EINet Alert ~ Aug 10, 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)
- Germany (Bavaria): Avian influenza H5N1 detected in 3 ducks
- Italy: Low pathogenic avian influenza H7N3 detected in ornamental birds
- India: Children under surveillance test negative for avian influenza
- Indonesia: To keep withholding avian influenza H5N1 virus samples for now
- Viet Nam: Teenager dies of avian influenza H5N1

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

2. Articles
- CDC EID Journal, Volume 13, Number 8—Aug 2007
- New Study Finds Community Measures Prevent Deaths During Pandemic
- NIH Scientists Target Future Pandemic Strains of H5N1 Avian Influenza

3. Notifications
- Towards a unified nomenclature system for the highly pathogenic H5N1 avian influenza viruses

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

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

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

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

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)

Cambodia/ 1 (1)
China / 3 (2)
Egypt / 20 (5)
Indonesia / 27 (23)
Laos / 2 (2)
Nigeria / 1 (1)
Viet Nam 2 (0)
Total / 56 (34)

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 319 (192).
(WHO 7/25/07 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 7/259/07)

WHO's maps showing world's areas reporting confirmed cases of H5N1 avian influenza in humans, poultry and wild birds (last updated 8/8/07): http://gamapserver.who.int/mapLibrary/

WHO’s timeline of important H5N1-related events (last updated 7/30/07): http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html.


Europe/Near East
Germany (Bavaria): Avian influenza H5N1 detected in 3 ducks
3 ducks found dead near Munich in southern Germany tested positive for the H5N1 bird flu virus. The 3 ducks were found dead near Speichersee, a lake to the northeast of Munich, the Friedrich-Loeffler-Institut, said. The surrounding area would be searched for any other dead birds.
(Promed 8/3/07, 8/7/07)


Italy: Low pathogenic avian influenza H7N3 detected in ornamental birds
On 27 Jul 2007, it was reported that there was a low pathogenic avian influenza H7 outbreak in a holding with ornamental birds in the commune of Fiesso Umbertino, province of Rovigo, region of Veneto. The specific strain was found to be H7N3 and is closely related to another strain detected in May [2007]. The outbreak was detected in a holding with more than 2000 ornamental birds (ducks, geese, pheasants, peacocks, ostriches, etc.).
(Promed 8/3/07)


India: Children under surveillance test negative for avian influenza
The Indian health care authorities have completed health checks on thousands of people after an outbreak of bird flu in the remote northeast, and cleared 4 boys who had been suffering from fever after handling dead or sick poultry. Throat swab and tissue samples of the boys had been sent for testing but no sign of bird flu was found. Thousands of people in Manipur state were also checked after the outbreak of the H5N1 strain of bird flu in chickens on a small poultry farm. The 4 boys, who are reportedly all under 14, lived within a 5-km radius of the affected farm. Another 21 people living or working on the farm and 9 veterinary workers were cleared earlier. Authorities in Manipur stopped culling operations 2 Aug 2007 after killing and burying nearly 300 000 fowl. But officials in Tripura, another northeastern state, were on alert against bird flu after around 300 chicken died in a district bordering Bangladesh, where avian flu has spread to a number of areas this year. An official in the state said chicken blood and tissue samples had been sent for testing.
(Promed 8/3/07)


Indonesia: To keep withholding avian influenza H5N1 virus samples for now
Indonesian officials said this week they will continue withholding samples of the H5N1 avian influenza virus at least until a new virus-sharing mechanism is worked out at an international meeting Nov 2007. In Dec 2006, Indonesia stopped sharing its H5N1 samples with WHO as a protest against the cost of commercial vaccines derived from such samples. The samples are needed for tracking the mutations and spread of the virus and for developing vaccines. Indonesia said it would resume sharing its H5N1 samples in May when the World Health Assembly passed a resolution asking the WHO to establish an international stockpile of H5N1 vaccines and create an interdisciplinary working group to draw up new "terms of reference" for the sharing of flu viruses by WHO collaborating centers and reference laboratories. The resolution requests WHO to develop a mechanism for sharing of viruses and prepare a report on intellectual property issues related to vaccine development.

