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EINet Alert ~ Feb 01, 2008


*****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:

1. Influenza News
- Global: Cumulative number of human cases of avian influenza A/(H5N1)
- Global: Seasonal influenza vaccine may help in fight against H5N1 avian influenza
- Global: Researchers report that engineered antibodies protect mice from H5N1 avian influenza
- Saudi Arabia (Al-Kharj): New outbreak of H5N1 avian influenza leads to mass culling of poultry
- Turkey (Zonguldak): Officials point to wild ducks as cause of H5N1 avian influenza
- Bangladesh: Experts dub deaths amongst crows and ducks "alarming"
- Cambodia: H5N1 avian influenza infection may go undetected in children
- China (Tibet): China confirms new H5N1 avian influenza cases in Tibet
- India (West Bengal): Outbreak of H5N1 avian influenza spreads to over half the state
- Indonesia: New H5N1 avian influenza infections and deaths
- Indonesia: Experts probe high H5N1 avian influenza mortality rate in Indonesia
- Indonesia: Economy launches a new three-year plan to combat H5N1 avian influenza
- Thailand (Phichit): H5N1 avian influenza infection confirmed in Phichit poultry

2. Updates
- AVIAN/PANDEMIC INFLUENZA

3. Articles
- Transmissibility of the Influenza Virus in the 1918 Pandemic
- Emerging Infectious Diseases – Volume 14, Number 2 – January 2008
- Cross-Clade Protective Immune Responses to Influenza Viruses with H5N1 HA and NA Elicited by an Influenza Virus-Like Particle
- Avian influenza: genetic evolution under vaccination pressure
- Emergence of seasonal influenza viruses type A/H1N1 with oseltamivir resistance in some European Countries at the start of the 2007-8 influenza season

4. Notifications
- APEC EINet Pandemic Influenza Preparedness Virtual Symposium: Partnerships and Continuity Planning for Critical Systems
- The FBIIC/FSSCC Pandemic Flu Exercise of 2007: After Action Report
- Highlights from the Bangkok International Conference on Avian Influenza 2008: Integration from Knowledge to Control
- WHO Influenza Virus Tracking System (interim)


1. Influenza News

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

2008
Indonesia / 7 (6)
Viet Nam / 1 (1)
Total / 8 (7)

2007
Cambodia / 1 (1)
China / 5 (3)
Egypt / 25 (9)
Indonesia / 42 (36)
Laos / 2 (2)
Myanmar / 1 (0)
Nigeria / 1 (1)
Pakistan / 1 (1)
Viet Nam 8 (5)
Total / 86 (58)

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)

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

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

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

Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 357 (224). (WHO 1.30.07 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 1.21.08)

WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 1.22.08): http://gamapserver.who.int/mapLibrary/

WHO’s timeline of important H5N1-related events (last updated 1.30.07): http://www.who.int/csr/disease/avian_influenza/ai_timeline/en/index.html.

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Global: Seasonal influenza vaccine may help in fight against H5N1 avian influenza
Animals that have previously been vaccinated against seasonal flu appear to respond far quicker to experimental H5N1 bird flu vaccines, a study has found.

Many doctors believe that seasonal flu vaccines offer little or no protection against the H5N1 virus, which experts say may unleash a pandemic that could kill millions of people. But a study by biotechnology firm MedImmune Inc, which produces influenza vaccine, found that ferrets that had been vaccinated against seasonal flu appeared to be more responsive when they were later administered the H5N1 vaccine.

"If you have previously received normal seasonal flu vaccine, you may have better response to the H5N1 vaccine," MedImmune's scientist Hong Jin told a bird flu conference in Bangkok.

In the MedImmune study, a group of ferrets was given seasonal flu vaccine, while a control group of ferrets were given nothing. After 40 days had elapsed, both groups were given H5N1 vaccines designed using seed virus taken from outbreaks of the disease in Hong Kong in 2003 and Viet Nam in 2004. They were then monitored for the production of H5N1 antibodies.

"We found much more response in ferrets that received (seasonal flu) vaccine, before, whereas in control ferrets, you don't see the response," Hong said. Huge volumes of antibody producing cells were seen in the ferrets that had both vaccines on day 45, but there was no antibody response in the control group, MedImmune said.
(ProMED 1.27.08)

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Global: Researchers report that engineered antibodies protect mice from H5N1 avian influenza
A researcher from Crucell, a Dutch biotechnology company, reported at the Bangkok International Avian Flu Conference that engineered human monoclonal antibodies to the H5N1 virus protected mice from several strains of the virus.

