On High Alert

Whe

n World Health Organization (WHO) parasitologist Carlo Urbani was treating the first cases of an unknown respiratory disease in the Hanoi-French Hospital in late February and March of 2003, he believed he might be facing the front end of an avian-flu epidemic. Dr. Olivier Cattin, the medical coordinator at the hospital, had alerted Urbani and told him the Chinese-American patient currently in the emergency ward suffering from high fever, severe muscular pains and labored breathing had possibly come down with the disease. Virologists in Hong Kong soon determined that the agent was a novel coronavirus, not a mutant flu. But Urbani, who would die of SARS on March 29, went to his grave suspecting the world was on the verge of another influenza pandemic.

Nearly a year later, his worst fear may be coming true. If a virus, as Nobel laureate Peter Medawar described it, "is a piece of bad news wrapped in a protein," the past few weeks have had all the bad news the world can handle as avian influenza has broken out in Korea, Japan, Taiwan and Vietnam. Already, the disease appears to have jumped the species barrier, killing at least four people, and the virus is suspected of causing another 10 deaths. Asia has stared down avian-flu outbreaks before, notably in Hong Kong in 1997 when the city's Agriculture, Fisheries and Conservation Department officials culled 1.4 million chickens, as well as ducks, geese and other birds, after 18 human cases resulted in six fatalities. This time around, however, the spread of the outbreak to several countries has public-health officials on high alert, wary of the potential for a pandemic.

		THIS WEEK'S COVER STORY Mission to Mars January 26, 2004 Issue Past Covers Mind & Body Jan. 19, 2004 ----------------- Howard Dean Jan. 12, 2004 ----------------- Person of the Year Dec. 29, 2003 ----------------- Saddam Captured Dec. 22, 2003 ----------------- The Insurgents Dec. 15, 2003 ----------------- Kids and Drugs Dec. 8, 2003 ----------------- America and Bush Dec. 1, 2003 ----------------- Russell Crowe Nov. 24, 2003 ----------------- Jessica Lynch Nov. 17, 2003   ASIA  Avian Flu: Asia on High Alert  India: The BJP's New Look  Viewpoint: Moderate Victory?  Timeline: History of the BJP  Pakistan: The Monster Within ARTS  Books: India's Glorious Parasites BUSINESS  China IPOs: Get'em While They're Hot NOTEBOOK  Philippines: The Fire Next Time  Cambodia: Court Intrigue  Milestones  Verbatim  Letters GLOBAL ADVISOR  Tokyo: Hipster Hotel  Sicily: Market Research  Bangkok: Undiscovered Temples CNN.com: Top Headlines

In Vietnam, where already more than 1 million birds have died from the virus, and at least another 800,000 have been slaughtered as a precaution, Ministry of Agriculture and Rural Development (MARD) officials were reassuring the public as late as Jan. 7 that "there has been no sign the disease will affect human health"—even though 12 patients had already turned up at the National Institute of Pediatrics with an "unusual" virus, according to hospital director Dr. Nguyen Thanh Liem. Even more worrying, it now appears that there were mass chicken die-offs in Vinh Phuc province in northern Vietnam as early as last July, six months before the government officially acknowledged the emergence of avian flu. Giapfa Comfeed Vietnam Ltd., a poultry company in Vinh Phuc's Tam Duong district, told TIME that 20,000 of its chickens died with symptoms correlating with avian flu. The company says it sent blood samples to the MARD's Veterinary Department, whose tests revealed that the chickens had been killed by an unknown agent. Van Dang Ky, a veterinarian from the department's epidemiology unit, admits, "The first signs of an epidemic were found in Tam Duong district in July 2003. At the time, Vietnam was preparing actively for the 22nd Southeast Asian Games and we thought we could control the disease, so we did not announce it for political and economic reasons." Anton Rychener, a United Nations Food and Agriculture Organization representative in Vietnam, confirmed that ministry officials told him there had been previous outbreaks. (Ministry of Foreign Affairs officials have denied MARD's assertions.)

The appearance of avian flu in July, and the apparent Vietnamese cover-up, would mean that this virus has had months to roll through the chicken population, possibly mutating and becoming more pathogenic as it goes. The culprit this time is the same as in Hong Kong in 1997: the H5N1 influenza virus. Historically, this virus has wreaked havoc mainly on poultry. Among chickens, the disease manifests itself as a hemorrhagic fever, turning a pen of healthy birds into a bloody mass of goop and feathers within 24 hours. Since the 1960s, each reported appearance of the disease has drawn a rapid response from international health officials concerned more about the potential for human infection than the loss of a few feathered friends.

