4/23/08-4/29/08|Weekly Bird Flu Thread: Indian state suffers second bird flu outbreak

Link to last weeks thread:

HEALTH - 4/15/08-4/21/08|Weekly Bird Flu Thread:Bird Flu Spreading Towards Seoul

http://www.timebomb2000.com/vb/showthread.php?t=284755&highlight=bird


Johns Hopkins on influenza:

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

National Avian Influenza Surveillance Information:

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

CDC

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

WHO

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

CIDRAP

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

Official U.S. Government Web site

http://www.pandemicflu.gov/

FAO

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

Public Health Agency of Canada

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

European Union

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

The World Bank

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

Indian state suffers second bird flu outbreak​

http://news.yahoo.com/s/afp/20080423/wl_sthasia_afp/healthfluindia

AGARTALA, India (AFP) - An Indian state reported new bird flu cases Tuesday, little more than a week after it finished culling thousands of chickens to contain an outbreak of the disease.
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Laboratory tests confirmed the presence of the deadly H5N1 strain of the virus in dead chickens in northeastern Tripura state, which borders Bangladesh.

"This is the second time that the deadly bird flu virus has been detected in the state," Ashish Roy Barman, head of the state's animal resource department, told AFP Tuesday.

Health officials are visiting homes to check people for symptoms. India, which reported its first outbreak of avian flu in 2006, has not reported any human infections.

Checkpoints have been put in place to stop the transportation of chickens or poultry products outside the bird-flu zone.

Border guards along the 864-kilometre border with Bangladesh, which all but surrounds the tiny state, have also been put on alert.

Indian officials have expressed fears the virus may be spreading from Bangladesh.

Tripura is the second state after West Bengal in the country's east to report an outbreak of avian influenza this year.

Earlier this month, more than 40,000 birds were culled in the state following an outbreak of the disease.

The H5N1 strain of the virus has killed more than 230 people worldwide since late 2003. Health experts fear the strain could mutate into a form easily transmitted from person to person, leading to a pandemic.

U.S. rejects bird flu allegations​

http://www.thejakartapost.com/news/2008/04/23/us-rejects-bird-flu-allegations.html

The United States Embassy on Tuesday denied allegations it was "seeking to spread avian influenza (AI) or cause harm to human life through biological weaponization of the AI virus as false and without merit".

In a press release sent to The Jakarta Post, it said such allegations "are preposterous and a grave injustice to the people of the United States".

It referred to Indonesian Health Minister Siti Fadilah Supari, whom it said had made false claims that the United States was developing biological weapons from avian influenza samples.

In her recently released book Saatnya Berubah, Tangan Tuhan Dibalik Bird Flu (It's Time To Change, Divine Hands Behind Bird Flu), the minister alleged Washington was using bird flu samples shared by affected countries to create biological weapons.

Indonesia since February last year has stopped sharing bird flu samples with the World Health Organization pending an agreement that would benefit Indonesia in terms of vaccine distribution.

The press release said the United States was dedicated to working with other governments and international organizations to help prevent the spread of this disease, to avert any possible avian influenza pandemic and to plan for possible health contingencies.

The United States and Indonesia, it said, have a close partnership in combating avian influenza and the United States has provided more than US$50 million in support for Indonesia's efforts to prevent and control avian influenza since 2005. -- JP/Tony Hotland

H5N1 Media Spin In Korea Raises Pandemic Concerns​

http://www.recombinomics.com/News/04230801/H5N1_Korea_Media.html

Recombinomics Commentary 03:17
April 23, 2008

The soldier, whose family name is Cho, allegedly had body temperatures of up to 39.8 degrees Celsius, and was in and out of a coma. The high fever dissipated after he was treated with antibiotic and anti-viral drugs.

The Korea Center for Disease Control and Prevention says while Cho's symptoms are those of avian influenza, it's also possible that he might be affected with bacterial pneumonia.

The above comments by the Korea Center for Disease Control and Prevention raise serious credibility issues, since the patient has already tested positive for H5 by PCR and the test were done by the Korea Center for Disease Control and Prevention. Since the soldier developed symptoms after culling H5N1 positive chickens and ducks, a bacterial infection is of little consequence.

The patient and hospital contacts have been treated with Tamiflu, and the issue of bacterial pneumonia just serves to confuse.

This confusion is similar to earlier reports which tried to make distinctions between confirmed H5N1 and confirmed HPAI H5. The HPAI H5 will be H5N1 when the testing is completed because the sequence of the H5 is the same as the sequence of the H5N1.

These efforts to confuse raise serious credibility issues. Since the patient appears to have responded quickly to treatment, the case will likely be relatively mild. Therefore, detection of additional cases may be influenced by Tamiflu treatment. Such data can be easily affected by agencies that put out confusing statements and press releases.

These confusing statements remain a cause for concern.

2 New Suspected Cases of Bird Flu Reported​

http://www.koreatimes.co.kr/www/news/nation/2008/04/113_22912.html

Two more suspected cases of bird flu have been reported in the southwestern region of the country amid intensifying efforts to prevent further spread of the deadly disease, government officials said Tuesday.

The Ministry for Food, Agriculture, Forestry and Fisheries said it is checking cases reported at two chicken farms in Iksan, North Jeolla Province, to determine whether the recent deaths of poultry there were caused by avian influenza.

The two farms, which reported the deaths of 2,500 and 450 chickens, respectively, are located around 25 kilometers from an area where a bird flu outbreak was confirmed last Thursday, the ministry said. Samples tested positive in preliminary tests but the ministry said further investigation is required.

The latest cases in Iksan brought the number of suspected avian influenza outbreaks to 49 as of Tuesday morning. Of them, 26 have been confirmed to be related to a highly pathogenic bird flu virus, according to authorities.

Soldier With Mild Confirmed H5N1 Raises Pandemic Concerns​

http://www.recombinomics.com/News/04220804/H5N1_Korea_Mild.html

Recombinomics Commentary 15:08
April 22, 2008

Tests have shown that the virus detected in the patient's body was an H5 strain, according to the Korea Center for Disease Control and Prevention. It will take up to three weeks for a lab to confirm whether or not the strain is the deadly H5N1 strain, which has caused massive outbreaks in the Jeolla region since April 1.

The young corporal, identified only by his family name Cho, was sent to help kill infected chickens and ducks on Friday and Saturday. He suffered from high fever and was transported to an army hospital Sunday.

Authorities said his sickness was not related to the bird flu and that his condition has improved.

The above comments provide more detail on the H5N1 infected soldier in South Korea. The “H5” designation for the soldier is similar to comments on the H5 infected birds in South Korea. There is no data supporting anything other than H5N1 for the outbreaks in South Korea. In the OIE report, some were H5N1 confirmed while others were HPAI H5 confirmed at the time of filing. No H5 had been confirmed to be low path H5.

The rapid recovery could have been due to both antibiotic and Tamiflu treatment, if the patient had secondary bacterial pneumonia. However, the bacterial infection does not invalidate the H5 detection.

More detail on how the soldier was infected would be useful. Pictures of culling operations showed cullers in PPE’s from head to toe. Moreover, cullers are usually on prophylactic Tamiflu (oseltamivir).

The denial of the associated of bird flu symptoms with H5N1 infections raise concerns of additional H5N1 patients that are not considered H5N1 infections because of arbitrary and capricious definitions. The infected culler also raises concerns about infected farmers who have not used PPE’s or Tamiflu.

The H5 positive result raises concerns of widespread mild H5N1 patients in South Korea as well as Bangladesh and India. The passage of H5N1 through human hosts increases the likelihood of human adaptation and efficient transmission.

More information on the patient, PPE’s and prophylaxis would be useful.

Health department Don't touch dead birds​

http://www.sun-herald.com/Newsstory.cfm?pubdate=042308&story=tp3np3.htm&folder=NewsArchive2

SARASOTA -- The deaths of two teenage boys within five days of each other last month from avian flu in Indonesia reminded U.S. health officials of the threat of a pandemic flu outbreak.

They were the first such cases reported leading to death. One of the boys, an 11-year-old, had been in contact with sick and dead poultry.

A 19-page pamphlet titled, "What to do about Bird or Avian Flu," and published by the Sarasota County Health and Human Services Department, admonishes residents to avoid touching dead birds.

Even though the avian flu virus has not yet grown into a pandemic strain that can infect and be transmitted by people, health experts insist that preparations against it should continue.

