It has been reported that a substantial proportion of the new cases arise from the previously infected population. Hence, it appears that exogenous reinfection and/or endogenous reactivation play a major role in the development of post-primary disease. Though the risk of disease associated with exogenous reinfection and endogenous reactivation has not been computed in Indian conditions, the data collected during a longitudinal study by National TB Institute, Bangalore was analysed to estimate the above mentioned risk rates.

The risk of disease associated with exogenous reinfection was 6.55% per year compared with 0.21% yearly due to endogenous reactivation. To test the validity of the computed risk rates these were applied to the interval between the 3rd and 4th surveys. It was then estimated that 64 new cases should have been diagnosed in that survey interval as against 57 cases actually diagnosed. It was also estimated that 1.9% of the total population would be having recent infection, 1.3% would be previously infected with recent reinfection and 32.7% with previous infection but no recent infection leaving 64.1% who are not infected at all (uninfected). Among the new cases diagnosed, 28% would have progressive primary disease, 41% cases arise due to exogenous reinfection and 31% due to endogenous reactivation. In other words, the 1.9% population with recent infection contributes 28% of the total new cases, the 1.3% reinfected population contributes 41% and the 32.7% previously infected population contributes the remaining 31% of the total new cases.

A study was conducted in 1983-84 by the National TB Institute (NTI) in the districts of Dharmapuri (Tamil Nadu) & Ananthapur (Andhra Pradesh). Thirteen health personnel were trained in census taking, tuberculin testing & reading and data keeping etc., at the NTI according to the standard methodology. The trainees were repeatedly assessed and only those who achieved a reasonably high inter-reader correlation with the standard reader were chosen for the field work. Field work was carried out by these health workers and supervised by the team leaders of NTI. Children between 0-9 years were tested with 1 TU RT 23 with Tween 80 in tuberculin testing centres specially set up in each village and the reactions were read between 48 & 72 hours after the test. The tuberculin testing/reading coverage was very high. Of 6702 eligible children, 5904 (97%) were tuberculin test read.

Individual reading assessment carried out at Ananthapur and Dharmapuri for the State Field Workers (SFWs) showed that agreement with Standard Reader (SR) of NTI at three induration levels i.e., 10+ mm, 14+ mm and 18+ mm were very high. The demarcation line between infected and uninfected appeared to be about 18 mm. In Ananthapur, the agreement at 18+ mm was 99% and at Dharmapuri it was 100% for SFW, and 98.4% for SFW-2. The estimates of prevalence rate of infection were 9.3% - SFW V/s 9.7% - SR at Anantapur, 5.2% - SFW V/s 5.2% - SR and 7.2% - SFW.2 V/s 7.2% - SR at Dharmapuri. The study further showed that it was possible to train general health workers, within a period of 3 months to attain a high level of efficiency. The general health services can successfully organise on their own a programme of tuberculin testing in the community with proper liaison and supervision by some nodal agency. The training and field supervision responsibilities may be shouldered initially by NTI or another suitable organisation, till these nodal agencies come up.

Screening of the population by Mass Miniature Radiography (MMR) followed by sputum examination by culture of the X-ray abnormals is the customary method for arriving at the prevalence rate of cases in the community. It is not possible to use this methodology by states to carry out prevalence surveys in these areas, even if they desire to evaluate the effect of anti tuberculosis measures implemented by them. Therefore, simpler means of screening population through chest symptom for sputum examination has been studied by National Tuberculosis Institute (NTI). The objectives of the present investigation were to find out the prevalence of bacillary cases by screening the population through identification of chest symptomatics by Social Investigators (Sls) or General Health Workers (GHWs) compared to that by MMR. In a peri urban area 10 kms away and around Bangalore city all the villages were listed and of the 60 villages were selected on the basis of a sample random sample. Of them, 30 were covered by Sls of NTI and the other 30 by GHWs of the state government. The methodology adopted was that (1) After census taking and registration of the entire population aged 15 years and above, Sls questioned the persons house to house for presence of cardinal chest symptoms of any duration. All chest symptomatics were subjected to MMR and sputum examination. (2) Similar methodology was adopted by GHWs in the other 30 villages allotted to them. (3) Without knowing the symptom status of all the registered persons, aged 15 years and more belonging to all the 60 villages, were subjected to MMR and from among those having X-ray abnormalities, to sputum examination.

