This paper estimates the natural trend of tuberculosis in rural south India and the potential epidemiological impact of a few selected programmes on this trend, by using the values of important variables and parameters derived from a longitudinal epidemiological study conducted in 1961-68 in Bangalore district by the National Tuberculosis Institute (NTI), Bangalore. The values are fed into an epidemetric model and the final outputs of computerization derived are incidence of disease (in both absolute and relative terms) and cumulative future prevalence of disease.

(1) An annual average input of new generations of 3.16% has been derived for a population of 1 million by using a simplified fertility rate formula. A constant reduction 0f 1% per year has been assumed until fertility rate has reached 50% of its starting value. The assumption is that any reduction in fertility due to current family planning programmes will have a considerable impact on the size of the population and on the epidemiological situation. Further demographic assumptions are, excess mortality applied to groups of active cases and fatality among untreated cases. (2) The population is subdivided into the following epidemiological groups: (i) non-infected, (ii) infected for – (a)< 5 years, (b)= 5 years, (iii) protected by BCG, (iv) active cases - (a) non-infectious, (b) infectious and (v) previous cases. Initially groups (iii) and (v) are given zero values. The future risk of infection is adjusted to the force of infection, which is assumed to be reduced to 1/7th when a case is successfully treated. Morbidity rates include transfers from infected group to active cases group during 5 year periods. (3) A spontaneous healing rate of 50% and a cure rate of 80% after chemotherapy are assumed. Protective effect of BCG is given three values: 30%, 50% and 80%, with uniform annual reduction of 1% (4) Case detection and treatment (CF/T) is given two values: 66% and 20%. Coverage for BCG limited to 0-20 years is assumed to be 66% or 30%.

The computer simulation output for natural trend shows that the absolute number of new cases increases considerably while the incidence rate do not warrant firm conclusions about any long term trend. All programmes considered have considerable potential impact. The CF/T programmes will reduce the incidence after 25 years by only 12% compared to reduction of 17% by the BCG programme. In general, the effect of CF/T will be more immediate and of BCG will be seen much later. To avoid the drawbacks of incidence as an indicator of tuberculosis situation, the cumulated future prevalence is taken as the tuberculosis problem. To adjust for the present significance of future cases as part of the problem certain discount rate have been applied. The CF/T programme and the BCG programme with 50% protection lead to 69% problem reduction, if not discounted. With increasing discount rates, CF/T has an advantage over BCG. The actual problem reduction will be higher than that estimated if improvements in the standard of living are expected during the coming years.

In conclusion, data on the dynamics of tuberculosis situation in rural south India, obtained by NTI, Bangalore when fed into a mathematical model, many predictions about the future tuberculosis situation were made under a wide range of hypothetical assumptions.

At present most of the districts in India have a TB clinic at the district headquarters, where TB patients are diagnosed and treated. Most of the clinics serve the town population and only a small proportion of the rural population are able to attend the clinics due to long distances. The wide distribution of patients in rural areas will necessitate the provision of extensive anti-tuberculosis services and they should be provided as near to the patients' home as possible. This cannot be achieved by creating large number of specialised services (TB clinics) in the district, as this will not only be beyond the resources but wasteful. As such, provision of anti-tuberculosis services in rural areas can be achieved by integration of the primary health centres and dispensaries. The problems of treatment in rural areas are envisaged as technical, organizational and personnel. Under the technical problems, the choice of anti-microbials is considered. The anti-microbials should be effective, cheap and acceptable to the patients. INH PAS, INH alone or INH Thiacetazone are considered suitable. Streptomycin containing drug regimens are difficult for the health services to deliver them to the patients in rural areas. Even with oral drugs INH + PAS or INH alone, drug regularity are 26.3% and 24.6%. The other technical limitation of treatment is the probability of increase in drug resistance due to the wide application of drug treatment which might be irregular. This has not been considered as enough justification for withholding treatment to the vast majority of patients, as its epidemiological and clinical significance in India are yet to be fully understood. The District TB Programme provides a firm organisational structure on the basis of which improvement can constantly be introduced for smooth functioning, constant supervision, proper orientation training and demonstration of the programme by the District TB Centre if necessary.

