10/07-10/13/06 | Weekly Bird Flu Thread:Bird Flu Virus Infects Pigs in Bali

Link to last week's thread:

http://www.timebomb2000.com/vb/showthread.php?t=213488


Johns Hopkins on influenza:

http://www.timebomb2000.com/vb/showthread.php?t=212670

National Avian Influenza Surveillance Information:

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

Bird Flu Virus Infects Pigs in Bali​

http://www.tempointeractive.com/hg/nasional/2006/10/06/brk,20061006-85557,uk.html

Friday, 06 October, 2006 | 16:12 WIB

TEMPO Interactive, Jakarta: The Team of Veterinary Faculty at Udayana University found evidence that avian influenze (AI) virus has infected pigs in Bali. Wider scale research is now in the process.

AI finding on pigs was due to some college students’ research which diagnosed several ill pigs from May to June, 2006. Out of 20 pigs, two were positively infected by H5N1 virus. “The pigs are in Gianyar and Tabanan,” said I Gusti Ngurah Mahardika, a professor at the faculty, Friday (6/10).

The virus grows in ill pigs and the pigs cannot be cured by a series of medical treatment. After surgery, there are red blotches on the spleen. By imono histokimia technology, the red blotches are viruses on the pig’s tissue.

However, H5N1 virus was not found in the animal’s tissue. “Probably the virus only passed by, or is called an ‘opportunistic’ virus,” said Mahardika.

The finding has not yet been publicized as scientific study, but it has been conveyed to the Bali Breeding Service as a warning.

Virus contagion, according to Mahardika, is likely because with the pattern of chicken and duck breeding, the animals are free to enter pig stalls. In Bali, 900,000 pigs live side by side with other cattle.

Rofiqi Hasan

Cats can carry bird flu, study says​

http://www.thejakartapost.com/detailnational.asp?fileid=20061007.H06&irec=5

Adisti Sukma Sawitri, The Jakarta Post, Jakarta

Recent studies have revealed that cats can contract the avian influenza virus and that there is no evidence that migratory birds are responsible for the spread of the disease.

A study conducted by the Indonesian Environment Information Center (PILI) in Yogyakarta found that stray cats had caught the H5N1 virus through contact with infected poultry at traditional markets.

"We are positive that cats can have the virus, although it is yet to be proven that they can transmit the virus to other animals or humans," PILI director Iwan Setiawan said Thursday after a discussion on the role of migratory birds in the spreading the virus.

The discussion, which was held by National Geographic Indonesia, concluded that migratory birds were not to blame for the movement of bird flu.

A vet from the Bogor Institute of Agriculture, I Wayan Teguh Wibawa, said separate studies had shown there was no proof anywhere in the world that migratory birds carried the virus.

Studies of migratory birds in Malaysia, China and Australia that have been carried out over the past six years have shown no migrant birds in the three regions had the H5N1 virus, he said.

Wayan, who is also a member of the National Commission for Bird Flu, said that the poultry trade was the most likely cause of the spread of the virus to 29 of Indonesia's 33 provinces. So far 69 people have been infected with the virus and 52 have died.

"It is very important to vaccinate poultry and keep home environments free of poultry feces," he said.

A recent serology test conducted on 20 chickens around the houses of victims in Bandung showed that the virus could also be transmitted by healthy chickens.

PILI began last year the country's first study of the possible role of migratory birds in the spread of bird flu. The study, which is taking place in Yogyakarta and Indramayu in West Java, is still in progress. The group plans to extend the study to several other coastal regions in Java, where about 2 million birds from northern Indonesia usually come for mating season.

Bird Flu Meeting Brings World’s Top
Influenza and Waterfowl Authorities to the Table​

http://www.ducks.org/news/950/BirdFluMeetingBrings.html

Memphis, October 6, 2006 - Officials from Ducks Unlimited (DU) and the U.S. Fish & Wildlife Service (FWS) met today with Robert Webster, PhD, at St. Jude Children’s Research Hospital to discuss the latest developments in bird flu research. Webster is a world-renowned flu expert and professor of virology.

“The purpose of this summit was to talk about the current state of knowledge regarding bird flu and the implications for waterfowl hunters, the general public and habitat conservation,” said Ducks Unlimited Executive Vice President Don Young.

“Dr. Webster is the world’s leading bird flu authority,” Young continued. “DU is the world’s largest waterfowl conservation group. And the Fish and Wildlife Service is conducting some of the first comprehensive sampling for the flu of its kind. It only makes sense to get the three groups together to discuss where we are and what we know about this virus.”

In addition to his position at St. Jude, Dr. Webster is a consultant to both the World Health Organization and the National Institute of Allergy and Infectious Diseases (NIAID) and is the Director of the U.S. Collaborating Center of the World Health Organization dealing with the ecology of animal influenza viruses.

Several key points emerged from the meeting. Most important is the virus hasn’t been found in the Americas.

“There is none of this virus in this part of the world,” Dr. Webster said. “Without the virus in this hemisphere, standard practice of good hygiene is all you need to do.”

Dr. Webster says waterfowl hunters aren’t at risk, but they need to stay informed.

“There are no additional risks this year involved with hunting,” Dr. Webster said. “Hunters should simply be aware that something is going on in other parts of the world, and stay informed.”

U.S. Fish & Wildlife Service Director Dale Hall provided an update on its monitoring efforts regarding the virus. The U.S. Fish and Wildlife Service oversees migratory bird laws, and sets the season framework for waterfowl hunting seasons in the U.S.

“We’ve sampled almost 15,000 birds, and through the remainder of the hunting season we will continue those efforts,” Hall said. “We expect to sample between 50,000 and 70,000 birds. So far, we have found no highly pathogenic H5N1 virus.”

Hall says some low pathogenic H5N1 flu has shown up, but that is normal.

Dr. Webster agreed, saying that the low pathogenic H5N1 strain is not uncommon in waterfowl, and does not cause illness in humans.

“People have got to understand that it’s out there, and will likely show up throughout the season,” he said. “The public should not be worried when that happens.

“At this time, I see no risk to hunters at all,” Dr. Webster added.

According to Dr. Webster, surveying and sampling for avian influenza has never been done so extensively as it is now.

“These guys (FWS and DU) are doing what they need to do,” Dr. Webster said. “So I’d tell hunters to continue to do what you do, but stay informed. After you hunt, follow standard hygiene practices.”

Mammalian H5N1 Evolution in Indonesia​

http://www.recombinomics.com/News/10070602/H5N1_Indonesia_Mammalian.html

Recombinomics Commentary
October 7, 2006

The recent announcements of H5N1 bird flu in cats in Indonesia, coupled with results from expanded sequencing of poultry strongly signal the existence of a separate mammalian H5N1 reservoir in Indonesia that is responsible for the vast majority of human cases.

This separate reservoir creates significant problems, because most of the attention has focused on infected poultry, and the mammalian reservoir has been significantly under investigated and under reported.

Therefore, a review of the evolution of this mammalian reservoir is useful. Although Indonesia did not acknowledge H5N1 infections until 2004, the first isolates were from birds in 2003. Sequence analysis of the 2003 and 2004 isolates indicated the H5N1 was Clade 2 and had a number of genetic markers that were specific for Indonesia.

The first human case was reported in July of 2005, and the sequence of the isolate, A/Indonesia/5/2005 had the Indonesia specific markers, but also had a number of unique polymorphisms, including one that created a novel HA cleavage site, RESRRKKR. However, the second human isolate, A/Indonesia/6/2005 had the more common HA cleavage site, RERRRKKR, and was similar to bird isolates. Subsequent human isolates in 2005 had the novel cleavage site, but several had an additional silent change, so although the cleavage site matched the first sequence at the protein level, there were a number of changes at the nucleotide level that divided the sequences with the novel cleavage site into two groups.

However, as the number of sequences increased in early 2006, it became increasingly clear that the human sequences were separating from the poultry sequences, all of which had the common bird cleavage site. The first match of the human sequences was from H5N1 from a throat swab of a cat in Indramayu near a residence were two siblings died from H5N1 infections. The sequence of the cat isolate not only matched the more recent human sequences, but was very close to the sequences of the isolates from the two siblings, A/Indonesia/283H/2006 and A/Indonesia/286H/2006, as well as other human isolates from Indramayu, A/Indonesia/292H/2006 and A/Indonesia/304H/2006. New isolates in 2006 collected from patients in East and West Java were sequenced and all were matches of more recent sequences such as the four human and one cat isolate from Indramayu.

In May of 2006 however, there was a new cluster in the Karo regency in north Sumatra. This outbreak was the largest to date and involve secondary and tertiary transmissions of H5N1. Consequently a meeting was call by WHO and consultants in Jakarta in June. Included in the presentation was a phylogenetic tree that summarized the H5N1 Indonesian isolates as of June 12, 2006.

The tree, which had the human sequences in green and the Karo cluster shaded in pink, clearly showed the match problem. All of the sequences with the novel cleavage site were on the lower portion of the tree and there were no poultry sequences on these two lower branches. Moreover, all of the recent human sequences from Java were on the lowest branch, which was even further from the poultry isolates. Thus, the human isolates were evolving away from the poultry isolates, suggesting the existence of a separate mammalian reservoir.

However, all of the human isolates were from July, 2005 or later, while most of the bird isolates were from earlier dates. Therefore 91 samples were schedule for shipment to Australia for virus isolation and sequencing. The samples were from infections between September, 2005 and March, 2006.

As sequences from these more recent and geographically dispersed isolates began to be published, it was becoming increasingly clear that the vast majority of the human infections on Java were not from domestic poultry. Each human sequence mapped to the lower portion of the tree and which was more distinct from the bird sequences.

The second set of new bird sequences included an isolate with the novel cleavage site. It was from a duck on Indramayu isolated in 2006. However, that isolate match the upper branch of the human sequences, which were composed of six isolates from three patients in 2005. Thus, although every human isolate in 2006 was matching the lower branch, the one duck sequence matched the upper branch.

The third set of poultry sequence had two matched with the lower branch. However, the two matches were from chickens in central Sumatra from 2005. Thus, none of the poultry isolates matched the lower human branch, while all human isolates, as well as the cat isolate, matched the lower human branch.

These data again supported a separate reservoir for the human sequences, and the only matches on Java were from the one cat, and all human isolates. The recent announcement indicates more H5N1 has been detected in cats, but the sequences of those isolates have not been released. Swine H5N1 sequences have been reported, but none match the human sequences.

The match failures pose a major problem because testing of humans is largely limited to patients how have been near dead or dying poultry. However, the poultry association has not been linked to the human infections, so an expanded testing of patients with symptoms is warranted. Similarly, more sequencing of H5N1 from other reservoirs is warranted by the match failures between mammalian and avian sequences.

False Negatives in H5 Positive Montana Pintail Ducks​

http://www.recombinomics.com/News/10070603/H5N1_Montana_False.html

Recombinomics Commentary
October 7, 2006

The USDA National Veterinary Services Laboratories (NVSL) confirmed the presence of low pathogenic H5N3 avian influenza through virus isolation in two of the 16 samples collected from wild pintails in Cascade County, Montana. Initial screening results announced on Sept. 21 indicated that H5 and N1 subtypes might be present in the collected samples

Because these rapid screening tests are highly sensitive, it is not uncommon to have positive results for a specific subtype on the initial screen test and yet not be able to isolate a virus of that subtype. This was the case for the N1 subtype in this sample which tested as a weak positive in the initial screen test. During confirmatory testing, an N1 subtype was not isolated but instead an N3 was found.

