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EINet Alert ~ Sep 07, 2007


*****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: WHO confirms 5 Vietnam avian influenza H5N1 cases, lists lab test criteria
- Indonesia (Sumatra): Man's death raises Indonesia's avian influenza H5N1 toll to 85
- Russia (Krasnodar): Avian influenza H5N1 hits poultry farm
- Egypt: Migrant birds test positive for the H7 strain of avian influenza

1. Updates
- Avian/Pandemic influenza updates

2. Articles
- CDC EID Journal, Volume 13, Number 9—Sep 2007
- Prioritization strategies for pandemic influenza vaccine in 27 countries of the European Union and the Global Health Security Action Group: a review
- Childhood Influenza: Number Needed to Vaccinate to Prevent 1 Hospitalization or Outpatient Visit
- Testing of Diagnostic Methods for Detection of Influenza Virus for Optimal Performance in the Context of an Influenza Surveillance Network
- Host Single-Nucleotide Polymorphisms and Altered Responses to Inactivated Influenza Vaccine
- Vesicular stomatitis virus vectors expressing avian influenza H5 HA induce cross-neutralizing antibodies and long-term protection
- Enhanced growth of seed viruses for H5N1 influenza vaccines

3. Notifications
- Asian officials discuss avian influenza surveillance at FAO 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 / 13 (8)
Djibouti / 1 (0)
Egypt / 18 (10)
Indonesia / 56 (46)
Iraq / 3 (2)
Thailand / 3 (3)
Turkey / 12 (4)
Total / 116 (80)

2007
Cambodia/ 1 (1)
China / 3 (2)
Egypt / 20 (5)
Indonesia / 30 (26)
Laos / 2 (2)
Nigeria / 1 (1)
Viet Nam 7 (4)
Total / 64 (41)

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 327 (199).
(WHO 8/23/07 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 8/31/07)

WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 9/5/07): http://gamapserver.who.int/mapLibrary/

WHO’s timeline of important H5N1-related events (last updated 8/27/07): http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html.

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Global: WHO confirms 5 Vietnam avian influenza H5N1 cases, lists lab test criteria
WHO recognized 5 human H5N1 influenza cases from Vietnam dating back to May 2007, after publishing formal criteria for accepting positive test results for H5 flu viruses from national laboratories. The 5 cases include 4 fatal ones, which pushes Vietnam's H5N1 toll to 100 cases with 46 deaths. The country has the second highest number of avian flu cases, after Indonesia. The 5 cases now confirmed by WHO had been reported earlier by Vietnam. WHO now has confirmed all the cases announced by Vietnamese authorities this year. So far this year Vietnam has had 7 H5N1 cases with 4 deaths, and the resurgence in human infections appears to have coincided with fresh poultry outbreaks, mainly in the northern and Mekong delta.

WHO said it will now accept positive polymerase chain reaction (PCR) results from national reference laboratories that (1) have participated successfully in the WHO's new External Quality Assessment (EQA) project and (2) have accurately identified H5 flu viruses in at least 3 previous cases. Tiffany Domingo, a technical officer in WHO's outbreak and pandemic communications department, said WHO will now confirm positive H5N1 results from Vietnamese labs—as it did for the latest 5 H5N1 case patients—so long as the labs meet the new testing criteria. Most countries that have had human H5N1 cases have had to send specimens to WHO reference labs elsewhere for confirmation. However, WHO has accepted positive H5N1 results from a few countries, such as China and, in recent months, Indonesia.

Established in July, the EQA project is conducted by the WHO Global Influenza Programme and the WHO reference laboratory at the National Influenza Centre in Hong Kong. The program is designed to build the capacity of labs to use PCR to diagnose both seasonal and avian influenza and to support good laboratory practices. To participate in the EQA project, laboratories must test a simulated panel of RNA specimens twice a year and fill out a "Good Laboratory Practice" questionnaire. The RNA specimens include H1, H3, and H5 virus subtypes. WHO analyzes the test results and reports on the performance of each laboratory.

