Fears of flu pandemic spurring preparations

Vaccine production is based on chicken eggs, but more would be needed in a pandemic. Sanofi Pasteur's federal contract will help the company produce eggs year-round.
They gathered around a hotel conference table in Howard County, planning for what might be Maryland's worst public health crisis.

The public health and safety experts spun a shocking scenario arising from the threat of an avian flu pandemic from Asia: 12,000 deaths in the state early on, with the possibility of many more later.

More conservative estimates from the U.S. Centers for Disease Control and Prevention suggest 1,600 to 3,700 Maryland deaths and 16,000 hospitalizations. But public health leaders can't be optimists.

"We have to plan for the worst-case event," said Dr. Jean Taylor, who heads Maryland's pandemic-planning efforts at the state Department of Health and Mental Hygiene.

To safeguard Americans against a pandemic that scientists generally agree is inevitable, federal, state and local officials are developing extensive plans encompassing needs such as hospital and mortuary capacity and production of antiviral medication and vaccines. Local health departments have begun identifying locations such as school gyms and community centers that could accommodate temporary hospitals -- space that might be needed for months.

This month, President Bush signed an executive order authorizing use of quarantines for avian flu cases.

Despite the enormous efforts, critics are warning that the federal government hasn't done enough. Among them are Andrew Pavia, chairman of the Infectious Diseases Society of America's task force on pandemic influenza. He told Congress late last month that "the United States is woefully unprepared for a pandemic that might occur in the next few years."

Essential tools

Much of the concern focuses on the nation's capacity to provide antiviral medications and vaccines.

Antiviral drugs like Tamiflu are essential tools in slowing the spread of disease until a vaccine can be developed to immunize people -- a process that can take six to eight months from the time a killer virus is identified. The United States has enough Tamiflu on hand to care for 2.3 million people, significantly less than some other nations.

But federal authorities said substantial progress is being made:

  • The Centers for Disease Control and Prevention have paid $13.9 million for the manufacture and stockpiling of 2 million doses of an experimental vaccine for the H5N1 virus, which has killed millions of chickens and a small number of people in Asia. The vaccine is being tested at the University of Maryland School of Medicine in Baltimore and two other sites. It is intended for research, shelf-life studies and, if approved, possibly for limited human innoculations.

  • To beef up the capacity of the only flu vaccine plant left in the United States, authorities invested $41 million last fall to expand and maintain the chicken flocks used by the company Sanofi Pasteur in Swiftwater, Pa. By September, that will allow year-round production of the millions of fertile eggs vital to vaccine production.

  • Sanofi Pasteur has also won a $97 million contract to develop a technology for vaccine production in a line of human cells, which could reduce by months the time needed to produce a new vaccine.

  • A Swiss maker of antiviral medication has committed to producing it in a new U.S. plant next year.

    This summer, the National Vaccine Program Office will finalize a Pandemic Influenza Preparedness and Response Plan. State health departments are expected to have their plans ready by September.

    But there's only so much the government can do to prepare.

    Despite years of worry about an avian flu outbreak in Asia, virologists don't know for sure which virus they would face in a pandemic, where it would evolve, how deadly it will be or how easily it would be passed from person to person.

    Pharmaceutical manufacturers can't begin making vaccines until that new virus emerges. Even then, they'll need months, while the disease is spreading, to grow the vaccine proteins in fertilized chicken eggs.

    Also, public health authorities, elected officials, hospital managers and health care providers can't be sure that what they'll face will amount to a very bad flu season -- or a public health calamity that exhausts medical supplies, overwhelms mortuaries and brings the economy to a crawl.

    But scientists and public health officials are in substantial agreement on this much: Sooner or later, the world will face a severe influenza pandemic, borne by a newly evolved virus against which humanity has little or no natural immunity.

    All that's needed to touch it off, scientists said, is a chance exchange of viral DNA inside a single pig or human victim. That could produce a virus with the virulence of H5N1 and the easy communicability of an ordinary flu bug.

