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Volume 9, Number 11—November 2003
Perspective

Risks and Benefits of Preexposure and Postexposure Smallpox Vaccination1

Martin I. Meltzer*Comments to Author 
Author affiliation: *Centers for Disease Control and Prevention, Atlanta, Georgia, USA

Main Article

Table

Model input variables and values used

Variable Symbol Values
Base cases Sensitivity analyses
Probability of attack
 PR
 1:10 –1:100,000
No. of cases before detection of attack
 XCASE
 1,000
 100,000
General population “at risk”a
 XPOP
 9 million or 280 million
No. of susceptible HCWb
 XHCW
 100,000 or 1,000,000
Probability of exposure to smallpox, for an:
 PE
Individual member of general populacec
1:9,000 or 1:280,000
 1:1j
Individual HCWb contacting infectious persond
1:100 or 1;100,000
 1:1j
Individual member of investigation teame
1:2.5 or 1:5
 1:1j
Probability of transmission of smallpox, for an:
 PT
Individual member of general populacef
1.0
 0.01 –0.70j
Individual HCWb contacting infectious persong
0.70
 0.01 –0.70j
Individual member of investigation teamh
0.40
 0.01 –0.70j
Probability of vaccine effectiveness, preexposure
 PVEpre
 0.98l
Probability of serious vaccine-related adverse eventsi
 PSideEffect
 1:100,000
 1:500–1:1,000,000j
Probability of vaccine effectiveness, postexposure
 PVEpost
0.01 - 0.60j
Relative individual valuation; case of smallpox : Case(s) of serious vaccine related adverse eventsk PValuation 1:1 1:35

aTwo populations “at risk” are modeled: a population of 9 million, representing a metropolitan area assumed to be the sole target of a smallpox attack and the entire U.S. population of approximately 280 million. Exactly how a given metropolitan area would be defined as the single target at risk is a matter of speculation.
bHCW, healthcare worker.
cRisk for exposure for member of the general populace is defined as the risk of contracting, and subsequently developing, a clinical case of smallpox before detection of the event (for individual person in general populace, PE = XCASE/XPOP). See text for further details.
dRisk of a HCW’s becoming exposed is a function of the number of cases divided by number of susceptible HCWs (for HCW, PE = XCASE/XHCW).
eProbability of a member of an investigation team being exposed to smallpox includes the probability of being sent to a site where smallpox may be present, such as in a container. There are no data that can be used to accurately define such a risk, and the data used here are assumed.
fProbability of transmission of smallpox = 1 indicates that the model only considers those members from the general populace in whom a clinical case of smallpox develops. See text for further details.
gProbability of transmission represents when HCWs are not using any effective barrier-type protection (e.g., gloves, gowns, masks). The rate of transmission used, 0.70, is equivalent to the upper estimates of the rates of transmission to unvaccinated household members living with a smallpox patient (Appendix 1 in ref. 2).
hProbability of transmission for investigation teams represents a risk after barrier-type protection is used. There are no data representing the actual reduction in risk, and the value of 0.40 is assumed.
iSerious vaccine-related adverse events are defined as those adverse events which require “notable” amounts of medical care, such as vaccinia immunoglobulin, hospitalization, or a number of visits to a physician’s office. The rate of 1:100,000 is derived from the number of “serious” adverse events (e.g., death, postvaccine encephalitis, progressive vaccinia) measured in 1968 among first-time adult smallpox vaccinees (19,20)
jThese values are used to examine the risk-benefit of an individual person’s accepting smallpox vaccination, including those being revaccinated, for preexposure and postexposure scenarios. See text for further details.
kIn the base case, it was assumed that a person would value 1 case of smallpox equal to 1 case of serious vaccine-related adverse events. However, a person may be more worried about contracting a clinical case of smallpox than experiencing vaccine-related adverse events. Thus, in the sensitivity analyses, the valuation was altered to reflect a higher valuation of a case of smallpox relative to a case of serious vaccine-related adverse events (see text for further details).
l Fenner et al. (22) reviewed five separate studies and reported vaccine efficacy to range from approximately 91% to 97%.

Main Article

References
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Main Article

1This article presents further ethodologic details and results of a study presented at a workshop entitled “Scientific and policy considerations in developing smallpox vaccination options,” Washington, DC, 2002 (1).

2Assume that only a single metropolitan population of 9 million is at risk from an initial attack, and the initial attack results in 1,000 cases before discovery. For a person in that population, the risk for death from smallpox is approximately 33 times greater than the risk for death from the smallpox vaccine [smallpox risk for death/vaccine-related risk for death = (1,000 cases/ 9 million x 0.3)/0.000001]. For a person in a population of 280 million, the risk of dying from smallpox in the initial 1,000 cases is approximately equal to the risk for death from the vaccine.

3In data reported by Rao from Madras, India (Figures 17/1 and 17/3 [23]), among the unvaccinated, approximately 80% of all cases of smallpox occurred in children <10 years of age. A distinct shift in age of the case-patients occurred among the vaccinated, with <10% of cases occurring in children <10 years of age, 19% of cases occurring in children 10–19 years, and 46% of cases occurring in persons 20–30 years of age. Rao did not report at what age most of those vaccinated received vaccine (a likely hypothesis would be before 2 years of age). Further complicating the analysis of such data is the fact that many persons in Madras received more than one smallpox vaccination (Figure 17/5, [23]). A similar age-shift in occurrence of cases among the vaccinated can be discerned from the data reported by Hanna (24) from Liverpool, England, in 1902–03. The data from both Rao (23) and Hanna (26) further indicate that even a 20-year-old vaccination may reduce the severity of disease. The risk for death is markedly reduced 20–30 years postvaccination (23,26,27).

4In addition to the estimates quoted in the main text, Rao et al. (39) found that successful postexposure vaccination reduced, on average, the rate of smallpox among contacts by approximately 38% (from 48% among unvaccinated to 30% among postexposure vaccinees). Dixon (40) reported that in a group of 59 contacts under 5 years of age “. . . approximately half of those who had a successful vaccination after contact developed disease.” The wide variations in reports of the degree of protection afforded by postexposure vaccination are probably due to a number of reasons, including small sample sizes and difficulty in determining when exposure and potential transmission actually took place.

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