[Where do we stand with BCG vaccination programme in Japan?]

The current BCG vaccination program of Japan is critically discussed based on recent knowledge, especially with regard to its epidemiological aspects, in order to put the problem into perspective for Japan's future tuberculosis control program. 1. EFFICACY AND OVERALL EFFECTIVENESS: Various indicators of BCG efficacy have been proposed, and the meticulous analysis on the variability and the quality of these indicators seems to have formed a consensus on the efficacy, as seen in the recent meta-analysis studies. However, much has been left unanswered concerning the conditions under which the efficacy is guaranteed. The impact of the vaccination program on the population should also be considered in order to make decisions on the program. Comparing the age-specific tuberculosis notification rate between Japan and the USA, where there has been no BCG vaccination program, shows that the rate for 0 to 4 year olds is clearly lower in Japan than in the USA, while it is more than five times higher for all ages in Japan than in the USA. The statistics for Japanese children are superior to those of US children with respect to the speed of decline in notification rate as well. These observations support the overall effectiveness of BCG vaccination in Japan. 2. MECHANISMS OF BCG VACCINATION EFFICACY AND ITS DURATION: Two possible mechanisms of how BCG works to prevent tuberculosis were proposed. Epidemiological models based on each mechanism were subsequently tested by simulating 20 years' development of cases in the BCG vaccination trial by BMRC. In mechanism 1, the BCG-induced immunity is assumed to boost TB immunity in inhibiting the clinical breakdown of tuberculosis during the 10 to 15 years after the vaccination. In mechanism 2, the immunity makes the infection process abort (presumably, at 90%, during the seven years after infection, for example), leading to a smaller risk of future clinical development. So far, most epidemiological models implicitly assume mechanism 1 above. In animal experimental models, however, it has been difficult to simulate the mechanisms differentially, which has been one of the drawbacks to this argument. 3. EFFECTIVENESS OF REVACCINATION: Revaccination with BCG vaccine aims to restore or to endow immunological resistance through repeating vaccination to those who have partially or totally lost the immunity acquired from the primary vaccination. Although some animal experiments support the efficacy of revaccination with BCG, studies in humans have been rare and the results are variable. The observation of Polish infants and schoolchildren is suggestive of the efficacy, but it is not randomized and of questionable value. The recent study of Malawi is a randomized trial. It demonstrated that BCG revaccination protects against leprosy, but does not protect significantly against tuberculosis. It is possible, however, that it does protect against tuberculous lymphadenitis. The two above-mentioned possible mechanisms of BCG immunity were applied to a model analysis of BCG revaccination. It was known that revaccination effectiveness is very limited under any assumption, given the current Japanese epidemiological situation of tuberculosis, so that the demerits due to revaccination, such as strong local reactions, must not be neglected but should be carefully considered. At the same time, we should remember that this model analysis assumes that the primary vaccination is given to new borns with advanced and uniform techniques, which is not always true, and revaccination may supplement the technical failure of the primary vaccination. 4. DECIDING ON THE TOTAL DISCONTINUATION OF BCG VACCINATION PROGRAMME, JAPAN: The recommendations of WHO or IUATLD on the discontinuation of the BCG vaccination program are just conventional ones and the theoretical reasonings is difficult to accept. After all, the decision making should depend on the lay decision makers' subjective judgment balancing benefit and loss in terms of costs and health incurred by the policy, as shown by Waaler and Rouillon. The current Japanese BCG vaccination program is very expensive, but brings about some, though very small, benefit. This balance was compared with that of Sweden around 1975, when the program was discontinued. The comparison clearly showed that the cost-effectiveness of the program in Japan today in superior to that of Sweden in 1975.