Crucell created the human antibodies by mixing antibody fragments taken from nine blood donors with antigens from two H5N1 strains found in Viet Nam and Indonesia. Mark Throsby, project director for antibody discovery at Crucell, told the conference that in vitro studies showed that one line of the engineered antibodies neutralized several strains of the H5N1 virus, including strains isolated in Hong Kong in 1997, Indonesia in 2005 and Viet Nam in 2003. In the animal studies, he said, researchers injected the engineered antibodies into mice that had been given normally lethal doses of H5N1 virus three days earlier.

"We were able to protect all the animals," Throsby was quoted as saying. "It reduced their disease and they became well again."
(ProMED 1.27.08)

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Europe/Near East
Saudi Arabia (Al-Kharj): New outbreak of H5N1 avian influenza leads to mass culling of poultry
The Saudi agriculture ministry ordered a cull of 158,000 chickens on 29 Jan 2008 following the confirmation of a new outbreak of the H5N1 strain of bird flu. The outbreak was detected on a poultry farm in the Al-Kharj region [Riyadh Province], 80 km (50 mi) south of Riyadh, said a ministry statement. Since the latest outbreak of bird flu was discovered on 15 Nov 2007, some four million birds have been culled on at least 15 separate infected farms. There have been no reports of the disease spreading to humans.
(ProMED 1.29.08)

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Turkey (Zonguldak): Officials point to wild ducks as cause of H5N1 avian influenza
The governor of the northern province of Zonguldak has stated that several chickens in a village in the province were contaminated with a deadly strain of bird flu after they consumed a dead wild duck. In a press conference held on Wednesday 23 Jan 2008, Zonguldak Governor Yavuz Erkmen said the necessary measures had been taken to contain a potential pandemic, and pointed to wild ducks as the source of the disease. "After a series of analyses, we found out that the disease broke out after a family ate a wild duck and gave the leftovers to their chickens. The H5N1 virus in the duck, which spread among the chickens, is the cause of the bird flu case in our province," he said.

Officials from the Ministry of Agriculture and Rural Affairs stated on 21 Jan 2008 that several dead chickens found in Zonguldak's Saz village during a routine inspection conducted on 19 Jan 2008 tested positive for the bird flu virus. The village was immediately put under quarantine, and teams from the local government started culling poultry in the village. "Some 600 chickens, ducks and turkeys have been culled so far. Members of the family who consumed the wild duck in question are currently receiving medical care. Everything is under control; thus, there is nothing to fear," stated Erkmen.

ProMED moderator MHJ states, "I suspect that the domestic poultry were not given the leftovers from the cooked wild duck but that the feathers, feet and unused raw viscera were tossed out into the yard, from which their domestic chickens acquired the virus, if that were the route. An observant reader will note however that no ducks have been tested. Only dead domestic chickens have been tested and the Ministerial presumption then made that it had all started from this culinary duck. There are no reports of sick or dead wild ducks."
(ProMED 1.25.08)

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Asia
Bangladesh: Experts dub deaths amongst crows and ducks "alarming"
Avian influenza is spreading across Bangladesh. From 25-29 Jan 2008, over 1,000 crows died in Barisal, Patuakhali and Dinajpur districts, with laboratory tests confirming they were infected with the H5N1 virus.

Initial reports suggest the crows had eaten bird flu-infected dead chickens thrown away by farmers. Despite government efforts to burn or buy the dead birds, in many places the carcasses of dead chickens and crows can be seen rotting in the open. Habibur Rahman and ASM Alamgir, leading bird flu experts, now describe the situation as "alarming."

On 27 Jan 2008, bird flu was reported at a poultry farm in Peelkhana in Dhaka, nearly a quarter of whose 12 million people live in overcrowded shanties with minimum health and hygiene facilities. Special assistant to the country's chief adviser Manik Lal Samaddar conceded at a press conference that the government was unable to address the situation alone. He called on poultry farmers to help tackle the problem. Every vehicle at 11 border crossings with neighboring India, which is now battling its own outbreak of the virus, is to be sprayed with anti-viral disinfectant. Spraying is also taking place at other key points. Security forces were closely checking for any illegal poultry and egg imports from India. A 16-member government health team was also working at district level to detect and observe the disease, Samaddar said. In addition, 150 volunteers had been appointed under the Directorate of Livestock to prevent the spread of the disease, while's the UN's Food and Agriculture Organization (FAO) was supporting the government in its effort to bring the disease under control.

