5/31/08- 6/7/08Weekly Bird Flu Thread: bird flu viruses becoming more adapted

Link to last weeks thread:

HEALTH - 5/23/08- 5/30/08Weekly Bird Flu Thread:WHO confirms first bird flu case in Bangladesh

http://www.timebomb2000.com/vb/showthread.php?t=288896


Johns Hopkins on influenza:

http://www.iom.edu/Object.File/Master/33/450/Rashid Chotani.pdf

National Avian Influenza Surveillance Information:

http://wildlifedisease.nbii.gov/ai/

CDC

http://www.cdc.gov/flu/avian/index.htm

WHO

http://www.who.int/csr/disease/avian_influenza/en/index.html

CIDRAP

http://www.cidrap.umn.edu/

Official U.S. Government Web site

http://www.pandemicflu.gov/

FAO
http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/special_avian.html

Public Health Agency of Canada

http://www.phac-aspc.gc.ca/influenza/avian_qa_e.html

European Union

http://ec.europa.eu/dgs/health_consumer/dyna/influenza/country_en.htm

The World Bank

http://web.worldbank.org/WBSITE/EXT...68427~piPK:64168435~theSitePK:1793593,00.html

North American bird flu viruses becoming more adapted to humans: study​

http://canadianpress.google.com/article/ALeqM5gNcxp7Ae1ILxfVkoRKTL-RTKeCGg

TORONTO — North American avian flu viruses of the H7 subtype - like the H7N3 viruses responsible for British Columbia's massive poultry outbreak in 2004 - seem to have adapted to more easily invade the human respiratory tract, a new American study suggests.

The adaptation is still only partial and the findings do not suggest the viruses are imminently poised to trigger a pandemic. But experts say they underscore the fact that H7 flu viruses need to be watched and studied.

"I think this is certainly amongst the most dangerous (avian flu) viruses out there," said virologist Dr. Ron Fouchier, with the Erasmus Medical Centre in Rotterdam, the Netherlands.

"And I think we need to continue to develop vaccines for H7 just as well as H5(N1)."

Fouchier was commenting on a scientific paper published Monday by the journal Proceedings of the National Academy of Sciences. Fouchier's research on avian influenza includes study of the H7N7 outbreak in the Netherlands in 2003, but he was not involved in this work.

Scientists from the U.S. Centers for Disease Control reported on their research on a number of H7 viruses, looking both at the types of receptor cells - bird or human - each was more inclined to latch onto and whether the viruses transmitted from infected to uninfected ferrets.

Of all available animal models, influenza infection in ferrets is considered to mirror most closely the course the disease takes in humans.

Human flu viruses that circulate every winter have adapted to be able to bind to the receptors that predominate in the human respiratory tract, known as alpha 2-6 receptors. Avian viruses, on the other hand, prefer the alpha 2-3 receptors found in the guts of wild birds (their natural host) and domestic poultry. Those receptors are scarce in the human upper respiratory tract.

It is assumed that an avian virus would need to make this kind of adaptation - learning to latch onto the human-type receptors - before it could transmit easily to and among humans.

Among the H7 viruses the CDC scientists studied were H7N3 viruses recovered from the two British Columbians infected during an outbreak in the poultry farm-dense Fraser Valley in 2004. More than 17 million chickens were destroyed in the efforts to stop that outbreak.

Also tested was a virus recovered from a strange H7N2 infection in the Yonkers area of New York City. A man who had no known contact with poultry was hospitalized in November 2003. Because he was suffering from other ailments, the fact that he was also harbouring an avian flu virus was not detected at the time. In fact, it was thought he had human flu.

Several months later testing at the CDC revealed the rare infection. How the man caught the virus remains a mystery.

Of all the H7 viruses studied for this work, the New York man's seemed most adapted to humans. It bound more easily to the receptors found in the lining of the human upper respiratory tract and had decreased binding to bird receptor cells. And when ferrets were inoculated with the virus, it spread from the infected animals to healthy animals placed in the same cages.

But in general H7 viruses from North America that have been isolated from about 2002 onwards seem to have developed an increasing affinity for the human-type receptors, said Dr. Terrence Tumpey, the CDC scientist who led the work.

"These viruses are partially adapted to recognize the receptors preferred by human influenza viruses, but not completely," he said in an interview from Atlanta.

"It needs to be adapted further. But I think it shows that potentially that these viruses are changing."

"Because we can look at an older North American H7 or Eurasian H7s or H5s and they have the characteristic avian influenza binding properties. Whereas these seem to be different and possibly changing."

At this point it is unclear what additional changes would be needed for an H7 virus to fully adapt to a human host - or whether H7 viruses could acquire all those changes.

When H7 viruses have caused human cases, the ensuing disease has typically been mild, with people suffering conjunctivitis (pink eye) and-or mild respiratory symptoms. There is one exception - a veterinarian infected with an H7N7 virus died during the Dutch outbreak.

The mildness of the disease may have lulled some people into a sense of complacency about H7 viruses, said Dr. Danuta Skowronski, an influenza expert at the British Columbia Centre for Disease Control.

But she insisted the fact that H7 viruses don't induce the life-threatening disease seen in H5N1 infection doesn't mean they shouldn't be viewed as a serious pandemic threat.

"H7, with its mildness, may be more - I hate to anthropomorphize - but more devious. Because through surreptitious spread - because it's milder, it's unrecognized, people might dismiss it more - it may actually have more opportunity to adapt to the human respiratory tract," she said from Vancouver.

"And even though it may be mild today, even though it may not transmit easily today, the potential is always there for it to change. And basically we don't want new (flu) subtypes in the human population. We've got enough to deal with the humanized strains."

Hoarding of Influenza Sequences Increases Pandemic Concerns ​

http://www.recombinomics.com/News/05300801/H7N2_Hoarding_Concerns.html

Recombinomics Commentary 20:55
May 30, 2008

In view of the possible threat posed by H7 viruses, the National Institute of Allergy and Infectious Diseases (NIAID) is sponsoring several studies of human H7 vaccines, according to NIAID Director Dr. Anthony S. Fauci.

A phase 1-2 clinical trial of a vaccine based on a US H7N7 virus was launched in March, Fauci told CIDRAP News today. The trial, based at Baylor School of Medicine in Houston, involves 125 volunteers who received doses ranging from 7.5 to 90 micrograms of antigen to study the vaccine's safety and immunogenicity. The egg-based vaccine was made by Sanofi, he said.

In addition, the NIAID recently conducted an intramural phase 1 clinical trial of a cold-adapted H7N3 vaccine made from the British Columbian strain, Fauci reported. He said the results show that the vaccine is safe, but the immunogenicity findings are still being analyzed.

Fauci said some additional research on H7 vaccines is under way in NIAID labs in Bethesda, Md. "The bottom line is there is stuff going on," he said.

The above comments describe some of the H7 vaccine projects ongoing with North American sequences. This update was presented in response to this week’s PNAS paper on increased affinities for human receptors by North American isolates in general, and the H7N2 isolate, A/New York/107/2003.

However, there is no H7N2 in the detailed programs in part because the increased binding of the isolate to human receptors and the ferret to ferret transmission was not well appreciated until these properties were described in last year’s J Virol paper and this week’s PNAS paper.

However, those activities have come under a cloud since the underlying sequences were pulled shortly after being made public. The sequences were made public at the end of last month, and pulled this month. The significance of the removal remains unclear because the removal was not mentioned in interviews associated with the publication, or follow-up comments or stories.

If the removed sequences represent the virus that infected the patient in 2002, then the virus is more dangerous than presented in the paper, because the New York patient would have almost certainly have been infected by another person. On the other hand, if the sequences deposited represent a lab artifact, then much of the data associated with the isolate would have to be re-evaluated or repeated with the virus that actually infected the patient.

If the virus truly is a human / avian reassortant, then the strain would be subject to more intense research and surveillance, coupled with an increase in vaccine studies (and would have been listed above).

The current fiasco associated with this virus is largely linked to sequence hoarding. A full sequence should have been generated before the animal studies were initiated. Instead, it seems that at best only HA and NA were sequenced and the presence of human genes was not known until 4 ½ years after the infection and after the sequences were made public last month.

Since the virus has been in the lab for over 4 years, there was ample time to generate a complete sequence. It is ironic that the same lab that has been deliberately creating human / avian reassortants in the lab, either accidentally created such a reassortant, or has been growing or maintaining a reassortant for the past four years in the absence of any real analysis.

Unfortunately, this sequence hoarding extends to most of the WHO regional labs, which can use the NIAID sequencing program to generate sequences on all eight gene segments at no cost, but have elected to generate sequences in house to control (and hoard) the data.

