SURVIVOR: Avian flu victim Nguyen Sy Tuan holds an X-Ray of his lungs. At one stage, doctors prematurely declared him dead
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h5n1 is unusually lethal. Roughly half of those who have contracted the disease have died, despite the use of artificial respirators and antiviral drugs. That compares with the 10% mortality rate among those who contracted sars. Ha has watched the virus ravage the lungs of healthy young patients in a matter of days. He says the key to treatment is applying just the right amount of breathing assistance — too much, and an h5n1 patient's weakened lungs can burst. But survival ultimately comes down to "the patient's immune system and the will to fight."
It's a fight that can take everything from survivors but life itself. Before he caught h5n1 this past February, 21-year-old Nguyen Sy Tuan was already slim, carrying just 50 kg on his 1.65-m frame. On his release from Bach Mai Hospital in May, he weighed merely 32 kg. Today, just below his prominent ribs, his body bears two angry red scars where doctors inserted tubes that pumped fluid out of his lungs; another scar on his throat marks the entry wound for a ventilation tube. Because he passed in and out of consciousness during his 82-day hospital stay, Tuan doesn't remember the tubes piercing his skin, or the local press mistakenly reporting his death. What he held onto was his will to endure. "I remembered that some people had already survived this disease, so I knew I could live," says Tuan, whose younger sister Nguyen Thi Ngoan also beat bird flu. "I always believed in my resistance."
Cases like Tuan's remain rare, because for all its lethality, h5n1 is still an avian virus adapted to killing birds, not people. A flu virus infects a cell by linking its hemagglutinin gene — the H in h5n1 — with chemical receptors on the surface of the cell, like a key fitting a lock. Right now h5n1 remains a poor fit for most human cells, and even when it does cause an infection, the virus is concentrated in the lower respiratory system, making it harder to spread to someone else. (Common flu invades the upper respiratory system, and can be spread easily by coughing or sneezing.) But influenza is a master lockpicker, albeit by accident; flu viruses are so mistake-prone in their genetic replication process that they mutate constantly. Flu viruses can also mutate by swapping genes with other strains through reassortment, a process that's believed to have generated the last two pandemic flus. Although the vast majority of mutants prove unfit for survival, there's always a small chance that a new strain could arise that can be transmitted easily from human to human — either through a one-shot reassortment, or through the accumulation of minor mutations. "It's like a frequent-flyer program," says Michael T. Osterholm, the head of the Center for Infectious Disease Research and Policy at the University of Minnesota. "Take enough trips and you can go anywhere." And every instance of a person catching h5n1 increases the odds that a deadlier strain will emerge — one with a genetic makeup that is better suited to human hosts. "You're playing Russian roulette every time you have a human infection," says Earl Brown, a virologist at the University of Ottawa.
New research suggests the chances that h5n1 will trigger a pandemic may be greater than first thought. A team of scientists led by Dr. Jeffrey Taubenberger, chief of the molecular pathology department at the Armed Forces Institute of Pathology in Washington, has managed to reconstruct the full genetic sequence, or genome, of the virus that caused the deadly 1918 pandemic. Taubenberger and his colleagues extracted bits of viral genes from the preserved tissue of three people who had died in the pandemic — two U.S. soldiers, and an Eskimo woman in Alaska whose body had remained frozen below the ground — and over 10 years put the pieces together like a jigsaw puzzle. The results, published last week in Nature, show that the 1918 virus jumped directly from birds to people, without reassorting with a human flu virus, as the pandemic strains of 1957 and 1968 did. Should h5n1 — which also managed to jump directly from birds to humans — become easily transmissible, it could be more likely to trigger a catastrophe like 1918 than the last two relatively mild pandemics.
Scientists at the cdc, meanwhile, rebuilt the 1918 virus with Taubenberger's genetic blueprints, and used it to experimentally infect mice and human lung cells in a biosecure laboratory. Their results, published last week in the journal Science, confirm just how virulent the 1918 virus was: in four days, it produced 39,000 times more viral particles in the animals' lungs than a modern flu strain. The research also indicates that the 1918 virus only needed relatively minor mutations — genetic changes in just 25 to 30 of the virus' 4,400 amino acids, according to Taubenberger — to become a killer, and bird-flu viruses like h5n1 already share some of those changes. H.K.U.'s Guan points out that because we have no genetic information on the ancestor avian flu virus that eventually mutated to become the 1918 strain, we still don't know how close h5n1 is to becoming a pandemic-triggering strain. Still, he says, "I think this is very bad news."
If h5n1 turns nastier, Ha knows he will not be able to stem the toll of fatalities. With its eight respirators, only six of which currently work, Bach Mai is as well-equipped as any hospital in the country to deal with a pandemic — which means it's barely equipped at all. Per-capita health expenditure in Vietnam is just $8, enough to buy a single rapid test for influenza. A pandemic, says Ha, "would be a disaster."
the lab tests confirmed the vietnamese boy had died of h5n1, but his parents were sure the 13-year-old had never been in contact with sick poultry. For epidemiologist Dr. Tim Uyeki at the cdc, part of a team responding to a bird-flu outbreak in Vietnam in January 2004, that was a red light, a possible sign of a human-to-human transmission. Uyeki traced the victim's contacts, investigating his family and friends, before neighbors finally provided the answer: the boy was an avid cockfighter, and held the roosters close when preparing them for a bout. "Influenza virus is excreted in the feces. Chickens and ducks have fecal matter all over them," Uyeki says in his office at cdc headquarters in Atlanta. "This boy was holding roosters with the rear end pointing toward his face, and that's direct contact." One more case closed, another lucky outcome on h5n1's genetic roulette wheel.