As previously announced, genetic testing ruled out the possibility that the samples carried the highly pathogenic strain of H5N1 avian influenza that is circulating overseas.

The above comments on the failure to isolate H5N1 from the N1 positive duck samples highlight the limitations of the testing procedures. The most likely explanation of the above data is a dual infection by H5N3 and H5N1. The H5N3 was likely present at a higher concentration, and the H5N3 serotype was isolated. Isolating a serotype not detected in the original sample is not uncommon.

Dual infections in wild birds are common.

However, the above comments leave the status of the H5N1 unknown. Genetic testing merely shows that the H5N1 was below the testing limits. The results do not rule out the presence of HPAI H5N1. Since the highly sensitive rapid screening gave a weak positive, the failure to detect the H5N1 sequence was not unexpected, and did not rule out the presence of low levels of H5N1.

In this case, the lack of an H5N1 isolate raises clear concerns. However, the presence of low path H5N1 in other samples raises similar concerns because the low path may be present at higher levels and obscure the HPAI H5N1. However, unlike the above case, there would not be clear evidence of a second serotype.

Detection of H5N1 HPAI in live wild birds is rare. It has been detected in Russia, but most countries that detect HPAI find the virus in dead wild or domestic birds. It can also be found in sick poultry, but that detection is usually after other birds begin to die.

H5 was detected in a dead goose from a farm on Prince Edward Island. The H5 confirmatory PCR test was also said to be weak and the size of teh insert was withheld. However, the deaths of four geese after showing symptoms that matched those of Qinghai H5N1 infections strongly suggests HPAI H5N1 is in North America.

The above data raises serious questions about false negatives. H5N1 frequently recombines in dually infected hosts, and the presence of the second virus can be seen in the sequence of the first virus. Recent sequences of H5N1 from wild and domestic birds in Northern China have extensive evidence of recombination. Those sequences have been made public in initial and confirming deposits.

Sequences from the H5N1 isolates should be made public immediately, so appropriate sequence analysis can be conducted.

China warns of seasonal bird flu outbreaks​

http://www.terra.net.lb/wp/Articles/DesktopArticle.aspx?ArticleID=309279&ChannelId=19

China has reportedly asked local authorities to be on guard against a resurgence of bird flu with the onset of the autumn migration season.

"Autumn and winter are the prime period for bird flu outbreaks," said Yin Chengjie, vice-minister of agriculture, told the official Xinhua news agency, adding that officials "should not underestimate the difficulties in virus control."

Yin said Thursday the situation in China remained serious and warned there was still much to be done to prevent the spread of the virus, as the annual migration risked sparking new outbreaks.

On Wednesday, China's health ministry announced that a new outbreak of bird flu had killed about 1,000 poultry in northern China, the second such case in a week.

Twenty-one people in China have contracted bird flu and 14 of them have died, according to official figures. The most recent fatality occurred in July in the western region of Xinjiang.

More than 220 people have contracted the virus in Asia since the end of 2003 and 139 have died.

China confirmed in August that its first human bird flu victim died in late 2003, two years earlier than previously reported.

Scientist urge to prepare for a bird flu pandemic​

http://www.clipp.org/health/content/78.php

08/Oct/2006: ‘Start preparing for the next flu pandemic’, is the message from the organizer of an expedition to unearth samples of the devastating Spanish flu pandemic in 1918 and 1919. Kristy Duncan, a scientist at the University of Toronto, warns that it is just a matter of time before another deadly bird flu pandemic strikes the world.

Building supplies of food, water, medication and other essential items could help us to tide over the bird flu pandemic, if one strikes.

Duncan, who is also the author of the book, ‘Hunting the 1918 Flu: One Scientist’s Search for a Killer Virus’ said that there are strong similarities between how the Spanish Flu virus killed and how today’s H5N1 strain kills, which raises fear of another deadly pandemic. Duncan had led a scientific expedition during the 1990’s, to exhume the bodies of a group of Norwegian miners, who died in the Spanish flu pandemic.

The subtype of the H1N1 strain (responsible for the Spanish flu endemic) and the current H5N1 strain of the Influenza virus, mainly kill the young and healthy, instead of the elderly and the infants.

Many countries have not yet prepared any emergency plans to counter a bird-flu out break. Only 15% of the U.S businesses have a contingency plan in place for a pandemic, even after the U.S president urged all the businesses in U.S to develop an emergency plan to face a pandemic. The case is much worse in Canada, where only 4% of the businesses have a contingency plan for flu pandemic.

An estimate by the U.S Centers for Disease Control, say that the next pandemic to hit a place like Toronto would leave 700,000 people needing medical attention and 40,000 needing hospitalization. Duncan said that a crisis of this proportion could not be managed, if people are not prepared for it.

She added that, to prepare for a pandemic, people should stock pile food and water that could last up to 6 to 8 weeks and store prescription and non-prescription drugs and other medicines that could last for the same period.

The World Health Organization has been warning of another pandemic ever since 1968, when the last of the three pandemics of the 20th century, occurred. Duncan feels that people are lucky this time, as this is the first time in history they have an opportunity to prepare for a pandemic.

Key protein found in flu fight​

http://www.bradenton.com/mld/bradenton/news/local/15712219.htm

KAWANZA NEWSON
Milwaukee Journal Sentinel

MILWAUKEE - In an intriguing finding, University of Wisconsin-Madison researchers have unveiled a critical protein that prevents influenza viruses from entering cells, a mechanism that could spark production of anti-viral medications to fight multiple flu strains, including the deadly strain of bird flu that's circulating globally.

The authors said the findings provide a basic understanding of how to block replication in both seasonal flu strains and the avian influenza H5N1 virus inside cells, thus halting their ability to spread infection.

For the study, published this month in the Journal of Virology, UW researchers tested a small protein molecule, known as an entry blocker, in the presence of several influenza subtypes. An entry blocker is a fragment of a larger human protein that helps substances pass through membranes.

To the scientists' surprise, the protein prevented each virus they tested - both seasonal strains and H5N1 - from attaching to the cell and from entering it, thus inhibiting the virus' ability to replicate and infect more cells.

Furthermore, the protein improved survival among mice treated after exposure to the virus. Normally, infected mice die within a week, but all the animals given the protein survived.

A little more information;

Bird flu found in pigs in Indonesia's Bali​

http://today.reuters.co.uk/news/art...56_RTRUKOC_0_US-BIRDFLU-INDONESIA.xml&src=rss

JAKARTA (Reuters) - The H5N1 bird flu virus has infected pigs on the Indonesian resort island of Bali, a senior agriculture ministry official said on Monday.

"There were two pigs that were infected by bird flu in Bali. These were old cases that happened last July," Musni Suatmodjo, agriculture ministry director of animal health, told Reuters.

Koran Tempo newspaper had reported on the weekend that a team from the veterinary faculty at Udayana University had discovered avian influenza infected two pigs in the regencies of Gianyar and Tabanan in Bali.

It was not clear if the pigs died.

Pigs are a concern because they are susceptible to many of the viruses that infect humans. Swines can act as mixing vessels in which genetic material from avian flu viruses can mix with human influenza viruses, potentially producing new and deadly strains for which humans have no immunity.

I Gusti Putu Suwandi, head of the Tabanan agriculture office, said there have not been new cases of avian influenza in the area since July.

"As for the pigs' cases, we haven't received a formal report of the finding from the university," Suwandi told Reuters by telephone.

The agriculture ministry's Suatmodjo said bird flu had been detected in 30 out of 33 provinces in the country, with the latest cases in North Sulawesi province.

He said that although that was an increase from 29 provinces last year, the percentage of deaths in poultry was lower thanks to better vaccination and other control measures.

"The number of death cases in poultry due to bird flu were relatively small as commercial farms have done proper vaccination and biosecurity, but the main problems remain on the backyard farms," Suatmodjo said, referring to the many Indonesians who keep a handful of chickens at their homes.

Indonesia has become one of the frontlines in the battle against the disease. So far, 52 people have died of bird flu, the highest of any country, with the majority of deaths occurring since the beginning of this year.

Worldwide, 148 people have died of bird flu since 2003.

Although the human death toll has climbed, the Indonesian government has resisted mass culling of birds, citing the expense and impracticality in a huge, populous country where keeping a few chickens or ducks in backyards is common.

Culling at selective farms and their immediate surroundings has been the preferred method.

Millions of chickens and other fowl in Indonesia have died from the disease or been killed to prevent its spread since it first surfaced in the archipelago in late 2003.

Study finds signs virus resistant to oseltamivir​

http://www.bangkokpost.com/News/10Oct2006_news08.php

APIRADEE TREERUTKUARKUL

The bird flu virus has already developed signs of resistance to oseltamivir, the drug widely used to treat the disease's symptoms in humans, a research study has found. Yong Poovorawan, who headed a group of researchers, said his team learned of the resistance which was reflected in the change of the position of amino acids in the virus samples. It was the first scientific study that could pinpoint such changes _ a result of the genetic shift of avian flu _ and its resistance to oseltamivir. The study would soon be published in the Emerging Infectious Diseases Journal and Journal of Virological Methods.

''This study will enable medical science and health personnel to precisely diagnose bird flu-like symptoms among patients for immediate, appropriate treatment,'' he said.

Avian flu resistance to oseltamivir had been confirmed in four bird flu patients in Vietnam, three of whom died last year. The Vietnam cases showed the possibility that oseltamivir might be less effective than anticipated, particularly as resistant strains of bird flu become more prevalent.

A previous study in Japan also found a genetic shift in the H3N2 flu strain in 18% of patients who took oseltamivir, he said.

Dr Yong, a virologist at Chulalongkorn University's faculty of medicine, earlier warned the Public Health Ministry and the hospitals run by the Bangkok Metropolitan Administration to exercise caution when prescribing oseltamivir in patients with influenza and bird flu-like symptoms, saying continuous and frequent use of the medicine without precise diagnoses was likely to trigger viral resistance.

During bird flu outbreaks, health personnel treated people with flu and bird flu-like symptoms with oseltamivir, even if they had not been in contact with poultry.

Disease Control Department director-general Thawat Sundarachan agreed that the anti-viral drug made it harder for doctors and epidemiologists to identify the virus due to the absence of related bird flu symptoms, citing the latest death case in Nong Bua Lam Phu province. Several laboratory tests had to be conducted before the death was confirmed as the country's 17th bird flu fatality.

But Dr Thawat insisted only patients with records of touching or eating chickens that had died mysteriously would be treated with oseltamivir. He believed that the medicine was still the best defence against the lethal H5N1 strain of bird flu and other types of human flu.

The closely-related zanamivir drug was also effective, but since the drug had to be inhaled, it was almost impossible for patients with severe lung damage to use it, he said.

Highlight the significance of genetic evolution of H5N1 avian flu​

http://www.cmj.org/Periodical/paperlist.asp?id=LW200694391205609707&linkintype=pubmed

LU Jia-hai, ZHANG Ding-mei, WANG Guo-ling

LU Jia-hai School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; ZHANG Ding-mei School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; WANG Guo-ling School of Public Health, Sun Yat-sen University, Guangzhou 510080, China

A growing concern has focused on the recent identification of influenza A H5N1 virus in Asia. Previously thought to infect only wild birds and poultry, H5N1 has now infected humans, cats, pigs, and other mammals in an ongoing outbreak, often with fatal results. According to a report from the World Health Organization (WHO), 217 human H5N1 cases have been confirmed and 123 of them have been fatal as of May 19, 2006.1 But many questions remain unanswered, for example how the H5N1 virus could cross species barriers and acquire the ability to infect humans; when and how the H5N1 virus will transmit effectively between humans and cause an influenza pandemic; and what are the determinants of its high virulence. This article summarizes research progress on the origin of H5N1 virus, factors determining pathogenicity, the contribution of genetic evolution to H5N1 species barrier traversal, human-to-human transmission, and problems in prevention and treatment of H5N1 avian influenza virus.

