're hesitant to perform culling,'' Coordinating Minister for People's Welfare Aburizal Bakrie told reporters today.

The world's fourth-most-populous nation yesterday confirmed its 43rd fatality from the H5N1 virus, surpassing Vietnam as the country with the most deaths. Problems enforcing measures to stem the spread of the lethal H5N1 avian influenza virus have led to more Indonesians becoming infected.

Some local government leaders were deliberately ignoring culling orders, hampering efforts to stamp out infections in birds, Vice President Jusuf Kalla said on July 22.

``It's not that easy to cull because there are social issues that must be considered,'' said Bakrie, who is also the head of the nation's committee for avian influenza control and pandemic influenza preparedness. Authorities will continue to cull, ``like it or not,'' he said.

Bird flu has infected 55 people in Indonesia since July last year, according to the World Health Organization. Vietnam reported 93 cases since 2003, including 42 deaths. It hasn't reported any avian flu cases this year.

Bakrie said it is a challenge to conduct surveillance in Indonesia, the world's largest archipelago, which has 70,000 villages across 17,000 islands.

Backyard Poultry

The virus has spread in poultry in two-thirds of the country's 33 provinces since late 2003. Poultry is raised in the backyards of about 80 percent of the country's 55 million households.

Since 2004, 28.93 million chickens have been culled, about 20 percent of which were backyard poultry, and authorities have vaccinated 262 million chickens, Agriculture Minister Anton Apriantono said.

Experts are concerned the virus may infect people until it's controlled in poultry. The disease may spread to people in close contact with infected live birds, according to the Geneva- based WHO. Cooking kills the virus and no cases of transmission from cooked food have been recorded, the agency said.

Delays in finding and isolating cases risk exposing people to the virus and increase opportunities for it to mutate into a pandemic form.

There's a lack of trained personnel and equipment and many Indonesians are ignorant about the disease-deterring progress to control the virus, Larry Allen, senior technical coordinator with the U.N. Food and Agriculture Organization, said in a phone interview today.

``There's more disease outbreaks taking place than the central government is aware of,'' said Allen. ``It's a big problem out there but there's limited resources available to deal with it.''

To contact the reporter on this story:
Karima Anjani in Jakarta at kanjani@bloomberg.net.

Last Updated: August 9, 2006 08:41 EDT

Indonesia Records 43rd Bird Flu Death

2006-08-07T22:43:00.000-05:00

Indonesia Records 43rd Bird Flu Death

By ALI KOTARUMALOS
The Associated Press
Monday, August 7, 2006; 11:09 PM

JAKARTA, Indonesia -- A 16-year-old boy in Indonesia died Monday from bird flu according to local test results that, if confirmed, would push the country's death toll from the disease to the highest in the world.

Normally reliable tests performed at a local laboratory showed the boy had the H5N1 virus, said Dr. Santoso Suroso, the director of the capital's infectious diseases hospital.

The boy, whose name was not released, was admitted to the hospital on Saturday.

Health officials said he had come into contact with sick chickens at his home, just east of Jakarta.

If confirmed by a World Health Organization-accredited laboratory, the death would be Indonesia's 43rd from the virus since July 2005, a third of which occurred this year.

Neighboring Vietnam is the second hardest hit at 42, but it has not recorded any deaths in 2006.

The H5N1 virus has killed at least 135 people worldwide since it began ravaging Asian poultry stocks in late 2003, according to WHO. That figure does not include Monday's death in Indonesia.

Most human cases have been traced to contact with infected birds, but experts fear the virus _ which remains hard for people to catch _ will mutate into a form that spreads easily among people, potentially sparking a pandemic.

Experts say Indonesians will continue to die until the nation stops the rampant spread of infection among its hundreds of millions of backyard poultry.

"You've got to worry about the humans, but if you don't clean up the animals, it doesn't matter what you do," Dr. Anthony Fauci, the U.S. National Institutes of Health's infectious disease chief told The Associated Press by phone.

Vietnam largely controlled the spread of the virus by launching a nationwide mass vaccination campaign for poultry last year. Thailand, which has reported 16 deaths, relies on strong village-based surveillance and mass slaughtering when outbreaks are discovered.

Bird flu in Indonesia grabbed the world's attention in May when seven members of a single family died of the virus _ the largest recorded cluster to date. The WHO concluded that limited human-to-human transmission likely occurred, but the virus did not spread beyond the blood family members.

___

Associated Press medical writer Margie Mason contributed to this report.

© 2006 The Associated Press

Are hospitals ready for a flu pandemic?

2006-08-07T22:19:00.000-05:00

Are hospitals ready for a flu pandemic?
Editor's note: This is another in an occasional series exploring how the suburbs and state are preparing for the possibility of a deadly flu pandemic.

BY MARNI PYKE and DAVE ORRICK
Daily Herald Staff Writers
Posted Sunday, August 06, 2006

A Daily Herald survey of suburban hospitals shows many aren't fully prepared for a potentially deadly flu pandemic - a situation that reflects a national trend.

Seventeen medical centers were surveyed on their readiness for a global epidemic in the wake of concerns about avian flu. Another seven hospitals declined to take part in the study, which was based on recommendations by the federal government.

Results for the 17 medical centers that did participate, indicated that although some were well on the way to preparedness, others lagged behind.

The survey found shortfalls in critical areas.

• More than 40 percent of hospitals did not have complete plans for allocating life-saving medical resources to patients in the event of a pandemic.

Mark Welsh/ Daily Herald
The Alexian Brothers Medical Center ER prepares for a pandemic flu by staging a Code Three Drill.

• Nearly 60 percent hadn't conducted an avian-flu-specific drill.

• At total of 18 percent answered yes to all the survey questions.

"I think if anything, your survey shows we better hope there isn't a pandemic in the near future because the system isn't ready," said Jeffrey Levi, executive director of the Trust for America's Health, a nonprofit national organization that focuses on epidemic prevention.

However, other experts gave suburban hospitals higher grades, given the state of readiness nationwide and the exorbitant costs involved.

Right now, avian influenza is not a pandemic. But international scientists are cautiously tracking the spread of the H5N1 strain of bird flu.

More than 100 people, mostly in Asia and Africa, have died as a result of contact with infected birds, according to the World Health Organization. The virus has left an estimated 150 million birds dead.

Avian flu doesn't easily transmit between humans. The fear is if H5N1 mutates to a virus that spreads quickly from person to person, millions could die worldwide.

That's why health experts say it's essential hospitals be prepared for the worst.

"Pandemics have occurred many times in the past. They do occur and will occur in the future," said Dr. John Agwunobi, assistant secretary of health with the U.S. Department of Health and Human Services. "Therefore it is important that every part of the world prepare for and stay prepared for a pandemic."

Yet, "No matter how much preparation we do, it will be a very bad situation," Levi said.

No sense of urgency

Imagine a deadly disease spreading rapidly through the metropolitan area, infecting hundreds and killing 44 people, including two nurses and a doctor, within five months.

It sounds like a movie of the week, but it played out for real in early 2003 when severe acute respiratory syndrome, or SARS, made a deadly appearance in Toronto.

Brought to Canada by a woman returning from Hong Kong in February 2003, the virus wasn't identified for weeks. By that time, many medical workers had fallen sick after caring for SARS patients.

"I think SARS was a wake-up call for many," Agwunobi said.

"SARS was global, so like a pandemic it threatened more than one nation. The other thing that made it unique was that it really was a hospital-based infection. It prompted greater attention to infection control in hospitals."

Since 2003, 134 people have died as a result of coming in contact with the H5N1 virus, according to the WHO. The latest fatality occurred July 24 in Thailand, when a 17-year-old man died 14 days after burying chicken carcasses.

Despite the grim statistics, pandemic expert Dr. Eric Toner fears some hospitals are asleep at the switch.

"Most hospitals haven't taken avian flu seriously. Most have not really drilled on it," said Toner, a senior associate with the Center for Biosecurity. The center, based at the University of Pittsburgh Medical Center, focuses on societal effects of infections and diseases.

"Almost no hospitals have the necessary resources to prepare for a pandemic," he said.

By the numbers

The Daily Herald's one-page questionnaire was based on a lengthy checklist issued early this year by the federal government. The analysis of the survey was conducted using data collected in May, June and July.

Among the hospitals that participated in the study, only 41 percent had conducted an avian flu-specific drill.

About 47 percent reported carrying out a related exercise or indicated that they intended to do so in the future.

