EINet Alert ~ Apr 25, 2008

2008
China / 3 (3)
Egypt / 7 (3)
Indonesia / 15 (12)
Viet Nam / 5 (5)
Total / 30 (23)

2007
Cambodia / 1 (1)
China / 5 (3)
Egypt / 25 (9)
Indonesia / 42 (37)
Laos / 2 (2)
Myanmar / 1 (0)
Nigeria / 1 (1)
Pakistan / 3 (1)
Viet Nam 8 (5)
Total / 88 (59)

2006
Azerbaijan / 8 (5)
Cambodia / 2 (2)
China / 13 (8)
Djibouti / 1 (0)
Egypt / 18 (10)
Indonesia / 55(45)
Iraq / 3 (2)
Thailand / 3 (3)
Turkey / 12 (4)
Total / 115 (79)

2005
Cambodia / 4 (4)
China / 8 (5)
Indonesia / 20 (13)
Thailand / 5 (2)
Viet Nam / 61 (19)
Total / 98 (43)

2004
Thailand / 17 (12)
Viet Nam / 29 (20)
Total / 46 (32)

2003
China / 1 (1)
Viet Nam / 3 (3)
Total / 4 (4)

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 381(240).
(WHO 4.17.08 http://www.who.int/csr/disease/avian_influenza/en/index.html )

Avian influenza age distribution data from WHO/WPRO: http://www.wpro.who.int/sites/csr/data/data_Graphs.htm.
(WHO/WPRO 4.17.08)

WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 4.17.08): http://gamapserver.who.int/mapLibrary/

WHO’s timeline of important H5N1-related events (last updated 4.11.08): http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html

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"Bird flu has been confirmed for the second time in Tripura," Kartick Debbarma, a senior animal resources official said in Agartala, Tripura's capital. "It is the H5N1 strain."

The remote northeastern state borders Bangladesh, where the virus has affected more than half the country’s districts. In India, the virus resurfaced in the eastern state of West Bengal in January 2008, forcing authorities to cull more than four million birds. Since then the virus has flared up intermittently, hitting poultry sales in the region. Many states banned poultry products, pulling down prices sharply and prompting farmers to cut production. The World Health Organization (WHO) described the January 2008 outbreak in West Bengal as the worst ever in India. Officials in Tripura said they were holding meetings and drawing up their strategy to contain the disease, which has hit Mohanpur, a town just 20 km (12 miles) west of Agartala.
(ProMED 4.23.08)

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India (Guwahati): Officials blame outbreak on Bangladesh, many experts disagree
Authorities battling an outbreak of bird flu in poultry in Tripura blamed Bangladesh for the spread on 24 Apr 2008, 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 this month after it was hit by the H5N1 strain. "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 the virus has affected more than half the country’s districts.

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

But many people disagreed. For days, while hundreds of birds mysteriously died in remote villages, state authorities largely ignored complaints, 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 said. "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. They sat on our report and did nothing."

Local politicians also voiced 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 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.
(Reuters 4.24.08)

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India (Kolkata): Response to H5N1 avian influenza outbreaks threatens country chicken
The indiscriminate culling of country chickens in the wake of the bird flu outbreak in the state might soon lead to their disappearance or even extinction, warn scientists and experts. Their number has already dwindled alarmingly and their sales have gone down to just 15 percent of the total number of chickens sold in the state. More than one lakh (100,000) country chickens have so far been culled at Birbhum, South Dinajpur and Murshidabad.

The killing of chickens threatens to destroy their gene bank in India, experts said.

"There are 17 varieties of country chickens in India. From them, thousands of new breeds can be developed that would be better than broiler chickens. The way they are being culled, we run the risk of wiping out a few varieties. Even if that doesn’t happen immediately, it is a possibility since birds are being culled due to flu outbreaks almost every year," said Barun Roy of West Bengal University of Animal and Fisheries Sciences, a member of the expert team that supervised culling in Rampurhat.

Experts also pointed out that the culling has affected rearing chicken in the backyard — the only source of country chickens. Farmers have started backing away fearing losses. While the sale of chickens dropped by 30 percent following the flu scare in 2007, this time they have plummeted by over 60 percent. Every day, the poultry industry in Bengal is losing the equivalent of 70 million rupees.

"While the organized farms are in a better position to recover, the country chicken farmers have to just give up the trade. So, every time flu strikes, country chickens are pushed a step towards extinction," explained Roy.

Broiler chickens sold by the farms have been the beneficiaries. But in taste and nutrition, they are still way behind the indigenous varieties, said experts.

"Broiler strains were imported from United States, United Kingdom, Canada, and other countries. They grow faster and are easier to rear. But we need to develop our own gene bank since the strain import has been stopped," said a scientist.

Gene sequencing of the H5N1 virus could have prevented the culling.

