BCG VACCINES FOR THE PREVENTION OF TUBERCULOSIS IN THE WORLD

Tatsuichiro HASHIMOTO

The BCG vaccines will celebrate the 100th anniversary of their discovery in a decade at the beginning of the next century since Albert Calmette and Camille Guerin had presented it before the Academie des Sciences in 1908. At present tuberculosis kills more people than any other infectious disease about 3 million people a year, including almost 300,000 children under 15, and is producing over 7,000 deaths and over 24,000 new cases every day. Therefore, WHO declared a global health emergency in 1993. More worse, recently multi-drug resistant tubercle bacilli are emerging rapidly making TB patients incurable. Under these situations we need a potent anti-tuberculosis vaccine. So first of all, we must check the century-old BCG before proceeding further. At moment, the BCG vaccines are being used worldwide in the largest quantities in the world, but still most controversial vaccines anywhere. I would like to describe here their success and failure in the combat against the white plague. 1. The Expanded Programme on Immunization (EPI). In 1974, when the EPI was launched by WHO, less than 5% of the world children were immunized against six infectious diseases including tuberculosis. In 1995 statistics, BCG gave the highest vaccination coverage, 87% higher than any other 5 vaccines of EPI for children. The BCG in EPI must have saved a lot of infants as the vaccine, has been proved to be most effective against the blood-born tuberculosis of child type. 2. The efficacy of BCG vaccination against tuberculosis. Results of each 10 of randomized controlled trials (RCT) and Case-control studies (CCS) showed the protective efficacy against tuberculosis as uncertain, unpredictable, as protective efficacy varied from 80% to 0%. More recently, a Meta-analysis of selected papers on BCG field trials which were so far collected. They recalculated vaccine protective effect separately for pulmonary TB and for meningeal/miliary TB in the trials. As the result, it was found that protective effect against pulmonary TB could not be calculated, but protective effect against meningeal and miliary TB was calculated as 86%, 75% respectively, in RCT and CCS, being higher than against pulmonary TB. 3. The duration of BCG efficacy against tuberculosis was confirmed to continue for 15 years after vaccination. The incidence of every form of tuberculosis decreased steeply during the 15 years following vaccination. 4. BCG revaccination. A WHO statement was issued in 1995 mentioning that there is no definitive evidence that repeated BCG vaccination confers additional protection against tuberculosis. Therefore WHO has not recommended to repeat BCG vaccination because of no scientific evidence to support this practice. Multiple BCG revaccinations are not indicated in any persons. 5. Complications with BCG Second IUATLD study (1988) on complications induced by BCG was reviewed, especially following two points: 1-2) Regional suppurative lymphadenitis 3) Generalized lesions: fatal cases 1-2 Several African regions had experienced that the risk of outbreak of suppurative BCG lymphadenitis was low for vaccines with Glaxo and Japanese strains, but much higher for vaccines with Pasteur. This experience in nineteen eighties has led EPI to replace the Pasteur BCG vaccine with less reactogenic BCG, Japanese or Glaxo BCG to solve the outbreak of suppurative adenitis complication. 3 At moment, the only contra-indication of EPI BCG vaccination is symptomatic HIV infection (AIDS), but in the future asymptomatic HIV infection should be placed on alert, because fatal BCG generalized disseminations have already been experienced by HIV positive vaccinees although in a few cases in USA. 6. BCG seed lots for use of vaccination in the world. Nearly 10 seed lots (BCG) are being used in the world at present. However, they are more or less different each other in various characteristics: morphological, biochemical, biophysical, immunological, vaccinological and so on. None of them is the same