Avian Flu: How Scared Should We Be?

By Christine Gorman

For the past two years, scientists, public-health officials and even a high-ranking government official or two have warned about the potential danger of a deadly worldwide outbreak, or pandemic, of avian flu. But it took a couple of furies named Katrina and Rita to really bring home how much can go wrong if you don't plan for major emergencies.

Suddenly old warnings about flu, which had seemed so remote, were sounding a lot scarier. The World Health Organization (WHO) declared in September, once again, that as far as an influenza pandemic is concerned, the question is not if but when, not whether millions would die but how many millions. President George W. Bush talked last week for the first time about how he, as Commander in Chief, might respond to an epidemic, raising the possibility of using troops to enforce quarantines. He also recommended that folks read John Barry's book on the 1918 pandemic that killed more than 50 million people worldwide and that serves as a reminder of the kind of threat that the world could face (see ESSAY). A reconstruction of the 1918 virus, reported in scientific journals last week, shows it to be an avian strain that mutated just enough to infect humans directly and easily.

The prospect of a flu epidemic makes us wobbly. We bounce back and forth between being scared silly and just plain apathetic. Influenza regularly kills 1 million people a year--36,000 of them in the U.S.--yet most of us don't get vaccinated. The new threat requires a different response--a healthy respect for the toll that even a moderate pandemic may take on our society and just enough genuine fear to figure out some smart steps to take to minimize the damage. "We need to scare people into their wits, not out of them," says Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. With that in mind, here's a primer on the risks of a flu epidemic and the government's preparations for countering it.

o HOW DOES A FLU THAT KILLS BIRDS BECOME A FLU THAT KILLS PEOPLE?

All influenza viruses--if you trace their lineage back far enough--got their start in birds, and the great majority stay there. But a handful of flu viruses adapt to the point that they can infect people. Each year the viruses capable of invading human cells mutate slightly in a way that leads to fresh outbreaks, but most people will still have a partial immunity because of previous exposure to similar viruses. Occasionally, though, a strain that had seemed to infect only birds will cross over more or less intact into humans. Because this new strain is so different from garden-variety flu viruses, few people are immune. That is apparently what happened in 1918 and in Hong Kong in 1997, then later in Vietnam and Thailand and in Indonesia this summer and fall.

Virologists named the newest strain of avian flu H5N1, after two proteins (hemagglutinin and neuraminidase) that dot the surface of the virus like spikes on a mace. Since 2003, more than 100 people have become sick enough to come to the attention of health authorities, and at least 60 of them have died. So far, the vast majority have been infected through close contact with birds; human-to-human infection is still extremely rare. What gives health authorities nightmares is the possibility that the lethal H5N1 could mutate into a virus that is easily passed among humans.

o WHAT MAKES THIS PARTICULAR AVIAN FLU SO DEADLY?

For reasons that aren't entirely clear, the current H5N1 flu, unlike common flu, strikes deep within a patient's lungs, making it harder to spread to someone else and unusually lethal. Dr. Nguyen Hong Ha of Hanoi's Bach Mai Hospital has probably treated more cases than anyone else. Two-thirds of the deaths from bird flu since 2003 have occurred in Vietnam. Ha has watched the virus ravage the lungs of healthy young patients in a matter of days. He says the key to treatment is applying just the right amount of breathing assistance. Too much, and an H5N1 patient's weakened lungs could burst. But, he says, survival ultimately comes down to "the patient's immune system and the will to fight."

Antiviral medications like oseltamivir (Tamiflu) have shown promise in tests but must be taken within 48 hours of the first symptoms' appearance--requiring a very swift diagnosis. More in-depth study is needed to assess how well those drugs would work against a pandemic--something that's tough to do with so few patients and viral samples.

In the end, the best course of action is not to treat this sort of flu but to prevent it. Preliminary results, released in August, of an experimental vaccine against bird flu suggest that a high-dose vaccine given in two shots a month apart would yield the best response. "What is sobering is how much was required, which puts an added pressure on vaccine production," says Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

o HOW CLOSE ARE WE TO A PANDEMIC?

There have been 10 pandemics in the past 300 years. The most recent one was the relatively mild Hong Kong flu of 1968. But you can't say that we're overdue because biology is not that simple. Nor is it even certain that H5N1 is the strain that will eventually cause the next pandemic.

There are troubling signs, however, that H5N1 is on the move. The virus killed thousands of wild geese in China this past spring and popped up among migratory birds in parts of Siberia this summer. There was a report in May about a handful of infected pigs in western Java. Even more worrisome, Indonesian health authorities said last week that a number of chickens on household farms in Jakarta had been testing positive for H5N1 without showing signs of illness. If confirmed, that development could severely complicate efforts to track and control bird flu in poultry. Without dead chickens, you can't tell where the disease is moving.

But so far, tests on samples taken from two of the most recent human victims of bird flu show no cause for immediate alarm. "There are no obvious changes in the virus that we tested," says Dr. Guan Yi, an avian-flu expert at the University of Hong Kong who has helped sound the pandemic alarm. For now, he says, there's "nothing new. Nothing to worry about." The viral genes are still the same avian-flu genes that haven't figured out how to spread easily from one person to another.

That's important, because other than direct evidence of sustained human-to-human transmission, the first tip-off to an imminent pandemic could be a prominent mutation in H5N1, perhaps as the result of genetic mixing between two types of flu viruses. Pigs and people would be the most likely incubators. But it's also possible, as a series of papers in Nature and Science concluded last week, that flu viruses from birds could clear the critical hurdles on their own. Researchers who managed to re-create the 1918 flu virus from snippets of lung tissue stored decades ago showed that perhaps a couple of dozen mutations in a more or less purely avian-flu virus were all that was needed to trigger that long-ago pandemic.

o WHAT WOULD A PANDEMIC BE LIKE?

