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EINet Alert ~ Dec 15, 2006


*****A free service of the APEC Emerging Infections Network*****
APEC EINet News Briefs offers the latest news, journal articles, and notifications for emerging infections affecting the APEC member economies. It was created to foster transparency, communication, and collaboration in emerging infectious diseases among health professionals, international business and commerce leaders, and policy makers in the Asia-Pacific region.
In this edition:
- Global: Cumulative number of human cases of avian influenza A/(H5N1)
- Global: Donors pledge $475 million for global avian flu fight
- Global: Agencies to seek accord on naming of H5N1 strains
- South Korea: Report of third avian influenza incident confirmed
- Indonesia: Coordinated donor funding plays major role in fight against bird flu
- Viet Nam: Donor funding still needed to ensure long-term success
- Viet Nam: Expert says late antiviral treatment may still help H5N1 patients
- Australia (Canberra): Update on influenza outbreak in an aged care facility
- Africa: Bamako avian influenza meeting: a successful outcome

1. Updates
- Avian/Pandemic influenza updates
- Seasonal Influenza

2. Articles
- Hajj and the risk of influenza; a threat that can no longer be ignored
- Validation of influenza and pneumococcal vaccine status in adults based on self-report
- Effectiveness of an influenza vaccine programme for care home staff to prevent death, morbidity, and health service use among residents: cluster randomised controlled trial
- Questioning Aerosol Transmission of Influenza
- Comparison of the influenza virus-specific effector and memory B-cell responses to immunization of children and adults with live attenuated or inactivated influenza virus vaccine
- Newcastle disease virus-based live attenuated vaccine completely protects chickens and mice from lethal challenge of homologous and heterologous H5N1 avian influenza viruses
- Prevention of antigenically drifted influenza by inactivated and live attenuated vaccines
- Effectiveness of School-Based Influenza Vaccination
- Antiviral agents active against influenza A viruses
- Influenza vaccination: The paediatric perspective
- Influenza vaccination coverage among children aged 6--23 months--six immunization information system sentinel sites, United States, 2005-06 influenza season
- Lower clinical effectiveness of Oseltamivir against influenza B contrasted with influenza A infection in children
- Ready or Not? Protecting the Public's Health from Disease, Disasters, and Bioterrorism, 2006
- IOM: Modeling Community Containment for Pandemic Influenza: A Letter Report
- The Canadian Pandemic Influenza Plan for the Health Sector

3. Notifications
- OIE, FAO and IZSVe Scientific Conference on Vaccination
- Paris Anti-Avian Influenza 2007 Conference


Global
Global: Cumulative number of human cases of avian influenza A/(H5N1)
Economy / Cases (Deaths)

2003
Viet Nam / 3 (3)
Total / 3 (3)

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

2005
Cambodia / 4 (4)
China / 8 (5)
Indonesia / 17 (11)
Thailand / 5 (2)
Viet Nam / 61 (19)
Total / 95 (41)

2006
Azerbaijan / 8 (5)
Cambodia / 2 (2)
China / 12 (8)
Djibouti / 1 (0)
Egypt / 15 (7)
Indonesia / 55 (45)
Iraq / 3 (2)
Thailand / 3 (3)
Turkey / 12 (4)
Total / 111 (76)

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 258 (154).
(WHO 11/29/06 http://www.who.int/csr/disease/avianinfluenza/en/ )

Avian influenza age & sex distribution data from WHO/WPRO: http://www.wpro.who.int/sites/csr/data/data_Graphs.htm.
(WHO/WPRO 11/29/06)

WHO's maps showing world's areas reporting confirmed cases of H5N1 avian influenza in humans, poultry and wild birds (last updated 12/13/06): http://gamapserver.who.int/mapLibrary/

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Global: Donors pledge $475 million for global avian flu fight
International donors pledged US $475 million to battle H5N1 avian influenza, according to the UN Food and Agriculture Organization (FAO). Dr. David Nabarro, the UN's avian and pandemic influenza coordinator, has been saying that $500 million to $750 million per year will be needed for the next 2 to 3 years. The pledged funds will add to about $600 million in loans and credit that is still in the pipeline from a Jan 2006 conference, where donors pledged a total of $1.9 billion. The US contributed $100 million of the pledged total, while Canada added $92.5 million. The European Union promised $88.2 million and Japan pledged $67 million. Other donors promised a total of $128.2 million.

FAO Assistant Director-General Alexander Muller urged donors to make Africa "a top priority for resources and technical assistance in the battle against avian influenza" and warned that "one weak link can lead to a domino effect, undoing all the good that we have achieved so far," the FAO said. Much of the money pledged would be earmarked for boosting veterinary, early warning, and reporting systems in Africa. FAO said it has received $66 million from donors and has agreements signed for another $25 million, with another $60 million in the pipeline. FAO has spent $10 million of its own funds to help battle avian flu.
(CIDRAP 12/8/06 http://www.cidrap.umn.edu/ )

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Global: Agencies to seek accord on naming of H5N1 strains
International health officials who met with Chinese health experts last week said the dispute over the "Fujian-like" strain of H5N1 avian influenza reflects confusion over names and vowed to seek an agreement on terminology for the various H5N1 subgroups. The meeting in Beijing came a few weeks after US and Hong Kong scientists reported that the Fujian-like strain had emerged as the predominant H5N1 strain in southern China in the past year and caused increased poultry outbreaks. Chinese authorities rejected the report, saying the strain did not exist as a distinct subgroup.