ORIGIN OF H5N1 VIRUS

The influenza viruses are grouped into three types, designated A, B, and C. Both B and C viruses are essentially human viruses. The influenza virus genome is segmented, and consists of eight fragments of RNA encoding approximately 8 proteins, including haemagglutinin (HA or H), neuraminidase (NA or N), nucleocapsid protein (NP), polymerase A protein (PA), polymerase B1 protein (PB1), polymerase B2 protein (PB2), matrix protein (M), and non-structural protein (NS). HA and NA are the surface proteins. There are 15 HA subtypes and 9 NA subtypes, designated H1-H15 and N1-N9 respectively. Influenza A is classified into serologically defined antigenic subtypes of the HA and NA major surface glycoproteins. An individual virus strain is designated by letters H and N, each followed by the number of the subtype. All of these HA and NA subtypes have been detected in waterfowl, which are the natural reservoir of all influenza A viruses. Occasionally, viruses are transmitted to other animals, including mammals and domestic poultry, resulting in transitory infections and outbreaks. Through adaptation by mutation or genetic reassortment, some of these viruses may establish species-specific permanent lineages of influenza A viruses that can lead to epidemics or epizootics in the new host.2

Three influenza pandemics occurred during the last century, the 1918 influenza, the 1957 pandemic influenza, and the 1968 pandemic influenza. The 1918 virus was an avian virus that adapted to humans through a series of point mutations.3 By contrast, the 1957 and 1968 pandemic influenza viruses were the products of reassortment, that is, three genes were derived from an avian influenza virus and the remaining five genes from the previously circulating human influenza viruses.4 Analysis of the sequences of all eight RNA segments of the influenza A/Goose/Guangdong/1/96 (H5N1) virus, isolated from a sick goose during an outbreak in Guangdong Province, China, in 1996, revealed that the HA gene of the virus was genetically similar to those of the H5N1 viruses isolated in Hong Kong in 1997.5 However, the replicative complex of H5N1/97 is highly homologous with that of the A/quail/Hong Kong/G1/97 (H9N2) virus6 and with that of the A/teal/Hong Kong/W312/97 (H6N1)7 virus. Therefore the H5N1, H6N1, and H9N2 influenza virus represent possible ancestors of the viruses that were transmitted to humans. These viruses continue to co-circulate in wild aquatic birds and poultry in China.8,9 Meanwhile the quail were found to be highly susceptible to A/Goose/Guangdong/1/96 (H5N1) virus, and the H6N1 and H9N2 virus continue to circulate in quails.10 Therefore quail were thought to be the likely original host of the H5N1/97 virus.

Early in 2005, the H5N1 virus was isolated from six apparently healthy migratory ducks at Poyang Lake, and 3.1% of the 1092 captured migratory ducks were found to have antibodies to H5N1. The H5N1 viruses were also isolated from 1.8% of all ducks of the markets in six provinces in southeastern China.11 Ducks experimently infected with H5N1 viruses isolated between 2003 and 2004 shed virus for 17 days, during which variant viruses with low pathogenicity were selected.12 Most of the infected ducks showed no signs of illness.13 These H5N1 viruses become less pathogenic to domestic ducks, but remain pathogenic to other domestic poultry and potentially to humans. Therefore the domestic ducks in southern China had a central role in the generation and maintenance of this virus. The wild birds may have contributed to the increasingly dissemination of the virus in Asia.14,15

FACTORS DETERMINING PATHOGENICITY

Broad tissue tropism and the ability to replicate systemically are important factors determining high pathogenicity in domestic chickens. Low pathogenic avian influenza viruses (LPAIV) replicate in limited tissues where host proteases, such as trypsin-like enzymes, are found. Highly pathogenic avian influenza viruses (HPAIV) possess inserted multiple basic amino acid residues in their HA, and the HA is cleaved into HA1 and HA2 by ubiquitous proteases such as furin. For this reason, HPAIV viruses can replicate in a broad range of tissues.16

Like other highly pathogenic influenza viruses, the 1918 virus has an HA protein that is cleaved into an active form in the absence of trypsin. However, unlike any other HA protein from highly pathogenic influenza viruses that have been characterized so far, the HA of 1918 virus does not have a multibasic cleavage site that can be cleaved by furin and furin-like proteases. Instead, its own NA protein is involved in cleavage of HA by a mechanism that is not yet understood. As a result, low pathogenic influenza viruses could potentially increase their virulence not only through mutations in their HA gene but also through mutations in their NA gene.17

H5N1 avian influenza virus strains where HA contains multiple basic amino acids at the cleavage site differ significantly in their ability to cause disease and death on animal models.8,18 Hence, other poorly characterized genotypic differences may contribute to the virulence, too.19 Further investigation revealed that in addition to the multiple basic amino acid cleavage site, pathogenicity is also determined by amino acids 97, 108, 126, 138, 212, and 217 of HA and an additional glycosylation site within the NA protein globular head.18 The NA protein facilitates the mobility of virions by removing sialic acid residues from the viral HA during entry and release from cells. Virus particles with low NA activity cannot be efficiently released from infected cells. Greater NA activity results in higher HA cleavage in multiple organs thereby enhancing virulence, specifically neurovirulence in mice.20 The NS gene also contributes to pathogenesis by disarming the interferon-based defense system of the host.21 Reverse genetic studies have found that an Asp→Glu substitution at residue 92 of the NS1 molecule of the human isolate A/HK/156/97 (H5N1) is associated with the induction of severe pathology in pigs.22 A sequence motif on the carboxyl terminus of NS1 protein may allow the H5N1 virus to bind to host cells and disrupt the activity of certain proteins in human cells, and therefore acts as a virulence factor. The carboxyl terminus of the NS1 proteins of the vast majority of avian H5N1 viruses contains a sequence motif Glu-Ser-Glu-Val (ESEV). Glu-Pro-Glu-Val (EPEV) was identified in the carboxyl terminus of the NS1 proteins of all virulent H5N1 viruses isolated from humans. By contrast, the carboxyl terminus of the NS1 proteins of low-virulence human influenza A usually contains a different sequence, Arg-Ser- Lys-Val (RSKV). The avian version of NS1 protein (ESEV, EPEV) seems to be more damaging to human cells than the NS1 (RSKV) that is usually found in human influenza strains. The NS1 protein in H5N1 virus and the high-mortality 1918 pandemic virus both have an avian motif, while the NS1 protein in low-mortality flu outbreaks in 1957 and 1968 contains a human motif that appears to be less capable of interacting with host proteins.23-25

The polymerase complex (including the PB1, PB2, and PA proteins) are also implicated in virulence. Some mutations can enhance the activity of polymerase and increase virulence in mice, and some of these mutations have been found in H5N1 HPAIV strains.26 A Glu→Lys substitution at residue 627 of the PB2 protein can increase the virus pathogenicity.22 Numerous studies indicate that pathogenicity depends on the functional integrity of each gene and a gene constellation that is optimal for infection. The pathogenicity of the same virus strain differs in different animals,16 indicating that the virulence is not only related to the etiological agent but also to the host condition. Therefore the virus-host interaction should be considered when carrying out research on pathogenicity.

H5N1 viruses isolated from 1997 to 2001 were not consistently transmitted efficiently among ducks and did not cause significant symptoms. However, in late 2002, outbreaks of highly pathogenic H5N1 influenza virus caused deaths among wild migratory birds and resident waterfowl including ducks in two Hong Kong parks.27 H5N1 influenza viruses isolated from apparently healthy domestic ducks in mainland of China have become progressively more pathogenic for mammals.22

CROSSING THE SPECIES BARRIER

Learning the precise molecular changes that allow the influenza virus to cross host species barriers is essential to develope an effective means of prevention. In aquatic birds, the natural hosts of influenza viruses, infection is usually asymptomatic and localized to the intestinal tract. H5N1 viruses have been actively reassorting and crossing interspecies-host barriers, moving from aquatic poultry to land-based poultry and, more recently, to wild terrestrial birds and humans.28 The molecular basis of the transmissibility of avian influenza viruses to mammals is not resolved, but undoubtedly involves multiple viral genes.

A deletion in the stalk of the NA molecule and increased glycosylation of the HA globular head are thought to be associated with adaptation to chickens.28,29 The HA gene is thought to be a determinant of host range because of its role in host cell recognition and attachment. The HA proteins of avian influenza virus species contain Gln226 and Gly228 residues, which form a narrow receptor binding pocket that favors binding of α2, 3 sialic acid. On the other hand, human species usually contain Leu226 and Ser228, which form a broad pocket that prefers α2, 6 sialic acid. These avian influenza viral strains gained human transmissibility, in part, by altering the binding preference of their HA proteins for human host cell receptors bearing sialic acid residues of the α2, 6 form.17

Cell surface receptors for both human and avian influenza viruses were identified in pig trachea, providing a milieu conducive to viral replication and genetic reassortment. Phylogenetic and epidemiologic analyses indicate that avian and human viruses have also been transmitted to pigs in nature and that they have reassorted in pigs and transmitted to humans.30 Virological and serological evidence of pig infection of H5N1 virus in Fujian Province has been obtained.22 A study on the pathogenicity of a HPAIV in different species of birds and mammals indicated that pig susceptibility to HPAIV virus is very low, so genetic reassortments of HPAIV virus in pigs is a possibility.16 Moreover, with continued replication, some avian-like swine viruses acquired the ability to recognize human virus receptors, raising the possibility that they may be directly transmitted to human beings.30

However, HA of the 1918 virus shows its avian-like Gln226 and Gly228 residues which create a narrow avian-like binding pocket that still allows for high-affinity binding of α2, 6 sialic acid. In fact, a Asp→Glu mutation at residue 190 in the HA of the 1918 virus switches its receptor binding preference to α2, 3 sialic acid. Consequently, just a single 190Asp→Glu mutation in the HA of the H5N1 strain could potentially switch its binding preference to α2, 6 sialic acid, and this is expected to be required for its evolution into a pandemic virus.17 Meanwhile, the Hong Kong-origin H5N1 viruses isolated from humans show receptor-binding properties that are typical of avian but not human viruses,29 yet they were still able to replicate and cause disease and death in humans. These observations indicate that receptor specificity is not the sole factor determining host range, and also that an intermediate host is not necessarily required for the first stage of transmission from birds to humans.31 Genes, such as polymerase, NA, and nucleoprotein are also known to contribute to the host range restriction of influenza A viruses.32 The enhanced activity of viral polymerase enables HPAIV to adapt to a mammalian host. The viral polymerase may be the driving component of early evolution of influenza A viruses in a new host that paves the way for new pandemic viruses. PB1 13Pro, 678Asn, PB2 627Lys and amino acids 362 to 581 sequences could also play an important role in virus replicating in mammalian cells.26,31 Recent evidence, however, suggests that extremely high doses of avian virus can directly infect humans. α2-3-linked sialic acids have now been found on ciliated cells of the human airway epithelium, which may help explain why these bird viruses have infected humans, especially when challenged in doses high enough to counter the inhibitory effects of respiratory mucins that contain α2-3-linked sialic acids.33