WHO has called for a paradigm shift on the sharing of information on influenza research, and is long over for such a shift to begin at WHO, where WHO consultants hoard the data in their labs and the WHO private sequence repository.

Avian Influenza Genome Sequences Released​

http://www.ars.usda.gov/is/pr/2008/080530.htm

By Sharon Durham
May 30 , 2008

WASHINGTON, May 30, 2008--The complete genetic coding sequences of 150 different avian influenza viruses were released today by U.S. Department of Agriculture (USDA) scientists and government, industry and university collaborators. The information improves scientific understanding of avian influenza, a virus that mainly infects birds but that can also infect humans.

"This is a major milestone in avian influenza research," said David Suarez, research leader of the Exotic and Emerging Avian Viral Diseases Research Unit at the Southeast Poultry Research Laboratory (SEPRL) operated at Athens, Ga., by the Agricultural Research Service (ARS). ARS is the chief intramural scientific research agency of USDA. Suarez oversees the ARS avian influenza virus repository at SEPRL.

"This sequence information, deciphered by our large team, will help researchers better understand virus biology and improve diagnostic tests for avian influenza viruses," Suarez added.

Today's release to GenBank, the National Institutes of Health's genetic sequence database, was part of a special sequencing project supported by the presidential initiative on avian influenza. Partners involved in collecting the viruses included USDA's Animal and Plant Health Inspection Service's Wildlife Services, as well as researchers at the University of Georgia (UGA), Ohio State University (OSU) and the University of Alaska-Fairbanks, and others.

After the virus isolates were prepared at SEPRL, the virus' noninfectious genetic material, called ribonucleic acid or RNA, was sent to industry collaborator SeqWright Corporation in Houston, Texas, which used its expertise to fully sequence the genome of each virus. The sequence information was reviewed and annotated at SEPRL for release to GenBank.

"The project's ultimate goal is to sequence 900 avian influenza viruses from the SEPRL repository," said Suarez. "These include avian influenza viruses collected from both poultry and wild bird species in the United States and around the world."

The sequence information will be combined with studies comparing the viruses' ability to infect and cause disease in several poultry species including chickens, turkeys and domestic ducks. The analysis of the sequence and biological data will provide new insights into how these viruses cause disease in man and animals. The biological characterization was performed with collaborations with UGA, OSU and University of Delaware collaborators.

Homologous Recombination in H3N2 Seasonal Flu Confirmed ​

http://www.recombinomics.com/News/06010801/H3N2_Recombination_Confirmed.html

Recombinomics Commentary 06:55
June 1, 2008

HA sequences from approximately 13,000 H3N2 isolates were released today at Genbank. These sequences were generated under a broad consortium as listed for the Science paper, “The global circulation of seasonal influenza A (H3N2) viruses.”

Included in these sequences were examples of obvious recombination from patients in South Korea in 2002. These sequences had been generated by the Korean CDC and deposited at Genbank in 2004. Although the six sequences with recombination fell into two related groups, all sequences had been generated by the same lab, raising concerns of lab error.

The data had been presented on August 21, 2006 at the vaccine meeting, “Targeted Immunotherapeutics & Vaccine Summit” demonstrating (see slide 17) the recombination and showing the two groupings with A/Cheonnman/323/2002, A/Cheonnman/338/2002, A/Cheonnman/340/2002 in one group and A/Kyongbuk/320/2002, A/Daejin/258/2002, and A/Incheon/260/2002 in a second group. Although the two groups were easily distinguished, all six isolates had clear cut homologous recombination. The recombinants matched the contemporary sequence, A/Wyoming/03/2003 for the first 574 positions, and then switched to the 1991 isolate, A/Seoul/45/91, for positions 575-963. However, the first set switches back to contemporary sequences over short stretches.

A recent Journal of Virology paper, “Homologous recombination is very rare or absent in human influenza A viru,” found short stretches of recombination, but only found two examples of longer regions of recombination, which it attributed to lab error. The study severely limited the sequences analyzed, and excluded the six examples from Korea through a number of restrictions. The study only looked at sequences generated under an NIAID influenza sequencing program, which was limited to a small number of contributing institutions over a relatively short time frame for the vast majority of sequences. The study also required identification of the parental sequences, which had to come from the limited dataset.

The recombination in Korea was limited by a number of criteria. Only 2 of the 8 gene segments from the Korean patients had been sequenced, so in addition to not being sequenced under the NIAID program, the sequences were excluded because they where not generated by whole genome analysis. Moreover, the parental sequences were from human sequences circulating a decade earlier, and these sequences were also not in the NIAID program. Moreover, the public sequences were only of HA and were partial sequences. However, although the recombinant and parental sequences did not meet the criteria of the study, they did represent sequences that were either generated via homologous recombination or lab error.

The sequences in the Science paper confirmed that the data was not due to lab error. One isolate, A/Cheonnman/323/2002, representing the first group, was re-sequenced in Japan and the sequence matched the original sequence. Another isolate, A/Incheon/260/2002, was re-sequenced by the CDC in Atlanta and also matched the original sequence.

Thus, the original examples of homologous recombination in the six sequences generated by the Korean CDC, were independently confirmed by labs in Japan and the United States.

These confirmations demonstrate the need for broader analysis in the search for homologous recombination in human influenza. The first set of isolates also demonstrates multiple template switches, which decreases the size of the acquired sequences. These shorter sequences were found in the J Virology study, where the likelihood that the NA data was due to chance instead of homologous recombination was one billion to one. However, the most common exchanges happen between closely related sequences, resulting in acquisitions of single nucleotide polymorphisms, such as the example of G743A in NA of H5N1.

These acquisitions from previously described sequences allow for predictions of changes, leading to vaccine targets more representative of future emerging genomes.

Study shows hybrids of bird flu and human flu viruses fit well, could occur​

http://www.mytelus.com/ncp_news/article.en.do?pn=world&articleID=2931418

Helen Branswell, Medical Reporter, THE CANADIAN PRESS

TORONTO - An experiment mating H5N1 avian flu viruses and a strain of human flu in a laboratory produced a surprising number of hybrid viruses that were biologically fit, a new study reveals.

And while none of the offspring viruses was as virulent as the original H5N1, about one in five were lethal to mice at low doses, showing they retained at least a portion of the power of their dangerous parent.

The work suggests that under the right circumstances - and no one is clear what all of those are - the two types of flu viruses could swap genes in a way that might allow the H5N1 virus to acquire the capacity to trigger a pandemic. That process is called reassortment.

"This study is just showing exactly that: There is a risk this virus can successfully reassort with a human virus," said Richard Webby, director of the World Health Organization's collaborating centre for influenza research at St. Jude Hospital in Memphis, Tenn.

"The problem is we don't know at this stage whether there's a benefit to these H5N1 viruses in doing that."

Nor can anyone say why, if the viruses swapped genes so readily in the laboratory, that hasn't seemed to have happened in the parts of the world where H5N1 has been circulating for years.

"This is the million dollar question," says senior author Dr. Ruben Donis, of the U.S. Centers for Disease Control's influenza division.

Reassortment is one of two ways in which a pandemic virus can evolve. The other is for a bird virus to acquire a number of mutations that allow it to more easily infect people and transmit among them.

The latter, called adaptive mutation, is thought to be the way the 1918 Spanish flu virus emerged. The viruses responsible for the milder pandemics of 1957 and 1968 arose through the mixing of human and avian flu virus genes.

This work, done at the CDC, was conducted to study the reassortment potential of H5N1 and H3N2 viruses. H3N2 is one of two human influenza A viruses that cause disease during flu season.

The study was published in PLoS Pathogens, one of the Public Library of Science journals.

Reassortment studies can be done one of two ways. One involves simultaneously infecting cells with the two viruses and seeing what nature produces. The other involves making viruses by piecing together combinations of synthesized human and avian genes.

"It's like Lego," Donis, head of the molecular virology and vaccines branch, says of this approach, which was the one used for this study.

But this is a game of Lego where it's not clear from looking at the pieces which will go together into a structure that will hold. "We really don't understand the rules of engagement for playing the Legos. We don't know what makes these things connect well or not connect well," he admits.

The researchers created 63 viruses representing the various potential combinations of human and avian internal genes, using an H5N1 virus that circulated in Thailand in 2004 and an H3N2 virus recovered in Wyoming in 2003.

All but one of the hybrids carried the hemagglutinin and neuraminidase genes - the H and N in a flu virus's name of H5N1. The remaining one used the neuraminidase from the human virus, creating an H5N2 virus that grew virtually as well as the H5N1 virus and was almost as lethal in mice.

Once the viruses were made they were placed in a medium to see if and how well they grew. Viruses were then harvested to use to infect mice, to test for virulence.