A postmeeting statement from WHO, UN Food and Agriculture Organization (FAO), and World Organization for Animal Health (OIE) affirmed the existence of the Fujian-like strain, but said it has been called several different names. Participants agreed that "a number of significant H5N1 virus groups have been identified from poultry and wild birds in China since 2004," the statement said. "One such identified group of viruses has been termed differently by several groups. Terms include the 'waterfowl clade', 'clade 2.3', and 'Fujian-like'." The statement also said, "It was agreed there is a need for a shared understanding and a common nomenclature for influenza A(H5N1) groups and that some of the recent confusion about the avian influenza situation in China resulted from multiple terms used to describe the same virus groups. "FAO/OIE/WHO will establish an international working group including Chinese experts to develop global consensus on terminology to be used when describing different influenza A(H5N1) virus groups." Reportedly, WHO's David Heymann said, "It's very important that naming of viruses is done in a way that doesn't stigmatize countries, that doesn't stigmatize regions and doesn't stigmatize individual people."

The FAO-OIE-WHO statement affirmed some aspects of the Hong Kong–US researchers' report, which was published by the Proceedings of the National Academy of Sciences. For example, the statement said the Fujian-like strain has grown more common in parts of southern China since 2005 and has been found in poultry in Laos and Malaysia this year. The statement also said, "This virus group has been documented to cause some human infection in 2005 and 2006 in China," as the Hong Kong–US researchers had said. But contrary to another possibility the researchers have suggested, "There is no evidence to date to link the emergence of this virus group with use of poultry influenza vaccination in China." The statement added, "China has recently strengthened poultry surveillance to include serological (antibody) and virus surveillance as well as surveillance for disease outbreaks". The FAO-OIE-WHO statement said there has been no evidence that the Fujian-like strain is more transmissible to humans than other H5N1 viruses and no evidence that it has sparked human-to-human transmission.
(CIDRAP 12/11/06 http://www.cidrap.umn.edu/ )

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Asia
South Korea: Report of third avian influenza incident confirmed
South Korea's agriculture ministry said 11 Dec 2006 it had found a third incident of highly pathogenic bird flu in North Cholla province south of Seoul. In Nov 2006, South Korea confirmed its first 2 outbreaks of the H5N1 strain in about 3 years, saying the virus had been found at 2 poultry farms close to each other in North Cholla province. The third case was discovered at a quail farm in the same province about 170 km south from Seoul, some 18 km from the original outbreak. "The case has been confirmed as the H5N1 strain of avian influenza," the ministry said, adding thousands of birds at the farm had died over the past 4 days. The fresh case emerged after South Korea had completed culling all 760 000 poultry near the 2 farms already discovered to have been infected with H5N1.
(Promed 12/11/06)

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Indonesia: Coordinated donor funding plays major role in fight against bird flu
To help Indonesia come to grips with the threat from bird flu, FAO is training government veterinarians and community animal health workers in the latest bird flu surveillance and response techniques. Called participatory disease surveillance and response training, the course enables animal health workers to become part detective, part diplomat. After a few basics in the classroom, they fan out to villages near the training centres to get to know the local people who raise chickens in their yards and on small suburban farms. The idea behind FAO’s training is that building trust leads to the discovery of more sick birds. Farmers are often afraid to admit there are sick birds for fear of losing a source of food and sometimes their livelihoods.

Dr Jeff Mariner who was training Indonesian vets for FAO, said: “Indonesia has a very large poultry population. There are about 300 million backyard poultry and what we found, in all the areas where we look, is that bird flu is fully endemic and basically you couldn’t get any more bird flu occurring in the country. . .” Mariner further explained, “Decision-making is decentralized so it is very difficult to set a policy at the national level. It’s not automatic that all the different districts and so forth will automatically pick up that policy.” With the problem so widespread, veterinary services are strained to their limits as they find infected birds and safely cull and disinfect village after village, while mounting surveillance operations that must continue indefinitely. Experts estimate that a full-scale vaccination programme alone would cost US$88 million in Indonesia just for 1 year. According to Dr John Weaver, FAO Senior Technical Advisor on avian influenza in Indonesia, “One of the problems we face is that a lot of the funding support that FAO and Indonesia are getting is short term. . .we are really looking at a situation in Indonesia that is not short term.”
(FAO 12/6/06 http://www.fao.org/newsroom/en/field/2006/1000455/index.html )

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Viet Nam: Donor funding still needed to ensure long-term success
Viet Nam decided early on to make the fight against bird flu priority number one. Because of that decision and the strong commitment that followed both from the government and from the international donor community, many veterinary experts consider Viet Nam one of the most successful countries when it comes to containing the H5N1 bird flu virus. Everywhere in Viet Nam people are on guard for signs of the disease. When it is found, culling follows almost immediately. These days it is rarely found, partly because the government has been systematically vaccinating poultry in much of the country. But vaccination only works if a high percentage of birds in a designated area are vaccinated repeatedly. Commune Veterinarian Hoang Trong Kien explained how it is done: “We vaccinated 100 percent of the chickens in this village, about 12 000, because a few days ago we had an information campaign about this and people signed letters of commitment promising to bring their chickens here so we can vaccinate all the poultry in a village.”