HUMAN-TO-HUMAN TRANSMISSION

Whether an H5N1 influenza pandemic will occur hinges on whether the viral strains acquire additional mutations that facilitate efficient human-to-human transmission. Studies have confirmed that H5N1 virus could infect cats, and that felines can transmit the virus to other cats and perhaps to humans.34 To date, in most of the human cases, the patients had well-documented exposure to sick or dying poultry, but there have been several episodes of possible person-to-person spread. Two health care workers who cared for patients in Hong Kong in 1997 were later found to have antibodies to H5, and one recalled having had a respiratory illness after exposure to one of the patients.35 In a family cluster of the disease in Thailand, the index patient became ill three to four days after her last exposure to dying household chickens. Avian influenza infection of the mother and aunt without exposure to poultry probably resulted from person-to-person transmission of this lethal avian influenza virus during unprotected nursing care to the critically sick index patient.36 In 2005, a 14-year-old Vietnamese girl was infected with H5N1 virus. She had no known direct contact with poultry, but had cared for her 21- year-old brother while he had a documented H5N1 virus infection. The NA gene and HA gene of the brother's virus were identical to that in the girl. The timing of infection in these two patients, together with the lack of known interaction of the girl with poultry, raised the possibility that the virus could have been transmitted from the brother to the sister.37

It is not known when, or even if, the H5N1 virus will evolve effective human-to-human transmission. The sequences of the polymerase proteins (PA, PB1, and PB2) of the 1918 virus and subsequent human viruses differ by only ten amino acids from the avian influenza virus consensus sequence (PB2 199Ala→Ser, PB2 475Leu→Met, PB2 567Asp→Asn, PB2 627Glu→Lys, PB1 375Asn/Thr→Ser, PA 55Asp→Asn, PA 100Val→Ala, PA 382Glu→Asp, PA 552Thr→Ser). Many or all of these residues must account for the ability of the polymerase complex to acquire human transmissibility by an avian influenza virus. The seven human forms out of the ten polymerase residues have already been observed individually in currently circulating H5N1 influenza viruses isolated from birds and humans. Under the selective pressure of a suboptimal growth rate in humans, the polymerase genes of an avian H5N1 virus that is currently circulating could potentially mutate at these ten residues and convert to the “human” forms. As a result, the virus may become better suited for efficient human-to-human transmission.3,4,17 Even if human-to-human transmission has not been conclusively identified at this point, we can anticipate that with more human cases, the risk of a more efficient human-to-human transmission of the virus remains a possibility.38

PROBLEMS IN PREVENTION AND TREATMENT

Inactivated influenza vaccines will provide the main method of prophylaxis against pandemic influenza. Influenza vaccines are currently prepared from virus that is grown in chicken embryos and inactivated by either formaldehyde or β-propiolactone.39 In a clinical trial, 451 healthy adult volunteers were vaccinated with two intramuscular doses of an inactivated H5N1 vaccine. Preliminary data indicate that the vaccine was well-tolerated and induced an antibody response predictive of protection.4 However, other clinical trials have shown that inactivated H5 vaccines induce minimal immune responses in humans.40 On the other hand, attempts to produce large quantities of vaccine from a highly pathogenic avian virus would be disastrous, since the virus would kill chicken embryos, vaccine yield would be substantially reduced, and vaccine quality would be compromised by contaminants from dead eggs. Recent technological developments such as reverse genetics have allowed us to manipulate the influenza virus genome so that we can construct safe, high-yielding vaccine strains. An H5 influenza virus vaccine derived from a 2003 human isolate has been developed using reverse genetic technology.40 All of the recombinant viruses grew well in eggs, were avirulent in chicks, and protected animals against a wild-type virus infection. However, the transition of reverse genetic technologies from the research laboratory to the manufacturing environment has presented new challenges. Production of a pandemic vaccine involves identification of a relevant strain, development of a strain that grows in eggs, incubation of eggs, harvesting allantoic fluids, purification and inactivation of the virus, potency testing, and clinical trials. Even under optimal conditions, and even if the virus was grown in a cell culture instead of eggs, this process requires 6 to 8 months. A pandemic influenza strain could spread around the world in half that time.41

A replication-incompetent, human adenoviral-vector- based, haemagglutinin subtype 5 influenza vaccine (HAd-H5HA) was developed, which induced both humoral and cell-mediated immune responses against avian H5N1 influenza viruses isolated from people.42 The Ad-vector-based delivery system may be an alternative way for the development of a pandemic influenza vaccine. Chickens were inoculated with a vaccine that expressed the full-length HA gene, then challenged with a dose of whole H5N1 virus. All immunized chickens survived developed strong HA-specific antibody responses, and showed no clinical signs of disease. All of the chickens immunized with a control vaccine died.23 Future vaccine strategies that may include more robust induction of responses from T cells such as cytotoxic T lymphocytes may provide better protection. Because manufacturing capacity is limited and cannot be augmented quickly, more research is needed to establish the smallest amount of antigen per dose that will confer sufficient protection. For example, the use of certain adjuvants can reduce the antigen requirement per vaccine by one-half to three-quarters.43

Currently, there are two groups of anti-influenza virus drugs: M2 blockers (amantadine, rimantadine) and neuramidinase inhibitors (oseltamivir, zanimivir). Rapid development of resistant influenza variants after amantadine treatment is one of the main drawbacks of M2 blockers. The molecular basis for the resistance to M2 blockers is the mutation at the 26, 27, 30, 31, and 34 amino acid residues of M2 protein.44 All of the H5N1 viruses isolated after 2003 contained the 31Ser→Asn mutation of M2 protein, hence the H5N1 virus is resistant to M2 blockers.45 Combination chemotherapy can reduce the emergence of drug-resistant influenza variants in vitro using an M2 blocker together with a neuramidinase inhibitor.46 Early therapy with NA inhibitors is probably beneficial, and even therapy initiated later in the illness may also limit ongoing viral replication. H5N1 virus infections may require higher doses of oseltamivir for longer periods than other types of influenza do.47 But oseltamivir- resistant H5N1 variants were isolated from two Vietnamese patients who died of the infection, in one case despite early initiation of treatment. The 292Arg→Lys, 294Asn→Ser, 274His→Tyr substitutions in the NA gene confers a high level of resistance to oseltamivir. The emergence of resistance to oseltamivir may have been due to the use of insufficient doses of the drug and resultant failure to eradicate the virus.47 But the worrisome prospect was raised that even with a therapeutic dose, oseltamivir resistance may develop during the course of illness and may affect clinical outcomes. However, antiviral treatment could still be expected to be beneficial when there is evidence of ongoing viral replication.47,48 A passive immunotherapy for influenza A H5N1 virus infection with equine hyperimmune globulin F(ab')2 can protect mice from H5N1 virus infection effectively, indicating an alternative method for H5N1 avian influenza therapy.49

CONCLUSION

Avian species constitute the origin of the human H5N1 avian influenza virus. The virus has not yet manifested effective human-to-human transmission, but the situation may change if the virus continues to mutate and assort during an epidemic. To respond to the H5N1 outbreak, it is necessary to detect the variation trends in the virus. To develop effective vaccine and drugs, it is important to clarify variation trends, the molecular epidemic character, and the pathogenic basis and the molecular mechanism allowing the virus to cross the species barrier.

In Netherlands/Germany in 2003, the highly pathogenic H7N7 influenza viruses that was lethal to poultry infected the eyes of more than 80 people and killed one person; H6 and H9 have spread from a wild aquatic bird reservoir to domestic poultry over the past 10 years. H9N2 viruses have also been associated with human infections in the mainland of China and Hong Kong. Avian influenza H10N7 seems to have crossed the species barrier from poultry to people for the first time. Hence, it is possible that the next influenza pandemic may not be due to H5N1.

REFERENCES

1. WHO (World Health Orgnization). Cumulative number of confirmed human cases of avian influenza A/(H5N1) reported to WHO. (Accessed April 26, 2006 at: http://www.who.int/csr/disease/avian_influenza/country/cases_table_2006_05_19 /en/index.html.)

2. Jong MD, Hien TT. Avian influenza A (H5N1). J Clin Virol 2006;35: 2-13.

3. Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature 2005; 437:889-893.

4. Fauci AS. Emerging and re-emerging infectious diseases: influenza as a prototype of the host-pathogen balancing act. Cell 2006; 124:.665-670.

5. Xu X, Subbarao, Cox NJ, Guo Y. Genetic characteri- zation of the pathogenic influenza A/Goose/Guangdong/ 1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong. Virology 1999; 261:15-19.

6. Guan Y, Shortridge KF, Krauss S, Webster RG. Molecular characterization of H9N2 influenza viruses; were they the donors of the “internal” genes of H5N1 viruses in Hong Kong? Proc Natl Acad Sci U S A 1999; 96: 9363–9367.

7. Hoffmann E, Stech J, Leneva I, Krauss S, Scholtissek C, Chin PS, et al. Characterization of the influenza A gene pool in avian species in southern China: was H6N1 a derivative or a precursor of H5N1? J Virol 2000; 74:6309–6315.

8. Govorkova EA, Rehg JE, Krauss S, Yen HL, Guan Y, Peiris M, et al. Lethality to ferrets of H5N1 influenza viruses isolated from humans and poultry in 2004. J Virol 2005; 79: 2191–2198.

9. Cauthen AN, Swayne DE, Schultz-Cherry S, Perdue ML, Suarez DL. Continued circulation in china of highly pathogenic avian influenza viruses encoding the hemagglutinin gene associated with the 1997 H5N1 outbreak in poultry and humans. J Virol 2000; 74: 6592–6599.

10. Webster RG, Guan Y, Peiris M, Walker D, Krauss S, Zhou NN, et al. Characterization of H5N1 influenza viruses that continue to circulate in geese in southeastern China. J Virol 2002; 76: 118-126.

11. Normile D. Evidence points to migratory birds in H5N1 spread. Science 2006; 311:1225.

12. Hulse-Post DJ, Sturm-Ramirez KM, Humberd J, Seiler P, Govorkova EA, Krauss S, et al. Role of domestic ducks in the propagation and biological evolution of highly pathogenic H5N1 influenza viruses in Asia. Proc Natl Acad Sci U S A 2005;102: 10682-10687.

13. Normile D. Ducks may magnify threat of avian flu virus. Science 2004; 306: 953.

14. Li KS, Guan Y, Wang J, Smith GJ, Xu KM, Duan L, et al. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature 2004; 430: 209-213.

15. Chen H, Smith GJ, Li KS, Wang J, Fan XH, Rayner JM, et al. Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control. Proc Natl Acad Sci 2006; 103: 2845-2850.

16. Isoda N, Sakoda Y, Kishida N, Bai GR, Matsuda K, Umemura T, et al. Pathogenicity of a highly pathogenic avian influenza virus, A/chicken/Yamaguchi/7/04 (H5N1) in different species of birds and mammals. Arch Virol 2006; 151: 1267-1279.

17. Russell CJ, Webster RG. The genesis of a pandemic influenza virus. Cell 2005;10:368-371.

18. Hulse DJ, Webster RG, Russell RJ, Perez DR. Molecular determinants within the surface proteins involved in the pathogenicity of H5N1 influenza viruses in chickens. J Virol 2004; 78: 9954-9964.

