September 27, 2002
Diary Prequel Package, pp.55-57 · diary_prequel:entry:00100
Page text: p.55, p.56, p.57 · original PDF
- Date
- 2002-09-27 00:00 (day precision)
- Type
- diary entry · diary
- author
- Anthony S. Fauci
September 27, 2002
NOTE TO CAROL KUNTZ
From: Anthony S. Fauci, M.D.
Director
National Institute of Allergy and Infectious Diseases
National Institutes of Health
Carol:
As per your request, I will summarize below the information that I discussed with
you over the phone and will provide as attachments (1 through 5) some data sheets:
1) The question arises whether the rate of serious complications due to primary vaccinia
vaccination is greater in children versus adults and whether, because children will be
obviously excluded from the cohort of health worker and first responder vaccinees, this
will result in a lower than anticipated rate of complications for the first 2 stages of the
vaccine program, i.e. up to 10,000,000 people. My reference is Lane JM et al:
Complications of smallpox vaccination, 1968. National surveillance in the United States.
N Engl J Med 281:1201, 1969. I worked from Table 1 of the paper (attachment #1) and
analyzed the "Primary vaccinations". I divided the cohort into 2 groups of <1 yr to 9 yrs
old and 10 through 20+ yrs old in order to compare the actual rate per million
complications in each group. I found the following:
There were 4,900,000 individuals in the <1 to 9 yr olds and 694,000 individuals in the 10
to 20+ yr olds. The rate of complications in the 2 groups were as follows:
<1 - 9 y.o. 10 - 20+ y.o.
per million
Postvaccinial encephalitis 3 1
Vaccinia necrosum 0.4 4.0
Eczema vaccinatum 10 14
Generalized vaccinia 22 26
Accidental inoculation 26 10
Deaths 1 1.44
Therefore, one can conclude from this analysis that the younger group has a higher
incidence of encephalitis, but the older group is similar, if not slightly worse off, when
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
San
smallpox. There just were not that many widespread smallpox outbreaks to boost the
population of Europe consistently during that time frame. In fact, from 1950 through
1971, there were only 680 cases of smallpox in the countries in question. Therefore, I
would have to conclude (not definitively, but likely) that previously immunized people
do have a variable, but significant, degree of residual protective immunity against death
from smallpox.
I hope that you find this information useful. Please give me a call if you have any
questions at (301) 496-2263. Thank you and best regards.
Sincerely,
Anthony S. Fauci, M.D.