The secret of Viet Nam’s success has been strong government support for the battle against the highly pathogenic avian influenza virus strain H5N1, supported by coordinated donor contributions from the international community. While vaccination has been at the heart of the country’s strategy to control the disease, it is only one element in a comprehensive national strategy that includes culling infected and exposed birds, tight control on the movement of poultry, widespread surveillance and testing, improved hygiene measures and better laboratories. Donor funding has helped upgrade Viet Nam’s national laboratories to deal with the constant surveillance that continues across much of the country.
(FAO 12/6/06 http://www.fao.org/newsroom/en/field/2006/1000456/index.html )

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Viet Nam: Expert says late antiviral treatment may still help H5N1 patients
A virologist who has treated H5N1 avian influenza patients in Vietnam said the antiviral drug oseltamivir may help avian flu patients even when started later than 2 days after illness onset—generally considered too late. The standard advice about oseltamivir for treatment of seasonal flu is that it can shorten the illness if it is started within 2 days after the first symptoms. But Menno de Jong of the Hospital for Tropical Diseases in Ho Chi Minh City said the drug seemed to help 4 of his patients even though it was started later. De Jong said the assumption that oseltamivir works only if started within 48 hours may be true only for human flu viruses. He said the H5N1 virus is known to continue replicating in humans on the seventh or eighth day of symptoms. De Jong said, "If you can decrease the viral load [with drugs], you can have a good outcome. Even those who are treated late had good results." De Jong, who treated 17 H5N1 patients in 2004 and 2005, of whom 12 died, agreed with other experts that starting treatment early is still best.

WHO recommends oseltamivir as first-line treatment for H5N1 avian flu (with zanamivir [Relenza] as the second choice). The WHO guidelines do not say that treatment must be started within the first 2 days of illness to be effective. CDC says oseltamivir and zanamivir have been shown to reduce the duration of seasonal flu by about 1 day, provided treatment is begun within 48 hours of the first symptoms.
(CIDRAP 12/12/06 http://www.cidrap.umn.edu/ )

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Australia (Canberra): Update on influenza outbreak in an aged care facility
Between 11 Oct and 6 Dec 2006, 55 (42 percent) of 132 residents and 22 (12 percent) of 173 staff in a Canberra Aged Care Facility reported onset of symptoms including cough, fever and runny nose. Of these, 18 (32.7 percent) of affected residents and 1 (4.5 percent) affected staff member have had laboratory-confirmed Influenza A infection. Laboratory confirmation of Influenza A required either a PCR positive result, and/or a positive immuno-fluorescence (IF) result on a nose or throat swab, and/or a 4-fold rise in convalescent sera or a single titre of 64 or more specific for Influenza A. 35 of 55 (65 percent) affected residents and 10 (45 percent) of 22 affected staff were appropriately immunised with the 2006/2007 influenza vaccine prior to the outbreak. 6 (17 percent) of 35 vaccinated residents and 2 (20 percent) of the 10 vaccinated staff were subsequently laboratory confirmed with Influenza A. 9 residents and no staff have died during the outbreak period. The mean age at death is 88 years, median 91 (range 75 to 100 years). 2 residents who died were fully vaccinated for influenza with the 2006/2007 vaccine.

Vaccination clinics for staff and residents, enhanced infection control including exclusion of unvaccinated staff and visitors, isolation of cases, restricting resident transfers and admissions, cancellation of group activities and restrictions for staff on working in other nursing homes were key features of the outbreak control strategy. Oseltamivir prophylaxis was provided to asymptomatic staff and recommended to residents' medical practitioners. Treatment doses were prescribed for those who had respiratory symptoms.
(Promed 12/8/06)

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Africa
Africa: Bamako avian influenza meeting: a successful outcome
The fourth international conference on Avian influenza ended in Bamako (Mali) after 3 days of work. It was co-organized by the AU/IBAR (African Union/Interafrican bureau for agricultural resources), the European Union and the Government of Mali (with the technical support of the OIE), and focused on the needs of Africa for the fight against avian influenza. The importance of backyard poultry, the close proximity between poultry and people, the lack of resources and appropriate governance in compliance with OIE standards on the quality of the veterinary services as well as the lack of proper compensation mechanisms make the efforts for the prevention and the control of avian influenza in Africa particularly difficult.

In this context, the ALive Platform, which has been developed by the World Bank together with its partners including OIE, FAO and AU/IBAR, was identified as an optimal coordination mechanism not only for the fight against avian influenza but also for the prevention of future emerging and re-emerging animal diseases. The assessment of financial needs presented under the ALive platform for the prevention and control of avian influenza in animals was estimated to be of around 720,000,000 USD over 3 years.

Considering the complexity of setting up an avian influenza strategy particularly in Africa, the OIE in direct partnership with the AU/IBAR and the European Commission has established a virtual vaccine bank for Africa to rapidly assist countries who would have to vaccinate poultry populations at risk. While vaccination is not to be considered the only tool in the fight against avian influenza, it has proven to be effective in eradication campaigns in Africa and other regions of the world. The existence of such a bank allows for the immediate deployment from the provider to any area affected or at risk. Using this mechanism, several million doses of H5N1 vaccines have already been delivered to different African countries.

The conference also stressed the need for rapid diagnostic capabilities in supporting early detection and rapid response. The lack of sufficient diagnostic and reference laboratory capabilities in Africa further exacerbate that problem. To overcome this deficiency, the OIE presented its concept of “laboratory twinning” as an integrated concept to improve capacity building in veterinary laboratories in developing and in transition countries. The main objective of twinning is for existing OIE reference laboratories to assist directly laboratories under the OIE auspices to strengthen their diagnostic capability and scientific expertise and to eventually become OIE reference laboratories in their own right.