Agwunobi recommended every hospital conduct a drill.

"The reason we conduct exercises is not to show what works," he said. "Exercises should be geared to find out at what point the system breaks down."

Many medical centers - 88 percent - had created plans to prioritize workers and offer them medications to lessen the likelihood of infection.

The study also showed more than 90 percent of hospitals had named an influenza preparedness coordinator.

However, just 67 percent of medical centers had set a threshold for how many avian flu cases it would take to activate emergency plans.

And, only 56 percent had tackled tough ethical issues, such as how to ration resources if hospitals are swamped with influenza patients.

Northwest Community Hospital is at a high level of preparedness, but Emergency Response Coordinator Mary Casey-Lockyer noted the Arlington Heights-based facility is still fine-tuning issues such as rationing ventilators - a situation she said reflects what's happening nationwide.

"We don't have very many ventilators in the country," she said. "It's a question of how we disperse them and how we triage patients - who gets a ventilator and who doesn't."

One of the many challenges medical centers face as they prepare is the lack of health-care workers, said Darlene Gallagher, infection control manager at Adventist GlenOaks Hospital in Glendale Heights.

"There's a shortage of nurses, respiratory therapists, pharmacists, radiologists," she said. "What happens when they get sick? You can have the greatest plan on the books but you have to have the people."

The saving grace, Gallagher noted, is that agencies such as the Centers for Disease Control and the World Health Organization are closely monitoring the spread of H5N1.

"We will know when the virus changes to become a pandemic. It's not something where tomorrow it would be in the Northwest suburbs," she said.

Overall, the Center for Biosecurity's Toner was impressed by the survey results.

"I think the 41 percent who have done an avian-specific drill is higher than the national average," he said.

But Toner pointed out answering "yes" doesn't necessarily indicate how thorough is the planning.

"The devil's in the details," he said.

The Daily Herald consulted with experts familiar with pandemic planning to make sure the study was informed, fair and filled with questions the public should know.

Still, seven hospitals either refused to participate or submitted a generic statement.

Centegra Health System, which runs two hospitals in McHenry County, was one such organization.

"We just don't feel that the survey is a fair indicator of our level of preparedness," said Melissa Matusek, Centegra spokeswoman.

Health-care experts contend that the more information made public about a potential pandemic, the better.

"No matter how much preparation we do, this is going to be a very bad situation," Levi said. "A public that has been warned will be much more accepting."

Toner agreed. "The public needs to know this information," he said.

'Mass confusion'

Across the country, health-care leaders are worried about inadequate funding and insufficient guidance for hospitals in the event of an influenza-type pandemic.

"Hospitals have the biggest burden to address, and it's going to take far more resources than the government is willing to put on the table," Levi said.

The Center for Biosecurity estimates it will cost $5 billion to get hospitals across the country "minimally" prepared for a severe flu pandemic.

Being truly ready goes beyond drills and protocols, Toner said.

"A lot of being prepared involves stockpiling things such as masks, gowns and gloves," he said. "That's very expensive and few hospitals have resources to put away serious supplies. It also involves stockpiling medications."

Condell Medical Center in Libertyville is one hospital in the midst of ordering negative-pressure tents to deal with a surge in capacity. These high-tech tents equipped with ventilation systems could be draped over a patient's bed and filter out contaminants before air is released in the open.

"We have 11 negative-pressure rooms, but if you have 30 or 40 patients, we wouldn't have enough," said nurse Emily Bergman, Condell's Infection Prevention and Control Program coordinator. One tent alone could cost up to $6,000.

Another dilemma is a lack of detailed guidance from federal or state agencies, some experts contend.

"You will find once a hospital gets its teeth into this issue, then it starts churning out more questions," said Dr. Charles Baum, vice president for health affairs at Alexian Brothers Hospital Network.

As an example of the "mass confusion" being experienced by hospitals, Baum cites debate over flu vaccines. In the event of a pandemic where vaccines are mandatory, it's unclear who carries the insurance liability if someone falls sick as a result.

"Nationally, no one is stepping forward and saying, 'We'll relieve you of your liability for vaccination,'æ" Baum said.

Agwunobi said government agencies are issuing guidelines on a regular basis but pandemic readiness is a broad field and all the questions can't be answered at once.

Another uncertainty is paying for the uninsured.

"We have a large number of uninsured people, and we want them to come and get care," Levi said. "If hospitals take care of these individuals, the government needs to step forward and say costs will be covered. We want hospitals to be financially viable at the end of the pandemic."

Toner acknowledged that the federal government can't handle the financial burden alone. "It's (funding) got to come from a variety of sources, he said.

Agwunobi said Congress already has given out $325 million for hospital preparedness and another $250 million is on the way.

"States, local governments, the federal government - we should all be involved in a partnership to strengthen the system," he said.

Agwunobi avoided criticizing hospitals that refused to participate in the Daily Herald's study.

He said the checklist is voluntary and each hospital is unique. "The key is going to be having hospitals working closely with each other."

Overall, the state is in good shape, said Jay Bogdan, deputy director of the Illinois Department of Public Health's Office of Preparedness and Response.

"We are more prepared today than we were five years ago," he said, "and we continue to get more prepared."

Toner also saw signs for optimism. "Hospitals are beginning to get the message," he said. "Even if they're not doing what we think is necessary, they are drawing up plans and doing drills and that's at least a step in the right direction."

Daily Herald staff contributed to this report.
dailyherald.com

Vietnam kills wild storks to prevent bird flu spread

2006-08-07T22:15:00.000-05:00

Vietnam kills wild storks to prevent bird flu spread
05 Aug 2006 03:54:14 GMT
Source: Reuters

HANOI, Aug 5 (Reuters) - Vietnam's animal health workers have killed 53 wild storks at a theme park in Ho Chi Minh City after random tests showed two of the birds carried an avian influenza virus strain, officials said on Saturday.

An official at the park said the findings of the H5 component, part of the H5N1 poultry virus, led to the slaughter of the birds even though they all appeared healthy.

Wild birds are natural hosts of bird flu viruses and often don't show symptoms but can pass the viruses to poultry. H5N1 can kill chickens within 24 hours of infection.

H5N1 is an influenza type-A virus that has killed 42 people in Vietnam since late 2003, but there have been no human infections detected in the Southeast Asian country this year.

The latest outbreaks in Laos and Thailand, where bird flu killed a teenager in late July, fanned fears that the virus known to have killed 134 people worldwide was flaring up again in Asia.

Vietnamese officials say a failure to control waterfowl, which can be silent carriers of bird flu, made the country vulnerable to new outbreaks and wild birds believed to carry H5N1 would soon migrate from the north, raising the risk of infection.

With Indonesia's say so, WHO to share bird flu data with scientific community

2006-08-07T22:13:00.000-05:00

With Indonesia's say so, WHO to share bird flu data with scientific community
17:26:18 EDT Aug 4, 2006
HELEN BRANSWELL

Canadian Press: HED IS 77 CHARACTERS
(CP) - The World Health Organization on Friday welcomed the announcement that the Indonesian government had agreed to share with the global scientific community the genetic blueprints of the H5N1 avian flu viruses retrieved from human cases in that country.

A WHO official said the Geneva-based organization has instructed the WHO reference laboratories that sequenced the viruses for Indonesia to deposit their blueprints into Genbank, a databank which places no restrictions on who can study the genetic information it contains.

"What we will do is ensure that the labs - i.e. CDC and Hong Kong - that would have specimens from Indonesia are aware of the announcement from Indonesia . . . that there is permission," said Dr. Paul Gully, a former top official of the Public Health Agency of Canada who was seconded to the WHO's global influenza program earlier this year.

"It's not a very difficult process for the labs to actually upload that information. So I think we're just waiting to hear from them that that's actually happened."

Sequencing of viral isolates from Indonesia's human H5N1 cases has been done by a laboratory at the University of Hong Kong run by leading influenza authority Dr. Malik Peiris and by the U.S. Centers for Disease Control in Atlanta.

Indonesia only began recording human cases of H5N1 in early July of last year. But in the intervening 13 months, its problem with the devastating virus has become acute. At least 54 people in Indonesia have been infected and 42 of those people have died. Only Vietnam - with 93 infections and 42 deaths - has suffered a similar human toll.

Like authorities in several other countries, Indonesian officials have been reluctant to share their viruses with outside scientists eager to use them to try to track the evolution of the H5N1 virus and crack the mysteries of its remarkable virulence.

