Why Hong Kong's `Bird Flu'
Signals a Serious Threat
by Robin Marantz Henig

Copyright 1998 The Washington Post Company
Reprinted with permission of The Washington Post (January 4, 1998)

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While researching a book about emerging viruses in the early 1990s, I asked the same question of every virologist I interviewed: What would be the next plague? The answer was almost invariably one disease: influenza.

Such an answer was not especially interesting, I discovered, to most people. Influenza was too familiar, too intimately known as "just the flu." Generating widespread concern about its power as a global threat was as hard as creating interest in the power of asthma, another hidden killer. Why worry about influenza while there were so many more bizarre, more colorful, and more gruesome viruses, like Ebola, to fret about?

The recent outbreak of Hong Kong "bird flu" has focused new attention on the threat of influenza. It's about time. Since my book came out five years ago, I have watched in frustration as influenza was relegated to the back pages while the media agonized over outbreaks that were more dramatic but of far less importance to the public health -- outbreaks such as bubonic plague in India and Ebola virus in Zaire.

Though we're advised to get flu shots and warned that the flu can be deadly, plain old influenza just isn't sexy enough to lead the evening news. It sends people to bed for a week or two, and then they get better. Its symptoms are certainly not photogenic, nothing like the blood-red eyes of Ebola victims or the huge buboes (grossly enlarged lymph nodes) on people with the plague. And almost everyone eventually recovers from the flu, little the worse for wear.

For all its familiarity and apparent harmlessness, though, influenza has always been a killer. Even in a normal year, complications kill 10,000 to 20,000 Americans -- most of them aged or chronically ill. And in an unusual year, like this one might yet turn out to be, influenza presents the most imminent viral threat to people on the planet.

That is why the new strain emerging in Hong Kong frightens me so much.

The last devastating influenza pandemic occurred in the winter of 1918-19. ("Pandemic" refers to a higher-than-expected rate of disease occurring on several continents at once, as opposed to "epidemic," where the excess disease is confined to a particular area.) In October 1918 alone, the "Spanish flu" killed 196,000 people in the United States, almost twice as many in a single month as died of AIDS during its first 10 years.

Before the dreadful winter was over, 2 billion people around the world had come down with influenza. An estimated 20 million to 40 million died. The pandemic caused more death and destruction in one six-month period than any other in any comparable period, before or since -- more than the Black Death of the 14th century, more than the smallpox of the 16th century, more than AIDS has killed so far.

We like to believe that whatever was killing people so ruthlessly in 1918 must certainly be something we can treat by now. It's true, of course, that modern medicine has given us an influenza vaccine, an anti-influenza drug (amantadine), and plenty of Antibiotics to prevent or treat secondary bacterial infections. But during the 1918 debacle, many victims were felled far too quickly to be treated. One man, for instance, got on a streetcar feeling well enough to go to work, rode six blocks, and died.

Then, too, vaccines must be concocted more than nine months before the flu season begins, based on an educated guess of what strains of virus will be circulating. The current flu vaccine offers no protection at all against bird flu, because no one could see it coming.

In the face of a virus that can spread and kill so rapidly, then, all the antiviral vaccines and drugs in the world would be virtually impotent.

This is why we must pay close attention to the current outbreak, even though it is halfway around the world and so far has killed only four people. What makes it so worrisome is that the virus responsible for the Hong Kong deaths and chicken slaughter contains a unique combination of proteins on its outer shell that renders it unrecognizable to the human immune system -- and therefore able to wreak its havoc before the body, even a previously young and healthy body, knows what hit it.

The influenza virus is a masterful quick-change artist. It changes the outer proteins on its shell, known as antigens, easily. The changes occur because the influenza virus lacks the genetic "proofreading" ability seen in many more stable viruses (as well as in every other life-form). When it makes an error in reproducing its own genetic material, the influenza virus passes along these errors to progeny viruses. In these ways, even a tiny error becomes permanent -- or as permanent as a mutable agent like the flu virus is likely to become.