The organisational problems listed are: irregularity of drug intake and drug collection; their identification, default at drug collection, intake and remedial action, maintenance of records, check up while on treatment and follow up after completion of treatment. The paper suggests that regular collection could be taken as an index of regular drug intake. Defaulter actions could retrieve about 30% of the defaulters. Check up during treatment as well as follow up after treatment were found to be not acceptable to the patients due to a number of reasons. Training of staff to render services is also one of the biggest hurdles. The remedial measures are stressing tuberculosis as a community problem at the undergraduate and post graduate levels, training of the staff at every level of the programme and arrangement of seminars and group discussions with the administrators and medical personnel.

The broad relationship between the extent and pattern of sickness in a south Indian rural community, attendance at the Area Health Centre (AHC) and service rendered to the sick at the centre were studied by National Tuberculosis Institute (NTI), Bangalore. The objectives were to study (i) point prevalence of symptoms of all kinds and their pattern (ii) attendance at the AHC and the pattern of symptoms among them: and (iii) number of visits for each spell of sickness, by nature of symptom, laboratory tests offered, and referral to better equipped health institutions. A 30,000 population served by the Bettahalasur Primary Health Centre (PHC) which is 20 km. away from Bangalore city was chosen. The selection of villages was done by random sample so that about 1000 persons from each of 5 field health workers' area was available for symptoms questioning. The out patients at the PHC were questioned for symptoms by the PHC medical officer in a manner exactly similar to that for the community by the trained NTI para medical staff. The answers given by patients were recorded by NTI staff both at the centre and at the community. On revisits made for the same spell of sickness, the interval in days from the first visit, any laboratory tests done and reference to better equipped institutions were also recorded.

The point prevalence of sickness in the area was 9.5%; cough, pain and fever, in that order were the three cardinal symptoms that accounted for 68% of the total sickness in the community. Only 1.3% of the sick, at any point of time, had attended the AHC but the attendance by the sick persons residing in the village where the health centre is located was 9.2%. The composition of the out patients attendance was significantly different from that of the sick in the community in respect of age, sex and symptoms. Thus, women and the elderly persons who also constitute a major reservoir of tuberculosis, tended to disregard their symptoms while younger persons in the productive age group had availed the health centre facilities more freely. Among symptoms, cough was the most ignored. Of the total out patients, 71% had attended only once, 18% twice and 11% three times or more for any particular episode of sickness. Only 7 9% were offered laboratory examination and an insignificant number were referred to better equipped health institutions.

A study was carried out to investigate the applicability of INH-Thiacetazone (TH) combination with special reference to acceptability and toxicity in Tumkur district. 150 patients from Tumkur town and some nearby villages were discovered during a mass Case-finding programme. Of them, 127 including 43 sputum positives were given chemotherapy with 300 mgm INH and 150 mgm thiacetazone (TH), in a single tablet to be taken once a day. All but one patient had the treatment on an ambulatory basis. Results of treatment in respect of 103 patients are presented in the paper.

The overall death rate was of the order of 15%. About twice the number of deaths occurred among the sputum positive patients than among the negative ones. About 40% of deaths occurred during the first quarter. In all, 23 patients developed side effects, in 18 of them thiacetazone had to be withdrawn. Serious side effects occurred among 5 (4%) patients. These patients did not report to the treatment centre by themselves and could not have been detected, if home visits were not made, thus giving an erroneous impression about side effects with TH. The sputum conversion at the end of one year was of the order of 50% among all survivors. Among those who were drug sensitive and examined at one year, conversion rate was 63%. Favourable radiological response was seen in 74%.

Thus, though cheap and clinically effective, Thioacetazone in combination with INH was found to produce serious and significant side effects. Hence, vigilance by the treatment centres were thought to be necessary when the patients are on this regimen.

