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EINet Alert ~ May 23, 2009*****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 - Cumulative number of human cases of influenza A/(H1N1) - Cumulative number of human cases of avian influenza A/(H5N1) - Global: WHO group envisions greater production of H1N1 vaccine - Global: WHO is urged to go slow on declaring pandemic - Global: Health groups criticize focus on influenza A/H1N1 at WHO meeting - Global: WHO director hopeful agreement can be reached on virus sharing - UK: Attempts to contain influenza A/H1N1 questioned by experts - China (Qinghai): Low pathogenic avian influenza H5N1 confirmed in migratory birds - Japan: Reports spike in influenza A/H1N1 infection, majority of cases locally acquired - Canada: PHA update on influenza A/H1N1 - Canada (Alberta): Scientists map genetic sequence of virus found in swine - Mexico: APEC update on outbreak of influenza A/H1N1 virus infection - USA: CDC update on influenza A/H1N1 - USA: CDC says influenza A/H1N1 spreads about as readily as seasonal flu - Egypt: Human infection avian influenza H5N1 reaches 74 cases, children heavily burdened 2. Updates - INFLUENZA A/H1N1 - AVIAN INFLUENZA 3. Articles - Serum Cross-Reactive Antibody Response to a Novel Influenza A (H1N1) Virus After Vaccination with Seasonal Influenza Vaccine - Pandemics: avoiding the mistakes of 1918 - Pandemics: good hygiene is not enough - Hospitalized Patients with Novel Influenza A (H1N1) Virus Infection--California, April-May, 2009 - Novel H1N1 influenza in people: global spread from an animal source? - Why are Mexican data important? 4. Notifications - Weekly Epidemiological Record Bulletin - Influenza in the Asia-Pacific 1. Influenza News Global Cumulative number of human cases of influenza A/(H1N1) 42 countries have officially reported 11,168 cases of influenza A/H1N1 infection, including 86 deaths.
Economy / Cases (Deaths)
An additional first case has been confirmed in Russia.
APEC economy updates: Malaysia reported its first two confirmed cases of influenza A/H1N1, while the Philippines confirmed its first case. All individuals reported travel to the United States. Chinese Taipei reported its first confirmed H1N1 case. Illness was detected in an airport screening upon return from the United States. Chile confirmed its first two cases of H1N1 infection. The two people had a history of travel to the Dominican Republic with a connecting flight in Panama. Peru reported it first confirmed case of H1N1; the individual had a history of travel to the United States. Japan reported its first confirmed case of locally acquired H1N1 infection and a large spike of infections among students in Kobe and Osaka. Australia also reported its first case of locally acquired H1N1 infection. Cumulative number of human cases of avian influenza A/(H5N1)
2009
***For data on human cases of avian influenza prior to 2009, go to:
Total no. of confirmed human cases of avian influenza A/(H5N1), Dec 2003 to present: 429 (262).
Avian influenza age distribution data from WHO/WPRO: WHO's maps showing world's areas affected by H5N1 avian influenza (last updated 5/10/09): http://gamapserver.who.int/mapLibrary/
WHO’s timeline of important H5N1-related events (last updated 3/23/09): Global: WHO group envisions greater production of H1N1 vaccine
The four-page report is based on a 14 May 2009 teleconference of about 40 stakeholders, called the Ad Hoc Policy Advisory Working Group on Influenza A (H1N1) Vaccines. It was released late on 18 May 2009. The report says that vaccine makers are expected to produce about 480 million doses of seasonal flu vaccine for the northern hemisphere's 2008-09 flu season. About 350 million doses will be ready by 30 June 2009 and 430 million doses by 31 Jul 2009. The report continues, "It is estimated that up to 4.9 billion doses [of novel H1N1 vaccine] could be produced over a 12-month period after the initiation of full-scale production," if production yields are about the same as for seasonal flu vaccines and if "the most dose-sparing formulations" are used. The estimate of 4.9 billion doses is far above the 1 billion to 2 billion doses mentioned by the WHO's Dr. Marie-Paul Kieny. She said that was based on an estimated global production capacity of about 900 million doses for seasonal vaccine. The report says that a monovalent vaccine is the preferred option for the H1N1 vaccine. There has been speculation about adding a novel H1N1 vaccine to the seasonal flu vaccine, which targets three flu strains, creating a four-strain vaccine that could protect against seasonal flu and the novel virus. But the report says this "would have significant regulatory implications," implying it would cause delays.