Moreover, a bird flu ward had been set up in the National Institute of Diseases of the Chest and Hospital in Dhaka, while a laboratory had been established to diagnose infected persons. "The government is well prepared to face any situation," Alamgir said. "Rapid Response Teams (RRT), with 11 trained members in each team, has been put in place in all 64 districts. Personal protective equipment has been provided to five trained RRT members in each of 471 sub-districts. Enough antiviral drugs have been stored at district hospitals for the use of those who cull sick birds," he said. More than 225,000 volunteers had been trained at more than 4,400 unions (elected local government unit at community level) across Bangladesh. "Volunteers are visiting rural households and educating people to report dead or sick birds, safe disposal of solid poultry waste, safe disposal of dead birds, proper hand washing, and other safe health practices," Alamgir explained. Since August 2007, the government of Bangladesh has been implementing a project — with financial assistance of USD 22.3 million from the World Bank — for training livestock officials on bird flu surveillance.
(ProMED 1.29.08)

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Cambodia: H5N1 avian influenza infection may go undetected in children
Bird flu infections in some children may be going undetected because the virus causes mild or no symptoms, researchers in Cambodia found, indicating more human cases have probably occurred than have been officially recorded. A study of 674 people exposed to the deadly H5N1 avian influenza in two villages in Cambodia found seven had developed antibodies against the virus, indicating prior infection. All of the cases occurred in people aged four to 18, the researchers said in a study presented at a conference in Bangkok on 24 Jan 2008. The finding indicates more people, particularly children and adolescents, may be contracting the virus without developing the high fever and severe pneumonia that's the hallmark of H5N1 in humans. A total of three of every five reported human cases worldwide have been fatal. Higher rates of milder disease might indicate the virus has found a way to spread more efficiently in the human population.
(ProMED 1.25.08)

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China (Tibet): China confirms new H5N1 avian influenza cases in Tibet
The Ministry of Agriculture (MOA) announced on 29 Jan 2008 that it had confirmed a new bird flu case among poultry in southwestern Tibet Autonomous Region. The National Bird Flu Reference Laboratory confirmed on 29 Jan 2008 that the case that had affected Jiedexiu Town, Gongga County, on 25 Jan 2008 was caused by the highly pathogenic H5N1 subtype avian influenza virus. The outbreak killed 1,000 birds and led to the culling of another 13,080. No human infections were reported. Bird flu control and prevention efforts were going smoothly, the MOA stated. It said that it had sent experts to coordinate these efforts as the local government blocked off the infected region and stepped up quarantine and oversight to contain the outbreak. The outbreak came less than a month after another case in Turpan, in north western Xinjiang Uygur Autonomous Region, killed 4,850 birds and resulted in the culling of another 29,383.
(ProMED 1.29.08)

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India (West Bengal): Outbreak of H5N1 avian influenza spreads to over half the state
On 25 Jan 2008, bird flu appeared right at the doorstep of Kolkata with two more districts of West Bengal, Purulia and Howrah, falling prey to the deadly virus that has now spread to more than half of the state.

Expert teams were accompanied by police force at many places in culling operations in view of resentment among many villagers fearing loss of livelihood. The culling process has been hindered in most of the affected districts of West Bengal due to incessant rain. However, the district officials have geared up to control the bird flu by distributing Tamiflu drugs among poultry owners. Isolation camps have been set up in the government hospitals for treating the individuals who show clinical symptoms of contracting bird flu.

On 25 Jan 2008, the High Security Animal Disease Laboratory in Bhopal confirmed avian influenza (H5) in samples from Sankrail block of Howrah district and Santuri block of Purulia district.

The virus has now spread to more than half of the state's 19 districts. The 11 districts affected by bird flu are Birbhum, South Dinajpur, Murshidabad, Nadia, Burdwan, Bankura, Malda, Coochbehar, Hooghly, Purulia and Howrah. The samples from Mayureswar-II and Khoyrasole blocks of Birbhum district and Kandi block of Murshidabad district have also tested positive for avian influenza. Official sources in Kolkata said at least 10 lakh [one million] chicken have been culled in the nine affected districts while 1.46 lakh [146,000] eggs have been destroyed as of 24 Jan 2008. At least 901 rapid response teams were deployed today in the state for carrying out culling and surveillance operations.