Application of a combined regimen of INH and Thioacetazone (TH) under conditions of District Tuberculosis Programme having become a distinct possibility, the study observed its applicability and toxicity. In all, 127 patients discovered during a mass Case-finding investigation were treated in their homes with 300 mgm of INH and 150 mgm of thioacetazone in a single tablet once a day. Close supervision of patients, laboratory or clinical examination to elicit toxic/side effects were not practicable. During their initial motivation, patients were asked to report back in the event of occurrence of unpleasant symptoms. At subsequent drug collection, indirect questioning for side effects was done. An active search for toxicity was also made by the home visiting staff when they visited patients' homes for defaulter retrieval.

In all, 23 patients complained of possible side effects of thioacetazone, of which 5 were major and 18 of minor nature. Among the 5 patients, two had exfoliative dermatitis and three had generalised petechial haemorrhages. All were males above the age of 40 years. All recovered with withdrawal of drugs and anti histamines. The minor side effects were giddiness and vomiting. None died of thioacetazone toxicity. It is concluded that TH regimen can be used for mass application on account of therapeutic efficacy and low price but consequences of side effects must be borne in mind while using this drug combination under district programme conditions.

In the formulation and evolution of a National Tuberculosis Programme some assumptions are made which require to be tested under the normal administrative set up with minimum interference by the investigating team. The objectives of the study were to understand some operational aspects of Case-finding in the Peripheral Health Institutions (PHIs) in an integrated programme. First, what is the frequency of persons showing symptoms suggestive of pulmonary tuberculosis among the normal out patients attendance (OPA), how many cases can be found by direct microscopy of sputum of those symptomatics, what will be the workload of TB Case-finding at a PHI and, what proportion of symptomatics will be willing to and will actually attend the District TB Centre (DTC) when referred there for X-ray examination. The study was conducted in a district with a population of 1.5 million having one DTC and 55 PHIs. 15 PHIs were selected on the basis of stratified random sampling. At each PHI an National Tuberculosis Institute (NTI) investigator worked for a period of one month. All new out patients were questioned for symptoms (non- suggestive and suggestive) and any patient with chest symptoms mainly cough for more than one week fever, chest pain and haemoptysis was subjected to a sputum examination and also referred for X-ray examination at the DTC.

It was found that 381 (2.5%) of the 14881 total new out patients of all age groups complained of cough for 2 weeks and more. From these chest symptomatics, 11% were new cases of pulmonary tuberculosis. When the symptomatics were referred for X-ray examination, although 66% agreed to go for X-ray to DTC but only 16% (of the total referred) actually went for X-ray. Each PHI had to examine only one or two sputum specimens per working day. As the study was conducted in a representative sample of PHIs for a representative duration of time, the material permits the estimation of the potential yield of cases in a District TB Programme (DTP) during a period of time (say one year). It was estimated that about 45% of the total estimated prevalence cases in a district can be diagnosed in a DTP during a period of one year, if all PHIs function according to the programme recommendations. The workload due to tuberculosis Case-finding is small and can be managed with the existing staff and Case-finding by direct smear examination of sputum at the PHI has to be relied upon.

A study was undertaken in Bangalore city, Karnataka, to find out whether people with chest symptoms, including tuberculosis patients, attend General Health Institutions or report directly to tuberculosis clinics. The objective was to investigate the proportion of persons with chest symptoms (cough, fever, pain in chest and haemoptysis) among out patients attending the general city dispensaries, and the proportion of pulmonary tuberculosis cases among them. The findings of this study are based on examination of one day's attendance at each of the 19 general dispensaries of Bangalore city, consisting of 2,506 persons aged 10 years or more who had attended the dispensaries for the relief of any ailment. The investigation consisted of symptom questioning, examination of spot sputum sample and 70 mm chest photofluorogram. Sputum specimens were examined by direct smear and culture. Study intake period of 19 days was spread over three months.

The study showed that of the 2506 out patients, 1170 (47%) had visited dispensaries primarily for relief of chest symptoms. Of these, 31 (2%) had evidence of active or probably active pulmonary tuberculosis and 20 (0.8%) were sputum positive cases. It is concluded that even though there are special tuberculosis institutions in the city, a fair number of new and old tuberculosis patients contact general dispensaries. These dispensaries can therefore contribute considerably to tuberculosis case-finding in the city.

