March 22, 2004

Influenza, smallpox outbreaks can be contained

By Holly Korschun

Research by two professors in the Rollins School of Public Health has yielded encouraging insights into the nation's preparedness in case of future outbreaks of influenza or even smallpox.

In work that will appear in a special article in the American Journal of Epidemiology on April 1, biostatistics Professors Ira Longini and Elizabeth Halloran showed that, in an outbreak of pandemic influenza--such as the three pandemics that sickened millions and killed hundreds of thousands of people during the 20th century--supplies of flu vaccine might not be available quickly enough to contain the spread of disease.

However, many thousands of deaths could be prevented if antiviral agents were given to the close contacts of those with suspected cases of flu until adequate supplies of vaccine could be manufactured and distributed.

The scientists used a dynamic stochastic simulation model of an influenza pandemic or bioterrorist attack for an agent similar to the strain of influenza that caused the Asian   pandemic of 1957-58 and resulted in approximately 70,000 deaths in the United States (a stochastic model includes elements of chance or probability).

They determined that if no interventions were used in a similar pandemic, 33 percent of the population would become ill, resulting in a death rate of 0.58 per 1,000 people. But if antiviral prophylaxis was given to close contacts of 80 percent of suspected influenza cases--a strategy the authors called "targeted antiviral prophylaxis" (TAP)--the epidemic could be contained. If TAP were begun within one day of identifying suspected flu cases and used for up to eight weeks, only 2 percent of the population would become ill, and the death rate would be only 0.04 per 1,000 people. The researchers found that eight weeks of TAP would be nearly as effective as vaccinating 80 percent of the population.

"The ability to rely on targeted antiviral therapy in the case of a major public health threat from influenza would be an extremely valuable strategy, due to the characteristics of influenza pandemics," Longini said. "Epidemics are usually caused by strains of flu that acquire genetic variations that differ slightly from earlier strains, while pandemics occur when there is a dramatic shift in the current flu strain.

"Annual flu vaccines are designed to counter the strain of flu from the previous season, and often there is insufficient time to catch up with making enough vaccine to counter the first wave of a new outbreak," he continued.

Although the surveillance and containment strategy (i.e., isolation of cases and quarantine of close contacts) was recently used to successfully contain the spread of severe acute respiratory syndrome (SARS), influenza has a much shorter incubation period (1.9 days as opposed to 6.4 days) and a much broader range of clinical illness, from asymptomatic to primary pneumonia. Thus the surveillance and containment strategy is unlikely to work in containing an influenza epidemic.

In a separate research project, Longini and Halloran demonstrated that, in the event of a large, intentional release of smallpox, the current government policy of post-release surveillance and containment--if quickly implemented--would be sufficient to prevent a widespread epidemic.

Delays in isolating cases by even one or two days, however, could hamper control of an epidemic. The pair presented this research at the American Association for the Advancement of Science annual meeting in Seattle on Feb. 14.

Although mass vaccination during or before a smallpox attack would result in fewer cases and deaths than would surveillance and containment, the researchers concluded that an increased rate of vaccine-related serious illness and death would offset the slightly lower number of smallpox illnesses and deaths, especially since no one knows when or where an intentional release of smallpox could take place. They also concluded that, even if a particular smallpox virus were altered to cause more serious or hemorrhagic cases than the ordinary virus, surveillance and containment still would be effective, although more deaths would occur.

In an earlier study published in Science on Nov. 15, 2002, Longini and Halloran maintained that targeted vaccination of the close contacts of infected individuals during a smallpox outbreak following a small attack could approach the effectiveness of mass vaccination, given a sufficiently high level of immunity within the population. However, as of May 2003, fewer than 35,000 people had been newly vaccinated against smallpox, and many states had temporarily halted their smallpox vaccination programs. Although routine smallpox vaccinations were stopped in 1972, recent studies have shown that previously vaccinated individuals retain substantial immunity.