While 13 of the hybrid viruses either didn't grow or barely grew, the other 50 grew to some degree. And 28 replicated nearly as well as the original H5N1. Donis admits he was surprised by how well the avian and human gene combinations performed.

"I was expecting more incompatibility," he says.

By studying the combinations that succeeded and failed, the scientists were able to start to see patterns of which gene combinations are critical for an H5N1 virus to thrive.

When the most viable viruses were tested in mice, none was as nasty as H5N1. "That's the good news," Donis says, alluding to the fact that if reassortment turns H5N1 into a pandemic strain, the resulting virus could be less virulent than the current version.

Since late 2003 there have been 383 confirmed human cases of H5N1 infection and 241, or 63 per cent, of those people have died.

The virus that most closely matched H5N1 for virulence was one with three avian genes, the hemagglutinin and neuraminidase, plus the PB1 gene combined with five genes from the human virus.

Both the viruses from the 1957 and 1968 pandemics carried an avian PB1 gene. The authors suggest that picking up an avian PB1 gene may be a critical step in a potential pandemic virus arising through reassortment.

But just because the viruses mated successfully in a laboratory doesn't mean those viruses could go on to trigger a pandemic. In order to have that potential, a virus would have to be able to transmit from person to person - a skill that has so far eluded H5N1.

"The bottom line is it comes back down to transmission really being the key," Webby says. "But to say that we understand what are the factors involved in transmission is certainly an overstatement."

Earlier work at the CDC on some H5N1-H3N2 reassortant viruses showed they failed to transmit from infected to uninfected ferrets, an animal often used in flu research.

Donis says his team hopes to test its reassortant viruses in ferrets as well, but is still going through the approvals process.

More Human Avian Influenza Genetic Reassortment Failures​

http://www.recombinomics.com/News/06020801/H5N1_Shift_Failures.html

Recombinomics Commentary 15:20
June 2, 2008

And while none of the offspring viruses was as virulent as the original H5N1, about one in five were lethal to mice at low doses, showing they retained at least a portion of the power of their dangerous parent.

The work suggests that under the right circumstances - and no one is clear what all of those are - the two types of flu viruses could swap genes in a way that might allow the H5N1 virus to acquire the capacity to trigger a pandemic. That process is called reassortment.

"This study is just showing exactly that: There is a risk this virus can successfully reassort with a human virus," said Richard Webby, director of the World Health Organization's collaborating centre for influenza research at St. Jude Hospital in Memphis, Tenn.

"The problem is we don't know at this stage whether there's a benefit to these H5N1 viruses in doing that."

Nor can anyone say why, if the viruses swapped genes so readily in the laboratory, that hasn't seemed to have happened in the parts of the world where H5N1 has been circulating for years.

The above comments on the recent paper in PLOS demonstrates the inherent problem with human / avian reassortants involving H5N1. H5N1 has already evolved into an effective killing machine that not only can kill a wide variety of avian species, but can also kill mammals. This has been demonstrated time and again with humans, as well as mammals that eat H5N1 infected birds. Moreover, H5N1 has evolved into multiple sub-clades capable of producing confirmed fatal infections in humans. Clade 1 has produced fatal human infections in southeast Asia (Vietnam, Thailand, Cambodia). Clade 2 has been divided into three major subclades. Clade 2.1 has produced confirmed fatal infections in Indonesia. Clade 2.2 (Qinghai strain) has produced confirmed fatal infections in Turkey, Iraq, Azerbaijan, Egypt, Nigeria, Pakistan. Clade 2.3 (Fujian strain) has produced fatal infections in China, Vietnam, Laos, Cambodia. All of these fatalities have been in the past few years, demonstrating that relatively minor changes in individual genes can extend the lethality for humans to a variety of H5N1 sub-clades currently in circulation.

The property required to move H5N1 into the pandemic categoiry is not grow in mammals or virulence in mammals, it is efficient transmission between mammals. Virtually all of the clusters in the above countries include human to human transmission between family members or close contacts. However, such transmission chains have generally been limited to a few transmission cycles.

For clade 2.2, most of the clusters have been associated with receptor binding domain changes which enhance affinity for human receptors, and in several cases decrease affinity for avian receptors. However, these changes involve alterations at one or two positions. They do not involve reassortment, which swaps one or more entire genes.

Thus, the examples in the recent PLOS paper are primarily the “B list” of reassortants that are viable, but are usually not lethal in mammals. The small list of those that retain lethality have not been shown to increase transmission. Those candidates, which represent the “A list”, were published earlier in a PNAS paper. However, the “A list” also failed to match the growth or transmission efficiencies of H5N1 with eight avian gene segments, representing naturally evolving H5N1.

The failures of reassortants have led some to question whether H5N1 will develop into a pandemic strain. However, it is the successes in increased transmission efficiencies in H5N1 with receptor binding domain changes in human clusters that suggests a pandemic is only one or two nucleotide changes away.

Ironically, it is an H7N2 human / avian reassortant that has produced enhanced transmission in a ferret model, but the removal of the H7N2 sequences from Genbank shortly after the sequences were made public has created confusion on the true genetic composition of A/New York/107/2003, which was isolated from a case infected in 2002 in New York. The deposited sequences have 3 avian genes (HA, NP, NA) and 4 human genes (PB1, PA, MP, NS). The 8th gene sequence, PB2, wasn’t made public. The enhanced receptor domain binding and ferret to ferret transmission was highlighted in a recent PNAS paper. Moreover, if the submiited gene sequences are correct and the patient tested negative for H3N2, then the infection was likely transmitted human to human.

Although the published results have generated a great deal of media attention, the removal of the underlying sequences has not, and the authors of the study have not publicly commented on the sequences, which are not currently marker with a red banner stating that This record was removed at the submitter's request because the source organism cannot be confirmed.

Ironically, the CDC in Atlanta was involved in both studies, as well as a recent paper in Science on the global spread of H3N2. That paper included sequences, including one submitted by the CDC, which confirmed H3N2 HA recombination in patients in Korea in 2002. Both reassortment and recombination involve swapping of genetic information in hosts co-infected with two or more influenza viruses. While the ressortment swaps whole gene segments, recombination involves swapping portions of genes, which may lead to exchanges of single nucleotide polymorphisms, which is the type of change than can alter binding affinities for human or avian receptors.

The ressortment, or swapping of whole genes, is called genetic shift, while the changes in single nucleotide polymorphisms is called drift. One of the basic tenets of influenza genetics holds that the drift is due almost exclusively to de novo copy errors which happen during viral replication. However, the number and patterns of changes support acquisition via recombination.

Regardless of mechanism, sequence analysis demonstrates that stable small changes are far more frequent than stable reassortants, which is why an H5N1 pandemic is much more likely to involve a change in the receptor binding domain that increases affinity for human receptors, than a swapping of whole avian genes fro human genes.

Hybrids of bird and human flu viruses possible​

http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20080602/flu_hybrid_080602/20080602?hub=Health

Updated Mon. Jun. 2 2008 3:19 PM ET

The Canadian Press

TORONTO -- An experiment mating H5N1 avian flu viruses and a strain of human flu in a laboratory produced a surprising number of hybrid viruses that were biologically fit, a new study reveals.

And while none of the offspring viruses was as virulent as the original H5N1, about one in five were lethal to mice at low doses, showing they retained at least a portion of the power of their dangerous parent.

The work suggests that under the right circumstances - and no one is clear what all of those are - the two types of flu viruses could swap genes in a way that might allow the H5N1 virus to acquire the capacity to trigger a pandemic. That process is called reassortment.

"This study is just showing exactly that: There is a risk this virus can successfully reassort with a human virus," said Richard Webby, director of the World Health Organization's collaborating centre for influenza research at St. Jude Hospital in Memphis, Tenn.

"The problem is we don't know at this stage whether there's a benefit to these H5N1 viruses in doing that."

Nor can anyone say why, if the viruses swapped genes so readily in the laboratory, that hasn't seemed to have happened in the parts of the world where H5N1 has been circulating for years.

"This is the million dollar question," says senior author Dr. Ruben Donis, of the U.S. Centers for Disease Control's influenza division.

Reassortment is one of two ways in which a pandemic virus can evolve. The other is for a bird virus to acquire a number of mutations that allow it to more easily infect people and transmit among them.

The latter, called adaptive mutation, is thought to be the way the 1918 Spanish flu virus emerged. The viruses responsible for the milder pandemics of 1957 and 1968 arose through the mixing of human and avian flu virus genes.

This work, done at the CDC, was conducted to study the reassortment potential of H5N1 and H3N2 viruses. H3N2 is one of two human influenza A viruses that cause disease during flu season.

The study was published in PLoS Pathogens, one of the Public Library of Science journals.