Vaccines have been developed. Stockpiles of masks and Tamiflu have grown. Many countries, cities, companies and school systems have written plans to deal with the disease.

The severity of the current flu season, the worst in three years, in terms of doctor visits and deaths from flu and pneumonia, have drawn further attention to the fear of pandemic flu.

A more virulent type of virus was blamed for the season's increased severity by the U.S. Centers for Disease Control and Prevention.

In the United States, according to federal health and human services experts, hospitals now have wards for patients suspected of having bird flu. Contacts with the disease are traced very quickly by epidemiologists, and are treated with Tamiflu.

Fear of a pandemic flu such as the one that struck the United States in 1918 -- it caused 50 million deaths worldwide -- drives the preparations. Similar outbreaks in 1957 in Great Britain and 1968 in Hong Kong killed 3 million more.

From 250,000 to 500,000 people die from influenza and other respiratory diseases in a typical year, according to the World Health Organization.

A test of the reaction of staff members to a pandemic flu outbreak will be held next month at the Venice Community Center by the county health department.

It is part of a training program for people on response teams. Dianne Shipley, a health educator with the department, reported that the county has stepped up the effort.

Dr. Barri B. Burrus, a community health psychologist who lives in Nokomis, has been investigating how cities and towns can ready themselves for an outbreak of pandemic flu.

"How could greater Venice, for example, respond to such an event in the absence of vaccine and anti-viral medicines?" she asked.

Part of a team assembled by RTI International, a nonprofit research organization, she and colleagues interviewed hundreds of people in nine North Carolina counties. Those interviewed represented corporations, schools, governments and public health officials.

"One finding we made," Burrus said, "is that disaster planning fatigue probably impedes pandemic flu planning. Public health officers told us that taxpayers were troubled by the costs when no event materialized."

Vaccinating millions against avian flu has its advocates. But that would require manufacturing more than 1 billion doses, and take more than 12 months.

A pandemic flu cycle could circle the globe in 90 days, according to a study by the University of Minnesota.

Burrus's team concluded that local health departments will have to take the lead in responding to an outbreak.

Thanks, JPD

for the collection of news reports the last couple of weeks. Just read them together and it's really cranking up.

Indonesia defends its bird flu stance against US criticism​

http://news.yahoo.com/s/ap/20080424/ap_on_re_as/indonesia_us_bird_flu

JAKARTA, Indonesia - Indonesia does not want money for its samples of a deadly bird flu virus, a health official said Wednesday after the U.S. criticized his country for refusing to share the samples with the international community.

Instead, Indonesia wants governments and pharmaceutical companies to come up with a mechanism that will ensure future pandemic vaccines are accessible to developing nations, said Widjaja Lukito, an adviser to Health Minister Siti Fadilah Supari.

That could include creating a multilateral trust that would enable price tiering or bulk purchasing of lifesaving vaccines, Lukito said.

The adviser was responding to comments made by Health and Human Services Secretary Mike Leavitt, who accused Indonesia of withholding virus samples from the World Health Organization since early 2007 because it wanted royalties or other monetary benefits.

"This is not a line we want to cross," Leavitt told The Associated Press at the end of a quick stopover in Indonesia last week. "Because it means the next unique virus we come across, wherever it is, we'll end up with people who say there is a price to pay for the virus."

He repeated the allegation on his blog, saying Supari's bottom line appeared to be "share samples, get paid."

Indonesia — seen as a potential hotspot for a pandemic because of its high density of chickens and humans — denied that was the case. Lukito said he thought there may have been poor communication on both sides.

"There are many types of benefit programs that can be discussed," he said, noting that the U.S. and Indonesia agreed during Leavitt's visit to set up an expert panel on the issue. "One could be a kind of revolving fund developed by pharmaceutical companies."

Another, Lukito said, could be to create a multilateral trust — funded by contributions from governments, influenza vaccine manufacturers and individuals — to make sure vaccines are produced and distributed in a fair and equitable manner.

Suggestions at a WHO meeting in Geneva late last year included tiered pricing of vaccines, bulk purchasing and other procurement mechanisms that take into consideration how much governments could afford for vaccines, he said.

Under the existing virus-sharing system, poor countries are obliged to send samples to WHO, which then makes them available to a handful of pharmaceutical companies to use in vaccine production. Wealthy nations have stockpiled tons of bird flu vaccines, while Indonesia and other developing countries have limited supplies.

U.S. Ambassador to Indonesia Cameron R. Hume, meanwhile, appeared to downplay claims by Leavitt that Indonesia was trying to put a price tag on its H5N1 virus samples.

"Frankly, I think Indonesia's basic concern is that you have a very high mortality rate from avian influenza here," with nearly 80 percent of all humans infected dying, he said. "They are concerned about trying to be sure ... Indonesians don't face this totally unacceptable risk of death."

Indonesia has been hardest hit by bird flu since it began plaguing Asian poultry stocks in late 2003, with its 107 human deaths accounting for nearly half the 240 recorded fatalities worldwide. The virus remains hard for people to catch, but scientists worry it could mutate into a form that spreads easily among people, potentially sparking a pandemic that could kill millions.

Many international health experts said Supari had a point when she bucked WHO's decades-old virus sharing system. But by withholding bird flu samples, health experts note, she is impeding the global body's ability to monitor whether the virus is morphing into a more dangerous form.

Leavitt vowed in his blog on April 15 to give Indonesia another two months to work toward a solution.

"The cost of Indonesia's refusal to share influenza samples is incrementally small. However, the damage done by accepting Indonesia's view is profound, and simply unacceptable," Leavitt wrote.

Foreign observers to witness bird flu-handling exercise in Indonesia​

http://news.xinhuanet.com/english/2008-04/23/content_8037874.htm

JAKARTA, April 23 (Xinhua) -- At least 42 representatives of international agencies and foreign governments are to witness a bird flu handling exercise in Bali on April 25-27, sources close to the event's organizers said on Wednesday.

"They will be able to see from close quarters the seriousness with which the Indonesian government, including the Bali provincial administration, is handling bird flu," Antara news agency Wednesday quoted the sources as saying in Denpasar, capital of Bali province.

The simulation would involve related agencies and ordinary people and be staged in three districts and one municipality in Bali. It would also take place at Tabanan district's general hospital, Ngurah Rai airport and Sanglah General Hospital in Denpasar.

Observers would also come from professional organizations, various central government agencies, referral hospitals and public health offices in all other Indonesian provinces,

Indonesian Health Minister Siti Fadilah Supari is slated to open the demonstration in Jembrana District on April 25.

Chemoprophylaxis for H5N1 Confirmed Soldier in Korea ​

http://www.recombinomics.com/News/04230802/H5N1_Korea_Chemo.html

Recombinomics Commentary 12:22
April 23, 2008

Nearly 2,000 other South Korean soldiers have culled chickens and ducks since April 17. Those soldiers are being monitored every morning and evening for signs of H5N1, and are taking a 10-day course of Tamiflu, a flu treatment drug, the MND spokesman said.

The soldiers were given human influenza vaccinations before the culling, as well as protective uniforms, gloves and masks, which were destroyed after use.

The above comments from Stars and Stripes provide more detail on the military involvement in culling operations in South Korea. As expected, the cullers have PPE’s and are under chemoprophylaxis, minimizing the chances of infection. They are also vaccinated against seasonal flu to minimize co-infections.

However, in spite of these precautions, the Special Forces corporal developed an H5N1 infection. Although he (22M) developed a high temperature and lost consciousness, he responded well to antibiotic and Tamiflu treatment (concentrations are double the prophylactic dose).

However, although he developed bird flu symptoms and was H5 positive by PCR, media reports are raising alternative explanations for the symptoms, including bacterial pneumonia. However, a secondary infection does not negate the PCR positive result.

The media treatment of this lab confirmed case is cause for concern. Frequently Tamiflu treatment lowers viral load to a level that is below detection. Similarly, virus can be quickly cleared from the nose and throat, leading to false negatives. Since the soldier responded quickly to treatment, detection of similar cases may be difficult.

Media reports describe the hospitalization of 15-20 cases with similar symptoms, but these cases have tested negative. On a related note, the military has withdrawn all troops from culling operations, even though new confirmed cases in birds are being announced daily (see satellite map), and testing has expanded to asymptomatic ducks.

