The specter of the 1918 Spanish flu—which may have started in the United States, not Spain, and killed about 20 million to 50 million people worldwide—has prompted public-health authorities to predict that we are unprepared to deal with a pandemic based on a highly pathogenic new strain of the H5N1 avian flu. The strain first appeared on poultry farms in China in 1996. As of December 2005, it had infected more than 130 people, killed more than 65, and spread—in birds—as far as Eastern Europe.
WHICH FLU WHEN
1918 • H1N1 A virulent strain emerges during World War I and sweeps the globe, claiming up to 50 million lives. A weakened version still circulates.
1957–58 • H2N2 A strain from China reaches the United States, where it kills 70,000 people.
1968–69 • H3N2 First detected in China, the strain causes about 34,000 deaths in the United States. It still circulates today.
1997 • H5N1 This lethal bird flu hops directly into humans for the first time. Six people in Hong Kong die.
2003 • H5N1 The strain reemerges, killing one man in Hong Kong.
2004–05 • H5N1 The deadly bird strain strikes poultry throughout Southeast Asia, becoming entrenched in domestic chickens and moving west to Europe. By the end of 2005, the virus has infected more than 130 people, killing more than 65.
What is Avian flu? Experts believe all flu strains originate in wild birds. Avian flu appears in two forms: mild and highly deadly. Wild birds rarely sicken enough to die from avian flu. If they did, they would not be able to spread the disease effectively, because dead birds don't fly. Thus, scientists have found that wild bird flu is almost always mild. But when these strains infect domestic poultry in the crowded conditions found in Southeast Asia and on many big U.S. farms, the virus can become deadly because infected birds needn't be healthy enough to move around in order to spread it. Exposure to large doses of some virulent avian flus, including the H5N1 strain now circulating among poultry in Asia, can kill people. Most human deaths from H5N1 occur when people drink raw duck's blood or handle dead infected chickens. The few cases that seem to have spread from person to person involved close and prolonged contact.
What was the Spanish flu? It seems to have begun as a normal human flu strain that circulated in the United States in the spring of 1918. By summer, the virus had reached the battlefields of World War I. There, among people packed into the trenches, trucks, trains, and hospitals of the western front, it turned lethal, just as the avian flu does among birds on crowded chicken farms today. The key to its virulence, says University of Louisville evolutionary biologist Paul W. Ewald, is that the congested living conditions enabled the virus to spread from people immobilized by the infection to the healthy. The result was the deadliest flu humanity has ever seen. Yet within 18 months, the virus lost its power to kill. It still circulates around the world today.
What makes a flu virus easily transmitted from bird to human and then from human to human? The human airway is lined with two kinds of epithelial cells—those that possess hairlike fringes called cilia and those that don't. Human flu strains can infect both kinds of cells, but avian flu strains can bind to and infect only the ciliated kind, which are similar to cells in the airway and the gut of birds. An autopsy of one victim of H5N1 showed that most of the virus had grown deep in the lung tissue. According to Earl Brown, professor of medicine at the University of Ottawa, the more limited ability of the avian flu virus to infect cells in the human airway thus also appears to be associated with infection of the deep areas of the lung where oxygen and carbon dioxide are exchanged. This would make it less likely that the H5N1 virus could be coughed out of the lungs and transmitted from person to person. That may be another reason few humans have contracted it, despite the fact that there are millions of people who work and live with chickens in Asia. H5N1-infected patients have not been contagious to the health-care workers treating them.
Avian flu can become highly transmissible from person to person in two ways. The first is when avian and human flu strains combine genes, or reassort. This genetic mixing can occur when a person is infected by both avian flu and a human flu strain at the same time, in the same cell. This is how at least two of the three human pandemics of the 20th century (the Asian flu of 1957 and the Hong Kong flu of 1968) arose. The second way is through a chain of human infections that allows the bird virus to evolve in people and become increasingly adapted to them. While this process may have produced the 1918 flu, that virus acquired virulence only under the conditions of World War I trench warfare.
How is the H5N1 flu migrating?
How migratory birds are spreading this flu from Asia to Eastern Europe is a mystery. Wildlife veterinarian William Karesh of the Wildlife Conservation Society thinks that wild birds infected with virulent flu may be able to fly for a few hundred miles after infection and then shed the virus into water for a week or more. In lakes and marshes, the virus could, in turn, infect other birds, which may then fly somewhere else, carrying the disease with them. Through such a domino effect, wild birds might be able to transport the virus for a little while, but Karesh thinks H5N1 could not survive longer than a single migratory season in the wild bird population. Instead, he fears that wild birds may be reinfected during migration the following spring by contact with poultry.
Nial Moores, a bird expert and head of the conservation group Birds Korea, argues that if wild birds from China or Southeast Asia had taken the virus to Siberia early last summer and then to Europe—as many have argued—there would have been evidence of the disease spreading backward in autumn as the birds returned from their summer breeding grounds. There was no sign last fall of such secondary infections occurring along migratory routes. Moores says the outbreaks have followed railway lines, roads, and national borders, an indication that the legal and illegal poultry trades are probably spreading the disease.
Has the H5N1 flu spread to the United States? There is no highly pathogenic strain of H5N1 in the United States and very little chance that migratory birds can spread it over such long distances. Outbreaks of other virulent flu strains in poultry have occurred in the United States, including one in Texas in 2004, but they were quickly eradicated and did not infect people.
How is the spread of H5N1 flu being controlled? Despite extensive campaigns that destroyed millions of infected chickens throughout Southeast Asia, the H5N1 flu seems entrenched. Whenever a country like Vietnam or Thailand appears to have stamped it out, the disease flares up again. One culprit is the movement of smuggled poultry, including fighting cocks, as well as the trade in exotic birds. Moreover, some countries, including China, may have tried to minimize the extent of the problem by denying widespread poultry infection. China began a new poultry vaccination campaign in November 2005.
How is H5N1 flu in human beings and poultry treated? There is no proven treatment for either chickens, which are killed when infected, or people. One antiviral drug, Tamiflu, interferes with the action of neuraminidase, a viral protein that helps the flu virus move from infected to healthy cells in the respiratory tract. No one knows how useful the drug would be in a pandemic or whether it would produce serious side effects in some people.
Is there a vaccine for humans? The National Institute of Allergy and Infectious Diseases announced last year that a possible H5N1 vaccine had been developed. Although the vaccine produces an immune response in volunteers who receive the shots, it must be given in two large doses. The vaccine may protect people from the current H5N1 flu, but no one knows if the vaccine will work if the virus evolves to allow person-to-person transmission.
What is the worst-case scenario?
A pandemic strain could develop from H5N1 flu, either through reassortment with human flu viruses or through a long chain of person-to-person transmission. Recombination may be more likely, because the virus has so far shown no ability to transmit itself effectively among people. A new pandemic strain that spreads the way normal human flu spreads, without the intensely crowded conditions of World War I, may be as virulent as the 1957 flu, which killed about 70,000 people in the United States. Like all flu strains, it will depend on transmission among mobile hosts. One factor in the 1957 strain's virulence was that it carried avian-flu-derived variations of the H (hemagglutinin) and N (neuraminidase) proteins. Because these were new to humans, no one had any immunity. In the 1968 pandemic, however, just the H protein type was new, and the disease killed about 34,000 in the United States—a bit more than twice the previous year's flu-death toll. As for H5N1, it may prove less deadly in humans than in birds because variants of H1N1, descendants of the 1918 flu, have been circulating again since 1977 in Southeast Asia, and exposure to that N1-bearing strain may provide some protection.