WHO spelled out the 2 main requirements for accepting positive H5 test results from national laboratories: 1) The lab must participate in the EQA project and must have correctly detected all H5 viruses in the most recent set of samples, without reporting any false-positive H5 findings; 2) Since 2004, the lab must have tested for human H5 infections and must have made at least 3 positive diagnoses that were later confirmed by a WHO H5 reference lab. Countries that don't have a national influenza reference lab, or have a national lab that has not met the WHO criteria, must have their positive H5 test results confirmed by a WHO reference lab or by another WHO-approved national reference lab.

Recommendations and laboratory procedures for detection of avian influenza A(H5N1) virus in specimens from suspected human cases (Revised August 2007): http://www.who.int/csr/disease/avian_influenza/guidelines/labtests/en/index.html
(CIDRAP 8/31/07)

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Asia
Indonesia (Sumatra): Man's death raises Indonesia's avian influenza H5N1 toll to 85
Indonesian officials reported a fatal H5N1 avian influenza infection in a 33-year-old man from Sumatra. Joko Suyono, an official at the health ministry's avian flu center, said the man was from Riau province and had contact with chickens before becoming ill Aug 25. "He processed chicken that he bought from a nearby market," Suyono said. Reportedly 2 laboratory tests came back positive. The man, a plantation worker, was hospitalized 10 days ago with a high fever, a cough, and breathing difficulties, Arman Zubair, another health ministry official, said. He said the man previously seemed to be recovering, but his infection worsened suddenly and he died. If the case is confirmed by WHO, it will go down as Indonesia's 85th avian flu fatality and 106th case. Indonesia has the world's highest toll of H5N1 cases and deaths. Animal-health experts believe the H5N1 virus has become endemic in poultry in some parts of Indonesia.
(CIDRAP 9/6/07; Promed 9/7/07)

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Russia (Krasnodar): Avian influenza H5N1 hits poultry farm
Russian officials announced that hundreds of chickens at a farm in southern Russia died of H5N1 avian influenza. This was Russia’s third avian influenza outbreak in 2007. The poultry deaths were discovered in the town of Razdolny in Krasnodar territory Sep 2. The disease struck about 500 chickens. A spokesman for the territorial veterinary agency said a regional laboratory identified the H5N1 virus in the dead birds and that further tests were under way to confirm the results. Authorities planned to cull 22,000 birds on the affected farm, the veterinary official said. The new wave of poultry deaths occurred in the same territory as a January outbreak that marked a recurrence of the disease in Russia after a 5-month lull. In February, the virus struck backyard birds at several locations on the outskirts of Moscow. Measures were being taken to contain the outbreak. Russia last month [Aug 2007] banned poultry from Italy and Germany after bird flu was discovered at farms in both countries. Russia expects to boost poultry meat output 16 percent this year [2007] to about 1.8 million tonnes, cutting the share of imports [for] domestic consumption. Russian poultry producers last year [2006] supplied about 53 percent of the country's consumption.
(CIDRAP 9/4/07; Promed 9/6/07)

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Africa
Egypt: Migrant birds test positive for the H7 strain of avian influenza
The H7 strain of the bird flu virus has been detected in Egypt for the first time. A total of 9 migrant birds, all of them ducks, tested positive for the virus when 6432 samples were taken from the approximately 1 million birds that annually migrate over Al-Manzalah Lake in the Sharqiya governorate from central and eastern Europe. The recently identified H7 strain is thought to pose little risk, compared to the virulent H5N1 strain. The H7 strain samples are now being tested at both the Ministry of Health and Population (MOHP) and Naval Medical Research Unit (NAMRU) laboratories in order to determine the N subtype. Avian influenza has 16 H & 9 N subtypes. Only viruses of the H5 and H7 subtypes comprise the pathogenic form of the disease, though not all H5 and H7 subtypes cause severe disease in poultry.