***Read the report: “Highly Pathogenic Avian Influenza in Africa: A Strategy and Proposed Programme to Limit Spread and Build Capacity for Epizootic Disease Control”. Available at: http://www.fao.org/docs/eims/upload//217651/hpai_strategy_africa_en.pdf
(FAO 12/6/06 http://www.fao.org/newsroom/en/news/2006/1000454/index.html )
(OIE 12/8/06 http://www.oie.int/eng/press/en_061208.htm )

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1. Updates
Avian/Pandemic influenza updates
- UN: http://influenza.un.org/. UN response to avian influenza and the pandemic threat; managed by UN System Influenza Coordination (UNSIC).
- WHO: http://www.who.int/csr/disease/avian_influenza/en/index.html.
- UN FAO: http://www.fao.org/ag/againfo/subjects/en/health/diseases-cards/special_avian.html. Documents from the International Conference on Avian Influenza in Mali are available.
- OIE: http://www.oie.int/eng/en_index.htm. Link to “Vaccination: a tool for the control of avian influenza”
- US CDC: http://www.cdc.gov/flu/avian/index.htm.
- The US government’s web site for pandemic/avian flu: http://www.pandemicflu.gov/. The public is also being asked to comment on vaccine prioritization.
- Health Canada: information on pandemic influenza: http://www.influenza.gc.ca/index_e.html. Check out the Canadian Pandemic Influenza Plan for the Health Sector. Information on avian influenza: http://www.hc-sc.gc.ca/dc-ma/avia/index_e.html.
- CIDRAP: http://www.cidrap.umn.edu/. Frequently updated news and journal articles.
- PAHO: http://www.paho.org/English/AD/DPC/CD/influenza.htm.
- US Geological Survey, National Wildlife Health Center Avian Influenza Information: http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp. Global updates.
(UN; WHO; FAO, OIE; CDC; Health Canada; CIDRAP; PAHO; USGS)

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Seasonal Influenza
Seasonal influenza activity in APEC economies
During weeks 45–46, overall influenza activity worldwide remained low. During this period, low influenza activity was reported in Canada (A and B), Hong Kong (H1, H3 and B), Japan (H1), Mexico (A and B), Russian (H1, H3 and B), and the United States (H1, H3 and B).
(WHO http://www.who.int/csr/disease/influenza/update/en/ 12/1/06)

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2. Articles
Hajj and the risk of influenza; a threat that can no longer be ignored
(references removed)
Gatrad AR et al. BMJ. 2006 Dec 9;333(7580):1182-3.
http://www.bmj.com/cgi/content/full/333/7580/1182.
“At the end of next month [January 2007], Saudi Arabia will again host the Hajj -- the largest annual gathering in the world -- which attracts more than 2 million pilgrims from almost every country on earth. . . From a public health perspective. . .such a gathering makes the possible rampant spread of the influenza virus and a global pandemic -- which many experts believe is overdue -- a potentially devastating prospect that has been inadequately prepared for. Recent work highlighting the high rates of infection and carriage of influenza virus in pilgrims returning from Mecca has emphasized the need for internationally agreed to strategies to minimize the risk of a pandemic. Such a strategy should center on ways to prevent transmission but must also include facilities for prompt diagnosis and treatment of infected individuals. No such comprehensive strategy currently exists. . . .mandatory influenza vaccination for all pilgrims should be considered. Mandatory meningococcal vaccination was introduced after a meningococcal epidemic among pilgrims and their contacts. As pilgrims already need to seek medical attention to obtain a meningococcal vaccination, this extra vaccination should not be too inconvenient and should be readily acceptable. . .Virus surveillance studies to identify newly emerging strains are needed urgently. Currently, Saudi Arabia is not among the 100 centers around the world where such structured surveillance studies are being undertaken.”

Details of vaccination requirements and travel advice for pilgrims intending to participate in the 2007 Hajj are contained in Eurosurveillance Weekly release: http://www.eurosurveillance.org/ew/2006/061130.asp#1. The congregation of so many people from different parts of the world in unavoidably overcrowded conditions within a confined area for a short period of time presents many public health challenges. The Saudi authorities take these challenges very seriously and continually review arrangements to improve the pilgrims' environment. 2006-2007 vaccination requirements and advice have been issued by the Saudi Ministry of Hajj: http://www.hajinformation.com/main/p3001.htm.
(Promed 12/9/06)

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Validation of influenza and pneumococcal vaccine status in adults based on self-report
Mangtani P, Shah A, Roberts JA. Epidemiol Infect. 2007 Jan;135(1):139-43. Epub 2006 Jun 2.
Abstract: “Self-report of polysaccharide pneumococcal vaccination is not thought reliable because of the increased risk of adverse events from inadvertent re-vaccination in elderly people. Some studies suggest a high sensitivity of self-report and hence a low risk of adverse events if vaccination is administered when medical records are unavailable. Self-report of pneumococcal and influenza vaccination in a sample of >64-year-olds in the United Kingdom was compared with information in their medical records. Self-report of pneumococcal vaccination, in contrast to some of the other studies had a low sensitivity. The findings here support the need for accurate knowledge of prior vaccine status before offering the polysaccharide pneumococcal vaccine. The study also confirms that self-report of influenza vaccination could be relied upon if rapid knowledge of uptake is required.”