This investigation was to find out the drug consumption among tuberculosis patients put on domiciliary self administered chemotherapy, in terms of proportion of patients that make various levels of drug collections and proportion among them that consume drugs at different points of time during the course of treatment. In all, 816 tuberculosis patients aged 5 years and above residing in Bangalore city were admitted to the study. They were randomly divided into 6 groups at the time of inclusion into the study, for examination of urine samples for the presence of INH and PAS. One surprise urine sample was collected from each patient at the pre determined time after the drug collection. The samples of urine were collected from one group at first month, another at second month, third at fourth month, fourth at sixth month, fifth at ninth month and sixth at twelfth month of treatment. Urine samples were collected within 33 days of drug collection for the month because the drugs were supplied at a time for the said period. Urine specimens were examined for the presence of drugs or their metabolites. For INH, NM test & acetyl INH test and for PAS, ferriechloride and case test were performed. The drug collection was judged on the basis of treatment record and its consumption on the basis of results of urine examination.

Of the total patients included in the study, 54% made 10 or more drug collections over a period of 15 months. The initial radiological or bacteriological status or severity of disease did not influence the drug collection; however smaller proportion of old persons in both sexes collected the drugs for 10 months or more. Urine specimens of 71% of patients who had collected drugs were positive for INH on any one day. Bacteriological quiescence was obtained among the 82% INH sensitive patients who had made 10 or more collections. The above findings suggest that the patients who collect drugs also consume with fair amount of regularity and achieve a high degree of bacteriological quiescence.

The relative merits of a fully supervised twice weekly regimen of Streptomycin and INH (SHtW) and an unsupervised daily regimen of INH and Thioacetazone (TH) in routine programme conditions in an urban area are compared in terms of acceptability and response to treatment at one year. Of the 474 newly diagnosed sputum positive cases at Lady Willingdon TB Demonstration & Training Centre, Bangalore during 1968-69, 134 were allocated to SHtW regimen and 189 to TH regimen. All others who were unwilling to take the allocated regimen or were excretors of bacilli resistant to INH and or SM were analysed as a subsidiary group.

About 25% of the patients allocated to SHtW regimen expressed unwillingness to start treatment on account of unsuitability of working hours and or distance. Refusal to TH regimen was negligible (5%). As regards drug acceptability after start of treatment, while the duration of treatment taken was similar for both the regimens, the level of drug intake achieved by the SHtW patients was lower compared with TH patients i.e., 31.3% of the SHtW patients and 56.1% of TH patients took more than 80% of treatment. If concealed irregularity among TH patients is taken into consideration, it is likely that the drug intake among TH patients would be similar to the drug intake among SHtW patients. The acceptability was therefore almost similar among SHtW and TH patients. Very low level (28%) of treatment completion was achieved by SHtW patients. With TH regimen, 46% had made 10 or more monthly collections during 12 months. Among the SHtW patients there was greater irregularity in the later months which was not apparent among TH patients. However, the favourable response among patients on SHtW and on TH regimen was 68% and 60% respectively. Deaths among SHtW patients were 4%, 13.5% among TH patients, the difference being statistically significant. The response was directly related to the level of drug collection or supervised consumption. The large proportion of the patients who stopped treatment prematurely, continued to remain positive with drug sensitive organisms, if initially they were so. In the subsidiary group there were 62 patients who were excretors of drug resistant organisms. They were treated with drugs to which their organisms were resistant and nearly 30% of these patients had negative culture at the end of one year.

It is concluded that (i) SHtW regimen was superior to TH as it prevented deaths and showed better bacteriological conversion among patients with level 3 & 4 of treatment and (ii) treatment organization is the most important factor in obtaining better results in routine chemotherapy with available drug regimens.

A study was conducted to augment Case-finding in the programme by increasing case yield through repeated sputum examinations by collecting 2-3 samples on the same day. The study was conducted in nine Peripheral Health Institutions (PHIs) of Bangalore district. They were all Microscopy Centres and were drawn on the basis of random allocation. A Health Visitor (HV), Laboratory Technician and Laboratory Attendants of National TB Institute (NTI) were posted at the PHIs during the entire study period. After collection of first sputum sample from the eligible chest symptomatics, 2nd, 3rd or 4th samples were collected at an interval of half an hour from those whose first specimen was negative. Separate smears were prepared from all the specimens for examination at NTI. The duration of the study was nine months.