In May 2007, Indonesia sent three H5N1 samples to WHO, which appeared to end its embargo. However, David Heymann, the WHO's assistant director-general for communicable diseases, said Aug 6 that the samples contained no live viruses. "Indonesia is putting the public health security of the whole world at risk because they're not sharing viruses," Heymann said. Indonesia is the only country that is not sharing samples from its human H5N1 cases, he said. Triono Soendoro, Indonesia's deputy health minister for research, said the samples the country sent WHO in May were adequate for determining if a viral mutation had occurred. Indonesia will resume sending samples only when a formal system is established that ensures developing countries receive equitable access to affordable vaccines made from the samples they share, Soendoro said. "If that's not all ready and we send samples, anything could happen. It's a simple request to be transparent, to be accountable," he said. Lily Sulistyowati, an Indonesian health ministry spokesperson, said the country would wait for the new virus-sharing mechanism to be approved before resuming sending virus samples. "However, anyone who needs the virus can file a special request to us officially," she said.
(CIDRAP 8/7/07, 8/9/07)


Viet Nam: Teenager dies of avian influenza H5N1
Vietnam said the death of a 15-year-old boy last week was caused by H5N1 avian influenza. The teenager died Aug 3, 2007 while being transferred from a hospital in his home province of Thanh Hoa to Hanoi. Test results showed the boy had avian flu, said Nguyen Huy Nga, director of Vietnam's Preventive Medicine Department. Nga said the boy had had contact with ducklings bought from a local market. The boy's illness marked Vietnam's seventh human H5N1 case and fourth death from the disease this year. The country has had a total of 100 cases with 46 deaths since 2003. 5 cases reported by Vietnamese officials have not yet been confirmed by WHO, whose current avian flu tally for Vietnam is 95 cases with 42 deaths. In an Aug 6 news briefing, a WHO official said Vietnam has been trying to ship samples from avian flu patients to WHO but has run into delays.

Currently poultry in only 3 provinces remained affected by avian influenza, and 160 million head of poultry had received bird flu shots in the year's first round of vaccinations which was ongoing or finished in all provinces. Last week [30 Jul - 3 Aug 2007] WHO spokesman Gregory Hartl said global bird flu cases appeared to have stabilised among humans but that several developing nations had not been able to stem its spread among poultry and domesticated birds. "In the northern hemisphere, the number of cases in summer has declined marginally from the winter," Hartl said.
(Promed 8/7/07, 8/8/07)


1. Updates
Avian/Pandemic influenza updates
- UN: http://influenza.un.org/. UN response to avian influenza and the pandemic threat. 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.
- 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/.
- 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.
- US Geological Survey, National Wildlife Health Center Avian Influenza Information: http://www.nwhc.usgs.gov/disease_information/avian_influenza/index.jsp. Updated 3 Aug 2007.


Seasonal Influenza Update
Influenza Activity--United States and Worldwide, 2006--07 Season, and Composition of the 2007--08 Influenza Vaccine During the 2006--07 season, influenza activity peaked in mid-Feb in the US and was associated with less mortality and lower rates of pediatric hospitalizations than during the previous three seasons. In the United States, influenza A (H1) viruses predominated overall, but influenza A (H3) viruses were isolated more frequently than influenza A (H1) viruses late in the season. Although influenza A (H1), A (H3), and B viruses cocirculated worldwide, influenza A (H3) viruses were the most commonly reported type in Europe and Asia. Sporadic cases of avian influenza A (H5N1) virus infections associated with severe illness or death were reported among humans in Cambodia, China, Egypt, Indonesia, Laos, Nigeria, and Viet Nam. This report summarizes influenza activity in the United States and worldwide during the 2006--07 influenza season (Oct 1, 2006--May 19, 2007) and describes the composition of the 2007--08 influenza vaccine.

Composition of the Influenza Vaccine for the 2007--08 Season The Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee recommended that the 2007--08 trivalent influenza vaccine for the United States contain A/Solomon Islands/3/2006-like (H1N1), A/Wisconsin/67/2005-like (H3N2), and B/Malaysia/2506/2004-like viruses. This represents a change only in the influenza A (H1N1) component. A/Solomon Islands/3/2006 is a recent antigenic variant of the 2006--07 vaccine strain A/New Caledonia/20/99. The influenza A (H3N2) and influenza B components remain the same. These recommendations were based on antigenic analyses of recently isolated influenza viruses, epidemiologic data, postvaccination serologic studies in humans, and the availability of candidate vaccine strains and reagents.