Abdel-Rahman Shahin, spokesman at the MOHP, explains that the H5 and H7 viruses are usually introduced to poultry in a low pathogenic form. It is only after several months that they mutate into highly pathogenic strains. The appearance of the H7 strain is therefore a cause for concern. The virus has been known to infect humans but is less virulent than the H5N1 strain. Since the H5N1 virus was first detected in poultry in Egypt Feb 2006, 38 cases of human infection have been reported, of which 15 resulted in fatalities. The most recent case was a 25-year-old from Damietta governorate, who tested positive for the H5N1 virus late Jul 2007. Veterinary experts, though, warn that the presence of both the H7 and H5N1 viruses in Egypt could facilitate further genetic mutations, which can be caused by the combination of the 2 types of avian influenza virus which are currently present in Egypt. Meanwhile, Minister of Agriculture and Land Reclamation Amin Abaza issued a press release saying that 38 percent of poultry in Egypt had been vaccinated against the H5N1 bird flu virus. Abaza notes that while the ministry has managed to contain the virus, the fact that an estimated 5 million people continue to raise poultry at home, especially in the rural areas, constitutes an ongoing threat.
(Promed 9/2/07)

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1. Updates
Avian/Pandemic influenza updates
- UN: http://www.un-influenza.org/ : the website has been moved and updated. Also, http://www.irinnews.org/Birdflu.asp provides information on avian influenza.
- 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. Link to supplement to Journal of Wildlife Diseases on avian influenza.
- OIE: http://www.oie.int/eng/en_index.htm.
- US CDC: http://www.cdc.gov/flu/avian/index.htm. News on federal updates.
- The US government’s web site for pandemic/avian flu: http://www.pandemicflu.gov/. Link to North American Plan for Avian and Pandemic Influenza.
- Health Canada: information on pandemic influenza: http://www.influenza.gc.ca/index_e.html.
- CIDRAP: http://www.cidrap.umn.edu/.
- 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. Updated 7 Sep 2007.
(UN; WHO; FAO, OIE; CDC; Health Canada; CIDRAP; PAHO; USGS)

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2. Articles
CDC EID Journal, Volume 13, Number 9—Sep 2007
CDC Emerging Infectious Diseases Journal Sep 2007 issue is now available at: http://www.cdc.gov/ncidod/EID/index.htm. Expedited articles can be viewed at: http://www.cdc.gov/ncidod/eid/upcoming.htm.

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Prioritization strategies for pandemic influenza vaccine in 27 countries of the European Union and the Global Health Security Action Group: a review
Masja Straetemans et al. BMC Public Health 2007, 7:236. doi:10.1186/1471-2458-7-236. 7 September 2007. http://www.biomedcentral.com/1471-2458/7/236/abstract
Abstract (provisional): Background: Although there is rapid progress in vaccine research regarding influenza pandemic vaccines it is expected that pandemic influenza vaccine production can only start once the pandemic virus has been recognized. Therefore, pandemic vaccine capacity will be limited at least during the first phase of an influenza pandemic, requiring vaccine prioritization strategies. WHO recommends developing preliminary priorities for pandemic vaccine use. The goal of this review is to provide a thorough overview of pandemic vaccine prioritization concepts in the 27 European Union (EU) member states and the four non-EU countries of the Global Health Security Action Group. Methods: Between September and December 2006 data was collected for each country through two data sources: (i) the national influenza pandemic plan; (ii) contacting key persons involved in pandemic planning by email and/or phone and/or fax. Results: Twenty-six (84%) countries had established at least one vaccine priority group. Most common reported vaccine priority groups were health care workers (HCW) (100%), essential service providers (ESP) (92%) and high risk individuals (HRI) (92%). Ranking of at least one vaccine priority group was done by 17 (65%) of 26 countries. Fifteen (88%) of these 17 countries including a ranking strategy, decided that HCW with close contact to influenza patients should be vaccinated first; in most countries followed and/or ranked equally by ESP and subsequently HRI. Rationales for prioritization were provided by 22 (85%) of 26 countries that established vaccine priority groups. There was large variation in the phrasing and level of detailed specification of rationales. Seven (32%) of 22 countries providing rationales clearly associated each vaccine priority group with the specific rationale. Ten (32% of the 31 countries studied) countries have consulted and involved ethical experts to guide decisions related to vaccine prioritization. Conclusion: In the majority of the countries the establishment of vaccine priority groups, ranking and underlying rationales are in line with WHO recommendations. In most public plans the criteria by which prioritized groups are identified are not easily recognizable. Clarity however, may be necessary to assure public acceptability of the prioritization. Ethical experts, results of modelling exercises could play an increasing role in the future decision making process.