From among 4233 total new outpatients, 458 chest symptomatics were identified. Of them, 451 gave the first specimen, 416 the second specimen and 379 and 332 the 3rd and 4th specimen respectively. There were a total of 25 smear positive cases; 18 were detected by the first specimen, 3 were added by second and the remaining 4 by the 4th specimen. Of the 451 chest symptomatics, 185 were selected by the PHI Medical Officers (MOs) and 266 were picked up by the NTI HVs from the remaining outpatients. Of the 25 cases detected, 10 came from the chest symptomatics selected by the MOs and 15 came from those selected by the NTI HV. The study has shown the feasibility of collecting multiple specimens of sputum from each symptomatic on the same day. A loss of 60% cases was due to casual symptom questioning by the MOs. It was further observed that the intensity of the physical suffering has influenced the behaviour of patients towards action taking. The sputum positivity rate was 5.5%

In the BCG Mass Campaign low outputs and coverages of BCG vaccination done after tuberculin test were due to slowness of the campaign because of two visits to an area, the fear of two pricks and tuberculin tested absenting themselves from reading of the test. It was thought that if BCG vaccination could be given without prior tuberculin test and without causing any complications then the speed of work and outputs could be more than doubled and coverages improved appreciably. For this, the following three studies were carried out: In the first study 1,891 persons belonging to a rural population were randomly divided into four groups (i) those tuberculin tested and vaccinated, (ii) tested but not vaccinated, (iii) not tested but vaccinated, and (iv) neither tested nor vaccinated. Induration site of tuberculin test and vaccination were read on the 3rd, 6th and 90th day. Later on, another tuberculin test was done on the 90th day and read 3 days later. Both axillae were examined on 0, 14th and 90th day and X-ray pictures were taken on 0 day, 90th day and after one year. Tuberculin indurations on 3rd day were compared with BCG induration on 3rd, 6th, 14th and 90th day. Majority of tuberculin reactors had large BCG indurations upto 14th day. By 90th day very few persons have large indurations left. Among non-reactors also large BCG reactions were seen in 25%-53% of the persons. There were no differences as regards to the size of lymph nodes (regional reactions) between reactors and non-reactors; neither was there any evidence of exacerbation of existing disease nor any flaring up of dormant foci (Primary complex) in the form of new disease as shown by X-ray.

In the second study out of 1,520 persons from 4 villages, 1,186 were both tuberculin tested and simultaneously vaccinated. Examination of local reactions daily from one to nine days, on 19th and the 29th day, confirmed the findings of first study with regard to the local reactions. In this study neither axillae were examined nor X-ray pictures taken. In the third study, influence on acceptability of direct BCG vaccination due to large local reactions was tested. Twelve villages in Gubbi taluk of Tumkur district were taken in pairs. Vaccination of 2nd village of each pair was done after 1-4 weeks of the vaccination in lst village to observe the influence of BCG reaction on the people. Vaccinations were given to 5363 (64.2%) persons from the total registered population with Madras liquid vaccine. The large local reactions showed no adverse effect on the acceptability of BCG vaccination in the neighbouring villages, rather a slight improvement in BCG vaccination coverages with time was seen.

A study was carried out in Bangalore city corporation area with the following objectives; when BCG vaccination is administered simultaneously with primary smallpox vaccination to infants; (i) whether any immunological interferences take place as indicated by the development of vaccination lesion and post-vaccination allergy due to BCG vaccination and the development of the local lesion (take rate) of smallpox vaccination; (ii) whether the incidence of complications are higher among those simultaneously vaccinated and, (iii) whether the population will accept a procedure involving two vaccinations. BCG technicians and the smallpox vaccinators registered all the eligible children after house to house visit and randomly allocated to three groups. A total of 789 children aged below one year were admitted to the study. While 315 were vaccinated simultaneously with BCG and smallpox vaccines (BCG on the right arm and smallpox on the left), 255 were vaccinated with smallpox vaccine only and 219 with BCG vaccine. All 789 children were followed up on the 5th, 21st, 90th and 93rd day of vaccination. The 5th and 21st day followups were to study the development and healing of smallpox vaccination lesions, whereas the 21st, 90th and 93rd day followups were for BCG vaccination lesions. The 90th and 93rd followups were for tuberculin testing and reading.

