Avian Influenza MAY Lab Report: Scientific Developments In The Fight Against H5N1

PCViking

Lutefisk Survivor
Bird flu virus hardier, lives for longer -experts
02 May 2006 07:32:59 GMT
Source: Reuters

By Tan Ee Lyn

SINGAPORE, May 2 (Reuters) - Leading influenza experts urged nations not to lower their guard against the deadly and hardy H5N1 virus, saying it now survives longer in higher temperatures and in wet and moist conditions.

Scientists previously found the virus to be most active and transmissible among birds in the cooler months from October to March in the northern hemisphere, and many people were hoping for some respite in the coming summer months.


But influenza expert Robert Webster warned against complacency and underestimating the virus, which made its first documented jump to humans from birds in 1997 in Hong Kong, killing six people.

"When we tested the virus in Hong Kong from 1997, the virus was killed at 37 degrees Celsius (98 Fahrenheit) in two days. The current H5N1 is still viable for six days at 37," said Webster, from St Jude Children's Research Hospital in the U.S. city Memphis.

"H5N1 at room temperatures can stay (alive) for at least a week in wet conditions," Webster told Reuters on the eve of a bird flu conference organised by the Lancet medical journal in Singapore.

"One of the often overlooked facts about influenza is that it's more heat stable than people realize, especially under moist, damp conditions ... Don't trust it,"
he said.

Webster said heat-stable strains of H5N1 were already circulating in ducks in Vietnam, Indonesia, China in 2004 and 2005 and experts would have to test if this trait was in the variants now circulating in India, Africa, Europe and parts of the Middle East.

Since re-emerging in Asia in late 2003, the H5N1 virus is known to have infected 205 people, killing 113 of them. In the past few months, it has spread from Asia to parts of Europe, the Middle East and Africa.

Although it is predominantly a bird disease and most of the victims contracted the virus directly from poultry, experts fear it might change into a form that transmits easily among people and trigger a pandemic.

BREAKING THE CHAIN

The virus's growing adaptability to water has ominous implications because it means untreated water might no longer be safe,
Webster said, and it was important to drink boiled water.

"This means that water supplies for feeding chickens, or water supplies where people are swimming and water supplies for villages have got to be treated,"
he said.

Other experts also called for concerted action and determination in breaking the chain of transmission of the virus, which resides largely in the world's reservoir of 250 billion domestic birds and 50 billion migrating birds.

"You can break the chain of transmission into the human population. The best place to break it is either to protect the domestic birds from the migratory birds. Or alternatively, remove humans from the domestic birds and break the chain of transmission and you are halfway there," said John Oxford, virology professor at the Royal London Hospital.

Kennedy Shortridge, who spent three decades studying influenza viruses, called for a complete rethink of the way poultry should be raised in parts of Asia, where ducks -- natural reservoirs of flu viruses -- are raised in padi fields to get rid of rice pests. Ducks are also raised alongside chickens, and cross infection is all too common.

"When I first saw the beginnings of intensive raising of poultry in the early 1980s in southern China, to me, the alarm bells were there,"
said Shortridge, who described these padi fields as "nothing more than fecal soups of influenza viruses".

In an interview, he also called for a change in the ways chickens are now raised. Conditions were often too stressful for the birds and this made them vulnerable to disease.


"We've got to find other sources of protein, other than just chicken. And the chickens have to be raised in such a way that the birds are not going to be stressed and not susceptible to so many infections,"
he said.

http://www.alertnet.org/thenews/newsdesk/T151771.htm

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PCViking

Lutefisk Survivor
Live bird flu virus found in victim's blood

HELEN BRANSWELL

Canadian Press

Toronto — Live H5N1 avian flu virus can be isolated in the blood of its human victims, a finding that will be reported by Thai researchers in an upcoming issue of a scientific journal.

Evidence that H5N1 can spread via the bloodstream to parts of the body not normally attacked by influenza viruses confirms this particular flu strain poses special challenges for both patient treatment and infection control, experts say. It also raises theoretical questions about the safety of the donated blood system should H5N1 trigger a pandemic.

“This is the first report of a high amount of (H5N1) virus in blood in humans,”
University of Ottawa virologist Earl Brown said of the findings, outlined in a letter slated for publication in the June issue of Emerging Infectious Diseases.

“That's a bit surprising because blood is poisonous to flu virus. If you take any blood ... and add it to flu, you kill it (the virus). This showed that the virus was living in the blood,”
said Dr. Brown, who was not an author of the letter.

While some types of viruses spread well in blood, cases of viremia — viral infection in the bloodstream — have only rarely been reported with influenza.

The researchers — from Chulalongkorn University, Srinakharinwirot University and the National Institute of Animal Health, all in Bangkok — reported on the case of a five-year-old Thai boy who died of H5N1 infection Dec. 7.

A blood sample drawn on the day he died contained high levels of live virus.

The finding helps to explain reports that some humans with H5N1 experience what is called systemic infection, with the flu virus spreading beyond its normal home in the respiratory track to organs that would typically go untouched by human flu viruses.

Other research groups have reported finding traces of H5N1's RNA in blood. Those findings were highly suggestive that the virus was using the bloodstream to disseminate throughout the body, but were not strong enough evidence to rule out that spread was actually occurring via other routes such as the lymphatic system.

Researchers at Oxford University's clinical research unit at the Hospital for Tropical Medicine in Ho Chi Minh City in Vietnam, for instance, reported last year on a boy whose H5N1 infection spread to his brain, causing encephalitis.

The lead author of that report, virologist Menno de Jong, said his group has found viral RNA in the blood of about half of the H5N1 patients in which they've looked for it.

“It was really surprising for influenza, because the case reports of human influenza and viremia are so rare,” he said from Ho Chi Minh City.

“It's probably quite common in H5N1 infected patients.”

That poses challenges for treating patients infected with H5N1 because if the virus is spreading through the blood, so too must drugs that aim to combat the infection.

Currently there are only four flu antivirals on the market and one, zanamivir (sold as Relenza) is administered to the respiratory tract by inhalation. The drug would need to be formulated in an injectable form to be useful for systemic infection, Dr. de Jong said.

It also raises concerns about infection control for health-care workers and laboratory scientists coming in contact with the blood of H5N1 patients — although precautions against contact with blood are widespread as a consequence of years of experience with blood-borne infections like HIV and hepatitis C.

“I think for this kind of flu, infection control measures should include all bodily secretions, basically,” Dr. de Jong said.

The findings also raise questions about whether blood transfusions could be a source of infection if H5N1 were to become a pandemic strain.

Canadian Blood Services and the American Red Cross have been studying the issue, but currently it is believed that the risk is more theoretical than real, because influenza's incubation period is so short. Once people develop symptoms they would be unlikely to want to give blood and would probably be turned away if they showed up to a blood-donor clinic.

"From the blood-donor and blood-supply point of view, the issue would be whether there's virus in the blood before the patient becomes ill,” said Dr. Jeffrey McCullough, who holds an American Red Cross professorship in transfusion medicine at the University of Minnesota.

“Once you've got somebody that's sick, of course, they wouldn't be acceptable as a blood donor,” he said.

http://www.theglobeandmail.com/serv...fluu0504/BNStory/specialScienceandHealth/home

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PCViking

Lutefisk Survivor
the 1918 flu was an entirely birdlike flu that adapted to humans

Bird flu could mirror deadly 1918 disease
BY DELTHIA RICKS
Newsday Staff Writer

May 6, 2006

Reaching into history hoping to better understand the future, two research teams have reconstructed the devastating 1918 flu virus, discovering it was of avian origin and effectively jumped from birds to humans.

The scientific finding is virtually the same scenario feared by global health officials who are keeping an eye on the growing number of bird flu cases in Southeast Asia.

There, 116 people have contracted the infection -- probably from direct contact with fowl -- and nearly half of those sickened since late 2003 have died. If the virus changes genetically to allow easy transmission from person to person, scientists predict bird flu could become a replay of the 1918 global pandemic that killed at least 50 million people. No continent was left unscathed.

Trekking into the permafrost region of Alaska to unearth the remains of an Inuit Indian woman who died of the so-called Spanish flu, researchers in 1997 gathered tissue to retrieve fragments of the killer virus.

