The Next Pandemic?

Laurie Garrett

From Foreign Affairs, July/August 2005

Summary:  Since it first emerged in 1997, avian influenza has become deadlier and more resilient. It has infected 109 people and killed 59 of them. If the virus becomes capable of human-to-human transmission and retains its extraordinary potency, humanity could face a pandemic unlike any ever witnessed.

Laurie Garrett is Senior Fellow for Global Health at the Council on Foreign Relations and is the author of The Coming Plague and Betrayal of Trust.

Influenza viruses contain eight genes, composed of RNA and packaged loosely in protective proteins. Like most RNA viruses, influenza reproduces sloppily: its genes readily fall apart, and it can absorb different genetic material and get mixed up in a process called reassortment. When influenza successfully infects a new species -- say, pigs -- it can reassort, and may switch from being an avian virus to a mammalian one. When that occurs, a human epidemic can result. The transmission cycles and the constant evolution are key to influenza's continued survival, for were it to remain identical year after year, most animals would develop immunity, and the flu would die out. This changing form explains why influenza is a seasonal disease. Vaccines made one year are generally useless the following.

Among the eight influenza genes there are two, dubbed H and N, that provide the code for proteins recognized by the human immune system. Scientists have numbered the many types of H and N proteins and use this system to classify a virus. A different viral combination of H and N proteins will trigger a different human immune response. For example, if a strain of H2N3 influenza circulates one year, followed by a different variety of H2N3 the next year, most people will be at least partially immune to the second strain. But if an H2N3 season is followed by an outbreak of H3N5 influenza, few people will have any immunity to the second virus, and the epidemic could be enormous. But a widespread epidemic need not be a severe or particularly deadly one: a virus' virulence depends on genes other than the two that control the H and N proteins.

Scientists first started saving flu virus samples in the early twentieth century. Since that time, an H5N1 influenza has never spread among human beings. According to the World Health Organization (WHO), "No virus of the H5 subtype has probably ever circulated among humans, and certainly not within the lifetime of today's world population. Population vulnerability to an H5N1-like pandemic virus would be universal." As for virulence, within about 48 hours of infection, H5N1 avian influenza kills 100 percent of infected chickens -- although the virulence of a potential human-to-human transmissible H5N1 is impossible to predict.

A team of Chinese scientists has been tracking the H5N1 virus since it first emerged in Hong Kong in 1997, killing 6 people and sickening 18 others. The strain came out of southern China's Guangdong Province, where it apparently was carried by ducks, and hit Hong Kong's chicken population hard. After authorities there killed 1.5 million chickens -- almost every single one in Hong Kong -- the outbreak seemed to stop. But the virus had not disappeared; rather, it had retreated to China's Guangdong, Hunan, and Yunnan provinces, spreading once again to aquatic birds.

From 1998 to 2001 the virus went through multiple reassortments and moved back to domestic birds, spreading almost unnoticed in Chinese chicken flocks. It continued to evolve at high speed: 17 more reassortments occurred, and in January 2003 the "Z" virus emerged, a mutant powerhouse that had become tougher, capable of withstanding a wider range of environmental challenges. The Z virus spread to Vietnam and Thailand, where it evolved further, becoming resistant to one of the two classes of antiflu drugs, known as amantadines, or M2-inhibitors.

In early 2004, it became supervirulent and capable of killing a broad range of species, including rodents and humans. That permutation of the virus was dubbed "Z+." In the first three weeks of January 2004, Z+ killed 11 million chickens in Vietnam and Thailand. By April 2004, 120 million chickens in Asia had died of flu or been exterminated to slow the influenza brushfire. The avian epidemic stopped for a while, but in July another 1 million chickens died from the disease. The Z+ virus was causing massive internal bleeding in the birds. By the beginning of 2005, with chickens dying and customers shying away from what remained, the Asian poultry industry had lost nearly $15 billion.

By April 2005, the H5N1 virus had also moved to pigs. Scientists isolated the disease from swine in a part of Indonesia where pigs are raised underneath elevated wood-slatted platforms that house chickens. Less rigorous investigations had previously indicated that pigs in China and Vietnam may also have been infected by H5N1 influenza. The discovery in Indonesia provided disturbing evidence that the virus was infecting mammals, although it was not yet known how widely the swine disease had spread or how lethal it was for the animals.

HARD TO KILL

Over the course of this brief but rapid evolution, the H5N1 virus developed in ways unprecedented in influenza research. It is not only incredibly deadly but also incredibly difficult to contain. The virus apparently now has the ability to survive in chicken feces and the meat of dead animals, despite the lack of blood flow and living cells; raw chicken meat fed to tigers in Thailand zoos resulted in the deaths of 147 out of a total of 418. The virus has also found ways to vastly increase the range of species it can infect and kill. Most strains of influenza are not lethal in lab mice, but Z+ is lethal in 100 percent of them. It even kills the very types of wild migratory birds that normally host influenza strains harmlessly. Yet domestic ducks, for unknown reasons, carry the virus without a problem, which may explain where Z+ hides between outbreaks among chickens.