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S DEVADATTA

Publications and source records attributed to S DEVADATTA.

At least 19 recordsLinked to original sources
PubMed1964

THE EMERGENCE OF ISONIAZID-RESISTANT CULTURES IN PATIENTS WITH PULMONARY TUBERCULOSIS DURING TREATMENT WITH ISONIAZID ALONE OR ISONIAZID PLUS PAS.

Previous reports from the Tuberculosis Chemotherapy Centre, Madras, have described a comparison of four regimens (three of isoniazid alone and one of isoniazid plus PAS) in the treatment of pulmonary tuberculosis and an investigation of the serum isoniazid levels in the patients concerned. The present report studies the emergence of isoniazid-resistant organisms in these patients during treatment. All patients with an unsatisfactory response to treatment yielded resistant cultures, showing that the isoniazid dosage was never too low to inhibit sensitive organisms. From the degree of resistance of the first resistant cultures and of the six-month cultures from the patients treated with isoniazid alone it was concluded that resistance emerged in two stages. In the first stage, very earlyin treatment, highly resistant mutant bacilli grew freely whatever the isoniazid dosage, but mutants of lower resistance were prevented from growing to an extent dependent on the peak isoniazid concentration in the serum. Consequently, when the isoniazid dosage was increased the proportion of patients with resistant organisms decreased, since fewer low-resistance strains were able to develop. In the second stage, organisms with relatively low resistance continued to multiply, though still partially inhibited by isoniazid, and became more resistant, particularly in slow inactivators. The first-stage events determined the results of treatment since, once resistance had emerged, its extent was unrelated to the patient's eventual progress. These findings emphasize the importance of early intensive chemotherapy and adjustment of the isoniazid dosage according to peak serum concentrations rather than concentrations measured three or six hours after the dose. Concomitant administration of PAS prevented emergence of isoniazid resistance in many patients and in others delayed its emergence and reduced its degree, possibly because growth in the second stage was slow.

Aminosalicylic Acid↗
PubMed1962

The course of pulmonary tuberculosis in patients excreting organisms which have acquired resistance. Response to continued treatment for a second year with isoniazid alone or with isoniazid plus PAS.

This study from the Tuberculosis Chemotherapy Centre, Madras, summarizes the progress during the second year of the patients in a concurrent comparison of four domiciliary chemotherapeutic regimens (isoniazid plus PAS and three regimens of isoniazid alone) who had bacteriologically active or bacteriologically relapsed pulmonary tuberculosis, with isoniazid-resistant organisms, at the end of the first year of treatment.Of the 57 patients who continued on the same chemotherapy during the second year, nine had attained bacteriological quiescence by the end of that year, 15 still had bacteriologically active disease and 33 had during the year had a serious radiographic deterioration necessitating a change of treatment. An association was observed between the response to treatment in the second year and both the extent of cavitation and the degree of culture-positivity at the end of the first year, but no association was found between the response to treatment in the second year and the level of isoniazid-resistance, the catalase activity, the susceptibility to hydrogen peroxide or the virulence in the guinea-pig of cultures isolated in the last months of the first year.It is concluded that persisting bacteriological positivity at the end of one year's treatment with isoniazid, either alone or in combination with PAS, is likely to lead to serious radiographic deterioration, irrespective of the level of isoniazid-resistance or of the catalase activity of the cultures of tubercle bacilli, and that, consequently, treatment of patients with bacteriologically active pulmonary tuberculosis must aim at rendering the sputum culture-negative in all instances.

4-Aminobenzoic Acid↗
PubMed1961

Progress in the second and third years of patients with quiescent pulmonary tuberculosis after a year of chemotherapy at home or in sanatorium, and influence of further chemotherapy on the relapse rate.

