Oct 31, 2008

DNI Avian Influenza Daily Digest

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Intelink Avian Influenza Daily Digest

Avian Influenza Daily Digest

October 31, 2008 14:00 GMT

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Article Summaries ...

Regional Reporting and Surveillance

Indonesia: September 2008 Poultry update
10/30/08 Poultry Indonesia--[edited, see link for full text article]--In the past two and half years, Muhammadiyah has seen 12,000 members in 12,000 villages carry out bird flu campaigns across the country, Ahmad said.
Regional Reporting and Surveillance

Science and Technology

First steps in the design of a system to monitor vaccine effectiveness during seasonal and pandemic influenza in EU/EEA Member States.
10/08 Euro Surveillance--[Abstract]--Estimating influenza vaccine effectiveness (IVE) early in the season helps measuring the consequences of a mismatch between the vaccine and the circulating strain and guiding alternative or complementary interventions. The European Centre for Disease Prevention and Control is funding a project to develop pilot studies to monitor IVE in the Member States (MS) of the European Union and European Economic Area (EU/EEA) during seasonal and pandemic influenza. To identify key methodological and practical issues in developing protocols for pilot studies, we conducted a survey among EU/EEA MS, a literature review on IVE methods, and consultations of experts. The survey and literature review highlighted the variety of the data sources used to estimate IVE and the difficulty to interpret data on IVE, which varies with age, risk group, outcome specificity and virus-vaccine mismatch. We also found that negative and positive confounding can bias IVE. The experts consultations lead to the following recommendations: to measure IVE in the same population in various seasons; to control for positive/negative confounding (including pre- and post-influenza season IVE estimates); and to include laboratory confirmation as outcome in various study designs. In the 2008-9 influenza season, two cohort studies using general practitioners' databases and six case control studies will be piloted in EU/EEA MS and will adhere to the above recommendations. The pilot studies will be the basis for the development of robust methods to monitor IVE in EU/EEA MS.
AI Research

Neutralizing human monoclonal antibody against H5N1 influenza HA selected from a Fab-phage display library
10/08 Journal of Virology--[Abstract]--Identification of neutralizing antibodies with specificity away from the traditional mutation prone antigenic regions, against the conserved regions of hemagglutinin from H5N1 influenza virus has the potential to provide a therapeutic option which can be developed ahead of time in preparation for a possible pandemic due to H5N1 viruses. In this study, we used a combination of panning strategies against the hemagglutinin (HA) of several antigenic distinct H5N1 isolates to bias selection of Fab-phage from a naive human library away from the antigenic regions of HA, toward the more conserved portions of the protein. All of the identified Fab clones which showed binding to multiple antigenically distinct HA were converted to fully human IgG, and tested for their ability to neutralize the uptake of H5N1-virus like particles (VLP) into MDCK cells. Five of the antibodies which showed binding to the relatively conserved HA2 subunit of HA, exhibited neutralization of H5N1-VLP uptake in a dose dependant manner. The inhibitory effects of these five antibodies were similar to those observed with a previously described neutralizing antibody specific for the 140s antigenic loop present within HA1 and highlight the exciting possibility that these antibodies may be efficacious against multiple H5N1 strains.
AI Research

Peptide mimics of a conserved H5N1 avian influenza virus neutralization site
10/08 Journal of Biochemestry--[Abstract]--A panel of 52 murine monoclonal antibodies was found to recognize antigenic determinants that had been conserved among all major genetic subgroups of the H5N1 avian influenza virus prevalent since 1997. Approach. We screened a phage display library for peptides recognized by one such antibody (8H5). 8H5 specificity of reactive peptides was analyzed as they were presented as fusion proteins of hepatitis B core protein (HBc) and hepatitis E virus structural protein, p239, and related to that of native HA molecule according to the capacity of fusion proteins to compete for 8H5 binding with different strains of H5N1 virus and that of antisera generated against fusion proteins to bind native HA molecules and to inhibit hemagglutination and arrest infection by the virus. Result. Nine reactive peptides of different amino acid sequences were identified, 6 of which were also reactive with the antibody in association with HBc and 4, in association with p239. Binding occurred with dimeric form of the 4 p239 and one of the HBc fusion proteins, but not with the monomeric form. The HBc fusion proteins blocked 8H5 binding with 4 strains of H5N1 influenza virus. Mouse antisera generated against fusion proteins bound to HA molecules, but did not cause HAI or arrest HEV infection. Conclusion. Findings inferred that 8H5 recognizes discontinuous sites presented by secondary and possibly higher structural orders of the peptides in spatially favorable positions for binding with the antibody, and that the peptides partially mimic the native 8H5 epitopes on the H5N1 virus.
AI Research

Emergence of Amantadine-Resistant H3N2 Avian Influenza A Virus in South Korea
10/08 Journal of Clinical Microbiology--[Abstract]--We found a relatively high frequency of unique amantadine-resistant H3N2 and H9N2 avian influenza viruses (Val27Ile on M2 protein) isolated from live poultry markets in South Korea and confirmed that a Val27Ile single substitution in the M2 protein is enough to acquire the amantadine resistance phenotype by using reverse-genetically created human-avian reassortant viruses.
Science and Technology


Full Text of Articles follow ...