Michael Leavitt, Secretary of Health and Human Services (HHS), recalls walking through 17 devastated cities in the weeks after Katrina and wondering what it would be like if there were disasters in all 50 states. "A pandemic is a substantially different emergency than a natural disaster," Leavitt says. "A pandemic takes place over the course of a year. It can happen in 5,000 venues at the same time."

There wouldn't necessarily be a lot of warning. An outbreak anywhere in the world could circle the globe in just a few hours. Shutting down airports, computer simulations have shown, results in at most a couple of weeks' delay in transmission. WHO says it is reasonable to prepare for 2 million to 7.4 million deaths, although the number could be higher.

o ARE WE READY?

Finally, an easy question. The answer is no. Only a fifth of the world's countries have a pandemic-response plan, according to the WHO; those plans vary greatly in comprehensiveness. Fewer than 10 nations have domestic vaccine companies trying to produce an avian-flu vaccine. Even common flu vaccines are notoriously unprofitable--among other things, they have to be thrown out each year--which is why U.S. companies have all but abandoned the field.

The U.S. Department of HHS began working on a pandemic-flu plan in 1993. It finally released a 50-page draft last year; a completed version is due later this month. A leaked 381-page draft obtained by the New York Times last week is long on dire predictions and short on chain-of-command specifics, according to the newspaper.

Secretary Leavitt admits that U.S. preparedness for a pandemic contains gaps and that a recent holdup has been negotiations with the drug industry over how to encourage vaccine development and production. Those talks got a high-level boost last week when President Bush met with six pharmaceutical executives. "The Katrina situation has really influenced him," says a White House official. "The hardest thing to wrap your head around and get data on is, What's the likelihood? Nobody really knows. But everybody believes that we've got to prepare for the worst." One possibility the White House is considering is a plan to spend $10 billion on stockpiling vaccines.

But vaccines aren't the whole solution. Should a pandemic take hold, demand would soar for surgical masks, hospital beds, mechanical ventilators--which help people breathe when their lungs are fighting an overwhelming infection--and other items. "We have only 105,000 ventilators right now in America, and 95,000 are being used," says Tommy Thompson, a former HHS Secretary who startled a lot of people last December when he said pandemic flu was one of the two things that kept him awake at night (the other was the safety of the food supply).

o WHO'S IN CHARGE?

That's still being worked out. As things stand, HHS would be in charge of the federal medical response. The Department of Homeland Security would handle the emergency response, as it does after a hurricane. But most of the authority sits with the states, which are free to call on the Centers for Disease Control and Prevention.

States are in charge of public health, with help from local officials. That is great news if you live in a place like Seattle, Los Angeles or New York City--places that health experts cite as relatively well prepared. Others may want to contact their officials and ask what they are doing.

o WOULD A QUARANTINE MAKE A DIFFERENCE?

Despite what the President said earlier last week, a quarantine would probably not be an effective solution for a bird flu that has become pandemic. It is hard to tell who is sick because humans are contagious before they show symptoms. And communities today are much too interdependent to shut down their borders for months on end. (Quarantines worked to control the SARS epidemic because SARS is much less contagious than flu and has a longer incubation period.) That doesn't mean we won't have quarantines. "Politicians will be under a lot of pressure to demonstrate that they are doing something," says Monica Schoch-Spana, a medical anthropologist at the Center for Biosecurity at the University of Pittsburgh.

Far more realistic than a quarantine, health experts say, would be isolation and perhaps some kinds of movement restriction. Sick people, either at home or in hospitals, would be kept apart from healthy people. Caregivers would need to use masks, if there were enough of them, and other barriers to prevent infection. For the rest of the population, large gatherings might be discouraged. Schools, malls, churches and sports events might temporarily shut down--although even that would be of questionable effectiveness.

That is all scary stuff--and it may be years away--but a worldwide epidemic is brewing. No one can tell if it will be a Category 1 or a Category 5 storm or when it will hit. Katrina taught us you can survive the initial catastrophe and perish in the aftermath. "We are seeing the unfolding of a pandemic in slow motion," Dr. Klaus Stohr of WHO told a group of business leaders at Deutsche Bank in New York City last month. "We can reduce the damage, but we cannot avoid it."

TAKING FLIGHT

Since 1997, the H5N1 strain of the avian-flu virus has traveled steadily west across Asia. The current outbreak began in December 2003, infecting humans in Cambodia, Thailand, Vietnam and Indonesia. Although Southeast Asia has borne the brunt of the disease, scientists fear that infected migratory birds will spread it further, resulting in a global pandemic.

[A] Number of outbreaks in birds [B] Number of known human cases [C] Number of known human deaths [D] Areas with H5N1 outbreaks during the past eight years [E] Areas with H5N1 outbreaks in 2005

CENTRAL ASIA [E] o 53 [A]

JAPAN and SOUTH KOREA [D] o 24 [A]

CHINA [D][E] o 55 [A]

HONG KONG [D] 1997 and 2003 o 4 [A] o 20 [B] o 7 [C]

SOUTHEAST ASIA [D][E] 2003 to 2005 o 2,989 [A] o 112 [B] o 57 [C]

INDONESIA and MALAYSIA [D][E] 2004 to 2005 o 226 [A] o 4 [B] o 3 [C]

Sources: WHO; World Organization for Animal Health; Food and Agriculture Organization of the U.N.

With reporting by Reported by Mike Allen, Amanda Ripley, Eric Roston/ Washington, Helena Bachmann/ Geneva, Kay Johnson/ Hanoi, Jason Tedjasukmana/ Jakarta, Bryan Walsh/ Hong Kong