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Indonesia: New H5N1 avian influenza infections and deaths
The Ministry of Health in Indonesia has confirmed an additional four cases of human infection with the H5N1 avian influenza virus. Of these cases three were fatal. There is no evidence of an epidemiological link between the cases.

The first case, a 31-year-old woman from East Jakarta, Jakarta Province, developed symptoms on 18 Jan 2008, was hospitalized on 22 Jan 2008, and is currently in hospital. The investigation indicated that she visited a wet market where live poultry are sold, three days prior to her onset of symptoms.

The second case, a nine-year-old boy from Depok Municipality, West Java, developed symptoms on 16 Jan 2008, was hospitalized on 23 Jan 2008, and died on 27 Jan 2008. Investigations into the source of his infection indicate that the case lived next door to a wet market where live poultry are sold.

The third case, a 32-year-old man from Tangerang Municipality, Banten Province, developed symptoms on 17 Jan 2008, was hospitalized on 24 Jan 2008, and died on 29 Jan 2008. Investigations into the source of his infection are ongoing.

The fourth case, a 23-year-old woman from East Jakarta, Jakarta Province, developed symptoms on 19 Jan 2008, was hospitalized on 24 Jan 2008, and died on 27 Jan 2008. Investigations into the source of her infection are ongoing.

Of the 124 cases confirmed to date in Indonesia, 101 have been fatal.
(ProMED 1.30.08)

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Indonesia: Experts probe high H5N1 avian influenza mortality rate in Indonesia
Medical experts are worried about how death rates for H5N1 bird flu have shot up in places like Indonesia, and studies are being carried out to see if victims require higher dosages of drugs. Although the H5N1 has only infected 352 people since 2003, it has killed 219 of them, with mortality rates rising to more than 80 percent in places like Indonesia in the past two years.

"It could be they are treated later, or the virus is different, more virulent. There are many maybes, including differences in susceptibility," Menno de Jong, a doctor who has treated bird flu victims in Viet Nam, said at the bird flu conference in Bangkok.

He said a major concern was the H5N1 variant in Indonesia appeared to be less susceptible to oseltamivir, the antiviral used to combat the disease. "It's not a drug resistant virus, it's just that a bit more drug may be needed to inhibit these (H5N1) clade 2 viruses," he said, referring to the sub-category that Indonesia's H5N1 virus has been classified under. Studies are being conducted in Thailand, Viet Nam and Indonesia to see if H5N1 patients need to be given higher dosages of oseltamivir.
(ProMED 1.25.08)

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Indonesia: Economy launches a new three-year plan to combat H5N1 avian influenza
Indonesia, on 30 Jan 2008, launched a new three-year plan to fight bird flu, just days after the confirmed death toll topped 101 in the country hardest hit by the H5N1 virus. The plan will be funded by a USD 20 million European Union (EU) grant channeled through the World Health Organization (WHO), the health ministry's disease control director Nyoman Kandun said. Indonesia accounts for just under half of the 224 human bird flu deaths worldwide, according to WHO figures. The 101st victim died on 29 Jan 2008.

Kandun said Indonesia would need to meet with EU and WHO officials on a "routine basis" in order for the plan to work. WHO's Indonesia representative Subhash Salunke said the strategy would focus on preventing new infections, better monitoring of the spread of the virus and continued scientific research. "Prevention of new cases remains an urgent priority, while improving survival [rates] of those infected is another major priority," he said. The prevention campaign would include ramped up efforts to improve hygiene in the country's wet markets and public awareness initiatives. "The persistence of H5N1 in Indonesia has serious (global) consequences for health, economies and food security," Salunke said. "Out of 33 provinces, in 31 provinces this is an endemic virus ... because it is present in such a vast area, the opportunity for virus and human being contact is immense," Salunke said.
(ProMED 1.31.08)