"Flu outbreaks have become regular during the last eight years. The authorities could have done the sequencing earlier to find out if the gene is likely to affect humans," said Roy. Farms admitted that country chickens face a bleak future. "Very few make it to Kolkata. Another flu outbreak might see them disappear altogether," said Abhijit Kanjilal, manager, Shanti Fortune Hatcheries.
(ProMED 4.22.08)

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Indonesia (Jakarta): Government wants access to vaccines, not money
Indonesia does not want money for its samples of a bird flu virus, a health official said on 23 Apr 2008 after the United States 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 said 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 might have been poor communication on both sides.

"There are many types of benefit programs that can be discussed," he said, noting that the United States 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 2007 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."

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 15 Apr 2008 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.
(Associated Press 4.24.08)

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Japan: Pre-pandemic vaccine trial approved
The Ministry of Health, Labor and Welfare in Japan (MHLW) announced on 16 Apr 2008 that it would organize a clinical trial for pre-pandemic influenza vaccines against H5N1 on 6,400 volunteers to further make sure its safety and effectiveness which had already been tested for a smaller number and been approved by the national regulatory authority. The 6,400 volunteers will include quarantine officers, health care workers and emergency response workers. MHLW will consider expanding pre-pandemic vaccination to wider prioritized targets (up to 10 million) if the trial proves its safety and effectiveness. It would also consider increasing its stock of pre-pandemic vaccines. In the meantime, MHLW is always endeavoring to improve the safety and effectiveness of vaccines and their manufacturing process, including introducing cell-culture-based vaccines to increase the speed of their production.
(ProMED 4.18.08)

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South Korea (North Jeolla): Economy confirms fresh H5N1 avian influenza outbreak in poultry
South Korea's Farm Ministry reported on 19 Apr 2008 a new outbreak of bird flu at a chicken farm in the southwest, taking the total confirmed cases to 16 in poultry in just over two weeks. A ministry official said test results were confirmed positive for the H5N1 strain of the virus at a farm in Jeongeup, North Jeolla province, an area that saw an outbreak earlier in April 2008. It was one of three new suspected cases authorities said on 18 Apr 2008 that they were investigating, as the worst outbreak in four years spread despite massive culling. Agricultural ministry officials said on 21 Apr 2008 that as many as 5.32 million birds will be culled, the largest such operation in the country's history of battling the disease. South Korea has already culled 3.7 million chickens and ducks. No human deaths from the disease have been reported so far from the country.
(ProMED 4.21.08 & CIDRAP 4.21.08)

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Steiger, who accompanied Leavitt on the tour, said the NAMRU-2 lab has functioned in Indonesia for several years. Like other Department of Defense labs in foreign nations, NAMRU-2 originally focused on investigating diseases affecting US troops stationed abroad but has grown into a larger mission, he said.

"Over time, the labs have evolved into collaborative public health assets, often in consultation with the World Health Organization (WHO) and host governments," he said.

The NAMRU-2 lab is situated near other government buildings in Jakarta and has been integrated into the country's health system, Steiger added. The lab has connections to several private and public hospitals in Indonesia and has played a key role in tracking pathogens in the country. However, Indonesia's health minister recently prohibited all tissue samples — not just those containing H5N1 influenza viruses — from being sent to NAMRU-2, he said.

Leavitt asked Steiger and Ambassador John Lange, the State Department's special representative for avian and pandemic influenza, to spend the next two months working on a solution to the virus-sharing issue. He said a small contingent of the WHO's virus-sharing working group met in early April 2008 and that the larger group's next formal meeting is in November.

In Singapore, Leavitt visited the health ministry and spent time at the Regional Emerging Diseases Intervention (REDI) Center, a joint venture of the United States and Singapore that opened in 2004 to serve as an early warning and research center for infectious diseases in Asia. Steiger said the REDI Center shares a building with other research institutes, which fosters collaboration. For example, he said a trilateral project between Singapore, Indonesia, and the United States is focusing on the H5N1 outbreaks in Tangerang, a suburb of Jakarta that has been a hot spot for human cases.

"This is very much a regional effort that leverages Singapore's technical expertise with avian influenza," he said.

