Fuss and Feathers

"The indication is that we will see a return of the 1918 flu virus that is the most virulent form of flu," warns America's top health official. "In 1918, half a million people died. The projections are that this virus will kill one million Americans . . . "

A quotation ripped from today's papers about an impending "bird flu" pandemic? No, the year was 1976 and the prediction of a deadly "swine flu" overshot the mark by 999,999 deaths (although dozens did die from the vaccine campaign). That's something to remember amid the current alarms. Another is that we've been here before with the identical virus over which the feathers are now flying, avian influenza type H5N1, which first hit poultry flocks in 1997. "Race to Prevent World Epidemic of Lethal 'Bird Flu,'" and "Hong Kong 'Bird Flu' Could be the Next Big Outbreak," blared the headlines then.

The world death toll from that "wave"? Six. And let's not forget the outbreak of SARS (severe acute respiratory syndrome) two years ago, which led to 750 stories in the New York Times and Washington Post – one per death worldwide, as it turned out. The 71 U.S. cases of SARS, which resulted in zero deaths, did not "Overwhelm U.S. Health System," as CNN had predicted.

None of which is to say there won't be another flu pandemic. There were three in the last century, after all. But that gives us absolutely no idea when the next will come, nor whether it will be any relative of H5N1, nor what its impact will be. Two of those 20th-century pandemics weren't particularly severe, while the other was catastrophic. (Pandemic, by the way, does not mean "deadly epidemic" – it means "worldwide epidemic.")

What we can say with confidence is that there is never such a thing as helpful hysteria. And the line between informing the public and starting a panic is being crossed every day now by politicians, public health officials, and journalists.

Officials at the Centers for Disease Control and Prevention (CDC) have been handling numerous fearful phone calls from the public and the media, fielding questions about the safety of bird feeders and Thanksgiving turkeys. "It's been insane," spokesman Dave Daigle told MSNBC. In a recent Q&A session with Wendy Orent, science writer and author of the book Plague, a Nashville resident asked why "don't we just kill off all the domestic birds and poison the food on the migratory bird routes?"

Headlines like "Flu Pandemic Could Kill 150 Million, U.N. Warns" (Reuters) certainly haven't helped. Never mind that the figure was tossed off by a single official who provided a range of "5 million to 150 million." (Translation: "We haven't the foggiest.") Similarly, the media have generally morphed the federal government's estimate of 200,000 to 1.9 million deaths to simply "1.9 million deaths." Also not helping is the media propensity to seek out the most alarmist "experts."

High on the list of scaremongers is Laurie Garrett, former Newsday reporter and now a senior fellow at the Council on Foreign Relations. Garrett is to pandemics what Paul Ehrlich is to population growth, having amassed fame and fortune by being consistently and spectacularly wrong. Just as he became famous predicting a Population Bomb that fizzled, she came to prominence through a 1995 book, The Coming Plague. No, it hasn't come yet, but – trust her – it will.

Garrett’s rise began with her prediction of an Ebola virus pandemic. This was notwithstanding the fact that Ebola is just about last on any realistic list of possible pandemic pathogens, since it's terribly difficult to transmit. But guess who won the 1996 Pulitzer Prize for Ebola coverage? Lessons like this aren't lost on other journalists.

Then there's University of Minnesota School of Public Health professor Michael Osterholm, who has spent the last several years trying desperately to outdo Garrett. He came up with a worldwide avian flu death toll estimate of 180-360 million simply by extrapolating the estimated death toll from the Spanish flu of 1918-19 to today's world population.

But the winner in this grim game of one-upmanship is Dr. Irwin Redlener, director of the National Center for Disaster Preparedness at Columbia University, who claimed on ABC News's Primetime on September 15, "We could have a billion people dying worldwide."

When I later questioned him on this figure, he rather sheepishly admitted he meant to say "one billion ill." Quite a faux pas. But Garrett and Osterholm were on the same show, and neither made a peep to correct the misstatement. ABC used it as part of the introduction. "It could kill a billion people worldwide, make ghost towns out of parts of major cities, and there is not enough medicine to fight it," declared the somber voiceover. "It is called the avian flu." So the billion figure is out there and, no, this single article won't succeed in pulling it back.

Yet the more serious the potential threat, the less excuse there is for running around like infected chickens with our heads cut off. If we do face a pandemic flu in the coming months or years, there are numerous actions we can take that will save an enormous number of lives, and some of the most important you probably haven't even heard about because they don't work as melodrama.

Let's break the pandemic issue down to its simpler parts, namely: How likely is avian flu to become readily communicable between humans? How contagious would it be? What interventions could be taken if it did become pandemic? How deadly would it be?

But first, How exactly does "avian" flu differ from "normal" flu? Every year several strains of flu circulate around the globe, usually reaching U.S. shores in late October and infecting 5 to 20 percent of the population. Flu leads to the death of about 36,000 Americans in an average year. To reduce the level of illness and death, we vaccinate. Unfortunately, flu mutates rapidly, so the antigens on the virus's protein coat change each year. This is known as "antigenic shift" and explains why we need to get new vaccines every fall – the protective antibodies we received from last year's vaccination were designed for last year's antigens. Health authorities tell us the white lie that there is no carry-over immunity from being vaccinated or infected the previous year; but actually there is some.