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Thailand (Phichit): H5N1 avian influenza infection confirmed in Phichit poultry
The re-emergence of avian flu was confirmed in Phichit, a day after Nakhon Sawan province was declared a bird flu outbreak zone on 24 Jan 2008, according to Livestock Development Department chief Sakchai Sriboonsue. Sakchai said the H5 strain of bird flu was detected at a chicken farm in tambon Sak Lek of Sak Lek sub-district following lab tests on carcass samples. Phichit is the second outbreak location in 2008 after Nakhon Sawan. A total of 70 chickens were being raised in the farm. Of them, 30 began to fall sick on 8 Jan 2008. On 22 Jan 2008, the farm owner told livestock officials to inspect and collect some carcass samples for lab tests. The H5 strain of bird flu was later confirmed. Sakchai said further tests were needed over the next couple of days to determine whether the poultry was infected with the deadly H5N1 virus, which was transmissible to humans.

Meanwhile, Agriculture and Cooperatives Minister Thira Sutabutra said the authorities had mounted regular surveillance operations to prevent H5N1 outbreaks in the country. Hence, there was unlikely to be an impact on poultry consumption at Chinese New Year, he said. Consumers could buy avian flu-free poultry products at outlets guaranteed by the Livestock Department or labeled ''Q-Mark'' by the ministry. Thira added that poultry exports might not feel the pinch from the re-emergence of bird flu because authorities had managed to keep outbreaks under control immediately.
(ProMED 1.25.08)

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2. Updates
AVIAN/PANDEMIC INFLUENZA
(UN; WHO; FAO, OIE; CDC; Health Canada; CIDRAP; PAHO; USGS)

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3. Articles
Transmissibility of the Influenza Virus in the 1918 Pandemic
White LF, Pagano M. PLoS ONE. 2008;3(1): e1498.
doi:10.1371/journal.pone.0001498
http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/index.html .

Background
With a heightened increase in concern for an influenza pandemic we sought to better understand the 1918 Influenza pandemic, the most devastating epidemic of the previous century.

Methodology/Principal Findings
We use data from several communities in Maryland, USA as well as two ships that experienced well-documented outbreaks of influenza in 1918. Using a likelihood-based method and a nonparametric method, we estimate the serial interval and reproductive number throughout the course of each outbreak…

Conclusions/Significance
These results illustrate the importance of considering the population dynamics when making statements about the epidemiological parameters of Influenza. The methods that we employ for estimation of the reproductive numbers and the serial interval can be easily replicated in other populations and with other diseases.
(CIDRAP 1.30.08)

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Emerging Infectious Diseases – Volume 14, Number 2 – January 2008
This issue includes articles on antiviral stockpiling to combat pandemic influenza, atypical BSE in France, the emergence of new norovirus strains on cruise ships, and many other infectious disease topics. New issue online at: http://www.cdc.gov/ncidod/eid/

Cost-effectiveness of Antiviral Stockpiling and Near-Patient Testing for Potential Influenza Pandemic
Siddiqui MR, et al. Emerging Infectious Diseases. Volume 14, Number 2–February 2008
http://www.cdc.gov/eid/content/14/2/267.htm

Abstract
A decision analytical model was developed to investigate the cost-effectiveness of stockpiling antiviral (AV) drugs for a potential influenza pandemic in the United Kingdom and the possible role of near-patient testing in conserving AV drug stocks. Under base-case assumptions (including a fixed stockpile that was smaller than the clinical attack rate), the treat-only option (treating all symptomatic patients with AV drugs) would be considered cost-effective (£1,900–£13,700 per quality-adjusted life year [QALY] gained, depending on the fatality scenario), compared with no intervention (nonintervention but management of cases as they arise). The test-treat option (testing all symptomatic patients but treating those with positive tests results only) would result in moderate gains in QALYs over the treat-only option but at relatively large additional costs. Stockpiling sufficient AV drugs (but not near-patient tests) to treat all patients with clinical cases would be cost-effective, provided AV drugs are effective at preventing deaths from pandemic influenza.

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Cross-Clade Protective Immune Responses to Influenza Viruses with H5N1 HA and NA Elicited by an Influenza Virus-Like Particle
Bright RA, et al. PloS ONE. 2008;3(1): e1501. doi:10.1371/journal.pone.0001501
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001501

Background
Vaccination is a cost-effective counter-measure to the threat of seasonal or pandemic outbreaks of influenza. To address the need for improved influenza vaccines and alternatives to egg-based manufacturing, we have engineered an influenza virus-like particle (VLP) as a new generation of non-egg or non-mammalian cell culture-based candidate vaccine.

