Bay Area technicians on alert for avian flu
State's Richmond disease lab steps up viral surveillance
Sabin Russell, Chronicle Medical Writer
http://www.sfgate.com/cgi-bin/article.cgi?file=/c/a/2005/03/07/MNGOTBLIIP1.DTL
Monday, March 7, 2005
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As world flu experts anxiously monitor the spread of a lethal strain of influenza among birds and people in Southeast Asia, Dr. Carol Glaser and her crew of lab technicians in Richmond are carefully watching for the first sign of the disease in California.
The state-run Viral and Rickettsial Diseases Laboratory is operating under a program of "enhanced surveillance" for the H5N1 strain of influenza, which last year killed or required the culling of 120 million birds. Since January 2004, the strain has infected 55 people in Vietnam, Thailand and Cambodia -- and killed three out of four of them.
Using rules set up to watch for the SARS virus -- which killed nearly 800 people worldwide in 2003 before it was contained -- Glaser's lab tests sputum samples sent by California doctors from patients who came down with flulike symptoms shortly after traveling through regions in Asia hit by avian influenza.
Since the state stepped up its watch for bird flu one year ago, the lab has screened three suspected cases, including one in which a patient died. All three cases were negative for the H5N1 strain.
But testing of suspected avian influenza cases has become the highest priority at the state lab, Glaser said.
"We hold our breath, every time it happens," she said. "We call these cases 'drills' -- but only after the fact."
H5N1 is a strain of bird flu that does not appear to infect human beings easily, but the fear is that this could change. Should it retain its lethal traits while becoming easy to spread among people, the results could be catastrophic.
Dr. Julie Gerberding, director of the Centers for Disease Control and Prevention, told a gathering of American scientists last month that avian influenza was "the most important threat we are facing right now."
At the World Health Organization in Geneva, the shadow of the 1918 Spanish flu pandemic hangs over the effort to stop avian influenza. The U.N. agency estimated that 40 million people died in that outbreak, which scientists now believe was caused by an avian flu virus that mutated into one that could readily infect humans.
Particularly virulent strains of influenza struck the global population three times in the past century, in 1918, 1957 and 1968. Each pandemic marked the arrival of a new family of flu viruses so genetically distinct from predecessors that the human immune system had a difficult time recognizing it and mounting an antibody defense.
Epidemiologists have been warning for years that the world is due for another pandemic -- just as geologists know that various regions of the Earth are due for major earthquakes. With the increasingly ominous news out of Southeast Asia, health officials around the globe are reviewing plans drawn up to deal with a new pandemic.
Key elements of these plans call for stepped-up surveillance, the development of a vaccine and the stockpiling of antiviral drugs. Of these major components, only surveillance is well in place.
The global flu-watching network first spotted the avian influenza threat in Hong Kong in 1997, when 18 people there were sickened by an outbreak of H5N1 among chickens and six patients died. Hong Kong health authorities ordered the slaughter of all 1.3 million chickens, ducks and other avian species in the district, and the threat receded.
That global surveillance effort has since documented the disturbing resurgence of the virus in nine Asian nations -- and its transmission to humans in Vietnam, Thailand and Cambodia. This time, chicken-culling efforts have fallen short. The WHO concluded in a report on avian influenza that "H5N1 is now endemic in parts of Asia, having established a permanent ecological niche in poultry."
California's role as a gateway from Asia to the United States has heightened the importance of surveillance for avian flu. The state is conducting what Dr. Glaser called passive surveillance -- relying on doctors to reporting suspicious cases. Should evidence emerge from Asia that bird flu is passing quickly among humans, Glaser said the state would switch to active surveillance, dispatching trained team of epidemiologists to hospitals to review medical records in search of potential infections.
Health authorities in the United States are gearing up for the first human tests of an H5N1 vaccine. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said the first of 8,000 doses developed by French vaccine-maker Sanofi-Pasteur probably will be given to American volunteers later this month.
"We'll start off with 450 young, healthy adults," Fauci said. Then it will be tested on a group of volunteers over the age of 65, and finally, among a group of children. Locations for the three experiment sites have yet to be chosen.
No human being has ever received a flu vaccine made with the H5 protein found on the surface of the bird flu virus. There is some evidence that the extreme lethality of the 1918 pandemic strain and the H5N1 strain found in Hong Kong are due to the unique structure of that protein. It is unlikely that the vaccine, made of debris from killed viruses, would be dangerous, Fauci said, adding the caveat, "We have to be careful."
Chiron Corp., the Emeryville company whose Liverpool plant failed British quality control inspections last year, condemning half the yearly U.S. flu shot supply, has contracted to produce 10,000 doses of H5N1 vaccine. The experimental vaccine is made at a different facility in Liverpool, but Chiron's regulatory problems have delayed its test two months.
