Scientists in Desperate Race With Bird Flu

Will Killer Flu Bug Emerge Before We Are Ready?

From the WebMD Archives

Sept. 28, 2005 -- Bird flu has scientists on the edge of their seats about when and if it will become a human pandemic, a sobering report shows. That's the bad news.

The good news: Bird flu still doesn't spread easily among humans. Infected poultry was the source of virtually all of the 115 confirmed human infections with what scientists call H5N1 avian influenza. So far, only very few people seem to have caught it from other people, and then only after extremely close and sustained contact.

The bad news: More than half of the people who got bird flu have died. The true death rate for human cases of bird flu is not known. Mild cases don't show up in hospitals and don't get counted. But a new report on human bird flu infection shows that this is a very bad bug indeed.

The report comes from a May 2005 meeting of doctors and researchers held in Hanoi, Vietnam, by the World Health Organization. Among them is Frederick G. Hayden, MD, professor of clinical virology and internal medicine at the University of Virginia, Charlottesville.

"The news is concerning," Hayden tells WebMD. "Most cases are in apparently healthy adults and children. About half of them die from what appears to be a viral pneumonia, sometimes with secondary bacterial infections. Some suggest this virus behaves differently from human flu."

Hayden and colleagues' report appears in the Sept. 29 issue of The New England Journal of Medicine.

Bird Flu: Early Symptoms, Frequent Death

Even though people obviously do get bird flu from poultry, it's not something that happens often. Millions of domestic chickens and ducks have been infected. Yet relatively few people show evidence of infection, notes flu expert John Treanor, MD, professor of medicine and director of the vaccine and treatment evaluation unit at the University of Rochester in New York.

"When you think of the totality of human experience with infected poultry, fewer than 150 cases is only a small number," Treanor tells WebMD. "The opportunities for whatever needs to happen for this to spread among humans have been, thankfully, quite limited."

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The earliest symptom of bird flu is a lot like that of human flu: a sudden high fever. After that, the symptoms tend to be different. Bird flu patients only sometimes have a runny nose. They tend to have lower respiratory symptoms, especially cough and shortness of breath. Other early symptoms may include diarrhea, vomiting, abdominal pain, lung pain, and bleeding from the nose and gums.

There may also be symptoms highly unusual for flu. Two patients had brain infections and diarrhea but not respiratory symptoms.

Typically, about five days after illness onset, patients have shortness of breath. Severe breathing problems are common; there may be bloody sputum. Patients often progress to acute respiratory distress in about six days, which requires oxygen therapy and may require assisted breathing with a machine. Multiple organ failure is common. Death usually comes from respiratory failure.

The disease has been particularly deadly for children. In Thailand, 89% of patients under the age of 15 years died an average of nine or 10 days after illness onset.

Early Treatment May Help

Two flu drugs are active against bird flu: Tamiflu and Relenza. Tamiflu is taken orally, while Relenza must be inhaled. Because bird flu can infect organs other than the lungs, Tamiflu is considered the treatment of choice.

However, treatment must begin very soon after symptoms appear. Hayden and colleagues say that for severe cases of H5N1 bird flu, it's reasonable to use high doses of Tamiflu -- double the usually recommended dose.

A Bird Flu Pandemic

What experts worry about is that bird flu could learn to spread more easily among humans. This could happen in two ways. The bird virus could simply adapt to humans over time. Or a person could get infected with bird flu and human flu at the same time. Two viruses infecting the same person could swap gene segments. This "reassortant" virus might end up with the gene that lets it spread among humans.

It seems very easy for this to happen. Is it possible that for some reason bird flu just can't evolve into a human flu?

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"I am not reassured that because it hasn't happened yet it will not occur," Hayden says. "I think we are watching an evolving event. There is real concern that either through transport of poultry or migratory birds, the virus will spread further. And that will increase the possibility it will reassort with a human virus or adapt to humans. Then one would be into a pandemic event."

Pandemic flu -- a flu bug that sweeps the globe -- happens every 10 to 40 years, says Stephen Morse, PhD, founding director of the Center for Public Health Preparedness at Columbia University's Mailman School of Public Health.

"All of us virologists and infectious disease epidemiologists who worry about flu for a living, we all feel a pandemic is virtually inevitable -- as inevitable as any unpredictable event can be," Morse tells WebMD. "We don't know if it will be a 1918-like epidemic, which is what we all fear -- the worst natural disaster we know of in history -- or whether it will be more of a standard pandemic like 1957 or 1968, where we have 4 million deaths rather than 100 million."

But if the next pandemic is bird flu, there really is no precedent. The terrible 1918 flu had a mortality [death] rate of only 2%, Morse says.

"The extra charge on that bomb is that H5N1 bird flu has a high mortality rate," he says. "That is one of the things that is very worrisome about this virus: A pandemic would mean a lot of people who are very sick. An H5 pandemic would be something very serious to contemplate."

Race Against Time

Nobody knows whether bird flu really will cause a pandemic. But researchers, governments, and drug companies are taking it very, very seriously.

There's already a prototype vaccine. This vaccine may not match the pandemic virus that eventually breaks out. But making it, testing it, and licensing it will greatly speed a better vaccine should the need arise, Treanor says.

The current vaccine requires two high-dose shots, many weeks apart. Treanor and others already are working on higher-potency vaccines. And the U.S. National Institute of Allergy and Infectious Diseases today announced that it is working with a drug company to use new technology to rapidly produce live vaccines using weakened, genetically engineered flu viruses. Such vaccines could protect against any possible flu virus.

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Meanwhile, governments are racing to stockpile Tamiflu and Relenza. Right now, there is not nearly enough. But drug manufacturers are stepping up production. If the bird flu waits a few more years, the world will be in a lot better position to fight back.

"I do believe that this is now getting attention at the highest levels -- and we need that," Morse says. "Our capacity to make vaccines now is woefully inadequate. The nimbleness with which we can make new vaccine is questionable. We need the capacity to make vaccines rapidly. We need a stockpile of antiviral agents. If pandemic flu happened in the next year, we would have to do a lot of scrambling. If it happened in 10 years, the question is how much we are able to sustain the concern we have now."

SOURCES: Hayden, F.G. The New England Journal of Medicine, Sept. 19, 2005; vol 353: pp 1374-1385. Frederick G. Hayden, MD, professor of clinical virology and internal medicine, University of Virginia, Charlottesville. John Treanor, MD, professor of medicine; and director, vaccine and treatment evaluation unit, University of Rochester, New York. Stephen Morse, PhD, founding director, Center for Public Health Preparedness, Mailman School of Public Health, Columbia University, New York.

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