The journal Nature recently reported that the country has exported few, if any, virus samples retrieved from domestic poultry over the past year.

"I've learned that scientists across the world have complained that they could not access the data and made statements as if we had hidden it," Indonesian Health Minister Siti Fadilah Supari said Thursday in a news conference at which she announced the decision to share the sequence data from the human cases.

"For the sake of basic human interests, the Indonesian government declares that genomic data on bird flu viruses can be accessed by anyone."

The decision will increase dramatically the amount of sequence data on human H5N1 cases in the public domain. Many of the genetic blueprints of H5N1 cases are held in a password-protected database only available to scientists from the WHO and the laboratories which sequence viruses for it - a situation that has been harshly criticized.

Ownership of a virus rests with the country in which is was isolated. And only that country can agree to allow a viral isolate to be shared. But critics of the system suggest the reluctance to share extends beyond individual countries to some of the labs in the WHO network.

Steven Salzberg, director of the Center for Bioinformatics at the University of Maryland, is among the system's critics. And on Friday, he applauded Indonesia's decision not just to share, but to share openly.

"I think this is very good news and I'm very pleased that the Indonesian health minister has decided that it's important to share the samples and these data with the rest of the community," he said.

"I think it will help us to understand better how the flu is mutating and spreading in the population."

According to the Jakarta Post, the Indonesian health minister said the decision to put the genetic sequence information into an open-access database was based on a recommendation from the medical committee of the Indonesian Academy of Sciences, a forum of experts that advises the government.

The newspaper quoted a member of the academy, Professor Sangkot Marzuki, as saying the committee felt emerging diseases like H5N1 should be addressed promptly, by as many experts as possible. Marzuki said in making its recommendation, the academy weighed potential economic benefits to Indonesia of restricting access to the information, including possible uses for vaccine and drug manufacture as well as potential royalties from intellectual property rights.

© The Canadian Press, 2006

Avian flu pops up in German zoo

2006-08-07T22:08:00.000-05:00

Avian flu pops up in German zoo
Aug 4, 2006 (CIDRAP News) – A swan tested positive for H5N1 avian influenza at a German zoo yesterday, signaling the virus's re-emergence in the country after a 3-month lull.

A black Australian swan at the Dresden Zoo in eastern Germany was found dead on Aug 1, but zoo officials weren't too concerned at first because deaths in the breed are common, zoo biologist Ron Brockmann told Deutsche Presse-Agentur (DPA). But after the bird tested positive for H5N1 yesterday, he said, the zoo quarantined other animals and sought government permission to vaccinate the rest of the zoo's collection of 720 birds of 112 species.

The swan was the first zoo animal infected in Germany, according to the story. Brockmann said the virus might have entered the zoo last winter when wild birds visited the zoo's ponds. The staff is worried that other animals in the zoo may become infected with the H5N1 virus if they eat dead birds, he said.

Germany's last outbreaks of H5N1 avian flu were in February among wild birds and in April in farm poultry, Agence France-Presse reported today.

In other developments, a man in Vietnam who was hospitalized with possible avian flu tested negative yesterday, according to news services. The patient is from the southern province of Kien Giang, on the Cambodian border in the Mekong Delta. Vietnam hasn't had a confirmed human H5N1 case since November 2005.

Three people in Thailand have also been cleared of H5N1 infection, according to the Bangkok Post. One is a 9-year-old girl from Lop Buri province in central Thailand who died 2 days ago. The other two patients—a 17-year-old boy and a 42-year-old woman—are from Chachoengsao province, east of Bangkok. The tests indicated that all three patients had a type A flu virus, but not H5N1, the newspaper said.

As of yesterday, the Thai Health Ministry reported that 97 patients from 24 provinces were under surveillance for possible avian flu. Those numbers were down from 164 patients in 21 provinces the previous day.

Thailand's only confirmed human H5N1 case this year was in a 17-year-old boy from Phichit province who died of the disease Jul 24. A report in the Aug 3 Eurosurveillance Weekly suggests that the boy's death indicates that poultry deaths in Thailand are being underreported. The authors observe that poultry deaths in the country were not reported until Jul 24, the day the boy died.

The boy's case may be an example of a "sentinel human," meaning a human H5N1 case that triggers reporting of the disease in poultry, the report says.

See also:

Eurosurveillance Weekly report on avian influenza in Thailand
http://www.eurosurveillance.org/ew/2006/060803.asp#1

Center for Infectious Disease Research & Policy
Academic Health Center -- University of Minnesota
Copyright © 2006 Regents of the University of Minnesota

Thailand confirms second bird flu death this year; raises health awareness

2006-08-05T19:15:00.000-05:00

Thailand confirms second bird flu death this year; raises health awareness
13:35:55 EDT Aug 5, 2006
Canadian Press: RUNGRAWEE C. PINYORAT
BANGKOK, Thailand (AP) - A 27-year-old man has died of bird flu, becoming the second person this year to be killed by the disease in Thailand, a Health Ministry official said Saturday.

Dr. Thawat Suntrajarn, chief of the Department of Communicable Disease Control, said the man the local media identified as Thiangthong Singsamran came from Uthai Thani province in the country's north.

"I can confirm the man tested positive for the H5N1 virus," Thawat said, referring to results of tests carried out at Bangkok's Siriraj hospital.

The man became sick on July 24, a few days after burying one of his 16 free-range chickens that had died, a health ministry statement said.

On July 31, he was diagnosed with pneumonia and was given the anti-viral drug oseltamivir that is used to treat bird flu in humans. But his condition worsened and he died on Thursday, the statement said.

His wife has been given oseltamivir and will be monitored for the next 14 days, it added.

At least 134 people have died worldwide since the disease began spreading in Asia in late 2003, according to the World Health Organization, including 15 in Thailand.

The WHO has not yet confirmed the latest death in Thailand.

In the past two weeks, Thailand has confirmed two outbreaks of H5N1 in poultry and recorded its first human fatalities from the disease in eight months.

News of the new outbreaks triggered increased concern about the disease, and hundreds of people who earlier had bird flu-like symptoms but were cleared after testing were being checked again.

Health officials also said a special committee will be created in the northern province of Nakhon Phanom, where one of the outbreaks occurred, to assist health agencies while the province will receive equipment for rapid testing of suspected cases.

Authorities will also do more to educate people about the disease, and volunteers in every village will look for symptoms among their neighbours.

In his weekly radio address Saturday, Thai Prime Minister Thaksin Shinawatra called for farmers to quickly report the death of chickens. In the past, he has accused some farmers of trying to cover up outbreaks.

"When people who have contacted chicken become sick, it is advisable for them to immediately inform the authorities so that they could control the disease from spreading," Thaksin said.

© The Canadian Press, 2006

Thai Bird Flu Case Suggests Under-Reporting in Fowl

2006-08-05T19:10:00.000-05:00

Thai Bird Flu Case Suggests Under-Reporting in Fowl (Update1)
Aug. 4 (Bloomberg) -- A 17-year-man who died of bird flu in Thailand last week, the country's first case this year, suggests the virus is being under-reported in poultry, the influenza team at the European Centre for Disease Surveillance and Control said.

The youth from a northern province was hospitalized on July 18 suffering fever, cough and headache and died six days later, the Thai Bureau of General Communicable Diseases said in a July 26 report. A week before his symptoms appeared he buried 10 dead chickens, touching the carcasses with his bare hands. His phlegm tested positive for the H5N1 avian flu strain.

The case ``could be an example of the phenomenon of a sentinel human already seen in other countries, where it is only the severe illness or death of a person from H5N1 that triggers detection or reporting of H5N1 in poultry,'' the team in Stockholm said in a report. ``This suggests under-detection or under-reporting of poultry deaths.''

Thailand widened the search for avian flu patients and improved surveillance for the virus in poultry as a result of the death of the youth. New cases create chances for H5N1 to mutate into a pandemic form and world health authorities are tracking the disease for signs it's becoming more contagious.

The virus is known to have infected 232 people in 10 countries, killing 134 of them. Most infections occurred in Asia through contact with birds. The disease may kill millions should it start spreading easily between people, researchers have said.

Respiratory Symptoms

Thailand is awaiting laboratory tests on 259 people with respiratory symptoms, of whom 32 are from Phichit, the same province where the teenager died last week, the country's Bureau of General Communicable Diseases said on its Web site today.

So far this year, Thai health authorities have investigated more than 2,300 clinical influenza or pneumonia patients as part of routine surveillance. Only one of these has been found to be infected with H5N1.

