The aim of modern Public Health Programmes, is a reduction in the total amount of disease in the community. The unit for treatment and cure is not an individual but a sick community. With this new aim, it becomes essential to know the size and extent of tuberculosis in the community as it will be helpful not for purposes of planning only but essentially for the assessment of their effect on the problem. An attempt is made to review the important features of the available knowledge about infection, morbidity and mortality through various surveys. (i) Prevalence of Infection: Tuberculosis infection is widespread in both urban and rural areas of almost all parts of the country. Nearly 40% of the population are infected. To avoid the effect of non- specific allergy and get a more reliable demarcation, tuberculin reactions of 14mm and more were considered as positive by National Tuberculosis Institute. (ii) Prevalence of morbidity: The prevalence of radiologically active tuberculosis in the population is likely to be 1.5%, Prevalence of bacteriologically confirmed diseases is 0.4%. Based on single sample of sputum examination, the prevalence of infectious cases in the country is probably an under estimate. About two million are infectious at any one point of time. (iii) Mortality: Deaths from tuberculosis in the country is not definitely known. The impression of clinicians that death due to tuberculosis have fallen sharply may not be true. Half a million deaths will appear an underestimate. About 250 per 1,00,000 persons i.e., one million deaths due to tuberculosis per year seems to be a reasonable estimate. (iv) Bovine Tuberculosis: Only a few cases in man caused by the bovine tubercle bacillus have been reported although 2.75% to 25% of cattle have been found tuberculin reactors.

To put in a nut shell, the problem of tuberculosis in India is a gigantic one and our means of fighting it with the single tool of BCG, do not even touch the fringe of the problem.

A study was undertaken with the following objectives: (1) To estimate the proportion of population that would be available for resurvey after 5 years. (2) To ascertain five years later the fate of persons with X-ray pathology. (3) To compare the prevalence of tuberculosis in the villages at an interval of 5 years. Population of 15 of the 31 villages from the Madanapalle zone, was selected for this study. About 9,500 persons were registered and 7,200 were X-rayed at the initial survey. Five years later the same population was re-examined and nearly 70% were available for X-ray examination. Sputa were collected from persons with abnormal X-ray shadows interpreted as such by either of the two readers. Two spot samples were collected within an interval of 1-3 days and were examined by direct smear and by culture.

Analysis of the data shadow showed that: (1) There was no significant difference in the prevalence rates i.e., 3.6 and 4.6 per thousand respectively at two points of time. (2) During the interval, 30% of active cases had died and 20% were still active at the end of 5 years. (3) There was almost complete turn over of the bacillary cases during the 5 years interval.

Survey with MMR remains as one of the most important methods available for measuring the size and extent of tuberculosis, specially in developing countries. Its value in case-finding programmes is well recognised. Nevertheless, mass miniature radiography with a single picture of the chest has a wide margin of error owing to the intra & inter-individual differences in X-ray reading. A study was undertaken to know the errors involved by repeating an X-ray picture after an interval of 3 to 4 months and judging the first picture in the light of a comparative reading of the two pictures. It is postulated that two pictures taken at an interval, may afford better judgement regarding the assessment of a case than a single picture only. A prevalence survey was carried out in Tumkur district in 1960-61, among 62 villages and 4 towns; 20 villages were selected for this study. A total of 8,000 persons were registered, 5,300 of them were X-rayed and re-read by two readers. Photofluorograms were repeated after three and a half months after the first picture. At the time of repeat X-ray, a spot sample of sputum was collected from persons with abnormal shadows.

Briefly the findings of the study were: (1) About 20% of bacillary cases were among those with inactive or non- tubercular shadows on the basis of a single X-ray film. (2) Inter-individual agreement for X-ray active cases was of the order of 50%. (3) Intra-individual agreement for X-ray active cases was 52% for one reader and 69% for the two readers. (4) Mass miniature radiography with a single film, in spite of its inherent limitations, is the best available method both for surveys as well as for case-finding programmes due to its ability to find cases as well as potential cases in a short time. (5) Even the agreement between two sputum samples collected within an interval of 1-3 days was 42% for positive results.

