The Fight Against the Flu

One parrot, imported from South America and held in quarantine in Britain, along with a shipment of birds from Taiwan.

One swan, in the Romanian village of C.A. Rosetti, near the border with Ukraine.

One man, Bangorn Benpad, 48, a sometime driver and gardener in the Thai province of Kanchanaburi, who had helped himself on a couple of occasions to chickens from a neighbor's flock. The flock had been dying off, and the chickens he took were close to death anyway. Days after he killed, plucked, grilled and ate the birds, he developed a cough and a fever and visited a local clinic, where they took an X-ray of his lungs and suggested he check himself into a hospital. Instead, he went home, but last Monday his condition worsened, and a new X-ray showed a rapid deterioration in his lungs. By Wednesday he was dead.

In ordinary times these deaths last week would have gone unnoticed by the world at large, but this is not an ordinary time: the world is on edge, stalked by a virus that travels the great migratory flyways and kills where it lands. After incubating for eight years in East Asia, where it was responsible for the death of 140 million birds (including those intentionally destroyed to stop its spread) and 68 people, the H5N1 variant of avian flu suddenly and mysteriously expanded its range this year, north to Mongolia and Siberia, then west into Ukraine, Croatia and Turkey. Through innumerable generations and hundreds of mutations, it maintained its extraordinary lethality, without yet evolving the ability to be transmitted directly between people. Almost all cases have involved people who came into close contact with chicken blood or droppings; when and if that changes, it could be the trigger for a global pandemic that, in a worst-case extrapolation from the toll of the 1918 Spanish flu, could kill 150 million people--2.5 percent of the world's population--in a matter of months. Epidemiologist Michael Osterholm of the University of Minnesota calls that scenario "the single greatest risk to our world today." Governments--indeed, civilizations--have collapsed from less; even if you survive, Osterholm asks, "what happens to you when the global economy shuts down?" Thus the fate of the world hung in the balance between the invisible forces of mutation and natural selection, and the preparations undertaken by governments with far more visible problems close at hand. All over the world people were asking two things: Is the government doing everything it can? and What can I do to protect my family? And the answers were: not yet and only so much . "There have been many who foresaw this and urged the country to begin preparations sooner," Health and Human Services Secretary Mike Leavitt said last week in a remarkably frank interview with NEWSWEEK, "--and it would have been better if we had done so."

There is flu every year, of course, and it typically kills about 36,000 Americans, mostly the elderly. But for that very reason, most people have been exposed to it and have acquired at least partial immunity to the common varieties, which typically are hybrids of human and animal viruses. But H5N1--like the 1918 virus, which has just been reconstructed by researchers--crossed the species barrier from chickens almost intact. Almost no one on Earth has any immunity at all, and ordinary vaccines are useless against it. It is, moreover, devastatingly lethal, for reasons not fully understood, killing nearly half the people known to have contracted it (although some researchers think mild cases might have gone unreported, making the mortality rate seem higher).

And, also like the 1918 variety, H5N1 has the ability to kill directly. Most ordinary flu viruses destroy the cells that line the upper respiratory tract, the body's first line of defense against airborne germs; the patient usually dies of bacterial pneumonia. That's why the elderly and immune-compromised are particularly at risk. But Spanish flu attacked deep within the lung, destroying tissue and also provoking a furious immune response that literally drowns the lungs in hemorrhage; if H5N1 follows the same pattern, as it appears to do, it would kill quickly and take a disproportionate number of healthy young adults.

No one knows why the virus suddenly spread into Europe this year or what it portends, although epidemiologists consider it an ominous development. "Something has happened to the relationship between the virus and wild birds that hadn't happened before," Osterholm said. Nevertheless, the only immediately obvious threat was to Europe's waterfowl and poultry farms. The likely ground zero for a pandemic is still the vast rural expanses and teeming urban markets of China and Southeast Asia. But the virus is now squarely in the path of birds migrating to Africa, where people also live in close proximity to animals and public-health facilities are often primitive--and millions are already infected with HIV, which raises the risk of serious complications.