Reassortment studies can be done one of two ways. One involves simultaneously infecting cells with the two viruses and seeing what nature produces. The other involves making viruses by piecing together combinations of synthesized human and avian genes.

"It's like Lego," Donis, head of the molecular virology and vaccines branch, says of this approach, which was the one used for this study.

But this is a game of Lego where it's not clear from looking at the pieces which will go together into a structure that will hold. "We really don't understand the rules of engagement for playing the Legos. We don't know what makes these things connect well or not connect well," he admits.

The researchers created 63 viruses representing the various potential combinations of human and avian internal genes, using an H5N1 virus that circulated in Thailand in 2004 and an H3N2 virus recovered in Wyoming in 2003.

All but one of the hybrids carried the hemagglutinin and neuraminidase genes - the H and N in a flu virus's name of H5N1. The remaining one used the neuraminidase from the human virus, creating an H5N2 virus that grew virtually as well as the H5N1 virus and was almost as lethal in mice.

Once the viruses were made they were placed in a medium to see if and how well they grew. Viruses were then harvested to use to infect mice, to test for virulence.

While 13 of the hybrid viruses either didn't grow or barely grew, the other 50 grew to some degree. And 28 replicated nearly as well as the original H5N1. Donis admits he was surprised by how well the avian and human gene combinations performed.

"I was expecting more incompatibility," he says.

By studying the combinations that succeeded and failed, the scientists were able to start to see patterns of which gene combinations are critical for an H5N1 virus to thrive.

When the most viable viruses were tested in mice, none was as nasty as H5N1. "That's the good news," Donis says, alluding to the fact that if reassortment turns H5N1 into a pandemic strain, the resulting virus could be less virulent than the current version.

Since late 2003 there have been 383 confirmed human cases of H5N1 infection and 241, or 63 per cent, of those people have died.

The virus that most closely matched H5N1 for virulence was one with three avian genes, the hemagglutinin and neuraminidase, plus the PB1 gene combined with five genes from the human virus.

Both the viruses from the 1957 and 1968 pandemics carried an avian PB1 gene. The authors suggest that picking up an avian PB1 gene may be a critical step in a potential pandemic virus arising through reassortment.

But just because the viruses mated successfully in a laboratory doesn't mean those viruses could go on to trigger a pandemic. In order to have that potential, a virus would have to be able to transmit from person to person - a skill that has so far eluded H5N1.

"The bottom line is it comes back down to transmission really being the key," Webby says. "But to say that we understand what are the factors involved in transmission is certainly an overstatement."

Earlier work at the CDC on some H5N1-H3N2 reassortant viruses showed they failed to transmit from infected to uninfected ferrets, an animal often used in flu research.

Donis says his team hopes to test its reassortant viruses in ferrets as well, but is still going through the approvals process.

Removed Human Sequences in H7N2 Replaced With Avian ​

http://www.recombinomics.com/News/06020803/H7N2_Replaced.html

Recombinomics Commentary 21:12
June 2, 2008

Today the CDC replaced the four human sequences in A/New York/107/2003 (PB1, PA, MP, and NS) with avian sequences closely related to H7N2 sequences from New York. The original deposits were human H3N2 sequences for these genes. Thus, the apparent reassortant was presumably due to submission errors for these four genes. The banner was removed from the three avian genes (HA, NA, NP), which were deposited in March and released in April.

The H7N2 isolate from a patient who was hospitalized in New York in 2002 attracted significant interest because of increased affinity for human receptors and transmission from ferret to ferret.

Based on the revised sequences this enhanced transmission appears to be due in large part to the HA sequence, which has an 8 amino acid deletion proximal to the receptor binding domain, and three basic amino acids at the HA cleavage site.

Release of the PB2 sequence would be useful.

Bird flu drugs successes in Hong Kong​

http://www.radioaustralia.net.au/news/stories/200806/s2263324.htm?tab=latest

Scientists in Hong Kong say they have used a cocktail of three drugs which appeared to raise the survival rates of mice infected with lethal doses of the bird flu virus.

They say the drugs suppressed the virus and toned down an over-reaction of the immune system.

A leading microbiologist at the University of Hong Kong says the team used an antiviral drug and two non-steroidal anti-inflammatory agents.

During the experiment, the scientists infected mice with lethal doses of the H5N1 virus and did not start treating them until 48 hours after they were infected.

Mystery epidemic hits N. Korea: aid group​

http://www.straitstimes.com/Latest+News/Asia/STIStory_244003.html

SEOUL - A MYSTERY epidemic spreading along some North Korean border towns with China has claimed the lives of dozens of children, a Seoul-based humanitarian group said on Tuesday.

The highly contagious disease has sparked a health alert with an estimated five or six children dying every day since April 27 in the northeast city of Hoeryong, the Good Friends group said.

North Korean health authorities have been unable to stop the spread of the epidemic or to come up with an exact diagnosis or cure, it added.

Doctors in the North suspect it may have been caused by avian influenza or hand-foot-mouth disease. 'Bird flu is spreading,' the group quoted one doctor as saying.

Good Friends, which operates in the communist North, quoted another doctor as saying hand-foot-mouth disease could be spreading from China, where it has killed several dozen children.

The outbreak is spreading mainly among state-run child daycare centers and kindergartens and no cases of adult infections have been reported, the doctor said.

Good Friends said the epidemic had spread to other towns along the border, with patients showing flu-like symptoms such as fever, cough, sore throat and loss of appetite.

Impoverished North Korea launched an all-out campaign to prevent bird flu after avian influenza spread widely in South Korea this year.

The North has reported no new case since it destroyed 210,000 birds during an outbreak in 2005 and actively taken part in programmes offered by the World Health Organisation.

The South is still struggling to contain the spread of bird flu since the latest outbreak began on April 1. -- AFP

Tyson Foods Killing Hens Exposed To (Mild) Bird Flu​

http://www.wtkr.com/Global/story.asp?S=8429137&nav=ZolH0yEI

(AP) Tyson Foods Inc. has begun killing and burying the carcasses of 15,000 hens in northwest Arkansas that tested positive for exposure to a strain of the avian flu that is not harmful to humans, state officials said Tuesday.

Jon Fitch, director of the state's Livestock and Poultry Commission, said routine blood tests conducted Friday found the possible exposure. Further tests done by the state and the U.S. Department of Agriculture found the birds did not have active infections, but rather were exposed to a subtype of the disease.

Fitch said the company immediately began disposing of the birds.

"There is absolutely no human health threat," Fitch said. "But we take this very seriously."

Fitch said state officials decided against announcing the infection to the general public because the birds tested positive for exposure to the H7N3 strain of the virus. The strain that ravaged Asian poultry stocks in late 2003 was H5N1 bird flu virus. That version of the virus has killed 240 people worldwide and scientists worry it could mutate into a form that spreads easily among people.

Gary Mickelson, a spokesman for Springdale-based Tyson, said the hens showed no signs of sickness before their pre-slaughter blood tests. He said the exposed birds all came from a contractor.

"As a preventive measure, Tyson is also stepping up its surveillance of avian influenza in the area," Mickelson said in a statement. "The company plans to test all breeder farms that serve the local Tyson poultry complex, as well as any farms within a 10-mile radius of the affected farm."

Matt DeCample, a spokesman for Gov. Mike Beebe, said the governor was alerted about the tests Monday.

Stock in Tyson, the world's largest meat producer, fell by 8 percent in trading Tuesday, down $1.47 to $16.98 per share.

AVA monitoring import of Tyson chicken products from US​

http://www.straitstimes.com/Latest+News/Singapore/STIStory_244403.html

This follows reports that 15,000 chickens have tested positive for bird-flu exposure in northwest Arkansas.
THE Singapore Agri-Food and Veterinary Authority (AVA) is monitoring the import of Tyson chicken products following reports that the US meat company has begun culling some 15,000 chickens that had been exposed to a strain of the avian flu in northwest Arkansas.

An AVA spokesman said on Wednesday that Singapore imported 289 tonnes of Tyson chicken products.

'We are monitoring the situation and are in close contact with our counterparts. Only chicken that are safe to eat and free from birdflu are allowed to be imported into Singapore,' said the spokesman.

He added that AVA ensures a resilient supply of safe and wholesome food by enforcing stringent food safety regulations and standards that are consistent with international practices.

Officials of the Arkansas Livestock and Poultry Commission said routine blood tests conducted last Friday found the possible exposure of the chickens to the H7N3 strain of virus.

Further tests done by the state and the US Department of Agriculture found the birds did not have active infections, but rather were exposed to a subtype of the disease. The company immediately began disposing of the birds.

'There is absolutely no human health threat,' said Jon Fitch, director of the commission. 'But we take this very seriously.'

