IBM Races H5N1

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

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

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

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

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

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

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

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

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?

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

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

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

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

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

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

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

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


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Winged Disaster Business continuity planning should already be in place in preparation for avian flu (or other) pandemics

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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