Access the whole report at http://www.who.int/csr/resources/publications/swineflu/tc_report_2009_05_14/en/index.html. Global: WHO is urged to go slow on declaring pandemic
With the novel H1N1 virus spreading widely in the United States and Mexico, the current pandemic alert level is phase 5, meaning community outbreaks are occurring in more than one country in one WHO region. But cases in Japan jumped from 4 to 129 over the weekend of 15 May 2009, signaling possible community spread in a second region. In the current WHO system, that would mean it's time to declare phase 6, a full-scale pandemic. "We remain in phase 5 today," Chan said. "The virus may have given us a grace period, but we do not know how long this grace period will last. No one can say whether this is just the calm before the storm." WHO officials last week emphasized that the pandemic alert phases are based on how widely a virus is spreading, not on how severe the illness is or how great the possible impact on society.
Officials worry about sowing panic Johnson asserted that a pandemic declaration should in part reflect the severity of the disease, not just its geographic extent. "It's very important that that's reflected in your ability as to whether to move from 5 to 6," he said. "So I would like to propose that you have more flexibility in that rather than follow a mechanistic process." Johnson was backed by New Zealand, Switzerland, and the head of the Pan American Health Organization, according to an Agence France-Presse (AFP) report.
Protecting developing countries "Today, around 85% of the burden of chronic disease is concentrated in low- and middle-income countries," she said. "The implications are obvious. The developing world has, by far, the largest pool of people at heightened risk for severe and fatal H1N1 infections." She said the WHO hopes to offer advice on protecting people in vulnerable groups: "Ideally, we will have sufficient knowledge soon to advise countries on high-risk groups and recommend that efforts and resources be targeted to these groups." Chan also noted that diarrhea has occurred in about 25% of H1N1 cases, an unusual feature for influenza. If the virus is shed in fecal matter, that would mean trouble for places with poor sanitation, such as urban shantytowns, she said.
Chan also expressed concern about the chance of the new virus mixing with seasonal flu strains or H5N1 avian flu to spawn still other new strains. Noting that the novel H1N1 virus has reached the southern hemisphere, she said, "We have every reason to be concerned about interactions of the new H1N1 virus with other viruses that are currently circulating in humans." Global: Health groups criticize focus on influenza A/H1N1 at WHO meeting
Health officials from some poorer nations also could not understand why the diseases hurting them most were a distant second to H1N1 influenza. "Malaria, drug-resistant tuberculosis--they are killing people every day," said Dr. Sam Zaramba, Uganda's chief medical officer. "If all the emphasis that has been put on swine flu had been put on malaria and TB, we would have made a bigger impact on health." Zaramba and other African officials said they had to fight hard to get tuberculosis back on the agenda. So far, the H1N1 influenza virus that has infected more than 10,000 people -- mostly in Mexico and the United States -- appears little more dangerous than seasonal flu. Most people infected do not need treatment, but the concern of many of the world's leading health authorities is that the virus may somehow mutate into a more lethal disease. WHO spokesman Thomas Abraham said some issues had to be dropped when the agency's 193 member nations decided to shorten their annual meeting because their ministers were needed at home to prepare against a possible flu pandemic. But he said the assembly was still taking on a "broad agenda" that went far beyond swine flu to deal with improving basic health care and tackling global killers like TB. "H1N1 influenza is not taking up the major portion of discussions," Abraham said. "And just because a topic is not discussed here does not mean WHO programs are going to stop."
To fight the global influenza H1N1 outbreak, WHO has redirected some of its own staff from other health programs. The agency sent a memo to staff asking for volunteers to work on H1N1, saying "a sustained effort will be needed in the weeks/months to come to maintain this operation." Health campaigners called it a missed opportunity for a number of diseases that could use greater global attention. Global: WHO director hopeful agreement can be reached on virus sharing
The WHO's 193 member states have been holding negotiations since 2007 on tricky questions related to their readiness for a pandemic, prompted first by concerns about the H5N1 virus that has not yet spread easily between people. The biggest sticking point in those talks has been how and when biological samples of viruses would be shared with the world's pharmaceutical companies who need them to make vaccines, an issue known as "material transfer." Indonesia and other developing countries have been pushing for guarantees that vaccines developed from such virus samples they provide will be made available at an affordable price, and in sufficient quantities to protect poorer nations.