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Effectiveness of an influenza vaccine programme for care home staff to prevent death, morbidity, and health service use among residents: cluster randomised controlled trial
Hayward AC et al. BMJ. 2006 Dec 1; [Epub ahead of print].
Abstract: “OBJECTIVE: To determine whether vaccination of care home staff against influenza indirectly protects residents. DESIGN: Pair matched cluster randomised controlled trial. SETTING: Large private chain of UK care homes during the winters of 2003-4 and 2004-5. PARTICIPANTS: Nursing home staff (n=1703) and residents (n=2604) in 44 care homes (22 intervention homes and 22 matched control homes). INTERVENTIONS: Vaccination offered to staff in intervention homes but not in control homes. MAIN OUTCOME MEASURES: The primary outcome was all cause mortality of residents. Secondary outcomes were influenza-like illness and health service use in residents. RESULTS: In 2003-4 vaccine coverage in full time staff was 48.2% (407/884) in intervention homes and 5.9% (51/859) in control homes. In 2004-5 uptake rates were 43.2% (365/844) and 3.5% (28/800). National influenza rates were substantially below average in 2004-5. In the 2003-4 period of influenza activity significant decreases were found in mortality of residents in intervention homes compared with control homes (rate difference -5.0 per 100 residents, 95% confidence interval -7.0 to -2.0) and in influenza-like illness (P=0.004), consultations with general practitioners for influenza-like illness (P=0.008), and admissions to hospital with influenza-like illness (P=0.009). No significant differences were found in 2004-5 or during periods of no influenza activity in 2003-4. CONCLUSIONS: Vaccinating care home staff against influenza can prevent deaths, health service use, and influenza-like illness in residents during periods of moderate influenza activity.”
http://www.bmj.com/cgi/content/abstract/bmj.39010.581354.55v1

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Questioning Aerosol Transmission of Influenza
Camille Lemieux et al. EID. Volume 13, Number 1–January 2007; references removed
“To the Editor: We have reviewed the literature cited in Tellier's Review of Aerosol Transmission of Influenza A Virus and disagree that it supports the conclusions drawn regarding the importance of aerosols in natural influenza infection. In certain cited studies, researchers recovered viable virus from artificially generated aerosols; this is not evidence that aerosol transmission leads to natural human infection. By standard definitions, the rarity of long-range infections supports the conclusion that effective aerosol transmission is absent in the natural state. The superior efficacy of inhaled versus intranasal zanamivir is referenced as support for the idea that the lower respiratory tract is the preferred site of influenza infection; however, 1 study cited is insufficiently powered, and the other 2 do not compare the intranasal and inhaled routes. The major site of deposition of inhaled zanamivir is the oropharynx (77.6%), not the lungs (13.2%). In another flawed study, study participants naturally infected with wild-type virus are compared with study participants experimentally infected with an attenuated strain.

In a review of such relevance, critical analysis of confounding factors is necessary. The Alaska Airlines outbreak is presented as proof of airborne influenza transmission; however, droplet/contact transmission remains plausible because passenger movement was not restricted and the index patient was seated in high-traffic area. In the Livermore Hospital study, serious confounders such as bed arrangements, number of influenza exposures, patient mix, and ventilation were not accounted for. We encourage readers of Teller's article to review the relevant primary literature. We believe that the only reasonable conclusion that can be drawn at this time is that aerosol transmission does not play a major role in natural influenza epidemiology. Whether aerosols play any role in the transmission of influenza is a question demanding an answer; it is clear that we do not yet have that answer.”
***Read also response by Raymond Tellier at: http://www.cdc.gov/ncidod/EID/13/1/173_174.htm

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Comparison of the influenza virus-specific effector and memory B-cell responses to immunization of children and adults with live attenuated or inactivated influenza virus vaccine
Sasaki S et al. J Virol. 2006 Oct 18; [Epub ahead of print]
Abstract: “Cellular immune responses to influenza virus infection and influenza vaccination have not been rigorously characterized. We quantified the effector and memory B cell responses in children and adults after administration of either live attenuated (LAIV) or inactivated (TIV) influenza vaccines and compared these to antibody responses. PBMC were collected at days 0, 7-12 and 27-42 after immunization of younger children (6 months - 4 years old), older children (5 to 9 years old) and adults. Influenza-specific effector IgA and IgG circulating antibody secreting cells (ASC) and stimulated memory B cells were detected using an ELISPOT assay. Circulating influenza-specific IgG and IgA ASC were detected 7-12 days after TIV and after LAIV immunization. 79% or more of adults and older children had demonstrable IgG ASC responses, while IgA ASC responses were detected in 29-53% of the subjects. The IgG ASC response rate to LAIV immunization in adults was significantly higher than the response rate measured by standard serum antibody assays (26.3% and 15.8% by neutralization and HAI assays respectively). IgG ASC and serum antibody responses were relatively low in the younger children compared to older children and adults. TIV, but not LAIV, significantly increased the percentage of circulating influenza-specific memory B cells detected at 27-42 days after immunization in children and adults. In conclusion, although both influenza vaccines are effective, we found significant differences in the B cell and antibody responses elicited after LAIV or TIV immunization in adults and older children and between young children and older age groups.”
http://jvi.asm.org/cgi/content/abstract/81/1/215

