Limitations of conducting community surveys to access the epidemiological impact of TB control programmes on the incidence of TB

Tuberculosis (TB) remains a major health problem in India, and accounts for nearly 20-30% of the global TB burden. A comprehensive review1 in 1993 of the National TB Control Programme (NTP), present in our country for four decades, documented the failure of NTP due to various drawbacks. These included poor management of the TB control programme, over-reliance on X-rays, poor treatment adherence, under-utilization of laboratory services, poor supply of quality drugs, inadequate funding and lack of proper documentation and case reporting. The Revised National Tuberculosis Control Programme (RNTCP), an application of the globally accepted WHO recommended Directly Observed Treatment Short-course (DOTS) strategy, was implemented in 1993 on a pilot basis, rapidly expanded from 1997 and achieved nation-wide coverage in March 2006

Seven year findings of short-course chemotherapy in 18 districts in India under district tuberculosis programme

The ICMR undertook a study project to find out the feasibility of introducing Short-Course Chemotherapy (SCC) under the existing programme conditions and evaluate its acceptability. Sputum positive pulmonary tuberculosis patients aged 15 years or more who had not received more than two months of anti-tuberculosis chemotherapy, belonging to 18 districts spread over 9 states and one union territory of India, were treated with one of the following regimens: Regimen 1 : Rifampicin, Isoniazid and Pyrazinamide for 2 months and Rifampicin and Isoniazid for the next 4 months, the drugs being given twice a week under supervision. Regimen 2 : Rifampicin, Isoniazid and Pyrazinamide daily for 2 months and Thioacetazone and Isoniazid for the next 6 months drugs being self-administered. Regimen 3 : As in regimen 2 for 2 months and Rifampicin and Isoniazid for the next 4 months, the drugs being given twice a week under supervision. In all, a population of 40 million was covered. Of the Peripheral Health Institutions where District Tuberculosis Programme had been implemented, 66% in 1985 and 93% in 1991 had implemented SCC. Of the newly diagnosed patients, 83% were eligible for SCC and 62% of these were started on SCC. Of the remaining patients, with data available, the reasons for not starting SCC were `patient-related' in 58% and had organisational/ administrative related aspects in 35%. Of those who were started on SCC, 49% in regimen I, 54% in regimen 2 and 61% in regimen 3 received 80% or more of chemotherapy. Concurrent cohort analysis of SCC and standard regimens showed that the overall treatment completion for SCC was fairly constant (51-55%), but ranged from 29% to 45% for the standard regimen. Conclusion : It is feasible to employ SCC under the existing programme conditions. However, additional efforts have to be made to improve case finding and case holding further

Evaluation of a Non-Rifampicin Continuation Phase (6HE) Following Thrice-Weekly Intensive Phase for the Treatment of New Sputum Positive Pulmonary Tuberculosis

Setting: Tuberculosis Research Centre, Chennai and Madurai, South India. Objective: To assess response to treatment, relapse and emergence of MDR TB in newly diagnosed patients with sputumpositive tuberculosis using an intermittent intensive phase followed by a non-rifampicin continuation phase. Design: Patients were treated in a controlled clinical trial with 2HRZE3/6HE with thrice-weekly direct dosing in the intensive phase and once-weekly with six doses self-administered in the continuation phase. Clinical and bacteriologic evaluation was done every month for 24 months. Results: The overall outcome was good, with 92% favourable response (cure) and 4.8% relapse in 450 patients including 103 who did not receive extension of intensive phase for positive smear, 38 with initial H-resistant cultures, 4 with MDR TB and 15 who received less than 75% of chemotherapy. In 392 patients with drug-susceptible cultures, 96%were cured and only 4% relapsed. There was no emergence of MDR TB among failures and relapses; toxicity was low. Conclusion: Newly-diagnosed Category I patients can be effectively treated with this regimen without emergence of MDR TB. It has immense potential in programmes where directly observed therapy cannot be ensured throughout, and when rifampicin is contraindicated in HIV-TB patients who require concomitant therapy with anti-retroviral drugs