The objective was to establish the prevalence rates for tuberculosis infection, radiologically active pulmonary tuberculosis and bacteriologically confirmed diseases for different age and sex groups. Tumkur District in Mysore State consisting of 2,392 villages, 10 towns of was selected for the study. The district headquarter town Tumkur was excluded from the survey. Random sample of 62 villages and 4 town blocks having a population of 34,746 persons constituted the study population. All the individuals available in the registered population were given a Mantoux test with 1 TU RT 23 with Tween 80. Longitudinal diameter of induration was read 3-4 days after the test. At the time of tuberculin test, all persons aged 10 years and above were offered a single 70mm photofluorogram. For each picture read as abnormal, a spot specimen of sputum of the individual concerned was collected at the time of reading the tuberculin test. Age and sex distribution of infection and disease were studied.

Various parameters concerning the prevalence of infection and disease in the community were reported. Prevalence rate of infection in all ages and both sexes of the population was found to be 38.3%, radiologically active tuberculosis 1.86% and 0.41% sputum positive disease. The infection and disease increased with age; of the total diseased, half were in age group 40 years and more and about 2/3 among males.

Limitations of a single X-ray picture for locating and interpreting shadows in the chest had been studied earlier. In order to reduce these limitations, it was suggested that two pictures of each person be taken where the second picture was to be taken after a vertical displacement of X-ray tube, up or down by about 4 to 5cms. The advantages of taking two pictures simultaneously as compared to a single picture have not been studied so far. Two mobile X-ray units each with an odelca camera were alternated for the single and double picture examinations. A total of about 2,000 persons were X-rayed and were read independently by 3 readers. A spot sample of sputum was collected 3-4 days later from persons with abnormal X-ray shadows and was examined by direct smear microscopy.

Comparison of the readings of the two sets of pictures did not show a better agreement between different (inter- individual) readers or between two different readings of the same reader (intra-individual) when the two picture technique was used. The X-ray cases detected by double picture only by any one reader were not confirmed, more often than those detected by single picture only. The X-ray pictures of the bacillary cases were also not interpreted more often as active tuberculosis by the two picture technique. It was concluded that the double picture technique does not offer any advantage over the single picture technique.

The incidence of infection with mycobacterium tuberculosis is an index of the risk of infection to which a community is exposed. An accurate estimation of incidence rate is of considerable importance in understanding the epidemiology of tuberculosis in organising control measures. A new method of estimating incidence of infection is discussed. The material from 3 studies of National TB Institute has been utilized. Study I: is a part of a survey of a random sample of 134 villages. No previous tuberculin testing or BCG vaccination had been carried out in the area, but each person was examined for BCG scar in order to exclude persons vaccinated probably from other areas. After a complete census, a Mantoux test with 1 TU of PPD RT 23 with Tween 80 given on two occasions (Round I and II). Those with reaction of 13mm or less at Round I were offered a test with 20 TU with Tween 80 within a week of 1 TU test. The interval between the rounds was about 18 months. From the analysis of the data from the first 50 villages for which complete information for both rounds was available, it was seen that there was a general increase in the size of reactions elicited in the second round. Study 2: tuberculin testing was carried out with 1 TU and 20 TU among selected ‘control’ groups which provided the data regarding the “enhancing of tuberculin allergy” seen in repeat tuberculin tests. Study 3: in the course of the longitudinal “survey reader assessments” were carried out periodically to judge the standards of the tuberculin test readers. Inter & intra-reader comparisons were made. The findings have been used to estimate the magnitude of reader variation. The data was also used to study variations in the technique of testing and reading.