Thai health officials recorded 65,100 cases of seasonal influenza in the first seven months of this year. Of those patients, 370 died, Thawat Suntrajarn, director general of the health ministry's disease control department, told reporters in the capital, Bangkok, today.

``Our biggest concern is the outbreak of seasonal flu in Pichit, where the bird flu virus is still active'' in poultry, and in nearby provinces, Thawat said. The initial symptoms of both avian and seasonal influenza are similar, he said.

Health officials are concerned that people may contract H5N1 flu while they're infected with seasonal influenza. The dual infections might allow the H5N1 to mutate into a pandemic form, Thawat said.

`Very Lethal'

``Bird flu is very lethal with a high fatality rate among infected patients, while seasonal flu is easily transmitted between humans,'' he said. ``Any combination of both viruses in a person would be very dangerous.''

Laboratory tests on a 9-year-old girl, who died earlier this week in Lop Buri province, showed she had seasonal flu, not the H5N1 strain, Paijit Warachit, director general of Thailand's Medical Science Department, said in a telephone interview today.

Tests on two suspected avian flu patients in Chachoengsao also showed they have seasonal flu and not H5N1, Thawat said.

Concern of fresh outbreaks of the disease have been fanned by reports of new infections in poultry. Laos, Thailand's northeastern neighbor, said the virus killed thousands of poultry in several farms owned by a commercial producer near the capital, Vientiane, last month.

``There remains a constant risk of outbreak reoccurrence'' because of the large numbers of free-range poultry that haven't previously been exposed to the virus, and the movement and mixing of fighting cocks, the influenza team at the ECD said in its report.

Wild Birds

``There is also the additional risk from wild birds mixing with the free-grazing birds,'' the team said. The report was published yesterday in Eurosurveillance, an online journal of peer-reviewed information on communicable diseases.

In Vietnam's Kien Giang province on the Cambodian border in the Mekong Delta, a man was hospitalized with damaged lungs and high fever about a week after eating duck, the Tuoi Tre newspaper reported yesterday.

Tests on the man were negative for H5N1, said Nguyen Thi Kim Tien, director of the Pasteur Institute in Ho Chi Minh City.

The Nguoi Lao Dong newspaper reported today that he virus was found in storks in the Suoi Tien district of Ho Chi Minh City, and in ducks from two flocks in the southern province of Tay Ninh.

Tests on the duck flocks were negative for the H5 avian flu subtype, said Nguyen Xuan Binh, deputy head of the Ho Chi Minh City regional center for animal health, which is responsible for carrying out tests on animal samples from southern provinces.

``We have just received samples from the stork flock in Suoi Tien today, and tests are underway,'' Binh said.

A swan found dead in Dresden zoo in eastern Germany was infected with H5N1, the first such infection in the country in almost three months, Agence France-Presse said yesterday, citing local authorities.

To contact the reporters for this story:
Jason Gale in Singapore at j.gale@bloomberg.net;
Anuchit Nguyen in Bangkok at at anguyen@bloomberg.net

Last Updated: August 4, 2006 06:10 EDT

Thailand, Vietnam probe possible human H5N1 cases

2006-08-05T19:02:00.000-05:00

Thailand, Vietnam probe possible human H5N1 cases
Aug 3, 2006 (CIDRAP News) – Concern about H5N1 avian influenza intensified in Thailand and Vietnam today as health officials reported more suspected human cases, but Indonesian officials said six people in two suspected case clusters in North Sumatra tested negative.

In Thailand, a 9-year-old girl from Lop Buri province died yesterday of suspected avian flu, the Bangkok Post reported. She is from the same province where a suspected case was reported in a 61-year-old woman yesterday.

A provincial health official, Pranor Khamthieng, told the Post the girl had initially tested negative for the H5N1 virus, but her symptoms suggested the disease. The Thai News Agency reported that the girl suffered fever, sore throat, and severe cough for 2 days before she was hospitalized with breathing difficulties. Samples were sent to a lab in Bangkok for a more thorough investigation, the Post reported.

The Thai News Agency said the girl’s family raises about 20 fighting cocks, but provincial authorities inspected her house and nearby areas and found that none had died suspiciously.

Elsewhere in Thailand, the Post reported today that two patients in Chachoengsao province, east of Bangkok, have been isolated at Ban Pho Hospital because of suspected avian flu. Doctors at the hospital told the Post that initial tests indicated the patients had regular influenza and that they were awaiting the results of avian flu tests.

One doctor said the patients, a 17-year-old boy and a 42-year-old woman, had touched ducks at a slaughterhouse where they both worked. A local livestock official, however, said no bird flu outbreaks had been reported on chicken farms in the province, according to the Post.

As of yesterday, the Thai Health Ministry reported that 164 patients from 21 provinces were under surveillance for possible avian flu.

Thailand’s only confirmed avian flu case so far this year was in a 17-year-old boy who died of the disease Jul 24 in Phichit province. The entire country is on bird flu alert after outbreaks surfaced in July in the northern and central provinces, ending a nearly 8-month hiatus.

In Vietnam—which hasn't had a confirmed human H5N1 case since November 2005—Bloomberg News reported today that health authorities are awaiting tests on a man from the southern province of Kien Giang, on the Cambodian border in the Mekong Delta. The report said the man was hospitalized with lung damage and a high fever about a week after eating duck.

Cao Bao Van, head of the molecular biology laboratory at the Pasteur Institute in Ho Chi Minh City, told Bloomberg that test results may be reported over the weekend.

Vietnamese news media have reported that ducks from two households in the southern province of Tay Ninh recently died suspiciously and test results were pending. Tay Ninh is also on the Cambodian border.

Meanwhile, in Indonesia, preliminary tests came back negative for H5N1 in six patients from the same district in Sumatra where the world’s first lab-confirmed human-to-human transmission of avian flu occurred in a family cluster, Agence France-Presse (AFP) reported today.

The suspected illnesses in the six patients had raised fears of more human-to-human transmission, because the group appeared to include two family clusters. Of the six patients, three were children: two siblings, aged 10 and 6, and an 18-month-old neighbor.

An Associated Press report yesterday had said there were a total of seven patients in the two possible clusters. But AFP reported today that a local hospital official in Kabanjahe village said it appeared that one patient had been counted twice.

Center for Infectious Disease Research & Policy
Academic Health Center -- University of Minnesota
Copyright © 2006 Regents of the University of Minnesota

Hybrid avian-human flu virus didn't spread in lab study

2006-08-02T23:09:00.000-05:00

Hybrid avian-human flu virus didn't spread in lab study
Robert Roos News Editor

Jul 31, 2006 (CIDRAP News) – In an experiment designed to mimic events that could launch an influenza pandemic, a synthetic influenza virus made by combining an H5N1 avian flu virus with a human flu virus turned out to be no more contagious in an animal model than the natural H5N1 virus, US scientists are reporting this week.

Researchers at the Centers for Disease Control and Prevention (CDC) made two hybrid viruses and infected ferrets with them, according to a report to be published in the Proceedings of the National Academy of Sciences. The viruses failed to spread from infected ferrets to healthy ones in neighboring cages.

"We found that they [the viruses] were not able to transmit efficiently," said CDC researcher Dr. Jackie Katz, speaking at a Jul 28 teleconference. "In fact, they were also not as able to cause severe disease as the original H5N1 virus."

The deadly H5N1 virus has infected 232 people and killed 134 since late 2003, but it has not yet found a way to spread easily from person to person. But scientists fear the virus could pick up that ability if it combined, or reassorted, with a human flu virus, which could happen if someone became infected with both types simultaneously. The CDC set out to create such a hybrid and test it in ferrets. The animals are considered good models for flu virus research because their susceptibility to flu viruses is similar to that of humans.

CDC officials cautioned against taking much comfort from the experimental results. Although the synthetic hybrid didn't spread among the ferrets in the experiments so far, that doesn't mean the scenario couldn't happen in nature, they said. (Also, experts say the H5N1 virus could become transmissible through accumulated small mutations, without reassortment.)

"These data do not mean that H5N1 cannot convert to be transmissible from person to person; they mean it's probably not a simple process and more than simple genetic exchanges are necessary," CDC Director Dr. Julie Gerberdng said at the teleconference.

The H5N1 virus used in the study was a strain collected in 1997, when the pathogen first infected humans in Hong Kong. The human flu virus used in the study was an H3N2 strain, which has been common in recent decades. The research involved four steps, according to Katz.

