Volume 9, Number 11—November 2003
Risks and Benefits of Preexposure and Postexposure Smallpox Vaccination1
|Base cases||Sensitivity analyses|
|Probability of attack
|No. of cases before detection of attack
|General population “at risk”a
||9 million or 280 million
|No. of susceptible HCWb
||100,000 or 1,000,000
|Probability of exposure to smallpox, for an:
|Individual member of general populacec
||1:9,000 or 1:280,000
|Individual HCWb contacting infectious persond
||1:100 or 1;100,000
|Individual member of investigation teame
||1:2.5 or 1:5
|Probability of transmission of smallpox, for an:
|Individual member of general populacef
|Individual HCWb contacting infectious persong
|Individual member of investigation teamh
|Probability of vaccine effectiveness, preexposure
|Probability of serious vaccine-related adverse eventsi
|Probability of vaccine effectiveness, postexposure
||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%.
- Meltzer MI. Model 1. In: Institute of Medicine. Scientific and policy considerations in developing smallpox vaccination options: a workshop report. Washington: National Academies Press; 2002. p. 15–7.
- Henderson DA, Inglesby TV, Bartlett JG, Ascher MS, Eitzen E, Jaheling PB, Smallpox as a biological weapon: medical and public health response. JAMA. 1999;281:2127–37.
- Meltzer MI, Damon I, Leduc JW, Millar JD. Modeling potential responses to smallpox as a bioterrorist weapon. Emerg Infect Dis. 2001;7:959–69.
- Alibek K. Biohazard. New York: Random House; 1999.
- Neff JM. The case for abolishing routine childhood smallpox vaccination in the United States. Am J Epidemiol. 1971;93:245–7.
- Lane MJ, Goldstein J. Evaluation of 21st century risks of smallpox vaccination and policy options. Ann Intern Med. 2003;138:488–93.
- Bozzette SA, Boer R, Bhatnagar V, Brower JL, Keeler EB, Morton SC, A model for a smallpox-vaccination policy. N Engl J Med. 2003;348:416–25.
- Bush’s comments on his plan for smallpox vaccinations across the U.S. New York Times (late edition) 2002 Dec 14; Sect. A:12.
- McKenna MAJ, Moscoso E. State vaccinations for smallpox begin. Atlanta Journal- Constitution 2003, Jan 30; Sect. A:3.
- Bicknell WJ. The case for voluntary smallpox vaccination. N Engl J Med. 2002;346:1323–5.
- de Rugy V, Pena CV. Responding to the threat of smallpox bioterrorism: an ounce of prevention is best approach. Policy Anal. 2002;434:1–16.
- Charen M. Bioterrorism defense plan unworkable. Atlanta Journal-Constitution 2002 Sept. 24; Sect. A:17.
- Blendon RJ, DesRoches CM, Benson JM, Hermann MJ, Taylor-Clark K, Weldon KJ. The public and the smallpox threat. N Engl J Med. 2003; 348–54.
- McKenna MAJ. Grady’s workers won’t be given smallpox shot yet. Atlanta Journal-Constitution 2002 Dec. 17; Sect. D:8.
- McNeil DG Jr. Many balking at vaccination for smallpox. New York Times 2003 Feb 07; Sect. A:1.
- McKenna MAJ. No vaccination for nations fear; unease hinders smallpox program. Atlanta Journal-Constitution 2003 Feb. 15; Sect. A:1, 5.
- McDonald L, Calenza J. Flags raised over smallpox vaccine. Atlanta Journal-Constitution 2003 Feb 20; Sect. A:19.
- Connolly C. Smallpox vaccine delay rejected. Atlanta Journal-Constitution 2003 Jan 17; Sect. A:3.
- Pear R. Officials seek smallpox vaccine compensation fund. New York Times 2003 Mar 7; Sect. A:15
- Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968; national surveillance in the United States. N Engl J Med. 1969;281:1201–8.
- Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 1968: results of ten statewide surveys. J Infect Dis. 1970;122:303–9.
- Fenner F, Henderson DA, Arita I, Jezek Z, Ladnyi ID. Smallpox and its eradication. Geneva: World Health Organization; 1988.
- Rao AR. Smallpox. Bombay: Kothari Book Depot; 1972.
- Dixon CW. Smallpox. London: J & A Churchill; 1962.
- Centers for Disease Control and Prevention. Update: cardiac-related events during the civilian smallpox vaccination program—United States, 2003. MMWR Morb Mortal Wkly Rep. 2003;52:492–6.
- Hanna W. Studies in smallpox and vaccination. Bristol, UK: Wright; 1913.
- Mack TM. Smallpox into Europe, 1950–1971. J Infect Dis. 1972;125:161–9.
- McCarthy K, Downie AW, Bradley WH. The antibody response in man following infection with viruses of the pox group. II. Antibody response following vaccination. J Hyg (Lond). 1958;56:466–78.
- el-Ad B, Roth Y, Winder A, Tochner Z, Lublin-Tennenbaum T, Katz E, The persistence of neutralizing antibodies after revaccination against smallpox. J Infect Dis. 1990;161:446–8.
- Chapman GB. Your money or your health: time preferences and trading money for health. Med Decis Making. 2002;22:410–6.
- Reeve AM. Vaccination against smallpox in the United States—a re-evaluation of the risks and benefits. J Iowa Med Soc. 1971;61:655–7.
- Lane JM, Millar JD. Risks of smallpox vaccination complications in the United States. Am J Epidemiol. 1971;93:238–40.
- Centers for Disease Control. Public Health Service recommendations on smallpox vaccination. MMWR Morb Mortal Wkly Rep. 1971;20:339.
- Hospital statistics; 1999 edition. Chicago: Health Forum, American Hospital Association; 1999.
- Pasko T, Seidman B. Physician characteristics and distribution in the US. 1999 edition. Chicago: American Medical Association; 1999.
- Gani R, Leach S. Transmission potential of smallpox in contemporary populations. Nature. 2001;414:748–51.
- Heiner GG, Fatima N, McCrumb FR. A study of intrafamilial transmission of smallpox. Am J Epidemiol. 1971;94:316–26.
- Mack TM, Thomas DB, Ali A, Khan MM. Epidemiology of smallpox in West Pakistan. 1. Acquired immunity and the distribution of the disease. Am J Epidemiol. 1972;95:157–68.
- Rao AR, Jacob ES, Kamalakshi S, Appaswamy S. Bradbury. Epidemiological studies in smallpox: a study of interfamilial transmission in a series of 254 infected families. Indian J Med Res. 1968;56:1826–54.
- Dixon CW. Smallpox in Tripolitania, 1946: an epidemiological and clinical study of 5000 cases, including trials of penicillin treatment. J Hyg (Lond). 1946;46:351–77.
- Ropeik D, Gray G. Risk. Boston: Houghton Mifflin Co.; 2002.
- Corso PS, Hammitt JK, Graham JD. Valuing mortality-risk reduction: using visual aids to improve the validity of contingent valuation. J Risk Uncertain. 2001;23:165–84.
- Rabin M, Thaler RH. Anomalies: risk aversion. J Econ Perspect. 2001;15:219–32.
- Rabin M. Psychology and economics. J Econ Lit. 1998;36:11–46.
- Ropeik D. What really scares us. Parade Magazine 2003 Mar 30;12–4.
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 ), 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, ). 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.