Short-course chemotherapy for tuberculosis of the spine. A comparison between ambulant treatment and radical surgery--ten-year report.

We performed a randomised, controlled clinical trial to compare ambulant short-course chemotherapy with anterior spinal fusion plus short-course chemotherapy for spinal tuberculosis without paraplegia. Patients with active disease of vertebral bodies were randomly allocated to one of three regimens: a) radical anterior resection with bone grafting plus six months of daily isoniazid plus rifampicin (Rad6); b) ambulant chemotherapy for six months with daily isoniazid plus rifampicin (Amb6); or c) similar to b) but with chemotherapy for nine months (Amb9). Ten years from the onset of treatment, 90% of 78 Rad6, 94% of 78 Amb6 and 99% of 79 Amb9 patients had a favourable status. Ambulant chemotherapy for a period of six months with daily isoniazid plus rifampicin (Amb6) was an effective treatment for spinal tuberculosis except in patients aged less than 15 years with an initial angle of kyphosis of more than 30 degrees whose kyphosis increased substantially.

A controlled clinical trial of short-course chemotherapy for tuberculoma of the brain.

OBJECTIVE: The efficacy of a short-course regimen in the treatment of brain tuberculoma and computerised tomography (CT) scan appearance before, during and after antituberculosis treatment was studied in a controlled clinical trial. DESIGN: Patients aged over 5 years with tuberculoma of the brain diagnosed by CT scan were randomly allocated to one of the following 2 regimens: Regimen 1: rifampicin, isoniazid and pyrazinamide daily for an initial 3 months followed by rifampicin and isoniazid twice-weekly for 6 months. Regimen 2: rifampicin, isoniazid and pyrazinamide thrice-weekly for an initial 3 months followed by rifampicin and isoniazid twice-weekly for 6 months. The patients were followed intensively for 2 years from the start of treatment. RESULTS: Of the 108 patients analysed (regimen 1: 56, regimen 2: 52), at the end of treatment clinical status was normal in 91% in regimen 1 and 88% in regimen 2. Of the 91 patients with scan assessments, CT scan lesions disappeared at 24 months in 77% of 47 patients in regimen 1 and 80% of 44 in regimen 2, and in both groups 88% of the patients were clinically normal. None had relapses requiring treatment. CONCLUSIONS: Short-course regimens of 9 months' duration are effective in the treatment of tuberculoma of the brain; clinical recovery was faster than scan clearance.

Five year results of a 3-month and two 5-month regimens for the treatment of sputum-positive pulmonary tuberculosis in south India.

A controlled study of three short-course regimens was undertaken in South Indian patients with newly diagnosed, sputum-positive pulmonary tuberculosis. The patients were allocated at random to one of three regimens: a) Rifampicin, streptomycin, isoniazid and pyrazinamide daily for 3 months (R3); b) the same regimen as above but followed by streptomycin, isoniazid and pyrazinamide twice-weekly for a further period of 2 months (R5); c) the same as R5 but without rifampicin (Z5). A bacteriological relapse requiring treatment occurred by 5 years in 16.8% of 113 R3, 5.2% of 97 R5, and 20.0% of 115 Z5 patients with organisms sensitive to streptomycin and isoniazid initially. The differences in the relapse rates between the R3 and R5 regimens and the R5 and Z5 regimens were statistically significant (p less than 0.01 for both). Considering patients with organisms initially resistant to streptomycin or isoniazid or both, 7 of 52 patients (4 R3, 2 R5, 1 Z5) had a bacteriological relapse requiring retreatment.

Controlled clinical trial of two multidrug regimens with and without rifampin in highly bacilliferous BL/LL south Indian patients: a five-year report.

A controlled clinical trial of two multidrug regimens in multibacillary lepromatous and near-lepromatous patients with a bacterial index (BI) of 2.5 or more was conducted. Patients were randomly allocated to either a two-drug regimen of dapsone plus clofazimine for 60 months or a four-drug regimen of rifampin, isoniazid, dapsone, and clofazimine for the first 3 months and clofazimine plus dapsone for the next 57 months. There was no difference between the rifampin and nonrifampin regimens with respect to the clinical improvement or bacteriological status of the patients at 60 months. Reactive states and neuritis were observed to be equal in the two patient groups.

A double-blind controlled clinical trial to assess the role of anti-histamines in the treatment of multi-bacillary leprosy.