Their fear is that of all the diseases in the world today—from SARS to AIDS, anthrax to Ebola—the single microbe with the greatest potential to become, as epidemiologists say, a "slate wiper," is influenza. Previous pandemics, such as the global outbreak of 1918 that killed an estimated 60 million people, have precipitated some of the greatest die-offs in history. We've all had the flu, of course, but those few days off from work with the sniffles are a completely different illness from that caused by a novel influenza against which we have no immunity. Without antiviral medications or a vaccine, a new influenza strain could kill you in days.

But how does a chicken flu become a human flu? The answer is in the RNA of the virus itself. Influenza viruses are known as shape-shifters, possessing the rare ability to swap proteins with other influenza viruses to create, essentially, new influenza viruses. As long as an H5N1 virus stays in its host species—ducks—then there is little risk of a human pandemic arising. But once that virus has infected chickens, then the chances of jumping to human beings, usually through contact with chicken feces, rise considerably. In humans, the virus is more likely to swap proteins with a human influenza virus and acquire greater infectiousness and enhanced pathogenicity. The result, researchers fear, could be a highly contagious flu bug with a mortality rate of one in three. The likelihood of such a shape shift is hard to quantify, but it is believed that previous pandemics, in 1918 and in 1968, were the result of this sort of gene swapping among different viral strains.

In an effort to curtail the current avian-flu outbreak before any killer mutations can occur, public-health officials, epidemiologists and virologists are now scrambling to figure out the origin and genomic sequence of the flu strains in Korea, Japan, Taiwan and Vietnam. A 14-strong WHO team, including experts from the U.S. Centers for Disease Control and Prevention, is expected to arrive in Hanoi by midweek. If they can determine where this virus came from, then perhaps better surveillance and monitoring of the poultry trade can curtail future outbreaks.

One clue might be simple geography. Every afflicted country or territory is contiguous, either by land or sea, with China. The mainland was the source of Hong Kong's previous outbreaks, and Agriculture, Fisheries and Conservation Department officials in the city sometimes turn back containers of chickens and ducks that have tested positive for antibodies to avian flu. China refuses to officially acknowledge that it has an H5N1 problem. But as recently as last March, according to a document obtained by TIME, China's Ministry of Health was requesting from the WHO H5N1 reagents, which are used to test for presence of antibodies to the virus. That would indicate, at the very least, that China suspected this type of influenza might be afflicting its poultry but did not yet have the means to test. Both Japan and Taiwan have intercepted shipments of tainted duck meat from the mainland in the past year. Kim Sun Jwong, an avian-diseases expert at Seoul National University, believes the Middle Kingdom is the most likely provenance of Korea's H5N1 outbreak. And live chickens are also frequently traded along China's border with Vietnam. If China is seeding these outbreaks, then greater cooperation from mainland officials is essential to plugging the microbial jug.

But there could be an even more ominous disease vector at work—or in flight. For years, the greatest fear of many influenza experts has been the possibility that the H5N1 strain would infect migratory birds. Since huge amounts of virus are shed in bird feces, such an epidemic among migratory birds would mean death raining down from the sky in the form of H5N1 virus. In November and December of 2002, there were numerous migratory-waterfowl deaths due to H5N1 in Hong Kong's Penfold and Kowloon parks. Mysteriously, when further screenings of migratory birds were conducted immediately after, no H5N1 was detected. "Did birds from Hong Kong, which nest in Siberia and North Korea, somehow spread the virus elsewhere?" asks Rob Webster, a pioneering expert in animal influenzas. "That's a frightening possibility."

In Asia, there is no program in place to systematically sample migratory birds to determine which viruses they carry. In Europe, virologist Albert Osterhaus of Erasmus University in the Netherlands has launched a survey in which fecal samples are submitted from around the continent for testing. "We've found the proteins that indicate the presence of various avian influenzas," says Osterhaus. The prevalence of viruses in migratory birds may have been responsible for an avian-flu outbreak in the Netherlands last year that infected 80 people, killing one. The virus responsible, an H7, which was less deadly than the H5 strain, did achieve human-to-human transmission.

If a similar infection pattern is occurring in Asia among migratory birds, then this killer flu virus will keep recurring in chickens, and possibly humans. That will be very bad news—wrapped around a virus.