Mr Fitch said state officials decided against announcing the infection to the general public as the birds tested positive for exposure to the H7N3 strain of the virus.

The strain that ravaged Asian poultry stocks in late 2003 was H5N1 bird flu virus. That version of the virus has killed 240 people worldwide and scientists worry it could mutate into a form that spreads easily among people.

However, the Centers for Disease Control and Prevention in Atlanta said an 2004 outbreak of H7N3 at a poultry plant in British Columbia, Canada, did sicken two workers there. The CDC said the two workers recovered after treatment with the antiviral medication.

Gary Mickelson, a spokesman for Springdale-based Tyson said, 'As a preventive measure, Tyson is also stepping up its surveillance of avian influenza in the area.'

The 15,000 hens will be killed by carbon-dioxide gas and buried at the farm to avoid spreading the disease, Mr Fitch said.

So far, he said officials have a working theory about how the virus spread to the hens.

'The speculation at this point in time was that a large group of Canadian geese made home on a pond very near this facility,' Mr Fitch said.

'Our speculation is someone stepped into some of those droppings and carried it into the poultry house.'

Avian flu case found in Oxfordshire​

http://www.first4farming.com/F4F/ne...=4AABAXF5JJSYJWNJH4WCFEQ?article_id=fwi110701

Avian flu has been found in a flock of chickens in Oxfordshire, the chief veterinary officer Nigel Gibbens has confirmed.Laboratory tests have so far shown that the birds have the H7 strain and all birds on the premises will be slaughtered as a precautionary measure.

Further testing will be carried out to establish whether the strain is high or low pathogenicity. A detailed epidemiological investigation to better understand the origin and development of the disease is underway, DEFRA said.

A temporary control zone with a 3km inner zone and a 10km outer zone has been established around the infected premises. DEFRA has stated that a number of conditions now apply. - All birds must be housed or otherwise isolated from contact with wild birds in the inner zone. - Bird gatherings are banned and all other movements of birds and some products are banned in the whole of the temporary control zone. Nigel Gibbens said:

I would stress the need for poultry keepers to be extremely vigilant, practice the highest levels of biosecurity and report any suspicions of disease to their local Animal Health Office immediately.

The Health Protection Agency has advised that it is important to remember that H7 avian flu remains largely a disease of birds. The virus does not transmit easily to humans. Dr Judith Hilton, Food Standards Agency head of microbiological safety, said:

This case of bird flu on a premises in Banbury, Oxfordshire poses no safety implications for the human food chain.

Properly cooked poultry and poultry products, including eggs, are safe to eat. The science shows that the virus isn't contracted by eating food but usually by close contact with infected birds.

All poultry keepers on the GB Poultry Register are being notified, and the EU Commission has been informed.

Japan suspends imports of British poultry due to bird flu​

http://news.yahoo.com/s/afp/20080604/wl_uk_afp/japanbritainhealthflutrade

TOKYO (AFP) - Japan said Wednesday that it was suspending imports of poultry from Britain after a bird flu outbreak on a farm there.

The Ministry of Agriculture, Forestry and Fisheries said in a statement that the suspension was expected to be a temporary measure aimed at reducing the risk of fresh bird flu outbreaks in Japan.

The move came a day after the British authorities confirmed that avian influenza had been discovered in chickens in southern England, although it was not the virulent H5N1 strain that sometimes claims human lives.

Preliminary tests were positive for the H7 strain, which poses a low risk to humans, the British Department for Environment, Food and Rural Affairs said in a statement posted on its website.

All birds on the premises where the virus was detected will be slaughtered, it added.

It is not the first time Japan has suspended imports of British poultry due to concerns about bird flu. The last time was in November. That suspension was only lifted last month.

Japan saw several outbreaks of the deadly H5N1 strain in early 2007, leading authorities to kill tens of thousands of chickens as a precaution, but it has reported no human deaths.

H7 Confirmed in England Again ​

http://www.recombinomics.com/News/06030801/H7_England_Again.html

Recombinomics Commentary 19:59
June 3, 2008

The Chief Veterinary Officer, Nigel Gibbens, has today confirmed Avian Influenza in chickens on premises near Banbury in Oxfordshire after preliminary tests were positive for the H7 strain.

The Health Protection Agency has advised that it is important to remember that H7 avian flu remains largely a disease of birds. The virus does not transmit easily to humans, as evidenced by the small number of confirmed infections worldwide to date. Almost all human H7 infections documented so far have been associated with close contact with dead or dying poultry. The risk to human health posed by H7 avian influenza viruses remains low. Nonetheless, the local Health Protection Unit will be identifying and following up those who may have had contact with the infected poultry and provide guidance and advice, and preventative medication as appropriate.

The above comments from DEFRA describe another H7 outbreak in England. Once again there was no warning provided by the wild bird surveillance program. There was an H7N2 in England almost exactly one year ago, and an H7N3 outbreak almost exactly two years ago.

H7 infections are easily transmitted to humans, and once again the DEFRA words of assurance highlight a lack of confirmed cases, which is largely dependent on an insensitive assay that fails to detect H7 in symptomatic and hospitalized patients.

Last year there were almost as many suspect human cases as avian cases. The suspect cases are almost certainly linked to H7N2 infections, because there is little seasonal flu at this time of the year in England. Last year H7 infections in the owners of the index farm were not confirmed.

The data was presented a year ago in Toronto. At the time most of the suspect cases were not aln confirmed, and although results were promised at the meeting, little new data was released and the number of confirmed H7N2 cases remained at four.

H7 infections are efficiently transmitted to humans, In the 2003 H7N7 outbreak, antibodies were detected in more than 1000 contacts, base on H7 antibodies. Most of the patients had mild or eye disease. Last year the H7N2 cases were more severe and respiratory, but most of the suspect cases were not confirmed.

Media reports are descibing H7N3 antibodies in culled poultry in northwet Arkansas.

The recent results with A/New York./107/2003(H7N2) has increased concerns over human H7 infections, DEFRA press releases notwithstanding.

H7 avian flu strain is highly pathogenic​

http://www.farmersguardian.com/story.asp?sectioncode=1&storycode=19019&c=1

THE strain of H7 avian influenza found in laying hens at a farm in Oxfordshire is highly pathogenic, further laboratory test have confirmed.

The 3km inner and 10km outer Temporary Control Zone established around the 20,000-bird unit in Shenington, Banbury, on Tuesday (June 3) will remain in place and existing restrictions continue to apply.

These restrictions include the housing or otherwise isolation from contact with wild birds in the inner 3km zone.

All bird gatherings in the Temporary Control Zone are banned. Other movements of birds and some products are also banned in the whole of the Temporary Control Zone. Defra said it was ‘urgently considering’ whether any wider measures may be needed.

Further laboratory tests are in progress to identify the exact strain of the virus and possible relationships with previously identified viruses. A detailed epidemiological investigation to better understand the origin and development of the disease is also underway.

The Health Protection Agency has confirmed that the risk to public health remains low. The Food Standards Agency has also confirmed that there are no safety implications for the human food chain.

Poultry keepers are urged to be extremely vigilant, practice the highest levels of biosecurity and report any suspicions of disease to their local Animal Health Office immediately.

Indonesia says it will no longer formally announce bird flu deaths​

http://hosted.ap.org/dynamic/storie...ME&TEMPLATE=DEFAULT&CTIME=2008-06-05-05-06-36

By ROBIN McDOWELL
Associated Press Writer

JAKARTA, Indonesia (AP) -- A 15-year-old girl died of bird flu last month, becoming Indonesia's 109th victim, but the government decided to keep the news quiet. It is part of a new policy aimed at improving the image of the nation hardest hit by the disease.

"How does it help us to announce these deaths?" Heath Minister Siti Fadilah Supari said Thursday, after confirming that the girl from southern Jakarta tested positive on May 13 and died one day later. "We want to focus now on positive steps and achievements made by the government in fighting bird flu."

Indonesia's decision could aggravate the World Health Organization, which waits to update its official tally of Indonesia's bird flu deaths until after they are formally announced by the government. The toll on its Web site stood at 108 on Thursday - accounting for nearly half the 241 recorded fatalities worldwide.

The country's health minister has clashed with WHO over bird flu before.

Supari stopped sharing bird flu samples with the global body in January 2007 after learning that some coveted data about the virus was being kept in a private database at a U.S. government laboratory in Los Alamos, New Mexico, and made accessible to only a handful of researchers.

She worried that pharmaceutical companies would use her country's viruses to make vaccines that were ultimately unaffordable for developing countries. She has called for the creation of a global stockpile of lifesaving drugs, price tiering or other multinational benefit-sharing programs.