Thus, the media comments on a culler that has been PCR confirmed, coupled with comments on H5 confirmed poultry, raise concerns that the level of H5N1 infections in poultry and people will be significantly under-reported.

H5N1 Spread in Korea Raises Co-Infection Concerns​

http://www.recombinomics.com/News/04230803/H5N1_Korea_Co_Infections.html

Recombinomics Commentary 12:22
April 23, 2008

The Ministry for Food, Agriculture, Forestry and Fisheries said a duck farm in Nonsan, 213 kilometers south of Seoul, was put under quarantine on Tuesday after birds started dying and there was a noticeable drop in egg production.

It is the first time that bird flu has been reported this year in South Chungcheong Province.

Most outbreaks reported this year have been centered in the southwestern Jeolla region in places like Gimje, Jeongeup and Yeongam. There was an isolated case of bird flu confirmed in Pyeongtaek, Gyeonggi Province, 70 kilometers south of the capital.

The ministry, meanwhile, said the suspected outbreak in Nonsan brings the total number of bird flu cases reported this year to 50. Of the total, 26 have been confirmed as avian influenza

The above comments describe the continuing spread of H5N1 in South Korea (see satellite map). Although the number of H5N1 outbreaks is at record levels, the military has withdrawn from culling operations after a soldier was H5 lab confirmed after developing bird flu symptoms while culling chickens and ducks. In addition, testing of asymptomatic ducks has expanded.

The detection of H5 in a culler raises concerns about H5 transmission. Testing of live markets in South Korea has identified a wide range of serotypes in domestic poultry, which provide genetic diversity for H5N1 evolution. Earlier sequencing of these isolates has demonstrated frequent recombination and a convergence of polymorphisms, suggesting similar changes can be transferred to H5N1. Recent reports have described lethal H3N2 in dogs in Korea, which is readily transmitted dog to dog. Since H5N1 has also been reported in dogs, co-infections of H3N2 and H5N1 is a cause for concern.

Recently, neighboring Japan has announced plans to implement an pre-pandemic vaccine program targeting first responders and up to 10-20 million residents, along with the possible expansion of their vaccine stockpile.

Important new flu paper in Cell: part I​

http://scienceblogs.com/effectmeasure/2008/04/important_new_flu_paper_in_cel.php?utm_medium=link

Category: Bird flu • Infectious disease • Influenza treatment • biology
Posted on: April 22, 2008 7:13 AM, by revere

The cells of your body don't just sit there, unmindful of what is going on around them. They have to respond to things, even cooperate with other cells to get things done for the common good. Humans do the same thing. We've developed a system of signaling to each other using an intricate vocal system, a complex grammar, ears, eyes and smell detecting systems. It's a very complicated package with a lot of moving parts. It's not so surprising, then, that cells also have complex signaling systems with a lot of parts that they use to respond to their environment. Just as we sometimes make a coordinated response to something in our lives (I touch a hot stove or I have a fight or flight response to a threatening situation), so do cells respond to their environment (there is a virus touching my cell surface). Communication in cells is tied up with almost everything, including tissue repair, development, cancer and a lot more. Now a new paper in the journal Cell describes how a particular cell signaling pathway might be involved in the catastrophic response of lungs when infected by certain viruses or bacterial toxins. Because of the potential importance of this paper we are going to take some time to explain it.

The central actor in the paper by Imai et al. ("Identification of Oxidative Stress and Toll-like Receptor 4 Signaling as a Key Pathway of Acute Lung Injury", Cell, Vol 133, 235-249, 18 April 2008 is a cell signaling receptor called TLR4, which stands for Toll-Like Receptor 4. The Toll-like receptors are a family of molecules, some, like TLR4, found on the surface of certain cells that are part of the innate immune system. The adaptive immune system produces antibodies and requires some previous exposure but the innate immune system sounds a non-specific alarm. It says, "Danger here, mobilize defenses." The TLRs get their name because they bear similarity to a gene on fruitflies that had the name Toll. Toll means "weird" in German:

Christiane Nüsslein-Volhard of the Max Planck Institute in Tübingen analyzed mutations in fruit flies. In 1985, she saw a weird-looking fly larva in which the ventral portion of the body was underdeveloped. Her spontaneous comment was "Das war ja toll!" meaning "That was weird!" and she coined the name Toll for the mutated gene. (Hansson GK, Edfeldt K, Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1085)

Not so weird that it prevented Nüsslein-Volhard from receiving the 1995 Nobel Prize for her work. But the story did get weirder. In 1995 it was found that this gene was not only associated with differentiating back to front in the developing fruitfly but also was somehow involved in its resistance to fungal infection. By the early 1990s other genes similar to the toll gene in fruitflies had been found in humans. While the initial thought was the gene was probably related to development as in the fruitfly, there was soon evidence that one of them, now called TLR4, was the button pushed by lipopolysaccharide (LPS), a component of the cell wall of gram negative bacteria and the endotoxin involved in "gram negative sepsis," the devastating multi-organ system collapse seen in some bacterial infections. Gram-negative sepsis in turn was also similar to the cytokine storm of Acute Lung Injury (ALI) seen in SARS, H5N1, 1918 H1N1, inhalation anthrax and some cases of Monkeypox. TLR4 is now part of a whole family (13 at last count) of Toll-like genes that produce generalized pattern recognition receptors for broad classes of pathogen components. As such they are part of the innate immune system that begins to act before there is any antibody selection or response. Our knowledge of the TLR system is very recent since their discovery is barely ten years old. But already the original TLR gene, TLR4, is becoming part of the bird flu story.

Unfortunately the story is still hazy and it isn't possible to draw any straight line conclusions from Imai et al.'s very interesting paper. But it feels like we're getting somewhere. This is only a piece of the puzzle but I'm guessing it will later be seen as a major piece. We'll have to see. Meanwhile, what did they show? We'll pick this up in the next post.

Important new flu paper in Cell: part II​

http://scienceblogs.com/effectmeasure/2008/04/important_new_flu_paper_in_cel_1.php

In our previous post we set the stage for discussing the results of a significant new paper by Imai et al. and colleagues on the mechanism of lung damage from diverse pathogens, including SARS, bird flu H5N1, 1918 H1N1 flu, inhalational anthrax and Monkeypox. If this work is verified it is a major step forward in our understanding of how the devastating consequences of Acute Respiratory Distress Syndrome (ARDS) and Acute Lung Injury (ALI) come about and may well provide clues about how to treat what is still an essentially untreatable and catastrophic medical condition.

There are two main parts to their elegant results. The first has to do with TLR4. Imai et al. first showed that the rapid impairment of lung function in mice caused by breathing an acid chemical depended on TLR4. They did this by exposing various inbred mouse strains and finding that one, the C3H/HeJ mouse, didn't react in the same way. It was known that this mouse also showed resistance to LPS because of a mutation in the TLR4 gene. Interesting. But the dissection of the mechanism was just beginning.

We return to the idea that TLR4 is part of cell signaling (see our previous post). While some kinds of cell signaling is relatively simple, much depends on pathways of protein - protein interactions. The receptor button gets pushed by something binding to it, say at the surface of the cell (that's the signal). Now we need a response. The binding of the receptor by the signaling molecule causes the receptor to modify another protein which then interacts with yet another protein, etc., etc., in a potentially long pathway of interactions. The path may also branch into two or more pathways. Branching allows complicated interactions and feedbacks to produce dynamics not possible with a single straight line bucket brigade style signal.

There is a branch right after TLR4 is activated. One branch starts with another protein called MD88 which then interacts with still others until it winds up activating an important cellular protein called NFkappaB. The other branch starts with a protein called TRIF. The MyD88 branch is the best studied. Surprisingly, though, when a mutant mouse deficient in MyDD88 mice was used it showed no resistance to ALI. That suggested that the ALI (remember that means Acute Lung Injury) was being mediated by the other branch, through TRIF. Sure enough, abolishing TRIF in another strain of mutant mice restored the resistance to ALI on exposure to acid mist.

They then looked at cytokine production. Cytokines are chemicals that are used for local signaling. They are released in the immune response during inflammation (among other things) and if the release is not well regulated a runaway inflammatory response can result. Local production of cytokines is characteristic of ALI. But there are a lot of cytokines and unraveling how they all interact and what part each plays is a difficult problem. In this case Imai et al. noticed that one particular cytokine, IL-6 (interleukin 6) was related to TLR4 signaling or lack of signaling. Sure enough, mice deficient in IL-6 were much more resistant to acid mist exposure than mice capable of producing IL-6. This doesn't mean other cytokines aren't also involved but it does point to a role for IL-6.