The weekly percentage of patient visits to U.S. sentinel providers for ILI exceeded or was at baseline levels (2.1%) during the weeks ending December 16, 2006--March 24, 2007 (weeks 50--12) and peaked twice, once at 3.0% for the week ending December 30, 2006 (week 52), and again at 3.5% for the week ending February 17, 2007 (week 7).

During Oct 1, 2006--Apr 28, 2007, the preliminary influenza-associated hospitalization rate reported for children aged 0--17 years was 0.81 per 10,000. For children aged 0--4 years and 5--17 years, the rates were 1.62 per 10,000 and 0.23 per 10,000, respectively. During Nov 5, 2006--May 26, 2007, the preliminary laboratory-confirmed influenza-associated hospitalization rate for children aged 0--4 years was 3.46 per 10,000.

During the 2006--07 influenza season, the percentage of deaths attributed to pneumonia and influenza (P&I) did not exceed the epidemic threshold in the 122 Cities Mortality Reporting System.

As of August 6, 2007, among persons aged <18 years, a total of 68 deaths associated with influenza infection occurring during October 1, 2006--May 19, 2007, were reported to CDC. 10 were aged <6 months, 10 were aged 6--23 months, nine were aged 2--4 years, and 39 were aged 5--17 years. Of the 63 patients for whom influenza virus type was known, 47 had influenza A and 16 had influenza B viruses. Of the 53 patients aged >6 months for whom vaccination status was known, 50 (94%) had not been vaccinated against influenza. These data are provisional.
(MMWR August 10, 2007 / 56(31);789-794)


2. Articles
CDC EID Journal, Volume 13, Number 8—Aug 2007
CDC Emerging Infectious Diseases Journal Aug 2007 issue is now available at: http://www.cdc.gov/ncidod/EID/index.htm. The following influenza articles may be of interest: Reduced Sensitivity of Influenza A (H5N1) to Oseltamivir; Ecologic Immunology of Avian Influenza (H5N1) in Migratory Birds; Avian Influenza (H5N1) Susceptibility and Receptors in Dogs; Ecoregional Dominance in Spatial Distribution of Avian Influenza (H5N1) Outbreaks (responses); Precautionary Behavior in Response to Perceived Threat of Pandemic Influenza; Effect of Interventions on Influenza A (H9N2) Isolation in Hong Kong’s Live Poultry Markets, 1999–2005; Detecting Human-to-Human Transmission of Influenza A (H5N1); Poultry Drinking Water Used for Avian Influenza Surveillance.


New Study Finds Community Measures Prevent Deaths During Pandemic
School closures and other community strategies designed to reduce the possibility of spreading disease between people during an epidemic can save lives, particularly when the measures are used in combination and implemented soon after an outbreak begins in a community, according to a new study based on public records from the 1918-1919 influenza pandemic. The findings, which are published in the Aug. 8 issue of the Journal of the American Medical Association, provide vital clues to help public officials planning for the next influenza pandemic and highlight the importance of community strategies. These strategies are particularly important because the intervention most likely to provide the best protection against pandemic influenza -- a vaccine -- is unlikely to be available at the outset of a pandemic. Community strategies that delay or reduce the impact of a pandemic may help reduce the spread of disease until a vaccine that is well-matched to the virus is available.

Scientists from the CDC and the University of Michigan Medical School′s Center for the History of Medicine completed an exhaustive review of public records such as health department reports, U.S. Census mortality data and newspaper archives. "Communities that were most successful during the 1918 pandemic quickly enacted a variety of measures," said Dr. Martin Cetron, director of CDC′s Division of Global Migration and Quarantine. "Those planning for the next pandemic need to carefully consider how to best use these strategies to protect people and decrease the potential impact of the next pandemic in their communities." These strategies – voluntary isolation and quarantine, dismissal of students from school classrooms, and social distancing in the workplace and community – form the basis for CDC’s guidelines for how American communities can empower themselves to confront the next influenza pandemic.