It was found that GHWs had identified the same proportion of the persons either having general symptoms or having chest symptoms from the general population, as Sls. Prevalence rates of culture positive as well as smear positive cases were similar by any of the three methods i.e., 0.18%, 0.23% & 0.25% respectively. Prevalence rates of smear positive cases obtained through symptom questioning, either by Sls or GHWs, were more or less similar to the estimates obtained by the more comprehensive screening method of MMR and/or symptom questioning. The culture positive prevalence rate following MMR screening was 0.25%, which was lower than the rates observed in other surveys. The paper discusses the possible hypothesis that could explain the observation. It also presents correction factors to compute rates comparable to the best estimate i.e., that obtained through comprehensive screening by MMR and/or symptom questioning, followed by sputum culture.

In a study of feasibility of treatment of smear positive patients with Short Course Chemotherapy (SCC) regimens under District TB Programme (DTP) conditions in a city, adverse drug reactions in terms of frequency of episodes, incidence in the cohort of patients, time of occurrence, major adverse reactions requiring modification of chemotherapy and or symptomatic treatment, were investigated.

Patients were allocated to one of the two 8 month SCC regimens i.e., Regimen 'A' 1 SHRZ/6TH, Regimen 'B' 2SHR/6TH. Overall incidence of adverse drug reaction in cohort of 265 patients was 37%, 9% of which were considered as major in nature. 34 episodes of such reactions resulted in modification of chemotherapy in 15 patients during intensive phase. Though gastro intestinal symptoms were predominant, cutaneous toxicity was the pre eminent cause of modification of regimen. No case of exfoliative dermatitis occurred. A total of 333 episodes of adverse drug reactions of minor nature occurred; 50% being gastro intestinal symptoms followed by cutaneous symptoms. More than 70% of all adverse drug reactions of intensive phase occurred in the first half of the period. There was no significant difference between the two regimens in the incidence of adverse drug reactions of either major or minor in nature.

SCC is being implemented in a phased manner in the DTP. Before introducing SCC in large number of districts, it would be prudent to find out whether SCC would be acceptable to both doctor and patient in terms of adverse drug reactions.
It can, therefore, be concluded that adverse reactions may not be a major constraint for inclusion of SCC under DTP for treating sputum positive tuberculosis patients provided that additional resources and man power are allocated to the DTCs to manage patients in the centre and extend effective guidance to staff working in peripheral centres.

An operational study of two regimens of Short Course Chemotherapy (SCC) to assess their efficacy under programme conditions, applicability and feasibility in District TB Programme (DTP) was undertaken in an urban TB centre. The two regimens studied were 1SHRZ/7TH and 2SHR/6TH. Their operational efficacy (efficiency) was found to be 87% and 92% respectively which had already been reported in an earlier paper. The various factors i.e., initial willingness, drug default, treatment completion pattern, adverse drug reactions and initial drug resistance with their potential harmful effects on the treatment outcome as well as work load and extra cost these regimens entail for DTP organisation are discussed in this paper.

Out of a total of 1822 smear positive patients diagnosed at the Lady Willingdon State TB Centre during intake period (Feb '84 to March '85), 1126 were residents of Bangalore City. Of these 695 (61.7%) were unwilling to attend the clinic daily for 2 months, 27 were unfit and one was excluded by mistake. Thus, 403 (38.3%) initially willing patients were classified either as 'core group' or 'Non core group’, according to the history of previous anti TB treatment (321 and 82 respectively). Of the 695 (77.6%) unwilling persons, majority were those who pleaded inability to attend daily for 2 months without specifying any particular reason. Refusal of SCC due to injections accounted for 12.8% and 9.5% wanted to take treatment elsewhere. Old age influenced willingness adversely.