At present, all of Indonesia's virus samples are kept at a Health Ministry laboratory. DNA sequencing - used for risk assessment, diagnosis and to signal possible mutations - is carried out by scientists at the nearby Eijkman Institute.

"We have the capability to do this ourselves," Supari said.

So far, the virus remains hard for people to catch. Most of the world's 388 recorded human cases fell ill after contact with infected birds. But scientists have been closely monitoring the H5N1 virus, fearing it could potentially mutate into a form that spreads easily among people, possibly sparking a pandemic.

Until recently, Indonesia's government announced bird flu deaths by e-mail and provided an almost 24-hour information center for confirmations.

It gradually abandoned that practice several months ago, often burying news of deaths on the ministry's Web site.

The latest policy shift means no posting will be made until deaths have already been reported in the media, said Supari, who wants the focus now to be on improvements made in fighting the H5N1 virus nationwide.

She said only 18 people have been infected in the first six months of 2008, compared to 27 during the same period in 2007 and 35 in 2006 - something she attributed to improved surveillance and public awareness.

But the U.N. Food and Agriculture Organization issued a critical statement in March, saying Indonesia's efforts to control the disease in poultry are failing. The H5N1 virus is entrenched in 31 of the country's 33 provinces and will continue to kill humans until it can be controlled in birds, it said.

Bird flu hits family hard​

http://www.oxfordmail.net/display.var.2319921.0.bird_flu_hits_family_hard.php

A family last night spoke of their devastation after bird flu decimated their flock.

The past 24 hours have been a nightmare for the Court family, culminating yesterday with the slaughter of their flock of 25,000 hens.

At the same time Defra announced laboratory results from dead chickens confirmed the outbreak of the highly contagious H7 strain of bird flu.
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Jonathon Court said the family had run Eastwood Farm, between Shenington and Shutford, near Banbury, for more than 50 years and the free range poultry unit for five years.

Mr Court said an increase in bird deaths had prompted them to call in a vet.

After monitoring the situation Defra was informed and carried out tests.

He said: "The source of the disease is not yet known and Defra will continue to make further investigations to try to identify this. All birds on the farm will be culled to try to help contain or eradicate the disease.

"We would urge everyone within the Defra surveillance zone to remain vigilant and to maintain suitable bio-security measures on their farms. This has been a devastating 24 hours for us and we would ask that we are now left to come to terms with what has happened and make plans for the future."

A 10km surveillance zone was placed around the farm banning all bird movement to prevent the spread of the disease.

Over the next few days Defra vets will visit all farms and small holdings within a 3km protection zone to test animals.

Yesterday teams of Defra staff arrived with equipment, and specialist vets carried out the slaughter.

Last night carcases were taken in sealed lorries to an incineration plant.

Local farmers have been seeking support and advice from the National Farmers' Union.

Spokesman Mike Wynn said: "It's still early days in terms of being able to know quite where this has come from, and Defra are there carrying out tests."

The family will be compensated by the Government for the slaughtered chickens and once the farm has been given the all-clear they can start to rebuild their flock.

The Health Protection Agency has confirmed that the risk to public health remains low and the Food Standards Agency also confirmed there are no safety implications for the human food chain.

Poultry keepers are urged to be extremely vigilant, practice the highest levels of biosecurity and report any suspicions of disease to their local Animal Health Office immediately.

More Media Myth on H7 Transmission​

http://www.recombinomics.com/News/06040803/More_H7_MM.html

Recombinomics Commentary 20:04
June 4, 2008

The most publicised case was recorded in the Netherlands during an extensive epizootic of HPAI H7N7 virus on commercial poultry farms, between March and May 2003. One case involved fatal respiratory distress syndrome in a veterinarian who was in close contact with infected poultry -- see ProMED ref. below. Reportedly, 86 cases in poultry workers and 3 cases in people with no poultry contact were initially confirmed by PCR.

The majority of H7 infections have resulted in self-limiting conjunctivitis, whereas probable human-to-human transmission has been rare.

The above ProMED comments are internally inconsistent. The first paragraph acknowledges the 89 PCR confirmed H7 human cases from the 2003 H7N7 outbreak in The Netherlands, including three cases with no direct link to poultry, and then claims that probable human-to-human transmission has been rare. The difference between H7 transmission to humans from humans or poultry is slight. The 89 confirmed cases indicate transmission of H7 to humans is common, and the three cases confirmed above would move the H2H transmissions from the “rare” category.

The 89 cases from a single outbreak are more than H5N1 cases in any country in any year, and only Vietnam and Indonesia have had more H5N1 infections over multiple years. H7 transmission to humans is much more common than H5N1, even though the sensitivity of H7 assays is exceedingly low.

The case for probable H2H transmission was significantly increased by follow-up studies on H7 antibodies in the above cases and contacts. Over 1000 cases were identified and 59% of culler contacts were positive, indicating the sensitivity of the PCR testing was very low and H2H transmission was very common.

The efficient H7 transmission was also supported by the H7N3 outbreak in British Columbia the following year. Fifty seven cases associated with the outbreak had suspected avian influenza, but only two were confirmed. Media reports indicated that many of the cullers had conjunctivitis, suggesting that most or all of the “suspect” cases had similar symptoms, and the low number of confirmed cases indicates they either tested negative or were not tested at all. 55 cases from a single outbreak would again signal efficient transmission to humans, which would again support H2H.

The same type of result was reported a year ago in England in the H7N2 low path outbreak. Although only four were confirmed, one of the four had no direct contact with poultry, and many of the negative patients had symptoms at a time when seasonal flu in England was minimal.

The human cases in the above H7 outbreaks involving three different serotypes and both high and low path avian influenza supports common transmission to and transmission between humans.

The data do not support the above Pro-MED statement or statements issued by DEFRA on transmission to humans. The mis-statements are used by the popular press to spread the misinformation, creating or extending a media myth, which continues to be hazardous to the world’s health.

Farmer devastated by bird flu outbreak​

http://www.yorkshirepost.co.uk/news/Farmer-devastated-by-bird-flu.4160517.jp

A farmer whose 25,000 bird flu-infected chickens are being culled said he was "devastated".

Richard Court, the owner of Eastwood Farm, at Shenington near Banbury in Oxfordshire, said in a statement issued by the NFU: "We have been on this family-run farm for more than 50 years.

"We started this free-range poultry unit more than five ye

ars ago and recently had built this up to a flock of around 25,000 free-range laying birds.

"This has been a devastating 24 hours and I would ask we are left now to come to terms with what has happened and make plans for the future."

The strain of H7 bird flu is the most dangerous type, officials said.

Locals said Mr Court and his wife Anthea had recently sold Rough Hill Farm with a view to building a new home on neighbouring Eastwood.

A police officer guarding an entrance to Eastwood Farm, sealed off by Defra officials, said the couple were living on-site in temporary accommodation.

Mr Court, in his statement, added: "We alerted our vet to mortality problems on the farm and after careful monitoring of the situation informed Defra vets, who confirmed the flock has avian influenza.

"The source of the disease is not yet known and all birds on the farm will be or are being culled to help contain and eradicate this disease.

"We would urge everyone in the area to remain vigilant and maintain their on-farm biosecurity."

While the H7 strain has been found in Britain on several occasions before now, this is the first time the highly pathogenic, or most deadly, form has been found.

A temporary control zone consisting of a 1.9-mile (3km) inner zone and a 6.2-mile (10km) outer zone has been set up around the infected premises.

Transmission Concerns for High Path H7N7 In England​

http://www.recombinomics.com/News/06050802/H7N7_UK_Transmission.html\\

Recombinomics Commentary 16:30
June 5, 2008

Report type Immediate notification
Start date 22/05/2008
Date of first confirmation of the event 04/06/2008
Report date 05/06/2008
Date submitted to OIE 05/06/2008
Reason for notification New strain of a listed disease
Causal agent Highly pathogenic avian influenza virus Serotype H7N7
Nature of diagnosis Laboratory (advanced)
This event pertains to the whole country

The above comments from the latest OIE report from England indicate the high path H7 is H7N7, the same serotype that caused the massive outbreak in The Netherlands in 2003. 89 cullers and contacts were H7 PCR confirmed and the outbreak resulted in the only bird flu fatality that was not H5N1.

Follow-up testing for H7 antibodies identified over 1000 contacts, most of whom were asymptomatic. The majority of the PCR confirmed cases had conjunctivitis, although a few had influenza-like illness and a few had both conjunctivitis and influenza-like illness.

Recent reports on H7 isolates with increased binding affinity for human receptors or ferret to ferret transmission has increased concerns regarding the human-to-human transmission potential of H7 outbreaks.