First, investigators assessed whether the H3N2 and H5N1 viruses would spread in ferrets, whose cages were arranged so that viruses could spread via respiratory droplets. The human virus did spread efficiently, whereas the avian virus didn't, which signaled that the ferrets were serving as good models for human infection, Katz said.

The next step was to generate reassortant viruses. "We made two viruses that contained surface protein genes from the H5N1 virus and internal genes from the human H3N2 virus," Katz said. "We found we could make these viruses and that some of them were viable."

Third, the scientists infected some ferrets with the hybrid viruses and waited to see if they would spread to healthy ferrets. The hybrid viruses caused less severe illness than the original H5N1 strain, and they failed to spread.

Finally, the investigators wanted to know if the hybrid viruses would naturally mutate to become more transmissible if they were passed through several ferrets in succession. So the researchers infected ferrets and, after the ferrets showed symptoms, took nasal secretions and used them to infect other ferrets, repeating this step five times. Further, the researchers assessed whether the virus could spread more easily after all these generations or "passages."

"We found that the virus did not acquire any additional capacity to transmit efficiently from infected ferrets to healthy ferrets," Katz said.

Katz didn't explain why the CDC used a 1997 strain of H5N1 instead of a more recent strain, but said more recent isolates will be used in further experiments. Later versions of both H5N1 and H3N2 will be used to make further hybrids for testing in ferrets, she said. Scientists have identified a number of mutations in the H5N1 virus since 1997.

"We did test the more recent strains [of H5N1] for their ability to transmit, and like the 1997 strains, they could not transmit efficiently from one animal to the next," she said. "We need to continue to study this."

The CDC officials were asked whether reassortment "dumbs down" or weakens the virus. Katz replied that the hybrids were less virulent than H5N1, but cautioned that the results apply only to the 1997 strain.

Gerberding commented, "The pandemics of 1957 and 1968 were caused by reassortant viruses. Those were not dumb viruses."

In answering other questions, Katz said some scientists believe the 1918 pandemic virus, unlike the 1957 and 1968 viruses, arose through slowly accumulating mutations in an avian virus rather than through a reassortment event. "We're looking at the approach of the 1957 and 1968 pandemics where there was a more sudden change," she said.

The most important lesson of the research so far, according to Katz, is "the knowledge that this process isn't simple, the procedure for the virus to acquire the properties of transmissibility."

She said the CDC also created a hybrid that involved H3N2 virus surface proteins and H5N1 internal genes—the reverse of the hybrid she first described—and "that was not sufficient for transmissibility either. . . . That points to the fact that it's a complex interaction of the surface genes and the internal genes."

Gerberding warned that the findings shouldn't lead to complacency.

"I'm not reassured from the public health perspective," she said. "This virus is still out there, it's still evolving, and influenza is always unpredictable. . . . So let's not use the word 'reassuring' with respect to what might happen with H5N1."

Because of the risk that the reassortant viruses could spread, the research was done under stringent containment, involving Biosafety Level 3 with extra precautions, Katz said.

Maines TR, Chen LM, Matsuoka Y, et al. Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. Proc Natl Acad Sci 2006 (published online Jul 31) [Abstract]

See also:

Jan 14, 2005, CIDRAP News story "CDC to mix avian, human flu viruses in pandemic study"

Center for Infectious Disease Research & Policy
Academic Health Center -- University of Minnesota
Copyright © 2006 Regents of the University of Minnesota

Prepare now for flu pandemic, officials warn

2006-08-02T23:00:00.000-05:00

Prepare now for flu pandemic, officials warn

By Rebecca Vesely, STAFF WRITER
Inside Bay Area

DUBLIN — Avian flu could arrive in California as early as this fall via migrating birds, and while that doesn't spell a flu pandemic, local communities need to do more to prepare, health officials warned at a day-long conference Tuesday.
"The truth is, we are largely on our own," said Dr. Anthony Iton, Alameda County's health officer.

This first countywide pandemic flu preparedness forum, held at the county's Office of Homeland Security and Emergency Services, brought together law enforcement, firefighters, community groups, school leaders and officials from hospitals and city governments.

The emphasis on pandemic flu preparedness stems from worries about the H5N1 virus, an avian flu strain that has spread to 51 countries, infected 230 people and killed 132.

Although a new study by the Centers for Disease Control and Prevention released Monday suggested that H5N1 may not mutate easily into a rapidly spreading strain, avian flu is making its way around the globe.

Avian flu will arrive via birds on the Alaskan flyway soon, said Dr. Peter Lichty, medical director of occupational medicine at Lawrence Berkeley National Laboratory. Infected birds have been found as close to the West Coast as Siberia, whose border is three miles from Alaska.

"I'm expecting infected birds in Cali-fornia by the end of this year," Lichty said. "That's why we decided to do this (conference) now."

But the presence of H5N1-infected birds doesn't necessarily equal a human pandemic. A pandemic is defined as infecting at least 25 percent to 30 percent of the population over a prolonged period.

"There's no way to say when there will be a pandemic," said Dr. Howard Backer, California's public health officer. "We know it will happen, but we don't know when." Some researchers had predicted avian flu in North America during spring's migratory season, which didn't come to pass.

Even so, decisions about quarantines, school closures, vaccine priorities, hospital diversions, supply allocation and resource coordination largely will be left up to local jurisdictions, according to federal and state flu pandemic preparedness plans.

This year's state budget includes $214 million to handle any so-called "surge capacity" in the health system, such as supplies, drugs, field hospitals and training in the event of a flu pandemic. An additional $40 million has been allocated for antiviral drug stockpiling, disease surveillance, training and response teams.

The county has been running a preparedness program on Comcast Cable, developing a pandemic flu pocket guide and building a volunteer database to draw on in case disaster strikes.

The health department is using emergency preparedness and bioterror funds for this effort. About $100,000 was allocated this fiscal year to the county for pandemic flu, and $400,000 in future years, but the county hasn't yet received the funds, Iton said.

"Our lesson from (Hurricane) Katrina is you start with people most likely to be impacted," Iton said.

The county needs to make stronger connections with others that would be touched by a flu pandemic, including the Port of Oakland, veterinarians, environmental health officials, the military and schools, Iton said.

The H5N1 virus could develop into a pandemic if it mutates to become easily transmissible between humans. Today, reports of human-to-human infections have been scattered.

The virus would likely first come via migrating birds or animals trafficked or smuggled into the country, not from local poultry populations or from people traveling by airplane from infected areas, officials at the conference said.

An infectious disease outbreak can lead to many unexpected issues, said Dr. Robert Kosnick, an occupational physician at the University of California, San Francisco. Kosnick was working at St. Michael's Hospital of the University of Toronto during the 2003 SARS outbreak, and developed the hospital's patient and worker safety protocols.

During the SARS outbreak, the hospital had to cancel elective surgeries and clinics, and close all but one entrance and exit point for workers, where they were screened for possible infection.

Fear of the virus and uncertainty about the epidemic's duration made establishing protocols essential. The Toronto epidemic lasted three months, and during that time, 375 people were infected and 44 people died.

"The logic at the time was, 'If you touch it, you will get it, and you will die,'" Kosnick said.

The absence of a viable vaccine to combat avian flu makes community-wide preparedness even more important, officials said.

Last week, drug maker GlaxoSmithKline reported positive results from a clinical trial of its avian flu vaccine. The company said it could produce the vaccine in large quantities by next year. The vaccine uses an inactive strain of H5N1 isolated in Indonesia last year.

Contact Rebecca Vesely at rvesely@angnewspapers.com.

''There's no way to say when there will be a pandemic. ... We know it will happen, but we

don't know when."

Dr. Howard Backer

CALIFORNIA PUBLIC HEALTH OFFICER

Researchers Develop New Way to Assess Pandemic Potential of Influenza Viruses

2006-08-02T00:53:00.000-05:00

Researchers Develop New Way to Assess Pandemic Potential of Influenza Viruses
--------------------------------------------------------------------------------

Posted on: 07/31/2006

Researchers at the Centers for Disease Control and Prevention (CDC) have developed a new research method that may help identify the types of genetic changes necessary for the avian influenza virus (H5N1) to be more easily transmitted among people.

After developing the research method, CDC scientists used it to investigate the ability of a lab-engineered combination of the avian influenza virus and a more common human virus to spread in lab animals. Efficient and sustained human-to-human transmission is the remaining property that H5N1 avian influenza viruses do not yet have that is needed to cause a pandemic.