Methodology/Principal Findings
We generated from a baculovirus expression system using insect cells, a non-infectious recombinant VLP vaccine from both influenza A H5N1 clade 1 and clade 2 isolates with pandemic potential. VLPs were administered to mice in either a one-dose or two-dose regimen and the immune responses were compared to those induced by recombinant hemagglutinin (rHA). Both humoral and cellular responses were analyzed. Mice vaccinated with VLPs were protected against challenge with lethal reassortant viruses expressing the H5N1 HA and NA, regardless if the H5N1 clade was homologous or heterologous to the vaccine. However, rHA-vaccinated mice showed considerable weight loss and death following challenge with the heterovariant clade virus. Protection against death induced by VLPs was independent of the pre-challenge HAI titer or cell-mediated responses to HA or M1 since vaccinated mice, with low to undetectable cross-clade HAI antibodies or cellular responses to influenza antigens, were still protected from a lethal viral challenge. However, an apparent association rate of antibody binding to HA correlated with protection and was enhanced using VLPs, particularly when delivered intranasally, compared to rHA vaccines.

Conclusion/Significance
This is the first report describing the use of an H5N1 VLP vaccine created from a clade 2 isolate. The results show that a non-replicating virus-like particle is effective at eliciting a broadened, cross-clade protective immune response to proteins from emerging H5N1 influenza isolates giving rise to a potential pandemic influenza vaccine candidate for humans that can be stockpiled for use in the event of an outbreak of H5N1 influenza.
(CIDRAP 1.30.08)

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Avian influenza: genetic evolution under vaccination pressure
Escorcia M, et al. Virology Journal. Virology Journal 2008, 5:15doi:10.1186/1743-422X-5-15
http://www.virologyj.com/content/5/1/15

Abstract
Antigenic drift of avian influenza viruses (AIVs) has been observed in chickens after extended vaccination program, similar to those observed with human influenza viruses. To evaluate the evolutionary properties of endemic AIV under high vaccination pressure (around 2 billion doses used in the last 12 years), we performed a pilot phylogenic analysis of the hemagglutinin (HA) gene of AIVs isolated from 1994 to 2006. This study demonstrates that Mexican low pathogenicity (LP) H5N2-AIVs are constantly undergoing genetic drifts. Recent AIV isolates (2002-2006) show significant molecular drifts when compared with the H5N2 vaccine-strain or other field isolates (1994-2000). This study also demonstrates that molecular drifts in the HA gene lineages follow a yearly trend, suggesting gradually cumulative sequence mutations. These findings might explain the increasing incidence of LP H5N2 AIV isolated from commercial avian farms. These findings support recent concerns about the challenge of AIV antigenic drift and influenza epidemics.
(CIDRAP 1.24.08)

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Emergence of seasonal influenza viruses type A/H1N1 with oseltamivir resistance in some European Countries at the start of the 2007-8 influenza season
Interim ECDC Risk Assessment - January 27th 2008
http://ecdc.europa.eu/pdf/080127_os.pdf

Summary
Preliminary results from a survey of antiviral drug susceptibility among seasonal influenza viruses circulating in Europe has revealed that some of the A (H1N1) viruses in circulation this winter are resistant to the antiviral drug, oseltamivir (also know by the brand name Tamiflu). So far, 148 samples of influenza A(H1N1) viruses isolated during November and December from ten European countries have been tested by the EU funded VIRGIL network. Of the 148 samples, 19 showed evidence of resistance to oseltamivir.
(ProMED 1.29.08)

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4. Notifications
APEC EINet Pandemic Influenza Preparedness Virtual Symposium: Partnerships and Continuity Planning for Critical Systems
APEC EINet is pleased to host a special videoconference on pandemic influenza preparedness. This videoconference is a follow-up to our first “virtual symposium”, which was conducted in January 2006 with great success (participating economies were Australia, Canada, China, Korea, Philippines, Singapore, Chinese Taipei, Thailand, USA, and Viet Nam). You can view a five-minute videoclip of our previous virtual symposium at: http://depts.washington.edu/einet/symposium.html. Our upcoming videoconference will be held in late May 2008. It will take place during the evening hours of 29 May in the Americas and in the morning hours of 30 May in Asia, for approximately 3.5 hours. Our objective is to describe how private and public sectors in the APEC region can cooperate and work effectively to prepare for and respond to an influenza pandemic.

