Bacillus Calmette–Guérin - History

History

The history of BCG is tied to that of smallpox. Jean Antoine Villemin first recognized bovine tuberculosis in 1854 and transmitted it, and Robert Koch first distinguished Mycobacterium bovis from Mycobacterium tuberculosis. After the success of vaccination in preventing smallpox, scientists thought to find a corollary in tuberculosis by drawing a parallel between bovine tuberculosis and cowpox: It was hypothesized that infection with bovine tuberculosis might protect against infection with human tuberculosis. In the late 19th century, clinical trials using M. bovis were conducted in Italy with disastrous results, because M. bovis was found to be just as virulent as M. tuberculosis.

Albert Calmette, a French bacteriologist, and his assistant and later colleague, Camille Guérin, a veterinarian, were working at the Institut Pasteur de Lille (Lille, France) in 1908. Their work included subculturing virulent strains of the tubercle bacillus and testing different culture media. They noted a glycerin-bile-potato mixture grew bacilli that seemed less virulent, and changed the course of their research to see if repeated subculturing would produce a strain that was attenuated enough to be considered for use as a vaccine. The research continued throughout World War I until 1919, when the now avirulent bacilli were unable to cause tuberculosis disease in research animals. They transferred to the Paris Pasteur Institute in 1919. The BCG vaccine was first used in humans in 1921.

Public acceptance was slow, and one disaster, in particular, did much to harm public acceptance of the vaccine. In the summer of 1930 in Lübeck, 240 infants were vaccinated in the first 10 days of life; almost all developed tuberculosis and 72 infants died. It was subsequently discovered that the BCG administered had been contaminated with a virulent strain that was being stored in the same incubator, and led to legal action being taken against the manufacturers of BCG.

Dr. R.G. Ferguson, working at the Fort Qu'Appelle Sanatorium in Saskatchewan, was among the pioneers in developing the practice of vaccination against tuberculosis. In 1928, BCG was adopted by the Health Committee of the League of Nations (predecessor to the WHO). Because of opposition, however, it did not become widely used until after World War II. From 1945 to 1948, relief organizations (International Tuberculosis Campaign or Joint Enterprises) vaccinated over 8 million babies in eastern Europe and prevented the predicted increase of TB after a major war.

BCG is very efficacious against tuberculous meningitis in the pediatric age group, but its efficacy against pulmonary tuberculosis appears to be variable. As of 2006, only a few countries do not use BCG for routine vaccination. The USA and the Netherlands have never used it routinely. In both countries, BCG vaccination is not routinely given to adults because it is felt that having a reliable Mantoux test and being able to accurately detect active disease is more beneficial to society than vaccinating against a relatively rare (in those countries) condition.

Recent research by the Imperial College London has focused on finding new cell wall proteins which trigger an immune response and are suitable for use in a vaccine to provide long-term protection against M. tuberculosis. The study has revealed a few such proteins, the most promising of which has been dubbed EspC; it elicits a very strong immune reaction, and is specific to M. tuberculosis.