A controlled comparison by the Tuberculosis Chemotherapy Centre, Madras, of the merits of home as compared with sanatorium treatment for pulmonary tuberculosis showed that, at the end of a year of chemotherapy with isoniazid plus p-aminosalicylic acid (PAS), the response of the home patients closely approached that of the sanatorium patients. The present report reviews the progress of those patients in the controlled comparison whose disease had attained bacteriological quiescence by the end of the year of combined chemotherapy. During the second year, half of the patients received further chemotherapy, with isoniazid alone, and half received a placebo, calcium gluconate. During the third year, half of those who were treated with isoniazid in the second year and whose disease remained quiescent continued to receive that drug and all the remaining patients with quiescent disease received the placebo. In the second and third years all the patients were treated at home and administered the medicaments to themselves.It has been concluded from this follow-up study that in the second and third years there was relatively little difference between the progress of the patients whose disease attained quiescence following a year of domiciliary treatment with isoniazid plus PAS and that of those whose disease attained quiescence following a year's treatment with the same drugs in sanatorium; that a second or third year of further treatment with isoniazid alone gave no better results than a year of combined chemotherapy, followed by careful observation of the patient and further chemotherapy if relapse occurred; and that the relapse rate among the patients with residual cavitation at the end of the year of combined chemotherapy was slightly higher than that among the patients with no residual cavitation at the end of the first year.

Aged↗
PubMed1961

Influence of segregation to tuberculous patients for one year on the attack rate of tuberculosis in a 2-year period in close family contacts in South India.

The authors present a second report from the Tuberculosis Chemotherapy Centre, Madras, on the incidence of tuberculosis in close family contacts of tuberculous patients. The patients initially received a year's chemotherapy either at home or in sanatorium in a controlled comparison of the merits of domiciliary as opposed to institutional treatment. The first report presented data relating to the prevalence and the attack rate of tuberculosis among the contacts during the first year of treatment of the index cases; this second report presents the attack rate for the 2-year period since the start of treatment for the index cases. During the second year all the index cases were managed at home, those with active disease, and half of those with quiescent disease, at the end of the first year receiving further chemotherapy. The findings of the 2-year study confirm those of the earlier study-namely, that the incidence of tuberculosis in the contacts of patients originally treated at home was no greater than that in the contacts of patients originally treated in sanatorium and that the major risk to the contacts resulted from exposure to the patient before diagnosis. As in the earlier report, the question of instituting chemoprophylaxis for the young contacts of tuberculous patients is discussed. The authors consider that close family contacts living in over-crowded, urban conditions in the developing countries are valuable groups for chemoprophylactic investigations.

Aged↗
PubMed1961

Response of patients infected with isoniazid-resistant tubercle bacilli to treatment with isoniazid plus PAS or isoniazid alone.

This study from the Tuberculosis Chemotherapy Centre, Madras, compares patients infected with isoniazid-resistant tubercle bacilli ("R" patients) with those infected with isoniazid-sensitive tubercle bacilli ("S" patients) as regards, first, their pretreatment status and, secondly, their response to a year's chemotherapy, either with isoniazid plus p-aminosalicylic acid (PAS) or with isoniazid alone. With regard to the first comparison, there was, on admission to treatment, little difference between the R and S patients in terms of the extent of the radiographic lesion, the extent of cavitation or the bacterial content of the sputum, but there were major differences in the age and sex distributions, the R patients showing a greater preponderance of young males than the S patients. As to the second comparison, statistically significant differences in the bacteriological response to treatment of the S and the R patients were observed in both the isoniazid-plus-PAS and the isoniazid-alone series, the response of the S patients being much better than that of the R patients. When the response to treatment was assessed in terms of radiographic progress and weight changes, however, hardly any difference was observed between the progress of the S and the R patients. The reasons for the response in the R patients are discussed.

Bacillus↗
PubMed1961

Rate of inactivation of isoniazid in South Indian patients with pulmonary tuberculosis. 3. Serum concentrations of isoniazid produced by three regimens of isoniazid alone and one of isoniazid plus PAS.