Regional Reporting and Surveillance

Indonesia: September 2008 Poultry update


10/30/08 Poultry Indonesia--[edited, see link for full text article]--In the past two and half years, Muhammadiyah has seen 12,000 members in 12,000 villages carry out bird flu campaigns across the country, Ahmad said.

Campaigners work to remove poultry from residential areas, train local residents to properly handle infected chickens by covering up and burying diseased fowl instead of dumping it in rivers, and promote regular use of disinfectants to kill the H5N1 virus.

Under the Muhammadiyah Team to Tackle Avian Influenza, the organization has also established a network of 7,000 "Avian Influenza Force" volunteer groups in nine provinces: Jakarta, North Sumatra, Lampung, Banten, West Java, Central Java, Yogyakarta, East Java and Bali. "Our approach is to make people believe there is nothing to be afraid of with bird flu, because it is preventable," Ahmad said.

However, he said, it was not easy to teach villagers about the epidemic, especially when it comes to changing their deep-rooted knowledge and behavior. "In many cases, villagers were confused about the difference between symptoms of bird flu and those of Newcastle disease (ND). So, when they found their H5N1-infected chickens died, they thought it was simply because of ND, resulting in improper burying and the spread of the virus," Ahmad said.

The government has said it cannot control the avian influenza epidemic on its own due to limited resources. "As the government can't walk alone in fighting bird flu, community groups can definitely act to bring bird flu campaigns closer to the public as they have members across the country," Health Ministry Director General for Disease Control and Environmental Sanitation, I Nyoman Kandun, said during the campaign.

He said Muhammadiyah, with some 30 millions members, could help the government prevent and control bird flu outbreaks across the country. "With 500 hospitals and health clinics, as well as 17,000 educational institutions across the country, Muhammadiyah can back the government's effort to fight the epidemic in remote areas," Kandun said.

Besides Muhammadiyah, professional and religious groups like the Indonesian Veterinarian Association and Muslim organization Nahdlatul Ulama have also been working with the government in fighting bird flu for the past few years, Kandun said.

THE number of poultry, mostly chickens, that died of bird flu in Purbalingga regency in the first half of 2008 has surpassed the 2007 total, the head of the local development planning agency said last month.
"Some 58,000 poultry died of bird flu in 2007, while more than 60,000 died during the first six month of this year," Heni Ruslanto said. "The poultry were confirmed to have died of bird flu."

Heni added people in the region had limited information about preventive health measures and how to handle bird flu cases. "Therefore, we are calling related institutes to pay attention to this problem," he said.

THE North Sumatra Health Office remains on "extraordinary occurrence" (KLB) alert status following the deaths of three people and the hospitalization of 13 others believed to have contracted bird flu.
Office head Chandra Syafei said his office had imposed KLB status because it had so far not received autopsy reports to determine the causes of deaths from the Health Ministry, including results on blood samples and bodily fluid from the patients from Air Batu district in Asahan regency. He personally learned that the patients' blood tests were negative for bird flu from the ministry's website, but remained wary due to the lack of an official report from the ministry.

"So far there has yet to be any report specifying whether the three victims in Asahan were positively or negatively infected with the bird flu virus. If the results are positive, we will have to monitor the area longer," Chandra said.

A number of health workers were still in Asahan to monitor the situation. "We are on full alert to monitor developments of a bird flu outbreak in Asahan. A team from the World Health Organization is still there to investigate the case," said Chandra.

He added that health officials were focusing on the three fatalities and the 13 current patients showing symptoms consistent with bird flu.

Authorities had disposed of 276 infected birds in Asahan and would continue to slay birds believed be infected with virus. Nearby Labuhan Ratu regency has killed 1,126 birds after seeing hundreds suddenly die in the past week.

Labuhan Batu Vice Regent Sudarwanto said the virus had affected the poultry population in six subdistricts of North Rantau: Padang Bulan, Cendana, Lobusona, Sirandorung, Ujung Bandar and Padang Matinggi. Sudarwanto said his office had taken several measures to prevent the spread of the disease, such as disposing of birds, conducting public awareness campaigns and using rapid testing. It has also set up posts in bird flu-prone areas. "We have so far carried out various anticipatory measures to curb the virus spread, and we urge people to remain alert," Sudarwanto said.