A double blind controlled clinical trial to assess the role of anti-histamines as a supplement in the treatment of leprosy was conducted in multi-bacillary cases of leprosy. In all, 120 patients with lepromatous or borderline leprosy were randomly allocated to a regimen of clofazimine and dapsone for 12 months with or without a supplement of pheniramine maleate for the first 3 months. During the 12-month period, 92% of the patients who received the supplement and 86% of the patients who had not received it had moderate or marked clinical improvement. The BI values decreased from 4.1 to 3.4 and 4.2 to 3.3, respectively. The results over the 12-month period showed that the addition of the antihistamine had not enhanced the efficacy of the regimen as evidenced by clinical and bacteriological findings.

An enquiry into the attitudes of South Indian patients to the coloration of their urine by rifampicin.

This report enquiring into patients' attitudes to their urine being coloured by rifampicin has shown that many of them regarded it as evidence of the potency of their medicine or of the elimination of the disease. Attention is drawn to the value of the coloured urine as a reminder to patients whether or not they have taken their due dose of rifampicin-containing medicine.

Hepatic toxicity in South Indian patients during treatment of tuberculosis with short-course regimens containing isoniazid, rifampicin and pyrazinamide.

Results are presented of the incidence of hepatitis, nearly always with jaundice, among 1686 patients in clinical trials of the treatment of spinal tuberculosis, of tuberculosis meningitis and of pulmonary tuberculosis with short-course regimens containing rifampicin, isoniazid, streptomycin and pyrazinamide. The incidence was high in patients treated with daily regimens of isoniazid and rifampicin: 16-39% in children with tuberculous meningitis, 10% in patients with spinal tuberculosis (non-surgical cases), and 2-8% in those with pulmonary tuberculosis. Hepatitis, in those receiving rifampicin occurred more often in slow than in rapid acetylators of isoniazid, the proportions amongst those whose acetylator phenotype had been determined being 11% of 317 slow acetylators and 1% of 244 rapid acetylators. In children with tuberculous meningitis, the risk of hepatitis with isoniazid 20 mg/kg (39%) was higher than that with 12 mg/kg (16%), and appreciably lower in patients given rifampicin twice-weekly (5%) rather than daily (21%). There was no indication that pyrazinamide contributed to the hepatic toxicity.

Species level identification of non-tuberculous mycobacteria from South Indian BCG trial area during 1981.

In 1981, non-tuberculous mycobacteria (NTM) were obtained from 8.6% of 16 907 sputum specimens in a trial in the Chingleput district of Madras state to test the efficacy of BCG vaccination in the prevention of tuberculosis, but from only 0.6% of 672 autoclaved specimens cultured as part of a quality control procedure. This finding suggested that the NTM were truly derived from the sputum of the BCG trial subjects. The mycobacterial species could be identified in 966 (96.6%) of the first 1000 isolates of NTM: 54.6% were potential pathogens and 73.0% were slow growing. The species isolated most frequently were M. avium/intracellulare (22.6% of all NTM), M. terrae (12.5%) and M. scrofulaceum (10.5%). Those species accounting for 8-5% of all NTM were M. fortuitum, M. chelonei, M. flavescens, M. gordonae and M. vaccae.

A novel system to obtain addresses of out-patients--assessment in routine clinic practice in Madras, S. India.

A novel method of obtaining accurate home addresses from out-patients was introduced as a routine procedure in 6 chest clinics of Madras City, following highly satisfactory results under study conditions. In this method, the patient is given a card (the address card), and asked to get his exact address entered on it by any knowledgeable person of his choice such as a landlord or neighbour. An assessment of the system was undertaken after it had been in operation for about 8 months. A complete and legible address was available for 82% of 3956 patients, the range in the 6 clinics being 74% to 91%. The main causes for failure were: not giving address card to patient (7%), patient not reattending the clinic (6%), and patient reattending but not returning the address card (3%). Corrective measures have now been introduced, and a re-assessment will be undertaken in due course.

Lack of relationship between hepatic toxicity and acetylator phenotype in three thousand South Indian patients during treatment with isoniazid for tuberculosis.

The results are presented of a retrospective analysis of the incidence of jaundice among 3,000 patients with pulmonary tuberculosis and of the activities of serum aspartate aminotransferase among 850 according to their isoniazid acetylator phenotype. The patients had been treated with a variety of isoniazid-containing regimens in a series of controlled clinical trials in South India. The results show that rapid acetylators are no more prone to develop isoniazid-induced hepatic toxicity than are slow acetylators.

Effect of storage of sputum specimens at room temperature on smear and culture results.

