Risks and benefits of preexposure and postexposure smallpox vaccination

Abstract

This article presents a model and decision criteria for evaluating a person's risk of pre- or postexposure smallpox vaccination in light of serious vaccine-related adverse events (death, postvaccine encephalitis and progressive vaccinia). Even at a 1-in-10 risk of 1,000 initial smallpox cases, a person in a population of 280 million has a greater risk for serious vaccine-related adverse events than a risk for smallpox. For a healthcare worker to accept preexposure vaccination, the risk for contact with an infectious smallpox case-patient must be >1 in 100, and the probability of 1,000 initial cases must be >1 in 1,000. A member of an investigation team would accept preexposure vaccination if his or her anticipated risk of contact is 1 in 2.5 and the risk of attack is assumed to be >1 in 16,000. The only circumstances in which postexposure vaccination would not be accepted are the following: if vaccine efficacy were <1%, the risk of transmission were <1%, and (simultaneously) the risk for serious vaccine-related adverse events were >1 in 5,000.

Figure 1

Risk-benefit analyses for individual persons evaluating the risk for smallpox versus the risk for serious smallpox vaccine-related adverse events: three scenarios. If the net risk is >0 (above neutral), then a person will accept preexposure vaccination. If the net risk is <0 (below neutral), then the person would not accept preexposure vaccination. Part a considers a person who is either a member of 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. In part b, the risk for contact by an individual healthcare worker is a function of probability of contact x probability of transmission (P_E x P_T, see Table and text for further details). In part c, investigation team members are assumed to take precautions against transmission (e.g., wear gloves, face masks, and gowns) to reduce risk to 0.4 (no data of the actual reduction in risk due to using such barrier precautions). Threshold values of risk for smallpox attack, when net risk = 0 (neutral), are rounded to the nearest 1,000. All three parts present data calculated on the basis of an attack that initially causes 1,000 cases before detection of the attack. See Table and text for other assumptions.

Figure 2

Sensitivity analyses: impact of altering a person’s value of a case of smallpox relative to a case of serious smallpox vaccine-related adverse events. If the net risk is >0 (above neutral), then a person will accept preexposure vaccination. If the net risk is <0 (below neutral), then the person would not accept preexposure vaccination. Both parts show the impact of altering a person’s valuation of a case of smallpox relative to a case of serious vaccine-related adverse events. Part a shows the net risks for an individual person’s considering preexposure smallpox vaccination with an attack causing clinical cases of smallpox to develop in 1,000 persons. Part b shows the net risks for a person when an attack causes clinical cases of smallpox to develop in 100,000 persons (see text for further details).

Figure 3

Risk-benefit analyses for persons considering postexposure smallpox vaccination: two scenarios. If the net risk is >0 (above neutral), then the person will accept postexposure vaccination. In the net risk is <0 (below neutral), then the person would not accept postexposure vaccination. Part a shows the net risk for postexposure smallpox vaccination for a person who has been exposed to somebody who may or may not have smallpox (i.e., the exposure is uncertain). Threshold values of risk for exposure to smallpox, when net risk = 0 (neutral), are rounded to the nearest 1,000. Part b shows the net risk for an individual person who has been exposed to a definite smallpox case (see text for further details).