NEW Zealand has called on Indonesia to exempt from tariffs, 12 beef and dairy products exported to Indonesia. As compensation, they will provide assistance in technology transfer to guarantee the quality beef and dairy products. This can support Indonesia in meeting the demands for beef and milk supplies.
Agriculture Minister, Anton Apriyanto, has not approved the request because the compensation offered remains unclear. Indonesia had previously negotiated with New Zealand, and hoped that New Zealand will invest in Indonesia. The request for no tariffs for the 12 products is linked with the ASEAN-Australia-New Zealand Free Trade Agreement.

ANIMAL feed and processed chicken manufacturer PT Charoen Pokphand Indonesia Tbk more than doubled its first semester net profit from last year's, despite higher production costs and selling prices. The company, accumulated Rp 209.6 billion (US$22.8 million) net profit in the first semester of 2008, 120 percent higher than the Rp 95 billion profit in the same period last year and surpassing the entire year's profit of Rp 185.5 billion in 2007.
"We have a growing market and increasing prices. The whole industry is growing despite the fuel increase," the vice president of the company, Thomas Effendy, said.
The profit comes mainly from three types of product, all of which saw rising sales in terms of volume and price. Animal feed contributed 78 percent of sales, day-old chickens 13 percent and processed chicken meat 7.8 percent.
Sales volume of animal feed increased by 30 percent to 1.2 million tons since last year and the price rose by almost two-fifths to Rp 4.015 per kilogram.
Processed chicken meat became more popular, with sales volume tripling despite being three times more expensive than during the first half of last year. The demand for day-old chicken increased by 13 percent to 258 million chicks, with the price rising by 30 percent.
Thomas was confident the company would reach the Rp 12 trillion sales target and associated Rp 300 billion net profit target by the year end.
"The price of commodities, which are our raw materials, increased by around 40 percent. It cut the profit margin from 13.6 percent last year to 12.8 percent this year, but because the base price of sales is higher, we made higher net profits," he said.
The demand, he explained, was driven by the relatively cheaper price of chicken compared to other meats and stronger purchasing power of consumers outside Java, especially in regions with agriculture and mining. "Java is still the biggest market, but the Java share has declined from 65 percent of total sales last year, to 60 percent this year," he said.
The company managed to keep the rise in operating costs under 20 percent, despite rising fuel prices, because its seven feed mills in Java, Sumatra and Sulawesi do not rely on diesel fuel to generate electric power. Four of them are powered by coal, two by gas and only one is connected to the power grid.
Pokphand plans to develop more production outside of Java. A plant in Makassar, South Sulawesi is under construction, while another one in Lampung is being planned, with an initial budgeted investment cost of Rp 54 billion, plus an additional Rp 30 billion subsequently. Three-fifths of the funds would come from the company's own cash flow and the rest from Citibank loans, Thomas was quoted as saying, in a report from the Investment Coordinating Board.
It also received Rp 429 billion in loans from banks last month to cover its capital expenditure and to pay current obligations.

AI Research

First steps in the design of a system to monitor vaccine effectiveness during seasonal and pandemic influenza in EU/EEA Member States.


10/08 Euro Surveillance--[Abstract]--
Valenciano M, Ciancio B, Moren A; Influenza Vaccine Effectiveness Working Group.Collaborators (48)

Aavitsland P, Alexandrescu V, Bonmarin I, Buchholz U, Castilla J, Ciancio B, Cohen JM, Czumbel I, Dancona F, De Mateo S, Dijkstra F, Elliot A, Enstone J, Falcao JM, Fleming D, Gergonne B, Giesecke J, Larrauri A, Leino T, Levy Bruhl D, Linde A, Molbak K, Maltezou H, Mangtani P, Mazick A, McMenamin J, Mosnier A, Moren A, Nicoll A, O'Donnell J, O'Flanagan D, Oroszi B, Ortqvist A, Paget J, Pebody R, Puig-Barbera J, Quolin S, Rizzo C, Savulescu C, Shay DK, Simondon F, Uphoff H, Valenciano M, Van Der Sande M, Sbarcea C, Van Tam J, Weber T, Wuillaume F.
EpiConcept, Health Information System, Paris, France. m.valenciano@epiconcept.fr

Estimating influenza vaccine effectiveness (IVE) early in the season helps measuring the consequences of a mismatch between the vaccine and the circulating strain and guiding alternative or complementary interventions. The European Centre for Disease Prevention and Control is funding a project to develop pilot studies to monitor IVE in the Member States (MS) of the European Union and European Economic Area (EU/EEA) during seasonal and pandemic influenza. To identify key methodological and practical issues in developing protocols for pilot studies, we conducted a survey among EU/EEA MS, a literature review on IVE methods, and consultations of experts. The survey and literature review highlighted the variety of the data sources used to estimate IVE and the difficulty to interpret data on IVE, which varies with age, risk group, outcome specificity and virus-vaccine mismatch. We also found that negative and positive confounding can bias IVE. The experts consultations lead to the following recommendations: to measure IVE in the same population in various seasons; to control for positive/negative confounding (including pre- and post-influenza season IVE estimates); and to include laboratory confirmation as outcome in various study designs. In the 2008-9 influenza season, two cohort studies using general practitioners' databases and six case control studies will be piloted in EU/EEA MS and will adhere to the above recommendations. The pilot studies will be the basis for the development of robust methods to monitor IVE in EU/EEA MS.