19. Lewis DB. Avian flu to human influenza. Annu Rev Med 2006; 57:139-154.

20. Goto H, Wells K, Takada, Kawaoka Y. Plasminogen- binding activity of neuraminidase determines the pathogenicity of influenza A virus. J Virol 2001;75: 9297-9301.

21. Russell CJ, Webster RG. The genesis of a pandemic influenza virus. Cell 2005; 10:368-371.

22. Chen H, Deng G, Li Z, Tian G, Li Y, Jiao P, et al. The evolution of H5N1 influenza viruses in ducks in southern China. Proc Natl Acad Sci U S A 2004; 101:10452–10457.

23. Hampton T. Avian flu researchers make strides. JAMA 2006; 295: 1107-1108.

24. Normile D. Genomic analysis hints at H5N1 pathogenicity. Science 2006;311: 457.

25. Krug RM. Clues to the virulence of H5N1 viruses in humans. Science 2006; 311:1562-1563.

26. Gabriel G, Dauber B, Wolff T, Planz O, Klenk HD, Stech J. The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host. Proc Natl Acad Sci U S A 2005; 102:18590-18595.

27. Sturm-Ramirez KM, Ellis T, Bousfield B, Bissett L, Dyrting K, Rehg JE, et al. Reemerging H5N1 influenza viruses in Hong Kong in 2002 are highly pathogenic to ducks. J Virol 2004; 78:4892-4901.

28. Guan Y, Poon LL, Cheung CY, Ellis TM, Lim W, Lipatov AS, et al. H5N1 influenza: a protean pandemic threat. Proc Natl Acad Sci U S A 2004; 101: 8156-8161.

29. Matrosovich M, Zhou N, Kawaoka Y, Webster R. The surface glycoproteins of H5 influenza viruses isolated from humans, chickens, and wild aquatic birds have distinguishable properties. J Virol 1999; 73:1146-1155.

30. Ito T, Couceiro JN, Kelm S, Baum LG, Krauss S, Castrucci MR, et al. Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. J Virol 1998; 72: 7367-7373.

31. Yao Y, Mingay LJ, Mccauley JW, Barclay WS. Sequences in influenza A virus PB2 protein that determine productive infection for an avian influenza virus in mouse and human cell lines. J Virol 2001; 75: 5410-5415.

32. Vines A, Wells K, Matrosovich M, Castrucci MR, Ito T, Kawaoka Y. The role of influenza A virus hemagglutinin residues 226 and 228 in receptor specificity and host range restriction. J Virol 1998; 72:7626-7631.

33. Stevens J, Blixt O, Glaser L, Taubenberger JK, Palese P, Paulson JC, et al. Glycan microarray analysis of the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities. J Mol Biol 2006; 355:1143-1155.

34. Kuiken T, Rimmelzwaan G, van Riel D, van Amerongen G, Baars M, Fouchier R, et al. Avian H5N1 influenza in cats. Science 2004;306:241.

35. Buxton Bridges C, Katz JM, Seto WH, Chan PK, Tsang D, Ho W, et al. Risk of influenza A (H5N1) infection among health care workers exposed to patients with influenza A (H5N1), Hong Kong. J Infect Dis 2000; 181:344-348.

36. Ungchusak K, Auewarakul P, Dowell SF, Kitphati R, Auwanit W, Puthavathana P, et al. Probable person-to-person transmission of avian influenza A (H5N1).N Engl J Med 2005;352:333-340.

37. Le QM, Kiso M, Someya K, Sakai YT, Nguyen TH, Nguyen KH, et al. Isolation of drug-resistant H5N1 virus. Nature 2005; 437:1108.

38. Riedel S. Crossing the species barrier: the threat of an avian influenza pandemic. Proc (Bayl Univ Med Cent) 2006; 19:16-20.

39. Wood JM, Robertson JS. From lethal virus to life-saving vaccine: developing inactivated vaccines for pandemic influenza. Nat Rev Microbiol 2004; 2: 842-847.

40. Horimoto T, Takada A, Fujii K, Goto H, Hatta M, Watanabe S, et al. The development and characterization of H5 influenza virus vaccines derived from a 2003 human isolate. Vaccine 2006; 24:3669- 3676.

41. Cinti S, Chenoweth C, Monto AS. Preparing for pandemic influenza: should hospitals stockpile oseltamivir? Infect Control Hosp Epidemiol 2005; 26: 852-854.

42. Hoelscher MA, Garg S, Bangari DS, Belser JA, Lu X, Stephenson I, et al. Development of adenoviral-vector- based pandemic influenza vaccine against antigenically distinct human H5N1 strains in mice. Lancet 2006; 367: 475-481.

43. Klaus Stohr. Avian influenza and pandemics-research needs and opportunities. N Engl J Med 2005; 352: 405-407.

44. Hay AJ, Zambon MC, Wolstenholme AJ, Skehel JJ, Smith MH. Molecular basis of resistance of influenza A viruses to amantadine. J Antimicrob Chemother 1986; 18 Suppl B: 19-29.

45. Scholtissek C, Quack G, Klenk HD, Webster RG. How to overcome resistance of influenza A viruses against adamantane derivatives. Antiviral Res 1998; 37: 83-95.

46. Ilyushina NA, Bovin NV, Webster RG, Govorkova EA. Combination chemotherapy, a potential strategy for reducing the emergence of drug-resistant influenza A variants. Antiviral Res 2006; 70: 121-131.

47. Moscona A. Oseltamivir resistance—disabling our influenza defenses. N Engl J Med 2005; 353:2633-2636.

48. de Jong MD, Thanh TT, Truong HK, Vo MH, Smith GJ, Nguyen VC, et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med 2005; 353:2667-2672.
49. Lu J, Guo Z, Pan X, Wang G, Zhang D, Li Y, et al. Passive immunotherapy for influenza A H5N1 virus infection with equine hyperimmune globulin F(ab1) 2 in mice. Respir Res 2006; 7: 43.

if this has mutated

then this is a big news story. transmission from Pig to Human is very easy... ugh.

Unconfirmed report raises suspicion of Bird Flu virus in Iran​

http://armenianow.com/?action=viewArticle&AID=1763&CID=1858&IID=1101&lng=eng

By Siranouish Gevorgyan and Marianna Grigoryan
ArmeniaNow reporters

A newspaper published in Baku, Azerbaijan has reported that about 2,000 dead birds have been found in a water reservoir in Iran near the Armenian border.

According to “Olaylar” (and republished on www.day.az), analyses taken from the carcasses has been sent to laboratories in Tehran and in Italy to determine whether the fowl was infected by Avian Influenza (Bird Flu).

Bird migration raises concern about Avian Influenza

The specific reservoir was not named in the article. There are two reservoirs on Iranian territory along the Arax River – the Arax-Hydro Unit in Nakichevan and the Horadiz, which borders Nagorno Karabakh. (Iran and Armenia share borders with the Arax.)

Health officials in Yerevan contacted by ArmeniaNow said they had not heard about any such discovery.

“I have talked to my Iranian colleague, and he doesn’t have any information, either,” said Grisha Baghyan, head of the State Veterinary Inspection Department of the Ministry of Agriculture.

Edward Stepanyan, deputy director of the same department told ArmeniaNow that the border with Iran is carefully monitored by Russian soldiers who are on alert for any suspicion of potential health hazards, particularly Bird Flu, and that no information has come from them.

Stepanyan says that, even if the report is true, Armenia has taken all measures – including stocking up on anti-virus vaccines – to resist any outbreak of the virus.

Over the summer, various international agencies, including World Bank, USAID, European Commission and World Food Programme, have provided training, equipment and conducted public awareness campaigns in Armenia.

In January, incidents of Bird Flu were reported in Azerbaijan, Georgia, Iran, and Turkey, near the border with Armenia. While neighbors had outbreaks, Armenian officials assured that no cases of the virus were found here.

Stepanyan said that, due to recent cooperation with international agencies and based on experiences of other countries, Armenia is “even more prepared than we were last year” to combat Bird Flu. The Ministry of Agriculture plans to open a telephone hotline later this month to aid public awareness of the issue.

ArmeniaNow has not yet been able to confirm the Azeri newspaper report.

Uganda: Vehicles From Sudan to Be Sprayed Against Bird Flu​

http://allafrica.com/stories/200610100279.html

New Vision (Kampala)

October 9, 2006
Posted to the web October 10, 2006

Kampala

VEHICLES from Sudan entering Uganda through Koboko and Arua districts are to be disinfected, reports Frank Mugabi.

This follows the confirmed cases of the deadly H5N1 strain of bird flu in the southern Sudanese capital of Juba last month.

Health officials at a three-day regional workshop on bird flu that ended in Arua town on Friday recommended spraying in light of the increased business traffic between Uganda and Juba.

The UN Food and Agricultural Organisation organised the workshop that involved district directors of health services, veterinary officers, chief administrative officers and health educators from the 14 northern districts bordering Sudan.

All vehicles will be subjected to drive through a disinfection wheel well to be sunk at Oraba border post in Koboko district while passengers will be required to disinfect their shoes.

The workshop also agreed that a check-point be set up at Oraba to check for smuggled fowl.

Recently, the Arua district bird flu taskforce banned the importation of poultry from Sudan and Congo.

Arua district veterinary officer Dr. Gordon Victor Toa said the district had put a ban on the re-entry of egg trays from the lucrative market in Juba.

He said a team comprising of mainly medical and veterinary experts was set up in the district to work on information provided by the Village Alert System.

Here, where I'm working there is huge push to vaccinate all healthcare workers...starting today. We couldn't break out the stash until today for patients and healthcare workers alike, heck looked like a cheerleading match to get workers to get vaccinated.

Deadly Bird Flu In Egypt

http://news.sky.com/skynews/article/0,,30000-1236849,00.html?f=dta

Deadly Bird Flu In Egypt
Updated: 23:11, Tuesday October 10, 2006

A new human case of bird flu has been detected in Egypt, authorities there have told the World Health Organisation.

According to Reuters news agency, a woman has been diagnosed with the deadly H5N1 strain of the virus.

MODS - Could you change the title from fly to flu? Thanks!

Egypt detects new human H5N1 bird flu case​

http://news.yahoo.com/s/nm/20061010/wl_nm/birdflu_egypt_dc

CAIRO (Reuters) - Authorities have detected Egypt's first human case of the highly pathogenic H5N1 bird flu virus since May, a
World Health Organization official said on Tuesday.

Hassan el-Bushra, regional adviser for communicable diseases surveillance at the World Health Organization, said the woman had tested positive for the avian influenza virus in tests carried out by Egyptian health authorities.

Hanan Aboul Magd, 39, has been in hospital since October 4 and has been treated with the drug Tamiflu. Her condition was stable, state news agency MENA reported.

Egypt has had the largest cluster of human bird flu cases outside Asia, and the fresh case came a month after authorities found a number of new cases in birds following a two-month lull in detected poultry cases.

The new infection brings the number of human cases in Egypt to 15, of whom six have died. All the previous infections were detected between March and May after the virus first surfaced in Egyptian poultry in February.

Doncha hate when that happens? Adgal, I think you can go into advanced edit and make your own change if the mods don't catch it...

I think it's kinda cute... Not so depressing at first.....

Is that like a Spanish fly?

Got my attention! I've been kinda lax on reading the Bird Flu threads, but I just HAD to find out about this deadly Bird Fly!! Don't change it, it'll get more of us to get back on the wagon.