If TLR4 signaling is involved, what is pushing the TLR4 button? One thought is that because lung cells are open to oxygen, maybe oxidative damage was the signal (I am skipping their experiments to rule out any hidden LPS involvement. Suffice to say there isn't.) Cells of the innate immune system, like macrophages (present as wandering scavengers and killers of pathogens in the lung), use the production of highly reactive oxygen species to kill pathogens. They do this with a "respiratory burst," again something that has to be controlled because the same reactive species that kills pathogens can cause damage to the host cell. TLR4 is embedded in the outside of the cell membrane (the bag that holds the cell contents). We discussed the make-up of the cell membrane in some earlier posts, connecting it specifically to the receptor the flu virus uses to glom onto cells. You can find those earlier posts here, here, here, here, here). Suffice it to say one possible consequence of a respiratory burst is some oxidative damage to the cell membrane, which is made up of a lipid bilayer composed of phospolipids (see the earlier posts for a complete explanation of phospholipids). The cell membrane is not the only place where there are abundant phospholipids in the lung, however. There is a soap-like agent in the lung, surfactant, whose main function is to reduce surface tension and make it easier for the lung to keep expanded. It is made up of 8-% to 90% phospholipid. With all these potentially oxidizable materials around, Imai et al. wondered if oxidative damage to the phospholipids might be the trigger setting TLR4 signaling in motion.

The answer is a qualified "yes." We'll discuss the evidence and the connection to H5N1, SARS and some other agents in the last post, next.

What horses can tell us now about the coming human flu pandemic​

http://www.physorg.com/news128179789.html

Stored safely in a freezer at Cornell's James A. Baker Institute for Animal Health are samples of the virus thought to be most like the one public health experts expect someday to afflict record numbers of the world's population. The virus was collected in 1973 during an outbreak of equine influenza at a Florida racetrack. Dorothy Holmes, an infectious disease specialist in Cornell's College of Veterinary Medicine, had obtained samples of the virus with the intention of using it to create nasal spray vaccines for horses.

Structural biologist and co-investigator Brian Crane, an associate professor of chemistry and chemical biology, is focusing on the static structure of HA. It is known that when viruses enter cells they undergo a change in their structure. Collaborator Lois Pollack, an associate professor of applied and engineering physics, is interested in the dynamics of this change -- how the protein undergoes a change in shape and structure when entering the cell. Susan Daniel, an assistant professor of chemical and biomolecular engineering and an expert in using solid-supported lipid bilayers as mimics of cell membranes, is looking at what happens next, when the virus enters the host's cell and contacts the plasma membrane of the cell (which is a lipid).

"With this highly talented group of people, we can go deeper and deeper into the mechanism of how the virus recognizes the cell and undergoes its conformational change, right through to when it fuses with the lipids," Whittaker explains.

There is another equally compelling reason to study the activity of surface proteins of the equine influenza virus.

"Mutations occurring at the entry site are very often what allow host switching; that is, the virus's ability to jump from one species to another -- say from birds to horses or from birds to people," Whittaker points out.

The H7 serotype -- the first documented equine influenza virus -- was isolated from an equine outbreak in Czechoslovakia in 1956 that spread around the world. Subsequently it was shown that the virus was a very highly pathogenic H7 virus in chickens and other birds that had moved into horses. Now H7 is prevalent in birds, a fact that gives public health officials great concern.

Whittaker thinks there's a significant probability that the characteristics of H7 (which has never been studied in any kind of molecular detail before) as it infected horses in the 1950s would be similar to the characteristics of virus behavior when the next virus pandemic occurs in horses and in humans.

"The horse," Whittaker says, "can give incredibly valuable information for our global understanding of influenza."

The investigators also plan to study the serotype of the virus that caused the 1918 flu pandemic and today's avian influenza serotypes to try to figure out what distinguishes those from flu viruses now circulating in the human population.

"We've shown that there's clearly an obvious difference between equine and avian viruses, but those between the human and avian viruses are more subtle, so we're going to have to do more work to find out what's going on there," Whittaker explains.

Source: Cornell University

India blames Bangladesh as bird flu spreads​

http://africa.reuters.com/commodities/news/usnDEL205431.html?rpc=401&

GUWAHATI, India, April 24 (Reuters) - Authorities battling an outbreak of bird flu in poultry in India's remote northeast blamed Bangladesh for the spread on Thursday, but many experts said India was not doing enough to contain the virus.

More than 25,000 chickens and ducks have already been slaughtered in Tripura state this month after it was hit by the H5N1 strain.

On Thursday, authorities chose to blame neighbouring Bangladesh after they received reports of new bird flu cases in the state.

"Unless bird flu is contained completely in Bangladesh, the virus will keep spreading in Tripura," U. Venkatateswarlu, a top official of the animal resource development department said.

The remote northeastern state borders Bangladesh, where more than half the country's districts have been affected by the virus.

"Our main problem in controlling the situation is because of close proximity with Bangladesh," Venkatateswarlu added.

But many people disagreed.

For the past two days, while hundreds of birds mysteriously died in remote villages, complaints from people were largely ignored by state authorities, some officials and animal experts said.

"It is foolish on their part to blame Bangladesh for their own doing," N.G. Jayasimha of the People for the Ethical Treatment of Animals (PETA), an animal rights group, told Reuters from Mumbai.

"We had warned the Tripura government about bird flu and we told them the reason for the spread of bird flu is because of bad farm practices," he said by telephone.

"They sat on our report and did nothing."

"TIME FOR STRONG ACTION"

Local politicians also voiced their concern over the government's slow reaction in dealing with bird flu.

"The government is going too slow and blaming Bangladesh will not solve this problem as it is time we should take strong action," said Ratan Lal Nath, a lawmaker from Mohanpur town, worst-hit by the recent outbreak.

Authorities said they would cull at least 15,000 more birds to control the virus in two new areas.

Most people had also stopped buying chickens in markets and traders said they were staring at huge losses.

When the virus resurfaced in the eastern state of West Bengal in January this year, many states banned poultry products, pulling down prices sharply.

Farmers cut production as sales went down by more than 70 percent.

The World Health Organisation said the rapid spread of bird flu throughout much of densely populated West Bengal was the most serious outbreak yet in India.

On Thursday, volunteers from the Tripura health department were also checking people for any flu-like symptoms.

India has not reported any human infections of the H5N1 bird flu virus since the country's first outbreak in 2006.

But experts fear the virus might mutate or combine with the highly contagious seasonal influenza virus and spark a pandemic that could kill millions of people.

Since the virus resurfaced in Asia in late 2003, at least 240 people have died from bird flu in a dozen countries, the WHO says.

More H5N1 Media Spin In Korea ​

http://www.recombinomics.com/News/04250801/H5N1_Korea_Media_More.html

Recombinomics Commentary 10:24
April 25, 2008

A Korean soldier who was involved in the culling process of poultry infected with bird flu has been found to be carrying a less deadly variant of avian influenza.

According to the Korea Center for Disease Control and Prevention, the corporal, identified only by his surname Cho, is not likely to be infected with the deadly strain of H5N1.

Authorities are also linking Cho's earlier symptoms of high fever to bacterial pneumonia.

The above comments on the status of the H5 positive soldier with confirmed pneumonia does not make sense scientifically or conceptually. The soldier was a culler of HPAI H5 positive chickens and ducks. To date Korea has described 11 outbreaks this season and all are HPAI H5. Six have been further characterized as HPAI H5N1, which is a deadly strain. The HPAI determination is based on the HA cleavage site. Last season the H5N1 in Korea was clade 2.2 (and was the Uvs Lake version of the Qinghai strain). That clade has an HA cleavage site of GERRRKKR and it is likely that all HPAI, including the strain that infected the soldier, will have GERRRKKR.

Thus, the claim that the H5 is not the deadly strain appears to be based on the quick recovery of the patient. However, similar quick recoveries were seen last season in Egypt. In the spring of 2007, only one in seventeen cases was fatal and most responded quickly to treatment. Moreover, many did not develop pneumonia. Thus, mild cases of clade 2.2 H5N1 have been documented.