Chan, who fought bird flu and Severe Acute Respiratory Syndrome (SARS) as Hong Kong's health director, said it appeared to be time to push the 2-1/2-year-old talks toward a conclusion. She won support for a proposal for her to "facilitate a process to finalize the remaining elements including the standard material transfer agreement" and then present a deal to the WHO's executive board in January 2010. Europe/Near East UK: Attempts to contain influenza A/H1N1 questioned by experts Flu experts are looking very closely at Britain, and some have decided that the UK's tactics for controlling influenza A H1N1 are problematic and may be hiding a much larger outbreak. Since Britain has the most confirmed novel H1N1 cases in Europe, how the outbreak develops there will have a significant influence on whether the World Health Organization decides to raise its flu alert to the highest level--phase 6 indicating a pandemic, or global epidemic. British authorities have relied on an aggressive strategy to try to snuff out the virus before it spreads, blanketing suspect cases and anyone connected to them with the antiviral medication Tamiflu. But experts criticize the strategy for wasting valuable medicine and say there's little point trying to contain H1N1, which the WHO says is at least as infectious as regular flu. "Containment using Tamiflu is a flawed concept," said Michael Osterholm, a flu expert at the University of Minnesota. "It's like trying to maintain the integrity of your submarine with screen doors." Osterholm, who has advised U.S. authorities on preparing for a pandemic, said the influenza H1N1 virus travels too fast to stop it with Tamiflu. "You are never going to contain a flu virus with this strategy and at the end of it all, you will have wasted time and drugs," he said, because it takes much more Tamiflu to prevent a case than it does to treat one. Similar strategies were initially tried in the US, Canada, and Japan but authorities quickly dumped the tactic. Authorities in Mexico never even tried to contain the virus, it was too widespread before they realized what it was. British health officials have confirmed 112 swine flu cases--the most in Europe, ahead of Spain. Still, that number has raised eyebrows among experts for being suspiciously low, given swine flu's infectiousness and its rapid spread elsewhere. Rumors have swirled among officials for weeks that Britain's caseload is far higher than officials are admitting. Swine flu was first detected in Britain in April 2009. Experts say flu viruses only need a couple of weeks to become established in a new location. Albert Osterhaus, a virologist at Erasmus MC University in the Netherlands, said once the virus has been circulating, it's time to abandon the containment strategy and save Tamiflu for patients. Experts said Britain's attempt to squash H1N1 might also be masking the true size of the outbreak. Antivirals work by reducing the amount of virus in a person's body, so people who have swine flu and are taking Tamiflu might test negative for the virus. Andrew Pekosz, a flu expert at Johns Hopkins University, said the low numbers of confirmed cases in Britain could also be due to limited testing. The U.S. Centers for Disease Control and Prevention is testing up to 400 specimens a day. But the British health agency has refused to say how many tests are being done daily. The UK is also only testing people with a history of visiting infected countries like Mexico or the United States, or people with links to already-established cases. That limited criteria means authorities could be missing lots of other cases if the virus has already spread into communities. "There's no reason to think this virus would behave differently in Europe than in North America," Pekosz said. "The numbers in the U.S. and Mexico suggest that once you have a certain number of cases, you can seed a relatively wide outbreak." For its part, Spain is taking much the same tactic as Britain. Health authorities have started announcing new H1N1 cases only once a week and are handing out antiviral drugs to both confirmed and suspected cases.
Countries outside of North America may be reluctant to admit they have a bigger outbreak on their hands, since that could prompt WHO to declare a pandemic. Many governments fear that announcing a pandemic would produce mass panic and confusion, with citizens clamoring for vaccines, antiviral medications, trade restrictions and travel bans, that could be costly or even ineffective. Asia China (Qinghai): Low pathogenic avian influenza H5N1 confirmed in migratory birds On 17 May 2009, the Chinese Ministry of Agriculture announced that the National Avian Influenza Reference Laboratory confirmed avian influenza among migratory birds in Qinghai province. The regional veterinary departments in Gahai found dead migratory birds on 8 May 2009. Specimens were collected and sent for testing. On 12 May 2009, the Qinghai Provincial Animal Disease Prevention and Control Center detected positive signals for highly pathogenic avian influenza. On 17 May 2009, the birds were confirmed to be infected with highly pathogenic H5N1 avian influenza by the National Avian Influenza Reference Laboratory. As of 17 May 2009, 121 wild birds had died.
