Will we be ready?

In the perennial conflict between germs and humans, the influenza virus has a distinguished roster of battlefield victories. But now, far from America’s shores, a new round of hostilities is brewing. For the first time, scientists and public health officials are preparing to fight back.

Across East Asia, an influenza virus known by the scientific designation H5N1 has killed at least 55 people and tens of millions of birds. As potential aggressors go, this one’s about as insidious as they get -- fast-moving, deadly and extremely unpredictable. Before it can mount an all-out offensive, this “bird flu” virus must change its genetic makeup so that it can jump easily from human to human. Once it has done so, the resulting germ could spread quickly, inflicting heavy casualties among a global population with no natural immunity against it.

That final shift might never happen -- or it could happen next week. But scientists think that roughly three times each century nature creates an influenza virus capable of global devastation, and a “pandemic” flu sweeps the world. The prospects increase when a virus long out of circulation extends its geographic range, its hold on different animal species and its contact with humans. By those measures, H5N1 is a virus on the march.

So can it be stopped? With a few more years to prepare, American public health experts say they may be able to prevail over an outbreak of pandemic flu. But its timing absolutely defies prediction. If the attack comes this year or next, experts acknowledge they can at best slow its march, and the death toll will be grievous.

Among officials and experts tracking the building force of the H5N1 virus, the anxiety is palpable. Dr. Anthony Fauci, who directs the National Institutes of Health office that oversees preparations for pandemic flu, says the sense of urgency is intense. “I feel it every day, and my staff feels it every day.”

Fauci calls pandemic flu “the mother of all emerging infections” and warns that the world is behind in building its defenses.

There is, however, a scramble to get ready. The United Nation’s World Health Organization has stepped up its monitoring of H5N1 throughout East Asia. It has brokered cooperation among countries to help stem the spread of the virus -- usually by killing flocks of infected birds. And it has exhorted countries to arm themselves with vaccine and antiviral medication.

In Washington, D.C., and across the United States, officials are racing to prepare for and counter the virus before it becomes efficient at jumping from human to human and is transported to America by a passenger aboard a plane.

They know how quickly the scenario could unfold. When a novel respiratory syndrome called SARS emerged in rural China in 2003, it spread to five countries in 24 hours; within several months, it had reached 30 countries on six continents. The East Asian countries most affected by bird flu so far -- Cambodia, Vietnam and Thailand -- are ill-equipped to track the spread of bird flu in animals and humans. Containing it, say experts, is beyond their powers.

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Rushing development

In the last several years, U.S. federal spending on influenza research has increased more than fivefold, to $400 million annually in 2005. Vaccines against two different strains of influenza -- one of them the H5N1 strain -- were rushed through development using new genetic engineering techniques, and have gone into large-scale production at the same time that clinical tests have gotten underway.

The unprecedented compression of the schedule for H5N1 vaccine is risky, Fauci says. But it is “an indication of the urgency” with which officials feel they need to have a vaccine in hand.

President Bush ordered 5.3 million doses of flu-fighting antiviral medications into the strategic stockpile, and in April signed an executive order authorizing the isolation and quarantine of foreigners suspected of arriving at the U.S. border sick with flu. The U.S. Centers for Disease Control and Prevention is expanding the number and capacity of quarantine stations at major U.S. ports. And chastened by flu vaccine shortages last year caused by a production glitch, CDC officials are drawing up plans for distributing limited vaccine and antiviral medication in the event of a pandemic.

“The stakes -- in dollars, resources and human lives -- are enormous,” said Rep. Thomas M. Davis III (R-Va.), who on June 30, presided over the fifth hearing this year that Congress has called on the subject.

Officials also face the uncertainty of not being able to predict how virulent a pandemic flu virus would be. Bird flu victims in Asia have been stricken with typical influenza symptoms at first, but their respiratory distress quickly worsens as their immune systems try to fight the virus. Of those confirmed infected with the bird flu, almost half have died.

The CDC calculates that even a “medium-level” pandemic could claim between 89,000 and 207,000 lives in the United States, with between 314,000 and 734,000 hospitalizations. Some warn that those estimates could be low. The Washington, D.C.-based Trust for America’s Health, using CDC methods and official reports of the bird flu virus’ virulence, has projected the U.S. death toll of a moderate pandemic at more than 500,000 -- including nearly 61,000 in California -- with more than 2.3 million hospitalized and almost 67 million Americans sickened.

The CDC estimates that the direct economic impact of a medium-level pandemic on the United States could reach $166.5 billion. But others point to the economic reverberations of the 2003 SARS scare and conclude that pandemic flu -- by triggering panic, protectionism and widespread illness and death among workers -- could bring the world’s intricately linked economy to a virtual standstill.

