EINet Alert ~ Jun 03, 2005

*****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. Updates
- "Nature" urges world to take pandemic threat seriously
- Indonesia: Pigs could be having avian flu virus without showing signs
- China: Bird cases of avian influenza double; no human cases
- China: Plans early warning system for avian flu
- New OIE standards on avian influenza (Unofficial versions)

1. Updates
"Nature" urges world to take pandemic threat seriously
The British magazine Nature trained a floodlight on the threat of an influenza pandemic with a collection of 10 articles that explore the danger and possible remedies and demand a more serious global response. "The level of current efforts is not commensurate with the threat we face," the editors write. "The time for diplomacy and denial is over. It is time for advocacy and action." The feature and commentary articles range from a call for stronger efforts to control avian flu in birds to a fictional Web log of an unfolding pandemic. Included are reports on the efforts to develop vaccines, the prospects for stalling a pandemic with antiviral drugs, and the need for detailed planning to prevent economic chaos. The virus has infected close to 100 people and killed 54 in Asia in the past year and a half, but it has not yet shown an ability to spread easily from person to person. But if it acquires that ability, it could spread around the world in months, experts fear. Following are some highlights from the other three feature articles, five commentaries, and one editorial.

'The flu pandemic: were we ready?'
This fictional blog traces the trajectory of a hypothetical pandemic from its recognition in late December of this year until its end in May 2006. By early February, the disease has raced through Paris, causing 2.5 million cases and 50,000 deaths, the account says. Later that month, troops are patrolling US streets, the antiviral drug oseltamivir (Tamiflu) is being reserved for medical first responders, and pharmacies are being looted.

'Is this our best shot?'
Erika Check, Nature biomedical correspondent in Washington, surveys current research on H5N1 and H9N2 flu vaccines. In addition to one clinical trial under way in the United States, at least 10 clinical trials are scheduled in five other countries. Check examines the obstacles facing vaccine development, including patents on the use of reverse genetics to tailor a vaccine to a flu strain and the financial risks for biomedical companies. Check quotes public health leaders as urging that rich countries draw up plans to share their vaccine supplies with poor ones in the event of a pandemic.

'What's in the medicine cabinet?'
The world's arsenal for battling pandemic flu includes a very limited supply of antiviral drugs that are most available in the developed world but might be most urgently needed in the developing world, writes Nature's Alison Abbott. Drugs that limit the power of ordinary flu, not vaccines, are likely to be the first line of defense against a pandemic strain. Developing countries are stockpiling antivirals, including the neuraminidase inhibitor oseltamivir, rimantadine, and amantadine. But even if manufacturers can fill the orders from developing countries, those countries will only have enough for a small percentage of citizens. Further complicating the picture, drug makers have a limited capacity, and production can be slow. In addition, poverty in developing countries already plagued with H5N1 may prevent those countries from obtaining antivirals, Abbott writes. Some public health experts propose an international supply of oseltamivir, which the WHO could ship as needed.

'Controlling avian flu at the source'
Robert Webster and Diane Hulse of St. Jude Children's Research Hospital in Memphis comment that relatively little has been done to develop a global strategy to stop avian flu at the source—in birds. They cite two examples of successful efforts to protect humans by controlling avian flu in birds, one in Hong Kong since 1997 and one recently in Thailand. When H5N1 avian flu emerged in Hong Kong in 1997, the city destroyed its entire poultry stock in 3 days. Since then, the city has used strict regulation of live-poultry markets to keep the virus from returning. Thailand has conducted intense surveillance of its poultry flocks and culled all infected duck flocks. Webster and Hulse credit these steps for the absence of human H5N1 cases in Thailand this year. They also see a possible role for vaccines in controlling avian flu in poultry. The writers call for a single international standard for a poultry vaccine that could reduce viral loads below the transmissible level.

'A weapon the world needs'
Existing pandemic flu preparedness plans are woefully inadequate to deal with the realities of a pandemic, writes Michael T. Osterholm, PhD, MPH. Existing international, national, and local plans don't really come to grips with such difficult problems as how to ration vaccines, antiviral drugs, and respirator masks, according to Osterholm, director of the University of Minnesota Center for Infectious Disease Research and Policy. Nor do existing plans grapple with the possibility that a pandemic would cripple economic activity, he writes. Osterholm advocates an international effort to develop a new type of flu vaccine that can be manufactured much faster than with the traditional egg-based method, which takes at least 6 months. He also warns that rich countries must share vaccines with poor countries, because a pandemic may mean economic disaster for all countries, regardless of their vaccine supply.