It was found that there was no evidence of immunological interference between the two vaccines when administered simultaneously i.e., the development of lesion of smallpox vaccination among the simultaneously vaccinated group was similar to the development of the smallpox vaccination lesion among the only smallpox vaccinated group and, the post-vaccination allergy due to BCG among the simultaneously vaccinated group was similar to the post-vaccination allergy among the only BCG vaccinated group. The complications due to vaccinations were very few and similar among the simultaneously vaccinated as compared to the other respective groups. The acceptability of simultaneous vaccination was higher than BCG alone. The above study has demonstrated that BCG and smallpox vaccinations can be administered simultaneously.

BCG vaccination is being conducted as a mass campaign. It is difficult to maintain a high coverage of the population at risk i.e., new borns. This can best be done by integrating the BCG vaccination services with the general health services. The present investigation was planned to study the feasibility of routine BCG vaccination of the new borns by the Primary Health Centre personnel using the normal records maintained by them. In a rural population of 33,128 persons (1971 census), served by PHC Bettahalasur of Bangalore district, BCG vaccination was administered to 0-15 months old children by 2 Block Health Workers (BHWs) and 3 Auxiliary Nurse Midwives (ANMs) after training them for about 3 weeks. They used a compact specially designed BCG kit and employed a conventional intradermal technique for BCG vaccination. Routine work was not to be disturbed in any way. Each worker prepared a list of children eligible for BCG vaccination from the register of unprotected children and updated the list for those not found registered. National Tuberculosis Institute (NTI) field staff registered a sample population, allotted to each worker for estimation of eligibles. Three months later they also examined BCG vaccination lesions in a sample of children. BHWS and ANMS were interviewed by a medical officer from NTI regarding their opinion on integrated work.
The findings showed that the ANMS and BHWS had already registered nearly 50% of the new borns in their records with variation in registration from 21 to 80% by the field workers; ANMS understandably having registered lesser numbers. All of them were, however, able to update the registrations to a level of 82%. They could pick up the BCG vaccination technique easily. Of the total eligibles, ANMS and BHWS could contact 86.4% and vaccinate 77%; remaining 23% either refused or were excluded from vaccination. In the total eligibles registered, however, the vaccination coverage was 66.6%. Of the children reported vaccinated, 96% had evidence of BCG vaccination indicating a high degree of reliability of reporting. The opinion of all the 5 field workers on integration was favourable. All the ANMS and BHWS workers, on interview, stated that they had done BCG work without detriment to their other duties and would be easily able to do so in future. The field workers can accumulate the new borns for a year and vaccinate them during a month. This has mainly operational advantages including less vaccine wastage. For urban areas a different operational design with the same principles may become necessary.

After the introduction of direct BCG vaccination, assessment of post-vaccination allergy and information about prevalence of infection could not be obtained. Few methods were tested i.e., i) retesting of persons with 0-13 mm reaction at site of vaccination on 4th day of vaccination, ii) retesting of all vaccinated persons of age 0-10 years. It is not only necessary to find out the size of BCG lesion that could separate them but also the day after vaccination on which the tuberculin reaction size best correlates with the BCG vaccination size. With this in view, two studies with regard to direct BCG vaccination done in India have been examined further. In Study I, 816 eligible persons were tested with 1 TU RT 23 read on 3rd day and vaccinated with either Indian or Danish vaccine. The vaccination lesions were examined on the 3rd, 6th and 90th day of vaccination. On the 90th day post-vaccination tuberculin test was done and read on 3rd day. In Study II, a total of 691 who had no previous BCG scar were simultaneously tuberculin tested with 1 TU RT 23 and vaccinated with either Indian or Danish vaccine. The BCG lesions were examined every day and on 39th and 90th day.