The study evaluated public health measures such as school closures and cancellation of public events, which 43 American cities took during the 1918 pandemic. The researchers sought to determine whether the timing, duration and combination of such measures impacted the city′s death rate during the pandemic. To determine the public health measures′ effectiveness, the researchers analyzed each city′s excess death rate - the number of pneumonia and influenza deaths in excess of the amount expected for the time period. During a 24-week period in 1918-1919, more than 115,000 excess pneumonia and influenza deaths in the 43 cities were attributed to the pandemic. Cities that began interventions earlier had more success in decreasing excess deaths than those that implemented the measures later, regardless of how long the later interventions were in place or how they were executed.

In a telling example, New York City′s early and sustained response, including isolation and quarantine and staggered business hours, resulted in the lowest excess death rate for any city on the East Coast during the time period reviewed. By contrast, Pittsburgh was well into its outbreak before implementing the interventions and experienced the highest excess death rate of any of the 43 cities. "In a world faced by the threat of avian influenza or other novel strains of influenza, it is critical to determine if such costly and socially harsh measures as school closures and cancellation of public gatherings might not only lower death and case rates, but also delay the spread and allow time for the development and distribution of effective vaccines and antivirals," said Dr. Howard Markel, director of the University of Michigan Medical School′s Center for the History of Medicine. "We have demonstrated that these measures can have a real impact."

The interventions assessed fell into 3 major categories: school closures, bans on public gatherings and isolation of sick people and quarantine of their healthy household contacts. The most common approach was closing schools combined with banning public gatherings. All but 3 of the 43 communities closed schools during the 24-week period studied. The 1918 pandemic sickened about 20 percent of the world′s population and caused an estimated 40 million deaths worldwide.

To read the article, “Nonpharmaceutical Interventions Implemented by US Cities During the 1918-1919 Influenza Pandemic”, Howard Markel et al. JAMA. Vol. 298 No. 6, August 8, 2007: http://jama.ama-assn.org/cgi/content/abstract/298/6/644

For more information about community strategies for pandemic influenza: http://www.pandemicflu.gov/plan/community/community_mitigation.pdf.
(CDC 8/7/07 http://www.cdc.gov/od/oc/media/pressrel/2007/r070807.htm )


NIH Scientists Target Future Pandemic Strains of H5N1 Avian Influenza
Preparing vaccines and therapeutics that target a future mutant strain of H5N1 influenza virus may be possible, according to a team of scientists at the National Institute of Allergy and Infectious Diseases (NIAID) and a collaborator at Emory University School of Medicine. Success hinges on anticipating and predicting the crucial mutations that would help the virus spread easily from person to person. Led by Gary Nabel, director of the NIAID’s Dale and Betty Bumpers Vaccine Research Center (VRC), the team is reporting in the Aug 10, 2007 issue of the journal Science that they have developed a strategy to generate vaccines and therapeutic antibodies that could target predicted H5N1 mutants before these viruses evolve naturally. This advance was made possible by creating mutations in the region of the H5N1 hemagglutinin (HA) protein that directs the virus to bird or human cells and eliciting antibodies to it.

“Now we can begin, preemptively, to consider the design of potential new vaccines and therapeutic antibodies to treat people who may someday be infected with future emerging avian influenza virus mutants,” says NIAID Director Anthony S. Fauci. Making a vaccine against an existing strain of H5N1 or any other type of influenza virus is relatively routine. Typically, samples of existing influenza virus strains are isolated and then grown inside eggs or in cell cultures. The virus is then collected, inactivated, purified and added to the other components of the vaccine. A flu shot prompts a person’s immune system to detect pieces of the inactivated virus present in the vaccine and make neutralizing antibodies against them. Later, if that same person is naturally exposed to a flu virus, these same antibodies should help fight the infection. Influenza viruses constantly mutate, however, and vaccines are most effective against the highly specific strains that they are made from. This makes it difficult to predict how effective a vaccine made today will be against a virus that emerges tomorrow.