The sample was compared with those preserved by the U.S. military from World War I soldiers who died of the infection. Such protein snippets provided enough biological information for scientists to genetically engineer the pathogen in the lab, resurrecting a killer that mysteriously rose in September 1918 and just as mystifyingly vanished -- though not forever -- a year later.

"The main goals of the work were to understand why the 1918 flu was so deadly," said Dr. Christopher Basler, assistant professor of microbiology at Mount Sinai School of Medicine in Manhattan. Basler and colleagues used the samples' blueprint to begin re-creating the pathogen that infected one in four in the United States and killed about 550,000 nationwide.

Known as H1N1, the virus that caused the 1918 flu still exists in the form of third and fourth cousin subtypes that are not nearly as infectious. Basler said the high degree of virulence 87 years ago stemmed from a lack of human immunity to this early form.

Working with Drs. Adolfo Garcia-Sastre and Peter Palese of Mount Sinai, Basler created "plasmids," a necklace-like arrangement of genes. The scientists then shipped the plasmids to the Centers for Disease Control and Prevention where the plasmids were insinuated into human lung cells. Within days they emerged as fullblown replicas of the 1918 virus.

"We performed this work under high-containment conditions," said Dr. Terrence Tumpey, who led the final steps of reconstruction.

The viral re-creation was announced Friday and is detailed in the journal Science. Completion of the genetic sequencing is reported in today's journal Nature.

Dr. Jeffrey Taubenberger, chief of molecular pathology at the Armed Forces Institute of Pathology in suburban Washington, began the quest for the 1918 killer. He traveled to Brevig Mission on the Seward Peninsula in Alaska nearly a decade ago to gather evidence, preserved in the permafrost.

"One of the important things we've found so far is that the 1918 flu was an entirely birdlike flu that adapted to humans. It is different from the 1957 and 1968 pandemics, which were a mix of human and bird viruses."

Neither the 1957 Asian flu nor the 1968 Hong Kong flu was nearly as deadly as the 1918 strain, which was particularly lethal in young, healthy adults.

Taubenberger said both teams' studies reveal that today's bird flu and the infection of 87 years ago share many of the same genetic features.

Resurrecting a viral killer from the past is not new to science. In July 2002 a team of scientists at Stony Brook University announced they had created a polio virus from scratch.

http://story.irishsun.com/p.x/ct/9/id/acee96d11094fd3b/cid/2411cd3571b4f088/

:vik:
 

PCViking

Lutefisk Survivor
H5N1 in blood might open way for new test

By Tan Ee Lyn
Wed May 10, 4:23 AM ET

Scientists in Thailand have detected live H5N1 bird flu virus in the blood of a boy who died in December, a discovery that might lead to a safer way to diagnose the disease in humans.

At present, respiratory secretions are collected to test for the H5N1 virus.
But that practice, which is physically irritating, can result in the patient coughing violently and spraying the virus, infecting doctors and nurses conducting the procedure.

During SARS in Hong Kong in 2003, scores of healthcare workers ended up infected when they carried out intubation on patients. Intubation is the procedure of passing a breathing tube through the mouth or nose and down the throat. The tube is then used to pass oxygen into the lungs and help a person breathe.

Parvapan Bhattarakosol, a member of the Thai team and a microbiologist from Chulalongkorn University, said a huge amount of live H5N1 virus in the blood plasma of the five-year-old boy was detected more than 12 days after the sample was collected.

This is unusual. According to other microbiologists, respiratory viruses generally are not present in the blood stream after such a long time because they are confined to the respiratory tract and do not replicate well in the blood.


Bhattarakosol also called for the scientific community to study if blood samples can be a reliable means for diagnosis.

"If we can find virus in blood, so maybe blood is another type of sample that we can take and use for diagnosis, instead of using only respiratory secretions," she told Reuters.

"It is easily done and better than taking respiratory secretions, which can be dangerous because it is the secretions that are very infectious."

"There must be another study to see if blood is a suitable sample. If there are other cases of human H5N1, we should draw blood samples and try to detect the virus in blood and then we can see if blood is suitable as a diagnostic test."

MULTI-ORGAN FAILURE

The finding, to be published in the June issue of the Centers for Disease Control and Prevention's Emerging Infectious Diseases Journal, might explain why H5N1 victims suffer from systemic infections, when the virus spreads throughout the body and victims die from multi-organ failure.

"When viruses get into blood, there is a risk of all organs in the body being affected,"
Bhattarakosol said.

There are implications for blood donation and people working with blood samples too. Although 207 people have reportedly been infected since late 2003, and 115 of them have died, scientists say many mild cases of H5N1 infection might have gone undetected.

In Hong Kong, where the virus made its first known jump to humans and killed six people in 1997, later tests showed some hospital workers and others who had not fallen sick during the period carrying H5N1 antibodies -- which means they were infected.

"We should keep this (that H5N1 can live in blood) in mind when donating blood or blood transfusions," Bhattarakosol said.

But Julian Tang, a microbiologist at the Chinese University in Hong Kong, said the finding gave reasons to be optimistic.

In systemic infections, such as those caused by chickenpox or measles, viruses might last longer than a week in the blood stream, allowing for the production of T and B memory lymphocytes in the patient's immune system, which tend to produce lifelong immunity.

"If avian H5N1 influenza produces a detectable blood viraemia for several days, then the response to an H5N1 vaccine may be more long-lasting and protective, than the response to other non-H5N1 influenza vaccines, as there will be a more intense antigenic stimulation to produce specific T and B memory lymphocytes,"
Tang said.

Lymphocytes, the blood cells that make antibodies, have memory cells and this function allows them to remember a past encounter with the H5N1 strain, and produce antibodies to neutralize the virus in future encounters, experts say.

"Those who survive avian H5N1 influenza may be more effectively protected for a longer period against the same strains of H5N1 (i.e. naturally acquired immunity), should they be re-exposed to the same strain in the near future."

http://news.yahoo.com/s/nm/20060510...wIhANEA;_ylu=X3oDMTA5aHJvMDdwBHNlYwN5bmNhdA--

:vik:
 

Fuzzychick

Membership Revoked
PCV, that's good news and bad news all wrapped into one...airborne and then blood borne pathogen isn't good news...
 

New Freedom

Veteran Member
This is a 4 part series on how well they are detecting BF. It is EXCELLENT and well worth the time to read it. There is also a lot of 'reading between the lines' in this article ..... for those who are interested in this subject, IMHO, this an important series......Dr. Yuen is very well respected in his field.



http://service.spiegel.de/cache/inte...5816-2,00.html


The Bird Flu Hunters

By Ullrich Fichtner, Ansbert Kneip and Gerald Traufetter

Bird flu has spread across the globe, but so far it poses little danger to humans. The World Health Organization has launched an ambitious project to battle the pandemic before it jumps the species barrier. The hurdles are many.

Each question about the virus triggers thousands of new questions. "We're in the middle of the problem," says Professor Yuen, a man who clearly has trouble sitting still, as he walks to the blackboard in the windowless conference room in Hong Kong's Queen Mary Hospital. The felt marker in his hand quickly glides across the surface, and within a few minutes the professor has outlined the global history of influenza in black and white. After listing annual figures, along with abbreviations identifying the different strains of the virus -- H2N2, H1N1 -- he taps the hastily written figures and, with the top edge of his glasses forming a line across his pupils, he asks: "And what do we learn from this? We learn that we know nothing, and that every calculation is taken from thin air."


Yuen Kwok Yung is Director of the Department of Microbiology at the University of Hong Kong, Co-Director of the Pasteur Institute, a member of the famed British Societies for Pathology and Surgery and an honorary member of all Hong Kong institutes relevant to his field. He has been a teacher and researcher for the past two decades, has discovered new bacteria, has explained the world of fungi and spores, bacilli and viruses to countless students, has written close to 300 scientific papers and, together with his research team, decoded the SARS virus in Hong Kong. If anyone has the answers, he ought to be the one. But when his lecture turns to H5N1, he says that he too faces more questions than answers. What's more, everything Professor Yuen and his colleagues in other research laboratories have learned about this virus in recent years -- a considerable amount -- has only made them more concerned.