Indon health minister silent on bird flu toll​

http://www.straitstimes.com/Latest+News/Asia/STIStory_245019.html

JAKARTA - INDONESIAN Health Minister Siti Fadilah Supari refused on Friday to say how many Indonesians had died of bird flu.

She also insisted it was no longer necessary to announce the toll on a case-by-case basis.

'Publicly announcing the toll every time a victim dies brings no benefit at all to efforts to contain the virus,' she said, without confirming a media report that a 15-year-old girl had become Indonesia's 109th bird flu victim.

The minister said she had decided to end the practice of publicly updating the national toll with every new death, and the names of victims would no longer be released to protect the families.

'We will announce the toll periodically, every three months or so,' she said.

Earlier this year Ms Supari closed a 24-hour information centre which provided confirmation of new human cases of avian influenza and stopped the ministry's practice of emailing bird flu alerts to journalists.

The last toll published by the World Health Organisation (WHO) says there have been 108 deaths from bird flu in Indonesia since 2005, out of 133 cases.

That is almost half of the world toll of 241.

WHO officials in Jakarta and Geneva refused to discuss the minister's comments, saying only that there had been no communication on the matter from the Indonesian health ministry.

Indonesia has been criticised for its reluctance to share information with international scientists battling the constantly mutating virus, without in return being guaranteed access to vaccines that may be developed abroad.

Transmissions have so far been from bird to human but experts worry that the deadly H5N1 strain of bird flu could mutate and allow human-to-human transmission, leading to a pandemic that could kill millions. -- AFP

Bird flu mixed with human virus could form pandemic: research​

http://www.abc.net.au/news/stories/2008/06/06/2267791.htm?section=justin

A new research paper has been published in the United States, proving that bird flu, which has so far only killed people in its pure form, is capable of combining with conventional human flu viruses.

A mutated virus combining human flu and bird flu is the nightmare strain which scientists fear could create a worldwide pandemic. The pure bird flu strain, called H5N1, has caused hundreds of deaths recently around the world.

The research was conducted in a laboratory by the US Centres for Disease Control.

Dr David Smith, a director of microbiology and infectious diseases at PathWest laboratories in Perth, told ABC radio's PM it increases the level of concern that a bad pandemic may occur.

"It doesn't change our ongoing uncertainty about whether and when the pandemic will occur," he said.

"That's something that is controlled by events that occur in nature and they are chance events that we can't accurately predict."

The research does not say whether the new variety of mixed virus could spread easily, but Dr Smith says it does further our understanding of what may happen.

"I think it's important information for us to understand how pandemic strains may emerge and how bad they may be," he said.

"Of course this was, if you like, deliberately created in a safe laboratory setting in order to show what might happen.

"However, in actual human populations, there are a lot of other things that can happen in terms of how the viruses might mix and what might results from it.

"So it really tells us a potential, it doesn't tell us what is going to occur and that's unfortunately the problem with predicting human pandemics."

'No warning system'

The research has emerged at the same time as other worrying news. The Indonesian Government has announced it will stop reporting bird flu deaths as they happen, apparently because it does not want bad news to spread.

Indonesia has suffered the greatest number of H5N1 deaths. Jakarta has admitted that a teenager died of the disease last month, but it only reported details of the incident this week.

Professor Anne Kelso from the World Health Organisation (WHO) Collaborating Centre in Melbourne says such a move would hinder efforts to contain any outbreak.

"The sharing of information and the sharing of viruses [for research] are the two most important things that countries can do to help the world prepare for a potential pandemic," she said.

"So this is, if it turns out to be true, [is] a worrying step on behalf of the Indonesian Government to no longer share information about deaths as they happen.

"We don't need to know who the people are. It's very important we know where the deaths are occurring and if possible to have access to the viruses to compare with other viruses from around the world."

She says if the Indonesian Government does not report H5N1 deaths, it means the world receives less warning of the spread of the disease.

"The WHO on behalf of all the member states will have less warning if there are changes happening that could lead to a pandemic," she said.

"In particular it's important to know whether the deaths are due to exposure to viruses in poultry or whether there's evidence that they are being transmitted from human to human."

Bird flu search finds none yet coming to N.America​

http://news.yahoo.com/s/nm/20080605/hl_nm/birdflu_usa_dc



By Maggie Fox, Health and Science Editor Thu Jun 5, 5:55 PM ET

WASHINGTON (Reuters) - The feared H5N1 avian influenza has yet to make it to North America in the bodies of migrating birds, researchers said on Thursday.
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Testing of more than 16,000 migratory birds between May 2006 and March 2007 showed no evidence of the H5N1 bird flu virus, which has become entrenched in many parts of Asia and which regularly pops up in flocks in Europe, the Middle East and Africa.

The birds are infected with virtually every other known strain of influenza, said Hon Ip of the U.S. Geological Survey, National Wildlife Health Center in Madison, Wisconsin. But not the highly pathogenic H5N1 virus.

"Maybe the Pacific Ocean is a nice, big biological barrier, for which I am forever grateful," Ip said.

"The general avian influenza infection rate is not really different in Alaska or North America than pretty much anywhere else. In spite of H5N1's spread through most of Asia and into Africa and Europe, that spread has not come into North America," Ip added in a telephone interview

About 1.7 percent of the birds were infected, but all with low-pathogenic strains of influenza viruses, which typically do not cause disease, Ip's team reported in the Virology Journal.

Highly pathogenic H5N1 avian influenza has forced the death or destruction of an estimated 300 million birds, according to the world animal health organization OIE.

SOURCE OF VIRUS

Birds are considered the original source of all influenza viruses. While H5N1 rarely infects people, it has killed 241 out of 383 infected in 15 countries.

Experts say the danger is that the virus will evolve just slightly into a form that people can easily catch and pass to one another, in which case the transmission rate could soar, causing a pandemic in which millions of people could die.

U.S. government officials have said it is inevitable that migratory birds will carry H5N1 to the Americas at some time.

An estimated that 1.5 million to 2.3 million birds migrate from Asia to Alaska each year.

But Ip, who worked with teams at the U.S. Department of Agriculture, the Fish and Wildlife Service and the Alaska Department of Fish and Game, says it has not happened yet.

The researchers are sampling birds that ornithologists say are the most likely to have migrated recently from Asia.

"Some of these viruses contain a mix of genes from both North American and Asian viruses," Ip said.

"We have direct evidence that the birds are carrying back at least a relative or descendant of viruses from Asia," he added. "This confirms we are sampling from those birds that are most likely to bring H5N1 back if H5N1 was to be brought back from Asia."

It also confirms that the viruses swap genes inside the birds -- a process that scientists believe gives rise to new and sometimes more dangerous strains.

The researchers have been testing birds since 2005 for H5N1, concentrating on Alaska but looking in all regions.

The birds most likely to be infected with any kind of flu virus are the dabbling ducks -- species such as mallards, Ip said. This reinforces the theory that the virus spreads as birds feed in the same water in which they are defecating.

Just this week U.S. chicken producer Tyson Foods Inc said it would eradicate about 15,000 chickens in Arkansas that carried antibodies to a mild H7N3 strain of bird flu, even though the birds were never sick and there was no risk to human health.

An outbreak this week of H7N7 flu forced the slaughter of all the chickens at a farm in Oxfordshire in Britain.

Delay and Denial Control of Indonesia H5N1 Clusters ​

http://www.recombinomics.com/News/06070801/H5N1_Indo_Delay_Denial.html

Recombinomics Commentary 04:13
June 7, 2008

The death of the 15-year-old girl described in the 2nd paragraph of the above report would raise the case total to 134 and the number of deaths to 109, if confirmed independently.

It is not clear, however, whether this case is one of the 2 suspected cases described in ProMED-mail on 14 May 2008 (see: Avian influenza, human (47): Indonesia, susp 20080514.1623). In this posting it was reported that: "A 16-year-old girl died 4 days after being admitted to the Persahabatan Hospital in the Indonesian capital on 8 May 2008
with laboratory test later confirming she had the avian flu virus. 10 days before her death, her 15-year-old brother died after a brief treatment at another hospital with symptoms similar to bird flu." The cause of death of the 15-year-old could not be confirmed because no blood sample had been taken. It is possible therefore that the death toll may now be at least 110. - Mod.CP

The above discussion from today’s ProMED commentary on the new Indonesian policy on delaying announcements of H5N1 fatalities is curious. Usually ProMED excludes any suspect H5N1 which are not lab confirmed, even when the unconfirmed case is in a fatal H5N1 confirmed familial cluster. The announcement by Indonesia may have served as an epiphany for ProMED commentator. \

The preceding Indonesia cluster was quite similar. The fatality of the index case was mis-diagnosed as dengue fever and the death was quickly followed by an H5N1 confirmed death in a sibling. That cluster was picked up by wire services and when director general of communicable diseases, Nyoman Kandun, was specifically asked about the cluster, the incorrect dengue fever diagnosis was used to deny the cluster, and this denial was accepted and supported by the same commentator cited above.