Dr. Nabel and his colleagues started their project by focusing narrowly on mutations that render H5N1 viruses better able to recognize and enter human cells. Bird-adapted H5N1 binds bird cell surface receptors. But these receptors differ slightly from the receptors on human cells, which in part explains why bird-adapted H5N1 can infect but not spread easily between humans. About a year ago, the research team began asking what mutations help the virus shift its adaptability. They compared the structural proteins on the surface of bird-adapted H5N1 influenza virus with those on the surface of the human-adapted strain that caused the 1918 pandemic. They focused specifically on genetic changes to one portion of the H5 protein — a portion called the receptor binding domain. They showed that as few as 2 mutations to this receptor binding domain could enhance the ability of H5N1 to recognize human cells.

Additional mutations would likely need to accumulate for H5N1 to spread more easily from person to person, says Dr. Nabel. The few mutations he and his colleagues identified are likely just a subset of those, he emphasizes. Moreover, they found that these mutations change how the immune system recognizes the virus. Mouse antibodies that target H5N1 were up to tenfold less potent against the mutants. Dr. Nabel and his colleagues used their knowledge of receptor specificity to create vaccines and isolate new antibodies that might be used therapeutically against human-adapted mutants. They vaccinated mice with the material from viruses they altered to contain the mutant receptors, and they discovered one broadly reactive antibody that could neutralize both the bird- and human-adapted forms of an H5N1 virus. According to Dr. Nabel, their findings should contribute to better surveillance of naturally occurring avian flu outbreaks by making it easier to recognize dangerous mutants and identify vaccine candidates that might provide greater efficacy against such a virus before it emerges. Dr. Nabel said, “Insight into the structure of the avian flu virus has enabled us to target a critical region of HA that directs its specificity. Such a structure-based vaccine design may allow us to respond to this future threat in advance of an actual outbreak.”
(NIH 8/9/07 http://www.nih.gov/news/pr/aug2007/niaid-09.htm )


3. Notifications
Towards a unified nomenclature system for the highly pathogenic H5N1 avian influenza viruses
Over the last four years, a variety of different names have been used in publications to refer to emerging lineages of the highly pathogenic H5N1 avian influenza viruses. As a result, discussion and comparison of the various lineages remains difficult. The H5N1 viruses appear to be evolving and diversifying and while most genes have undergone reassortment yielding many different genotypes, the haemagglutinin (HA) protein, remarkably, has not been replaced in the various isolates since 1996. Following the evolution of the HA protein provides an initial constant by which the strains may be effectively compared. It was proposed therefore to develop a clade nomenclature system based upon the evolution of the HA. This would enable: a unified system to be developed to facilitate the interpretation of sequence/surveillance data from different labs; the stigmatizing labelling of clades by geographical reference to be replaced; the phylogenetic tree to be expanded in the future; and a starting point to be established to develop a more extensive system in the near future that is based upon antigenic variation and reassortment into multiple genotypes.

An international core group of 8 scientists and their collaborators were convened to initiate this process with the encouragement and approval of WHO, the World Organisation for Animal Health (OIE) and the Food and Agriculture Organization (FAO). Phylogenetic analysis was performed using a variety of approaches on all of the publicly available H5 HA sequences that have evolved from the A/Goose/Guangdong/96 H5N1 isolate. The initial results support the idea that the currently circulating highly pathogenic avian influenza H5N1 viruses could be effectively grouped into numerous clades logically designated by a hierarchical numbering system. For example the so-called 'Fujian-like lineage' within the antigenically distinct Clade 2.3 of H5N1 would be designated Clade 2.3.4, with other distinct clade 2.3 branches called 2.3.1 and 2.3.2 and so on, while the 'Qinghai lineage' would be designated Clade 2.2.

If such a system were to become universally accepted, it might serve as a model for other influenza lineages and genes. Some of the data summarized by the Working Group were presented for evaluation at the 6th meeting on Options for the Control of Influenza held in Toronto, Canada from 17 to 23 June 2007 and it was decided that a summary of the publicly available H5N1 sequence data would be published on international websites and would be updated on an on-going basis. It is therefore recommended that the information and clade designations posted below be used by researchers when referring to the currently circulating highly pathogenic H5N1 avian influenza viruses.
(WHO http://www.who.int/csr/disease/avian_influenza/guidelines/nomenclature/en/index.html