Avian Flu - Infected Birds to Appear in a Neighborhood Near You?
by Jeffrey Norris
When UCSF hosted an avian flu symposium in December, outbreaks of the avian flu virus H5N1 were limited to China and Southeast Asia. The virus had killed dozens of people. Officials from those nations and the World Health Organization were grappling with how to cope and obtain funding.
The good news today is that H5N1 remains a bird flu. There is no place where the virus has evolved into a form that spreads easily among humans. With very few exceptions, people diagnosed with H5N1 infection are known to have been in contact with infected birds.
There still is no consensus among experts on the likelihood that H5N1 will evolve into a deadly, easily transmissible human influenza. Flu viruses mutate often as they replicate. In addition, they can trade genes with other flu viruses - those that more commonly infect pigs or humans, for instance.
As long as H5N1 is around, incubating in farm animals and the occasional human, it will continue to evolve - increasing the chances that one day an H5N1 strain will dial up a combination of genetic adaptations that triggers a human pandemic.
H5N1 Travels the Globe, Bound for California
The bad news is that the virus now has spread beyond Asia to dozens of countries in Europe, the Middle East and Africa. Hopes of containing it have diminished. H5N1 is becoming widespread among wild bird populations. The death toll has increased to more than 100 humans and millions of domestic poultry in affected countries. H5N1 can easily spread between wild birds and domestic fowl through contaminated water, and the virus is traveling with its bird hosts along migratory routes. Since December, however, it appears that the virus has spread to Africa through the smuggling of contaminated poultry or poultry parts. Smuggling is an ongoing, worldwide phenomenon. Importation of poultry products from countries with avian flu outbreaks is prohibited. According to a statement by California Department of Food and Agriculture Secretary A.G. Kawamura, "The best chance of preventing a human pandemic is through eradication of the virus in poultry." The virus is more likely to strike California as a bird epidemic, Kawamura says. "The likely means of exposure will be either through smuggling of birds, or wild birds." It is also possible that a human will be infected with H5N1 abroad, and then travel to the United States while still infected. The US Centers for Disease Control and Prevention has established quarantine centers at major airports to screen sick passengers. One way or another, the spread of H5N1 to the United States is now seen as nearly certain. Migratory birds trekking south from Alaska along their usual flyways might bring the virus into the lower 48 states sometime this year, according to US health officials. Despite the debate over H5N1's chances of morphing into a human flu, there is a consensus that populations around the globe should be prepared, just in case. "I don't think anyone believes that we are adequately prepared," says Lawrence Drew, MD, PhD, director of clinical virology and infectious diseases at UCSF Mount Zion. Vaccine is Key
Vaccine development is especially important because no population has residual immunity from prior exposure to H5N1. That's because nothing like the virus has circulated in humans. "It will be a real challenge to develop the technology to enable rapid production of a useful vaccine that will match the pandemic strain," Drew says. Results of human studies using a Sanofi-Pasteur vaccine indicate that large amounts of this first vaccine are needed to generate an immune response of a magnitude usually associated with preventing infection. H5N1 now has evolved into distinctly different viral populations, a bit different from the one used to develop the Sanofi-Pasteur vaccine. Bay Area-based Chiron, recently bought out by Novartis, plans to test an H5N1 vaccine formulated with a new, proprietary adjuvant intended to boost vaccine strength. Efforts also are underway to speed vaccine production by growing virus in cell cultures instead of chicken embryos. Officials are hoping that any vaccine that proves effective against recent H5N1 avian flu strains can be stockpiled, and that it will remain somewhat effective against any strain that emerges later to trigger a human flu pandemic. In addition, there will be an urgent race to develop, manufacture and distribute a better-targeted vaccine once a human pandemic strain emerges and is identified. But any vaccine developed is expected to remain in short supply for years. Furthermore, in the event of an outbreak, public health resources will be scarce. Hospitals