The usefulness of the application of STC—a new tetrazolium salt— for the earlier detection of bacillary growth in the mycobacterial examination using the stock strains and the isolated strains was presented in the report 1.
This paper presents the results of the ap p lication of STC for the isolation culture and the direct resistance test. First, the influence of 1% NaOH treatment on the application of STC was examined.
10^-3 and 10^-5mg of H₃₇Rv and Kurono strain treated with 1% NaOH were inoculated on 1% Ogawa's media.0.1 Jul of 0.5% aqueous STC solution was added immediately, 1, 7 an d 14 days after the inoculation, and bacillary growth was examined at 10, 14, 21, 28 and 42 days after the inoculation. The results were shown in table 1. In the case of 1 NaOH treatment, the immediate addition of STC solution was also favourable for the earlier detection of bacillary growth, similar to the results presented in the report 1. The inhibitory effect of STC was not seen even in the case of immediate addition of STC solution.
The addition of STC solution was applied for the direct resistance test in which the sputa treated with 1% NaOH were inoculated on 1% Ogawa's media containing drugs. The results were shown in table 2. In the last case discharging atypical mycobacteria, the bacillary growth was seen earlier on the STC added media than the control media.

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The clinical use of prothionamide has been increasing recently because of less frequent gastrointestinal disturbance compared with that of ethionamide. Some workers, however, reported the higher hepatic disturbance during prothionamide treatment than ethionamide treatment. In Japan, the type of preparation of both drugs is different; ethionamide is used as the type of enteric coated tablet and prothionamide is used as the type of sugar coated tablet.
This paper presents the hepatic disturbance during ethionamide or prothionamide treatment by the using the same type of preparation. For a comparative study on hepatic disturbance between ethionamide and prothionamide treatment, the enteric coated granule of both drugs was specially prepared.
The patients who were newly prescribed TH were divided into two groups—ethionamide and prothionamide groups—alternatively. In both groups, daily dose of drug was 0.5g, divided into three equal dose and given after meal. In many cases kanamycin and ethambutol were combined with ethionamide or prothionamide. The hepatic function tests during ethiona mide or prothionamide taeatment were performed 1 to 2 times a month.
The results were as follows;
The elevation of SGOT or SG P T unit more than 40 units was observed among 11 out of 47 cases (23.4%) during ethionamide treatment and among 16 out of 47 cases (34.0%) during prothionamide treatment. The elevation of transaminase activity more than 100 units was seen in 10.6% during ethionamide treatment and 14.9% during prothionamide treatment (Table 1). The hepatic disturbance appeared more frequently among prothionamide group than among ethionamide group, but the difference was statistically not significant.
The time of the hepatic disturbance first appeared is shown in Tables 2 and 3. The hepatic disturbance during TH treatment appeared within 6 months. The difference in the incidence rate of the hepatic disturbance was not seen between 1 to 3 months and 4 to 6 months.
The relationship between the incidence of the hepatic disturbance and the background factors of the patients was studied (Table 4), but no relation was found.
In summary,
the hepatic disturbance was seen more frequently during prothionamide treatment than during ethionamide treatment, but the difference was not significant.

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By combining the indices which were reported in part 1, the criteria used for the evaluation of tuberculosis control were established, as indicated in Table. They were composed of 1 criterion for the evaluation of case-finding, 7 criteria for registration and supervision of tuberculosis patients and 2 criteria for treatment.
By using these criteria for screening procedures, the problems in tuberculosis control are easily detected on regional level.
These problems should b e confirmed by detailed investigations, and the methods for the detailed investigations were discussed.
The fact that no problem is pointed out by these screening procedures in certain regions, does not necessarily indicate the well-organized tuberculosis control program. It might indicate that tuberculosis control program is conducted on the average national level. In the region where tuberculosis is still highly prevalent, present status of tuberculosis control must be examined carefully though no problem is pointed out by this method.

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The author made analysis on the trend of tuberculosis infection in Okinawa by applying modified Sqblo's method on the results of tuberculin testing obtained from the tuberculosis prevalence survey in Okinawa, 1968.
The conclusions are the follo w ing
1) The annual risk of in f ection has been decreasing exponentially from 7% in 1940 to 0.3% in 1970.
2) T h e decrease of infection risk is steeper in rural area than in urban area.
3) The risk of infection is somewhat higher in male than in female, thou g h the declining trend is equal in both sexes.
These are expressed in mathematical equations, from which the age-specific tuberculin positive rates by different observation points and by the cohorts are calculated and predicted.
Discussions are made on the assumption of the employed method, namely the risk of infection is equal in all age-groups. The data of serial tuberculin testing of the schoolchildren indicates the existence of the age-specifity of infection risk. However, the effect of the age factor becomes less influential on the tuberculin positive rate in higher age-groups, due to the decrease of population at risk among them and the decrease of the risk in later calendar years, namely older age-groups of each cohorts.