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Newcastle disease virus-based live attenuated vaccine completely protects chickens and mice from lethal challenge of homologous and heterologous H5N1 avian influenza viruses
Jinying Ge et al. J Virol. 2006 Oct 18; [Epub ahead of print]
Abstract: “H5N1 highly pathogenic avian influenza virus (HPAIV) has continued to spread and poses a significant threat to both animal and human health. Current influenza vaccine strategies have limitations that prevent their effective use for widespread inoculation of animals in the field. Vaccine strains of Newcastle disease virus (NDV), however, have been used successfully to easily vaccinate large numbers of animals. In this study, we used reverse genetics to construct a NDV that expressed an H5 subtype avian influenza virus (AIV) hemagglutinin (HA). Both a wild-type and a mutated HA open reading frame (ORF) from the HPAIV wild bird isolate, A/Bar-headed goose/Qinghai/3/2005 (H5N1), were inserted into the intergenic region between the P and M genes of the LaSota NDV vaccine strain. The recombinant viruses stably expressing the wild-type and mutant HA genes were found to be innocuous after intracerebral inoculation of 1-day-old chickens. A single dose of the recombinant viruses in chickens induced both NDV- and AIV H5-specific antibodies and completely protected chickens from challenge with a lethal dose of both velogenic NDV and homologous and heterologous H5N1 HPAIV. In addition, BALB/c mice immunized with the recombinant NDV-based vaccine produced H5 AIV specific antibodies and were completely protected from homologous and heterologous lethal virus challenge. Our results indicate that recombinant NDV is suitable as a bivalent live attenuated vaccine against both NDV and AIV infection in poultry. The recombinant NDV vaccine may also have potential use in high-risk human individuals to control the pandemic spread of lethal avian influenza.”
http://jvi.asm.org/cgi/content/abstract/81/1/150

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Prevention of antigenically drifted influenza by inactivated and live attenuated vaccines
Suzanne E. Ohmit et al. NEJM. Volume 355:2513-2522. December 14, 2006. Number 24.
Abstract: “Background The efficacy of influenza vaccines may decline during years when the circulating viruses have antigenically drifted from those included in the vaccine. Methods We carried out a randomized, double-blind, placebo-controlled trial of inactivated and live attenuated influenza vaccines in healthy adults during the 2004–2005 influenza season and estimated both absolute and relative efficacies. Results A total of 1247 persons were vaccinated between October and December 2004. Influenza activity in Michigan began in January 2005 with the circulation of an antigenically drifted type A (H3N2) virus, the A/California/07/2004-like strain, and of type B viruses from two lineages. The absolute efficacy of the inactivated vaccine against both types of virus was 77% (95% confidence interval [CI], 37 to 92) as measured by isolating the virus in cell culture, 75% (95% CI, 42 to 90) as measured by either isolating the virus in cell culture or identifying it through real-time polymerase chain reaction, and 67% (95% CI, 16 to 87) as measured by either isolating the virus or observing a rise in the serum antibody titer. The absolute efficacies of the live attenuated vaccine were 57% (95% CI, –3 to 82), 48% (95% CI, –7 to 74), and 30% (95% CI, –57 to 67), respectively. The difference in efficacy between the two vaccines appeared to be related mainly to reduced protection of the live attenuated vaccine against type B viruses. Conclusions In the 2004–2005 season, in which most circulating viruses were dissimilar to those included in the vaccine, the inactivated vaccine was efficacious in preventing laboratory-confirmed symptomatic illnesses from influenza in healthy adults. The live attenuated vaccine also prevented influenza illnesses but was less efficacious.”
http://content.nejm.org/cgi/content/full/355/24/2513
***Read the editorial on this article: http://content.nejm.org/cgi/content/full/355/24/2586

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Effectiveness of School-Based Influenza Vaccination
James C. King et al. NEJM. Volume 355:2523-2532. December 14, 2006. Number 24
Abstract: “Background Vaccination of children in school is one strategy to reduce the spread of influenza in households and communities. Methods We identified 11 demographically similar clusters of elementary schools in four states, consisting of one school we assigned to participate in a vaccination program (intervention school) and one or two schools that did not participate (control schools). During a predicted week of peak influenza activity in each state, all households with children in intervention and control schools were surveyed regarding demographic characteristics, influenza vaccination, and outcomes of influenza-like illness during the previous 7 days. Results In all, 47% of students in intervention schools received live attenuated influenza vaccine. As compared with control-school households, intervention-school households had significantly fewer influenza-like symptoms and outcomes during the recall week. Paradoxically, intervention-school households (both children and adults) had higher rates of hospitalization per 100 persons than did control-school households. However, there was no difference in the overall hospitalization rates for children or adults in households with vaccinated children, as compared with those with unvaccinated children, regardless of study-group assignment. Rates of school absenteeism for any cause (based on school records) were not significantly different between intervention and control schools. Conclusions Most outcomes related to influenza-like illness were significantly lower in intervention-school households than in control-school households.”
http://content.nejm.org/cgi/content/full/355/24/2523
***Read the editorial on this article: http://content.nejm.org/cgi/content/full/355/24/2586

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Antiviral agents active against influenza A viruses
Erik De Clercq. Nature Reviews Drug Discovery 5, 1015-1025 (December 2006)
Abstract: “The recent outbreaks of avian influenza A (H5N1) virus, its expanding geographic distribution and its ability to transfer to humans and cause severe infection have raised serious concerns about the measures available to control an avian or human pandemic of influenza A. In anticipation of such a pandemic, several preventive and therapeutic strategies have been proposed, including the stockpiling of antiviral drugs, in particular the neuraminidase inhibitors oseltamivir (Tamiflu; Roche) and zanamivir (Relenza; GlaxoSmithKline). This article reviews agents that have been shown to have activity against influenza A viruses and discusses their therapeutic potential, and also describes emerging strategies for targeting these viruses.”
http://www.nature.com/nrd/journal/v5/n12/abs/nrd2175.html

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Influenza vaccination: The paediatric perspective
Ramet J, Weil-Olivier C, Sedlak W. Vaccine. 2007 Jan 15;25(5):780-7. Epub 2006 Oct 2.
Abstract: “Influenza in young children represents a significant problem to families and to society, as this population is most susceptible to developing complications and is also a major route of disease spread within communities. However, there is a paucity of European data for the burden of disease in children and the health benefits and cost-effectiveness of vaccination, leading to a lack of awareness by governments, authorities, healthcare professionals and parents. The experience in elderly individuals and the paediatric experience in the US may provide some guidance in developing studies that will provide evidence for the creation of guidelines and educational strategies within Europe.”