In this series of experiments, published in the July 31, 2006 issue of the journal Proceedings of the National Academy of Sciences, genes from a human H3N2 influenza virus were added to genes from an H5N1 avian influenza virus to create new hybrid viruses. The new viruses were tested in ferrets because their susceptibility to flu viruses is similar to that of humans. The animals were then placed in close proximity, to see if infected ferrets passed the new virus to uninfected animals and whether they transmitted it more easily than the original H5N1 virus.

In this model, human H3N2 viruses transmitted efficiently between the ferrets, but avian H5N1 viruses did not. When the hybrid viruses were tested it was found that these viruses also did not pass easily between ferrets.

"This important science has established a new research method to help us learn more-in advance-about the genetic changes that enable new influenza viruses to spread efficiently and in a continuous manner among people," said CDC director Julie Gerberding, MD, MPH. "H5N1 viruses continue to spread among birds worldwide and their genetic properties are constantly changing. There is an urgent need to better understand how these viruses could acquire the ability to spread efficiently between people. This research increases our knowledge, and may enable us to more quickly identify H5N1 viruses and other influenza viruses that have the potential to cause a pandemic."

The avian flu H5N1 viruses currently circulating already possess two of the three characteristics that scientists believe are needed to cause a pandemic. The first characteristic is being a new virus to which humans have little or no immunity. The second characteristic is the ability to infect people and cause illness. The CDC studies were designed to help researchers learn what genetic changes would be needed for the virus to gain the remaining trait necessary to cause a pandemic: the ability to spread easily from person to person in a sustained manner within the population.

To do this, Dr. Taronna Maines and her CDC colleagues designed and tested a research method that involved three elements: ferrets; a caging system that enabled researchers to put healthy and infected animals in close proximity; and reverse genetics, a tool for combining the genes from human and avian influenza viruses. Several H5N1 viruses were used in the research along with a H3N2 strain, a common human influenza virus that circulates nearly every year. Infected ferrets were either placed in the same cage with uninfected ferrets to test transmissibility by close contact or in adjacent cages with perforated walls to test spread of the virus by respiratory droplets.

The studies showed that the H3N2 virus passed easily by droplets but the H5N1 virus did not, reflecting what is seen with these viruses in humans.

Researchers then swapped genes from a 1997 H5N1 avian flu virus with genes from an H3N2 virus, in a process called reassortment. When tested using the ferret model, these "hybrid" viruses (viruses that contained both avian H5N1 and human H3N2 influenza virus genes) did not pass easily between ferrets and, in fact, caused less severe disease than the original H5N1 virus. The reassortment work was designed to mirror the phenomenon that occurs in nature when two flu viruses combine to form a new virus, a process that led to the 1957 and 1968 pandemics. It is still unknown whether the H5N1 virus could reassort with a human influenza virus in nature.

In a final study, CDC researchers passed a hybrid virus through a series of ferrets to see if the virus would accumulate genetic changes necessary to transmit more easily. The researchers found the process introduced only one genetic change in the virus but didn't enhance its transmissibility.

Although the findings apply only to the specific viruses used in the study, the research suggests that significant genetic changes in the H5N1 virus would likely be needed to create a strain that could cause a pandemic. Future CDC studies will examine whether combining genes from H3N2 strains with more recent H5N1 strains makes the new virus more easily transmissible.

"This study provides for the first time an assessment of the risk of an H5N1 pandemic strain emerging through reassortment with a human influenza virus. However, there is still much we do not know about the molecular changes the virus would need to cause a pandemic," said Dr. Jackie Katz, a branch chief in CDC's Influenza Division and one of the lead researchers on the paper. "Influenza viruses are constantly changing so we need to be vigilant and continue our work using this research method to better understand if there are other possible virus combinations or emerging changes in the H5N1 viruses that would increase the risk of a pandemic strain emerging."

Most influenza experts believe another pandemic will occur, but it is impossible to predict which strain will emerge as the next pandemic strain, when it will occur or how severe it will be. As of late July, H5N1 had caused more than 230 cases of disease in humans worldwide and is widespread in bird populations in Asia, Africa and Europe. However, the virus has only rarely passed between humans and does not currently transmit easily from human to human. H5N1 avian viruses have not been found in the United States in either birds or humans.

Source: CDC

Study shows hybrid of human-bird flu viruses didn't transmit well in animals

2006-08-02T00:48:00.000-05:00

Study shows hybrid of human-bird flu viruses didn't transmit well in animals
19:07:33 EDT Jul 31, 2006
HELEN BRANSWELL

(CP) - U.S. scientists who artificially engineered viruses containing genes from both the worrisome H5N1 avian flu virus and one that causes human flu found the resulting offspring failed to achieve the one feature H5N1 lacks to trigger a pandemic - transmissibility.

The study, published Monday, reports that the resulting viruses did not transmit between ferrets, animals that are susceptible to human and avian flu viruses and which are commonly used as a laboratory surrogate for human infection.

The work, done at the U.S. Centers for Disease Control in Atlanta, may provide clues as to why H5N1 has not ignited a pandemic despite having circulated in Asia since at least 1996. To date the virus has infected at least 232 people in 10 countries and has killed at least 134 of those people.

But the study findings cannot be used to predict whether H5N1 is capable of acquiring the characteristics to easily transmit to and among people, the head of the CDC cautioned.

"These data do not mean that H5N1 cannot develop into a pandemic strain," Dr. Julie Gerberding told reporters in a telephone briefing before the paper was released by the journal the Proceedings of the National Academy of Sciences.

"Flu is always unpredictable. And though we weren't able to do this through some simple gene exchanges . . . there are many other combinations and subtle changes that the virus itself could make," Gerberding said, noting she is concerned the findings may lead people to conclude the worry over H5N1 has been overblown.

A number of leading flu scientists who were not involved in the research concurred with Gerberding's take.

"I think we would be foolish to assume that H5N1 cannot do this. It may not. But that does not mean we can rule it out," said Malik Peiris, an influenza authority at the University of Hong Kong.

The CDC scientists, led by senior author Jacqueline Katz, conducted what are called reassortment studies.

They artificially engineered flu viruses that contained different combinations of genes from an H5N1 virus recovered in 1997 and H3N2, one of two flu subtypes that currently circulate during the human flu season. The scientists did not work on the other circulating human flu subtype, H1N1.

There are 56 potential combinations of two viruses, though the CDC scientists only tried to engineer about a half dozen different hybrids, those felt to be the most likely to produce troublesome combinations. Katz said to try all 56 would have amounted to "years of work."

Some gene combinations failed to grow at all. And when the scientists infected ferrets with the combinations they succeeded in creating, the resulting infections rang no alarm bells.

Viruses with a human hemagglutinin and neuramindase (the H and N in a flu virus's name) and six genes from H5N1 infected ferrets but didn't pass well from an infected ferret to uninfected animals in nearby cages.

Viruses with H5N1's hemagglutinin and neuraminidase built onto human flu genes infected ferrets but did not pass at all to nearby, uninfected animals.

Flu viruses mutate constantly and it's not known whether more contemporary H5N1 viruses would come together with H3N2 viruses more readily, or with more alarming results.

"I want to stress that our results can't be generalized and they're only relevant for the viruses that we used in the study," Katz, a branch chief in CDC's influenza division.

Nor do they indicate how likely or unlikely H5N1 is to swap genes with H3N2 or H1N1 in nature, or how transmissible such naturally occurring reassortant viruses would be.

"I think it's an important paper (but) it doesn't tell us anything about the propensity to reassort, because the reassortants were made artificially," Peiris said.

"It's really a question of: If you do have a reassortment, will it transmit efficiently human-to-human, purely by the fact of the reassortment? And what they've found - to the extent that they've done it - is No."

To test what might happen in nature, scientists would have to conduct what are called classical reassortment studies, where H5N1 and human flu viruses are allowed to co-mingle in a lab dish, producing naturally occurring offspring viruses. CDC is currently conducting such work with more current H5N1 viruses, Katz said.

The results could be different, said Dr. Frederick Hayden of the World Health Organization's global influenza program.

"We may see surprises and different gene reassortant patterns there. But until you actually do the experiments, that would just be a matter of speculation," said Hayden, who echoed Gerberding in saying this study doesn't offer any insight about how likely or unlikely H5N1 is to cause a pandemic.