'Global task force for influenza'
A permanent global task force for pandemic flu is proposed in this commentary by four specialists at Erasmus Medical Centre in Rotterdam, the Netherlands. "Integrated and effective action from all the disciplines involved is urgently needed, rather than ad-hoc responses at the local level," write Ron Fouchier, Thijs Kuiken, Guus Rimmelzwaan, and Albert Osterhaus. They estimate that it would cost less than $1.5 million a year to operate such a task force.

'Is China prepared for microbial threats'?
China must apply lessons learned from other outbreaks and invest heavily in its public health infrastructure to prepare for avian flu, writes David Ho of the Aaron Diamond AIDS Research Center in New York City. Calling avian flu China's worst microbial threat, Ho suggests the country repair deficiencies in its public health system that came to light in the battle with SARS. He sees a need for more funding for disease surveillance, greater human resources and technical capacity, better training of healthcare workers, and strengthening of the country's disease-alert system. The country is likely to be among the first affected by a pandemic, its healthcare infrastructure is inadequate, authorities have no detailed pandemic plan, and technical resources to produce vaccines and drugs are limited. But there is reason to believe the country could accomplish its goals, Ho writes. "China brought SARS under control faster than anyone could have predicted…The success was not only commendable, but a testament to Chinese resourcefulness once a clear path is apparent."

'Race against time'
Anthony S. Fauci, director of the National Institute of Allergy and Infectious Disease, surveys US research related to the pandemic threat. Major efforts include sequencing of flu virus genomes, research on new antiviral drugs, clinical testing of inactivated H5N1 and H9N2 vaccines, plans for testing live attenuated H5N1 and H9N2 vaccines, a plan to develop live attenuated vaccines for all of the known avian flu viruses, and an effort to develop a flu vaccine based on viral components that are the same in various influenza A strains.

'On a wing and a prayer'
Nature's editors say that a far stronger, more coordinated international effort is needed to address the pandemic threat. They say the world isn't providing needed funding for proper surveillance in affected countries and is not doing enough to promote meaningful collaboration with them. Providing incentives such as antiviral drugs might help. "The international virology community needs to be permanently there, on the ground," the authors state. "We need to diagnose cases swiftly, and treat the patients and all their contacts immediately with antiviral drugs to try to kill the pandemic at the source."

Table of contents for May 26 2005 Nature: http://www.nature.com/nature/journal/v435/n7041/index.html (CIDRAP 5/26/05 http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/may2605nature.html)


Indonesia: Pigs could be having avian flu virus without showing signs
Avian influenza could be infecting up to half of the pig population in some areas of Indonesia, but without causing symptoms, Nature magazine reported in this week's edition. Chairul Nidom, a virologist at Airlangga University's tropical disease center in Surabaya, Java, was conducting independent research earlier in 2005. He tested the blood of 10 apparently healthy pigs housed near poultry farms in western Java where avian flu had broken out, Nature reported. Five of the pig samples contained the H5N1 virus. The Indonesian government has since found similar results in the same region, Nature reported. Additional tests of 150 pigs outside the area were negative. However, lack of funding for surveillance and testing is a concern to Nidom, who said he has samples from 90 more pigs from Banten, but he can't afford to test them or to broaden his investigation.

"I think pigs pose a much greater threat of spreading the disease to humans than poultry," Nidom told Nature. Pigs are often described as a mixing vessel in which human and avian flu viruses can swap genes, which could lead to a hybrid virus with the ability to spread easily among people. The Indonesian government sent a report to the World Organization for Animal Health (OIE) on May 23, 2005 that describes 3 surveys involving "purposive and pooled sampling" of pigs, with a total 187 samples.

The first survey, Nidom's Feb 23, 2005 study on one farm, yielded 5 positives out of 10 samples tested for H5N1. The second, on Apr 14 in another village, involved 10 nasal swabs from 31 pigs and produced positives in 6 of the 10. The third survey included six pigs from the same village as Nidom's small survey and yielded 1 positive swab. The report says that no pig has shown visible signs of avian flu. It lists the source of the pig infections as "contamination with chicken manure" from adjacent backyard chicken farms. Additional tests included 250 blood serum and swab samples from pigs in seven provinces, the report says. All the results were negative. Nature report on H5N1 virus in pigs in Indonesia: http://www.nature.com/nature/journal/v435/n7041/full/435390a.html (CIDRAP 5/27/05 http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/may2705avflu.html)


China: Bird cases of avian influenza double; no human cases
Nature said the H5N1 virus was found in pigs in China in 2001 and 2003, but two surveys in 2004, involving 8,457 pig samples, found no evidence of the virus. In China, more than 1,000 migratory birds have died of H5N1 avian flu in Qinghai province, according to a report by Xinhua, the Chinese news agency. The size of the outbreak, initially reported as not being H5N1, grew this week from 178 birds to 519, and now to more than 1,000. Emergency measures are being taken in Qinghai, including increasing infectious disease control and surveillance for animals and humans, Xinhua reports. The agency said earlier that authorities planned to vaccinate 3 million poultry in the region.