In response to the outbreak, access to the affected area was restricted for disinfection and culling of backyard poultry. All 121 dead wild birds and 600 culled poultry have been processed. No outbreak among poultry has been found in Qinghai province. Japan: Reports spike in influenza A/H1N1 infection, majority of cases locally acquired
Authorities in infected regions, who fear an imminent outbreak in the country, have decided to close educational centers and to ask facilities such as movie theaters to close down and prevent the spread of the disease. Prime Minister Taro Aso called on the public to remain calm. The spread of the new H1N1 strain of influenza A has prompted more than 4,000 schools in the two western Japan prefectures to close or consider closing, affecting more than 1.4 million pupils.
Meanwhile, two high school girls who live in the Tokyo area were found to have the novel H1N1 flu on 20 May 2009, two days after they returned from a trip to New York City, according to the Japan Times. Their cases are the first in the Tokyo area. Americas Canada: PHA update on influenza A/H1N1 PHA has confirmed 719 human cases of influenza A (H1N1) in ten provinces/territories, including one death in Alberta. Provinces most heavily burdened are Onterio (284), British Columbia (114), and Quebec (106). Provinces that have not reported cases are Newfoundland, Northwest Territories, and Nunavut. (PHA 5/20/09) Canada (Alberta): Scientists map genetic sequence of virus found in swine
Influenza viruses do not affect the safety of properly handled and cooked pork. In collaboration with their colleagues at Canada's National Microbiology Laboratory, CFIA scientists now have a complete picture of the virus detected in swine on an Alberta farm. This validates early results and confirms that the virus found in the pigs is the same as the virus causing illness in humans around the world. CFIA will share the diagnostic methods developed to identify the novel H1N1 influenza in swine with provinces and territories, international agencies and other countries to facilitate surveillance and detection activities.
Researchers are now focusing on how the H1N1 flu virus affects swine. Although more study is needed, early observations suggest that infected animals become sick and recover naturally, just as they would if exposed to influenza viruses commonly seen in swine herds at a global level. Ongoing CFIA research is examining whether or not other animals are susceptible to the virus. This information may be used to refine disease prevention and control measures. Studies are also underway to assess the effectiveness of current vaccines and to develop better and faster diagnostic methods. Mexico: APEC update on outbreak of influenza A/H1N1 virus infection
On 16 May 2009, President of Mexico, Felipe Calderon handed over to WHO the strain of influenza virus A/H1N1, to contribute to the development of a vaccine against this disease. Mexico also provided WTO with statistical information on patients, treatment and their location in the country. The Mexican government, along with hotels and airlines, launched an aggressive overseas campaign to restore tourism activities, encouraging tourists to visit Mexican destinations, such as Cancun. At the plenary session of the meeting of the World Health Organization, the Mexican Minister of Health proposed the creation of a Compensatory Fund, with resources from IMF and the World Bank, which would allow Mexico and other affected countries to overcome economic loss due to the impact generated by virus A/H1N1 in different sectors such as tourism and foreign trade. This fund would be directed to those countries which timely notify events of public health that could become of international concern, as a means of encouraging transparency and international cooperation.
Additionally, the Ministry of Foreign Affairs continues intense diplomatic process, aiming to eliminate unjustified flight and movement of people restrictions imposed against Mexicans. Several countries, including the USA, United Kingdom, Italy, Belgium, Switzerland, Israel, Argentina, Peru, and Ecuador have removed the preventive measures adopted towards Mexico. USA: CDC update on influenza A/H1N1
USA: CDC says influenza A/H1N1 spreads about as readily as seasonal flu
Early in Mexico's H1N1 epidemic, some studies suggested that each person sick with the new virus was spreading it to many others, Jernigan said. However, "The more we look at it here in the United States, what we're seeing is the attack rates really coming in at about what we would see with seasonal influenza," Jernigan said. From the studies so far, the transmission both within households and within communities seems to be about the same as with seasonal flu, he said. "From a policy standpoint, we expect this to be spreading the same as we would see with seasonal influenza, but again, remember that a larger portion of the population may have absolutely no immunity or any protection for this one, which is different than what would happen through normal seasonal influenza," Jernigan added.