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Childhood Influenza: Number Needed to Vaccinate to Prevent 1 Hospitalization or Outpatient Visit
Elizabeth N. Lewis et al. PEDIATRICS Vol. 120 No. 3 September 2007, pp. 467-472 (doi:10.1542/peds.2007-0167). http://pediatrics.aappublications.org/cgi/content/abstract/120/3/467
Abstract: OBJECTIVE. The goal was to assess the potential benefits of the influenza vaccine recommendations for children 6 to 59 months of age by estimating the number of children needed to be vaccinated to prevent 1 hospitalization or 1 outpatient visit attributable to influenza. METHODS. The influenza burden was obtained from published studies in which rates for children 6 to 23 months and 24 to 59 months of age could be ascertained. We assumed a range of influenza vaccine efficacies of 25% to 75%, consistent with the literature. We estimated the number of children who needed to be vaccinated to prevent 1 influenza-attributable hospitalization or 1 outpatient visit for each age group. RESULTS. As both vaccine efficacy and severity of the influenza season increased, the number of children who needed to be vaccinated to prevent 1 hospitalization or 1 outpatient visit decreased. The numbers of children who needed to be vaccinated to prevent 1 hospitalization in a year with 50% vaccine efficacy ranged from 1031 to 3050 for children 6 to 23 months of age and from 4255 to 6897 for children 24 to 59 months of age. For every 12 to 42 children 6 to 59 months of age vaccinated in a year with 50% vaccine efficacy, we estimated that 1 influenza-attributable outpatient visit would be prevented. CONCLUSIONS. With 1 outpatient visit being prevented through vaccination of <50 children, influenza vaccination can reduce influenza-attributable medical visits in children significantly, even in years with modest vaccine efficacy.

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Testing of Diagnostic Methods for Detection of Influenza Virus for Optimal Performance in the Context of an Influenza Surveillance Network
Mercedes Pérez-Ruiz et al. Journal of Clinical Microbiology, September 2007, p. 3109-3110, Vol. 45, No. 9 http://jcm.asm.org/cgi/content/abstract/45/9/3109 Abstract: Influenza surveillance networks must detect early the viruses that will cause the forthcoming annual epidemics and isolate the strains for further characterization. We obtained the highest sensitivity (95.4%) with a diagnostic tool that combined a shell-vial assay and reverse transcription-PCR on cell culture supernatants at 48 h, and indeed, recovered the strain.

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Host Single-Nucleotide Polymorphisms and Altered Responses to Inactivated Influenza Vaccine
Yi-Wei Tang et al. The Journal of Infectious Diseases. 2007;196:1021-1025
Abstract: We analyzed the relationship between host gene polymorphisms and responses in recipients of inactivated influenza vaccine, who were classified into poor, normal, or adverse response groups. The frequency of the mannose-binding lectin–2 codon 54 allele was significantly different among the 3 types of responders, with a decreased odds ratio for the development of poor or adverse responses (P = .033). There was no statistical relationship between responses and either tumor necrosis factor–α or interleukin (IL)–10 promoter polymorphisms among the 3 response groups. When poor and normal responses were combined, the -1082 A allele in the IL-10 promoter conferred a significantly decreased risk of the development of adverse responses (P = .041). These data indicate that host polymorphisms play a role in determining responses to influenza vaccine.