Of course, medicine has made great strides since 1918. On the other hand, in those years it took weeks, not hours, to travel from Hong Kong to New York. Dr. Margaret Chan, head of pandemic-flu preparedness for the World Health Organization, notes that "in history no human intervention has managed to stop a pandemic once it starts." But, she adds, "this is the first time we've been able to see a pandemic unfold before our very eyes." There is a window of "20 to 21 days" in which a local outbreak could be controlled before it gets loose, Chan believes. The key factors that will determine success are surveillance, the authority to impose and enforce a quarantine, the availability of vaccines and antiviral drugs, and the state of readiness in hospitals--and in almost all of these, the world has a long way to go.

Take surveillance, the ability to detect an outbreak at the source. "Right now, [the world's] surveillance is not adequate to protect us," Leavitt said last week, at the end of a trip to seven Asian countries. "We have to work with countries all over the world and instill a sense that if it happens anywhere, it's a risk everywhere." But, as he acknowledged, that's a hard case to make in countries where the annual income might be $600--and a family's entire wealth is tied up in livestock. At a briefing last Friday he described visiting a family in Vietnam whose flock was ordered destroyed when it showed signs of avian flu--so they frugally slaughtered and ate the birds that didn't seem sick. Within a week they were violently ill. (They survived.)

At the first sign of human-to-human transmission, the WHO plan calls for an immediate quarantine, freezing all traffic in and out of an area that could be as large as an entire city. Schools and businesses would be closed and public gatherings banned. Of course, these measures could be implemented only by the national government (or the states, in the United States), and would require the active cooperation of the population. To see how that could work in practice, you could have gone two weeks ago to the village of Ceamurlia de Jos, on the Danube Delta, where Romanian authorities imposed a strict quarantine after discovering avian flu in ducks, geese and chickens. Roads were blockaded by police and fire trucks, and anyone walking out of the village had to slosh through a shallow pit filled with disinfectant--including one elderly man who, compliantly stamping his feet in the tray, accidentally let loose a live chicken he'd been hiding under his jacket. Even in the United States, public-health officials have reason to worry that just as some people couldn't bear to leave their houses in the face of a hurricane, some will find it imperative to visit their relatives in another city at the start of an epidemic. States have laws to enforce quarantines, of course, but CDC officials admit that some are inadequate or have expired, and they're working urgently, if quietly, to bring them into compliance with the agency's model code. Other countries' situations are even more worrisome; in Indonesia, another country where H5N1 has been found, the Army is by far the only institution capable of enforcing a quarantine, but a military spokesman told NEWSWEEK last week that "bird flu is not within the purview of the armed forces. Talk to the Ministry of Health."

Antiviral drugs are an important part of the WHO's plan to combat avian flu. There are only two, Tamiflu and Relenza, and they both work the same way, by interrupting the virus's ability to replicate within the body. (Tamiflu, which is taken orally, is in wider use than Relenza, which is usually given by inhalation.) If taken at the very onset of symptoms, they are believed capable of reducing the severity and length of the disease. But their real value in public health, says Dr. Anne Moscona, an influenza expert at New York-Presbyterian Hospital/Weill Cornell Medical Center, would be to help contain an outbreak by treating healthy people in a "ring of prophylaxis" around it. Although reports suggest that some strains of H5N1 may be developing resistance to Tamiflu, Moscona still considers the drugs a useful tool, and the WHO recommends that nations stock-pile enough to cover 10 percent of their population.

Public-health officials, though, worry that there's too much emphasis in the media on the size of the Tamiflu stockpile. "I think it's a complete misdirection of energy to be so focused on the issue of stockpiling," CDC director Julie Gerberding said in an interview Friday. "There is no evidence that it will make a difference if we are hit with a pandemic." Leavitt agrees that antivirals are only a part of the answer. But at the same time, he increased his estimate of a desirable stockpile of Tamiflu from 20 million doses earlier in the month to a range of 20 to 30 percent of the population--or upwards of 60 million. (CDC is a branch of Leavitt's department.) In any case, we're a long way from getting there: as of two weeks ago Leavitt told reporters that the United States had stockpiled 2.3 million courses, and that 2 million more would be on hand within two days. His spokesman now says the secretary misspoke, and the additional doses are not expected until the end of November. France, with a population of 60 million, claimed to have 13 million doses on hand last week.

