The problem of drug resistance in tuberculosis is said to be on the increase in developing countries. This could adversely affect control measures. A knowledge of the prevalence and pattern of drug resistance would be of great help to the programme planners for purposes of monitoring and future planning. Hence, a survey on initial drug resistance to anti-TB drugs, as it occurs under programme conditions, was conducted in the urban situation of Bangalore and rural area of Kolar district. The proportion of Initial Drug Resistance (IDR) to anti tuberculosis drugs was estimated among new patients attending Bangalore (urban) and Kolar (rural) District Tuberculosis Programmes (DTPs). The sputum samples were collected from all newly diagnosed patients in this area and subjected for culture and drug sensitivity tests. It was observed that IDR to any drug was 34.9% (Isoniazid 32.87% and Rifampicin 4.4%) among Kolar patients. Among Bangalore patients, IDR was 20.57% (Isoniazid 17.35% and Rifampicin 2.89%). Combined resistance to isoniazid and rifampicin was 1.36% in urban DTC and 3.42% in rural DTP. With the introduction of Short Course Chemotherapy in DTP, combined resistance to isoniazid and rifampicin assumes paramount importance and needs to be monitored continuously.

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.

Under the National Tuberculosis Programme, Ziehl-Neelsen method (ZN) is the recommended procedure for AFB staining. However, at the Peripheral Health Institutions, the applicability of this procedure appears to be adversely affected due to non- availability of alcohol for heat fixing, heating and decolourisation steps. Hence, it has become necessary to look for procedures when the use of alcohol could be avoided completely. In this study, three different methods of cold staining, wherein the use of alcohol is avoided, have been tried in 489 sputum specimens. One set of smears was fixed with acetone (CSB method), the second set with candle flame (CSD) and third set was not fixed (CSC). All were stained by a modified cold staining procedure. The (a) sensitivity (b) specificity (c) degree of agreement with culture and the standard ZN method and also (d) applicability of these methods, were studied. All the specimens were subjected for culture and ZN smear examinations. ZN method was significantly superior to other methods. As far as the agreement with culture is concerned, ZN method was found to be superior to CSB method by 29.26%, to CSC method by 24.3% and to CSD method by 31.7%.

The sensitivity and specificity of various methods were: ZN-76.1%, 98.4%, CSB-72%, 96.6%, CSD-72.7%, 96% and CSC-76.6%, 96.9% respectively.

One of the hypothesis put forth for the failure of BCG vaccine to show protection against bacillary pulmonary tuberculosis in Chingleput trial was the interference from non-tuberculous mycobacteria that were prevalent in the trial area. In order to test this, a study was conducted with the following objectives: to investigate (1) Protection given by BCG and M.avium intracellulare (MAI) which is the most prevalent species, against the challenge with high and low virulent strains of M.tuberculosis in sensitised guineapigs. (2) Whether M.avium Intracellulare (MAI) interferes with the protective effect of BCG against challenge with both high and low virulent strains of M.tuberculosis. Sensitization was done with MAI in guineapigs using both oral and intradermal routes. Groups of species were immunized with BCG/Placebo and later challenged with high/low virulent strains of M.tuberculosis. Colony counts of M.tuberculosis bacilli from spleens of the animals were done to measure the protective effect.
The findings were: (1) BCG showed protection against both high and low virulent challenges. (2) MAI in both oral and intradermal routes had no effect against low virulent challenge. (3) There was no significant interaction between BCG and MAI against low virulent challenge. (4) MAI when given orally, showed a significant protection against high virulent challenge. The same was not seen with intradermal route. (5) MAI orally, interfered with the protective effect of BCG against high virulent strains of M.tuberculosis.

South Indian Variant strain of M.tuberculosis has been found to be less virulent to guineapigs through various studies from Madras and Bangalore. It was not known whether the low virulent nature of the tubercle bacilli was a fixed character or a change due to serial passages inside the body over a period of time. Hence, a study was conducted to see the behaviour of low virulent tubercle bacilli over a period of eight years during twenty passages in animals.

Ten low virulent cultures of M.tuberculosis isolated from patients belonging to Bangalore area were injected intramuscularly into guineapigs. The extent of lesions was assessed through Mitchison's Virulence scoring method. Bacilli recovered from the spleen of these guineapigs were passed into another set of animals and virulence scored. Twenty serial passages were thus performed over a period of eight years. The findings revealed that throughout the study in all the passages, the south Indian Variant of M.tuberculosis maintained its low virulent character.

Culture examination of sputum is known to be the best tool for assessing the prognosis of pulmonary tuberculosis patients. Controlled clinical trials with Short Course Chemotherapy (SCC) have shown that culture examination of sputum at the end of two months elicited a high degree of conversion, while smear results were inferior due to presence of dead organisms in the sputum. But, it is not possible to provide sputum culture facilities in the District TB Programme (DTP). Since smear examination facilities is widely available under the DTP, this paper examines the comparability of smear results with culture in patients treated with SCC. It also examines the value if any, of an early evaluation of the treatment outcome with SCC under operational conditions by doing smear examination at two months. Data from two operational studies on SCC are utilised for this purpose.

Of 256 total patients examined, 62 were smear positive at the end of two months, but 41 of them were excreting non- viable bacilli and were culture negative. Nevertheless, in predicting the final outcome of chemotherapy, no significant difference was observed between smear and culture examination at the end of two months. Smear positivity at the end of 2 months, by itself, cannot be considered to bode an unfavourable response, whereas negativity had a good probability of a favourable response. Microscopy in SCC gave as reliable a result as culture both during and at the end of chemotherapy. Hence, a properly conducted smear examination is as good as culture for diagnostic and prognostic purposes under operational conditions.