Yuen, a man driven by a sense of inner urgency, takes us on a hurried tour of his institute. The Department of Microbiology lies high up in the hills above Hong Kong, its windows affording a milky view of the bay and the dense, overpopulated city. It was here that they discovered the SARS virus in 2003 and, in 1997, helplessly studied the blood and tissue samples of a child, the first human victim of the H5N1 virus in history.

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By Walter Nowotny
The three-year-old boy from Hong Kong died on May 21, 1997, of a pathogen that had previously affected only animals. Researchers the world over began looking into why the young boy had to die. The hunt was on.

Soon Yuen and his team were examining the virus under the microscope. At first its structure was indecipherable, but as the analyses progressed, the researchers unraveled its code. But the deeper the researchers penetrated into the world of H5N1, the more puzzles they found.

The question of questions -- still -- is whether the virus will jump from human to human like a cold, through an act as simple as a kiss, and whether it can then grow just as virulent as the original strain which spreads like fire through geese and ducks. If so, mankind faces an epidemic of unknown proportions, a flu pandemic that could be even worse than the notorious 1918-1920 outbreak which claimed the lives of at least 20 million people worldwide.

This time around, doctors want to head nature off at the pass. The World Health Organization calls the effort mankind's first attempt to control a pandemic before it even starts. If successful, it would be the first time humanity thwarted a dangerous new virus.

Achieving this lofty goal would require constant and thorough monitoring of the entire globe. It would need a center of operations where all information about possible cases of the virus would be collected and correctly interpreted -- a sort of global emergency call center, staffed around the clock, which could be notified immediately when more people than usual show up at some local hospital in some isolated village, complaining of fever.

Geneva, Headquarters of the WHO

Precisely this kind of effort is underway in a former movie theater in the basement of a Geneva high-rise. The building houses the headquarters of the WHO, and until recently the theater was used to show short instruction films about healthcare.

But now the cinema seats have been removed, and the WHO has installed conference tables, computers, monitors and microphones. Everything, starting with the matte black computers, looks expensive. Instead of a movie screen, the front wall now holds six modern plasma TVs, which together form a giant flat screen.

The room, now called the "Strategic Health Operation Centre," is the agency's command post in its worldwide fight against influenza viruses, but also against Ebola, cholera, polio and the plague. It's from this base that WHO officials hope scientists will discover the sources of epidemics before they become a threat. It also represents the organization's ambitious move to gain control over the vagaries of nature, with the hunt for H5N1 presenting a model for the future.

Each morning at nine o'clock, about 30 WHO experts meet to discuss the situation. The room offers seats for 14 people; for the rest it's standing room only. The giant composite screen shows a computer map of outbreaks around the world. The words "Acute Diarrheal Syndrome" are outlined in yellow next to El Salvador. The color is significant. It means that this is a new incident about which officials have very little reliable information to date -- and also means that it could be an infectious disease. Cholera, for example. Purple is the color for "Ongoing Events," such as meningitis in Sudan and polio in Somalia.

Disinfecting a chicken coop in eastern Turkey in 2006.
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AFP
Disinfecting a chicken coop in eastern Turkey in 2006.
Brown indicates outbreaks that are still being observed and for which there are no updates and no new infections, but also no all-clears: cholera in Angola, respiratory illnesses in China. Finally there is influenza -- bird flu -- highlighted in places like Azerbaijan and China.

The group includes experts on the various regions of the globe, as well as specialists in individual diseases. Their job is to assess just how much of a threat the reports shown on the screen pose. The respiratory illnesses in China, for example, are not particularly worrisome. It just happens to be the time of the year for lung-related problems in the region. The scene at the Strategic Health Operation Centre conveys the reassuring impression that everything is under control, that there is no acute worldwide danger. But the situation would turn critical if there was a sudden jump in respiratory cases, or if they began occurring at a different time of the year.

The man whose job it is to keep a close watch on all this is a 46-year-old German named Thomas Grein, head of the "Alert and Response" team at the WHO. He and his staff make sure all current outbreaks of illness do in fact appear on the screen during each morning's meeting. His work represents the attempt to be faster than the illness itself.

Grein, who studied medicine in Germany, went to Australia before completing his state examinations. He later ran a hospital in Papua New Guinea and ultimately ended up at the WHO as an expert in infectious diseases. He's a wiry man who wears his shirt open at the collar and sports a sun burn from his last trip to Indonesia. His German is peppered with words and phrases in English, the unofficial language of record at the WHO.

"We haven't missed a single major outbreak in recent years," he says.

Hong Kong, Queen Mary Hospital

Back in Hong Kong, Professor Yuen shows off refrigerators filled with test tubes, and in passing greets employees busy working with cell cultures in flat dishes. Almost 80 technicians work around the clock, seven days a week in his laboratories, which are considered among the world's finest. But ever
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since H5N1 came into the world, Yuen's laboratory staff has been struggling to re-establish a routine. Everyone here seems to expect a suspicious saliva sample to appear any day -- the evidence that the deadly bomb of a worldwide flu epidemic has been ignited.

Back in 1997, when the first wave of H5N1 rolled through Hong Kong, patients were admitted who died within days of developing pneumonia or from kidney failure. But others, who had also contracted the virus, recovered quickly and without lasting damage. The killer virus was so puzzling, in fact, that it took researchers a while to realize that it was part of the Influenza A group.
__________________

PART 2

The Bird Flu Hunters (2)



When experts at laboratories in London, Rotterdam and Atlanta studied the material from Hong Kong, they first believed that they were dealing with faulty samples, and it took many weeks before the new abbreviation for fear, H5N1 -- also known as avian influenza or bird flu -- had been spelled out.

From the start, in laboratory tests, the virus behaved in completely unexpected ways. It reproduced far faster than every other known influenza strain; it survived in environments that would have killed other pathogens immediately; it kept appearing in different forms, with constantly changing surfaces and new variants; and it was always highly pathogenic.

Yuen's department, especially virologist Guan Yi, immersed themselves in the field of veterinary medicine to follow the source of the new disease. Working secretly at first -- even off the radar of state supervision -- they collected samples of sick and dead birds in China. Later, when it became impossible to conceal their work, they received official permission to travel throughout the country.

One of their most promising sources of material and information was practically at their doorstep in neighboring Guangdong Province, a region of small farms where man and beast have lived side-by-side for generations. Guangdong is the world's most densely populated region, says Professor Yuen, "when it comes to both humans and chickens." This makes the province an incubator for pathogens and a wide range of viruses. In fact, many waves of the flu that have struck mankind in the past had their beginnings in Guangdong.

At Lake Qinghai in northwest China, in May 2005, the researchers witnessed a mass dying of birds, when the virus killed 6,000 bar-headed geese, gulls and cormorants within hours. They visited the habitat of the wild birds and the places where migratory birds stopped to rest, and they went to poultry markets, where they took more than 160,000 samples.

Though now common knowledge for more than a year, what the researchers discovered was unheard-of until articles from Hong Kong were finally published in the respected scientific journals Nature and Lancet. The world discovered, through the findings of Guan, Yuen et al., that wild birds also contract the virus, that migratory birds must be involved in its transport, that transmission apparently takes place between wild animals and domesticated animals and that H5N1 isn't a single virus. In fact, it seems capable of constant mutation. Even more alarming, H5N1 is clearly on its way to overcoming even greater barriers than between domestic and wild animals -- namely the barrier between animals and human beings.

A flu virus can best be pictured as a microscopic body covered in cone-like appendages, which are formed by two groups of proteins, hemagglutinin and neuraminidase, or H and N. There are 16 subtypes of hemagglutinin and 9 of neuraminidase. The H protein allows the virus to attach itself to host cells.

For H5N1 to become a pandemic -- that is, transmissible from human to human -- the virus has to mutate. This change could take place in chickens, but the virus might also find another host, such as a person who has already contracted a conventional flu and who subsequently catches H5N1 through contact with (for example) an infected chicken. The different flu strains could mix their materials in the cells of this person and produce a new virus that would easily jump from human to human. That would be extremely dangerous -- because antibodies against this new mixed strain couldn't possibly exist yet.

In June 2005, Professor Yuen published what he knows about human infections with H5N1 in the Hong Kong Medical Journal. His conclusions are all the more devastating because they reveal just how little the scientific community knows about flu viruses in general, even though scientists learned how to break them down into their individual components long ago. It's almost as if all the pieces to a puzzle were spread out on a table, but no one knew what the final picture was supposed to look like.