    If it ever happens, said Dr. John Bartlett, chief of infectious diseases at the Johns Hopkins School of Medicine, "it's going to be awful."

    Bartlett said the United States needs to get ready now even if the H5N1 avian flu proves to be a dud. Influenza pandemics have occurred with regularity, and new ones will arise as new viruses evolve.

    The "Spanish flu" pandemic in 1918-1919 caused more than 500,000 deaths in the United States and more than 20 million worldwide. The "Asian flu" of 1957 killed 70,000 Americans, and the "Hong Kong" flu in 1968 left 34,000 dead.

    Conservative CDC estimates of the toll from a future pandemic in the United States predict up to 207,000 deaths and 734,000 hospitalizations. A virus as nasty as the 1918 flu bug would be expected to kill as many as 1.7 million Americans.

    About 100 humans are known to have contracted the H5N1 virus from animals since December 2003, with 54 deaths. Thai authorities reported one "probable" case of human-to-human transmission within a family last year.

    The Asian outbreak has focused the attention of public health officials worldwide on finding an effective vaccine.

    The University of Maryland and two other universities are testing 8,000 doses of H5N1 vaccine on 450 volunteers to see if it is safe and effective. The vaccine was produced by Sanofi Pasteur under a contract awarded by the National Institutes of Health in March 2004.

    Even if it proves effective, experts said there's no guarantee the vaccine will work should a pandemic occur. All influenza viruses are constantly mutating, a process known as "antigenic drift."

    "Even one or two changes, if they occur in the right spot, can affect whether the virus would be recognized by the immune system," said John Treanor, a professor of medicine at the University of Rochester and the principal investigator for the NIH trials.

    An old technology

    Vaccine production still relies on a 30-year-old technology based on millions of fertile chicken eggs.

    Sanofi Pasteur maintains flocks of millions of chickens. They produce eggs nine to 10 months a year -- all that's needed to make the vaccines to tackle the routine flu viruses we face every winter.

    But that would not be enough to take on an influenza pandemic. The new five-year, $41 million federal contract will help Sanofi expand and maintain its flocks to produce eggs year-round.

    The government is investing millions in Sanofi because it is the only remaining manufacturer of influenza vaccines in the United States. Low and inconsistent demand for the annual flu vaccines drove everyone else in the United States out of the business.

    FluMist, a flu vaccine that is inhaled, is made in bulk in Britain and finished in the United States. But it is based on a live, weakened virus that might not be safe for patients with weak immune systems.

    And in a global pandemic, officials said, the United States would probably not be able to turn to other countries for vaccine supplies. They will be facing their own public health crises.

    Several European countries, as well as Japan, Australia, Taiwan, Korea and Brazil, are also developing H5N1 vaccines or building manufacturing capacity.

    "The biggest concern I have globally is Africa," said James T. Matthews, director of external research and development at Sanofi. There is no vaccine in development on that continent, and "they are very vulnerable."

    Expanding capacity

    U.S. health authorities are planning campaigns to encourage more Americans to get annual flu shots, hoping that will increase demand, attract more drug manufacturers and expand the nation's domestic vaccine capacity.

    In a pandemic outbreak -- an epidemic over a wide geographic area -- vaccines would arrive late and slowly, officials said. Vaccination priority would go to critical services personnel and to the most vulnerable populations. As more supplies arrived, distribution would broaden to the wider population.

    Scientists are also working to determine whether and how a flu vaccine could be formulated or administered differently -- perhaps under the skin rather than into the muscle -- to stretch limited supplies.

    Meanwhile, Sanofi is trying to develop a new technology for vaccines that would grow in human cell lines instead of chicken eggs. The hope is that cell cultures would produce vaccine in as little as a month after a novel influenza vaccine is isolated.

    For now, the world is stuck with egg technology, and with the fact that, for months at the start of a pandemic, most of the population will not have been vaccinated.

    "If we assume that people will need two doses to be protected," said Dr. Benjamin Schwartz, senior science adviser to the National Vaccine Program Office, "a substantial proportion of the population would not have access to vaccine during that first year" of a pandemic that is likely to last two.

