Study: Poultry most likely to bring H5N1 to Americas

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

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

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

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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

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

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

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

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

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

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

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

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

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?

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

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

Britain vulnerable to drug-resistant bird flu

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

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

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

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)


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Inexpensive Test Detects H5N1 Infections Quickly and Accurately

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