A series of studies on the rate of inactivation of isoniazid in Indian patients with pulmonary tuberculosis in a 1-year comparison of four domiciliary chemotherapeutic regimens-three of isoniazid alone, either in moderate (HI-1 and HI-2 regimens) or in low (H regimen) dosage, and one of isoniazid in low dosage plus p-aminosalicylic acid (PAS) (PH regimen) -has recently been undertaken by the Tuberculosis Chemotherapy Centre, Madras. This paper-the third of the series-presents information on the length of time during which inhibitory concentrations of isoniazid (0.2 mug/ml or more) were maintained in the serum and on the estimated peak serum concentrations of isoniazid produced by the four regimens and relates these factors to the therapeutic effectiveness of the different regimens.THE RESULTS SUGGESTED THAT: (a) the therapeutic superiority of the PH regimen over the isoniazid-alone regimens was only in part due to the effect of PAS in enhancing the serum levels of isoniazid; (b) the therapeutic superiority of the HI-1 regimen (moderate dosage, given in one dose a day) over the HI-2 and H regimens (moderate and low dosage, respectively, given in two doses a day) was due to the higher peak serum concentration of isoniazid produced rather than to the period minimal inhibitory concentrations of isoniazid were maintained in the serum; and (c) there was a possibility that raising the peak serum concentration of isoniazid above a critical concentration of about 3 mug/ml had a greater therapeutic effect than similar proportional increases below this concentration. It also appeared that the slightly better therapeutic response observed in the slow inactivators of isoniazid than in the rapid inactivators was due to the higher peak serum concentrations of isoniazid produced; the enhanced therapeutic effect was approximately the same as would be expected from a 50% increase in isoniazid dosage.

Humans↗
PubMed1961

Progress in the second year of patients with quiescent pulmonary tuberculosis after a year of domiciliary chemotherapy, and influence of further chemotherapy on the relapse rate.

This study from the Tuberculosis Chemotherapy Centre, Madras, summarizes the progress during the second year of those patients in a 1-year comparison of four domiciliary chemotherapeutic regimens (isoniazid plus PAS and three regimens of isoniazid alone) whose pulmonary tuberculosis had attained bacteriological quiescence at the end of the year of chemotherapy. During the second year, about half of the patients received further chemotherapy, with isoniazid alone, and the remainder received a placebo, calcium gluconate. The main objects of the study were to determine the influence on the progress during the second year of (a) a second year of chemotherapy with isoniazid alone, (b) residual cavitation at the end of the first year, and (c) the chemotherapeutic regimen received during the first year, and to compare the results with those obtained in an earlier study by the Centre of the progress during the second year of patients with quiescent pulmonary tuberculosis after a year's chemotherapy with isoniazid plus PAS at home or in sanatorium.The results of the present study, which was planned on the same lines as the earlier one, showed that relapse in the second year was unrelated to the chemotherapeutic regimen received in the first year, and it was therefore permissible to amalgamate the findings in the two studies. The amalgamated results showed that the relapse rate in the second year was low (5.9%) and that a second year of treatment with isoniazid alone was of definite value for the patients with no residual cavitation at the end of the first year, but had no effect on the relapse rate of those with residual cavitation. The combined data from the two studies have thus clarified the position with regard to the effectiveness of isoniazid in preventing bacteriological relapse in patients without residual cavitation, slight evidence of which was apparent in the earlier study.

Aminosalicylic Acid↗
PubMed1961

Prevalence and early attack rate of tuberculosis among close family contacts of tuberculous patients in South India under domiciliary treatment with isoniazid plus PAS or isoniazid alone.

The authors present a report from the Tuberculosis Chemotherapy Centre, Madras, on the prevalence and attack rate of tuberculosis among close family contacts of tuberculous patients in South India undergoing domiciliary chemotherapy either with isoniazid plus PAS or with one of three regimens of isoniazid alone. The report gives (a) the prevalence of tuberculosis among the contacts at the time of diagnosis of the disease in the patients and (b) the incidence of tuberculosis in the contacts during the first year of treatment of the patients. The contacts were divided into four series, corresponding to the four chemotherapeutic regimens of the patients.The prevalence of active tuberculosis was found to be particularly high among children under five years of age, being 12.0% as compared with 7.6% for all age-groups combined. The incidence of active tuberculosis during the year of treatment of the patients was also found to be highest in the under five years' age-group-a further indication that child contacts are especially vulnerable to infection. The incidence was considerably higher in the first quarter of the year than in the other quarters, and it was lowest in the last quarter. This finding, together with the fact that the attack rates in the four contact series were not related either to the duration of bacteriological positivity in the patients or to the period of excretion of isoniazid-resistant organisms by the patients, suggests that the major risk to contacts in the first year results from exposure to the patient before treatment rather than from exposure during treatment. These results thus confirm the findings in an earlier study by the Centre of the contacts of patients in a controlled comparison of chemotherapy with isoniazid plus PAS at home and in sanatorium.