The Chinese government has repeatedly said that no people have been infected with avian flu, despite unconfirmed claims on Internet sites that as many as 120 people have died of the illness. WHO is seeking details on the provincial outbreak, according to a Canadian Press (CP) report quoting Maria Cheng, WHO spokeswoman. "We've seen those reports about possible human H5N1 cases, and have requested more information from the Ministry of Health," Cheng said. The WHO is urging China to share virus samples from the dead birds as well as information on human exposure to dead birds. In a separate report in Xinhua, Chinese researchers claimed to have developed two H5N1 vaccines that are "100%" effective for birds, animals, and people, CP reported. Officials at the WHO, however, described that research as involving only birds and said no animal or human clinical trials have been conducted. (CIDRAP 5/27/05 http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/may2705avflu.html)


China: Plans early warning system for avian flu
A Chinese official announced that China plans to launch an early warning system for outbreaks of avian influenza, according to a report by Xinhua, the state news agency. The system will include a nationwide virus database, epidemic analysis and information sharing among foreign experts, and regular announcements to the public, the Jun 1, 2005 report said. The information was attributed to Ma Juncai, assistant director of the Chinese Academy of Sciences' Institute of Microbiology.

China has been a focus of concern about H5N1 avian flu recently because of the revelation in late May 2005 that hundreds of migratory birds had died of the disease at a nature preserve in Qinghai province. Describing the early warning system at a conference in Shanghai, Ma said, "The system would warn people of an epidemic and help scientists find solutions to kill the virus as soon as possible." Ma and his colleagues are developing the system in eight provinces. "The high-tech system is under construction, but it's hard to say when it will be put to use," he was quoted.

Little new information about the Chinese outbreak in wild birds emerged this week. The outbreak has stirred concern because it is the first known H5N1 outbreak in China since July 2004 and because at least five species of wild birds were reported to have died of the disease. Wild waterfowl are recognized as the natural reservoir for all influenza A viruses and commonly carry them without getting sick, according to the WHO. A news report this week in the British magazine Nature said that until now, only a handful of migratory birds were known to have died of H5N1 infection. The Chinese outbreak implies that the virus has become highly infectious and lethal among migratory birds, prompting fears that the virus might have mutated in a dangerous way, the report said. The WHO has sought to obtain virus samples from the dead birds for analysis. "They have not provided any samples yet, though we would love to get our hands on them," WHO spokesman Dick Thompson told CIDRAP News. (CIDRAP 6/3/05 http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/jun30305avian.html)


New OIE standards on avian influenza (Unofficial versions)
New OIE standards on avian influenza, along with bovine spongiform encephalopathy and animal welfare, have been posted on its website (Unofficial versions): http://www.oie.int/eng/press/en_050602.htm. Below are points of interest from Promed’s 28 May 2005 posting:

2.1 Notification requirements and compartmentalization
The adopted chapter on Avian influenza incorporates several significant concepts that will lead to increased transparency in reporting and a more risk-based approach to trade recommendations. The new notification requirements include reporting on the presence of avian influenza, of low and high pathogenicity, in poultry. Poultry is defined to include all birds raised for commercial purposes, and the status of the country is determined only on the presence of AI in [domestic] poultry. This means that the presence of avian influenza in migratory water fowl should be notified without negatively affecting the health status of the country. Since Avian influenza is endemic in migratory water fowl, it is difficult to prevent poultry from becoming infected. The new Avian Influenza chapter incorporates the concept of compartmentalization, which describes the criteria for the separation of these 2 populations through biosecurity measures. Veterinary Services in conjunction with the industry can establish and enforce the necessary conditions to ensure the safety of a poultry subpopulation through compartmentalization, even when AI is found in the rest of the country.

2.2 Vaccination
The new chapter also incorporates criteria for trading commodities while vaccination is being applied as an additional tool for the control and eradication of AI. Vaccination should be carried out with approved vaccines and vaccination protocols identified in the OIE Terrestrial Manual. (OIE 6/2/05, Promed 5/28/05)