A second line of defense against the H5N1 strain is the antiviral drug oseltamivir, sold under the brand name Tamiflu, which laboratory tests suggest can suppress the H5N1 strain. Other older flu drugs are ineffective. But Tamiflu, developed by Gilead Sciences of Foster City, and made only by Swiss pharmaceutical giant Roche at its plant in Basel, is costly and in short supply.
A five-day course of Tamiflu -- two 75-milligram pills a day -- costs $65. The United States, which has a population of nearly 300 million, ordered a stockpile of Tamiflu last year sufficient to cover 2.3 million people. Britain has just ordered 14.6 million doses -- enough to cover a quarter of its population; France has ordered 13 million, covering 20 percent; and Canada, 5.4 million, covering 17 percent.
"We've been encouraging countries to stockpile now," said Roche spokesman Terry Hurley. "If they wait until it hits, it will be too late."
U.S. health authorities are considering the purchase of additional doses of Tamiflu, but have yet to make a commitment. Hurley said that Roche is working with the Food and Drug Administration to expedite approval of a U.S. manufacturing plant for Tamiflu. "We hope to have it up an running by the fall of this year," he said.
Doctors caution, however, that Tamiflu may not be the magic bullet to stop bird flu. The drug has been proven effective against it only in the laboratory. The course of medication must begin two days after the onset of symptoms, or it won't help. And other lab tests indicate the flu virus can mutate to make Tamiflu less effective.
"We have supplies of Tamiflu, but we are not stockpiling it," said Dr. Roger Baxter, director of flu programs at Kaiser Permanente. The Oakland-based health care giant serves 6 million Californians. "I don't want to buy into a fear-driven panic."
Baxter said the outbreaks of avian influenza are a disturbing trend that has gone on for some time. "It's a trend, but a trend does not make a pandemic, " he said.
Beyond the question of using vaccines and drugs to prevent or treat a new flu pandemic, planners are concerned about a shortage of hospital beds, ventilators and routine medical supplies that now ship "just-in-time" from warehouses. Another worry: the potential shortage of medical staffers either too ill, or too frightened, to care for patients.
"When a disaster such as an earthquake strikes, the focal area tends to be one site in one state. Flu may affect an entire state, or the entire nation, " said state virus lab director Glaser. "We constantly ask the medical community to be thinking about this."
Glaser authored a study of an outbreak of influenza in 1997, when the flu vaccine was simply a poor match for the strain that was circulating in the state. The Los Angeles hospital system was overwhelmed by the surge of patients. "Even that year, we didn't have enough ventilators," Glaser said.
Dr. Susan Fernyak, director of communicable disease control for the San Francisco Department of Public Health, said that years of training against a bioterrorist attack -- stepped up dramatically since the anthrax mailings of 2001 -- are helping communities prepare for the health consequences of a flu pandemic. "Whether its smallpox or influenza, a lot of the issues are the same, " she said.
Despite the stress on planning, the inherent unpredictability of influenza makes the task a daunting, if not impossible one.
"I don't think anyone is happy about the state of preparation," said Dr. Lisa Winston, director of infection control at San Francisco General Hospital. "But it's very hard to be prepared about something if you don't know if it will happen, when it will happen, or -- if it happens -- whether your area would be involved."
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FLU OUTBREAK
Life expectancy in the United States
The effect of the 1918 flu pandemic on life expectancy illustrates why officials are urgently laying plans to combat another possible pandemic. 1918: 39.1 years 2002: 77.3 years - Source: U.S. Department of Commerce 1976, Grove and Hetzel, 1968, Linder and Grove, 1943
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The likely course of a pandemic - Phase 0 – Inter-pandemic period
Identification of influenza viruses and development of a vaccine.
Preparedness level 0: (Inter-pandemic period)
Preparedness level 1: (Initial report of a new strain in humans)
Preparedness level 2: (Novel virus alert – human infection confirmed)
Preparedness level 3: (Human transmission confirmed) - Phase 1 – Confirmation of onset of pandemic
New virus spreads from one person to another, with several outbreaks in at least one country or region. Virus shows severe morbidity and mortality in at least one segment of the population. - Phase 2 – Regional and multi-regional epidemics
New virus causes outbreaks in multiple countries around the world. - Phase 3 – End of first pandemic wave
Influenza activity in initially affected country or region has stopped, but outbreaks continue elsewhere. - Phase 4 – Second or later waves of the pandemic
A second wave of outbreaks of the new virus occurs after 3-9 months within the initial country or region. - Phase 5 – End of the pandemic, back to Phase 0
Pandemic is officially declared over when infection rate returns to prepandemic levels. Based on history, that could take two years.Source: World Health OrganizationThe Chronicle
E-mail Sabin Russell at
srussell@sfchronicle.com.