Nevertheless, if there were a radical "antigenic shift," the annual vaccine would be worthless. We would then suffer another pandemic such as the Asian flu of 1957-58 that caused about 70,000 U.S. deaths and a million globally, the Hong Kong flu of 1968-69 that caused 34,000 U.S. deaths and 1-4 million globally, and the big daddy of all modern pandemics, the Spanish flu of 1918-19, that killed more than half a million Americans and about 25-50 million worldwide. (It should be noted that some experts, such as Dr. Edwin Kilbourne, emeritus professor of immunology at New York Medical College, believe avian flu is closely enough related to flus to which we've already been exposed that we would have some natural protection.)

Lots of animals get influenza, and it often jumps from species to species. Sometimes we give it to them, and other times they give it to us. That's the worry with avian flus. They were first recognized in Italy over a century ago, but the current epidemic of H5N1 among birds wasn't discovered until 1997 in Hong Kong, when it began killing chickens and then spread to humans, six of whom died. (This prompted the first panic.)

Poultry vaccines are available, and international bodies encourage their use, but compliance has varied tremendously. Vietnam appears to be making a heroic effort to inoculate all of its poultry, and other countries might follow suit, but vaccinations cost money, and the U.N. claims the West isn't forking over big enough premiums for an avian flu insurance policy. Once a flock is infected, nothing can be done but to slaughter every bird. In the meantime, migratory birds can carry it to another part of the country, or even to other continents, as we've recently seen.

As of November 9, 125 cases and 64 deaths have been reported from avian flu since late 2003, all in Indonesia, Thailand, Vietnam, and Cambodia. There have been a few cases of possible transmission from one family member to another, but that would have involved massive exposure and it could also be that the second family member got the disease directly from fowl. Nobody is saying that H5N1 is yet a threat to anybody other than bird farmers. But could it become one?

The Human Threat

With all flu viruses, to paraphrase a bumper sticker, mutation happens. Avian flu could randomly mutate to be transmissible between humans. But it would indeed be random, since the virus is doing just fine in the bird population, thank you very much. There is no evolutionary pressure for it to reach out and infect other species. Such mutations nonetheless come along now and then. The infamous Spanish flu, for example, appears to have started as an avian flu.

Another scenario is that somebody with human flu could contract avian flu at the same time and the two flus could "reassort" into hybrid avian-human flu. The latter two epidemics in the 20th century were such hybrids. The World Health Organization has just reported that there is no evidence this has occurred with H5N1. The best means of reducing this likelihood is to vaccinate as many people as possible (especially in Southeast Asia) against human flu, thus reducing the potential number of "mixing vessels."

The key question: What is the likelihood of either of these scenarios? Anybody who gives you an answer other than "No one really knows the risk," as Richard Webby says, is pulling your tail feathers. Webby is a virologist at the Department of Infectious Diseases, St. Jude Children's Research Hospital in Memphis.

There are no pat formulas, such as the chances of shooting snake eyes or drawing a royal flush. Nor is it just a matter of time. Indeed, one of the arguments against a human outbreak of H5N1 is that sick birds have been mixing with humans for years now without producing a pandemic.

It's practically a state secret that the discovery of H5N1 in poultry dates back not to 1997 but rather to 1959, when it was identified in Scottish chickens. Perhaps haggis had a protective effect on the farmers, but there was a terrible outbreak of the related H5N2 among both chickens and turkeys in Pennsylvania in 1983-85 (17 million birds were destroyed) that appears to have originated as H5N1 in seagulls. So H5N1 has been flying around the globe for over four decades and hasn't done a number on us yet. That doesn't mean it won't ever; but there's absolutely no reason to think it will pick this year or next.

True, you can't compare the massive flocks and tremendous human-bird contact on packed Asian bird farms with the way poultry was raised in Scotland or Pennsylvania. But at the very least, the disease has had eight years of Asian conditions to mutate or become a hybrid, and so far it has not.

The "Overdue" Flu

Still, there are those of great influence who would have us think a pandemic is just around the corner. Reassuringly, their explanations are unscientific. One is that "we're overdue" for a pandemic. Google "avian flu" and "pandemic" and "overdue," and you'll get over 40,000 hits. "In the 20th century there were three pandemics, which means an average of one every 30 years," explained one health official to the New York Times. "The last one was in 1968, so it's 37 years. Just on the basis of evolution, of how things go, we're overdue."

Really? It was 39 years from the first pandemic to the second, but only 11 from the second to the third. Is that a pattern, or some white-jacketed yokel demonstrating his ability to do long division? On the other hand, if you knew that this yokel was director of the National Institute of Allergy and Infectious Diseases, Dr. Anthony Fauci, you might be justified in thinking we do have something to be worried about. Nevertheless, Fauci also said some foolish things about the SARS threat, and somehow we managed to survive that.