Geneva, Headquarters of the WHO

In Geneva, Grein's team, hoping to learn about a new outbreak as early as possible, has created an informational network that circles the globe. When the highly pathogenic and fast-acting Marburg virus surfaced in Angola last year, it quickly killed several hundred people. But the WHO averted a catastrophe by promptly dispatching experts to the country.

One hundred and sixty of the WHO's national bureaus send regular information to the center in Geneva, which also receives official reports from health ministries -- although the health ministry reports, coming as they do through official channels, often arrive far too late to be of particular use.

It's no longer possible to conceal an outbreak of an infectious disease nowadays, says Grein, because the world has moved so close together. Rumors spread wherever large numbers of people fall ill at the same time, and rumors soon end up in the local media, as possibly exaggerated and certainly not medically substantiated news. But the reports tend to get posted on the Internet, where doctors in Geneva can read them. The WHO garners more than half of its information from Internet sources.

Each day, more than 1,000 reports that could somehow be relevant are posted on the Internet. The first reader of these reports at the WHO is a computer program, a search engine that looks for key words in seven languages, including Chinese. Each day 200 to 250 reports make it through the screening software, reports that Grein and his team must then review. Only a handful of these reports require more careful scrutiny, and maybe only one report per day is cause for true concern.

In 2005, there were 225 such alarming reports, including 54 reports of cholera and few of yellow fever, Ebola and polio. "Influenza/acute respiratory syndrome" was in second place, with 23 suspicious reports. These are the cases in which Grein gets the local WHO personnel involved. In most cases, he says, his colleagues already have more details. They know whether the rumors are true, they've already contacted the hospitals in question and possibly offered assistance to local health authorities. The WHO can send teams to affected countries, but only with invitations from their governments.

As the team leader, Grein usually flies along to the site. In 2004, for example, he went to Vietnam, where cases of humans contracting the bird flu virus had been reported. Grein contacted his man in Bangkok, Mark Simmerman, and they met in Hanoi. At that point, no one knew whether the victims had caught the disease from humans or poultry. Their families, employers and doctors had to be questioned. Who had been in contact with whom and when? Which path could the virus have taken?

This process is meant to produce recognizable patterns of infection, providing answers to questions such as: Who falls ill, and at what point, when the virus jumps from animals to humans? And what would this type of cluster look like if H5N1 were transmitted from human to human?

Three patients had died by the time Grein left the country, and all three had become infected via contact with chickens. Given the situation, this was good news. But Grein also knew that the disease would return. His colleague in Bangkok, Simmerman, moved to Hanoi to be closer to the front between the virus and human beings.

Hanoi, Vietnam, WHO Office

The WHO offices are in a colonial building south of Hanoi's old downtown, only a block from the "Market of December 19," where long rows of merchants sell vegetables, fresh meat, eggs and grilled dogs. Each morning, Mark Simmerman sees firsthand how fear of the virus is changing Vietnam. At stand 282, Ms. Ba has been selling nothing but dead chickens since January. Three plucked birds lie on a stand, top-quality, free range chickens with purple stamps on their skins, one from the slaughterhouse outside Hanoi and one from the government inspector who examines and gives his stamp of approval to poultry each morning between five and six a.m.

Ms. Ba has never objected to the rules. They make sense to her, she says. After all, 93 people have fallen ill with the H5N1 virus in Vietnam, and 42 of them died -- more than in any other country in the world. She is nostalgic for the good old days when the narrow alleys between booths were full of live poultry, making the market a much livelier place. But, she adds, resistance would be pointless. "The inspectors are very, very strict," she says.

The WHO's Mark Simmerman has nothing against such severity. He's a pale American who wears a tie in hot, humid Hanoi, a man who seems intent on not making any mistakes. It would be a mistake, for example, to publicly criticize the Vietnamese authorities. It would also be a mistake to exaggerate or understate the risks posed by the virus.



The Bird Flu Hunters (3)



Simmerman concedes that the business of inspections is difficult, given Vietnam's agricultural structure and its confusing communal hierarchies. The country, with its 11,000 communes, has 8 million "backyard farmers" who keep a few chickens. "A few," in this case, can mean anything from 5 to 500 birds. And then there are about 2,000 large-scale chicken farms. It's practically impossible to trace every dead chicken in this country. Instead, Simmerman takes a diplomatic approach and says: "Vietnam is well-prepared."

He meets almost daily with officials from the health ministry to discuss ways the WHO's prevention plan can be used to avert the threat of a pandemic. But, as has so often been the case in the history of the UN, clear intentions rub shoulders with a murkier reality. In Vietnam's case, the WHO's recommendations are likely to fail because of a lack of medical and technical equipment, logistical capacity, communication among government agencies, reliable data and trained personnel. To make matters worse, poultry is smuggled into Vietnam from southern China every day and sold in black market stalls on the outskirts of Hanoi.

Simmerman rejects the criticism. Instead, he asks: "So? Does that mean we shouldn't make plans? Does that mean we shouldn't put together the ideal situation? I want to find out what we know, not what we don't know. We have a virus that occurs in birds. We have a virus that has already spread a great distance, worldwide, in fact. This means that we must act. At least we have to try."

A drive into the countryside north of Hanoi offers a glimpse of the enormous task the WHO has undertaken. It leads through farmland where, in one roadside village after the next, chickens and ducks roam free in every small courtyard, in places where the boundaries between stalls and human residences are fluid, where man and beast live in seemingly idyllic harmony.

The region was already the site of a high-level alarm in early 2005, because it appeared that human-to-human transmission of the H5N1 virus had already become reality. Hospitals were admitting infected people who had not been in contact with poultry but had still contracted the virus. A decline in the death rate also caused uproar in the medical and scientific community. In the past, 80 percent of those infected had died -- a rate that had now dropped to only 34 percent. This sort of decrease is dangerous because it often shows that the virus has adjusted itself to its new host. There were clusters, or small groups of people, such as families, within which the virus may have been transmitted.

But in their laboratories, the scientists found nothing to support the assumption that this was a local outbreak of a human-to-human pandemic. However, they were also unable to find clear evidence to disprove the hypothesis, because autopsies are prohibited in Vietnam. As a result, what the rest of the world knows or believes about the outbreak remains unsubstantiated and hypothetical. Based on the most recent information, it appears possible that "limited" human-to-human transmission has already taken place. The fact that they did not lead to a global pandemic can only be interpreted as a good sign.

Oxford University Professor Jeremy Farrar, who treats flu patients in Vietnam, believes that fears of a global catastrophe are exaggerated. Farrar argues that "if it were so easy for the virus to jump from chickens to people, it would already have done so on a large scale."

Veterinary brigades have descended upon Vietnam's farms and villages in the past year to vaccinate 240 million chickens against H5N1 -- an astonishing operation. All farmers were required to register themselves and their animals at registration offices set up specifically for this purpose, with the government imposing penalties on those who refused. After that, and because no further human cases of H5N1 disease surfaced, the government declared the country "free of bird flu."

Whether this is true is anyone's guess. Even Simmerman, the cautiously diplomatic WHO officer, calls the government statement "tricky." "When a statement is phrased in such absolute terms," he says, "it's highly likely that it'll end up being proved wrong."

Geneva, Headquarters of the WHO

Indeed, the entire world has already been proved wrong, especially Europe. So much so that the virus trackers at the WHO's command center in Geneva have been able to keep meticulous accounts of H5N1's trail of devastation. Europe's governments and societies have felt safe for the longest time, trusting in the superiority of Western hygiene and the safety of the European agricultural industry. For Europeans, H5N1 was an Asian problem. But when the first dead birds were discovered in Turkey last October, it was clear that the virus had made its way to Europe's borders.

It had already taken a long journey, a journey monitored by WHO personnel. The 1997 Hong Kong outbreak, in which 18 people fell ill and six died, at first seemed to be an isolated occurrence. But the virus returned in 2003, more aggressively than before, breaking out in South Korea, Vietnam, Indonesia and, once again, in Hong Kong.

