Diary Prequel Package — page 56

compared to the younger group with regard to the other complications of primary vaccination. HOWEVER, the critical issue as I see it is the major difference between previously unvaccinated and previously vaccinated individuals with regard to the frequency of vaccine-related complications. Whether you look at the figures from the 1969 paper referred to above (attachment #2) or the 2001 MMWR (attachment #3), the rate of complications in the previously unvaccinated group is considerably higher than that in the previously vaccinated group. For example, in the Table 6 of the 1969 New England Journal of Medicine paper (attachment #2), the complications per million are as follows comparing previously unvaccinated versus previously vaccinated: Encephalitis - 2.9 versus 0; vaccinia necrosum - 0.9 versus 0.7; eczema vaccinatum 10.4 versus 0.9; generalized vaccinia - 23.4 versus 1.2. The differences are even more impressive in the Table from the 2001 MMWR (attachment #3) 2) Since the differences are so striking between previously unvaccinated and previously vaccinated individuals with regard to the incidence of serious adverse events associated with smallpox vaccination, I calculated the percent of people in the work force that we could predict would be previously vaccinated or not. I used the most recent US Census (2000) (attachment #4). I consider the work force to be individuals from 20 through 64 years old (this corresponded to natural breaks in the census data). In 2000, there were 281,421,906 people in the USA. I found that there were 59 million people or 21% of the total population and 36% of the work force between the ages of 20 and 34 years. These people will have not been previously vaccinated. Routine vaccinations stopped in 1972 and most children would not have been vaccinated before age 5 and so 34 years old is the cut off point. I further found that 107 million people between the ages of 35 and 64, i.e. 38% of the population and 64% of the work force were likely vaccinated. Thus, 64% of the people that we would be vaccinating in the first responder/health care worker category would fall into a group that historically has a much lower rate of serious adverse events than the previously unvaccinated group. I believe that this must at least be taken into consideration in our policy decisions. 3) You asked a question about residual immunity in people vaccinated decades ago. If you look at laboratory immunity (i.e. antibody levels and cell-mediated immune function), there is no question that the vast majority of studies indicate that there are variable levels of residual laboratory immunity in people who were immunized even decades ago. The question remains whether the laboratory immunity is totally reflective and correlated with clinical immunity to an actual exposure. There are several studies that indicate that previous immunization, even decades ago, provides real, but variable, degrees of protection against death (i.e. lower case fatality rates) compared to unimmunized individuals. It is impossible to determine the effect on actual infection without death. Some of these studies such as the 1902-1903 Liverpool outbreak study is partially flawed in that there was some smallpox circulating in the community that might have boosted immunity. However, several studies that are summarized in a paper by Mack TM et al: Smallpox in Europe 1950-1971. J. Infect. Dis. Vol.125, number 2, Feb. 1972 (attachment #5) indicate that case fatality rates are significantly less in individuals vaccinated even more than 2 decades before. I personally do not believe that all of these people were protected because that were intermittently boosted by naturally occurring