It's ... it's ... it's a ferocious flock swarming ala Hitchcockian, pecking the eyes out of thousands of Egyptians! and it carries a parasitic fly that spreads flubonic plague! There's no cure, and radar picks up flocks of deadly swarms migrating at breakneck spead straight for the United States. They're coming!

=

All avian flu threads are supposed to be on the daily (weekly) Avian Flu thread. (So as to keep them (articles) from floodiing the main board.

A forum was sit-up specfically for avian flu news, back when I was making regular postings to a daily thread - I managed to 'get' a single daily thread allowed to be the main board.

Since H5N1 has crossed over to humans in Egypt (this is a bell weather event - IMHO). I'll let this article 'stand-alone for a bit, before moving it to the daily / weekly avian flu thread.

Cascadians said:

It's ... it's ... it's a ferocious flock swarming ala Hitchcockian, pecking the eyes out of thousands of Egyptians! and it carries a parasitic fly that spreads flubonic plague! There's no cure, and radar picks up flocks of deadly swarms migrating at breakneck spead straight for the United States. They're coming!

Click to expand...

Wouldn't that be "fly"bonic plague?

Confirmed H5N1 Case in Egypt​

http://www.recombinomics.com/News/10100601/H5N1_Egypt_Confirmed.html

Recombinomics Commentary
October 10, 2006

The woman, 39-year-old Hanan Aboul Magd of the Nile Delta province of Gharbiya, has been in hospital since October 4 and has been treated with the drug Tamiflu, state news agency MENA said.

The woman was on a respirator but her condition was stable

MENA reported that the newly infected woman had raised a flock of 11 ducks from her home north of the Egyptian capital. Two became sick and died, and she then slaughtered the rest before she was hospitalized.

Chickens on rooftops may be particularly susceptible to catching the virus from infected migrant birds, which fly along the densely populated Nile valley during migration, experts have suggested.

The above confirmation of the first human H5N1 bird flu case this season in Africa is not unexpected. Recently Egypt reported new H5N1 infections in birds in several locations, and birds should be migrating into the area. The Ukraine has also reported recent H5N1 outbreaks as has Sudan..

Last season H5N1 infections were reported in Romania and Turkey in October. Although H5N1 had migrated into Europe, the Middle East, and Africa, most countries, including Egypt, did not report H5N1 until human fatalities were confirmed in Turkey in January of this year. Those reports were followed by acknowledgement of H5N1 in many countries in the region.

This year, most countries are again failing to detect or report H5N1 migration into the area. This lack of transparency is cause for concern.

Similarly, the sequences from most of the H5N1 in Europe have been withheld by Weybridge, who presented in May 2006 a phylogenetic tree of approximately 80 isolates from Europe in early 2006. They have only released one bird sequence, from a turkey isolated in October, 2005 as well as five human sequences (4 from Turkey and 1 from Azerbaijan). Although Weybridge has indicated they will release the sequences, they have hoarded the data for 8-12 months.

The sequences are critical for identification of the evolution of tehse isolates via recombination. Full sequences from the Capua lab are being released through the NIAID Influenza Sequencing program. It facilities like Weybridge do not have the resources for timely sequencing and release of the data, turning the samples over to NIAID would be appropriate. NIAID generates sequences at no charge, but sequences are made public instead of placing the data into the private WHO database.

Bejing Genomics Institute is releasing full sequences of H5N1 isolates China. These sequences clearly demonstrate the evolution of H5N1 via recombination, which is also seen in the recent Qinghai sequences. In the past examples of recombination has been hampered because most of the H5N1 sequences from Hong Kong and China generated by Hong Kong University and St Jude have been partial sequences. These sequences should also be completed or turned over to NIAID so a full data set can be generated to map out a more complete picture of the H5N1 evolution by recombination.

The scandalous lack of full sequences in H5N1 isolates should be corrected.

Resources are now available to rectify these sequencing shortfalls.

Thanks, Dutch for taking care of merging the link.

And, remember all of you who scoffed, add a fly swatter to your Bird Fly Prep. You just never know when it will come in handy!!!

Bird flu case in Thai dog raises questions about infection​

http://www.theglobeandmail.com/serv...ddog1011/BNStory/specialScienceandHealth/home

Canadian Press

Thai scientists have reported a case of H5N1 influenza infection in a dog, a finding that lengthens the unusually long list of mammals this avian flu virus can infect.

The report, which suggests the dog became infected by eating ducks killed by the virus, also underscores a need to figure out whether the virus can be transmitted through consumption of infected animals, a World Health Organization scientist said Wednesday.

“This is the third species or fourth species that has been infected by eating carcasses. So I think we really have to think about the risk of oral ingestion,” said Michael Perdue, an avian flu expert with the WHO's global influenza program.

“I mean, these guys are getting infected somehow and we don't know how.”
Related to this article

Since H5N1 flared up in Asia in late 2003, tigers, leopards, domestic cats and now dogs have become infected with the virus by eating infected chicken or duck carcasses. Other mammals — a stone marten, and a small number of pigs — have also been shown to be susceptible to infection, though in those cases the mode of transmission isn't yet documented.

There have also been some human cases where it's thought ingestion of virus was the mode of infection — most notably a trio of brothers in Vietnam who fell ill after eating uncooked soup made from duck's blood.

Influenza infection occurs in the respiratory tract, when the mucous membranes of the nose and throat come in contact with viruses propelled through the air by sneezes and coughs. A person can also become infected by touching items onto which viruses have been sneezed and then touch their nose or mouth.

It's not thought that infection can occur in the human gastrointestinal tract. And the WHO's official position is that there is no evidence people can become infected by eating properly cooked poultry or eggs.

When tigers and leopards cats in Thai zoos died after being fed infected chickens in late 2003 and again in 2004, scientists speculated infection occurred when the animals ripped apart the carcasses. They believe the cats breathed in viruses that had been lodged in the birds' feathers.

Perdue said that may indeed be the way these infections have occurred. But he questions whether something else might be at play — and thinks the scientific community ought to nail down the answer.

“Is there tissue that's infectible before it (the infected meat) gets to the stomach? That's the other option. Esophogeal tissue or mucosal tissue (in the gastric tract) that allows the virus to infect?” he wondered in an interview from Geneva.

The case of the dog, reported in the November issue of the journal Emerging Infectious Diseases, actually occurred in October 2004. Scientists and people who follow H5N1 developments on Internet blogs and websites were aware of it, but this article by scientists from Thailand's Kasetsart and Chulalongkorn universities is the first scientific publication showing canine infection with the virus.

The dog developed high fever, panting and lethargy about five days after eating infected duck carcasses and died the following day, the scientists reported. H5N1 viruses were recovered from the dog's lung, liver, kidney and urine.

The authors say the proof that dogs too can be infected with this virus “warrants concern and highlights the need for monitoring domestic animals during outbreaks in the future.”

Other scientists said that while it is important to determine whether dogs are becoming infected and could potentially transmit the virus to other animals or back to poultry, the evidence to date suggests they aren't falling victim to nearly the same degree as cats.

There have been multiple reports of domestic and stray cats dying from H5N1 infection in several Asian countries, especially badly hit Indonesia which has the highest H5N1 death toll of any country.

“We'll have to look into it,” said Dr. Peter Roeder, an animal health officer with the UN's Food and Agriculture Organization.

“(But) we've not seen any evidence for dogs . . . becoming sick. So it doesn't feature very highly in our understanding at the moment. But perhaps it's something else we ought to look at.”

Another expert, Dr. Ab Osterhaus, said it would be important to try to infect dogs in a laboratory, then see if they are able to transmit the virus to nearby uninfected dogs. Such work, which Dr. Osterhaus's lab undertook with cats, would indicate how easy or difficult it is to infect dogs and whether they are able to spread the virus.

“That type of experiment will tell you a little bit about the relative risk for dogs to become infected,” said Dr. Osterhaus, director of the Institute of Virology at Erasmus University in Rotterdam. He said his lab intends to conduct this experiment.

U.S. Pandemic Flu Plan: Hole Up at Home​

http://www.washingtonpost.com/wp-dyn/content/article/2006/10/11/AR2006101101092.html

By MARILYNN MARCHIONE
The Associated Press
Wednesday, October 11, 2006; 2:31 PM

SAN FRANCISCO -- Could you work from home for weeks at a time? How long could you hole up without needing to go to the grocery or drugstore? Would you be willing to wear a face mask and isolate yourself from others?

Harvard researchers are surveying Americans on questions like these as the government wraps up work on a plan to use primitive infection-control measures to deal with a killer flu outbreak until drugs and vaccine become available.

The federal Centers for Disease Control and Prevention is pitching the plan at medical meetings and aims to send it out for review by the end of the year. State and local governments have asked for unusually detailed and specific advice on such matters as closing schools and canceling public events, one CDC official said.

This week, CDC awarded $5.2 million in grants related to the plan, including research on whether to recommend face masks to the public. CDC also asked the Institute of Medicine, a group of scientific advisers, to meet on these measures later this month.

"We can't afford to neglect some of the traditional approaches to contagion control because we very well may find ourselves in a situation where that's all we've got for a period of time," said CDC's quarantine chief, Dr. Marty Cetron.

However, skeptics say parts of the plan amount to wishful thinking with little evidence they would work.

"A lot of these things sound good but they lack practical application," said Michael Osterholm, a University of Minnesota health expert involved in the planning.

Advising people in big office buildings to avoid elevators and stay 6 feet away from each other is impractical, and people can't stay in their homes for weeks or months without needing insulin and other medications, he noted.

The nationwide survey by the Harvard School of Public Health is an attempt to get a handle on how Americans would follow such advice.

As for hygiene tips like sneezing into your sleeve, "we have no data that that makes any difference" in controlling a pandemic, Osterholm said.

The bird flu that has ravaged poultry in Asia and killed at least 140 people is "still smoldering" as a human threat, showing no signs yet of morphing into one that spreads easily among people, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

If it does, severe travel restrictions would delay its spread in the United States by only a week or two and at extreme cost, the CDC's Dr. David Bell said at a recent meeting of public health and disease experts in San Francisco.

Bird flu patient has encephalitis​

http://www.thejakartapost.com/detailnational.asp?fileid=20061012.G01&irec=0

Yuli Tri Suwarni, The Jakarta Post, Bandung

A 67-year-old woman from Cisarua in Lembang, West Java was tested positive for bird flu Wednesday and is likely to be the country's first victim to suffer from brain inflammation due to the virus.

Head of the West Java Health Office, Yudi Prayudha, said Wednesday that he received confirmation of the woman's tests through a text message from a staff member of the Health Ministry's research and development laboratory in Jakarta, who said the results were confirmed after the third test.

"SM, 67, female, is currently being treated at Hasan Sadikin hospital in Bandung. The third sample shows she is bird flu positive," Yudi said, quoting the text message he received.

The woman's case is unique, as it is the first time in the country that the H5N1 virus has been reported to have caused encephalitis, or the inflammation of the brain. A similar condition was reported to have caused the deaths of two siblings in south Vietnam in 2004.

Yudi said that based on preliminary information from the hospital, the bird flu patient has been placed in isolation after suffering a fever for two days following the sudden death of her chickens.

When she was first admitted to the hospital Saturday afternoon, she was in poor health, suffering from a high fever, breathing problems and a loss of consciousness.

However, the hospital's team of doctors, led by Hadi Jusuf, did not find indications that her loss of consciousness was due to acute respiratory distress or pneumonia like other bird flu patients treated at the hospital.