In 2004 it reached Thailand, Japan, Malaysia and Cambodia, where it wreaked havoc on poultry farms. But it was wild birds that took H5N1 farther afield. In the spring of 2005, large numbers of birds died at central China's Qinghai Lake, where Professor Yuen had taken so many samples. The lake is an important resting and nesting site for migratory birds. In the summer, the birds carried the virus to the north and west, into Mongolia, Russia and finally Kazakhstan. In October it reached Romania, Croatia and Turkey, and was in Ukraine by December.

Europe, which had felt so safe, wasn't ready, and Turkey became a test case to demonstrate that lack of preparedness. Of 12 infected people, four children died, three of them from the same family, infected by sick chickens the children had been playing with.

On January 6, Grein and a four-person team went to Turkey and flew to the Kurdish city of Van, where Grein introduced himself to the local crisis team, taking pains to appear modest and avoid creating the impression that the WHO team had come to the region as inspectors. Grein asked many questions intended to ascertain that H5N1 had not been transmitted from human to human in Turkey -- an eventuality he was fortunately able to rule out. According to the WHO's most recent information, fears that the virus had changed in Turkey, making it easier for it to jump to humans, proved to be unfounded.

Nevertheless, the rate at which the virus was flying around the world had increased. Although it took eight years, from 1997 to the end of 2005, to infect 15 countries with avian flu, since the beginning of this year H5N1 has taken only four months to appear in 30 new countries, including Iraq, Israel, Gaza, Egypt, Pakistan, Myanmar, India, Nigeria, Niger, Cameroon and Burkina Faso. Nowhere in Europe has the bird flu spread as quickly than in Germany, where more than 300 cases demonstrate that the virus has found a foothold in most German states. However, Germany's infectious disease precautions have prevented human infection, as evidenced by the negative blood samples taken from those who had been in contact with infected animals. The fact that there were two deaths -- two poultry farmers who committed suicide out of despair for their livelihoods -- shows how quickly the virus can produce hysteria. Hysteria can be deadly, but so can carelessness.

Grein is especially worried about Africa. Nigeria, for example, was unprepared for the arrival of the virus. The country had no emergency plan for this type of outbreak: There was no coordination among government ministries and no crisis task force that could have been assembled. It took almost four weeks until the pathogen was detected in early February and reported to the WHO. It took nine days for the members of a crisis task force to begin work in the capital, Abuja. By early March, the WHO was already reporting 130 contaminated poultry farms in 11 provinces. In early April, the virus reached the slums and backyards of Lagos, a city of 15 million people, and probably as many chickens. To this day, the WHO lists Nigeria under its category "Human disease carriers: none." It would be amazing if that were true.

Since 2003, 113 people have died of avian flu, including 37 in the past four months alone. Whether the WHO manages to avert a flu pandemic depends first and foremost on how quickly it detects the outbreak in the first place. Computer models used at WHO have yielded a critical number: 21.

Mankind has just three weeks to bring a pandemic under control.

Within 21 days of the first human-to-human transmission, everyone who has been in contact with the first person to contract the disease from another human must be found, examined and isolated. Each of these people will be given antiviral drugs, as will doctors, nurses and laboratory workers. For the first three weeks, the number of those who were in contact with the first patient or his family and acquaintances is still relatively small. But it increases exponentially, and after three weeks an outbreak is no longer controllable. WHO officials have prepared a list of alarm signals. If three or more individual medical workers suddenly fall ill or die, this could be the point of departure of an epidemic. If five or 10 normal citizens fall ill or die without having had significant contact with birds, this is interpreted as an alarm, as it is when a laboratory detects a new type of virus containing both human and avian genetic material. By this point, perhaps 10 of the critical 21 days have already passed.

Can a country protect itself? Would it be effective to close borders and deny entry to anyone from affected regions? "That's an illusion," says Grein. "You have to assume that the entire world is so networked and mobile today that closing a border would give you a few days' respite at best. No more than that."

Hong Kong, Queen Mary Hospital

Hong Kong has experience with new epidemics, and the city's population is already familiar with what it's like to live in a nightmare the rest of humanity can only imagine. When the SARS virus was raging in 2003, six years after the first wave of H5N1, the city became a stage for an apocalyptic drama.




The Bird Flu Hunters (4)



Hong Kong's enormous downtown shopping malls were silent and empty. Subway trains, normally jam-packed, rattled through tunnels without a single passenger, even during rush hour. Restaurants were forced to close, supermarkets were shuttered and movie theaters went dark -- all because no one ventured outside anymore, except when absolutely necessary.

During the SARS outbreak, everyone hid behind masks and avoided even the slightest human-to-human contact. If everything goes wrong, H5N1 could be a replay of those days in Hong Kong, except on a much larger and more damaging scale. It's a scenario that Professor Yuen likes to conjure up whenever the discussion turns to politics. As a scientist, he's a natural skeptic. As a professor, he talks about nature being "so full of surprises, so overwhelmingly complex."

The virus's never-ending genetic mutation is random, and it has repeatedly adapted to new host animals. At first it raged only in domestic birds, where its range was restricted, but then it was discovered in wild, migratory birds that transported it across great distances. Then the virus "learned" to destroy the immune systems of mammals, killing cats, tigers and pigs. It began killing people with growing frequency, including individuals who had not been in direct contact with birds.

As a scientist, Professor Yuen -- like many of the virus hunters who are tracking H5N1's global path of destruction -- is anxious to find the right balance between alarm and caution, the right words for a threat that, though frightening, remains unreal for many. As a politician, Professor Yuen imagines the worst-case scenario, the devastating, all-encompassing flu pandemic that will "in all likelihood occur in the near future."

Such talk has led to the culling of 200 million birds worldwide, representing a financial loss of $20 billion. It's also prompted the UN official responsible for flu epidemics to issue a renewed warning -- just recently -- that the world must be prepared for a pandemic.

In Hong Kong, such talk has led to an official effort to separate human beings and animals as much as possible. In December 1997, for the first time in Hong Kong's history, all poultry in the city was culled within three days, a mass killing of 1.5 million animals. When the virus returned in 2001, another 1.4 million chickens, geese and ducks were slaughtered, and after a third wave in 2002, 919,000 birds were destroyed.

The city government has decided to build a central slaughterhouse out in the New Territories, so that all live poultry can be permanently banned from markets. Professor Yuen supports this policy. The government has appointed him its scientific advisor, and he is campaigning for a major break with tradition -- a shift away from fresh markets to a city that gets its food supply through more industrialized channels. This would have an enormous impact on the city, permanently changing its appearance and its character. But, says Yuen, the proposed move is part of an effort to avert an epidemic by introducing strict hygiene and, as such, ought to convince people to bid farewell to tradition.

Animals, not just birds, have become a problem in the overpopulated city of 7 million, with a number of neighborhoods hopelessly overcrowded. When reports emerged that domestic cats could also catch H5N1, Hong Kong's garbage collectors began finding dead cats lying on the streets below the apartment building windows of their former owners.

A ban was recently imposed on transporting live birds on buses and subways. The importation of new songbirds was stopped long ago. And in the city's major corporations, including banks like HSBC, the emergency management officers are making plans for doomsday. Will a third of the bank's 30,000 employees die if H5N1 becomes a pandemic? Will half of them simply not show up for work? Will the bank be forced to close all its branches?

The emergency management officer keeps up with everything the WHO and the universities know about bird flu, meeting with scientists and consulting with doctors. He's constantly improving the company's virtual private network so that it doesn't loose touch with its employees if the day of days ever becomes a reality and the world suddenly comes to a standstill. He prepares lists of relative importance, from A+ to D -- "completely indispensable" to "dispensable." At the top of his list are the major futures transactions, IPOs, mergers and acquisitions. Window cleaning and cafeteria operation are at the bottom.

A "crisis committee" consisting of representatives from HSBC's ten key departments already holds regular meetings in the HSBC Tower. The committee scrutinizes and fine-tunes scenarios and is already assigning responsibilities should the pandemic ever become reality. It seems an eerie planning game from a European perspective, but in Hong Kong, after the city's many experiences, it's merely proof of a sober sense of reality.

Hong Kong has experience with new epidemics, and the city's population is already familiar with what it's like to live in a nightmare the rest of humanity can only imagine. When the SARS virus was raging in 2003, six years after the first wave of H5N1, the city became a stage for an apocalyptic drama.