It was estimated that on an average inter & intra-reader variations between the rounds were unlikely to exceed 6mm or more in more than 5% of the observations. The reading errors have an equal chance of being positive or negative except at extreme ends of the distribution where zero readings of Round I can only show an increase, and the very large reactions had a greater chance of showing only a decrease at a subsequent round. The study mainly concerns with the problems of estimating the incidence of tuberculous infection in a community. Calculations based on age-specific prevalence rates or on rates of tuberculin conversion or both subject to gross error, leading to unreliable epidemiological conclusions. For estimating the newly infected, a new approach has been suggested based on the drawing of a curve for the distribution of differences in reaction size from one round of tuberculin testing to another. It is assumed that if new infection causes a distinct rise in the degree of tuberculin sensitivity which is greater than the combined rise due to enhancement and reader variation, the distribution of differences between the rounds should indicate the newly infected. It is shown that the newly infected probably constitute a homogeneous group with an increase in mean reaction size of about 24mm and standard deviation of 4mm. Accordingly, 98% of the newly infected show an increase in reaction size of 16mm or more.

Tuberculin tests repeated after an interval of time, at a different site have been reported to elicit reactions larger than the first test. A study was undertaken where reactors of 13mm or less to 1 TU have been tested with 20TU for the study of low grade reactions. Study was carried out in a previously untested and unvaccinated rural population (Longitudinal Survey), where only about 25% of the population showed 14mm or more to 1 TU and the remaining about 60% showed 10mm or larger reactions to 20 TU. These results confirm the high prevalence of non-specific allergy in the area.

It was found that a tuberculin test does enhance the allergy elicited by a subsequent test. The enhancing effect is associated with the initial allergy i,e., 8-13mm to 1 TU tuberculin, especially those elicited by a 20 TU test, increase being almost confined to those with 10mm and larger reactions to 20 TU. The enhancing effect increases with increase in age especially among those with 10mm or bigger reactions to 20 TU. It is possible that the enhancing effect is more in communities with high prevalence of non-specific allergy.

Studies on the distribution of tuberculous infection and disease in households have mostly been restricted to the examination of contacts of known cases. Clinical experience has lead to a strong belief that tuberculosis is a family disease and contact examination is a “must” for case-finding programmes. A representative picture of the distribution of infection and disease in households can be obtained only from a tuberculosis prevalence survey.

This paper reports an investigation, based on a prevalence survey in a rural community in south India. The survey techniques and study population have been described in an earlier report. Briefly, the defacto population was given a tuberculin test with 1 TU of PPD RT 23 with Tween 80 and those aged 10 years and above were examined by 70mm photofluorography. All the X-ray pictures were read by two independent readers. Those with any abnormal shadows by either of the two readers were eligible for examination of a single spot specimen of sputum by direct smear and culture. The defacto population numbered 29,813 and tuberculin test results were available for 27,115. After excluding BCG scars, the study population of 24,474 was distributed over 5,266 households which were further classified as “bacillary case household” with atleast one bacteriologically confirmed case, “X-ray case household” with atleast one radiologically active case but with no bacillary cases and ‘non-case household’ with neither a bacillary nor an X-ray case. Total bacillary cases were 77 and were distributed in 75 household. 74 households had one case each and one household had 3 bacillary cases.

The findings of the study have thrown considerable doubt on the usefulness of contact examination in tuberculosis control; (1) over 80% of the total number of infected persons, in any age group, occurred in households without cases, (2) cases of tuberculosis occurred mostly singly in households, and the chance of finding an additional case by contact examination in the same household is extremely small, (3) a common belief has been that prevalence of infection in children in 0-4 age group is a good index of disease in households, but in this study about 32% of households with cases of tuberculosis had no children in this age group, (4) in houses with bacteriologically confirmed case only 12% of the children in 0-4 age group showed evidence of infection, a possible explanation of such a low intensity of infection could be that there is resistance to infection. It is well known that some children even after repeated BCG vaccination do not become tuberculin positive. It is felt that a large number of children do inhale tubercle bacilli, but a primary complex does not develop or even if it develops, the children remain tuberculin negative. A hypothesis has been made that in addition to resistance to infection, there is something known as “resistance to disease”. Otherwise, it is difficult to explain why under conditions of heavy exposure in infection, only some individuals develop evidence of infection and very few develop disease thereafter.