A Controlled Comparison of a Twice-Weekly and Three Once-Weekly Regimens in the Initial Treatment of Pulmonary Tuberculosis

value of a fully supervised twice-weekly regimen of high-dosage isoniazid plus streptomycin in the treatment of newly diagnosed tuberculous patients with drug-sensitive cultures. A logical consequence of this finding was an investigation of regimens with a longer interval between successive doses. The present report describes the findings of a controlled study of 3 once-weekly regimens and the twice-weekly regimen. The results confirm that the twice-weekly regimen is highly effective and demonstrate that its efficacy is not influenced by the rate of inactivation of isoniazid or by a reduction (by one-fourth) in the dosage of streptomycin. The results also show that once-weekly chemotherapy from the beginning, whether with high-dosage isoniazid plus streptomycin or high-dosage isoniazid plus streptomycin plus high-dosage pyrazinamide, gives unsatisfactory results. However, when an initial daily phase of 4 weeks with a moderate dosage of isoniazid plus streptomycin preceded the once-weekly phase of high-dosage isoniazid plus streptomycin, the response was highly satisfactory in slow inactivators of isoniazid (as good as with the twice-weekly regimen) but was considerably less satisfactory in rapid inactivators. These findings suggest that if a method of compensating for the insufficiency of this regimen in rapid inactivators of isoniazid can be found, the prospects for evolving a highly satisfactory once-weekly regimen are bright

Influence of sex, age & nontuberculous infection at intake on the efficacy of BCG: re-analysis of 15-year data from a double-blind randomized control trial in south India

Background & objectives: To estimate the efficacy of BCG in preventing tuberculosis over a 15-year period, and also to assess the impact of infection with nontuberculous environmental mycobacteria in a rural community in Chingleput district in Tamil Nadu in south India. We re-analysed the 15-year follow up data of a large randomized trial conducted earlier. Methods: A double-blind randomized control trial was initiated in 1968, in which over 100,000 uninfected subjects with a normal radiograph were allocated to placebo, BCG in low dose (0.01 mg) or BCG in high dose (1.0 mg); two widely used strains of BCG were employed, each in one half of the vaccinated subjects. Sensitivity to purified protein derivative (PPD-B) was also determined. The study population was followed for 15 yr by radiographic surveys of the total population once every 2.5 yr, selective case finding in suspects once in 10 months, and investigation of those reporting voluntarily with chest symptoms. Results: Coverage by radiography was of the order of 80 per cent throughout, while coverage by sputum examination of suspects was usually 90 per cent or above. The annual incidence of culturepositive tuberculosis (irrespective of smear) was estimated to be 55 per 100,000, and neither strain of BCG had any effect. The failure to protect was seen in both males and females, and in children and adults. However, in a subset of over 40,000 subjects who were also nonreactors to PPD-B, BCG had a low level of protection, i.e., 32 per cent (95% CI=3-52%), 29 per cent with the Danish strain and 34 per cent with the French strain. Interpretation & conclusion: Our findings reaffirm that BCG was of little value in preventing sputumpositive cases of pulmonary tuberculosis

Controlled Comparison of Oral Twice-weekly and Oral Daily Isoniazid plus PAS in Newly Diagnosed Pulmonary Tuberculosis

A controlled clinical trial was undertaken in 247 patients with newly diagnosed pulmonary tuberculosis to assess the relative efficacies of a fully supervised twice-weekly oral regimen of isoniazid plus PAS (para-aminosalicylic acid) and a standard self-administered daily regimen of the same drugs following an initial intensive phase of two weeks of daily streptomycin, PAS, and isoniazid. Among patients who had isoniazid-sensitive cultures initially and who attended the clinic regularly the numbers with a favourable bacteriological response at the end of the year of chemotherapy were 79 (88%) out of 90 for the twice-weekly regimen and 72 (87%) out of 83 for the daily regimen; the numbers of patients with considerable radiographic improvement were 54 (60%) and 53 (64%) respectively. Complaints of vomiting or diarrhoea that did not require a reduction of the PAS dosage were made on one or two occasions by 23 (21 % ) out of 109 twice-weekly and 25 (23%) out of 108 daily patients, and on at least three occasions by 4 (4%) and 12 (11%) respectively. Finally, all five patients who had chemotherapy changed on account of hypersensitivity to PAS had been receiving the daily regimen, as also had one patient who died of agranulocytosis

Controlled Clinical trial of fully oral sort-course chemotherapy in the treatment of smear positive pulmonary tuberculosis

A prospective study to investigate three fully oral regimens of 6 or 8 months’ duration, with varying frequencies of attendance and different rhythms of drug intake is reported

Isoniazid plus Thioacetazone * compared with Two Regimens of Isoniazid plus PAS in the Domiciliary Treatment of Pulmonary Tuberculosis in South Indian Patients