If confirmed again, the H5N1 infection would be South Koreas first case meeting the WHO definition. In the past, confirmation of the first case in a country was frequently linked to a cluster. Moreover, the cluster was linked to one of a long series of testing shortfalls.

In 2005 the index case for Cambodia had been collecting dead bird prior to developing a fatal infection. He was never tested, but his sister became ill and was eventually brought to Vietnam for testing. After she died, she was H5N1 confirmed, so she was the first official case for Cambodia.

In 2005 siblings in Hunan China developed symptoms, One died and the other rfevered, but initially both tested negative. Eventually a rise in antibody levels was used to show that at least one was H5N1 confirmed.

In 2005 the first case for Indonesia was the father of the index case. Initially samples were not collected from the index case for the cluster. Eventually antibodies were determined for two samples. Both were strong positives (titers of 640 and 1280), but since the second collection wa only two fold higher than the first collection, the patient wasn’t an official case (although a early collection or a second collection more than 3 days after the first collection would have created a positive. The third fatality infected sibling was not tested.

In 2006 the first clade 2.2 infected paients were reported. In Turkey the first confirmed cases were siblings, but although three of the four were unconscious by the time they were tested in Van, all four initially tested negative. It was only after the three unconscious sublings began to die that they were declared H5N1 positive. The youngest sibling, who recovered, was never H5N1 confirmed.

The outbreak in Turkey was followed by Iraq. The index cases was said to have symptoms that exactly matched those of the siblings in Iraq. However, initially she was said to have died from a heart problem, a diagnosis that was supported by WHO. When her uncle developed symptoms, bith were declared H5N1 positive.

Turkey was followed by Azerbaijan, and the cardiac diagnosis was used on the index case there also. After relatives and a friend began to die, the index case as well as relatives and a friend were declared H5N1 positive.

In 2007 the first H5N1 in Nigeria was reported. However, testing of the index case returned equivocal results, although her daughter was H5N1 positive. The index case was never confirmed.

In 2007, the first cases in Pakistan were brothers. Although one fatal case was confirmed, the index case as well as another brother tested negative by WHO affiliates initially. The other fatal case was never tested. Eventually, two of the brothers were confirmed by antibody tests, because the original samples had degraded and were PCR negative.

Thus, as detailed above, the vast majority of index cases were in clusters, although in most cases at least one of the fatally infected cluster members was not firmed. However, the case in Korea also has similarities to the H5 infected geese in on Prince Edward` Island (PEI) in Canada. Like the soldier, only one positive was reported and the initial report was H5 PCR confirmed. The three dead geese had been on a farm and displayed neurological symptoms. They were dead the following day. Ten days alter a news conference was called to announce the H5 positive result. Since H5 rarely kills waterfowl, the likelihood that the geese were H5N1 positive was high. All birds on the farm were culled and the owners offered Tamiflu. However, after the other birds were found to be negative, the national labs in Winnipeg announced that the sample from PEI had degraded and the H5 results could not be confirmed. Consequently, there was no OIE report filed, and Canada and North America remained H5N1 free.

Thus, the history of index cases in a variety of countries remains clouded at best, even in high profile clusters.

More detail on testing results from the H5 infected soldier will be useful.

Indonesia holds major bird flu exercise in Bali​

http://africa.reuters.com/commodities/news/usnJAK112164.html

JEMBRANA, Indonesia, April 25 (Reuters) - Indonesia, which has the world's highest human death toll from bird flu, launched an exercise on the resort island of Bali on Friday to test its ability to deal with a pandemic triggered by the virus.

The three-day simulation, the country's biggest ever test, involves about 1,000 people, including police and military personnel, some wearing white protective suits and going from door to door in the test village in the west of the island.

"This is to show to the world that we are ready, that we are prepared," said Nyoman Kandun, director-general of communicable disease control at the health ministry.

The United Nations' Food and Agriculture Organisation (FAO) said last month that Indonesian efforts had done little to control bird flu and it needed more help in controlling the virus.

Under the exercise, poultry was culled and buried in infected areas and the village is due to be quarantined on Saturday.

Indonesia has suffered 107 human deaths from bird flu, out of 132 confirmed cases, compared with 240 deaths globally, according to data from the World Health Organisation.

Contact with sick fowl is the most common way of contracting the H5N1 virus, which is endemic in bird populations in most of Indonesia.

Experts fear the virus could mutate into a form that people can easily catch and pass to one another, in which case infections would soar, causing a pandemic that could kill millions of people worldwide.

"The keyword is preparedness... because we do not know where, when and how the pandemic will occur," Kandun said.

On Sunday, as part of the exercise, Bali airport will also be equipped with body-heat detectors to screen potential infections among travellers in and out of the island.

The Sanglah hospital in Bali has been designated to treat bird flu cases, while patients with other diseases at the hospital will not be allowed to leave until the quarantine period ends.

An Indonesian health official said this week that in the case of a pandemic an estimated five million Indonesians could be infected with the virus, with between 5 to 10 percent of those infected dying.

Indonesia has also been locked in a dispute with the international community over sharing bird flu virus samples, which is regarded as vital to developing vaccines.

U.S. Health Secretary Michael Leavitt said this month that he had stressed the need for transparent sharing of the virus during talks with Indonesian President Susilo Bambang Yudhoyono.

But Indonesia has refused to freely share virus samples with the WHO until a new global mechanism is in place to ensure that specimens will not be used for commercial purposes without the country's approval.

Jakarta says it wants guarantees from richer nations and drugmakers that poor countries would get access to affordable vaccines derived from their samples.

Indonesia, US wrangle over future of naval lab​

http://www.todayszaman.com/tz-web/detaylar.do?load=detay&link=140030

An agreement to secure the future of a "naval medical lab in Indonesia is being held up by disputes over diplomatic immunity for American staff as well as sharing of virus samples, a "official said on Thursday.


The "Naval Medical Research Unit No. 2, or NAMRU-2 for short, has been key to efforts to track bird flu in Indonesia, the country with the most human deaths from the H5N1 virus. But a memorandum of understanding allowing the lab to operate in Jakarta expired two years ago and has not been renewed, appearing to become ensnared in a wider dispute by Indonesian health officials over sharing samples of H5N1 with the rest of the world. "There's a section in the MoU ... that's not agreed yet," deputy "ambassador for Indonesia John Heffern told a news conference. He declined to elaborate, but denied that it was related to payments for samples. "Health and Human Services Secretary Michael Leavitt, who recently visited Indonesia, had said on Monday that Jakarta officials were seeking payments. Heffern said the "government also wanted diplomatic immunity for 19 Americans out of the roughly 170-staff at the lab, while Indonesia has only offered immunity to two staff.

Soldier affected by bird flu recovers: health authorities ​

http://english.yonhapnews.co.kr/business/2008/04/25/27/0501000000AEN20080425007900320F.HTML

혻혻 SEOUL, April 25 (Yonhap) -- A South Korean soldier who may have been infected with the bird flu virus has been declared "fully cured" by doctors, health authorities said Friday.

혻 혻 The soldier, who has been placed under quarantine since Sunday, has responded well to antibiotics and antiviral drugs, with his white cell count back to normal, the Korea Center for Disease Control and Prevention (KCDC) said.

혻혻 It said the soldier's fever, sore throat and other symptoms that could be linked to bird flu have vanished, but added the patient will remain in the hospital for the time being until more detailed test results come in.

혻혻 KCDC said earlier in the week that while the solider took part in the culling and burying of birds and initial tests showed he had been exposed to the avian influenza, his ill health may have been brought on by common flu.

혻혻 Doctors said that he had been feeling ill before being assigned to the bird culling detail.

혻 혻 A handful of South Koreans tested positive for bird flu antibodies in their blood in the past although none have actually become sick. Antibodies in the blood is a telltale sign that a person was infected with a certain virus even if he or she did not get sick.

혻혻 The Ministry for Food, Agriculture, Forestry and Fisheries, meanwhile, said one duck farm in Naju, South Jeolla province reported sudden deaths of birds on Thursday.

혻혻 This brings the total number of reported bird flu cases in the country to 52. Of that number, 28 tested positive for bird flu, while 12 were sick for other reasons. Other reports are being checked by animal quarantine officials.