The report describes the changes that occurred during second survey carried out after an interval of one and half years in the cases diagnosed at the first survey done during 1961-62 from among a total population of about 62,000 in 119 villages in Bangalore District. It was observed that (1) Of the 62 sputum smear positive cases also having suggestive chest X-ray shadows, 34% had died, 35% were sputum positive and 31% had become culture negative after 1½ years. Of the 10 smear positive cases who were X-ray normal, non-e was culture positive at the start and 7 were negative by culture and smear after 1½ years. Of the 67 scanty smear positive cases (1 to 3 bacilli seen), only 3 were sputum positive, 10 were having X-ray shadows and half were tuberculin negative after 1½ years. (2) Of the 88 culture only positive cases (20 or more colonies and with X-ray evidence of disease) 31% had died and 47% continued to be sputum positive after 1½ years. A much smaller proportion of these changes occurred among culture positive cases with less than 20 colonies. (3) There were 457 persons having radiologically active tuberculosis on the basis of interpretation of a single X-ray picture by two independent readers but whose sputum were negative for AFB (suspect cases). Of these, 38% were tuberculin negative also. Of those suspect cases who were tuberculin positive, 9% become sputum positive after 1½ years, while only 2% of the tuberculin negative suspect cases became sputum positive.

It is concluded that there is a lot of variation in fate among the different categories of cases of pulmonary tuberculosis. Further, attention has been drawn to the possibility of self healing in about 30% of the bacillary cases after 1½ years.

The material on resistant strains of mycobacterium tuberculosis is derived from the longitudinal survey conducted from 1961-68 in a random sample of 133 villages of 3 taluks of Bangalore district. About 54,000 persons aged five years or more were surveyed 3 times at an interval of 18 months, two samples of sputum were collected from persons whose chest X-rays were judged to have abnormal shadows. The sputum specimens were examined by direct smear and culture and sensitivity tests were performed.

An attempt is made to study prevalence, fate, source and infectivity of resistant mycobacterium tuberculosis in three rounds. PREVALENCE: In the 3 rounds, 199, 194 and 176 cases respectively yielded positive cultures; Of them, 30, 36 and 53 cases were having resistant strains. At round III, the number of culture positive cases has not fallen significantly, but the number of strains resistant to INH alone has sharply increased (13, 18 & 35). Both findings are likely to be due to the treatment with INH alone offered at round II and also due to the fact that treatment was taken very irregularly. FATE: Over period of 3 years, of the cases with INH resistant strains, more than 1/3rd were dead, 1/4th continued to remain positive and resistant, and 1/4th became culture negative. Whereas, of the cases with strains sensitive to INH, less than 1/3rd were dead, 1/3rd became negative and the remaining were positive, 1/2 with sensitive strains and 1/2 with resistant strains. SOURCE OF CASES: The prevalence of cases with resistant strains at any one round is not due to the persistence of such cases from previous rounds but by development of new cases with such strains at each round. INFECTIVITY: The incidence of infection among contacts with sensitive strain was significantly more than among the contacts of cases with resistant strain. It is inferred that the infectivity of sensitive strains is more than that of the resistant strains.

Generally there is no acceptable definition of the term “case of pulmonary tuberculosis”, although such a definition is of fundamental importance both in clinical medicine where results of various chemotherapeutic regimens are compared, as well as for the comparison of different epidemiological data. The main purpose of this paper is to focus attention on the difficulties of defining a case on the basis of bacteriological examination, X-ray examination and tuberculin test. Data from two successive prevalence surveys in a random sample of 134 villages in Bangalore district with a population 70,000 have been utilized to illustrate some of the difficulties in defining a “case” of pulmonary tuberculosis for reporting the prevalence or incidence of the diseases. The entire population was tuberculin tested with 1 TU RT 23 with Tween 80 at both rounds and those 5 years of age and older were examined by 70mm photofluorogram. The sputum specimens (spot and overnight) were collected from those with any abnormality on X-ray as recorded by either of the two independent readers. Both the specimens were examined by fluorescent microscopy and Ziehl-Neelsen technique and by culture.

