Nature urges world to take pandemic threat seriously

May 26, 2005 (CIDRAP News) – The British magazine Nature trained a floodlight on the threat of an influenza pandemic today 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 articles begin with a brief introductory piece on the threat posed by the H5N1 avian flu virus in Asia. "Trouble is brewing in the East," it warns. "The stage is set for the emergence of a fresh human influenza pandemic."

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. A sidebar describes US experiments to get a "preview" of what a pandemic virus might look like by inducing reassortment of H5N1 with human flu viruses and then exposing animals to the resulting hybrids.

'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 Alison Abbott, Nature's senior European correspondent.

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. Abbott predicts that countries would face difficult choices about what constitutes an essential worker during a pandemic.

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 World Health Organization (WHO) could ship as needed. Meanwhile, Abbott says, several issues linger, including how to boost drug production and how to optimize dosing.

'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. While current vaccines often do not yield sufficient immunity to prevent transmission, it may be possible to produce vaccines that can eliminate this problem. 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, publisher of this Web site.

Nor do existing plans grapple with the possibility that a pandemic would cripple economic activity, he writes. "Specific operating blueprints to get through 12 to 36 months of a pandemic are essential," including plans for maintaining food supplies, he asserts.

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 (severe acute respiratory syndrome). 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.

China faces multiple obstacles, Ho says. 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'
In this editorial, 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."

See also:

Table of contents for May 26 Nature, with links to articles and commentaries
http://www.nature.com/nature/journal/v435/n7041/index.html

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