Jernigan also commented on the possibility that older people have some protection against the new virus because of exposure to H1N1 viruses decades ago. In an earlier report, a World Health Organization advisory group said older adults were shown to have neutralizing antibodies to the new virus. He said older people most likely were exposed to H1N1 viruses—distant cousins of the new virus—before 1957, "and there's a possibility that having exposure to that virus many years ago may allow you to have some reaction to the new H1N1 that's now circulating." Jernigan said it's not yet known just how much protection older people may have. Africa Egypt: Human infection avian influenza H5N1 reaches 74 cases, children heavily burdened The Ministry of Health of Egypt has multiple new confirmed human cases of avian influenza H5N1 in children. A boy, age 3, began experiencing fever and runny nose on 12 May 2009. He was admitted to Mahalla Fever Hospital 15 May 2009. Infection with avian influenza was confirmed on 15 May 2009. His family reported contact with sick poultry. He was reported in good general condition on 17 May 2009. The boy is the 71st case of highly pathogenic avian influenza in Egypt. The 72nd case is a 4 year-old girl in Meet Ghamr District of Dakahlia Governorate. She began experiencing symptoms on 9 May 2009. She was admitted to Mansoura Chest Hospital with pneumonia on 17 May 2009. Infection with avian influenza was confirmed on 18 May 2009. A history of close contact with sick poultry was reported. The girl died on 18 May 2009. In Dakahlia Governate, Sherbun District, a 4 year-old boy began experiencing fever on 18 May 2009. He was admitted to Mansoura Chest Hospital on 18 May 2009. Infection with avian influenza was confirmed 20 May 2009. A history of close contact with dead and sick poultry was reported. He was reported in a good general condition on 20 May 2009 and referred to Manshiyet El Bakry Hospital in Cairo. The MOH reported this was the 73rd case of highly pathogenic avian influenza in Egypt. The 74th case is a 3 year-old boy in Sohag. He began experiencing symptoms of fever and cough on 17 May 2009. He was admitted to Sohag Chest Hospital on 18 May 2009. Infection with avian influenza was confirmed 20 May 2009. A history of close contact with dead and sick poultry was reported. He was reported in stable condition on 20 May 2009 and referred to Manshiyet El Bakry Hospital.
In addition, the Ministry of Health of Egypt announced the deaths of previously confirmed cases of H5N1 as follows: a 6 year-old boy from Qaliobia Governorate; a 33 year-old woman from Kfr El Sheikh Governorate; and a 25-year old woman from Cairo Governorate. 2. Updates INFLUENZA A/H1N1 The following websites provide the most current information and advice.
- WHO
- North America
- Other useful sources AVIAN INFLUENZA
3. Articles Serum Cross-Reactive Antibody Response to a Novel Influenza A (H1N1) Virus After Vaccination with Seasonal Influenza Vaccine US Centers for Disease Control and Prevention. MMWR. 22 May 2009; 58(19): 521-524. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5819a1.htm. As of May 19, 2009, a total of 5,469 confirmed or probable cases of human infection with a novel influenza A (H1N1) virus had been documented in 47 states and the District of Columbia. In addition, the virus had spread to 41 countries, with a total of 4,774 cases reported in countries outside the United States. Because producing a novel influenza A (H1N1) virus vaccine will take several months, determining whether receipt of seasonal influenza vaccine might offer any protection against the novel influenza A (H1N1) virus is important. Therefore, using stored serum specimens collected during previous vaccine studies, CDC assessed the level of cross-reactive antibody to the novel influenza A (H1N1) virus in cohorts of children and adults before and after they had been vaccinated with the 2005--06, 2006--07, 2007--08, or 2008--09 influenza season vaccines. The results indicated that before vaccination, no cross-reactive antibody to the novel influenza A (H1N1) virus existed among children. Among adults, before vaccination, cross-reactive antibody was detected in 6%--9% of those aged 18--64 years and in 33% of those aged >60 years. Previous vaccination of children with any of four seasonal trivalent, inactivated influenza vaccines (TIV) or with live, attenuated influenza vaccine (LAIV) did not elicit a cross-reactive antibody response to the novel influenza A (H1N1) virus. Among adults, vaccination with seasonal TIV resulted in a twofold increase in cross-reactive antibody response to the novel influenza A (H1N1) virus among those aged 18--64 years, compared with a twelvefold to nineteenfold increase in cross-reactive antibody response to the seasonal H1N1 strain; no increase in cross-reactive antibody response to the novel influenza A (H1N1) virus was observed among adults aged >60 years. These data suggest that receipt of recent (2005--2009) seasonal influenza vaccines is unlikely to elicit a protective antibody response to the novel influenza A (H1N1) virus. (Excerpt with references removed.) Pandemics: avoiding the mistakes of 1918