Important new flu paper in Cell: part III​

http://scienceblogs.com/effectmeasure/2008/04/important_new_flu_paper_in_cel_2.php

In the previous two posts (here and here) we laid out some new results that dissect what might be happening at the molecular level when a patient infected with SARS or bird flu descends into Acute Respiratory Distress Syndrome (ARDS) from Acute Lung Injury (ALI) in a just published paper in the journal Cell (Imai et al., "Identification of Oxidative Stress and Toll-like Receptor 4 Signaling as a Key Pathway of Acute Lung Injury", Cell, Vol 133, 235-249, 18 April 2008). We have already discussed their experiments showing that TLR4, a receptor that is part of the innate immune system, was needed for ALI caused by an acid mist; and that a locally released cytokine, IL-6, was connected with whatever was going on. We left off at the point where we were presenting the evidence connecting activation of TLR4, with oxidative damage to the phospholipids making up the lung cell membrane and the bath of surfactant in which they sit. Their results show that oxidized phospholipids can both cause ALI and induce expression of the cytokine IL-6 from pulmonary macrophages, the wandering scavenger/killer cells that patrol the lung looking for pathogens. The next step is perhaps the most dramatic:

Patients who died of H5N1 avian influenza or Spanish influenza developed ARDS, and extremely high levels of cytokines have been observed in patients and animals infected with these viruses (Beigel et al., 2005, Tumpey et al., 2005). Our data so far showed that acid aspiration triggers production of OxPLs [oxidized phospholipids] that can augment the severity of ALI and cytokine production via TLR4. We wanted to extend these findings to H5N1-mediated ALI. (Imai et al.)

They instilled inactivated H5N1 (i.e., virus that retained hemagglutin (HA) that could bind to host cell receptor but the virus could not infect or replicate) into mouse lung and showed that it acted like acid mist, i.e., it induced ALI and generated cytokine IL-6 by a pathway that was dependent on TLR4 through the TRIF branch (not the MyD88 branch). There was another interesting effect on the host cells. Inactivated H5N1 caused them to express more TLR4 on their surface. They also showed that H5N1 induced oxidative stress that led to oxidized phospholipids. Was the production of oxidized phospholipids caused by the lung injury or the other way around? By using mice that couldn't produce a respiratory burst (see previous post) they determined that the oxidative stress came first. Somehow H5N1 produced oxidized phospholipids which then stimulated TLR4 and consequent ALI and IL-6 production.

To cap things off, examination of tissues from two actual H5N1 patients showed "massive formation" of oxidized phospholipids, but patients who died of non lung diseases showed no such changes. It gets better. The same oxidized phospholipids were found in nine patients who developed ARDS after coming down with SARS and similarly in monkeys with pulmonary anthrax, Monkeypox and Yersinia pneumonitis (plague in the lung). The experiments with mice deficient in oxidative stress mechanisms seem to rule out the explanation that the oxidized phospholipids were the result, not the cause of the lung injury.

The bottom line here seems to be that Acute Lung Injury (ALI) with resulting ARDS is the result of oxidative stress coupled to the machinery of the innate immune system through one pathway leading out of TLR4. Does it matter that the path goes through TRIF and not MyD88? The authors make this intriguing suggestion. Since TLR4 utilizes both the classical MyD88 pathway and the TRIF pathway but the ALI is associated only with the TRIF path, by finding a way to suppress TRIF or some of its downstream proteins we might be able to treat ALI or ARDS without disturbing the functions of the innate immune system that work through MyD88. Thus many of the usual functions of ATLR4 would not be affected.

Assuming this story holds together we need to know more about what the TLR4-TRIF pathway is doing and what triggers the oxidation of phospholipids (and what phospholipids are involved and where). We know from recent work that blocking IL-6 doesn't stop damage from flu, so whatever TLR4 sets in motion might include IL-6 but clearly involves more, possibly other cytokines or maybe the cytokines are just effects, not causes of what is going on. The participation of TLR4 is somewhat surprising since it has been associated with defense against bacteria, not viruses. Moreover oxidized phospholipids have been shown to be protective against damage by bacterial LPS. Here's a possible explanation. The oxidized phospholipids are also produced by bacterial infection but they compete with LPS in someway. This might be some kind of brake on a runaway inflammatory response to LPS. In a viral infection there is no LPS to compete with and the oxidized phospholipids have nothing to counterbalance them. They thus make things worse, not better.

Of course I am just speculating. There's still a lot to learn. But this elegant series of experiments makes me feel as if we have just taken a big step forward and just as importantly, suggested a direction to go. All we need is enough time and the will and resources to use what we find out.

Bird flu spreads in Tripura​

http://timesofindia.indiatimes.com/India/Bird_flu_spreads_in_Tripura/rssarticleshow/2984104.cms

NEW DELHI: Bird flu has now started to spread fast and wide in Tripura.

Blood and faecal samples of dead birds picked up from Nadilagh village in Bishalgarh sub-division of West Tripura have now tested positive for bird flu. This is third area in the state in less than two weeks to have come under the grip of the deadly disease.

Final test reports sent to the state government by Bhopal's High Security Animal Disease Laboratory (HSADL) on Thursday night confirmed the presence of the highly pathogenic H5N1 virus in Nadilagh village, which is just 25 km from Agartala.

Speaking to TOI from Bishalgarh, state animal resources department director A Roy Barman said: "The earlier outbreak sites — Mohanpur and Dhalai — were within half to four km from the Bangladesh border. So we were certain that the virus may have come into Tripura through illegal trade of poultry between villagers on both sides of the border.

However, the latest outbreak in Nadilagh has come as a surprise. It is 50 km away from the Bangladesh border."

Barman now suspects that migratory birds that are now nesting in the water bodies of Shipaijala forest area could be carriers of the virus. "The area around Nadilagh is frequently visited by migratory birds. They too could be carrying the virus. We are baffled. We don't know whether the virus is travelling or whether these are simultaneous outbreaks," he added.

No more avian flu on Sask chicken farm; Canada declared free of disease​

http://canadianpress.google.com/article/ALeqM5h0KhibyQexOwvFvm03eFJLqFg2kw

OTTAWA — Canada has been declared free of a highly infectious strain of avian flu by the Canadian Food Inspection Agency.

The agency says there's been no sign of bird flu on a Saskatchewan farm since cleaning and disinfection were completed 90 days ago. That means Canada can be considered free of the infection as per international regulations overseen by the World Organization for Animal Health.

About 50,000 birds on James Glen's chicken farm north of Regina were destroyed in September after avian flu was discovered.

The strain is not dangerous to humans, but the outbreak led 20 countries to ban imports of Canadian poultry products.

The avian flu virus in Saskatchewan was the same one involved in a 2004 outbreak in British Columbia that saw 17 million chickens destroyed.

Bird flu drill gives residents golden lesson​

http://www.thejakartapost.com/news/2008/04/27/bird-flu-drill-gives-residents-golden-lesson.html

There's no such thing as "bird flu" in Dangin Tukad Daya village in Jembrana, about two hours' drive west of Denpasar. The avian influenza has become Flu Yang Mematikan (deadly influenza), the words splashed across banners of various sizes placed at eye-catching spots throughout the village.

The banners seem to give a hint of what's in store.

On Friday, some residents complained of severe respiratory problems and other cold symptoms. A laboratory check confirmed they had avian influenza caused by H5N1 -- originally a poultry disease.

When one villager reported his chickens had died, officials from the local animal husbandry agency came to examine the carcasses: bird flu was confirmed. The officials took the standard procedure of culling all chickens in a 1 kilometer radius from the infected backyard farm.

In the afternoon, Jembrana Regent I Gede Winasa publicly announced an extraordinary situation after receiving reports from virology and epidemiology tests on the incidents.

By Saturday, 20 villagers had caught the influenza and were rushed to nearby hospitals. Many others were given antiviral prophylaxes to prevent widespread illness.

Health Minister Siti Fadillah Supari declared the village an avian influenza epicenter, which meant get-tough measures were required, such as quarantining the infected residents and shutting off access to and from the village. The school was closed and the students were sent home. Local administration officials distributed supplies for the quarantined families.

This might have been reality, but for one thing: a wailing siren on a car and an official's repeated announcements through a microphone of what to do during a pandemic: Stay calm, seek information from reliable sources, keep the environment clean and "remember what is happening today is just a simulation. It's just a simulation".

Everything went as planned in the scenario with residents showing a degree of candor and the necessary spontaneity to play their roles.

The village is hosting a three-day bird flu pandemic drill, which started Friday. About 1,000 people were involved in the drill, which was funded by the Atlanta-based Centers for Disease Control and Prevention.