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Although it has been proposed that atypical mycobacteriosis developed after a prolonged chemotherapy for pulmonary tuberculosis may due to the microbial alternation, convincing proof for this is not yet obtained.
The present study wa s designed to clarify whether an appropriate combination of antituberculosis drugs, when administered to the mice infected both with tubercle bacilli and atypical mycobacteria, enables the latter to survive solely in vivo.
Experiment I. Mice of dd-N strain were injected intraveno u sly with a mixture of each mg of strain H₃₇Rv and strain Mori, non-photochromogen. They were divided into 0t. w1o groups; one served as 'a control without chemotherapy and the other received two successive combined regimens of chemotherapy with the following daily doses: INH 0.1 mg SM 0.4 mg CS 0.15 mg for the first one and half months and KM 0.8 mg EB O.5 mg PAS 4 mg for the next five and half months. These combinations were devised on the basis of a previous experimente, which showed the therapeutic effect of seven months' single administrati on of drugs on mice infected with strain Mori as follows: INH, slight or no; SM, marked; CS, KM, EB, and PAS, adverse (i. e. worse). Animals were sacrificed three, five, and seven months after injection and viable bacterial units contained in each 1 mg tissue of lungs and spleen were calculated by Ogawa's method for quantitative cultivation. The nonphotochromogens were differentiated from tubercle bacilli by growth on media containing 1 mcg/ml PAS. The results were summerized in Table 1. The ratio of nonphotochromogens to tubercle bacilli in the spleen of the control mice tended to decrease gradually whereas the ratio in the treated animals maintained a very high level throughout the whole period of chemotherapy. On the other hand, all the bacilli obtained from the lungs of the control mice at three and five months were tubercle bacilli, but the ratio of nonphotochromogens to tubercle bacilli in the lungs of the treated animals increased gradually and reached to the high level after seven months of chemotherapy.
Experiment II. Male mice, dd-N strain, were injected intravenously with a mixture of each 0.1 mg of nonphotochromogens strain Morita and strainH₃₇Rv. They were divided into two groups one week later; one without treatment and the other treated with two successive regimens of chemotherapy consisting of INH 0.1 mg + SM 0.4 mg EB 0.5 mg for two months and then INH0.1mg + PAS 4 mg + CS 0.15mg sulfamethoxypyrazine (SF) 0.4 mg for two and half months. In the previous experiment therapeutic effects of the single use of drugs for four and half months on mice infected with strain Morita were as follows: INH, adverse; SM, marked; EB, slight; PAS, adverse; CS, slight; and SF, adverse. Animals were s acrificed two, three and half, and four and half months later. Differential viable counts were made on the lungs and spleen as described in Exp.1. As shown in Table 2, almost all the bacilli recovered from the lungs and spleen of the control mice especially from the latter were tubercle bacilli. On the contrary, the tissues of the treated mice were or became almost occupied by the nonphotochromogens at the later stage. Drug sensitivity tests were carried out on colonies isolated from the treated and non-treated animals after four and half months observation. Colonies grown on PAS medium were regarded as nonphotochromogens and those of R-form on drug-free medium as tubercle bacilli. Table 3 shows that all the tested colonies, ecept one, were very similar in their drug-susceptibility to their original strains, i. e. strain Morita and H₃₇Rv. One colony, c.2, was found to be a mixture of tubercle bacilli and nonphotochromogens.

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The present study deals with the comparison on the effect of combined use of Rifampicin (RFP) and Ethambutol (EB) with that of Viomycin (VM) and Ethambutol (EB) in retreatment cases of cavitary pulmonary tuberculosis resistant to various drugs.
The subjects were allocated at random to RFP group (51 c ases) and VM group (49 cases)by means of the envelope method, and the therapy was conducted for 6 months.
RFP was administered orally in the dose of 450 mg once daily before breakfast; EB orally in the dose of 1, 000 mg to cases with body weight more than 47 kg, 875 mg to cases with b. w. between 41-46 kg and 750 mg to cases with b. w. between 34-40 kg, once daily after breakfast; 1 g of VM was injected intramuscularly twice a week.
The background factors of the RFP group and the VM g roup are shown in Table 1. All cases were culture positive and showed resistance to two or more anti-tuberculous agents. Comparing the two groups, patients with a history of disease longer than five years occupied 43% and 41%, and far advanced cases 67% and 63%, in the RFP and VM groups, respectively. Thus, no significant difference was observed between both groups.
As presented in Table 2, negative conversion rate on c u lture reached to 92.2% already at 3 months and 92.0% at 6 months in the RFP group, and 66.7% each at 3 and 6 months in the VM group, and the difference was significant at 1% level.
The cases continued negative status both on smear a nd culture for more than 3 months at 6 months of treatment, were 40 (80%) out of 50 cases in the RFP group and 26 (62%) out of 42 in the VM group.
The majority of cases were occupied by cases with fibrocaseous or far advanced-mixed type in both groups, and favorable response on X-ray findings is hardly expected. As shown in Table 3, however, moderate and slight improvement of basic lesions on chest radiogram was observed in 12.0% and 30.0%, respectively, of the RFP group at 6 months, whereas slight improvement in 28.6% of the VM group. The RFP group also showed better improvement in cavities than in the VM group as shown in Table 4.
The effects on various clinical symptoms at two months are shown in Table 5. The body temperature became normal or fell down in 75%, and the erythrocyte sedimentation rate was improved in 64% of the RFP group, but no significant difference was recognized between the RFP and the VM groups.
Side effects du e to medication are shown in Table 6. Though side effects were observed in 5 (9.8%) out of 51 cases of the RFP group, drug administration had to be discontinued in none. On the other hand adverse reactions were found in 9 (18.4%) out of 49 cases of the VM group, and medication was discontinued in 4 cases (8.2%), 3 due to VM and 1 due to EB.
Elevation of S-GOT and S-GPT was seen in a few cases of both groups, but the elevation was transient in all cases, and it was unnecessary to discontinue the treatment.
In retreatment of resistant pulmonary tuberculosis with cavity, the combined use of RFP and EB showed better therapeutic effects and less side effects than the combination of VM and EB.

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