Of the 321 patients in the core group, 56 were excluded due to missing more than 50% of intensive phase doses. Among the remaining patients, 61 (48%) out of 127 patients on Regimen A and 48 (34%) out of 138 on Regimen B, did not make a single default in the intensive phase. Of the total 910 defaults for which actions were taken, 640 (70%) were retrieved by letter writing, among the remaining 293 (72%) were retrieved by home visiting. Main reasons for default elicited during home visits were: going out of station (52.9%) followed by patients being busy with work (19.1%). Compensatory phase was availed by 156 of the 265 patients who missed one or more doses due to default in the treatment. The pattern of treatment completion of 321 core group patients in the two regimens were similar i.e., in both the phases 65% for Regimen A and 63% for Regimen B. Incidence of minor adverse reactions was 28% and major toxic reactions were experienced by 8.4% of patients. Workload for treating 321 patients was due to supervised administration of drug 45 patients per day. Letter writing to 3.1 per patients, home visiting 1.1 per patient and doctor's attention for adverse reaction 2 occasions per patient. This could be managed with the existing staff. The cost of Regimen A was Rs.220/ per patient and for Regimen B, 268/ per patient. Cost to patient for transportation was Rs.70/ and Rs.113/ for Regimen A and B respectively.The major disturbing finding of the study was initial low acceptability of about 40% for SCC. The home visiting which was crucial in increasing the completion rate in this study is usually not available in most of the DTCs. Workload, adverse reactions etc. were not of any problem for implementation of SCC in the programme.

The fate of patients with isoniazid (H) resistant pulmonary tuberculosis, treated with 3 different Short Course Chemotherapy regimens (Regimen A-1 SHRZ/7TH, Regimen B-2SHR/6TH, Regimen C-2EHR/4H2R2) was examined in two sequential studies. One hundred H resistant patients belonging to two groups-one without history of previous treatment(core group) and second with history of previous treatment >=15 days (non-core group), were followed up at the end of 12th, 15th and 24th/36th month of chemotherapy. Bacteriological favourable response among patients in the core group at the end of chemotherapy with Regimen A, B and C were 65.2% of 23 patients, 50% of l8 patients, and 57.1% of 18 patients respectively. The response among patients in the non-core group were 27.3% with Regimen A and 52.6% with Regimen B.

At the end of 24/36th month of chemotherapy, 62.5% patients in the core group and 2 out of 7 in the non-core group on regimen A and 68.7% patients on regimen C in the core group and 5 out of 15 in the core group and 41.7% in the non-core group on regimen B were culture negative. The relapses were significantly high in regimen B & C in comparison with regimen A. Thus, of the total 100 patients, 99.3% were eligible for examination (1 died during chemotherapy), 67 were examined and of them 37 (62.7%) were culture negative, 22 positive and 8 were dead. The development of drug resistance to rifampicin was directly related to the duration of its use.

Five districts in which short course chemotherapy (SCC) was introduced during 1987-88 (DTP-SCC) and an equal number of districts without an SCC programme (DTP-SR) but having comparable new sputum examinations performance (NSE) in 1986 were selected from the states of Gujarat and Tamilnadu. Data obtained by the monitoring cell of the National Tuberculosis Institute (NTI) for 15 consecutive quarters from the lst quarter of 1986 were analysed. It was possible to study operational variables: NSE, number of pulmonary patients diagnosed (TBP) and number of bacillary cases detected (BCASE). While the figures of first six quarters were used to represent pre SCC performance, those of the last six quarters depicted the post SCC scenario. However, the trend analysis has been done using the whole data.