"There's a strong indication that the virus has entered the victim's brain membrane. A sample of fluid from her spinal cord has been taken to confirm the nature of the virus," Yudi said.

Hadi Yusuf said the first test was negative but the lab then conducted the tests five times. The tests included serology tests as well as swabs from her throat and lungs and cerebrospinal fluid from her spinal cord.

"If the tests show she is infected with H5N1, then this will be the first reported Avian Influenza case that has caused brain inflammation in the country," Hadi told The Jakarta Post.

He admitted, however, he had not received an official report from the Health Ministry's laboratory.

Examinations by the hospital's neurology team, he said, has shown that MK is suffering from brain inflammation caused by a virus.

The patient was still in poor health Wednesday although it seemed like she had started regaining consciousness after briefly moving her hand.

Yudi asked people to remain calm about the latest bird flu development. "It's very rare that H5N1 causes brain inflammation, so there's no need to worry. Just follow instructions to prevent Avian Influenza infection," he said.

According to the Health Ministry, a total of 69 people have contracted bird flu across the country. Of those, 52 have died. West Java has so far recorded the highest number of fatalities. MK is the province's 24th bird flu victim, of which 17 have died.

The H5N1 virus made the first known jump to humans in Hong Kong in 1997, infecting 18 people and killing six of them.

=




<B><center>How long could you hole up during pandemic?
<font size=+1 color=red>Researchers quizzing Americans on plans to cope with killer flu outbreak</font>

Updated: 2:26 p.m. CT Oct 11, 2006
http://www.msnbc.msn.com/id/15223542/ </center>
SAN FRANCISCO - Could you work from home for weeks at a time? How long could you hole up without needing to go to the grocery or drugstore? Would you be willing to wear a face mask and isolate yourself from others?

Harvard researchers are surveying Americans on questions like these as the government wraps up work on a plan to use primitive infection-control measures to deal with a killer flu outbreak until drugs and vaccine become available.</b>

The federal Centers for Disease Control and Prevention is pitching the plan at medical meetings and aims to send it out for review by the end of the year. State and local governments have asked for unusually detailed and specific advice on such matters as closing schools and canceling public events, one CDC official said.

This week, CDC awarded $5.2 million in grants related to the plan, including research on whether to recommend face masks to the public. CDC also asked the Institute of Medicine, a group of scientific advisers, to meet on these measures later this month.

“We can’t afford to neglect some of the traditional approaches to contagion control because we very well may find ourselves in a situation where that’s all we’ve got for a period of time,” said CDC’s quarantine chief, Dr. Marty Cetron.

However, skeptics say parts of the plan amount to wishful thinking with little evidence they would work.

“A lot of these things sound good but they lack practical application,” said Michael Osterholm, a University of Minnesota health expert involved in the planning.

Advising people in big office buildings to avoid elevators and stay 6 feet away from each other is impractical, and people can’t stay in their homes for weeks or months without needing insulin and other medications, he noted.


The nationwide survey by the Harvard School of Public Health is an attempt to get a handle on how Americans would follow such advice.

As for hygiene tips like sneezing into your sleeve, “we have no data that that makes any difference” in controlling a pandemic, Osterholm said.

The bird flu that has ravaged poultry in Asia and killed at least 140 people is “still smoldering” as a human threat, showing no signs yet of morphing into one that spreads easily among people, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.


If it does, severe travel restrictions would delay its spread in the United States by only a week or two and at extreme cost, the CDC’s Dr. David Bell said at a recent meeting of public health and disease experts in San Francisco.

Thermal scanning to try to detect people with fevers during the SARS outbreak turned up no cases and caused many false alarms. But voluntary quarantine, voluntary isolation of infected people and hygiene measures like hand washing, “cough etiquette” and face masks did help and might for flu, too, Bell said.

Dr. Frederick Hayden, a University of Virginia virologist currently working on global flu planning for the World Health Organization, agreed.

“The classic public health measures did work in SARS,” he said. They won’t be enough to stop a flu pandemic but could prolong and spread out its impact to prevent hospitals from being swamped and running out of respirators to keep the sickest alive.

Voluntary quarantines

The CDC plan will list multiple scenarios for pandemics that range in severity or attack certain age groups like children or college students, and recommend corresponding control measures.

These will include voluntary isolation of sick people, voluntary quarantine for those exposed to the germ but are not ill, and protective sequestration to separate healthy people or communities from a source of infection.

“Quarantine has gotten a very bad name and for very good reason. It has been abused in the past. It works best when we obtain and maintain the public trust,” Bell said.

However, Osterholm said there’s not enough science to recommend some measures, like “keep your distance” campaigns. Scientists know flu spreads through hand contact and big droplets when people cough or sneeze, but they don’t know how far tiny particles remain in the air, or how important that is for spreading the germ.

In fact, experts know surprisingly little about what enables a flu germ to spread.

Health officials need to give advice but should be honest about the limits of what is known “and not oversell it, which there is a tendency to do in times of crisis,” Osterholm said.

If that happens, “we will lose credibility quickly,” he said.

=





<B><font size=+1 color=blue><center>Flu pandemic: it's not 'if' but 'when'</font>

October 12 2006
<A href="http://www.bedfordtoday.co.uk/ViewArticle2.aspx?SectionID=182&ArticleID=1816806">www.bedfordtoday.co.uk</a></center>
The Bird Flu that hysterical sections of the media predicted would have wiped out many thousands of the UK population by now may have failed to arrive – but complacency would be foolish, health experts warn.

It's not a question of "if" but "when" the next flu pandemic strikes the UK, stresses Dr Mike Lilley, a consultant in communicable disease control from Beds and Herts Health Protection Unit.</b>

It may or may not come about as a result of avian flu mutating into a form that attacks humans, but history tells us a flu pandemic will come.

Predicting such events is not simple, but pandemics occur roughly ten to 40 years apart, or approximately every 30 years.

Depending on which statistics are used, the most recent were in 1969 or 1977, making another imminent.

And – showing just how seriously our experts take the threat – the Bedfordshire and Luton Local Resilience Forum carried out a mass vaccination exercise on hundreds of "patients" to test the efficiency of their plans for coping when that pandemic arrives.

In the space of just three hours, 865 were "vaccinated".
The first exercise of its kind in the country, its venue was Redborne Upper School, Ampthill, and the patients were 120 volunteers from the school's sixth-form, portraying a typical cross-section of the population – all ages and
backgrounds, some with disabilities and health conditions that might cause problems.

Each one went through the whole process – arriving, having their medical history checked, a simulated injection, and a 15-minute wait afterwards in case of an allergic reaction – to see how many people could be vaccinated during the exercise.

The atmosphere was one of calm efficiency on the part of the health teams, each nurse working steadily towards a target of vaccinating 60 people per hour.

As for the young "patients", while it was inevitably fairly light-hearted, they had been well prepared and took their roles very seriously.

Imagination was not required – each time a volunteer went through the loop, they were given a sheet with a new identity and medical history – but those whose
instructions indicated a somewhat nervous disposition hammed it up impressively, screaming and "passing out" on sight of the "needle"!

But if there could be none of the tension that would permeate a real situation, from people desperate to be vaccinated against a potentially deadly virus that would have already claimed many lives, there was a tangible underlying feeling that one day this could be for real.

Everyone wanted to play their part in ensuring that good solid emergency planning will pay dividends.

The good news is that it all went extremely well, with Dr Lilley and Robert Flute, health emergency planning manager for Beds and Luton, delighted at the speed and efficiency with which nurses and the back-up teams managed to process and vaccinate so many people.

Mr Flute said: "The teamwork has been absolutely brilliant."
Dr Lilley added: "There has been a huge amount of publicity
surrounding a flu pandemic, and this exercise does not mean one is coming any sooner.

"However, it is important we plan for it and test our ability to respond, so that the care we provide is of the highest order when it really matters.

"We hope it will not only have helped our own health care
workers and colleagues practice for this unique situation, but go a long way to reassure the public that our ability to plan, practice and respond in the event of an emergency is guaranteed."

11 October 2006

=




<B><center>October 12, 2006
<font size=+1 color=purple>Fiji warned about bird flu risks </font>

http://english.peopledaily.com.cn/200610/12/eng20061012_311247.html </center>
The South Pacific country Fiji has been warned that if the Bird Flu virus hits the country, it could kill 5,000 people.

The Fiji Sun, a suva-based daily newspaper, reported Thursday that the warning has been given by the Pandemic Influenza Preparedness Specialist at the Secretariat of the Pacific Community, Dr. Narendra Singh. </b>

Singh said Fiji could be headed for a pandemic that could affect about 240,000 people of whom 12,500 could be hospitalized and thousands killed.

Singh note that Fiji encountered such a pandemic in 1918 when an influenza epidemic killed 9,000 people or about five percent of the total population.

He said bird flu is already prevalent in Indonesia, has reached parts of the Pacific and could reach Fiji.

Singh said bird flu could be transmitted to human beings from fowls and also from one human being to another.

He said Fiji's 39-million U.S. dollar poultry industry could also be at risk.

Singh said Fiji's health sector has been so occupied with many reported outbreaks of diseases this year that there has been little time to prepare for a bird flu pandemic.

Source: Xinhua

=




<B><font size=+1 color=brown><center>U.N. launches bird flu rapid reaction squad</font>

Thu Oct 12, 2006 4:18 PM BST
By Robin Pomeroy
<A href="http://today.reuters.co.uk/news/articlenews.aspx?type=worldNews&storyid=2006-10-12T151749Z_01_L12904752_RTRUKOC_0_UK-BIRDFLU-FAO.xml&src=rss">today.reuters.co.uk</a></center>
ROME (Reuters) - The United Nations' Food and Agriculture Organisation on Thursday launched a global crisis centre to monitor the spread of bird flu and despatch experts to help countries crack down on the killer virus.

The FAO's "Crisis Management Centre" will be staffed round the clock, taking calls from countries that discover outbreaks of bird flu and sending specially trained vets anywhere in the world within 48 hours.</b>

"It's a sort of commando approach," the FAO's chief veterinary officer Joseph Domenech said at an inaugural session of the Rome-based organisation. "We have a type of 'fire brigade' equipped with the most modern equipment."

The centre was set up after pressure from the United States and the European Union to establish a single centre to coordinate global efforts to combat the H5N1 strain of the virus which has killed 146 people since 2003.

It will operate in cooperation with the World Organisation for Animal Health (OIE) and the World Heath Organisation (WHO) and send staff especially into developing countries which lack the resources to cope on their own.

FAO Director-General Jacques Diouf said that although many countries had succeeded in eradicating bird flu in poultry flocks, there were still major problems in Africa and Indonesia and risks the virus could return even after eradication.

The biggest fear is that the virus could mutate into a form that can be passed between humans, creating a global pandemic.

"Only when H5N1 has been totally eradicated will the sword of Damocles, or more pessimistically the time bomb, of a human pandemic be removed," Diouf said, adding that the centre would also be used to control any future outbreaks of other cross-border animal-based diseases.

The United States is providing the biggest chunk of the funding -- $5.1 million (2.7 million pounds) -- and has sent three vets to join the staff in Rome.

=





<B><font size=+1 color=green><center>Specialist warns of major flu pandemic</font>

UNAISI RATUBALAVU
Thursday, October 12, 2006
http://www.fijitimes.com/story.aspx?id=49780 </center>
AN epidemiologist has warned of Fiji losing its young and productive talent and population if the country was hit by an influenza pandemic.