Meanwhile, many people were trying to build their own stockpiles of the drug--an activity better described as hoarding. The Washington Post reported that 1.7 million prescriptions were filled in the United States in the first eight months of 2005, three times the rate last year. (A full course of Tamiflu--10 pills over five days--costs $80 to $90; they were being sold on British eBay for as much as double that, until the company pulled the listings last Tuesday.) Although not illegal, personal stockpiling is "a really bad idea," says Moscona, who worries both about competing with the government for the limited supplies of the drug and about people taking it indiscriminately, which could foster the growth of resistant strains of the virus. Late last week the Swiss drug company Roche, the sole supplier of Tamiflu, said it would begin negotiating with four other companies to license its production. But that didn't head off an announcement by Taiwanese health officials that they would manufacture their own generic version of Tamiflu, which they said was "99 percent" identical to the patented drug--a clear indication that if a pandemic struck, it would be every man or nation for itself.

The best weapon against H5N1 would be a vaccine; at least two have been developed--one in the United States and one in Hungary--and are reportedly showing promise in tests. But there's a Catch-22 in vaccine production: the virus now in circulation, which infects humans only by way of birds, is not the one we have to worry about. It will have to mutate to cause a human pandemic, and the existing vaccine may or may not be completely effective against the new strain. (It presumably would offer at least some protection, but the standard vaccine now being given for this year's "seasonal" flu variety offers no protection at all against H5 viruses.) "We don't have the capacity to manufacture the vaccine necessary to combat a pandemic," Leavitt acknowledged. "We need the ability to isolate a virus and convert it to a vaccine and produce enough vaccine for 300 million people--and we need to do that in six months. That capacity doesn't exist today." Flu-vaccine production is still in the horse-and-buggy stage of inoculating chicken eggs by hand. New technologies can speed the process, either by growing vaccines in cell cultures, or manufacturing them directly from DNA--but progress on those, says Leavitt, "will be measured in years, not months."

The final line of defense against a pandemic is the hospital, where more than 2 million Americans, according to a study by Trust for America's Health, might need treatment. Their points of entry in many cases will be emergency rooms that would have trouble coping with even a bad regular flu season, warns Dr. Rick Blum, president of the American College of Emergency Physicians. "We've pumped billions of dollars into preparedness since 9/11, but virtually none of that has gone to the one place where we know 80 percent of patients go first," Blum says. Many of them will probably be extremely sick, with respiratory and multiple-organ failure and in need of intensive care. They would need ventilators to help them breathe, but there are only 105,000 in the country, according to Osterholm, and three quarters of them are in use already on any given day. Leavitt fears that most localities simply haven't planned for the "surge" in medical admissions resulting from a pandemic; he compares the situation to a great hurricane, with the difference that a pandemic can strike all over the country at the same time, so Philadelphia, say, couldn't count on help from Chicago or Atlanta. "All states have pandemic plans that are insufficient," he says.

So Leavitt's department will work to improve their plans. There is no question that the administration is taking the threat of avian flu seriously, even though it's still hypothetical at this point; epidemiologists agree that a flu pandemic is inevitable sooner or later, although there's no way to predict if H5N1 will be the germ to cause it. White House aides say President George W. Bush himself raised the question of preparedness, after reading historian John Barry's definitive account of the 1918 pandemic, "The Great Influenza." Barry believes the country is sadly unprepared for an epidemic, a situation he blames on Congress-- "they cut every [budget] request in half." If the past year has shown us anything, it's how startlingly ill-equipped modern bureaucracies can be to cope with a fast-moving natural disaster. As Barry noted, Bush read his flu book because he liked the historian's earlier work. It was an account of the great 1927 flood along the Mississippi River.