It's instructive that one reason for the 1976 swine flu panic was that "experts warned that pandemics tended to be cyclical and that another one was about due," according to the New York Times. What kind of a "cycle" can be either 11 years or 39 years long? Risk-management expert Peter Sandman correctly refers to the concept of the "overdue" pandemic as nothing more than a superstition.

Another source of alarm is a series of reports of mammals becoming infected, including tigers and leopards. But these were zoo animals in Thailand, fed the carcasses of infected poultry. A somewhat alarmingly titled medical journal article, "Probable Tiger-to-Tiger Transmission of Avian Influenza H5N1," actually says nothing more than that such transmission is "possible."

The best surrogate for humans has long been thought to be swine. "Pigs are probably very much like humans," says Webby. "But we showed [in a recent study] that there's not a lot of [H5N1] infection going on with them. The other important factor is that when swine become infected, according to theory, [the virus] becomes better adapted to infect humans. But there's no evidence that's happening," Webby says.

When government researchers finished decoding the genetic sequence of the Spanish flu earlier this year, allowing it to be studied for the first time, some claimed that its genetic code showed great similarity to H5N1. But all influenza viruses are related. Like the avian flu, the Spanish flu had eight gene segments; all flu viruses do. They're both what are called Type A influenzas; but the main type of human flu that circulates each year is Type A. More than 99 percent of the amino acids (basic structural building units of proteins) are identical. But humans and chimpanzees share 96 percent of their DNA. What counts isn't the similarity, but the difference.

The leader of the sequencing team naturally tried to connect the Spanish flu to the avian flu. Jeffery Taubenberger, a molecular pathologist at the Armed Forces Institute of Pathology in Rockville, Md., told the Washington Post that of the roughly 4,400 amino acids in the avian flu, perhaps only 25 would have to mutate properly to create a new Spanish flu. "It could theoretically provide a checklist for surveillance," he told the Post. "You might be able to say: this strain has six of these changes; it's a worrisome virus we need to keep our eye on. Or this one has none."

That's a gross oversimplification, though. It's not as if there were a thief intelligently picking a lock with 25 tumblers one by one. When mutations occur, as one tumbler randomly falls into place, another can as easily fall out of place. And remember, those tumblers have been turning for at least 46 years, since the Scottish outbreak. Long before H5N1 becomes transmissible from human to human, it may mutate into a 98-pound weakling, capable of causing little more than a sniffle in humans. Or it may simply wait a few more years before striking, by which time we'll be inundated with vaccine and have so much antiviral medicine stockpiled they'll be giving it away in Crackerjack boxes.

Slowing the (Hypothetical) Spread

What about contagiousness (also called "virulence") if avian flu does become a human disease? We have no idea. But we do know that those who enjoy scaring us with images of 1918 have yet again pegged that pandemic wrong in a very important way. Until recently, estimates were that during the Spanish flu each victim infected 20 others. But a Harvard study published in Nature last December found that on average each infected person infected only 4 others. This indicates that if one insists on using 1918 as the model, an avian flu pandemic might be brought under localized control more readily than was thought.

Quarantines won’t work with flu because of the time lapse between infection (and infectiousness) and the appearance of symptoms, and because some flu carriers never become symptomatic. People will have already spread the disease before they show any signs of it themselves. How about the surgical masks that everyone started wearing in Asian cities in 2003, and which became the symbol of the SARS scare? There's such a split of opinion on the effectiveness of masks that the contradictions appear within a single official document. "The use of surgical or procedure masks by infectious patients may help contain their respiratory secretions and limit exposure to others," says a CDC posting from August. "However, no studies have definitively shown that mask use by either infectious patients or health-care personnel prevents influenza transmission." Thanks a lot.

Washing your hands frequently with soap and hot water (or better yet, with alcohol) probably helps, as may keeping your immune system strong with a good diet and enough sleep. And for goodness' sake, don't shake hands with people who sneeze into their own. In other words, practice ordinary good hygiene. And get your annual flu shot to reduce the chances you'll be battling two flus at once.

One possible method of both containment and treatment would be administration of antiviral drugs called neuraminidase inhibitors. Neuraminidase (the 'N' in H5N1) is a protein on the surface of the virus that must multiply in order for the virus to create copies of itself. One such inhibitor is Roche's Tamiflu, which has already become an object of obsession within the larger hysteria. Both governments and individuals are stockpiling it, perhaps in large part as a response to a medical journal article early this year encouraging them to do so. (By coincidence the authors worked for Roche.)

Tamiflu reduces the duration and severity of acute human influenza, and work at St. Jude's has shown that H5N1 appears to express the highest level of neuraminidase of any flu since 1957. Petri dish studies also show the twice-daily oral drug strongly inhibits replication of the virus, and it appears to greatly increase survival rates in infected birds. Unfortunately, at least one study published in August in the Journal of Infectious Diseases – comparing the current H5N1 and that circulating in Hong Kong in 1997 – indicates that Tamiflu may be losing its effectiveness. But computer models suggest that quick administration of antivirals in a localized outbreak just might keep it contained.

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