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A horror script for health officials

The metaphor that public health officials invoke when talking about a global flu epidemic is the same one that lies at the heart of the scariest horror movies.
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The metaphor that public health officials invoke when talking about a global flu epidemic is the same one that lies at the heart of the scariest horror movies.

It is the idea of a small and deadly thing that is poking and prodding for a weak spot in whatever is protecting its intended victims. It is patient, because it knows it will eventually succeed. When it does, a horrible metamorphosis makes it huge and unstoppable.

This plot was a deadly hit in 1968, 1957 and, most notoriously, 1918, when pandemic influenza killed about 50 million people worldwide. Today, virologists fear a remake is underway in East Asia.

Over the past month, a strain of bird flu that has killed thousands of chickens in nearly half a dozen countries has broken through the "species barrier" to claim a few human victims. This time, though, the public health community hopes to write a different end to the script.

"There is a chance that something can go wrong," Klaus Stohr, head of the World Health Organization's flu program, said Friday in Geneva. "But it looks as if we act decisively and timely now, there is a window of opportunity here to control the disease before it takes global proportions."

That action consists of exterminating chickens carrying the virus, protecting people in contact with the birds from infection and understanding the pathogen at the molecular level -- all as quickly as possible. Cross-border traffic of live birds and poultry products has stopped in much of the region, and there is talk of vaccinating millions of chickens.

So far, there is no evidence that this bird flu can be passed from person to person -- a trait it would need to acquire to make it a global threat.

"Everyone has their ear to the ground. That is the big question, isn't it?" said Robert G. Webster, one of the country's leading influenza experts, who jetted to Hong Kong two weeks ago to study the new strain.

Stakes could be higher than SARS
If evidence of person-to-person contagion appeared, the already urgent response would escalate dramatically. Borders would close, the ill would probably be quarantined, and a crash program to make a new version of the annual flu shot would begin. The response would be much like the one mounted against severe acute respiratory syndrome (SARS) a year ago.

The stakes would be much higher, however, because the flu virus, once fully adapted humans, can spread with a speed and ease that SARS never showed. A lot has to happen, though, for bird flu to gain that capacity. The trouble is that in influenza's world, a lot can happen very quickly.

Health authorities in Vietnam are investigating 30 suspected cases of bird flu in people. Fourteen have died, most of them children under age 12. In six cases, laboratory testing identified a strain of avian influenza designated H5N1. Late last week, two children in Thailand -- both still alive -- were diagnosed with H5N1 flu.

The H and N denote two proteins, hemagglutinin and neuraminidase, that sit on the outer shell of the virus. Together, they provide a virus's chemical appearance to the immune system. The particular combination of H and N is the key to a strain's identity and the first hint of whether it might be a danger to people.

There are 15 forms of hemagglutinin and nine of neuraminidase in the most populous class of flu viruses -- influenza A. (The less common and less dangerous influenza B has only one type of H and N).

When a virus with a new H-N combination appears, immunity built up to older ones is no help. What follows can be a worldwide epidemic -- assuming the virus also grows well in people and is spread easily in coughs and sneezes.

How pandemics happen
The great pandemic of 1918 was H1N1. It was unquestionably new, although what strain it replaced is not known. In 1957, an H2N2 virus appeared in southern China, triggering a pandemic of "Asian flu." In 1968, an H3N2 virus appeared, causing the global "Hong Kong flu." In 1977, H1N1 reemerged -- by then, nearly everyone under age 20 had never seen it -- and caused a mini-pandemic.

There are many H-N combinations, however, seen only in other species, particularly birds, which are the real home range for flu virus. The feared H5N1 is one of them. It can tear through chicken flocks with a mortality approaching 90 percent. But virologists did not think it could infect people -- at least, not until 1997.

That year, 18 people in Hong Kong became infected with H5N1 -- the first time direct bird-to-people transmission had been seen. Six died, most of them healthy young adults -- a disturbingly high percentage.

Previously, scientists believed that to infect and kill a person, a bird flu virus would first have to acquire at least a few genes from the flu viruses that regularly circulate in human populations. That is possible because unlike viruses whose genes reside on a single unbroken strand of RNA or DNA, flu carries its genetic information on eight separate strands. Under the right conditions, it can trade one of more of them with another flu virus, like a card player in a game of hearts.

Virologists once believed these "reassortments" occurred only in pigs, because that species were capable of being infected by both human and avian flu. With the 1997 Hong Kong cases, however, it was clear reassortment might also occur in a person simultaneously infected by both.

The chance of that occurring depends on how much avian flu is around. What scares scientists this winter is that it is all over the place -- in flocks in Japan, Vietnam, South Korea and now Thailand.

"It is an unprecedented situation with H5N1 virus in so many countries around Asia," Webster said. "The extent of the spread of this virus has not been seen before."

Chickens slaughtered across Asia
How H5N1 became so widespread is not known. The urgent chore is to get rid of the animals harboring it.

In recent weeks, tens of thousands of chickens have been killed in flocks in Japan, Vietnam and Thailand. The number could go much higher.

It is important to protect the workers culling the flocks from getting human flu, lest they themselves become the "mixing vessels" in which a reassortment occurs. WHO is urging they be vaccinated, and if possible be given preventive medicines.

Even without reassortment, it is possible that avian influenza could become a pandemic strain, but that is far less likely.

"Given enough time and enough opportunity, viruses could go through a process of human adaptation and become more transmissible than these ones are at the moment," said Nancy J. Cox, the head of the influenza program at the Centers for Disease Control and Prevention. "We know, though, that in 1968 and in 1957 the strains were reassortments between human and avian viruses."

Curiously, Hong Kong, where the first human cases of bird flu occurred, is reporting no H5N1 now.

That region changed its poultry-marketing practices after the 1997 outbreak. Waterfowl, which can carry H5N1, were separated from chickens. Quail, also viral hosts, were banned.

Markets were also required to be cleaned twice a month. People were thought to have been infected by breathing an infectious dust stirred up when chickens, whose feathers were contaminated with virus-containing feces, were taken flapping from their cages.

Still, H5N1 continued to turn up occasionally until last year, when a poultry vaccine began to be used widely, Webster said. Today in Hong Kong's markets, he said, "every chicken has had its shots."