Said to be the world's first-ever massive pandemic simulation, the drill was designed to try out the recently authored National Pandemic Preparedness.

The World Health Organization's representative in Indonesia, Subhash Salunke, said after Friday's opening ceremony the simulation is a very positive step taken by Indonesian government.

"It's a learning process for all and this simulation will contribute a lot to the global community," Subhash said.

Since reporting its first human case of bird flu infection in 2005, Indonesia has led the world's human bird flu death toll with a staggering 107 deaths. Two of the fatalities were in Bali.

One of the victims was a resident of Dangin Tukad Daya, while the other was from Tabanan. The drill, therefore, was warmly welcomed by the administration and most of residents.

Putu Arini -- who played a wife whose husband became the first patient reported to a community health clinic -- said she was glad she was involved in the drill.

"It (the simulation) will surely be useful. I learned about bird flu after a villager died of bird flu last year. We were told then not to keep free-range chickens. I haven't had any chickens since then.

"It sounds ridiculous to say people get sick from chickens, but it's possible. The subdistrict officials told us in detail how it could happen. I hope it's not going to happen here," said the mother of one.

Nyoman Mardi, who played an infected resident in the drill, said he believed it was necessary for him to monitor his environment and take the threat of bird flu seriously.

"We were told not to keep chickens in our backyard after a villager died (from bird flu) last year. But most people went back to their old ways in a few months after nothing happened," said the vendor.

Fifty-six-year-old Wayan Suwarni said the villagers started to learn simple preventive measures such as washing their hands and keeping their chickens in coops.

"I still keep chickens but I know it's a must to wash my hands after touching them. My chickens are not kept in a coop but I won't touch them if they look sick or they're dead," she said.

Indonesia runs airport bird flu drill​

http://economictimes.indiatimes.com...irport_bird_flu_drill/articleshow/2987526.cms

JAKARTA: Indonesian authorities on Sunday wrapped up a major three-day bird flu drill on the resort island of Bali with an exercise focused on passengers at the island's international airport.

In the simulation, departing passengers were made to pass a scanner that detects body temperature. Among the travellers were three undercover personnel who simulated having high fever but insisted on leaving on their flights.

Staff steered them to a clinic at the airport and when test results showed they might have bird flu infections, the three were sent to the main hospital in Denpasar.

Despite posters notifying the public of the exercise, some tourists appeared concerned by the operations, as all personnel involved in the operation were wearing face masks.

"We were a bit worried but then we saw the posters. It's fine, better be prepared," said Angela Foster, an Australian tourist who was to fly back home through the airport.

"It is important as part of our bird flu containment efforts. We do not want to export a disease," I Nyoman Kandun, the health ministry's director general for handling of infectious disease, told journalists at the airport.

The simulation was the last part of a national exercise practising how to contain the spread of a bird flu outbreak.

Indonesia is the nation worst hit by the bird flu so far, with 107 dead since the first human case appeared here in 2005.

Transmissions have so far been from bird to human but experts worry that the H5N1 virus that causes the disease could mutate and allow human-to-human transmission, leading to a pandemic.

Bird flu spreads to Indo-Bangladesh border​

http://www.ndtv.com/convergence/ndtv/story.aspx?id=NEWEN20080048037&ch=4/27/2008 8:28:00 AM

Bird flu has hit Tripura and has spread to Kamalpur in Dhalai district while Mohanpur and Bishalgarh near Agartala are already infected.

All three places are right on the Bangladesh border where there have several outbreaks of the disease.

''Unless the border is sealed, it is not possible to control the spread of the virus and it is hard to believe that there is no movement across the border. The border is too porous,'' said Mrinmoy Burman, assistant director of Animal Resource Development Department.

''The areas affected are all bordering Bangladesh. If Bangladesh doesn't take this up immediately, it will affect us very badly. There is fear psychosis now,'' said D C Das, SDM Sadar, Agartala.

Unless vigilance is improved on the border, the spread of the flu may soon become unstoppable.

Bird flu virus found in 3 dead swans in Akita​

http://www.japantoday.com/category/national/view/bird-flu-virus-found-in-3-dead-swans-in-akita

AKITA —

The avian influenza virus has been detected in three dead swans and one weakening one along Lake Towada in Kosaka, Akita Prefecture, the Akita prefectural government said Monday. The Akita government said it has asked the state to determine whether the virus belongs to the deadly H5N1 strain.

Local officials said they have yet to find a link between the virus and the deaths of the swans. The officials said they see a low possibility of the virus damaging human health as there have been no reports of many birds or animals dying in the northeastern Japan prefecture.

Bali airport in 'chaos' as flu pandemic drill ends​

http://www.thejakartapost.com/news/2008/04/28/bali-airport-039chaos039-flu-pandemic-drill-ends.html

It was not business as usual at Ngurah Rai International Airport in Denpasar, Bali, on Sunday morning.

Security was heightened throughout the airport, but this time it had nothing to do with terrorism, but was part of a simulation to test the country's response to an avian influenza pandemic.

With surgical masks and radios, airport security, police officers and local administration officials stopped vehicles outside the airport and asked drivers and passengers for IDs.

All were asked if they were residents of Dangin Tukadaya in Jembrana or if they had visited the village in the last two days. Vehicles coming from the village were sprayed with disinfectant and all passengers and drivers were told to report to a nearby tent for health checks.

Further checks were done inside the airport, including at the departure terminal where two thermal scanners were placed to screen all passengers.

Anyone with a temperature of 38 degrees Celsius or above and who showed symptoms of influenza or respiratory problems would not be allowed to leave, being sent instead to a field hospital for further examination.

There were sporadic commotions as people refused to comply with officials' orders to report to a nearby office where they would be questioned about their time in Bali -- checking if they had been to Dangin Tukadaya village or had contact with villagers there.

Complaints were mostly about fear of missing flights.

Japanese national Etsuko Fukuoka and her daughter Amari Fukuoka and Etsuko's friend Reiko Yamamoto said they were not allowed to enter the departure terminal because they were returning from Dangin Tukadaya village.

This "unusual business" was part of an avian influenza pandemic simulation, which previously took place at Dangin Tukadaya village, about a two-hour drive west of Denpasar.

The airport was the final venue for the three-day simulation, allowing officials the chance to see how an emergency could be handled at the international gateway.

The head of the airport's healthcare unit, Nur Hasan, said there were no delays or schedule adjustments at the airport as a result of the simulation, adding that airline associations had been invited to take part in the simulation.

"They (airlines) are very supportive and it doesn't take long so there is no need to delay the flights," he said.

Some (real) passengers who had to go through the checks, including filling out health status declarations, said they understood the need to organize the simulation.

Couple Ni Made Sutria and Joseph Headley said they were at first surprised to see the extra security checks, reminding them of the measures that were taken in the wake of the Bali terrorist bombings.

"I didn't know what was going on. I was in the backseat so they asked my driver to show his ID card.

"Now I know. It (the simulation) is a good thing, it's very important," said Headley.

Sunday's drill, funded by the Atlanta-based Centers for Disease Control and Prevention and involving at least 1,000 people, ended the three-day bird flu simulation.

Now the real work begins for the organizers -- the Health Ministry, local administrations and international agencies -- to put into practice all they learned from the event.

"Our pandemic simulation may not have been as perfectly executed as we planned, but it was not a disappointment. We're going to have similar activities of various scale this year.

"With this kind of preparation, we can assure the world that we're preparing ourselves to contain emerging signs of pandemic in Indonesia," said the chief executive of the National Commission of Avian Influenza and Pandemic Preparedness, Bayu Krisnamurthi, in a speech during the closing ceremony for the simulation.

Also speaking during the ceremony was the Health Ministry's director general for communicable diseases and environmental health, I Nyoman Kandun, who said this exercise showed the world that Indonesia did not want to "export any diseases and instead wanted to contain them at home".

Bird flu hits one more Vietnamese locality​

http://news.xinhuanet.com/english/2008-04/28/content_8066224.htm

HANOI, April 28 (Xinhua) -- Bird flu has recently hit Vietnam's northern Son La province, raising the total number of localities currently affected by the disease to three, according to local newspaper Young People reported Monday.

Specimens from 95 died chickens and ducks out of a flock of 135 fowls raised by a household in the province's Son La town were tested positive to bird flu virus strain H5N1, the paper quoted the country's Department of Animal Health as reporting.