Hong Kong's enormous downtown shopping malls were silent and empty. Subway trains, normally jam-packed, rattled through tunnels without a single passenger, even during rush hour. Restaurants were forced to close, supermarkets were shuttered and movie theaters went dark -- all because no one ventured outside anymore, except when absolutely necessary.

During the SARS outbreak, everyone hid behind masks and avoided even the slightest human-to-human contact. If everything goes wrong, H5N1 could be a replay of those days in Hong Kong, except on a much larger and more damaging scale. It's a scenario that Professor Yuen likes to conjure up whenever the discussion turns to politics. As a scientist, he's a natural skeptic. As a professor, he talks about nature being "so full of surprises, so overwhelmingly complex."

The virus's never-ending genetic mutation is random, and it has repeatedly adapted to new host animals. At first it raged only in domestic birds, where its range was restricted, but then it was discovered in wild, migratory birds that transported it across great distances. Then the virus "learned" to destroy the immune systems of mammals, killing cats, tigers and pigs. It began killing people with growing frequency, including individuals who had not been in direct contact with birds.

As a scientist, Professor Yuen -- like many of the virus hunters who are tracking H5N1's global path of destruction -- is anxious to find the right balance between alarm and caution, the right words for a threat that, though frightening, remains unreal for many. As a politician, Professor Yuen imagines the worst-case scenario, the devastating, all-encompassing flu pandemic that will "in all likelihood occur in the near future."

Such talk has led to the culling of 200 million birds worldwide, representing a financial loss of $20 billion. It's also prompted the UN official responsible for flu epidemics to issue a renewed warning -- just recently -- that the world must be prepared for a pandemic.

In Hong Kong, such talk has led to an official effort to separate human beings and animals as much as possible. In December 1997, for the first time in Hong Kong's history, all poultry in the city was culled within three days, a mass killing of 1.5 million animals. When the virus returned in 2001, another 1.4 million chickens, geese and ducks were slaughtered, and after a third wave in 2002, 919,000 birds were destroyed.

The city government has decided to build a central slaughterhouse out in the New Territories, so that all live poultry can be permanently banned from markets. Professor Yuen supports this policy. The government has appointed him its scientific advisor, and he is campaigning for a major break with tradition -- a shift away from fresh markets to a city that gets its food supply through more industrialized channels. This would have an enormous impact on the city, permanently changing its appearance and its character. But, says Yuen, the proposed move is part of an effort to avert an epidemic by introducing strict hygiene and, as such, ought to convince people to bid farewell to tradition.

Animals, not just birds, have become a problem in the overpopulated city of 7 million, with a number of neighborhoods hopelessly overcrowded. When reports emerged that domestic cats could also catch H5N1, Hong Kong's garbage collectors began finding dead cats lying on the streets below the apartment building windows of their former owners.

A ban was recently imposed on transporting live birds on buses and subways. The importation of new songbirds was stopped long ago. And in the city's major corporations, including banks like HSBC, the emergency management officers are making plans for doomsday. Will a third of the bank's 30,000 employees die if H5N1 becomes a pandemic? Will half of them simply not show up for work? Will the bank be forced to close all its branches?

The emergency management officer keeps up with everything the WHO and the universities know about bird flu, meeting with scientists and consulting with doctors. He's constantly improving the company's virtual private network so that it doesn't loose touch with its employees if the day of days ever becomes a reality and the world suddenly comes to a standstill. He prepares lists of relative importance, from A+ to D -- "completely indispensable" to "dispensable." At the top of his list are the major futures transactions, IPOs, mergers and acquisitions. Window cleaning and cafeteria operation are at the bottom.

A "crisis committee" consisting of representatives from HSBC's ten key departments already holds regular meetings in the HSBC Tower. The committee scrutinizes and fine-tunes scenarios and is already assigning responsibilities should the pandemic ever become reality. It seems an eerie planning game from a European perspective, but in Hong Kong, after the city's many experiences, it's merely proof of a sober sense of reality.
 

New Freedom

Veteran Member
http://www.asianewsnet.net/stech.php?aid=1238


Why the bird flu virus is so deadly

By Tania Tan


Historically, humans were never at risk of being infected by the bird flu because the virus could not jump from birds into humans. Until 1997, that is.

The H5N1 avian influenza virus broke through the barrier that year, with the first human infections emerging in Hong Kong. The threat has not ebbed since.

Prior to the Hong Kong outbreak, which saw 18 human cases, six deaths and over 1.6 million chickens culled, previous outbreaks of the H5N1 virus in poultry were small and localised.

At the time, little was known about the virus, whose name is derived from the two types of protein that cover the particle surface--hemaggluttin type 5 (H5) and neuraminidase type 1(N1).

It is the hemaggluttin protein which recognises specific protein beacons on host cells. It sticks itself like a key onto the host protein--the lock--and gains entry that way.

Neuraminidase helps the virus exit the cell after it has completed replication.

It was previously believed that humans lacked the correct proteins (locks) for the viral particles (keys) of the H5N1 to bind to.

But now, some studies show that the H5N1 virus recognises some of the 'locks' --specifically those in the air sacs of the human lung.

Fortunately, because the H5N1 virus binds poorly to human proteins, infection has been limited to people with very close contact to infected poultry.

Once inside, the virus hijacks the cell's protein-making machinery to produce more copies of itself. The host cells effectively become virus factories.

They eventually burst and die when the virus exits to infect other cells.

It is also believed that, unlike other flu viruses, H5N1 can also infect cells outside the airways, such as the liver, kidneys and brain. Two infected children in Vietnam also suffered severe diarrhoea and seizures, which indicated that the virus had spread to the gut and nervous system.

But scientists do not know for sure yet how the virus affects other organs.

Speaking at the Lancet Asia Medical Forum held here last week, virologist Robert Webster said that only three or four autopsies have been done of people who died of H5N1, which makes it difficult for scientists to study the virus' effect.

The bird flu virus has infected 206 humans worldwide. It has also been reported in cats, pigs and even tigers.

With its affinity for mammals, scientists fear that the bird flu could mutate to spread easily between people. Right now, it is most likely to be spread through close contact with infected poultry.

Webster, a world-renowned virologist at the St Jude's Children's Research Hospital in Memphis, predicted that it would take at least 10 mutations before the H5N1 virus could transmit from human to human.

He added that there was no way of predicting how soon--or if--such an event would take place.

The two-day international forum brought together many of the world's foremost experts on the avian flu. Altogether there were 25 speakers.

Dr Malik Peiris from the University of Hong Kong has been researching viruses for over 20 years.

It is "fortunate" that the H5N1 virus does not spread easily among humans, noted Malik.

But what makes the virus especially dangerous, is its ability to reassort.

Peculiar to influenza, reassortment refers to how the viruses constantly swop genetic material among themselves. The new combination of genes may enable the virus to perform new functions.

"H5N1 may become pandemic when it reassorts with the human flu virus," cautioned Malik.

Pigs pose a particular danger.

As virus "melting pots" pigs can act as a meeting place for the human and avian virus to exchange material, explained Malik.

Scientists believe it is just a matter of time before the H5N1 becomes a human virus. When that happens, many people will be infected and many may die.

The oft-quoted example is the Spanish Flu pandemic of 1918, which is reported to have killed 20 to 50 million people. That too came from a bird flu virus.

But there is no need to hit the panic button just yet.

While the prognosis may seem bleak, experts are doubtful that the virus will maintain its virulence if a pandemic occurs.

Professor John Oxford of St Bartholomew's and the Royal London Hospital explained the most deadly diseases do not spread much because the host dies before the virus can be passed on.

He gave the example of the Ebola virus, a horrific disease which has not led to a widespread outbreak because it burns itself out so quickly.

These viruses tend to become less deadly as they become more infectious since it does no good to them to kill their host, he said.

Another promising outlook is that a vaccine for the H5N1 virus may not be far off. Initial human trials have been encouraging.

Tests in the United States and France have showed that high doses of antiserum are effective and that patients have few or no side effects.

It is, however, too early to tell how the battle against the flu will shape up.

Fortunately, the effects of a pandemic can be lessened with planning and preparation.

Already a global effort is under way to mount a pre-emptive strike against H5N1.

One of the immediate priorities is to prevent the further spread of the virus within poultry populations.

By implementing more hygienic farming practices and vaccinating persons at high risk of exposure, the chance of transmission can be reduced greatly.