The correlation of pre-vaccination tuberculin test and BCG lesion size showe d that sixth day in first study and fifth day in second study was the highest. Tuberculin reaction size of 10 mm or more correlated well with 14 mm or more induration size of BCG in classifying the persons as infected and non-infected. Correlation between the size of BCG scar at 3 months and size of pre-vaccination tuberculin reaction was poor. Considering the two studies together vaccination induration of 14 mm or more on 5th or 6th day appears to be the best criterion for demarcating the infected from non-infected. Some other choices are 12 or 14 mm levels on 2nd day, 10 and 12 mm levels on 5th day and 10 mm levels on 8th day seems to be nearly as good and operationally useful.

A BCG Vaccination induration size of 14 mm and above between 5th and 6th day of vaccination, for all practical purposes may be considered satisfactory for demarcating persons infected with M.tuberculosis from those non-infected. It can be concluded that estimation of prevalence of infection, when BCG vaccination is given to all without prior tuberculin testing, can be made on the basis of BCG vaccination induration size of 14 mm or more.

The Freeze-Dried BCG vaccine manufactured in India is sealed under vacuum. This though adds to its stability involves expensive production procedures. Sealing in presence of nitrogen is both simpler and economical. Before producing this vaccine for use on a large scale, it was considered necessary, to study the influence of storage at higher temperatures on the allergy inducing capacity on the basis of the size of local lesion and viable counts of Freeze-Dried BCG vaccine sealed either in vacuum or in the presence of nitrogen. For this, half of the ampoules of a batch of vaccine prepared in Madras BCG Vaccine Laboratory were sealed in vacuum and the other in presence of nitrogen. Randomly selected ampoules of both types of vaccine were exposed to 37o and 44o for 2, 6, and 18 weeks and another set at 4oC for 18 weeks. Two batches of liquid BCG vaccine were made as controls: 16 types of ampoules thus obtained were randomly repeated 5 times according to Standard Lattice Design. About 3000 school children without BCG scar, aged 5-14 years In Bundi and Kota districts of Rajasthan were vaccinated as per the study design. post-vaccination allergy with 5 TU RT 22 by measuring the size of vaccination lesions was recorded 3 months later. Viable counts on samples of ampoules from Freeze-Dried BCG vaccines exposed differently were done in the production laboratory after 18 weeks of storage.

The vaccine in 16 types of ampoules was significantly different. Liquid BCG vaccine resulted in higher level of allergy and larger vaccination lesions than Freeze-Dried BCG vaccine sealed under either method. The study has shown that Freeze-Dried BCG vaccine sealed under either method vacuum or nitrogen, gave satisfactory level of post-vaccination allergy and induration size of vaccination lesions, provided the vaccine was preserved at 4oC. Storage at 37o for more than 2 weeks and even 2 weeks storage at 44oC affected both types of vaccine badly as shown by post-vaccination allergy and viable counts. However, decrease in viable count with time and temperature was more pronounced in vaccine sealed in presence of nitrogen. Hence, there is a need to provide cold chain facility for Freeze-Dried vaccine all throughout the period.

The limitation of microscopy, culture and radiology in the diagnosis of tuberculosis, especially smear negative and extra pulmonary, are well known. Hence, attempts have been going on to find a suitable serodiagnostic test. One such test was based on Kaolin Agglutination using tuberculo phosphatide as antigen. A study was done to find out the usefulness of this test in the diagnosis of pulmonary tuberculosis. Serum specimens from 297 newly diagnosed tuberculosis patients and 208 healthy controls, were subjected to Kaolin Agglutination Test (KAT) using tuberculo phosphatide as antigen. Of the 297 X-ray positives, 184 were sputum smear positive and 237 were culture positive for M.tuberculosis. A titre of >= 16 was taken to be diagnostic.

The test picked up 53.6 percent of the culture positives and 54.0 percent of the microscopy positives correctly. Also, 48.8 percent of the X-ray positives and 14.2 percent of the healthy controls were found positive. The overall sensitivity of KAT was 53.6 percent and specificity 85.8 percent which does not make the test suitable for diagnosis of tuberculosis.

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.