Howard Fischer
Uppsala, Sweden

 

Early French advertisement for BCG (“BCG Protects Against Tuberculosis”). Retouched crop of photo by Rathfelder on Wikimedia. CC BY-SA 4.0.

“Perseverance, secret of all triumphs.”
– Victor Hugo

 

Tuberculosis of the lungs (“consumption”) was one of the two main causes of death (along with pneumonia) at the start of the twentieth century.¹ In the US, pulmonary tuberculosis killed 194 persons per 100,000 in 1900.² In one Missouri hospital, nearly 25% of patient deaths were attributed to tuberculosis.³

An infection caused by a bacillus, Mycobacterium tuberculosis, the disease progressively destroys lung tissue, lung function, and general health. Tuberculosis (TB) killed many infants younger than one year of age if their mother or another household member was infected. In 1922, 24% of French babies, 32% of Parisian infants, 22% of Belgian infants, and up to 70% of infants in Stockholm died before one year of age under these conditions. After one year of age, the risk of a childhood tuberculosis-caused death was less than two percent.⁴

In 1906, Drs. Albert Calmette (1863–1933) and Camille Guérin (1872–1961) demonstrated that giving a small quantity of TB bacillus to cows produced pulmonary TB, which would later resolve, giving the animals immunity from reinfection. Two doses of the bacillus, however, produced infection that did not resolve. Their idea was to expose an animal as early as possible, one time, with a live, non-virulent bacillus. To accomplish this, they needed to create a live TB bacillus without virulence for any animal species. They accomplished this after thirteen years of work, passing a bovine TB bacillus successively 230 times in a specially devised culture medium. They wrote that “we were able to convince ourselves” that the vaccine injected intravenously or intraperitoneally into rats, rabbits, and guinea pigs was “perfectly inoffensive” but highly antigenic, allowing the animal to produce large amounts of antibody.⁵

The vaccine, known as BCG (for bacille Calmette-Guérin) was given to 21,200 children between 1924–1927. Only 1% of vaccinated children between the ages of one and two died from TB when there were cases of TB in the child’s household. Vaccinated children older than two years had no TB deaths. They proceeded to give BCG vaccine to newborns of mothers with symptomatic, active TB and saw a 1.9% mortality rate among the infants. This was an impressive improvement from the 20% or more mortality rate in 1922.⁶ Calmette and Guérin also saw no reason to think that the BCG bacillus would later revert to a virulent type.

Nearly one hundred years later, BCG is still a valuable vaccine. Its protection may last for decades if a later booster dose is given. The World Health Organization recommends BCG vaccine for all infants “soon after birth” in countries or communities with a high burden of TB. BCG should not be given to infants with HIV (human immunodeficiency virus) infection, but should be given if the mother’s HIV status is unknown.⁷ BCG is also used as immunotherapy to treat early-stage bladder cancer. In addition, a study showed that patients thus treated had lower rates of Alzheimer’s disease.⁸

Tuberculosis, despite the existence of this effective vaccine, is still a major problem. Partly because of public health authorities’ complacency as TB rates began to fall, and partly due to increased susceptibility in people with HIV infections, there are 7.6 million people infected with TB in the developing world, and one half million in the industrialized world.⁹

 

References

1. Susan Speaker. “Revealing data: Collecting data about TB, ca. 1900.” Circulating Now from NLM Historical Collections, January 31, 2018.
2. Gordon Snider. “Tuberculosis then and now: A personal perspective on the last 50 years.” Ann Intern Med, 126(3), 1997.
3. Office of the Secretary of State, Missouri. “Quest for a cure. Care and treatment in Missouri’s first state mental hospital: 1900-1960: Tuberculosis.” Missouri State Archives, 2003. https://www.sos.mo.gov/archives/exhibits/quest/treatment/1900-1960tb.
4. Albert Calmette, Camille Guérin, et al. “Sur la vaccination preventive des enfants nouveau-nés contre la tuberculose par le BCG.” Annales de l’Inst Pasteur, 3, March 1927.
5. Calmette et al, “Sur la vaccination.”
6. Calmette et al, “Sur la vaccination.”
7. Precision Vaccinations. “Bacille Calmette-Guérin (BCG) vaccine 2023.” https://www.precisionvaccinations.com/vaccines/bacille-calmette-guerin-bcg-vaccine-2023
8. Precision Vaccinations, “Bacille Calmette-Guérin.”
9. Snider, “Tuberculosis then and now.”

 

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HOWARD FISCHER, M.D., was a professor of pediatrics at Wayne State University School of Medicine, Detroit, Michigan.

 

Summer 2023  |  Sections  |  Infectious Diseases