Right now, not many countries are well-prepared to face the disease but global agencies like the World Health Organisation are trying to change that.

The organisation has already drawn up a global response plan which includes the provision of antivirals and medical support teams to affected areas.

Experts at the forum pointed out that this level of preparation against a pandemic has never happened before, and may be our best chance against it. The best defence is offence.

As Webster so aptly put about a pandemic: "It may never happen. We hope it doesn't happen. But we should not be complacent tha
 

PCViking

Lutefisk Survivor
Scientists Fear Bird Flu Virus May Have Mutated

May 18, 2006

World Health Organization officials are increasingly concerned that a thus far unexplained outbreak of the bird flu virus could mean that a long-feared scenario has been borne out -- that the virus may have mutated so that it can be passed from one human to another.

The concern began with reports that seven members of one family in a remote Indonesian village had come down with the disease.

Doctors were immediately troubled by the fact that there had been no outbreaks of the disease among birds in the region. To date, all of the more than 200 people infected with the virus have gotten it from contact with a diseased bird.

Health authorities hoped that their investigation would disclose a common contact among the seven infected people. So far, that contact has not been found.

At this point, health officials say they cannot rule out that the seven infected family members passed the virus to each other.


Scientists from the Centers for Disease Control and Prevention have joined their WHO colleagues on the scene to continue the probe.

Unless they can find a connection among all seven family members with one or more diseased birds, they say they may be forced to conclude that a mutation has occurred.

Some scientists have said that if the disease can be transmitted easily among humans, the resulting pandemic could be catastrophic, resulting in millions of fatalities worldwide.

At least 115 of the 208 people known to be infected with the bird flu have died in the last three years, mainly in Asia.

http://www.consumeraffairs.com/news04/2006/05/bird_flu_mutate.html

:vik:
 

PCViking

Lutefisk Survivor
WHO backs dual antiviral therapy for some bird flu cases

Fri May 19, 2006 3:47 PM ET

By Stephanie Nebehay

GENEVA (Reuters) - Bird flu patients should receive Tamiflu as a frontline treatment, but doctors may also consider combining it with an older class of effective flu drugs, the World Health Organization (WHO) said on Friday.

The option of so-called "dual antiviral therapy" was among the latest clinical recommendations issued by the United Nations agency for countries battling outbreaks of the deadly H5N1 virus among humans.

The recommendations were drawn up at a closed-door meeting of 30 international experts in late March, hosted by the WHO, which published them on its website on Friday.

It said the experts strongly recommended Tamiflu, a flu drug made by Swiss-based Roche, be used. Zanamivir -- which is marketed as Relenza by GlaxoSmithKline -- was a second choice. Relenza is available only for inhalation.

Both drugs belong to a new class called neuraminidase inhibitors and can prevent the virus from infecting cells in the first place.

But the experts said amantadine and rimantadine -- in an older class of drugs known as M2 inhibitors which are cheaper -- may be used alongside the newer drugs in certain cases.

"Clinicians might administer a combination of a neuraminidase inhibitor and an M2 inhibitor if local surveillance data show that the H5N1 virus is known or likely to be susceptible,"
the WHO report said.

Nahoko Shindo, a WHO medical officer who took part in the experts' meeting, said the dual therapy could block the virus from replicating in two different ways.

"This is the first time we clearly state the possibility of dual therapy to be considered in case you are facing a H5N1 outbreak," Shindo, who advised hospitals in eastern Turkey during the country's outbreak last January, told Reuters.

"Even if you are in the middle of an outbreak, dual therapy can do good. You can even start at the early stage of illness," the Japanese doctor added.

The WHO said as there were currently no clinical trials in patients with the deadly disease, it was difficult to base judgments on the quality of evidence. More research was needed, it said, cautioning over possible side effects of dual therapy.

"This recommendation places a high value on the prevention of death in an illness with a high case fatality. It places a relatively low value on adverse effects, the potential development of resistance and costs associated with therapy,"
the WHO report said.

Animal studies have suggested that adding amantadine to Tamiflu might help suppress the virus better, even though many influenza viruses, including H5N1, have developed what is known as resistance to amantadine.

Bird flu remains primarily an animal disease and has been confirmed in birds in more than 50 countries. It has killed 123 of the 217 people in 10 countries who have caught it since late 2003, according to the Geneva-based agency.

http://today.reuters.com/news/newsA...KOC_0_US-BIRDFLU-WHO-DRUGS.xml&archived=False

:vik:
 

PCViking

Lutefisk Survivor
Avian Influenza H5N1 in Naturally Infected Domestic Cat

Vol. 12, No. 4
April 2006

Highly pathogenic avian influenza (HPAI) H5N1 causes death in many avian species and mammals, including humans (1–5). In Thailand, infection by HPAI H5N1 has been reported in mammalian species such as tigers (1,3) and cats (6). Most infected mammals had high fever, panted, and showed symptoms of depression, myalgia, and nervousness (4). This article reports H5N1 infection in a cat during the early H5N1 outbreaks in Thailand and characterizes the genome of H5N1 virus isolated from the infected domestic cat.

The Study

In early February 2004, during the outbreak of HPAI (H5N1) in Thailand, a carcass of a 2-year-old male cat (Felis catus) was taken in an icebox 6 hours postmortem to the Faculty of Veterinary Medicine at Kasetsart University, Nakornpathom, Thailand. The cat's owner volunteered the information that the cat had eaten a pigeon (Columba levia) carcass 5 days before illness onset. The owner reported that the cat had a temperature of 41°C, was panting, and appeared to be depressed. Furthermore, the cat had convulsions and ataxia and died 2 days after onset of illness. The cat was given a single dose of 75 mg aspirin 1 day before it died; however, its body temperature remained elevated. Many dead pigeons were found in the area where the cat lived. Necropsy of the cat showed cerebral congestion, conjunctivitis, pulmonary edema, severe pneumonia, renal congestion, and hemorrhage in the intestinal serosa. Tissues from brain, trachea, lungs, mesenteric lymph nodes, intestines (duodenum, jejunum, and ileum), kidneys, liver, pancreas, spleen, and heart were collected, fixed with 10% buffered formalin, and processed for histopathologic examination. Histopathologic examination results showed nonsuppurative encephalitis, gliosis, mononuclear infiltration into the Virchow-Robin space, vasculitis, and congestion in both cerebrum and cerebellum. A microscopic lesion in the lung was caused by severe pulmonary edema, interstitial pneumonia, and congestion (Figure 1A). Multifocal necrosis in the liver (Figure 1B), tubulonephritis, and lymphoid depletion in the spleen were found. No abnormalities were detected in any other organs.

The paraffin-embedded tissues, including brain, lung, kidney, heart, spleen, pancreas, liver, and intestine tissue, were examined immunohistochemically.A polyclonal goat anti-HPAI H5N1 (Kasetsart University, Nakornpathom, Thailand) diluted 1:400 in phosphate-buffered saline was used as the primary antibody. The secondary antibody was polyclonal mouse anti-goat immunoglobulin G (Zymed Laboratories, Inc., San Francisco, CA, USA) diluted 1:200 in phosphate-buffered saline. Diamino benzidine was the substrate developed as a chromogen. Tissue from a cat that had been hit and killed by a car was used as the negative control. Sites displaying a positive H5N1 antigen reaction were in cerebral neurons (Figure 1C), heart (myocardial cells) (Figure 1D), pneumocytes, renal tubular epithelial cells, hepatic cells, and white pulp of the spleen (macrophages). The pancreas and intestine were negative for H5N1 antigen.

Parts of frozen brain, lung, liver, kidney, spleen, and duodenum content were ground separately, and virus isolation testing was conducted by using embryonated egg injection. Virus isolation testing was also conducted on pleural fluid and urine. Virus isolation testing was conducted by injecting pleural fluid, urine, and filtrates obtained from the ground tissues into the allantoic sac of 10-day-old embryonated chicken eggs. Embryonic death occurred 18 hours after injection. The allantoic fluids of the dead embryos were subjected to hemagglutination (HA) and hemagglutination inhibition tests. All fluids from the dead embryos were positive for avian influenza A (H5). The virus could be isolated from all injected specimens. To identify the subtype, reverse transcription–polymerase chain reaction was conducted, and the virus was confirmed to be influenza A H5N1 (7,8). The HPAI H5N1 isolate recovered from the infected cat's lung was labeled A/Cat/Thailand/KU-02/04. In addition, an isolate of HPAI H5N1 from an infected pigeon in the area where the cat lived was included in the study and labeled A/Pigeon/Thailand/KU-03/04.