“The arrival of a pandemic influenza would trigger a reaction that would change the world overnight,” writes Michael T. Osterholm in an article in the July issue of the journal Foreign Affairs. Trade and travel across foreign and domestic borders would slow or stop, as countries and communities scramble to protect themselves from infection, writes Osterholm, who directs the University of Minnesota’s Center for Infectious Disease Research and Policy. “Global, regional and national economies would come to an abrupt halt,” he says.

Such disaster scenarios are spurring local, state and federal health officials to develop plans of action. At Rep. Davis’ June 30 hearing, Shelley Hearne, executive director of the Trust for America’s Health, said U.S. preparations for a pandemic were “lagging” behind those of Great Britain and Canada. Planning designed to ensure the availability of vaccine and anti-viral medicines, is “incomplete or fragmented,” Hearne added.

Critics such as Hearne say the U.S. is woefully unprepared for an outbreak. But some who study the risk of catastrophic events suggest that the government’s efforts are a reasonable response to the uncertainties of bird flu. Julie Downs, director of Carnegie-Mellon University’s Center for Risk Perception and Communication, says it may be wiser for the federal government to invest in the capability to mass-produce a flu vaccine rapidly than to stockpile millions of doses of a vaccine formulated to counter bird flu.

But such a strategy, adds Downs, must acknowledge that “our canaries in a coal mine” -- the early victims of a pandemic flu outbreak -- will not be helped by the government’s preparations. “That’s a trade-off that we have to decide as a country, and that’s a scary thought for a lot of people,” Downs says.

In California, a board of medical professionals and public health officials has met to draw up lists of who, in the event of pandemic flu, would have early access to vaccines. If a pandemic struck California today, said Dr. Ronald Bangasser, a Redlands physician who sits on the board, healthcare workers, governmental leaders, critical infrastructure workers (from trash collectors to power plant engineers), and those most likely to spread the disease, such as schoolchildren, would get priority.

Experts warn that state officials and business leaders also should be -- but are not -- planning for a potential crisis of capacity in the event of a pandemic; in many cases there are too few hospitals and ventilators for the critically ill, and shortages of bedsheets, protective gloves and respiratory masks.

To thwart entry of a new virus, the CDC this summer will open six quarantine stations in international airports and ports, including San Diego, Anchorage, Boston and Minneapolis. They join 12 existing stations, including quarantine facilities at Los Angeles International, San Francisco International and Seattle airports. Federal health officers staffing these quarantine facilities will have the legal power to hold foreign citizens suspected of being ill with flu for a limited time. Beyond those ports of entry, however, experts say that U.S. and state laws give officials little or no authority to take measures aimed at stopping the spread of a virus.

The final line of defense lies in vaccines to prevent infection and antiviral medications to treat those infected with a flu virus. Although activity in both areas is intense, officials acknowledge that the United States is vulnerable, and could be for some time.

Of the antiviral medicines available, only one class of drugs, the best known of which is Tamiflu, may help treat a case of bird flu in humans or prevent illness if a person has been exposed to the virus. So far, 2.4 million doses of Tamiflu have been stockpiled and 2.9 million more have been ordered for the nation’s emergency stores. But Tamiflu is manufactured by Roche Pharmaceuticals in a single plant in Switzerland, and a lengthy production process means it can take a year to fulfill orders. In a pandemic, with production lines stressed, deliveries interrupted and countries clamoring for more, the U.S. is unlikely to get much more. If one-fourth of the U.S. population (about 73 million) become ill with flu -- an assumption seen as highly plausible -- the nation’s stockpile will quickly be exhausted.

That makes flu prevention key, say experts -- a goal best achieved by vaccinating large numbers of Americans. Currently, about 2 million doses of vaccine against the bird flu virus are in government stockpiles, and tests of the vaccine’s safety and effectiveness -- at least for non-elderly adults -- are expected to be complete soon.

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Scrambling to get ahead

Getting this far has been a feat of science and engineering, says NIH’s Fauci. But making a flu vaccine available quickly to a large proportion of the population will require even more effort, experts say. Vaccine development and production methods remain largely unchanged since the 1950s, and the number of drug makers making flu vaccine has dwindled to a handful, most operating outside of the U.S.

“The vaccine enterprise is very fragile, if not broken,” says Fauci. “There’s no flexibility ... We have got to fix that problem.”

For now, scientists working with Fauci are scrambling to devise ways to design flu vaccines, administer them more efficiently and stretch existing supplies. The Bush administration and Congress are considering measures that would provide incentives to vaccine manufacturers. States such as California are pondering how to distribute vaccines that, according to California’s emergency pandemic plan, probably would not arrive for six to eight months into a flu crisis.

That, says University of Minnesota’s Osterholm, is not good enough. Osterholm says leaders and officials at all levels need to do more to get ready for a public health disaster that will happen later if it does not happen now.

“This is a critical point in history,” Osterholm writes in Foreign Affairs. “Someday, after the next pandemic has come and gone, a commission much like the 9/11 Commission will be charged with determining how well government, business, and public health leaders prepared the world for the catastrophe when they had clear warning. What will be the verdict?” he asked.