In all, 1,259 students aged 11-19 years from three boys high school of Bangalore, formed the study group. They were tuberculin tested with 1 TU RT 23 containing Tween 80. Boys with a reaction of 13 mm or less to tuberculin test and willing for BCG vaccination were allocated in 3 groups: (i) to be vaccinated with Madras vaccine (211), (ii) to be vaccinated with Danish Vaccine (236), (iii) control with saline injection (231) (placebo). Strength of Madras and Danish vaccines used was same, 0.075 mg per dose. After 3 months of vaccination, second tuberculin test with 1 TU RT 23 with Tween 80 was given to 575 boys included in both the vaccinated groups and in the control group. A follow up at one year after vaccination was done among 328 boys, who were again tuberculin tested.

The analysis of data shows that the mean size of post-vaccination tuberculin test induration among Madras BCG vaccinated group was 11.8 mm and among Danish BCG vaccinated group, it was 11.9 mm, the standard deviation were 3.8 and 4.5 mm respectively. The above differences between the 2 vaccinated groups were not-statistically significant. Similarly, the post-vaccination allergy in the two BCG vaccinated groups at the end of one year was not-significantly different. The mean size of the scar produced by two vaccines were also smaller. The post-vaccination allergy among persons whose pre-vaccination tuberculin induration was 9 mm or more to 1 TU RT 23 with Tween 80, did not increase by more than 4 mm after vaccination. While the group whose pre-vaccination tuberculin induration was below 9 mm, had an increase of post-vaccination allergy of a little over 8 mm. It is concluded that the allergy producing capacity of the Danish and Madras vaccines was not different.

Liquid BCG vaccine produced upto 1955 at the BCG Laboratory, Guindy, Madras induced low and variable levels of post-vaccination allergy. However, subsequent to improvement in production, its potency was adjudged as equivalent to Danish BCG vaccine. Later on, lower levels of post-vaccination allergy in Mass BCG vaccination campaign and in research studies were observed. A study was planned to compare the Madras BCG vaccine with Danish vaccine in terms of the potency of the strains, production efficiency of the laboratory and stability on storage. This was done by comparing the allergising capacity and size of vaccination lesions. On a predetermined date in each of four consecutive months, both laboratories supplied to the Research Team one week of fresh vaccines from their respective BCG strains and also fresh vaccine of strains borrowed from the other laboratory. With these six vaccines every month, in two consecutive weeks randomly, vaccinations were given to 2,978 tuberculin non-reactors. post-vaccination allergy was elicited 10 weeks later when size of BCG lesion was also noted. Viable counts on all vaccines were done by Madras Laboratory.

Though the Indian and Danish BCG vaccines induced similar levels of allergy, on further analysis it was found that Madras BCG strain was inferior to the Danish strain and that Madras Laboratory produced better vaccine than Copenhagen Laboratory. The vaccine produced from Copenhagen strain in Madras Laboratory induced the highest level of allergy. The stability of vaccines produced from Madras strain was found to be unsatisfactory. Results according to vaccination lesion size and their correlation with tuberculin reaction more or less confirmed the above findings. They were however not corroborated in terms of viable counts. Considering that the inferior quality of Madras BCG strain was due to mutation over time, seed lots of suitable BCG strain would ensure uniformly potent vaccine from Madras Laboratory.

Even though BCG has been in use for last 60 years, it has always been the subject of controversy, as several scientific studies done all over the world showed the protective value of BCG varying from 0 percent to 80. Because of the controversy over its protective effect and its extensive use in India it was felt necessary to undertake further field trials, wherein all shortcomings of previous trials could be eliminated. The Government of India took the decision to undertake a BCG trial in India. In 1968, the study was carried out in Chingleput district in Tamil Nadu, where no BCG vaccination was previously offered. The objective of the study were to obtain i) precise estimate of the protective effect of BCG vaccination against tuberculosis in the non-infected, ii) effect of BCG vaccination in persons already infected and iii) protective effect of different strains of BCG and iv) epidemiological data on tuberculosis in the community. The entire population of 3,60,000 persons were registered during a period of two and a half years of intake. All the persons aged one month and above were randomly divided into three main groups. One group vaccinated with the Madras vaccine, the second with Paris vaccine and the third with Placebo. At the same time all persons were tested with tuberculin, those above 10 years and above were X-rayed and those having X-ray shadows were examined by direct smear and culture. The study population was systematically and intensively followed up by X-ray and sputum examinations to diagnose all the new cases occurring in the community. The protective effect of BCG vaccination is defined as the proportionate reduction in the occurrence of new cases among the vaccinated, initially tuberculin negatives as compared to a similar but unvaccinated group. The protective effect was studied among individuals who were not previously infected, who had no tuberculosis at the time of vaccination and who were either vaccinated or left unvaccinated. The results of 7½ years of follow up showed that the number of new cases that occurred among the group vaccinated by either of the vaccines or from the unvaccinated group were similar. This showed that BCG vaccination did not offer any protection against tuberculosis of the lung. The epidemiological characteristics of the population were high prevalence and incidence of tuberculosis infection and disease and high prevalence of non- specific sensitivity. The risk of manifest disease for this recently infected was relatively small, as most of the new cases occurred among those who were tuberculin positive at the time of intake and not from those who were not infected then. Implications : Several expert committees appointed both by the authorities in India and by the WHO have examined all the procedures followed up in the study and came to the conclusion that the study had been meticulously carried out and vaccine used in the trial were the best available ones. The implications of this study was 'should BCG vaccination be given up in India?' Yet another committee appointed jointly by ICMR and the WHO went into the epidemiological aspects of the causation of tuberculosis under Indian conditions and concluded that BCG may not protect against tuberculosis of lung which occurs mostly in adults; it could provide substantial protection against childhood form of tuberculosis such as tubercular meningitis, tuberculosis of bones & joints etc. The protective effect of BCG against these forms of tuberculosis was not studied in Chingleput Trial. In India BCG vaccination is recommended to be given at an early age preferably before the end of the first year after birth.