Aminosalicylic Acid↗
PubMed1960

Prevalence of tuberculosis among close family contacts of tuberculous patients in South India, and influence of segregation of the patient on early attack rate.

The results of a study by the Tuberculosis Chemotherapy Centre, Madras, of the merits of home as compared with sanatorium treatment for pulmonary tuberculosis have indicated that treatment at home is satisfactory in the majority of cases. Before domiciliary chemotherapy can be introduced on a large scale, however, it must be established that it does not expose the patient's contacts to a special risk of infection, avoided by his isolation in a sanatorium. Accordingly, a further study was undertaken by the Centre to determine (a) the prevalence of tuberculosis among the family contacts of patients, and (b) the incidence of clinical tuberculosis and of tuberculous infections in the family contacts of the home and sanatorium groups of patients during the first year of treatment. The findings of this study indicate that the major risk for contacts lies in exposure to the infectious case before diagnosis, whether the patient subsequently remains at home or is isolated in a sanatorium appearing to have little importance, if the patients at home are treated with effective chemotherapy. Children under seven years of age proved to be particularly vulnerable to infection. The management of young contacts by chemoprophylaxis or by BCG vaccination, or by both measures, has been discussed.

Chemoprevention↗
PubMed1960

Peripheral neuritis due to isoniazid.

It is well known that in the treatment of tuberculosis with isoniazid the complication of peripheral neuritis may arise. This complication is normally rare when small dosages of the drug are used, but a high incidence of the neuropathy has recently been observed in East Africa in a group of malnourished tuberculous patients receiving isoniazid in comparatively low dosage (4-6 mg/kg body-weight daily). The present paper reports on 20 cases of peripheral neuritis encountered in Madras, India, among 338 poorly nourished tuberculous patients during a trial of four isoniazid regimens, two of low and two of high dosage (3.9-5.5 and 7.8-9.6 mg/kg body-weight daily, respectively). Nineteen of the 20 cases occurred in the two groups of patients receiving the high dosage and these 19 patients were found to have a higher mean serum level of free isoniazid than the patients in the same groups who did not develop the complication. The authors consider that dosages of 7.8-9.6 mg/kg body-weight daily should not be used for the mass therapy of poorly nourished patients unless steps are taken to prevent the development of peripheral neuritis. Pyridoxine has been reported to be an effective preventive, but is too expensive for use on a large scale. This study indicates, however, that administration of the cheaper vitamin B complex might give satisfactory results and warrants further investigation.

Africa, Eastern↗
PubMed1960

Progress in the second year of patients with quiescent pulmonary tuberculosis after a year of chemotherapy at home or in sanatorium, and influence of further chemotherapy on the relapse rate.

A recent report by the Tuberculosis Chemotherapy Centre, Madras, showed that the response of patients to a year's domiciliary treatment for pulmonary tuberculosis with isoniazid plus p-aminosalicylic acid closely approached that of patients to a year's sanatorium treatment with the same combination of drugs. The present report summarizes the findings of a second year's study, carried out on those patients in the first-year study whose disease had attained bacteriological quiescence by the end of the year of combined chemotherapy. The main objects of this follow-up study were to determine (a) whether relapse in the second year was more frequent among the patients originally treated at home than among those originally treated in sanatorium, (b) whether a second year of antituberculosis chemotherapy, with isoniazid alone, would reduce the relapse rate and (c) the influence of residual cavitation at one year, the so-called "open negative" syndrome, on the results in the second year. During the second year all the patients were treated at home, either with isoniazid or with a placebo, calcium gluconate; in each case the medicine was administered by the patients themselves. It was found that there was very little difference in the relapse rates of the "home" and "sanatorium" groups, that a second year of treatment with isoniazid alone did not influence the likelihood of relapse, and that patients with the open negative syndrome fared slightly less well in the second year than patients without residual cavitation.

Aged↗