In Vietnam, Leavitt had similar talks with health and agriculture officials, Steiger said. One of the topics was US support of Vietnam's human H5N1 vaccine programs. These include a project at the National Institute of Hygiene and Epidemiology in Hanoi that is currently in phase one clinical trials and a smaller vaccine research project based in Nha Trang in southern Vietnam.
(CIDRAP 4.22.08)

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• UN: http://www.un-influenza.org/ : UNDP recently launched a new Web site for information on fund management and administrative services and includes the website of the Central Fund for Influenza Action. This site also includes a list of useful links to governments, international agencies, NGOs, and scientific organizations.
• WHO: http://www.who.int/csr/disease/avian_influenza/en/index.html The Influenza Virus Tracking System is now live and can be accessed by the public at: www.who.int/fluvirus_tracker .
• UN FAO: http://www.fao.org/avianflu/documents/key_ai/key_book_preface.htm Read the first installment of a major new and wide-ranging overview of avian influenza that has just been released by FAO.
• OIE: http://www.oie.int/eng/info_ev/en_AI_avianinfluenza.htm . Link to the Communication Portal gives latest facts, updates, and timeline.
• US CDC: http://www.cdc.gov/flu/avian/index.htm . View weekly US Flu Activity Report at: http://www.cdc.gov/flu/whatsnew.htm. >The US government’s Web site for pandemic/avian flu: http://www.pandemicflu.gov/ . Download the Business Pandemic Influenza Planning Checklist, developed by HSS and CDC, at: http://www.pandemicflu.gov/plan/businesschecklist.html .
• Health Canada: information on pandemic influenza: http://www.influenza.gc.ca/index_e.html .
• CIDRAP: http://www.cidrap.umn.edu/ See Pandemic preparedness tools: Find more than 130 peer-reviewed practices from 22 states and 33 counties aimed at furthering pandemic preparedness.
• PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm Link to National Influenza Centers in PAHO member states.
• US Geological Survey, National Wildlife Health Center Avian Influenza Information: http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp Read about the latest news on H5N1 in wild birds.

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Summary
Highly pathogenic H5N1 influenza A viruses have spread relentlessly across the globe since 2003, and they are associated with widespread death in poultry, substantial economic loss to farmers, and reported infections of more than 300 people with a mortality rate of 60%. The high pathogenicity of H5N1 influenza viruses and their capacity for transmission from birds to human beings has raised worldwide concern about an impending human influenza pandemic similar to the notorious H1N1 Spanish influenza of 1918. Since many aspects of H5N1 influenza research are rapidly evolving, we aim in this seminar to provide an up-to-date discussion on select topics of interest to influenza clinicians and researchers. We summarize the clinical features and diagnosis of infection and present therapeutic options for H5N1 infection of people. We also discuss ideas relating to virus transmission, host restriction, and pathogenesis. Finally, we discuss vaccine development in view of the probable importance of vaccination in pandemic control.
(CIDRAP 4.25.08)

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Children, avian influenza H5N1 and preparing for the next pandemic
Nicoll A. Archives of Disease in Childhood 2008;93:433-438
http://adc.bmj.com/cgi/content/abstract/93/5/433

Abstract
The emergence of avian influenza A/H5N1 viruses has driven pandemic preparations to become government priorities across Europe. To date these viruses have remained poorly adapted to humans and the risk of a pandemic based on H5N1 is unquantifiable. However, the risk of a future pandemic is 100%. Preparations are essential and without these many avoidable deaths will occur. Children will be affected at least as much as adults and may play an important role in amplifying transmission. Pharmacological and public health interventions focused on children will save lives through suggested community measures such as pre-emptive closures of schools, and need to be considered carefully, balancing benefits against negative consequences. Child health services will be hugely stressed by any pandemic but also have the potential to save many lives. The challenge will be to deliver core services in the face of major staff illnesses. Detailed local business continuity planning will be essential.
(CIDRAP 4.18.08)

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Identification of oxidative stress and toll-like receptor 4 signaling as a key pathway of acute lung injury
Imai Y, et al. Cell. 2008;133:235-249
http://www.cell.com/content/article/abstract?uid=PIIS0092867408003401

Summary
Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that toll-like receptor 4 (TLR4) mutant mice display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI.
(CIDRAP 4.18.08)

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Hydrophobic inactivation of influenza viruses confers preservation of viral structure with enhanced immunogenicity
Raviv Y, et al. Journal of Virology. 2008;82(9):4612-4619
http://jvi.asm.org/cgi/content/abstract/82/9/4612

Abstract
The use of inactivated influenza virus for the development of vaccines with broad heterosubtypic protection requires selective inactivation techniques that eliminate viral infectivity while preserving structural integrity. Here we tested if a hydrophobic inactivation approach reported for retroviruses could be applied to the influenza virus. By this approach, the transmembrane domains of viral envelope proteins are selectively targeted by the hydrophobic photoactivatable compound 1,5-iodonaphthyl-azide (INA). This probe partitions into the lipid bilayer of the viral envelope and upon far UV irradiation reacts selectively with membrane-embedded domains of proteins and lipids while the protein domains that localize outside the bilayer remain unaffected. INA treatment of influenza virus blocked infection in a dose-dependent manner without disrupting the virion or affecting neuraminidase activity. Moreover, the virus maintained the full activity in inducing pH-dependent lipid mixing, but pH-dependent redistribution of viral envelope proteins into the target cell membrane was completely blocked. These results indicate that INA selectively blocks fusion of the virus with the target cell membrane at the pore formation and expansion step. Using a murine model of influenza virus infection, INA-inactivated influenza virus induced potent anti-influenza virus serum antibody and T-cell responses, similar to live virus immunization, and protected against heterosubtypic challenge. INA treatment of influenza A virus produced a virus that is noninfectious, intact, and fully maintains the functional activity associated with the ectodomains of its two major envelope proteins, neuraminidase and hemagglutinin. When used as a vaccine given intranasally (i.n.), INA-inactivated influenza virus induced immune responses similar to live virus infection.
(CIDRAP 4.17.08)