are likely to be overwhelmed and only able to care for those whose lives are in immediate danger. Most people will have to take care of themselves and their loved ones who are sick in bed with fever. "After vaccine, the second most important strategy for preventing transmission is practicing respiratory etiquette," says Amy Nichols, director of infection control for UCSF Medical Center. "We saw that recently with the SARS experience." Unglamorous, rather mundane, low-tech - and effective - ways that individuals can take upon themselves to reduce the risk of spreading pandemic flu - or any airborne, saliva-spread disease - include staying home when sick, avoiding unnecessary contact with anyone who is sick, washing hands frequently, and sneezing or coughing into tissues, not into the open air. Human Deaths Have Mainly Been Due to Respiratory Distress
H5N1 kills a large percentage of humans it infects, usually due to acute respiratory distress syndrome (ARDS) caused by the virus itself. When ARDS strikes, fluid accumulates in the lungs and oxygen can't get to the body's tissues. ARDS also was responsible for a large percentage of the deaths from the 1918-1919 flu pandemic, although some experts have suggested that secondary bacterial infections may have played a greater role than the virus itself in triggering ARDS. Today, hospitals have mechanical ventilators, oxygen, antibiotics and other treatments for ARDS. But during a severe flu pandemic, UCSF Medical Center and hospitals throughout the country will likely be scrambling for additional equipment and supplies. Michael Matthay, MD, professor of medicine and anesthesia and perioperative care at UCSF - along with research colleagues at UCSF and other academic medical centers - has developed treatment protocols to improve survival among those with ARDS. These include better oxygen delivery with mechanical ventilators and lower-pressure ventilation. People who develop ARDS usually do so as a complication of a serious illness or injury. Even with improved treatment, nearly 40 percent of ARDS patients die, according to Matthay. While ventilators will be in short supply during a pandemic, it may be possible to meet the needs of many more patients with oxygen tanks and masks. "There's a way to give face-mask ventilation with high-flow oxygen and some positive pressure that will support many people - short of having to intubate and ventilate them," Matthay says. Beta agonists - inhalers used to treat asthma - also might help save lives, he adds. "They can be used to reduce the amount of fluid forming in the lung and enhance fluid removal, although definitive studies to test their efficacy are still in progress." Links: World Health Organization Epidemic and Pandemic Alert and Response US Department of Health and Human Services Pandemic Flu Plan California Pandemic Influenza Preparedness and Response Plan -- Draft San Francisco Department of Public Health Avian Flu Page
The bad news is that the virus now has spread beyond Asia to dozens of countries in Europe, the Middle East and Africa. Hopes of containing it have diminished. H5N1 is becoming widespread among wild bird populations. The death toll has increased to more than 100 humans and millions of domestic poultry in affected countries. H5N1 can easily spread between wild birds and domestic fowl through contaminated water, and the virus is traveling with its bird hosts along migratory routes. Since December, however, it appears that the virus has spread to Africa through the smuggling of contaminated poultry or poultry parts. Smuggling is an ongoing, worldwide phenomenon. Importation of poultry products from countries with avian flu outbreaks is prohibited. According to a statement by California Department of Food and Agriculture Secretary A.G. Kawamura, "The best chance of preventing a human pandemic is through eradication of the virus in poultry." The virus is more likely to strike California as a bird epidemic, Kawamura says. "The likely means of exposure will be either through smuggling of birds, or wild birds." It is also possible that a human will be infected with H5N1 abroad, and then travel to the United States while still infected. The US Centers for Disease Control and Prevention has established quarantine centers at major airports to screen sick passengers. One way or another, the spread of H5N1 to the United States is now seen as nearly certain. Migratory birds trekking south from Alaska along their usual flyways might bring the virus into the lower 48 states sometime this year, according to US health officials. Despite the debate over H5N1's chances of morphing into a human flu, there is a consensus that populations around the globe should be prepared, just in case. "I don't think anyone believes that we are adequately prepared," says Lawrence Drew, MD, PhD, director of clinical virology and infectious diseases at UCSF Mount Zion. Vaccine is Key