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Vesicular stomatitis virus vectors expressing avian influenza H5 HA induce cross-neutralizing antibodies and long-term protection
Schwartz JA et al. Virology. 2007 Sep 15;366(1):166-73. Epub 2007 May 23.
Abstract: Given the lethality of H5N1 avian influenza viruses (AIV) and the recurring spread from poultry to humans, an effective vaccine against H5N1 viruses may be needed to prevent a pandemic. We generated experimental vaccine vectors based on recombinant vesicular stomatitis virus (VSV) expressing the H5 hemagglutinin (HA) from an H5N1 virus isolated in 1997. The HA gene was expressed either from an attenuated wild-type VSV vector or from a single-cycle vector containing a deletion of the VSV G gene. We found that all of the vectors induced potent neutralizing antibody titers against the homologous and antigenically heterologous H5N1 viruses isolated in 2004 and 2005. Vaccination of mice with any combination of prime or prime/boost vectors provided long-lasting protection (>7 months) against challenge with AIV, even in animals receiving a single dose of single-cycle vaccine. Our data indicate that these recombinants are promising vaccine candidates for pandemic influenza.

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Enhanced growth of seed viruses for H5N1 influenza vaccines
Horimoto T et al. Virology. 2007 Sep 15;366(1):23-27. Epub 2007 Jul 24
Abstract: Seed viruses used to produce inactivated H5N1 influenza vaccines are recombinant viruses with modified avirulent-type hemagglutinin (HA) and intact neuraminidase (NA) genes, both derived from an H5N1 isolate, and all remaining genes from the PR8 strain, which grows well in eggs. However, some reassortants grow suboptimally in eggs, imposing obstacles to timely, cost-efficient vaccine production. Here, we demonstrate that our PR8 strain supports better in ovo growth than the PR8 strain used for the WHO-recommended seed virus, NIBRG-14. Moreover, inclusion of an alternative NA protein further enhanced viral growth in eggs. These findings suggest that our H5N1 vaccine candidates would increase the availability of H5N1 vaccine doses at the onset of a new pandemic.

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3. Notifications
Asian officials discuss avian influenza surveillance at FAO conference
Animal-health experts from a dozen countries are meeting in Bangkok at a conference sponsored by the UN Food and Agriculture Organization (FAO) to hear reports from Asian countries on their H5N1 wildlife surveillance efforts and discuss how countries can better coordinate their activities. Scott Newman, international wildlife coordinator for the FAO, said the virus hasn't been found in any of 300,000 to 350,000 healthy wild birds that have been sampled in global surveillance activities in the past 2 years. "We know now that we haven't found a species that even suggests that it would be a reservoir for this disease," he said. Experts said some countries test healthy wild birds, while others test for H5N1 only in sick or dead birds. So far the virus has been found in 90 species of birds. Scarce H5N1 findings in wild birds don't mean surveillance efforts should stop, Newman said. Instead, countries should fine-tune monitoring activities by, for example, improving testing at sites where domestic and wild birds mingle. Officials attending the meeting, which includes 70 experts, said the only way to get an accurate view of H5N1 in wild birds is to establish a uniform and comprehensive surveillance system. Last year, FAO officials expressed concern that migratory birds would spread the H5N1 virus from Asia and Europe to Africa. However, William Karesh, program director of the Wildlife Conservation Society's field veterinary program, said surveillance has found very few instances of the virus in Africa's wild birds. He said the illegal trade in wildlife in Africa and elsewhere makes tracking the virus particularly challenging.
(CIDRAP 9/4/07)

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 apecein@u.washington.edu