Dr Narendra Singh from the Secretariat of the Pacific Community told senators yesterday that influenza was serious and most cases being monitored now targeted the 15 to 45 year age group.</b>

"This is like the pandemic in 1918 which killed 9,000 people. The flu that went around Fiji at that time infected the same age group (15 to 45 years) and we were not aware that there is a pandemic of influenza," Dr Singh explained.

He said very little had been done to get everyone informed on what should be done and emergency plans in place to ensure that influenza did not spread rapidly.

Dr Singh said the Ministry of Health was doing everything it could to protect the people.

"I think more should be done and we should get the businesses involved, the people working at the airport and all sectors."

Dr Singh said Fiji was not far away from Asian countries where bird flu was found and spreading rapidly.

However, Dr Singh hoped that by talking to the senators and other stakeholders would get the ball rolling on how prepared we in Fiji were if there was an influenza pandemic.

Dr Singh also warned that a lot of gatherings and meetings could help spread influenza quickly.

"In gatherings, it is a good way of disseminating influenza.

"And in Fiji, we have lots of gatherings like church gathering, family meetings and others," he said.

=




<B><font size=+1 color=blue><center>APHA Launches Get Ready Campaign to Help Americans Prepare Themselves for Flu Pandemic</font>

10/12/2006 11:34:00 AM
http://releases.usnewswire.com/GetRelease.asp?id=74191 </center>
WASHINGTON, Oct. 12 /U.S. Newswire/ -- The American Public Health Association (APHA) today launched the Get Ready campaign to help the public prepare for a potential influenza pandemic and outbreaks of other emerging infectious diseases.

Unlike existing efforts to prepare the nation for a pandemic, APHA's campaign will speak directly to individuals, families and communities and help fill gaps by telling people exactly what they need to prepare themselves. The campaign includes a blog, fact sheets and podcasts, accessible through the Get Ready Web site at http://www.getreadyforflu.org. </b>

"With the increasing threat of a flu pandemic, the general public must be equipped with the necessary resources to protect themselves," said Georges C. Benjamin, MD, FACP, executive director of APHA. "Unlike many other efforts using technical language and lengthy articles, APHA's Get Ready campaign will provide straightforward information and tools that are crafted for and relevant to all Americans."

The Get Ready for Flu blog, at http://www.getreadyforflu.blogspot.com/ , provides readers with background information on avian and pandemic influenza and practical advice on how to prepare themselves, their families and their communities. The blog also provides a discussion forum that addresses emerging issues and allows visitors to share comments and knowledge with others. Current posts include information about the H5N1 strain, food safety, school preparedness and prevention tips.

In addition to the blog, a new series of podcasts featuring public health experts discusses the need for preparedness and the increasing threat of pandemic flu. Future podcasts will cover topics such as pandemic flu basics, the impact of pandemic flu on certain communities, safe cooking procedures and lessons learned from the Spanish flu from 1918 to 1919.

"The Get Ready campaign will draw on the expertise of APHA members to educate the public and give Americans the important information they need to get prepared," said Patricia Mail, Ph.D., MPH, CHES, president of APHA. "It fills a critical gap in our nation's preparedness efforts."

APHA's Get Ready campaign is part of the association's larger "Protect, Prevent, Live Well" movement that will enable Americans to protect themselves, their families and their communities from preventable, serious health threats. Long-term plans for the Get Ready campaign, which is seeking funding, include grassroots activities, toolkits, community partnerships, preparedness surveys and a calculator that will help people determine what supplies they will need to prepare for pandemic flu and other emerging infectious diseases.

=




<B><font size=+1 color=purple><center>Plans for flu pandemic include classic public health measures</font>

Thursday, October 12, 2006
BY MARILYNN MARCHIONE
Associated Press
<A href="http://www.nj.com/news/ledger/index.ssf?/base/news-9/1160632640125640.xml&coll=1">www.nj.com</a></center>
SAN FRANCISCO -- Could you work from home for weeks at a time? How long could you hole up without needing to go to the grocery or drugstore? Would you be willing to wear a face mask and isolate yourself from others?

Harvard researchers are surveying Americans on questions like these as the government wraps up work on a plan to use primitive infection-control measures to deal with a killer flu outbreak until drugs and vaccines become available. </b>

The federal Centers for Disease Control and Prevention is pitching the plan at medical meetings and aims to send it out for review by the end of the year. State and local governments have asked for unusually detailed and specific advice on such matters as closing schools and canceling public events, one CDC official said.

This week, the CDC awarded $5.2 million in grants related to the plan, including research on whether to recommend face masks to the public. The CDC also asked the Institute of Medicine, a group of scientific advisers, to meet on these measures later this month.

"We can't afford to neglect some of the traditional approaches to contagion control because we very well may find ourselves in a situation where that's all we've got for a period of time," said CDC's quarantine chief Marty Cetron.

However, skeptics say parts of the plan amount to wishful thinking with little evidence they would work.

"A lot of these things sound good but they lack practical application," said Michael Osterholm, a University of Minnesota health expert involved in the planning.

Advising people in big office buildings to avoid elevators and stay 6 feet away from each other is impractical, and people can't stay in their homes for weeks or months without needing insulin and other medications, he noted.

The nationwide survey by the Harvard School of Public Health is an attempt to get a handle on how Americans would follow such advice.

As for hygiene tips like sneezing into your sleeve, "we have no data that that makes any difference" in controlling a pandemic, Osterholm said.

The bird flu that has ravaged poultry in Asia and killed at least 140 people is "still smoldering" as a human threat, showing no signs yet of morphing into one that spreads easily among people, said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

If it does, severe travel restrictions would delay its spread in the United States by only a week or two and at extreme cost, the CDC's David Bell said at a recent meeting of public health and disease experts in San Francisco.

Thermal scanning to try to detect people with fevers during the SARS outbreak turned up no cases and caused many false alarms. But voluntary quarantine, voluntary isolation of infected people and hygiene measures like hand washing, "cough etiquette" and face masks did help and might for flu, too, Bell said.

Frederick Hayden, a University of Virginia virologist currently working on global flu planning for the World Health Organization, agreed.

"The classic public health measures did work in SARS," he said. They won't be enough to stop a flu pandemic but could prolong and spread out its impact to prevent hospitals from being swamped and running out of respirators to keep the sickest alive.

The CDC plan will list multiple scenarios for pandemics that range in severity or attack certain age groups like children or college students, and recommend corresponding control measures.

These will include voluntary isolation of sick people, voluntary quarantine for those exposed to the germ but are not ill, and protective sequestration to separate healthy people or communities from a source of infection.

"Quarantine has gotten a very bad name and for very good reason. It has been abused in the past. It works best when we obtain and maintain the public trust," Bell said.

However, Osterholm said there's not enough science to recommend some measures, like "keep your distance" campaigns. Scientists know flu spreads through hand contact and big droplets when people cough or sneeze, but they don't know how far tiny particles remain in the air, or how important that is for spreading the germ.

In fact, experts know surprisingly little about what enables a flu germ to spread.

Health officials need to give advice but should be honest about the limits of what is known "and not oversell it, which there is a tendency to do in times of crisis," Osterholm said.

If that happens, "we will lose credibility quickly," he said.

=




<B><center>Egypt:

<font size=+1 color=green>Another Human Case of Bird Flu</font>

UN Integrated Regional Information Networks
October 12, 2006
Posted to the web October 12, 2006
Cairo
http://allafrica.com/stories/200610120531.html </center>
Egyptian health officials on Thursday blamed the most recent case of human bird-flu infection in Egypt on poor observance of government regulations aimed at stamping out the virus.

This came after it was confirmed on Wednesday that a 39-year-old woman in the Nile Delta province of Gharbiya had contracted avian influenza, also known as the H5N1 virus.</b>

"People are sticking to their habits and they are forgetting our message," said Sayyid Abbasi, Ministry of Health spokesperson.

Earlier this year, the Egyptian government and international agencies embarked on a nationwide campaign to persuade the population not to keep poultry inside their homes.

Hanan Aboul Magd is the latest victim to be infected with avian flu in Egypt. She was admitted to hospital on 4 October after she reportedly contracted the virus after buying and slaughtering infected ducks at her home.

Magd is the 15th human case of bird flu in Egypt since the first signs of the outbreak were seen in the country in February. Six of those patients have since died.

Hanan is reported to be in a stable condition, and her family is being tested for the virus.

Egypt's densely populated Nile Valley saw the worst concentration of bird flu infection this year outside Asia. The Valley lies on major routes for migratory birds, and has a large rural population that has traditionally reared poultry for food and income.

The government has overseen the culling of some 30 million birds over the past eight months, and has put into place tough restrictions on poultry keeping. So-called 'backyard birds', which are chickens or ducks kept in small numbers in low-income homes for extra food or cash, have been outlawed.

"It is a matter of changing behaviour. People are sometimes not honest [about keeping birds]. They know they are in danger but for other reasons they still have them," said Dr John Jabbour of the Communicable Diseases Surveillance Department at the World Health Organization's regional office in Cairo.

Dr Jabbour added that the government has succeeded in removing poultry from the homes of people in Cairo "but in more rural areas people are not accepting that they have to get rid of backyard birds".

Minister for Health and Population Hatem el-Gabali said on Tuesday that hospitals across Egypt had been put on a high state of alert.

Abbassi, the Ministry's spokesman, said the government was "working to 'recharge' the media message, through all the available channels".

An incidence of the virus among poultry was also recorded last month in the Upper Egypt town of Edfu, although no human infection was reported.

U.N. Says Bird Flu Awareness Increases​

http://www.newsday.com/news/health/...105573.story?coll=ny-leadhealthnews-headlines

By MARTA FALCONI
Associated Press Writer

October 12, 2006, 11:58 AM EDT


ROME -- Bird flu awareness has increased worldwide since last year, but countries still must keep up surveillance and response plans against the disease, U.N. officials said Thursday.

"We've raised the level of awareness around the world," said Juan Lubroth, a senior officer for animal health at the U.N.'s Food and Agriculture Organization. "The situation has improved, but if we relax, the spillover could be even worse."



Lubroth was speaking on the sidelines of the launch of a new unit in charge of dealing with animal health crises, food safety and other health issues at the agency's headquarters in Rome.

The H5N1 strain of bird flu has killed at least 148 people worldwide since outbreaks in Asia three years ago. Almost one-third of the victims have been in Indonesia, the worst affected country, according to the World Health Organization.

Experts fear that the virus could mutate into a form that is easily transmitted from person to person, which could set off a flu pandemic.

"Veterinary services in most countries are better than last year," said Karin Schwabenbauer, manager of the newly launched Crisis Management Center, which is aimed at giving prompt assistance in case of a health crisis. "Our feeling is that (bird flu) will not explode as it did last year, and we suppose that virus carriers are fewer than they used to be," she said.

Schwabenbauer said, however, that no one could predict if or where an outbreak might occur.

Evidence on the role of wild birds is not always conclusive in the areas where H5N1 has appeared. Migratory birds introduced the disease in Russia and Eastern Europe, but in recent outbreaks in Africa, there was scarce evidence pointing to wild birds.

The FAO has been engaged in training people, providing equipment and helping officials worldwide ready emergency plans in case of outbreaks, Lubroth said. He stressed that infected poultry still needed to be quickly detected and isolated.

"Only one introduction of a sick animal where there are millions could be quite explosive," Lubroth said.