Avian flu threat intensifies need for preparedness (IDSA annual meeting)

Amid the growing international focus on vaccines and antiviral stockpiles to combat a predicted flu pandemic, a top global health official is underscoring the critical role to be played by doctors and nurses on the front lines of health care delivery.

Pharmaceutical interventions will be essential, but they aren't going to solve the problem on their own, according to Klaus Stohr, PhD, head of the World Health Organization's Global Influenza Programme.

"In the end, the effectiveness of the intervention all depends upon the physician, the hospital, the nurse and the technical equipment available at the local level," he said in a speech delivered at the Infectious Diseases Society of America's annual meeting Oct. 6-9 in San Francisco.

Although drugmakers are ramping up production capacity and nations are scrambling to stockpile the antiviral drug Tamiflu (oseltamivir), there simply will not be enough vaccine and drugs for everyone who needs them, Dr. Stohr warned. "We believe that if a pandemic comes, there will be a significant dependence on primary health care and hospital services for symptomatic treatment."

There also will be a heavy reliance on nonpharmaceutical interventions, such as quarantines, voluntary home stays and protective face masks to prevent the spread of infection, he said. "These barriers will be the ones to slow down the spread and help reduce morbidity and mortality."

Dr. Stohr's remarks at the IDSA meeting coincided with published reports that the deadly Spanish flu pandemic of 1918-19 first developed in birds and was similar to today's H5N1 avian flu virus, raising fears among national and international policy-makers that H5N1, like the earlier strain, could turn into a global human pandemic. Discoveries that the avian flu virus now has spread beyond Asia and as far as Turkey, Romania and Macedonia also have increased anxiety levels.

These and other developments suggest that H5N1 is accelerating its potential to cause an influenza pandemic, Dr. Stohr said. The virus is not just expanding its geographic reach, "it's increasing its pathogenicity."

By late October, global health officials feared that the deadly virus would jump next to East Africa, where countries are almost completely unprepared to control outbreaks. The virus also appeared to be flaring up again in Asia, where Thailand reported in October its first human cases of H5N1 in more than a year. So far, human cases of H5N1 infections remain limited to four countries in Southeast Asia, where the virus has caused at least 62 deaths. But experts warn that if the virus mutates into a form that is easily transmissible between humans, it is likely to spread rapidly with devastating consequences.

The need for speed

A significant aspect of avian flu is that its rate of transmission appears to be only two days, said Barry Bloom, PhD, dean of the Harvard University School of Public Health, who also spoke at the IDSA meeting. By contrast, the timeline for SARS was six to eight days.

"When one thinks of bird flu, with a serial interval of two days, I would like to be pre-armed with immunization, if I have a choice, rather than worry about recovering from an infection," Dr. Bloom said. Currently, there is no licensed vaccine that is considered effective in protecting humans from the H5N1 strain.

But experimental vaccines are undergoing human clinical trials, said Robert B. Belshe, MD, director of the Center for Vaccine Development at Saint Louis University School of Medicine. They include both active vaccines and live, attenuated vaccines.

One challenge, though, is predicting exactly which strain is going to emerge as a human threat. "Selecting a strain today may be a problem," Dr. Belshe warned.

According to Dr. Stohr, an effective vaccine is certainly not going to be available in the first three months of a pandemic outbreak, which is the length of time in which the virus is likely to spread worldwide. Even during subsequent months, the world's vaccine supply will be inadequate because of limited production capacity.

Without a vaccine, it is hoped that antiviral drugs could be used effectively to treat symptoms in patients who become infected with H5N1 and as prophylaxis in areas of pandemic flu outbreak. WHO has developed a "rapid response stockpile" of these treatments that it plans to deploy quickly to such areas in an effort to contain the virus and prevent it from spreading.

The intervention would need to be quick to be effective, Dr. Stohr said. "The window of opportunity to extinguish or eliminate the pandemic virus is very narrow -- between 20 and 30 days from when the virus emerges until the time it's too late."

In the scenario he outlined, at least four to five days will elapse between the onset of symptoms in patients infected by the pandemic flu strain and when they are admitted to the hospital. It would take several more days -- possibly a week or more -- to determine a diagnosis, conduct a field investigation and characterize the virus.

WHO then would have about 10 to 14 days to intervene by broadly distributing antiviral prophylaxis to the affected population. The strategy has never been used and may not be successful, he said. "But we would not be forgiven if we did not try it."

In the meantime, the United States and other nations are racing to increase their own stockpiles of antiviral drugs.

President Bush, for instance, announced Nov. 1 that he would ask Congress for $7.1 billion to begin implementing a preparedness plan. Specifically, the plan would provide $2.8 billion for research to speed vaccine development, $1.2 billion to buy vaccine effective against the strain of avian flu currently circulating and $1 billion for the purchase of antiviral medications.