Previous reports from the Tuberculosis Chemotherapy Centre, Madras, have established that ambulatory treatment of pulmonary tuberculosis with a standard daily regimen of isoniazid plus PAS for one year yields satisfactory results. However, this regimen may be unsuitable for large-scale use in many developing countries, because PAS is expensive, bulky and unpleasant to take, and has poor keeping qualities, especially in tropical countries. It might be possible to overcome these disadvantages, by substituting for the PAS a drug which is equally effective but less expensive and more acceptable, or by reducing the daily dosage of PAS and the period for which it is prescribed. This paper presents the results over a II-month period of a controlled comparison of (a) the standard regimen of isoniazid (average 4.5 mg/kg body-weight) plus sodium PAS (average 0.22 g/kg), daily in two divided doses ; (b) a regimen of isoniazid (average 6.9 mg/kg) plus thioacetazone (average 3.4 mg/kg), daily in one dose ; and (c) a 2-phase regimen of isoniazid (average 5.5 mg/kg) plus sodium PAS (average 0.17 g/kg), daily in one dose for 6 months, followed by isoniazid alone (average 6.8 mg/kg), daily in one dose for the second 6 months. The regimen of isoniazid plus thioacetazone was found to be therapeutically as effective as the standard regimen of isoniazid plus PAS ; however, it was associated with a higher incidence of minor side-effects, and three cases of exfoliative dermatitis. The 2-phase regimen of isoniazid plus PAS followed by isoniazid alone was less effective. These findings are encouraging for the large-scale use in developing countries of the relatively inexpensive regimen of isoniazid plus thioacetazone ; however, any such step should be preceded by carefully planned studies to investigate, under local conditions, the toxicity and the efficacy of the regimen

Trends in initial drug resistance over three decades in a rural community in south India

programme. Aims: To study trend of initial drug resistance over a period of three decades in a rural community in five panchayat unions in Chingleput district in south India. Methods: A total population survey of tuberculosis in the area was undertaken in 1968-70, comprising radiographic examination of all individuals aged 10 years or more and sputum examination of those with abnormal shadows. Subsequently, the total population survey was repeated on 6 occasions at intervals of 2.5 years along with new entrants found at each survey, and on two more occasions (1991-92, 1994-96) in a subset of two panchayat unions. Prevalence cases and (new) incidence cases of culture-positive tuberculosis were identified in each survey, and their susceptibility to Isoniazid and Streptomycin was determined. Results: Between 1968 and 1986, initial drug resistance to Isoniazid increased from 12.5% to 20.7% in prevalence cases, at an average annual rate of 3.1%. For Streptomycin, the increase was from 6.4% to 12.1%, at the rate of 4.9% per annum. In incidence cases, the corresponding annual rate of increase was 3.8% for Isoniazid and 7.4% for Streptomycin. In the subset of the population, that was surveyed in 1991-92 and 1994- 96, there was some evidence of a decline in the proportion of resistant cases after 1984-86. Conclusion: There was a steady increase in the magnitude of initial drug resistance in the community between 1968 and 1986, which probably indicates an unsatisfactory tuberculosis programme during the period

A Concurrent Comparison of Isoniazid plus PAS with Three Regimens of Isoniazid Alone in the Domiciliary Treatment of Pulmonary Tuberculosis in South India

Recent studies have shown that treatment of pulmonary tuberculosis with isoniazid plus p-aminosalicylic acid (PAS) at home is, in the majority of cases, as satisfactory as treatment with the same combination of drugs in sanatorium and does not appear to expose the patient’s contacts to any special risk. Before mass domiciliary chemotherapy can be introduced, however, a question that has to be decided is what drug or drugs and what dosage and rhythm of administration will be most effective. This paper presents the results of a controlled comparison of four chemotherapeutic regimens : (a) 3.9-5.5 mglkg body-weight of isoniazid plus 0.2-0.3 g/kg body-weight of PAS (sodium salt) daily in two doses (the standard combined chemotherapy) ; (b) 7.8-9.6 mglkg body-weight of isoniazid alone daily in one dose ; (c) 7.8-9.6 mg/kg body-weight of isoniazid alone daily in two doses ; (d) 3.9-5.5 mg/kg body-weight of isoniazid alone daily in two doses. Isoniazid plus PAS proved to be the most satisfactory regimen; it was clinically effective and there were very few toxic manifestations