The growth rates of NSE, TBP and BCASE were 14.1%, 1.7% and 13.0% respectively for DTP-SCC compared with 17.0%, 5.3% and 29% for DTP-SR. Both the DTCs and PHIs in DTP-SR showed negative growth in BCASE, inspite of their efforts as evidenced by increase in NSE and TBP, the introduction of SCC led to an increase in BCASE for both DTC and PHIs. While the PHIs in DTP-SCC showed increased efficiency in all the aspects (NSE 24.4%, TBP 19%, BCASE 16.7%), DTCs showed decreased activity in NSE ( -2.4) and TBP (-6.6%), indicating improvement at the periphery. Trend analysis corroborated the above findings.

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 treatment results of an unsupervised Short Course Chemotherapy (SCC) regimen used under conditions of District Tuberculosis Programme (DTP) are presented. The District Tuberculosis Centre (DTC), Kolar and six of its Peripheral Health Institutions (PHIs) formed the study area. No extra efforts except ensuring of adequate availability of drugs at the participating centres were made to obtain patients' compliance. In all, 584 smear positive tuberculosis patients were diagnosed during the study period but 28.3% of the patients could not be initiated on treatment with the chosen self administered SCC regimen -2EHRZ/6TH(EH).

Of the 382 put on treatment, only 33.2% completed over 75% drug collections in both intensive and continuation phases. The pattern of treatment compliance did not vary with the place of treatment, i.e. DTC or PHI. Irrespective of treatment compliance, nearly 72-77% of the patients attained smear negative status at the end of the period of treatment, there being no difference between PHI and DTC. However, deaths were higher in the PHI patients. This could be attributed to a significantly higher proportion of aged patients taking treatment at PHI than at DTC. Considering death as an unfavourable outcome, overall favourable response was 65.9%. Patients with drug sensitive bacilli had a higher rate of culture negativity (70%), as compared to those with drug resistant bacilli (48%). It was concluded that unsupervised SCC could give encouraging results in a DTP setting, provided adequate drug supply was ensured.

A study was done to compare (1) the filtration method with conventional centrifugation method for the recovery of tubercle bacilli from urine and (2) drug sensitivity profile, virulence for guinea pigs and phage type of the urine isolates with the corresponding isolates from the sputum of cases of bacillary pulmonary tuberculosis.

Urine specimens from 236 pulmonary tuberculosis patients were cultured by routine centrifugation method as well as filtration method. Filtration was done by passing urine through a 0.45 um membrane filter and treating the membrane with 5% oxalic acid for 15 minutes. LJ medium was used for culture in both the methods. Centrifugation yielded 27 positives (11.6%) whereas filtration gave 12 (12.6%) out of 95 specimens filtered. Contamination was more with filtration method. Comparison of the biological properties of M.tuberculosis isolated from urine and sputum of the same patients revealed difference in drug sensitivity profile or virulence for guineapigs for 13 of 25 (52%) of the pairs of isolates tested. Moreover 4 of 11 pairs subjected to phage typing were found to differ in both major and minor phage types. The significance of these findings in the light of the pathogenesis of tuberculosis is also discussed.

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.

The stimulatory effect of carbon dioxide (CO2) on the growth of tubercle bacilli was reported by a few authors. A study was done to see the effect of CO2 on primary isolation of mycobacteria on Lowenstein Jensen medium in terms of (1) positivity rate (2) improvement in the rate of growth in cultures and (3) contamination rate.

One thousand and five clinical specimens were inoculated, after processing by modified Petroff's method, onto LJ medium and incubated with or without addition of 10% of carbon dioxide. Of the total positive cultures, 30.8% grew only under 10% carbon dioxide and in 58.3% growth was first seen in that atmosphere. The results of this study show that (1) 10% carbon dioxide increases the yield of mycobacteria in primary culture (2) it stimulates the temporal growth rate resulting in reduction of lag period by one week (3) the increase in yield is largely from smear negative specimens and (4) there is no significant increase in the contamination rate to offset the stimulating effect on mycobacterial growth.

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.