J.B. Selkon

The Prevalence of Drug-resistant Tubercle Bacilli in Untreated Patients with Pulmonary Tuberculosis: a National Survey, 1955-56.

Summary The findings of a survey to assess the prevalence in England, Wales and Scotland of bacillary resistance to streptomycin, PAS and isoniazid among newly diagnosed and previously untreated cases of pulmonary tuberculosis are reported. A representative sample of 80 chest clinics, selected by a random process, participated in the survey, and with the co-operation of their chest physicians 1,404 sputum specimens, from the same number of patients, were cultured at a central laboratory. The collection of specimens started on June 15, 1955, and ended on March 8, 1956. Sensitivity tests to streptomycin, PAS and isoniazid were undertaken on all positive cultures. Of the 974 positive cultures obtained, 50 (5·1 per cent) were resistant to one or more of the three anti-tuberculosis drugs; 44 (4·5 per cent) yielded Myco. tuberculosis; and 6 (0·6 per cent) yielded resistant atypical mycobacteria. Of the 44 resistant strains of Myco. tuberculosis, 22 (2·3 per cent) were resistant to streptomycin, 21 (2·2 per cent) to PAS and 7 (0·7 per cent) to isoniazid; 5 of the strains showed resistance to more than one of the drugs. Those patients found to be infected with resistant organisms were further investigated; their contact histories were compared with those of a similar group of patients derived from those patients infected with sensitive organisms. For each drug separately more of the resistant group than of the sensitive group were known to have been in contact with cases treated with the drug. Definite evidence of contact with organisms resistant to the relevant drug was obtained for 3 of the 22 patients infected with streptomycin-resistant organisms, for 5 of the 21 patients with PAS-resistant strains and for 2 of the 7 patients with isoniazid-resistant strains. No evidence of contact with resistant organisms was found in the matched sensitive group. The clinical, radiographic and bacteriological progress in the two groups of patients are at present being compared and the findings will be reported later.

VIRULENCE IN THE GUINEA-PIG AND SENSITIVITY TO PAS AND THIACETAZONE OF TUBERCLE BACILLI FROM SOUTH INDIAN PATIENTS WITH PULMONARY TUBERCULOSIS.

Summary Isoniazid-sensitive strains of tubercle bacilli, obtained pretreatment from 280 South Indian patients, were tested for their virulence in the guinea-pig and for their sensitivity to PAS; strains from 209 of these patients were also tested for their sensitivity to thiacetzone. Strains of low virulence more often had a high proportion of PAS-resistant mutants and were more ofter resistant to thiacetazone than those of high virulence. There is suggestive evidence that Indian strains can be divided into two groups, the smaller group, comprising about one-quarter of the strains, resembling strains from British patients and the larger group characterized by a lower virulence, a higher susceptibility to hydrogen peroxide, a higher proportion of PAS-resistant mutants and thiacetazone resistance.

A controlled comparison of cycloserine plus ethionamide with cycloserine plus thiacetazone in patients with active pulmonary tuberculosis despite prolonged previous chemotherapy

Summary Twenty-seven patients with chronic pulmonary tuberculosis who had failed to respond to two previous chemotherapeutic regimens were allocated to treatment with cycloserine plus ethionamide (14 patients), or with cycloserine plus thiacetazone (13 patients). All had isoniazid-resistant strains and all but one had streptomycin-resistant strains at the start of the study. At the end of a year nine of 14 patients in the ethionamide series compared with three of 13 in the thiacetazone series had bacteriologically quiescent disease, one and three. respectively, had bacteriologically active disease; during the year, two patients (one in each series) deteriorated and had their chemotherapy changed and two patients (both on thiacetazone) died of tuberculosis. The difference in the proportions of unfavourable response attained statistical significance. There was one case of peripheral neuropathy due to ethionamide. Definite toxicity to thiacetazone was not observed. One of nine patients excluded from the main analysis had had intractable vomiting due to cycloserine.

The Niacin Test for Differentiating Human Tubercle Bacilli from other Mycobacteria.

Summary A test for the production of niacin was carried out on 13 human strains of tubercle and on 13 strains of bovine and avian tubercle bacilli, and other mycobacteria. The tests were always positive on cultures of human strains incubated for five to eight weeks, but were always negative with the other strains.

Solid and liquid medium tests of streptomycin sensitivity of Mycobacterium tuberculosis

Summary Thirty-six cultures obtained from patients who had never had streptomycin and 84 cultures resistant or possibly resistant to streptomycin were tested in three different laboratories for sensitivity to streptomycin on solid medium, in liquid medium containing Tween 80, in liquid medium containing Triton WR1339, and in liquid medium without surface-active agents. o (1) The presence of Tween 80, but not Triton WR1339, in the liquid medium resulted in failure to detect an appreciable number of streptomycin-resistant strains. (2) Discrepant results suggested that in two of the laboratories the liquid medium was of relatively poor quality although it was prepared and used in the same way as in the third laboratory, and that this was partly responsible for the failure of liquid medium tests to detect resistant strains. (3) Tests for streptomycin sensitivity in solid medium were the most satisfactory, and results should be expressed as resistance ratios.

The consistency of the virulence in the guinea-pig of tubercle bacilli isolated on different occasions from South India patients before treatment

Summary Isoniazid- and streptomycin-sensitive cultures of tubercle bacilli, isolated pretreatment from 12 South Indian patients when they first attended the Centre, and at 7 and 42 days thereafter, were tested for their virulence in the guinea-pig. The variation in virulence between patients was greater than the variation between cultures from the same patient. Thus, consistent differences exist between the virulence of strains of tubercle bacilli isolated from different Indian patients. No systematic alteration in virulence occurred during the 42-day period, during which no patient was receiving anti-tuberculosis chemotherapy. The variation in virulence between cultures obtained from the same patient was no greater than could be attributed to natural variation in the response of the guinea-pigs.