BCG vaccination remains an essential part of tuberculosis (TB) prevention strategy, especially in children. BCG is generally considered to protect against tuberculous meningitis and military and disseminated forms of TB among infants and young children. The efficacy against non-serious forms of TB has been a matter of debate with various studies showing it to be in range from 0 to 80%. Protective efficacy of BCG has been assessed by various methods, including tuberculin sensitivity. Positive tuberculin response after BCG vaccination has been considered to be an important marker of successful vaccination.

Historical background and past knowledge: BCG vaccine was named after two famous French scientists – Albert Calmette and Camille Guérin. The history of BCG vaccine dates back to 1900 when Calmette and Guerin started their research at Pasteur Institute, Lille. In next 20 years, they successfully completed the trials in animals. In 1921, BCG was given first time to a human. It was delivered by Dr Weil Hale to a baby whose mother died of tuberculosis few hours later. The vaccine was given orally and baby grew to a healthy boy with no signs of tuberculosis. From 1921-1924, 317 more infants were vaccinated. By 1928, Calmette released multiple reports showing BCG to be effective; although, the medical media had lot of criticism on the figures displayed in the reports. BCG got a major setback after the Lübeck disaster where 72 of 252 children died of tuberculosis within one year of vaccine. Though later, the cause was found to be contamination with a virulent strain at the local laboratory where the vaccine was made ready for administration [2].

The controversies kept persisting till BCG vaccine once again came into use after resurgence of tuberculosis after Second World War. Since then multiple studies were conducted across the world to assess the efficacy of BCG vaccine and found to be varying between no benefit to as high as 80% protection. The cause of this large variation is still not understood. Simultaneously, multiple countries started producing its own supply maintaining same stringent conditions as at the Pasteur institute [2].

Robert Koch, in 1890, first time described the tuberculin hypersensitivity at the site of injection of heat-killed tubercle bacilli. The work was further expanded by Von Pirquet in 1909. Tuberculin sensitivity test, further known by Mantoux test, first came into use in 1912 after the intradermal technique introduced by Charles Mantoux, a French physician who developed on the work of Von Pirquet. Further in 1939, Seibert prepared a large lot of PPD (lot 49608), which then became the reference standard for the US Public Health Service’s Bureau of Biologics Standards. It was further renamed as PPD-S (standard), and was adopted as International standard by WHO. By convention, 5 TU is the bioassayable skin test activity contained in 0.0001 mg of PPD. RT-23, another PPD prepared by Statens Serum Institute was introduced by WHO in 1958 [3].

The tuberculin reaction is read after 48 hours and needs an incubation period of 2-12 weeks after infection by M. tuberculosis to develop sensitivity. The reaction to intradermally injected tuberculin is the classic example of a delayed (cellular) hypersensitivity reaction. T-cells sensitized by prior infection are recruited to the skin site where they release lymphokines. These lymphokines induce induration through local vasodilatation, edema, fibrin deposition and recruitment of other inflammatory cells to the area.

Though tuberculin test has been considered as one of the criteria to show successful response to BCG, the wide variation in response has made it less dependable. A study by Faridi, et al. [9] shwed leucocyte migration inhibition test to be positive in 84.1% of babies who received BCG vaccine within 7 days of birth and found to have negative Mantoux at 3 months of age.

Regarding efficacy of BCG, in a recent systematic review and meta-analysis, Roy, et al. [10] reviewed all studies done to compare the infection rates with M. tuberculosis in vaccinated and unvaccinated children (age <16 y) with recent exposure to patients with pulmonary tuberculosis. The analysis included 14 studies with 3855 participants. Interferon gamma release assays were used for assessing the infection. They found that the overall risk ratio was 0.81 with protective efficacy of 19% against infection among vaccinated children after exposure compared with unvaccinated children.

In the nutshell, the diagnostic accuracy of tuberculin skin test for BCG uptake, as well as the efficacy of BCG for protection of tuberculosis, still remain controversial; however, both of these continue to be used widely in absence of better alternatives.

1. Dabral S, Ghosh S, Taneja PN. Tuberculin conversion after B.C.G. vaccination in neonatal period. Indian Pediatr. 1969;6:84-8.

2. TB Facts. Available from: https://www.tbfacts.org/bcg/. Accessed January 5, 2019.

3. Lee E, Holzman RS. Evolution and current use of the tuberculin test. Clin Infect Dis. 2002;34:365-70.

4. Dhanawade SS, Kumbhar SG, Gore AD, Patil VN. Scar formation and tuberculin conversion following BCG vaccination in infants: A prospective cohort study. J Family Med Prim Care. 2015;4:384-7.

5. Camargos P, Ribeiro Y, Teixeira A, Menezes L. Tuberculin skin reactivity after neonatal BCG vaccination in preterm infants in Minas Gerais, Brazil, 2001-2002. Pan Am J Public Health. 2006;19:403-7.

6. Colditz GA, Berkey CS, Mosteller F, Brewer TF, Wilson ME, Burdick E, et al. The efficacy of bacillus Calmette-Guérin vaccina-tion of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature. Pediatrics. 1995;96:29-35.

7. Karalliede S, Katugaha LP, Uragoda CG. Tuberculin response of Sri Lanka children after BCG vaccination at birth. Tubercle. 1987;68:33-8.

8. Sedaghatian MR. Shana’a IA. Evaluation of BCG at birth in the United Arab Emirates. Tubercle. 1990;71:17780.

9. Faridi M, Kaur S, Krishnamurthy S, Kumari P. Tuberculin conversion and leukocyte migration inhibition test after BCG vaccination in newborn infants. Hum Vaccin. 2009;5:690-5.