Vaccine development is especially important because no population has residual immunity from prior exposure to H5N1. That's because nothing like the virus has circulated in humans. "It will be a real challenge to develop the technology to enable rapid production of a useful vaccine that will match the pandemic strain," Drew says. Results of human studies using a Sanofi-Pasteur vaccine indicate that large amounts of this first vaccine are needed to generate an immune response of a magnitude usually associated with preventing infection. H5N1 now has evolved into distinctly different viral populations, a bit different from the one used to develop the Sanofi-Pasteur vaccine. Bay Area-based Chiron, recently bought out by Novartis, plans to test an H5N1 vaccine formulated with a new, proprietary adjuvant intended to boost vaccine strength. Efforts also are underway to speed vaccine production by growing virus in cell cultures instead of chicken embryos. Officials are hoping that any vaccine that proves effective against recent H5N1 avian flu strains can be stockpiled, and that it will remain somewhat effective against any strain that emerges later to trigger a human flu pandemic. In addition, there will be an urgent race to develop, manufacture and distribute a better-targeted vaccine once a human pandemic strain emerges and is identified. But any vaccine developed is expected to remain in short supply for years. Furthermore, in the event of an outbreak, public health resources will be scarce. Hospitals are likely to be overwhelmed and only able to care for those whose lives are in immediate danger. Most people will have to take care of themselves and their loved ones who are sick in bed with fever. "After vaccine, the second most important strategy for preventing transmission is practicing respiratory etiquette," says Amy Nichols, director of infection control for UCSF Medical Center. "We saw that recently with the SARS experience." Unglamorous, rather mundane, low-tech - and effective - ways that individuals can take upon themselves to reduce the risk of spreading pandemic flu - or any airborne, saliva-spread disease - include staying home when sick, avoiding unnecessary contact with anyone who is sick, washing hands frequently, and sneezing or coughing into tissues, not into the open air. Human Deaths Have Mainly Been Due to Respiratory Distress
H5N1 kills a large percentage of humans it infects, usually due to acute respiratory distress syndrome (ARDS) caused by the virus itself. When ARDS strikes, fluid accumulates in the lungs and oxygen can't get to the body's tissues. ARDS also was responsible for a large percentage of the deaths from the 1918-1919 flu pandemic, although some experts have suggested that secondary bacterial infections may have played a greater role than the virus itself in triggering ARDS. Today, hospitals have mechanical ventilators, oxygen, antibiotics and other treatments for ARDS. But during a severe flu pandemic, UCSF Medical Center and hospitals throughout the country will likely be scrambling for additional equipment and supplies. Michael Matthay, MD, professor of medicine and anesthesia and perioperative care at UCSF - along with research colleagues at UCSF and other academic medical centers - has developed treatment protocols to improve survival among those with ARDS. These include better oxygen delivery with mechanical ventilators and lower-pressure ventilation. People who develop ARDS usually do so as a complication of a serious illness or injury. Even with improved treatment, nearly 40 percent of ARDS patients die, according to Matthay. While ventilators will be in short supply during a pandemic, it may be possible to meet the needs of many more patients with oxygen tanks and masks. "There's a way to give face-mask ventilation with high-flow oxygen and some positive pressure that will support many people - short of having to intubate and ventilate them," Matthay says. Beta agonists - inhalers used to treat asthma - also might help save lives, he adds. "They can be used to reduce the amount of fluid forming in the lung and enhance fluid removal, although definitive studies to test their efficacy are still in progress." Links: World Health Organization Epidemic and Pandemic Alert and Response US Department of Health and Human Services Pandemic Flu Plan California Pandemic Influenza Preparedness and Response Plan -- Draft San Francisco Department of Public Health Avian Flu Page