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

  1. Bring together economies in a dynamic, real-time discussion on preparedness through the collaboration of the health and the business/trade sectors, with a focus on critical systems continuity.
  2. Share specific examples of current practices — e.g. scenario exercises, communication drills and policy evaluation.
  3. Use innovative technologies (e.g. Access Grid) for real-time, virtual interchange, enhancing their utility for future collaboration and response in the event of a pandemic.
Videoconferencing offers an alternative to in-person conferencing. It cuts down on the time and cost of traditional conferences requiring long-distance travel. Simultaneous communication with multiple sites is possible, with numerous visualization options. Real-time web-based information exchange is also possible, and, during an actual pandemic, the virtual medium would be a safe way to communicate when international travel is limited or prohibited.

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The FBIIC/FSSCC Pandemic Flu Exercise of 2007: After Action Report
Read full text at: http://www.fspanfluexercise.com/Pandemic%20Flu%20AAR.pdf

Beginning September 24, 2007, more than 2,700 U.S. financial services organizations participated in a three-week exercise simulating a severe global pandemic flu. The scenario for this exercise posed a realistic picture of the possible systemic risks to the sector and its dependencies on other critical infrastructures. Based on the findings of this exercise, it appears that while there will be significant impacts to the financial services sector, the sector overall will continue to operate and cope with these impacts. This free and voluntary exercise provided organizations from the banking, insurance and markets (securities and derivatives) industries, as well as financial utilities, trade associations and regulators, an opportunity to assess their pandemic plans against a rigorous and detailed scenario. The scenario was developed by a team of technical experts from diverse disciplines that few organizations have the ability to tap on their own.

The exercise was designed to use progressive absenteeism rates — reaching as high as 49 percent — to stress the contingency plans of participating organizations. Critical infrastructures that the financial services sector relies on were also stressed during the exercise to simulate likely degradation in available services. Through this approach, the sector was able to gauge how their individual organizations and markets might be expected to cope with different levels of a pandemic.
(CIDRAP 1.25.08)

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Highlights from the Bangkok International Conference on Avian Influenza 2008: Integration from Knowledge to Control
http://www.biotec.or.th/aiconf2008/home/index.asp

The Bangkok meeting drew about 500 experts from 40 countries to discuss research and ideas on a wide range of topics. Some other topics discussed included the idea that some human cases of H5N1 avian influenza escape detection due to mild or absent symptoms, stockpiling vaccine adjuvants to prepare for a pandemic, the use of engineered human antibodies as a defense against the H5N1 virus, and the high H5N1 case-fatality rate in Indonesia.

Cambodian study
The Cambodian researchers tested 674 people in two villages who were exposed to the virus and found that seven of them, all between the ages of four and 18, had antibodies signaling previous infection. The finding contrasts with previous serologic studies of people in areas affected by H5N1 outbreaks. A review published Jan 16 2008 in the New England Journal of Medicine (NEJM) said the few serologic studies since 2003 of people with potential exposure to H5N1 suggest that asymptomatic or mild cases are rare. The studies involved people living with backyard poultry, workers in live-bird markets and healthcare workers.

More cases of mild disease might suggest that the virus is improving its ability to spread among humans, while becoming less virulent. Based on the current global count of 353 cases with 221 deaths, the case-fatality rate is almost 63 percent. The Cambodian researchers, led by Sirenda Vong of the Pasteur Institute of Cambodia in Phnom Penh, conducted their study in early 2006. The researchers asked villagers about their exposure to poultry and tested their blood for antibodies to H5N1. The median age of the seven people who had antibodies was 12 years, compared with 27 years for those who had no antibodies. Vong and colleagues had conducted a similar study of 351 Cambodian villagers in 2005 and found that none had antibodies to the virus. The study was published in Emerging Infectious Diseases in 2006.

Malik Peiris, a microbiology professor at the University of Hong Kong, said, "Most of the children diagnosed in Hong Kong in 1997 had a very mild course of infection; they basically had a mild flu-like illness and they recovered… I don't think there is any evidence to say the situation has changed."

Stockpiling of adjuvants
Another topic raised at the meeting was the idea of separately stockpiling adjuvants, immune-boosting chemicals that enable vaccine producers to reduce the dose of antigen in a vaccine without reducing immune response. Global health officials, including those at the World Health Organization (WHO), hope this dose-sparing approach could dramatically increase the world supply of pandemic vaccine.

