Pandemic plan efforts move into high gear

HCWs would likely be a vaccine priority

The emergence of avian influenza A (H5N1) infection in humans in Hong Kong underscores that the United States flu pandemic plan must be finalized to address critical details if the nation is to swiftly respond to such a public health emergency, officials report.

"What is needed — and what is going on at the moment — is a more detailed series of protocols associated with the plan so we know exactly what needs to be done," says Brian Mahy, ScD, PhD, director of the division of viral and rickettsial diseases at the Centers for Disease Control and Prevention. "There are a couple of people working full-time trying to get this completed within the next two or three months."

U.S. draft pandemic plans have been under discussion for several years, but more detail is needed, for example, on what must be done to address the challenges of rapid vaccine production and distribution.

"This latest Hong Kong [outbreak] is alerting people to the need for getting this plan clarified and essentially produced," Mahy says. "It is certainly a wake-up call."

Prevention based on global surveillance

Federal agencies working on the plan with the help of non-government consultants include the CDC, the Food and Drug Administration, and the National Institutes of Health. A 1996 draft of the plan treats the emergence of another flu pandemic with a certain inevitability, saying an antigenic shift could occur that would create a highly transmissible, virulent virus that could reach susceptible populations before a vaccine could be produced and distributed.1 (See Hospital Infection Control, March 1996, pp. 35-36.) In addition to such an antigenic shift, the outbreak strain would have to begin causing infections in geographically dispersed regions before a pandemic is formally declared. Thus, the cornerstone of flu prevention in the plan remains global virologic surveillance, which consists of 110 designated laboratories in 79 countries.

"Everybody is very concerned, and we have gone to a lot a trouble to make sure that surveillance centers all over the world now can detect H5," Mahy says. "We are also considering the best way to develop potential vaccine candidates, and we are actively working on that here at CDC."

Even under optimum conditions, approximately six to eight months would be needed from the time a new variant is identified until large quantities of vaccine are ready for use, according to the draft plan. Current vaccine production techniques use embryonated chicken eggs, but that approach is proving a problem with the H5N1 avian strain, notes Arnold Monto, MD, a consultant to the CDC on emerging infections and professor of epidemiology at the University of Michigan school of public health in Ann Arbor.

"The problem with vaccine production for H5N1 is that it kills chickens," he says. "They harvest the fertile eggs after about nine days [normally]. By nine days the eggs are dead with this strain. They are looking for a surrogate that doesn’t do this."

In that regard, Aviron Inc., a biopharmaceutical company based in Mountain View, CA, recently announced plans to work with the CDC and NIH investigators in developing two vaccine candidates for H5N1. Researchers will attempt to develop a vaccine by taking weakened and modified hemagglutinin and neuraminidase surface proteins from avian influenza viruses and inserting them into human strains. The company announced the vaccine initiative at a meeting of the FDA Vaccines and Related Biologic Products Advisory Committee, which met Jan. 30 to discuss flu vaccine formulation for the 1998-99 U.S. flu season.

"We will take the H5 from the Hong Kong strain, modify it so it is non-pathogenic, and insert that in the background [human] virus," explains Martin Bryan, MD, PhD, vice president for research at Aviron. "The background virus that we use does not kill chicken eggs, so that is not a problem."

The FDA vaccine advisory committee recommended the company move forward with the research, even though the current H5N1 threat may subside and no vaccine may be needed, he adds. "One of the reasons for that is to make sure we have the processes in place to be able to respond any time in the future."

The primary roles for infection control professionals in a pandemic situation would likely be assisting with immunization efforts if vaccine is available, administering antivirals in outbreak situations, and assisting health departments with surveillance of incoming cases.

"Typically, flu is hospitalized relatively infrequently," Monto says. "The assumption would be with a pandemic that there would be enough severe cases that [hospitals] would certainly be seeing the tip of the iceberg — the most severe cases. The rest would be ‘underwater’ as asymptomatic infection [in the community]."

Although universal vaccination would be the goal in the event of a pandemic, a priority system would likely be implemented that included immunizing high-risk populations, key government officials, and people who provide essential community services. The latter would no doubt include health care workers, who have been historically reluctant to receive the annual immunizations.

"They’re blasé about it," Monto says. "One of the problems in flu immunization on a year-to-year basis is that we have to vaccinate each year for something that doesn’t occur each year. Even if you assume a 10% infection rate each year from flu, it takes somebody 10 years to get flu. It’s a hard sell, and that’s the basic problem."

Efforts to improve immunization rates must address some of the myths and misconceptions about adverse reactions and the efficacy of the vaccine, adds George Allen, MS, CIC, director of infection control at University Hospital of Brooklyn. A comprehensive education plan addressing the specific perceptions of influenza vaccine among various health care worker groups is needed, he says. Such efforts have raised the immunization level at University Hospital to around 25% after years of compliance in the range of 6% to 19%, he says. To determine reasons for lack of interest, Allen conducted a staff survey and found that health care workers are concerned that the vaccine may cause adverse reactions or flu infection, or simply may not work against the prevailing flu strain. For example, there are years when the flu vaccine is not as protective, reinforcing perceptions of questionable efficacy or that it may cause illness when those immunized become infected.

"There have also been incidents where someone takes the flu vaccine — but it takes a couple of days for it to really start to take effect — and two days later they come down with the flu," Allen says. "It is not because of the flu vaccine. They were incubating the flu before they took the vaccine. But they associate taking the flu vaccine with coming down with the flu a couple of days later. It’s not really related, but that is difficult to hammer home to them."

CDC guidelines note that "innovative methods" may be needed to increase influenza immunization rates among health care workers, including providing data to them on the low rates of systemic reactions to influenza vaccine among healthy adults.2,3 Also, traditional aversion to immunization may wane should a pandemic strain emerge, Monto adds.

"In a pandemic situation, they will want it, and that’s when the vaccine is going to be in short supply," he notes.


1. Federal Working Group on Influenza Pandemic Preparedness. Prevention and Control of Influenza in the United States: Preparing for the Next Pandemic. Draft # 6. Atlanta: Centers for Disease Control and Prevention; January 1996.

2. Centers for Disease Control and Prevention. Draft guideline for infection control in health care personnel, 1997; notice. 62 Fed Reg 47,276-47,327 (Sept. 8, 1997).

3. Nichol KL, Margolis KL, Lind A, et al. Side effects associated with influenza vaccination in healthy adults: a randomized, placebo-controlled trial. Arch Intern Med 1996; 156:1,546-1,550.