A study of 41 specimens of sputum stored for up to 28 days at room temperature in a tropical country showed that smear results were not affected by storage, the positivity being 83% before storage and 80-83% after. The culture positivity was 88% before storage, and 83%, 68%, 22%, 13% and 0% after 3, 7, 14, 21 and 28 days of storage respectively. The reduction in positivity on storage attains significance at 7 days (P = 0.05). Another study involved 163 specimens of sputum and storage for 3, 5 or 7 days. Each specimen was examined before storage and after 2 periods of storage, at random. The smear results were again not affected. There was, however, significant loss of viability, the proportion culture positive being reduced from 92% before storage to 83% at 3 days (P = 0.05), 71% at 5 days (P less than 0.01) and 63% at 7 days (P less than 0.001). The contamination rate was 5%, 7%, 12% and 18% respectively. It is concluded that sputum should not be stored at room temperature for longer than 3 days for culture but it can be stored for 4 weeks without any loss of smear-positivity.

Study of a policy to minimise the prescription of medicaments at first attendance at chest clinics.

In chest clinics in Madras, south India, medicaments are prescribed to many patients at the first clinic attendance, whether necessary on medical grounds or not, in the belief that this practice will increase the likelihood of the patients subsequently reattending the clinic. This study of 2608 patients in four chest clinics showed that the proportion prescribed medicaments ranged from 50% to 75%. Subsequently, a modified policy of prescribing medicaments only when they were medically essential was investigated on 956 patients in the largest of these clinics. The policy was found to be practicable, and it did not have any adverse consequences such as an increased rate of default or an unacceptable level of patient dissatisfaction. The advantages of the new policy are savings in money, man-power, and time and the potential for a reduction in the incidence of side-effects.

A randomised study of two policies for managing default in out-patients collecting supplies of drugs for pulmonary tuberculosis in a large city in South India.

A randomized controlled study was undertaken to compare 2 policies of default management in out-patients with smear-negative pulmonary tuberculosis attending a large chest clinic in Madras city. All the patients were due to collect monthly supplies of drugs for a year, for daily self-administration at home. In the routine (R) policy, if a patient failed to collect the drug supply on a due date, a reminder letter was posted on the fourth day and, if necessary, a health visitor visited the home a week later. In the intensive (I) policy, a health visitor visited the home on the 4th day and, if necessary, a week later and at 1 and at 2 months. The main analyses concern 150 patients (75 R, 75 I), of whom 16 R and 15 I patients had a positive culture. A total of 29 patients (11 R, 18 I) did not default at any time. For the remaining 64 R and 57 I patients, the mean numbers of defaults were 3.0 and 2.3, and the mean numbers of defaulter retrieval actions were 4.3 and 3.8, respectively. The home visit as the first action (I series) was successful in retrieving defaulters on 65% of 132 occasions, while the reminder letter (R series) was successful in 56% of 193 occasions (P = 0.1). Following the second action, which was a home visit in both the series, these proportions became 80% and 84%, respectively. in the I series, 22 third and 18 fourth actions were taken, but the patient was retrieved in only 4 and 0 instances respectively. The mean number of drug collections during the year was significantly higher in the I series (9.8) than in the R series (8.6). Finally, the proportions of patients who made 12 collections in a 15-month period, a satisfactory target under Indian Programme conditions, were 69% and 52%, respectively (P = 0.07).

An investigation of the accuracy of the home address given by patients in an urban community in South India.

Studies were undertaken in three tuberculosis clinics in Madras, a large Indian city with a good civic organization, to assess the accuracy of address recorded routinely by registry clerks at the patient's first clinic attendance. The accuracy was poor, with 20% to 30% of the letters posted not reaching the patients. It was appreciably improved, by 10% to 20%, by supplementing the clerk's efforts with questioning by a motivated, experienced health visitor. An address card, a card on which the patient's address was recorded by the local postman or a literate neighbour, relative or friend, was returned by 90% to 94% of the patients, and the accuracy of addresses was found to be at least as good as that obtained with the health visitor. Even when all three sources of information were considered, the patient's home could not be traced in 3% of cases and was found with difficulty in 4%.

Studies of immediate adverse reactions to different doses of a slow-release preparation of isoniazid.

'Double-blind' studies were carried out to assess the incidence of immediate adverse reactions to different doses of a slow-release preparation of isoniazid (matrix isoniazid). Individual doses of 30 mg/kg matrix isoniazid were well-tolerated but higher doses resulted in giddiness, the incidence being dose-related. The giddiness was characterized by a late onset and was usually present even at 24 hours. A few patients complained of gastro-intestinal symptoms. It is concluded that matrix isoniazid can be given to Madras patients in doses of 30-40 mg/kg without risk of an undue incidence of immediate adverse reactions.