H5N1 viruses isolated from the cat's (KU-02) and the pigeon's (KU-03) lung tissue were characterized in this study. The entire genome sequence was determined in the H5N1 isolate from the cat, while the H5N1 isolate from the pigeon was sequenced to specifically obtain the HA, neuraminidase, and PB2 genes. The sequences obtained from the cat (H5N1) (A/Cat/Thailand/KU-02/04) were submitted to the GenBank database under accession numbers PB2 (DQ236079), PB1 (DQ236080), PA (DQ236081), HA (DQ236077), NP (DQ236082), NA (DQ236078), M (DQ236084), and NS (DQ236083). The sequences obtained from the pigeon (H5N1) (A/Pigeon/Thailand/KU-03/04) were submitted to GenBank under accession numbers HA (DQ236085), NA (DQ236086), and PB2 (DQ236087). Sequencing and phylogenetic analysis of the HA (Figure 2A) and NA (Figure 2B) genes of HPAI isolates (cat and pigeon) showed that the HA and NA genes of the viruses were similar to each other as well as to those of the viruses isolated from tigers, chickens, and humans in Thailand. Genetic comparisons of each gene of the cat isolate (KU-02) to those of the viruses isolated from chickens (January and July 2004) and tigers (January and October 2004) are shown in the Table. The analyses showed that the cat isolate (KU-02) was closely related to other H5N1 isolates collected from the region in 2004. This finding indicated that the H5N1 infection in the cat resulted from the virus circulating during the H5N1 outbreaks in early 2004. The HA gene of KU-02 and KU-03 contained multiple basic amino acid insertions at the HA cleavage site (SPQRERRRKKRR) as well as glutamine and glycine (Q222–G224) at the receptor binding site. The NA genes of KU-02 and KU-03 also had 20 amino acid deletions at positions 49–68 and contained histidine at position 274, indicating absence of antiviral drug resistant residues. The NS gene of the KU-02 isolate contained a 5–amino acid deletion (79–83), and the M2 gene of the KU-02 isolate contained an amino acid (asparagine) at position 31, conveying amantadine resistance. In summary, the viruses from the cat and the pigeon were similar to the H5N1 viruses isolated in Thailand and Vietnam in 2004, which had then been identified as genotype Z (9). A single amino acid substitution at position 627 of the PB2 gene (glutamic acid to lysine) was observed in the cat isolate (KU-02), as had previously been shown in the tiger isolates (1). In contrast, the PB2-627 amino acid residue of the pigeon isolate (KU-03) remained unchanged (glutamic acid).

Conclusions

This study is the first to report entire H5N1 genome sequences in a naturally infected domestic cat in Thailand, although experimental infection by H5N1 in domestic cats has been reported (10). The case of H5N1 in a cat was reported during the early H5N1 outbreaks in Thailand in February 2004. The likely route of infection was eating an infected pigeon carcass. Our study confirmed H5N1 infection in pigeon carcasses from the same area. In our study, both H5N1 isolates from the cat and the pigeon displayed characteristics identical to H5N1 isolates from the epidemic in Thailand. Moreover, genetic comparison indicated that the virus isolated from the cat (KU-02) was more similar to the H5N1 viruses from early 2004 (Ti-1 and Leo-1) than those from late 2004 (CU-T3 and CU-23).

Our results demonstrated that domestic cats are also at risk for H5N1 infection
. Clinical signs and pathologic test results of the cat in this study are similar to those of an experimental study by Kuiken et al. conducted in 2004. Cats are companion animals and may live in very close contact with humans. Although no direct transmission of H5N1 from cats to humans has been reported, it is possible; therefore, cats in H5N1-endemic areas should be scrutinized. In Felidae, such as tigers and cats, probable horizontal transmission of H5N1 within the same species has been found (4). However, the risk for transmission from poultry to humans is probably much higher because poultry outnumber cats and excrete higher titers of the H5N1 virus (10). Hence, monitoring domestic animals for infection during H5N1 outbreak is recommended.

Acknowledgments

We thank the staff of Kasetsart University for assistance and Orawan Booddee for immunohistochemical work. We also thank Mettanando Bhikkhu and Petra Hirsch for editing the article.

Genomic research was supported by the Thailand Research Fund, Senior Research Scholar, and the Center of Excellence in Viral Hepatitis Research.

Dr Songserm is a veterinary pathologist at the Faculty of Veterinary Medicine, Kasetsart University, Kamphaengsaen Campus, Nakornpathom, Thailand. His research interests include avian pathology, duck and goose diseases, and emerging diseases in animals.

http://www.cdc.gov/ncidod/EID/vol12no04/05-1396.htm

:vik:
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Figure 1. Microscopic lesions of the infected cat, lung edema with homogeneous pink material and congestion (A) and multifocal necrosis in the liver (B). Positive sites are shown by immunohistochemical examination of the infected cat in neurons (C) and cardiac muscle cells (D) (magnification ×100).

Figure 2. Phylogenetic analysis of the hemagglutinin (A) and neuraminidase (B) gene sequences of highly pathogenic avian influenza H5N1 from the cat in this study, compared with other sequences from GenBank database.
 

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PCViking

Lutefisk Survivor
the virus might have made three consecutive human-to-human jumps

May 24, 2006
Bird Flu Case May Be First Double Jump

By DONALD G. McNEIL Jr.

Reacting to the death on Monday of an Indonesian man, the World Health Organization said yesterday that the case appeared to be the first example of the avian flu jumping from human to human to human.

But the health agency quickly cautioned that this did not necessarily mean that the virus had mutated into a strain that could start a pandemic by jumping rapidly between people as ordinary flu does.

It is a "definite possibility" that the virus jumped more than once inside a family cluster, said Maria Cheng, a spokeswoman for the W.H.O. in Geneva. Although a second jump sounds alarming, "It doesn't look like the trend has changed," she said. "Each case was in very close contact with the previous one."

In the past there have been at least three cases of suspected human-to-human transmission of the A(H5N1) strain of bird flu; all were between family members who spent hours in close contact and would have breathed in large amounts of virus-contaminated droplets. The virus is known to attach itself to receptors deep in the lungs, not in the nose and throat as seasonal flu does.


The man who died was 32 and became sick on May 15. He is believed to have caught the flu while caring for his 10-year-old son, who died of the disease on May 13.

The boy attended a family pork roast in the village of Kubu Sembilang in northern Sumatra on April 29. The hostess, a 37-year-old woman, had become sick on April 27 and was coughing heavily, and several family members slept in her small room, the health agency said. She died May 4 and was buried without any tissue samples being taken; she is presumed to have spread the flu only because of her symptoms.

Six more family members who were at the barbecue fell sick in the first week of May. Five of them, including the 10-year-old, died in the second week of May; only one, the hostess's 25-year-old brother, recovered.

Thirty-three other people in Kubu Sembilang who had contact with the family have been quarantined or have been treated with Tamiflu, an antiviral drug, Ms. Cheng said.

The W.H.O. assumes that the incubation time for bird flu in humans is 7 to 10 days, longer than that of regular flu, she said.

Henry L. Niman, who runs recombinomics.com, a Web site tracking the genetics of flu cases, argues that the incubation period is closer to the two to four days of regular flu,
so the boy may have been infected by another family member, meaning that the virus might have made three consecutive human-to-human jumps. But Ms. Cheng said the health agency's "working hypothesis" was still that it had jumped only twice.

An Indonesian health official, according to local news reports, said the boy's father had run away after falling ill and had been treated with Tamiflu. He was later found in the village again but refused treatment.

Ms. Cheng said the village had "not been as cooperative as we'd like."

Recalling outbreaks of Ebola in which African villagers had been terrified at the sight of foreign doctors arriving in hoods and white overalls, she said she thought that the W.H.O. team had worn civilian clothes, and put on masks only when talking to sick patients.

http://www.nytimes.com/2006/05/24/world/asia/24birdflu.html?_r=1&oref=slogin
 
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