Albert Osterhaus, a virologist at Erasmus Medical Center in the Netherlands who spoke at the conference on Jan 23 2008, said stockpiling adjuvants would be useful if the pandemic strain turned out to be a subtype other than H5N1. "There's a lot of discussion to vaccinate people against H5N1 with adjuvanted vaccines," Osterhaus said. "We might do that, but it's very expensive and it might well be that the pandemic outbreak may not be caused by H5N1 but by H7, H9 or H2 [viruses]." Osterhaus said adjuvants should be stockpiled separately from antigens. "Adjuvants can be stockpiled and H5 antigen as well," he said. "So if the pandemic is going to be H5N1, you just mix them and you get a vaccine. If not, you rapidly produce the antigen and add it together with the adjuvant."

Currently, the United States has no licensed influenza vaccines that contain adjuvants. However, a few studies of influenza vaccines with alum-based adjuvants have shown acceptable protection levels. In August 2007, researchers working on a GlaxoSmithKline vaccine reported positive results for a split-virus vaccine combined with a proprietary oil-and-water adjuvant. A month later, Sanofi Pasteur reported promising results for its inactivated vaccine paired with its own adjuvant.

Using engineered antibodies
In other developments, a researcher from Crucell, a Dutch biotechnology company, reported at the conference today that engineered human monoclonal antibodies to the H5N1 virus protected mice from several strains of the virus. Crucell created the human antibodies by mixing antibody fragments taken from nine blood donors with antigens from two H5N1 strains found in Viet Nam and Indonesia. In the animal studies, he said, researchers injected the engineered antibodies into mice that had been given normally lethal doses of H5N1 virus three days earlier. "We were able to protect all the animals," Throsby, project director for antibody discovery, was quoted as saying. "It reduced their disease and they became well again."

Drug resistance in Indonesia?
Menno de Jong, a virologist at an Oxford University clinical research unit in Ho Chi Minh City, Viet Nam, spoke on the topic of drug failure in the treatment of patients who have H5N1 infections. The case-fatality rate for the disease in Indonesia is especially high—82 percent, compared with about 63 percent overall, based on WHO figures. De Jong told the conference that researchers are conducting studies to see if H5N1 patients in places like Indonesia, Thailand and Viet Nam require higher doses of antiviral medications. "It could be they are treated later, or the virus is different, more virulent," de Jong told a Reuters reporter. "There are many maybes, including differences in the susceptibility of the virus." He said the H5N1 viruses in Indonesia appear less susceptible to osteltamivir, the antiviral recommended as first-line treatment for H5N1 infections. "It's not a resistant virus, it's just that a bit more drug [may be] needed to inhibit these [H5N1] clade 2 viruses," he said. De Jong was a member of the WHO expert panel that wrote the recent review in the NEJM on human H5N1 cases. In line with de Jong's observations at the Bangkok meeting, that article said clade 1 viruses appear to be 15 to 30 times more susceptible to oseltamivir than clade 2 viruses from Turkey and Indonesia. However, the panel wrote that the clinical relevance of this difference in oseltamivir susceptibility "remains to be determined."
(CIDRAP 1.25.08)

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WHO Influenza Virus Tracking System (interim)
http://www.who.int/fluvirus_tracker

WHO is developing an electronic system to track influenza A (H5) viruses that have been shared by Member States with WHO through the Global Influenza Surveillance Network (GISN). The tracking system, currently available in an interim version, indicates which H5N1 viruses/specimens have been shared with WHO, where they are located, analyses that have subsequently been conducted, further development into H5N1 vaccine viruses and recipients of the vaccine viruses and other viruses. Improvement of the interim system is ongoing and it is anticipated that this system will be upgraded in the future. The interim system contains data for the majority of viruses and clinical specimens that have been shared with WHO from 24 November 2007 onwards, as well as all H5N1 viruses that have been developed into vaccine viruses.

Data entry of the remaining viruses and clinical specimens (from 24 November 2007 onwards) is ongoing.

Currently the data entry is conducted by WHO Collaborating Centers, WHO H5 Reference Laboratories, and regulatory laboratories which are involved in the WHO H5N1 vaccine virus selection and development process.
(CIDRAP 1.22.08)

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 apecein@u.washington.edu