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Comparative efficacy of neutralizing antibodies elicited by recombinant hemagglutinin proteins from avian H5N1 influenza virus
Wei CJ, et al. Journal of Virology. Published online ahead of print on 16 April 2008
http://jvi.asm.org/cgi/content/abstract/JVI.00187-08v1

Abstract
Although human transmission of avian H5N1 virus remains low, the prevalence of this highly pathogenic infection in avian species underscores the need for a preventive vaccine that can be made without eggs. Here, we systematically analyze various forms of recombinant HA protein for their potential efficacy as vaccines. Monomeric, trimeric, and oligomeric H5N1 HA proteins were expressed and purified from either insect or mammalian cells. The immunogenicity of different recombinant HA proteins was evaluated by measuring the neutralizing antibody response. Neutralizing antibodies to H5N1 HA were readily generated in mice immunized with the recombinant HA proteins, but varied in potency depending on their multimeric nature and cell source. Among the HA proteins, a high-molecular-weight oligomer elicited the strongest antibody response, followed by the trimer; the monomer showed minimal efficacy. The co-expression of another viral surface protein, neuraminidase, did not affect the immunogenicity of the HA oligomer, as expected from the immunogenicity of trimers produced from insect cells. As anticipated, HA expressed in mammalian cells without NA retained the terminal sialic acid residues and failed to bind 2,3-linked sialic acid receptors. Together these results suggest that recombinant HA proteins as individual or oligomeric trimers can elicit potent neutralizing antibody responses to avian H5N1 influenza viruses.
(CIDRAP 4.16.08)

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Our upcoming videoconference will be held in late May 2008. It will take place during the evening hours of 29 May in the Americas and in the morning hours of 30 May in Asia, for approximately 5 hours. Our objective is to describe how private and public sectors in the APEC region can cooperate and work effectively to prepare for and respond to an influenza pandemic.

Through this videoconference, we hope to promote regional information sharing and collaboration to enhance pandemic preparedness. In order to improve preparedness regionally, it is vital to understand how each economy in the region is undertaking this task. In this process, EINet will:

1. Bring together economies in a dynamic, real-time discussion on preparedness through the collaboration of the health and the business/trade sectors, with a focus on critical systems continuity.
2. Share specific examples of current practices — e.g. scenario exercises, communication drills and policy evaluation.
3. Use innovative technologies (e.g. Access Grid) for real-time, virtual interchange, enhancing their utility for future collaboration and response in the event of a pandemic.

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Pandemic Planning for Academic Institutions (Webcast)
http://ualbanycphp.org/GRS/eventpast.cfm?id=101

This program is co-sponsored by the Upper Midwest Center for Public Health Preparedness, and features Elizabeth Hosmanek, who currently serves as facilitator for the University of Iowa Pandemic Influenza Task Force and also played an instrumental role in the ASPH/CDC Pandemic Influenza Collaborative Group, which developed the forthcoming "Pandemic Influenza Preparedness Resource Kit for Academic Institutions." She will share information and resources available to academic institutions to support their pandemic influenza preparedness efforts, and lessons learned during the development and execution of the April 2007 tabletop exercise designed to prompt rapid decision-making and test the current Pandemic Plan at the University of Iowa.
(RGPHP 4.18.08)

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AI.COMMuniqué: Preparedness for Influenza Pandemic
AI.COMMuniqué is a monthly series of notes on avian influenza communication and the unique challenges and issues it presents. The series is intended to serve as a reliable source on avian influenza communication issues, as well as to spark discussion and thinking for people who are actively involved or interested in avian influenza work. If you would like to subscribe to our newsletter, please contact avianflu@comminit.com.

Please see The Communication Initiative's Avian Influenza Theme Site at: http://www.comminit.com/avianinfluenza.html for a full display of avian influenza communication knowledge in support of your work. Also see the Academy for Educational Development's Avian Influenza website at http://www.avianflu.aed.org.

AI.COMMuniqué is very interested in your knowledge and experience in avian influenza communication - your projects and programs, strategic thinking, support materials, and any other relevant documentation. Please contact avianflu@comminit.com with any input.

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