    During that period, the United States would have to rely largely on antiviral medicines and infection control to stem or slow the tide of illness.

    Stopping it in Asia, or wherever it emerges, would be the first goal. If that fails, antivirals and infection control would be used at home to protect as many vulnerable people as possible until vaccines arrive.

    Antiviral medicines can be used to prevent infection. They are also valuable as therapy. Taken within 48 hours of the first symptoms of flu, they can limit the severity and duration of the illness. That helps to slow the spread of an epidemic.

    There are two types of antiviral drugs. But the H5N1 virus has developed a resistance to one of them, called adamantines.

    That leaves the neuraminidase inhibitors such as Tamiflu, made by the Swiss firm Roche. But there are problems there, too, health officials said: Tamiflu is made in Switzerland, it takes almost a year to produce, and supplies might be restricted in a global pandemic.

    Britain and France have set about buying enough antiviral medicine to treat 25 percent and 21 percent of their populations, respectively.

    The U.S. government has set no such target. But it has gotten Roche to commit to building a production plant in the United States. "They're anticipating that next year they would begin making the drug here," Schwartz said.

    Other remedies

    Public health officials said they won't be able to rely on drug remedies alone. In their pandemic plans, experts are looking closely at how best to control the spread of infection in the face of shortages of antivirals and vaccines.

    Drawing on bioterrorism and disaster plans, and on their experience with severe acute respiratory syndrome (SARS) and similar recent disease scares, federal and state agencies have begun to work out their pandemic plans.

    They include procedures for screening airline passengers arriving from places with pandemic flu outbreaks, educating health professionals to be alert for signs of flu and to ask patients about their travels.

    Plans are in the works for isolating sick people and placing people exposed to the virus in quarantine -- at home or in public facilities.

    In August, Maryland health officials will conduct a "table top" simulation with state and local school officials to figure out when and how to close schools -- a decision that would have enormous impact on the economy as working parents are forced to stay home with their kids.

    Hospitals, too, are hammering out plans for coping with high absenteeism and shortages of empty beds, medical supplies and equipment. Of particular concern are mechanical ventilators, vital for keeping alive flu victims with secondary lung infections.

    The list of potential disruptions seems endless -- absenteeism among prison guards and ambulance crews; shortages of blood donors and refrigerated storage as mortuaries are overwhelmed by the dead; a scarcity of volunteers needed to deliver meals and medicines to people isolated at home.

    Dr. Peter L. Beilenson, who announced last week his resignation as Baltimore's health commissioner, said the city is better prepared to respond to a bioterrorism attack than a flu pandemic. There are stockpiles of medicines for anthrax and smallpox, he said, but Baltimore lacks the weapons for flu.

    "There just aren't the vaccines and pharmaceuticals that we probably need," said Beilenson.

    Disturbing prospect

    While many public officials have been working on the issue for years, some got their wake-up to these kinds of issues at last year's exercise in Howard County.

    "For the few participants who, for the very first time, heard about pandemic flu and what it's implications were, it was stunning," said Jean Taylor, at the state health department.

    Seated at the table were representatives from the governor's office, state and local agencies for public health, transportation, public safety and emergency management, as well as leaders representing hospitals, nurses, morticians and academia.

    It wasn't just the deaths in the scenario that disturbed them. Medical supplies were in short supply. Absenteeism was soaring. Police, firefighters, medical workers and air traffic controllers were among the thousands of sick, dead or terrified. Hospitals and mortuaries were overwhelmed.

    The first small batches of vaccine were arriving, but they were reserved for health care and public safety workers. Crowds gathered, demanding vaccination, and small riots were breaking out.

    Planning for such events is valuable even if the H5N1 avian flu bug never mutates into a pandemic virus.

    "It's not a question of if, it's when," Bartlett said. "If we know how to respond to avian influenza in terms of building a vaccine and being able to have antiviral agents fast and have all the machinery in place, we'll be ready."

    Sun staff writers Jonathan Bor and Michael Stroh contributed to this article.

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