Analysis of data has shown that the term “a case of pulmonary tuberculosis” does not represent a single uniform entity, but embraces cases of several types, differing considerably in their tuberculin sensitivity, results of X-ray and sputum examination, in the reliability of their diagnosis and mortality experience. The status of cases found at initial and subsequent surveys showed changes with time, and such changes show considerable differences for the various types of cases. It was felt that a single straight-forward definition of a case was not possible to suit all situations. One has to use more than one definition. Although theoretically, finding a single bacillus in sputum should be adequate proof of pulmonary tuberculosis, it was shown that finding of a few bacilli (3 or less) was very often due to artifacts and should not be the basis for a diagnosis. It has also been found that positive radiological findings, in the absence of bacteriological confirmation, indicate only a high risk of the disease and not necessarily pulmonary tuberculosis. Direct microscopy appears to be a consistent index of disease but in community surveys has the limitation of missing a substantial proportion of cases and of adding some false ones.

In view of the difficulty of providing a single definition of a case of tuberculosis, four indices have been suggested. (1) Cases definitely positive by direct smear; (2) Cases definitely positive by culture; (3) All cases positive by culture (including less than twenty colonies); (4) Sputum positive cases which are radiologically active. Each of these could be used for different situations. However, it was concluded that, there seems to be no option but to use more than one definition for assessing the prevalence and incidence of disease.

The degree of the risk of infection and disease in man from drug resistant strains of mycobacterium tuberculosis is not clear. An increase in the prevalence of primary resistance indicates the extent of such risk while an increase of secondary or acquired resistance could be considered as a problem of the individual patient and may reflect limitations of his treatment.

The present report describes the prevalence of strains with acquired or primary resistance or of sensitive strains found in 3 successive surveys in a sizable random sample of village in a south Indian district. Changes in the status of cases with such strains from one survey to another and their infectivity among household contacts are also described. The prevalence of tuberculosis infection among household contacts of cases with acquired resistance to isoniazid was significantly higher than those with primary resistance or with sensitive culture. This was probably due to the longer duration of sputum positivity of isoniazid resistant strains at the time of diagnosis. But infectivity as judged by the incidence of new infection among household contacts was generally less for cases with acquired or primary resistance than for cases with sensitive cultures, though the difference observed was not statistically significant. A large number of culture positive cases especially those with primary resistance had no radiological evidence of active pulmonary tuberculosis. The prevalence of primary resistance was high in certain categories of cases and the differences between cases with primary resistance and those with acquired resistance were many and large. It was suggested that this could be due to the primary resistant cultures being those of atypical mycobacteria, despite positivity in the niacin test. There was a significant increase in the number of cases with acquired resistance to isoniazid at the third survey owing to the irregular treatment and supply of INH alone after the second round. The prevalence of primary resistance at the three rounds was almost the same.

Enhancing effect of tuberculin allergy as a result of repeat tests with 1 TU RT 23 on groups tested with I TU, 20 TU and placebo was studied by random allocation among population not vaccinated with BCG in 8 villages. In all, 2357 persons were tested with 1 TU and 759 with normal saline at first round. Based on testing at three rounds the study population could be divided into eight different groups and were labelled with alphabets 'a' to 'h' having been tested once, twice or thrice. The groups 'a', 'c', 'e' & ’g' were tested at 2 months, round two with 1 TU RT 23 and remaining half were not tested. However, all available persons in the 8 groups were retested at the third round, 18 months after the initial test. Thus, eight groups cannot be treated as independent samples but representative of the whole population.

The study did not show enhancing effect due to previous tuberculin test with 1 TU alone among groups tested once, twice or thrice after an interval of 18 months. Part of population was tested with 20 TU at round one; boosting effect was seen at 2 months when test was repeated. However, it was not seen after 18 months but when exactly the boosting effect disappeared was not known. Thus, there was no increase in reaction even among those who were tested with a higher dose of 20 TU earlier after 18 months. The groups provided the largest number for comparison between tested and the control groups. It is inferred from the study that boosting with high dose or repeat tests with the same dose does not persist after 18 months. Hence, for classifying positive tuberculin reactors, no correction is required to the same individuals/population after an interval of 18 months or more, as no boosting effect after 18 months has been observed, on the basis of this analysis.

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.