There are two ways a pandemic virus can emerge, by reassortment with another virus or by slowly mutating to acquire the ability to spread from human to human. This work offers no clue as to whether H5N1 could develop into a pandemic strain through the latter mechanism.

Interestingly, the attempted combinations included viruses modelled on the two that caused the last two pandemics, in 1957 and 1968 - both of which were triggered by viruses containing human and avian flu genes. But multiple tries failed to produce a viable living virus.

"Combinations that worked to create pandemics in '57 and '68 weren't the obvious combinations that we could achieve in this current study," Katz noted, adding this suggests that for reassortment, there may not be general patterns that hold true across subtypes.

"Probably it's a constellation of effects" that would result in reassortment, she said. "And you just have to hit upon the right combination."

To test the transmissibility of the viruses, the CDC scientists devised an elaborate system of exposing infected ferrets to non-infected ferrets in nearby cages. They also tested the system to determine whether a number of flu viruses, avian and human, provoked the same type of illness - moderate, severe, lethal - in the ferrets as they did in humans.

The results suggest this model would be an effective way to quickly test the transmissibility of a new reassortant virus, if it arose in nature, the authors reported.

Adolfo Garcia-Sastre, an influenza microbiologist at Mt. Sinai School of Medicine in New York, said the model would be a useful tool to gauge the pandemic threat of future reassortant viruses, and could help scientists puzzle out the molecular mysteries that dictate why some flu strains transmit well in humans while others do not.

That in turn could help in the development of drugs that could block transmission of flu from an infected person to others, he noted, "which would be a very interesting concept for a drug. It does not help the person with the disease, but it makes the disease not transmissible."

© The Canadian Press, 2006

In Vietnam, a Gateway for Bird Flu

2006-07-31T00:47:00.000-05:00

washingtonpost.com

In Vietnam, a Gateway for Bird Flu
Ignoring Chicken Import Ban, Smugglers Bring Virus Over Border From China

By Alan Sipress
Washington Post Foreign Service
Sunday, July 30, 2006; A23

DONG DANG, Vietnam -- The smugglers first appeared on the distant ridgeline and then, like ants, streamed down a dirt track carved from the lush, sculpted mountains that separate Vietnam from China. As the figures grew closer, their stooped posture became visible, backs heaving under bamboo cages crammed with live chickens.

On the road below, two young men identified by local officials as lookouts buzzed past on red dirt bikes, slowing down to check out a reporter and his government escorts who had stopped to watch. One man produced a two-way radio and started speaking urgently. Though his words were inaudible to the visitors, within moments the figures on the hillside melted into the brush.

These traffickers haul more than 1,000 contraband chickens a day into Lang Son, one of six Vietnamese provinces along the Chinese border, flouting a chicken import ban. In doing so, heath experts say, they have also repeatedly smuggled the highly lethal bird flu virus from its source in southern China into Vietnam, where the disease has taken a devastating toll on farm birds and killed at least 42 people since 2003.

As bird flu continues to spread across the Eastern Hemisphere, international health experts warn that illegal trade in poultry, poultry products and other birds is often the primary cause.

"Both between and within countries, commerce is an incredibly important factor," said Juan Lubroth, chief of infectious animal disease for the U.N. Food and Agriculture Organization. "We try to press with governments that it has to be controlled or managed better. But like trafficking in humans, weapons and drugs, with poultry it's not any easier."

The virus has already ravaged farm birds and wildfowl in more than 50 countries. At least 230 human cases have been recorded, and more than half have been fatal. Health officials fear that a new form of the virus that can jump easily from person to person will develop, bringing on a global epidemic among humans.

Vietnamese veterinary officials disclosed in April that they had found bird flu in a sample taken from smuggled chickens confiscated in Lang Son during a bust on the border. Days later, officials in the remote, neighboring province of Cao Bang reported the virus in poultry samples taken from three farms on the Chinese border after dozens of chickens had started dying and smuggling was suspected. These two episodes were the first official cases of bird flu in Vietnam since December.

In May 2005, researchers had already found evidence that smuggling was bringing in the bug: They isolated a strain of the H5N1 virus that was new to Vietnam but similar to one common in Guangxi, just over the mountains from Lang Son.

Lang Son's jagged border with China runs for about 150 miles through angular, misty mountains with craggy cliffs that seem drawn from a stylized painting. The highest peak, which lends its name, Mau Son, to the local rice wine, rises nearly 4,500 feet. For centuries, the extended families straddling this border have navigated treacherous footpaths to run goods from one side to the other, in recent years including electronics, DVDs, exotic wildlife and all nature of clothes and shoes.

The bootleg poultry business turned lucrative two years ago after Vietnam started slaughtering about 50 million chickens to contain its bird flu epidemic. The resulting shortage of chicken meat, a prime source of protein for the Vietnamese, sent prices soaring on their side of the border.

Much of this trade takes place at night. But in the broad daylight of a recent afternoon, more than a dozen smugglers were descending a steep, dark earthen track outside the border village of Dong Dang. Even after the motorbike lookouts apparently sounded the alarm, more traffickers appeared over the ridge from China. Others were spotted walking down another, narrower path largely concealed by trees about 100 yards away.

The local officials warned that the smugglers could turn violent, attacking outsiders with stones or firearms. According to Vietnamese press reports, chicken smugglers in Lang Son have battled soldiers trying to intercept them. In one instance, five soldiers were injured by stones, and their car was destroyed.

Do Van Duoc, director of animal health in Lang Son, explained that the huge difference in prices on opposite sides of the border makes for a flourishing business despite the ban on poultry imports from China. Prices fluctuate, but on average, chicken that sells for 30 cents per pound or less in China can fetch a dollar or more in Vietnam.

Duoc said the high cost of poultry in Vietnam also reflects the expense of importing vaccines and other medicine to combat bird flu. Chinese farmers are able to keep costs down because of the vast scale of their poultry industry and the inexpensive supply of feed and domestically produced vaccines, he said.

Moreover, Duoc alleged that Chinese farmers unload chickens from areas struck by bird flu at bargain prices. In some cases, he said, the farmers tell Chinese authorities they have culled their flocks to earn government compensation and then peddle the birds to smugglers.

"They try to get as much money as they can," he said. "They are selling sick chickens because of the outbreak."

China's Agriculture Ministry confirmed that poultry was being illegally transported from Guangxi into Vietnam. In response to written questions, ministry officials said that an investigation by Guangxi animal health investigators had discovered smuggling from three areas close to Lang Son province but that there were no reports of this poultry being infected with bird flu.

Chinese agriculture officials said government veterinarians were working with customs and border defense officers to stop the illicit trade. Chinese police have confiscated more than 23,000 chickens and 3,500 ducks this year, officials said.

The syndicates running the smuggling rings pay local villagers about 30 cents a bird to haul the contraband along mountain trails that in some cases snake for more than 10 miles, said Nguyen Thang Loi, director of market inspections in Lang Son. Some smugglers, especially women and children, can carry only a few birds, but fit men haul as many as 20 at a time. Over the course of a week, the earnings can far outstrip the salaries of animal health officers, inspectors and others charged with stemming the trade.

The traffickers are finding new ways to move even larger amounts. In recent weeks, Loi's inspectors captured a pair of makeshift wooden carts that were being used to transport up to a ton of chickens at a time along railroad tracks running through the mountains.

Once the smugglers descend the slopes, their haul is often moved by motorbike to local farms that serve as stopover points, Loi reported. From there, the chickens are loaded onto trucks for transport, in many cases to the markets of Hanoi and points farther south, Loi and animal health experts said.

An average of up to 1,500 birds are slipped over the mountains into Lang Son each day, Loi reported. Along the entire Vietnam-China border, the total could be thousands more, according to Vietnamese and international livestock experts.

Worldwide, the trade in illegal poultry and other birds is extensive, said Lubroth of the U.N. agriculture agency, though the specific scope is unknown.

This business includes large-scale commercial shipments of uninspected meat, often from China, to destinations as diverse as Europe, Africa and the United States. Last month, U.S. inspectors discovered 2,000 pounds of frozen chicken, duck and geese smuggled from China in a Detroit-area warehouse that supplies Chinese restaurants and Asian groceries in southeastern Michigan.

Last year, Taiwanese officials reported their first case of the deadly bird flu virus among more than 1,000 birds that were being smuggled by ship from China. A pair of eagles confiscated two years ago at Brussels International Airport from the hand luggage of a Thai passenger were found to be carrying the disease.