AI Research

Neutralizing human monoclonal antibody against H5N1 influenza HA selected from a Fab-phage display library


10/08 Journal of Virology--[Abstract]--Identification of neutralizing antibodies with specificity away from the traditional mutation prone antigenic regions, against the conserved regions of hemagglutinin from H5N1 influenza virus has the potential to provide a therapeutic option which can be developed ahead of time in preparation for a possible pandemic due to H5N1 viruses. In this study, we used a combination of panning strategies against the hemagglutinin (HA) of several antigenic distinct H5N1 isolates to bias selection of Fab-phage from a naive human library away from the antigenic regions of HA, toward the more conserved portions of the protein. All of the identified Fab clones which showed binding to multiple antigenically distinct HA were converted to fully human IgG, and tested for their ability to neutralize the uptake of H5N1-virus like particles (VLP) into MDCK cells. Five of the antibodies which showed binding to the relatively conserved HA2 subunit of HA, exhibited neutralization of H5N1-VLP uptake in a dose dependant manner. The inhibitory effects of these five antibodies were similar to those observed with a previously described neutralizing antibody specific for the 140s antigenic loop present within HA1 and highlight the exciting possibility that these antibodies may be efficacious against multiple H5N1 strains.

AI Research

Peptide mimics of a conserved H5N1 avian influenza virus neutralization site


10/08 Journal of Biochemestry--
Wenxin Luo, Yingwei Chen, Mingqiao Wang, Yixin Chen, Zhenhua Zheng, Huijuan Song, Honglin chen, Yi Guan, Mun Hon Ng, Jun Zhang and Ningshao Xia

National Institute of Diagnostics and Vaccine Development in infectious diseases, Xiamen University, Xiamen, Fujian 361005, China.
Background. A panel of 52 murine monoclonal antibodies was found to recognize antigenic determinants that had been conserved among all major genetic subgroups of the H5N1 avian influenza virus prevalent since 1997. Approach. We screened a phage display library for peptides recognized by one such antibody (8H5). 8H5 specificity of reactive peptides was analyzed as they were presented as fusion proteins of hepatitis B core protein (HBc) and hepatitis E virus structural protein, p239, and related to that of native HA molecule according to the capacity of fusion proteins to compete for 8H5 binding with different strains of H5N1 virus and that of antisera generated against fusion proteins to bind native HA molecules and to inhibit hemagglutination and arrest infection by the virus. Result. Nine reactive peptides of different amino acid sequences were identified, 6 of which were also reactive with the antibody in association with HBc and 4, in association with p239. Binding occurred with dimeric form of the 4 p239 and one of the HBc fusion proteins, but not with the monomeric form. The HBc fusion proteins blocked 8H5 binding with 4 strains of H5N1 influenza virus. Mouse antisera generated against fusion proteins bound to HA molecules, but did not cause HAI or arrest HEV infection. Conclusion. Findings inferred that 8H5 recognizes discontinuous sites presented by secondary and possibly higher structural orders of the peptides in spatially favorable positions for binding with the antibody, and that the peptides partially mimic the native 8H5 epitopes on the H5N1 virus.

Science and Technology

Emergence of Amantadine-Resistant H3N2 Avian Influenza A Virus in South Korea


10/08 Journal of Clinical Microbiology--[Abstract]--College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong Heungduk-Ku, Cheongju 361-763, Republic of Korea

Received 25 July 2008/ Returned for modification 7 August 2008/ Accepted 25 August 2008

We found a relatively high frequency of unique amantadine-resistant H3N2 and H9N2 avian influenza viruses (Val27Ile on M2 protein) isolated from live poultry markets in South Korea and confirmed that a Val27Ile single substitution in the M2 protein is enough to acquire the amantadine resistance phenotype by using reverse-genetically created human-avian reassortant viruses.

* Corresponding author. Mailing address: College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong Heungduk-Ku, Cheongju 361-763, Republic of Korea. Phone: 82-43-261-3384. Fax: 82-43-272-1603. E-mail: choiki55@chungbuk.ac.kr

UNCLASSIFIED