Table 1.

Summary of literature review of post-exposure vaccination efficacy against smallpox.

Year(s) of variola major outbreak	Location(s) of variola major outbreak	Outbreak case fatality rate (all cases)	Original author conclusions regarding the efficacy of post-exposure vaccination in previously unvaccinated contacts	Data gaps affecting interpretation of conclusions^a	Ref.
1942	Glasgow, Edinburgh and Fife, Scotland	24%	Patients vaccinated day 0–3 post-exposure had significant improvement in fatality and reduction in severity of disease. “Number of cases of smallpox in recently vaccinated contacts was small”.	Summary article, “reduction in severity” unexplained, quantitative results not reported.	[31]
1946	Tripolitania, Libya, North Africa	18%	Contacts vaccinated 1–5,6–10 or 10+ days after contact had mortality rates of 0%, 19% and 25% respectively. Patients vaccinated within 5 days of exposure had milder disease.	Small number of post-exposure vaccinees.	[32]
1947	Bilston, England	20%	Vaccination ~3–4 days post-exposure did not influence disease course. Modified cases of smallpox occurred where vaccination had been carried out 0–1 day post-exposure.	Survival of confluent cases unknown, quantitative results not given.	[33]
1950–1971	Cases imported into Europe	16%	The case fatality rate of patients vaccinated post-exposure was 29% - compared to a fatality rate of 52% in those that were never vaccinated.	No explanation of the timing of post-exposure vaccination is given.	[34]
1961–1972	Madras, India	43%	Vaccination post-exposure in 426 cases of ordinary smallpox resulted in a case fatality rate of 20.6% compared to a case fatality rate of 36.9% in 1296 unvaccinated persons.	Timing of post-exposure vaccination is unknown. Small number of post-exposure vaccinees.	[35]
1962	Bradford, England	50%	Vaccination within 24 h of exposure resulted in mild forms of disease. Primary vaccination on day 11 post-exposure was ineffective.	Descriptive case studies only, small number of relevant cases, outbreak had higher than normal fatality rate.	[36]
1965–1968	Madras, India	Not given	In this study of familial contacts, 47.6% of unvaccinated contacts developed smallpox, while only 29.5% of those contacts that received primary vaccination did. Of those 29.5%, those cases (excluding pregnant women) that were vaccinated after exposure also showed decreases in hemorrhagic disease presentation and increases in modified disease presentation.	No mention of fatality rates for outbreak, no discussion of when post-exposure vaccination was provided (day 1, 2,3 post exposure etc.). Data acquired during mass vaccination campaign	[37]
1967	Sheikhupura District, Punjab, West Pakistan	Not given	75% (12/16) of those who were vaccinated within 10 days of contact developed smallpox while 96% (26/27) of those not vaccinated within 10 days developed smallpox.	No mention of fatality rates for outbreak, small numbers, no discussion of post-exposure vaccination at specific day (day 1, 2,3 etc.).	[38]
1968–1970	Six rural districts, Punjab, West Pakistan	21%	Of contacts with no prior vaccination history, 78.5% (73/92) of contacts with no post-exposure vaccination developed disease compared to none (0/2) of the contacts that received post-exposure vaccination within 7 days of exposure.	Small study, no discussion of vaccine efficacy against morbidity. Post-exposure vaccination efficacy was reported in terms of subsequent attack rates, which assumes that all household contacts are exposed equally, and with similar timing.	[39]
1972	Bangladesh evacuees in Calcutta, India	50%	Primary vaccination 0–1 days post-exposure resulted in fatality rate of 37.1%, primary vaccination 2 days post-exposure had fatality rate of 41.9%, compared to 53.4% in the general unvaccinated population.	No discussion of vaccination efficacy against morbidity.	[40]
1972	Khulna Municipality, Bangladesh	27%	Contacts that received primary vaccination 5–7 days post-exposure had an attack rate of 7.9/1000 vs. 14.4/1000 in unvaccinated persons. Overall, 2.4% (10/414) of unvaccinated household contacts who received post-exposure vaccination developed disease compared to 9.2% (5/54) of unvaccinated household contacts who did not receive post-exposure vaccination.	Post-exposure vaccination efficacy was reported in terms of subsequent attack rates, which assumes that all household contacts are exposed equally, and with similar timing. Small number of cases. Not all post-exposure vaccination timing explained.	[41]
1973	Calcutta, India	32%	In patients whose primary vaccination occurred <9 days post-exposure the fatality rate was 41.1% compared to persons vaccinated 9–12 days post-exposure which had a fatality rate of 50% and unvaccinated patients which had a fatality rate of 53.4%.	No discussion of vaccination efficacy against morbidity.	[42]

All studies in this table share the following data gaps: vaccine strain not specified, vaccine administration method not specified, vaccine origin and quality not specified, individual patient numbers and demographics not specified, contacts that were vaccinated post-exposure and did not become infected are not discussed.