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Influenza vaccination coverage among children aged 6--23 months--six immunization information system sentinel sites, United States, 2005-06 influenza season
References removed
“Beginning with the 2004--05 influenza season, the Advisory Committee on Immunization Practices (ACIP) recommended that all children aged 6--23 months receive influenza vaccinations annually. Other children recommended to receive influenza vaccinations include those aged 6 months--18 years who have certain high-risk medical conditions, those on chronic aspirin therapy, those who are household contacts of persons at high risk for influenza complications, and, since 2006, all children aged 24--59 months. Previously unvaccinated children aged <9 years need 2 doses administered at least 1 month apart to be considered fully vaccinated. This report assesses influenza vaccination coverage among children aged 6--23 months during the 2005--06 influenza season by using data from six immunization information system (IIS) sentinel sites. The findings demonstrate that vaccination coverage with 1 or more doses varied widely (range: 6.6% to 60.4%) among sites, with coverage increasing from the preceding influenza season in four of the six sites. However, <23% of children in five of the sites were fully vaccinated, underscoring the need for increased measures to improve the proportion of children who are fully vaccinated. . .”
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5549a4.htm
(MMWR December 15, 2006 / 55(49);1329-1330)

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Lower clinical effectiveness of Oseltamivir against influenza B contrasted with influenza A infection in children
http://www.journals.uchicago.edu/CID/journal/issues/v44n2/40397/40397.text.html - fn1#fn1 Norio Sugaya et al. Clinical Infectious Diseases. 2007;44:000.
http://www.journals.uchicago.edu/CID/journal/issues/v44n2/40397/40397.html
Abstract: “Background. Recently, many Japanese physicians have claimed that oseltamivir is less effective in children with influenza B virus infection. This study assesses the effectiveness of oseltamivir against influenza A (H3N2) and influenza B in children on the basis of the duration of febrile illness. Methods. We used oseltamivir to treat 127 children with influenza A (H3N2; mean age, 6.97 years [range, 1–15 years]) and 362 children with influenza B (mean age, 5.16 years [range, 1–15 years]) in outpatient clinics. The duration of fever after the start of oseltamivir therapy was compared in the influenza A group and the influenza B group. Results. The mean duration of fever after the start of oseltamivir therapy was significantly greater in the influenza B group than in the influenza A (H3N2) group (2.18 days vs. 1.31 days, respectively; P < .001). The difference was marked in young children (1–5 years old; 2.37 days for the influenza B group vs. 1.42 days for the influenza A group) but was not significant among older children (11–15 years old). The 50% inhibitory concentration of oseltamivir against influenza B virus was 75.4 ± 41.7 nmol/L and was substantially higher than that for type A (H3N2) virus (0.3 ± 0.1 nmol/L). Only 3 (1.6%) of 192 influenza B viruses were resistant to oseltamivir. Conclusions. Oseltamivir is much less effective against influenza B virus infection in young children, probably because of the low sensitivity of influenza B viruses to oseltamivir. The effectiveness of oseltamivir against influenza B is influenced by age and host immunity. A few oseltamivir-resistant influenza B strains were isolated before the start of oseltamivir therapy.”
***Read the editorial commentary by Wright, PF: http://www.journals.uchicago.edu/CID/journal/issues/v44n2/41100/41100.html

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Ready or Not? Protecting the Public's Health from Disease, Disasters, and Bioterrorism, 2006
Trust for America's Health (TFAH) released the fourth annual "Ready or Not? Protecting the Public's Health from Disease, Disasters, and Bioterrorism," which found that 5 years after the September 11 and anthrax tragedies, emergency health preparedness is still inadequate in America. The report contains state-by-state health preparedness scores based on 10 key indicators to assess health emergency preparedness capabilities. All 50 U.S. states and the District of Columbia were evaluated. Half of states scored 6 or less on the scale of 10 indicators. Oklahoma scored the highest with 10 out of 10; California, Iowa, Maryland, and New Jersey scored the lowest with 4 out of 10. Some key recommendations include:

• The federal government should establish improved "optimally achievable" standards that every state should be accountable for reaching to better protect the public, and the results should be made publicly available. Appropriate levels of funding should be provided to the states to achieve these standards.
• Establishment of temporary health benefits for the uninsured or underinsured during states of emergency. This benefit is necessary to ensure that sick people will stay home, and the uninsured and underinsured will seek treatment in times of emergency, helping to prevent the unnecessary spread of infectious diseases, including resulting from acts of bioterrorism or a pandemic flu outbreak.
• A single senior official within the U.S. Department of Health and Human Services should be designated to be in charge of and accountable for all public health programs. The senior official would streamline government efforts and be the clear leader during times of crisis.
• Emergency surge capacity capabilities should be improved by integrating all health resources and partnering with businesses and community groups in planning, and increasing stockpiles of needed equipment and medications.
• The volunteer medical workforce should be expanded and an investment must be made in the recruitment of the next generation of the public health workforce.
• Technology and equipment must be modernized and research and development must be strengthened.
• The public should be better included in emergency planning, and risk communication must be modernized.
(Trust for America's Health 12/12/06 http://healthyamericans.org/reports/bioterror06/ )