In Africa, commerce spread the virus from Egypt to Sudan and likely took it to other countries on the continent, Lubroth said.

In Lang Son, Loi said he has only 22 inspectors at the border to stem the smuggling of everything from batteries to automobiles. Though joint efforts with police and soldiers have resulted in repeated arrests, he acknowledged that the organizers remain at large. "The real smugglers are behind the scenes, and even the people hired to carry don't know the names or have any information about them," Loi said.

As long as high prices in Vietnam make the illicit chicken trade lucrative, it will continue, said Jeffrey Gilbert, an animal health specialist in the U.N. Food and Agriculture Organization's Vietnam office. "You can put helicopters up there, really mobilize the army and put all kinds of resources in, and it would still go on," he said. "It's like the Ho Chi Minh Trail."

Researcher Vivian Zhang in Beijing contributed to this report.
© 2006 The Washington Post Company
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Glaxo touts bird flu vaccine

2006-07-29T00:25:00.000-05:00

Glaxo touts bird flu vaccine
Manufacturers race to develop effective virus inoculation
- Bernadette Tansey, Chronicle Staff Writer
Thursday, July 27, 2006

GlaxoSmithKline said Wednesday that its experimental bird flu vaccine delivered the best results shown so far among the manufacturers who are racing to develop an effective inoculation against the deadly avian virus.

Glaxo said an additive it included in the vaccine boosted its power, allowing the use of significantly lower doses while also producing a higher rate of response than the vaccine candidates of competitors whose data have already been reported.

The lower the dose needed, the more shots a factory can produce. And the world's drug manufacturing plants might need to churn out vaccine quickly, because an avian flu pandemic could rapidly sweep the world population.

The effectiveness of bird flu vaccines is evaluated by measuring by the level of antibodies produced by inoculated human subjects. Scientists predict that a sufficient level of antibodies will activate the immune system to attack the virus if the immunized person is exposed to it. But trial subjects are not exposed to the H5N1 virus, because that would be too dangerous.

The H5N1 strain is primarily a disease of birds that doesn't infect humans easily. But of the 232 cases reported by the World Health Organization, 134 have died. Most are believed to have had close contact with infected birds. The fear among public health officials is that the virus will mutate into a pandemic form transmitted easily from person to person.

Stockpiles of experimental H5N1 vaccines are on order by the United States and other governments. But it's not clear whether any vaccine manufactured in advance, based on H5N1 strains in circulation, will protect against a mutated variety that may eventually cause a pandemic. Glaxo is conducting studies to determine whether its vaccine will deliver cross-protection against different viral strains.

The government has been fostering the study of additives, also called adjuvants, as a strategy for stretching limited supplies of vaccine, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

"I'm totally delighted that GlaxoSmithKline has had this advance,'' said Fauci. "It's not the solution to the problem, but you can certainly say it's good news.''

Results had been disappointing for another manufacturer, Sanofi-Aventis. In March, the French company reported that its bird flu vaccine induced a significant immune response in only 50 percent of trial subjects when two doses of 90 micrograms each were injected. With the addition of an adjuvant called alum, the results improved. But not enough, Fauci said. Two doses of 30 micrograms each were required to spur immune responses in 67 percent of subjects.

With Glaxo's proprietary adjuvant, 80 percent of subjects responded when given two shots of 3.8 micrograms each. J.P. Garnier, GlaxoSmithKline's chief executive officer, said no other manufacturer has produced such a strong response at such a low dose of vaccine created from H5N1, the bird flu strain considered a leading contender to cause a pandemic.

"These excellent clinical trial results represent a significant breakthrough in the development of our pandemic flu vaccine,'' said Garnier. Glaxo will seek regulatory approval for the vaccine in the coming months, he said.

Fauci said he predicts similar results will be achieved by Novartis with an H5N1 vaccine developed by a Bay Area company it recently acquired, Chiron Corp. The Novartis vaccine includes an adjuvant similar to Glaxo's, he said.

Sanofi, in a prepared statement, said it will continue to study formulations that include alum, because it is "the world's most widely used and proven adjuvant currently licensed for vaccines. We believe following this initial clinical path with a time-tested adjuvant is a fast way to attain a licensable vaccine with the safest profile possible. Future initiatives will look at alternative adjuvants.''

Glaxo did not give details about the composition of its proprietary adjuvant. The company would consider licensing it to other manufacturers in the event of a bird flu pandemic, said spokeswoman Patti Seif.

Along with its bird flu vaccine news, Glaxo reported a 14 percent increase in second-quarter profit Wednesday. Glaxo shares dropped 87 cents, or 1.53 percent, to close at $56.04.

E-mail Bernadette Tansey at btansey@sfchronicle.com.

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©2006 San Francisco Chronicle

Thailand faces renewed avian flu fight

2006-07-25T01:05:00.000-05:00

Thailand faces renewed avian flu fight
Jul 24, 2006 (CIDRAP News) – Thailand is facing its first outbreak of H5N1 avian influenza in birds in 8 months, along with flu-like illnesses in a number of people in areas with sick birds, according to news services.

Thai agriculture officials said the virus was identified in a fighting cock from the northern province of Phichit, the Bangkok Post reported in a story published late today. The dead bird was from Bang Mun Nak district, where almost 300 birds were culled after the mysterious deaths of about 30 poultry 2 weeks ago, the story said.

The confirmation came shortly after poultry farmers and a senator accused the agriculture ministry of covering up the re-emergence of the disease following "massive deaths of poultry in many provinces" starting early in July, the newspaper reported.

Earlier today, the Thai newspaper The Nation said Agriculture Minister Sudarat Keyuraphan confirmed that 20 samples of dead fighting birds from Phichit had tested positive for avian flu, according to a report today by The Nation. Agence France-Press (AFP) quoted him as saying the virus was an H5 strain, but it was not yet known if it was H5N1.

Sudarat said the virus was detected in imported chickens, and he announced a ban on poultry imports, The Nation reported. To contain the outbreak, he said, officials have imposed quarantine near where the birds died and have prohibited the transport of birds.

Two other provinces, Phitsanulok and Uttaradit, also are reporting suspicious poultry deaths, The Nation said.

Meanwhile, a number of suspected human cases of avian flu have been reported. A United Press International report published 2 days ago said local news media were reporting that two sisters, aged 3 and 4, were in a Phichit hospital with suspected avian flu and that lab results were expected by July 27.

Today The Nation reported that three other patients were hospitalized in Phichit: two men, aged 59 and 86, and a 7-year-old boy. All three were reported to have had contact with dead chickens. Also, a Reuters report said an 11-year-old girl with flu-like symptoms was being treated in a Phichit hospital after chickens died on her family's farm.

In addition, a report yesterday in The Nation said two men, aged 67 and 35, were hospitalized in Uttaradit Provincial Hospital with avian flu–like symptoms that developed after they ate spotted doves. The report said blood samples were taken for testing at a nearby laboratory.

Fifteen other patients, two of them from Phichit, had been on a watch list for suspected avian influenza but were removed after tests came back negative, The Nation reported today. But the disease has not been ruled out in a 5-year-old boy from Phitsanulok, and Uttaradit province has three patients with flu-like symptoms, the story said.

Thailand has not had a confirmed human H5N1 case since last December. According to the World Health Organization (WHO), the country had 17 human cases with 12 deaths in 2004. Five more cases, two of them fatal, occurred in 2005.

Sudarat, the Thai agriculture minister, had said on Jul 6 that he hoped the country would be entirely free of avian flu within 3 years. At that point there had been no outbreaks in 239 days, he said.

In Indonesia, the lone survivor of the family cluster of H5N1 cases in North Sumatra left the hospital last week, according to an Associated Press report. The patient, 24-year-old Jones Ginting, had been hospitalized since May when he and seven other family members fell ill after a family gathering.

Ginting told the AP that he couldn't remember much of his battle with the illness. He said he was afraid to go to the hospital because that was where his relatives died. During his hospital stay, he said, he constantly struggled to breathe, experienced pounding pain in his head and hips, and was exhausted by 2-hour coughing fits. Later, he developed a stiff neck and headaches, and his doctors discovered that he had brain abscesses.

Ginting must return to the hospital for weekly checkups. He said he looks forward to living a healthy lifestyle, but will not avoid eating chicken. "I'm not afraid of chicken. I don't know why," he said.

See also:

WHO avian flu case count

Center for Infectious Disease Research & Policy
Academic Health Center -- University of Minnesota
Copyright © 2006 Regents of the University of Minnesota