The latest comments are a step in the right direction, but the commentary above fails to note that the brother was diagnosed with typhus. Thus, the delay in reporting the case above has already created confusion regarding the diagnosis of the fatal infection in the index case. The commentary also fails to note that the time gap between the index case and the confirmed cases in each cluster supports human to human transmission.

The time gap was also present in the cluster confirmed on the same day as the earlier cluster. That cluster was not picked up by the wire services, but a relative of the confirmed case had died of respiratory disease just prior to the death of the H5N1 confirmed case.

Thus, there are three recent clusters. In each cluster the index cases dies and the cause of death is mis-diagnosed (respiratory disease, dengue fever, and typhus), while the relative then dies of lab confirmed H5N1,

It seems likely that this series of denied clusters may have contributed to the decision to delay H5N1 reporting and reduce transparency. The delay in reporting is in violation of the International Health Regulations, which added H5N1 to the reportable disease list, which requires immediate notification of human H5N1 cases. These regulations were revised in 2005 to increase transparency and give WHO the authority to investigate suspect cases, even without direct participation of host country agencies.

The rapidly deteriorating situation in Indonesia indicates it is time for the WHO to exercise its newly acquired options.

Hong Kong finds H5N1 bird flu in poultry market​

http://uk.reuters.com/article/healthNewsMolt/idUKPEK26227220080607?rpc=401&

By Jeffrey Hodgson

HONG KONG (Reuters) - Hong Kong has found the feared H5N1 bird flu virus at a poultry stall in one of the territory's many markets and ordered the culling of 2,700 birds, a government spokeswoman said on Saturday.

The official said Hong Kong had banned poultry imports from mainland China for 21 days, as well as from local farms in the territory, while it worked to discover the source of the infection.
Photo

She added there had been no human infection detected. The virus was discovered in the Po On Road market in the city's Sham Shui Po neighborhood.

It is not the first appearance of the disease in the territory, with infected wild birds discovered in 2007.

Since the virus resurfaced in Asia in late 2003, it has killed 241 people in a dozen countries, according to the World Health Organization (WHO).

Although most people who have caught bird flu have had direct or indirect contact with infected fowl, experts fear the constantly mutating H5N1 virus could change into a form easily transmitted from person to person. This could sweep the world, killing millions.

WHO concerned by Indonesia's plan to announce bird flu deaths sporadically​

http://www.mytelus.com/ncp_news/article.en.do?pn=canada&articleID=2934190

Helen Branswell, Medical Reporter, THE CANADIAN PRESS

Indonesia's health minister announced Thursday that her country will no longer report H5N1 avian flu deaths as they occur - a threatened policy shift experts said would put the country in violation of the International Health Regulations, a key global health treaty.

And an international law expert said Indonesia, which has refused for over a year to share sample H5N1 viruses with the global scientific community, is playing a risky game if it intends to make good on the threat to only report H5N1 deaths at six-month intervals.

"Indonesia is rolling the dice here with this, both with the virus sharing and then again if these press reports are true with this as well," said David Fidler, director of the Center on American and Global Security at Indiana University.

"If H5NI mutates - I don't care where it is - it's going to be known as the Jakarta strain. Because people are going to associate it with the recalcitrance of Indonesia to participate fully in the global surveillance needs with regards to H5N1."

Fidler was reacting to comments made by Indonesian Health Minister Siti Fadilah Supari in interviews published Thursday.

The outspoken health minister seemed to be suggesting the ongoing announcements of Indonesian deaths were undermining the imagine of the country and overshadowing "the positive steps and achievements made by the government in fighting bird flu."

"How does it help us to announce these deaths?" Supari asked in an interview with The Associated Press.

Since early 2007, Supari has dramatically reduced the amount of co-operation her country has given to the World Health Organization's Global Influenza Surveillance Network, a group of influenza laboratories around the world. The group tracks changes in human flu viruses, advising on what strains should be included in annual flu shots.

It also keeps a close eye out for novel flu strains that might pose a pandemic threat. For the last five years, the highly virulent H5N1 virus has been at the centre of its radar screen.

But its efforts to assess what is happening with H5N1 have been hampered since early last year by Indonesia's refusal to share sample viruses. Supari has insisted the country won't release H5N1 viruses until it is assured a fair share of any vaccines that are derived from Indonesian viruses.

Throughout the standoff, the country has continued to report new H5N1 cases and deaths. And the suggestion it may now only report the latter from time to time rang alarm bells.

A spokesperson for the WHO said it had not received official notification of a change in policy but is seeking clarification of the minister's remarks.

"We want to confirm whether or not what's been reported in the press is in fact a change in Indonesian policy," John Rainford said from Geneva.

Fidler suggested Indonesia would be in violation of the International Health Regulations if Supari carries through on her threat.

The IHR, as the treaty is commonly known, requires prompt reporting of cases of diseases that have been designated as global health threats. When the IHR were revised in 2005, SARS, polio, smallpox and human cases of avian influenza infection were specified as notifiable diseases. The revised treaty was ratified by the WHO's 193 member states, including Indonesia.

The IHR stipulate that countries must report new H5N1 cases within 24 hours of confirmation and must report deaths in a timely manner.

Twice-a -year reporting of deaths would not meet the test of timeliness, Fidler said.

Rainford concurred that if Indonesia plans to go this route it will not be fulfilling its commitments under the International Health Regulations.

"It would be, I think, the position of any signatory to the IHR, 193 states...including Indonesia that this is a notifiable illness and that there are duties and obligations under that to report that detail," he said from Geneva.

"But again, this is speculation if we don't have confirmation of that. But if in fact it was the case, yes, that would be a cause of serious concern."

Dr. Michael Osterholm, director of the Center for Infectious Diseases Research and Policy at the University of Minnesota, also expressed dismay.

"This is a very slippery slope that flies in the face of good public health," he said from Minneapolis.

"And lessons around SARS should have been very instructive to countries in Asia about what happens when you do not have full disclosure of public health events in your country."

Since late 2003, there have been 383 confirmed human cases of H5N1 infection in 15 countries and 241 of those people - or 63 per cent - have died.

Indonesia has recorded about a third of all of the cases but has a substantially higher death rate - 81 per cent. The country has recorded 133 confirmed human cases and 108 deaths since July 2005.

Bird flu 'likely' to reach UK as disease kills French duck​

http://edinburghnews.scotsman.com/latestnews/Bird-flu-likely-to-reach.2752059.jp

THE Government has warned that bird flu is "likely" to reach UK shores following confirmation that a duck in France died of the disease.
The European Commission said it had been notified by the French authorities of a confirmed case of the highly pathogenic avian influenza virus H5 in a wild duck tested in Ain, near Lyon.

A sample from the duck was today being tested at the EU's l

aboratory in Weybridge, Surrey, to check whether the outbreak is, as expected, a case of the more deadly H5NI virus.

The Department for Environment, Food and Rural Affairs (Defra) said that the development - the closest reported case of bird flu to the UK - increased the chances of the disease arriving in Britain.

Fred Landeg, Britain's deputy chief veterinary officer, said: "We understand that the French authorities have not yet identified the specific strain, but they are reporting that it is highly pathogenic and bears close similarities to H5N1 Asian strain.

"The expert ornithologists have advised that ducks from the Lyon region do not normally fly to the UK at this time of the year.

"Yet we know that the pochard duck uses the East Atlantic flyway, which is the same migratory path under which the UK lies.

"We have existing robust surveillance measures in place and have taken over 3500 samples from wild birds, which so far have not detected H5N1 in the UK."

He encouraged the public to report any unusual wild bird deaths that they come across.

Authorities in France - the seventh European Union country to be hit by the disease - have already applied emergency containment measures set out at EU level as an obligation on all countries hit by bird flu outbreaks.

These involve establishing a three-kilometre protection zone around the outbreak and a surrounding "surveillance zone" an extra seven kilometres deep.

Holy toledo

Thanks, JPD. I had NO idea about the epidemic in NKorea. THe big risk there, of course, is that avian flu, which we know is in SKorea in a virulent form, will combine with whatever is killing those children and spread to SKorea and from there to the world. We keep spinning the wheel of fortune, millions of times a day.

That business of Indonesia cutting back on their bird flu announcements is chilling.

Link to next weeks thread:

HEALTH - 6/8/08- 6/15/08Weekly Bird Flu Thread:Bird flu detected again in Hong Kong

http://www.timebomb2000.com/vb/showthread.php?t=290559