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IOM: Modeling Community Containment for Pandemic Influenza: A Letter Report
An IOM committee said that a wide range of community interventions may be helpful to blunt the impact of an influenza pandemic, but there is no conclusive evidence for their effectiveness. Containment measures endorsed by the panel include home isolation of patients plus social support, voluntary sheltering at home, quarantine, hand hygiene, respiratory etiquette, preventive antiviral treatment, and community restrictions such as school closures. The group also supported standard public health measures such as disease surveillance and contact tracing. But the panel warned that public health officials, in recommending such steps, should take care not to overstate the evidence for their effectiveness.

The committee reviewed 6 mathematical simulations of community containment strategies and found none of them entirely convincing. Many key assumptions used in the models, such as those regarding virus transmissibility and compliance with interventions, were based on little evidence, the report says. The report also critiques existing models for focusing too narrowly on flu-related outcome measures and ignoring other effects of interventions. The committee also reviewed several analyses of data from the 1918 flu pandemic. Summarizing the lessons of the simulation models and historical analyses, the report says, "The models generally suggest that a combination of targeted antivirals and NPIs can delay and flatten the epidemic peak, but the evidence is less convincing that they can reduce the overall size of the epidemic. Delay of the epidemic peak is critically important because it allows additional time for vaccine development and antiviral production. Lowering the peak of the epidemic is crucial also because it can reduce the burden on healthcare infrastructure by avoiding an extremely large influx of patients."

Participants in the workshop said differences between the world of 1918 and today may limit the usefulness of historical data, the report notes. Population density is different today, and antibiotics now available to treat secondary infections could increase survival. The committee's conclusion on the key question of community restrictions, such as closing schools and limiting public gatherings, is that they have a role, but the evidence does not permit any predictions about the effects of specific types of restrictions or the comparative effects of voluntary versus mandatory restrictions. Other measures the committee affirmed as potentially beneficial, based on varying kinds of evidence, include:
• Surveillance and case reporting, rapid diagnosis, hand hygiene, and respiratory etiquette
• Antiviral prophylaxis and treatment in households and healthcare settings
• Contact tracing to allow contacts to take actions such as voluntary sheltering and quarantine
• Risk communication, meaning the identification of "key and trusted spokespersons" to promote public acceptance of community containment measures

The committee offers 11 recommendations for improving the understanding and use of community interventions. One calls for the development of "decision-aid models that can be readily linked to surveillance data to provide real-time feedback during a pandemic."
For full report: http://fermat.nap.edu/books/0309104114/html
(CIDRAP 12/14/06 http://www.cidrap.umn.edu/ )

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The Canadian Pandemic Influenza Plan for the Health Sector
Document from Public Health Agency of Canada released Dec 9, 2006. Contents include:
• Introduction
• Part 1 Understanding Influenza: Seasonal influenza - the "flu"; Influenza vaccination; Flu prevention checklist; Influenza pandemic; Avian influenza
• Part 2 What Canadian Governments are Doing to Prepare: Canadian Pandemic Influenza Plan for the Health Sector; Impact of an influenza pandemic in Canada; Origin and timing; Health impacts; Terminology;
• Key Components of Pandemic Planning (Surveillance and laboratory preparedness; Pandemic vaccine; Antivirals; Public health measures; Health services; Communications; Emergency preparedness and coordination).
http://www.phac-aspc.gc.ca/cpip-pclcpi/index.html

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3. Notifications
OIE, FAO and IZSVe Scientific Conference on Vaccination
Palazzo della Gran Guardia,Verona, Italy; 20-22 Mar 2007
OIE, FAO, and IZSVe scientific conference, "Vaccination: a tool for the control of avian influenza," will be held in Verona, Italy 20-22 Mar 2007, co-organized and supported by the European Commission. OIE and FAO, in collaboration with WHO, have been very active in coordinating the prevention and control of avian influenza and supporting infected countries in their eradication efforts. The scientific conference "Vaccination: a tool for the control of avian influenza," will be an opportunity to review the current methods and recent experiences in the use of vaccination as one of the tools to control and prevent losses due to avian influenza infections and to discuss the appropriate decision-making process for the implementation of a vaccination strategy. The conference will present scientific knowledge on the following topics: review of experiences; socio-economical effect of vaccination; the application of vaccination; vaccines and research; regulatory and trade aspects; vaccination: an integrated approach. For more information and online registration: http://www.avianfluvaccine2007.org.
(Promed 12/13/06)

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Paris Anti-Avian Influenza 2007 Conference
Venue: Institut Pasteur; 31 May - 1 Jun 2007
After the success of Paris Anti-Avian Influenza 2006, and in collaboration with the OIE, the International Society for Antioxidants in Nutrition and Health (ISANH), the French Society for Antioxidants (SFA), the Japanese Society for Antioxidants (JSA), the International Society of Preventive Medicine, the Japanese Research Group on Avian Influenza (JRGAI), and the Japanese Research Group on Emerging Viral Diseases are pleased to announce the Paris Anti-Avian Influenza 2007 Conference. Early registration fee due date: 25 Mar 2007. Abstract submission deadline: 30 Apr 2007. For more information, please visit: <http://www.isanh.com>.
(Promed 12/13/06)

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 apecein@u.washington.edu