The provincial veterinary agency has isolated the outbreak, and disinfected the affected farm to prevent the disease's spread.

Now, bird flu is hitting Son La, and Tien Giang province and Can Tho City in the southern region, said the department.

Bird flu outbreaks in Vietnam, starting in December 2003, have killed and led to the forced culling of dozens of millions of fowls in the country.

Japan confirms H5N1 bird flu strain in swans​

http://news.yahoo.com/s/nm/20080429/sc_nm/birdflu_japan_dc

TOKYO (Reuters) - Japan on Tuesday confirmed four swans found last week were infected with the H5N1 strain of bird flu.

It was the first case of bird flu in Japan since March 2007 when the highly virulent H5N1 strain was found in a wild bird in Kumamoto prefecture on Japan's southern Kyushu island.

The swans, three of which had died, were found on the shores of Lake Towada in northern Akita prefecture on April 21, the prefectural government said.

Inspectors had initially detected the H5 subtype of bird flu in the dead swans and conducted further tests, the local government said on Monday.

Japan has been stepping up checks of birds after a series of bird flu outbreaks in South Korea over the past month.

There are no chicken farms within a 10 kilometer (6 mile) radius of the area where the swans were found, and no unusual incidents were noted at other farms.

Local authorities plan to conduct on-site inspections on Wednesday and Thursday at 15 farms within a radius of 30 km (19 miles) of the site where the swans were found, the official said.

Earlier on Tuesday, South Korea reported a suspected bird flu outbreak at a chicken farm in Ulsan City which, if confirmed, would be the first in the southeast, as the country grapples with its worst outbreak of avian influenza.

South Korea previously confirmed 20 cases of the H5N1 strain in poultry in less than a month, despite having killed more than 5 million chickens and ducks, as the virus spreads at its fastest rate since the country reported its first case in 2003.

No human deaths from the disease have been reported in South Korea or Japan.

Nepal on bird flu alert, tests poultry on India border​

http://www.ynetnews.com/articles/0,7340,L-3537214,00.html

Nepal has issued a bird flu alert and is testing poultry along the border with India, where the virus rages despite the culling of tens of thousands of chickens since 2006, officials said.

Nepal, which has not reported any bird flu cases, banned the import of poultry from India in January. But it shares an open border with the Indian state of West Bengal which has reported repeated outbreaks of bird flu. "We are always alert, especially in the border areas which have been declared as high risk zones," Baikuntha Parajuli, chief of Nepal's animal health directorate said Tuesday. (Reuters)

Bird flu virus detected in Denmark​

http://news.xinhuanet.com/english/2008-04/29/content_8072723.htm

STOCKHOLM, April 28 (Xinhua) -- Bird flu virus has been detected on a farm in Denmark's central Fyn island, the country's veterinary department announced Monday.

Some 2,000 chickens on the farm in Stenstrup on the island will be culled Tuesday to contain the spread of the disease, the Danish Veterinary and Food Administration said in a statement .

Initial checks show that the virus detected is not the deadly H5N1 strain that has ravaged Southeast Asia over the past two years.

Denmark was earlier struck by avian influenza in 2006.

S Korea reports new case of suspected bird flu​

http://www.hindustantimes.com/Story...ine=New+case+of+suspected+bird+flu+in+S+Korea

South Korea on Tuesday reported a suspected bird flu outbreak at a chicken farm in Ulsan City, which if confirmed would be the first in the southeast, as the country grapples with its worst outbreak of avian influenza.

South Korea previously confirmed 20 cases of the H5N1 strain in poultry in less than one month, despite having killed more than 5 million chickens and ducks, as the virus spreads at its fastest rate since the country reported its first case in 2003.

No human deaths from the disease have been reported in the country.

On Tuesday, the Agriculture Ministry said a chicken farm in Ulsan, some 390 km (242 miles) southeast of Seoul, reported deaths of more than 100 chickens in a week and initial tests gave positive readings for the avian virus.

Seoul has stepped up the culling of birds in affected areas and launched an investigation into all of the country's 260 duck farms in a bid to prevent the spread of the virus.

South Korea had to kill 5.29 million birds during the first outbreak between late 2003 and early 2004. The second outbreak in 2006-2007 saw about half that number culled.

High Human Avian H7N2 Reassortant Levels in Ferret Noses​

http://www.recombinomics.com/News/04290801/H7N2_NY_Reassortant_Ferrets.html

Recombinomics Commentary 03:11
April 29, 2008

an lung viral titers of NY/107 were at least 10-fold higher than those of all other H7N2 viruses on day 3 p.i. and were significantly higher on day 6 p.i. (P < 0.03)

Both H7N7 viruses examined replicated to high titers in the nasal turbinates and lungs. NY/107 virus, but not Tky/VA virus, was found at a similarly high titer in the nasal turbinates.

It is noteworthy that despite the lack of substantial morbidity or mortality observed following infection of mice and ferrets with the North American viruses examined in this study, we observed efficient infection and replication within the respiratory tract in both animal models. Virus titers measured in the respiratory tract of ferrets were even higher than those observed following infection with human H3N2 viruses (40, 53). The isolation of NY/107 virus from tissues of the olfactory bulb of ferrets could be due to the proximity of the high virus titer attained in the nasal turbinates following i.n. inoculation with this virus and may not be an indicator of extrapulmonary spread, as a similar pattern of replication was also demonstrated with ferrets infected with a human H3N2 virus (53).

The above comments are from the paper, “Pathogenesis of Avian Influenza (H7) Virus Infection in Mice and Ferrets: Enhanced Virulence of Eurasian H7N7 Viruses Isolated from Humans,” which includes the isolate, A/New York/107/2003(H7N2), which is a reassortant with human flu genes (PB1, PA, MP, NS). The above comments describe the ability of the virus to cause respiratory disease and grow at high levels in ferret nasal passages, which were at levels higher than H3N2 seasonal flu. These data increase concerns that the virus can be efficiently transmitted human to human.

These properties may be enhanced by E627K in PB2. The PB2 sequence has not been released, but since the H7N2 virus has two human polymerases (PB1 and PA), it is likely that PB2 is also human, which would strongly suggest that the virus has E627K, which is in all human seasonal flu. E627K allows the virus to replicate more efficiently at lower temperatures, such as those found in a mammalian nose.

However, the paper, which was submitted in June, 2007 makes no mention of the fact that the avian isolates is a reassortant with 4 or 5 human genes, including at least two polymerase genes. The HA sequence was already known, because the isolate is in a phylogenetic tree in the paper, but it is curious that the PB2 E627K status isn’t mentioned, since it was discussed in relationship to the human H7N7 sequence from the fatal infection of a veterinarian, and its association with increase virulence in mice, which was the other model used in the paper.

The sequences were deposited at Genbank on March 24, 2008, so the timing of the sequencing remains unclear. However, since this is the first example of a human / avian reassortant in H7, it seems that it would have been mentioned in the above paper.

In any event, the presence of four or five human H3N2 genes in avian isolates is cause for concern. Detecting H7 in humans has been a challenge, so there may be more such reassortants in circulation in humans and birds. This circulation could lead to more interspecies interactions leading to additional exchanges of genetic information. The H5N1 PB2 in the vaccine resistant strain in Israel has a number of newly acquired human polymorphisms and HA has M230I encoded by sequences found in H5N1 as well as H7 isolates, which was reported in Egypt.

H7 has also been recently reported in North and South Korea, which may be related to Korea’s proximity to North America. H5N1 has been repeatedly detected in South Korea and Japan, including isolates linked to wild birds.

It is becoming increasingly clear that wild birds have an extensive distribution network which shuffles genes via reassortment and gene segment via recombination, creating increasing genetic diversity which will challenge vaccine efforts. Japan has announce a pre-pandemic plan and the US has recently order 38.5 million doses of vaccine directed against clade 2.2 (Qinghai strain), which is becoming increasingly widespread and likely cause a human infection of a soldier in South Korea.

The sequence of the H7N2 PB2 as well as reasons for the 4 ½ year delay in the release of the sequences from the reassortant would be useful.

Link to next weeks thread:

HEALTH - 4/30/08-5/6/08|Weekly Bird Flu Thread:Bird flu kills Indonesian, death toll now 108

http://www.timebomb2000.com/vb/showthread.php?t=286422