Essay Pandemics: good hygiene is not enough
Commentary And whatever the situation is like now, it won't be the end of the story. A mutated virus (more virulent or transmissible or resistant to drugs) could appear a few months later. (Excerpt.) Hospitalized Patients with Novel Influenza A (H1N1) Virus Infection--California, April-May, 2009
Since April 15 and 17, 2009, when the first two cases of novel influenza A (H1N1) infection were identified from two southern California counties, novel influenza A (H1N1) cases have been documented throughout the world, with most cases occurring in the United States and Mexico. In the United States, early reports of illnesses associated with novel influenza A (H1N1) infection indicated the disease might be similar in severity to seasonal influenza, with the majority of patients not requiring hospitalization and only rare deaths reported, generally in persons with underlying medical conditions. As of May 17, 2009, 553 novel influenza A (H1N1) cases, including 333 confirmed and 220 probable cases, had been reported in 32 of 61 local health jurisdictions in California. Of the 553 patients, 30 have been hospitalized. No fatal cases associated with novel influenza A (H1N1) infection had been reported in California. This report summarizes the 30 hospitalized cases as of May 17, including a detailed description of four cases that illustrate the spectrum of illness severity and underlying risk factors. This preliminary overview indicates that, although the majority of hospitalized persons infected with novel influenza A (H1N1) recovered without complications, certain patients had severe and prolonged disease. All hospitalized patients with novel influenza A (H1N1) infection should be monitored carefully and treated with antiviral therapy, including patients who seek care >48 hours after illness onset. (Excerpt with references removed.) Novel H1N1 influenza in people: global spread from an animal source?
The rapidly unfolding and evolving events, on a worldwide scale, relating to the human-to-human transmission of a novel H1N1 influenza A virus have dominated the news media in the past 2 weeks. In Europe to date, as in North America and Canada, there have been cases of laboratory-confirmed H1N1 infection in people returning from recent foreign travel in South America, specifically Mexico. In the vast majority of cases in people who are not from Mexico, the reported clinical presentation has been mild. Nevertheless, the emergence of this novel H1N1 influenza virus, and its rapid and worldwide spread, facilitated by the normal movement of people across international boundaries, highlights some important epidemiological features. It is relevant to note that while this H1N1 influenza virus has been termed "swine influenza" (or "swine flu"), the definitive scientific evidence base to support its origin in pig populations has not yet been confirmed. Furthermore, in the absence of contemporaneous reports of clinical disease in pigs infected with this virus, it is not possible to confirm the clinical signs that may be observed in infected animals. In common with other influenza A infections of pigs, where a range of clinical presentations can occur, asymptomatic infection with this virus is also a theoretical possibility. Why are Mexican data important?
Editorial 4. Notifications Weekly Epidemiological Record Bulletin WHO. 22 May 2009; 84(21): 185-196. Available at http://www.who.int/wer.
Contents Influenza in the Asia-Pacific
The Lancet and The Lancet Infectious Diseases have joined forces to develop a conference that will enable leaders in their fields to present and discuss management of influenza with key health administrators, experts from the medical and scientific communities, and industry representatives. We hope the meeting will provide valuable insight into fundamental public health and operation strategies to bring about change within the Asia-Pacific. Register now and take advantage of the early bird discount until May 31, 2009. To register, go to http://mail.elsevier-alerts.com/go.asp?/bELA001/qUQEAS8/x8BATS8
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