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.

Prevalence surveys are useful for estimating the tuberculosis problem in different countries. Three techniques are commonly used in surveys, tuberculin test, mass miniature radiography and sputum examination. Each has its own limitations. A limitation of sputum examination is that all the sputum positive cases in the community cannot be diagnosed when only one sample of sputum is examined from each eligible person. Multiple sputum examinations are not often possible under field conditions of surveys covering the whole community. It would be worthwhile to have some idea of the extent of under-diagnosis in sputum examination. For this purpose, during an epidemiological survey, four specimens of sputum were collected within seven days of X-ray examination from each person with an abnormal chest X-ray in 30 villages of a district of south India. Each specimen was examined by Fluorescent Microscopy (FM), Ziehl Neelson (ZN) technique and culture.

There were 34 culture positive cases among 2,164 persons for whom all the four culture examination results were available. Of them, 21 (62%) were found positive on one specimen. The second specimen increased the positivity to 32 (95%). Thus, for detecting both smear and culture positive cases two specimens are adequate. A third specimen is helpful for detecting cases positive by culture alone. An estimate of prevalence obtained from one sputum specimen can be estimated for the prevalence obtained from many specimens by applying correction factor of 1.67 and estimates based on two specimens by applying 1.26. Of the remaining 37 smear positive cases detected by one specimen, 20 were smear positive and culture negative. Of the remaining 17 smear positive and culture positive, 14(82%) were detected by one smear examination only.

ZN positives not confirmed by culture (mostly with less than four bacilli reported in the smear) increased from 7 from the first specimen to 18 from all four specimens, while positives confirmed by culture method showed only a marginal increase from 13 to 15. FM did not have this disadvantage as only two were culture negative among the 18 smear positive results by FM method. Examination of two specimens by FM detected about 95% of cases demonstrable by this method. But with the ZN technique additional specimens may add more “false positives”. Thus, for detecting cases both smear and culture-positive two specimens appear adequate. A third specimen is helpful for detecting cases positive on culture only.

Data from 62 randomly selected villages in a district of south India, which formed part of a prevalence survey carried out by the National Tuberculosis Institute, Bangalore, during 1960-61, has been made use of. The survey covered 29,813 persons in 5,266 households. There were 70 cases with bacilli demonstrable either in smear or culture and 300 suspect cases. Using the village map (prepared by survey staff), ‘case clusters’ were formed first, with each case household as nucleus and adjacent households within a maximum distance of about 20 meters on either side of the case households. Households closest to the nucleus household on either side have been called as 1st neighbourhood and those coming next in proximity on either side as a 2nd neighbourhood and so on. The case household and its four neighbourhood together was called a cluster. If another case household was found within 4th neighbourhood of the first case the cluster was extended by including the 4th neighbourhood of the new case also. Such clusters were called composite case clusters and clusters with only one case household as simple case clusters. Similarly, suspect case clusters were formed and differentiated as simple suspect clusters or composite suspect clusters. Further, to serve as a control group, non-case clusters were constituted from a systematic sample of 10% households that were not included in case or suspect case clusters.

Out of 60 case clusters formed, only 7 have multiple cases showing that there was no evidence of high concentration of disease in case clusters. While the percentage of child contacts (0-14 years) infected was considerably higher in case clusters (25.8%), there was not much difference between suspect case clusters (14.9%) and non-case clusters (9.8%). Similarly, there was not much difference between simple and composite clusters. Infection among child contacts was higher in case households as compared to their neighbourhoods. To get some idea of the zone of influence of a case or suspect case, prevalence of infection was studied for 10 neighbourhoods, in simple clusters to avoid the influence of multiple cases. It appeared that the zone of influence of a case may extend at least upto the 10th neighbourhood. It was also noted that there was very little difference between zones of influence of suspect cases and non-cases. Case clusters in which the nucleus case had shown activity of lung lesion (evident on X-ray reading) or had cough showed significantly higher infection among child contacts. Clusters around cases positive on both smear and culture did not show higher infection than those around cases positive on culture only. (This may be due to sputum examination of single specimen only).

