The CDC is "extremely concerned" over the "very ominous" threat of bird flu, CDC officials say.

It's not a new worry. Public health officials have been worried for years that a particularly nasty form of bird flu — H5N1 influenza A virus (search) — will learn how to spread easily from human to human. That hasn't happened yet.

If it did, the impact on world health would dwarf the SARS (search) outbreak, says CDC medical epidemiologist Tim Uyeki, MD.

"SARS is not that contagious, although there were super-spreading events," Uyeki tells WebMD. "Most people with SARS did not transmit the disease to social contacts. In contrast, human influenza virus (search) is very contagious. With a pandemic H5N1 influenza virus there would be no pre-existing immunity — most people would be very susceptible — so there would be efficient transmission to social contacts. … If it started where an infected person could get to Bangkok or Ho Chi Minh City and get on a plane, the spread could be very fast."

How likely is it this really will happen? Uyeki is quick to note that nobody really knows. All kinds of relevant information are missing. But the little that is known is pretty scary.

So far, the World Health Organization knows of 55 human infections with the H5N1 bird flu virus — 37 in Vietnam, 17 in Thailand, and one in Cambodia. It killed 42 of these people. It's likely that there have been many more cases than this, many of them probably fatal. Most people probably get milder cases, but that's far from clear. Only people with severe disease show up in hospitals.

Bird Flu Evolving

According to the CDC, the reported symptoms of avian influenza (search) in humans have ranged from the typical flu-like symptoms of fever, cough, sore throat, and muscle aches to eye infections, pneumonia, acute respiratory distress, viral pneumonia, and other severe and life-threatening complications.

"Of the 11 cases since the end of December 2004, 10 were fatal. That is very alarming," Uyeki says. "It is quite likely that there are more severe and fatal cases that have occurred and this is an underestimate of impact among humans. The surveillance has not been done for milder illness or asymptomatic infection. We are simply picking up cases of severe disease, among which a high proportion is fatal.”

The vast majority of these human infections came directly from chickens or ducks. There's been one case of possible human-to-human transmission (the tragic case of a young mother who caught it after holding her dying child overnight). There may have been others, but there's been no ongoing bird flu spread among humans.

"The good news is these viruses have not yet acquired the ability to transmit from person to person in a sustained manner. The key word is sustained," Uyeki says. "There have been a few instances of limited person-to-person transmission. This highlights the potential for a pandemic in the future."

The longer bird flu viruses continue to spread among poultry, the greater the threat. The first time H5N1 raised its head — in Hong Kong, in 1997 — the slaughter of all the city's millions of chickens and a massive cleanup of live poultry markets eliminated the virus. But now the virus seems to have taken root in Southeast Asia — not only among domestic chickens and ducks but in wild birds, too.

"The longer these viruses continue to circulate among poultry, it raises the potential for a [human] H5N1 pandemic, because of the capability of these viruses to evolve," Uyeki says.

And the direction of this evolution isn't reassuring, notes medical researcher Henry L. Niman, PhD, founder and president of Recombinomics, Inc.

"It's clear that the [H5N1] virus is evolving and getting a broad host range," Niman tells WebMD.

"We do know that these H5N1 viruses have been documented to transmit to a number of different animal species. That includes tigers and leopards and domestic cats," Uyeki says. "H5N1 is also confirmed to infect pigs in China; there have been a limited number of cases reported in pigs. The point is that these viruses are extremely concerning. They have transmitted to a number of animal species and have killed humans."

A recent report in the New England Journal of Medicine shows that human infection with H5N1 bird flu is more complicated than previously thought. The virus infected the brain and gut of two Vietnamese children who died with severe seizures and — ominously — severe diarrhea.

"The isolation of virus from a rectal specimen is a major source of concern, since it highlights a potential route of human-to-human transmission, especially in combination with crowded living conditions and diarrhea," Jenno D. de Jong, MD, and colleagues wrote.

The leader of this study, Jeremy Farrar, MD, PhD, is clearly worried.

"The great concern is there is an incredibly virulent avian flu that shows the ability to jump to humans," Farrar told WebMD in a December 2004 interview. "And when it gets to humans, it is clearly a very nasty disease with a high mortality rate."

Vaccine on the Way?

In a recent assessment of the threat posed by a bird flu pandemic, the World Health Organization noted that this is the first time in history people have had any warning that a killer flu might be on the way.

"A pandemic may be imminent," writes WHO director-general Lee Jong-wook, MD. "This time, the world has an opportunity to defend itself against a virus with pandemic potential before it strikes."

CDC and WHO researchers already have identified viruses from which they can make a bird flu vaccine. Candidate vaccines are scheduled for testing at the National Institutes of Health. And Uyeki says that Vietnam is testing its own vaccine in animal studies.

Even so, a vaccine will be years away. And — because the virus continues to evolve — there's no guarantee that it will work.

The bird flu is, unfortunately, resistant to one kind of flu drug. It's sensitive to Tamiflu — but supplies are short.

"Even in a scenario where we have a couple of months to plan for a pandemic, the answer is no, there are not enough antiviral drugs available for treatment or [prevention of infection] during a pandemic situation — even in the U.S., let alone the rest of the world," Uyeki says. "Other governments besides the U.S. are trying to stockpile it. Currently there is an insufficient supply. … What are needed are not only more availability and more production, but we need other kinds of antivirals as well."

By Daniel J. DeNoon, reviewed by Brunilda Nazario, MD

SOURCES: World Health Organization, “Avian Influenza: Assessing the Pandemic Threat," January 2005. de Jong, MD. The New England Journal of Medicine, Feb. 17, 2005; vol 352: pp 686-691. News release, American Association for the Advancement of Science. WHO web site. CDC web site. Tim Uyeki, MD, medical epidemiologist, Influenza Branch, National Center for Infectious Diseases, CDC. Jeremy Farrar, MD, PhD, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, Henry L. Niman, PhD, founder and president, Recombinomics Inc., Pittsburgh.