This misplaced information can lead to a minor change in the outer coat, a change known as "antigenic drift." The change is slight, but significant. It is as though the virus took off its purple coat and put on a red one. The body can recognize the new virus as familiar, but the difference in color alone means that its anti-purple antibodies will no longer be quite enough.

Antigenic drift occurs every year or so, rendering any prior immunity to influenza, whether acquired naturally or through a vaccine, ineffective after a very short time. Someone who received a flu shot in 1997 will have little immunological memory for the slightly changed influenza virus encountered in 1999. That is why the flu vaccine must be given annually, and why it's possible to come down with influenza (as opposed to chicken pox, which you can only get once) even though you have had it before.

A major change in the virus's surface antigens is something else altogether. It goes far beyond replacing a purple coat with a red one. This change, known as "antigenic shift," is more like taking off the virus's purple coat and putting on a white tunic, green scarf and spangly orange cloak. Everything is different, and the immune system fails to recognize the virus altogether. After an antigenic shift, a pandemic almost inevitably follows.

Antigenic shift has happened three times this century. What's going on now in Hong Kong may be the fourth. Animals are almost always involved in the process, and in each of the three pandemics -- the 1918 outbreak, the "Asian flu" of 1957, and the "Hong Kong flu" of 1968 -- the new influenza strain originated in Asia, most likely somewhere in China.

breeds many new flu strains because it has so many ducks. By some counts, the country has more wild ducks than it has people. Ducks are the main reservoir for human influenza virus; they can carry it without getting sick. When they are near other animals that are also flu reservoirs, as happens often on Chinese farms, the different viruses have a chance to combine. New hybrid viruses, known as "reassortants," may then emerge.

Although reassortants emerge fairly often, it is only rarely -- three or four times this century -- that the hybrid turns out to be capable of infecting humans.

That is what seems to have happened in Hong Kong this year. On the farms in mainland China where 80 percent of Hong Kong's chickens originate, fish farming puts ducks and barnyard animals near each other in the ponds dug to breed fish. When a duck lands on the pond and defecates, or takes in water through its cloaca, it is exposed to the pig manure often used as fish food in the very same pond. The result: The animal viruses can combine in the duck intestine, and the resulting chimera -- part-duck, part-swine, maybe part-human -- is an entirely new influenza virus.

This new virus, if it circulates at all, usually circulates only among animals. The same bird flu, known scientifically as H5N1, arose in Pennsylvania in 1983 and raged through poultry flocks in the region so quickly that all the chickens in the state had to be killed. It erupted in Mexico in 1994, and again in 1995. But in none of these poultry outbreaks was H5N1 ever able to infect humans -- even farmers who had intimate contact with the dead or dying birds.

Today's H5N1 influenza seems to be different. It is capable of making people sick. Nearly two dozen people have come down with influenza as a result of exposure to chickens. Four have died. No one yet knows exactly how H5N1 has changed, but it apparently has.

Why make a fuss when the number of infected humans is so small? This is precisely the right time to make a fuss. The last global influenza pandemic, in 1968, began with a single case; within five months it had spread around the world and killed more than 45,000 people, more than 60 percent of them (28,000) Americans. Coincidentally, that pandemic also began in Hong Kong.

The significance of all this is yet to play out. Investigators from the Centers for Disease Control and the World Health Organization hurried over to Hong Kong at the first word of the first case, which was described in the British journal Nature in early October.

Fortunately, Hong Kong health authorities are taking the threat seriously. They say they have slaughtered more than 1.3 million chickens, as well as other poultry raised near chickens, and have banned importation of chickens from mainland China, despite the economic and political hardships such measures signify.

And our scientific radar continues to be attuned to the real possibility that a massive influenza pandemic is indeed a public health threat of global significance. The general public is now gradually, grudgingly, learning what the scientific community has been trying to tell us for years: that all our medical sophistication is still relatively helpless in the face of the elusive tactics of our tiniest enemy.

Robin Marantz Henig, a Washington medical writer, is the author of "A Dancing Matrix: How Science Confronts Emerging Viruses" (Vintage).

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