Out of the total infected persons in the community, only 2% were in case households and 7% in suspect case households, over 90% being in non-case households. The zone of influence of a case extending at least upto the 10th neighbourhood and the overlapping of such zones of influence of cases, present and past, seems to be the most probable explanation for the wide scatter of infection in the community. Prevalence of infection among child contacts was definitely higher in case clusters. But, the significance of this could be understood only from a study of the incidence of disease during subsequent years in different types of clusters. It is significant that only 10% of the total infected persons in the community were found in case clusters. The case yield in general population, cluster contacts, household contacts and symptomatics attending general health institutions have been also compared. The case yield in the last group (10%) is much higher than the case yield from both types of contacts (0.7% and 0.6%) which where only slightly higher than the case yield from the general population (0.4%).

During a longitudinal survey, carried out in 119 randomly selected villages of Bangalore district for studying the time trend of tuberculosis, the average infectivity of a case over a period of one and a half years was found to be six. In 1986 i.e., 25 years after the start of I survey, 61 persons belonging to one village called Nunnur who were found newly infected between I & II surveys, were interviewed. Further, a general study of the layout of the houses and public facilities in the village was made. However, in Nunnur, there was just a single bacteriological case (index case) identified at the I survey. This index case was resident of household numbered 80 in the main village. This case study investigates the background of the observed high infectivity. The incidence rate of infection in Nunnur was 9.5% in 1½ years which is higher than the overall average rate of 4% as well as rate for 30 other single case villages i.e., 3.5%. The investigation reveals that at least 21 persons., found newly infected at II survey, had varying levels of contact with the index case. The remaining 40 infected persons could not be linked, either directly or indirectly, to any other known bacteriological case including the index case in the village. All the persons identified as infected at II survey were distributed throughout the village, beyond the likely zone of infection of the index case.

Feasibility of introducing limited active case-finding in tuberculosis involving Multi-purpose Health Workers (HWs) to supplement the existing methodology of detecting the cases through chest symptomatics attending Peripheral Health Institutions (PHIs) on their own, was studied earlier with encouraging results. The present study was undertaken to understand the existing working system of HWs and within that the priority areas of input which may lead to better case yield.

The study revealed that the population available at any beat schedule of HWs was about 42% of the eligible population of age 20 years and above. Only 60-75% of the field days were utilized for routine multi-purpose duties. Of the total area, 25% to 40% remained uncovered. The effective tuberculosis work was done only on 5% of the beat schedule days and the work was not uniformly spread throughout the month. Even so, the contribution by HWs was twice the number of cases diagnosed at PHIs under study in one year. Had the HWs covered the entire area of their beat schedule, 80 against 26 cases would have been diagnosed. Moreover, there is possibility of detecting more cases among the elderly patients who normally do not attend their area health centres. However, the success depends upon meticulous supervision and regular flow of supplies.

Radiography is a commonly used diagnostic tool for diagnosis of tuberculosis. It is still widely believed that tuberculosis of the lung can be diagnosed by chest radiography alone. However, practical experience and number of studies have proved beyond doubt that no radiographic picture or pattern is absolutely diagnostic or typical of tuberculosis. There are many conditions of the lung which show similar radiographic appearance and can easily be mistaken for tuberculosis. On the otherhand, in a substantial percentage of bacteriologically confirmed cases, radiological picture either did not show a shadow or was judged as non- tuberculosis. Lesions being hidden behind other shadows e.g., of the ribs etc. may be one of the reasons. A comparison of large X-ray with MMR indicates that large X-rays are easily readable and have low radiation dose but are more expensive and occupy more space. The paper critically discusses the reliability of chest radiography also. The concluding remarks are as follows: 1) 20% of lung fields are hidden behind bones, heart, soft tissues, etc. 2) Activity of an X-ray lesions cannot be determined on the basis of single X-ray picture. Even sequential X-rays or repeated serial X-rays of the patient over a period of time have their limitations and is not fool proof. 3) Inter-individual and intra- individual variations in interpretations seriously affect the diagnosis. Both over reading and under-reading are substantial. The latter can be improved to some extent by constant practice and experience in X-ray reading but cannot be eliminated entirely.