A general review was made on the development of the national tuberculosis control programme in Japan together with the discussions on its future direction. A principle of the national tuberculosis control programme was established and reported by Oka already in 1935. However, its implementation had been postponed until 1951 due to severe conditions during and soon after the World War II.
The Tuberculosis Control Law was legislated in 1951. One of the peculiarities of this law was to integrate the programme into the existing health care system in Japan including a network of general practioner's clinics and of health centres covering whole Japan. Another peculiarity was the public subsidy given to MMR, BCG vaccination and treatment.
Tuberculosis control programme has been ammended and improved by taking into consideration the changes in the epidemiological situation of tuberculosis and the development of techniques used for controlling tuberculosis.
Major difficulties which might be encountered in the coming turn of tuberculosis programmes are the following: 1) Japanese population is divided into two groups, tuberculosis polluted and clean generations, and the borderline of the two generations exists at 45 to 50 years of age. The control programme is different in these two groups, but the two groups are actually living in the same community and in the same family. 2) The speed of decline of tuberculosis differs by the area, sex, age, etc. Tuberculosis remains in groups to which the approach is more difficult. 3) To cut down the programme is more difficult than to expand them. 4) Concern of general public as well as of medical professions has been coming down faster than the decline of tuberculosis. 5) Due to the slowdown of the economical development since 1975, very strict regulations have been given for the national budget, and this is particularly true for the health and welfare budget as its expansions has been rapid.
Future direction of the national tuberculosis programme was discussed. The priority of case-finding will be given more and more to symptomatic visit to doctors. The delay in detecting tuberculosis patients might deteriorate in the future due to the lowering concern of both general public and of doctors on tuberculosis and the partial cutdown of the 100% coverage of expenses for medical treatment by the health insurance scheme for employees. Concerning treatment programme, the duration of treatment and of hospitalization is to be shortened, as it is still much longer than that in technically advanced countries. Method of tuberculosis prevention will be shifted from the mass BCG vaccination to chemoprophylaxis. A system of surveillance for tuberculosis and its control programme was already established, and the Research Institute of Tuberculosis, JATA, is working as a national tuberculosis surveillance centre.
One of the main great topics which remained unsolved is a tuberculosis programme in developing countries. Main reasons of failure in bringing tuberculosis under control in deveoping countries are the weakness and slow development of the basic health services to which the tuberculosis programme is to be integrated, and the weakness in the organization of supervisory and managerial teams in tuberculosis control. How to speed up the development of primary health care systems and how to integrate smoothly the tuberculosis programme into the basic health services are the problems which should be solved urgently.

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In the rabbits transplanted intradermally with Brown Pearse sarcoma cells (B-P cells), the mononuclear cell turnover in the skin lesions was studied periodically. The mononuclear cells (MNs), that were positive for β-galactosidase, made defense walls in the periphery of the tumor lesions from 4 to 16 days after B-P cells transplantation. During the days, the intradermal growth of B-P cells was enhanced more prominently in the rabbits with BCG inoculation on the day of the tumor transplantation than in the rabbits without BCG inoculation, while thereafter, the defense walls of the MNs became gradually loose and then disappeared in both groups.
Thereupon, a number of the MNs in 1 mm² of the peripheral lesion was counted periodically. The accumulation of the MNs in a tumor lesion of the rabbits without BCG lesions at the 7th day was about 2 fold higher than that with BCG lesions.
These results suggest that the MNs have a inhibitory capacity depending on a number of the accumulated MNs in the tumor lesions, and the inhibitory capacity of the MNs is reduced if the supply of the MNs is divided into the BCG lesions and the tumor lesions, thus causes the enhanced tumor growth.

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A short-course chemotherapy with SM, INH and REP supplemented for the first two months with Pyrazinamide (PZA) have been made since 1979.
Eighty two cases bacilli positive newly diagonosed pulmonary tuberculosis were subjected to the study, and 12 (15%) were dropped out due to adverse reactions by PZA (Table 7).
The rate of negative conversion of bacilli in sputum as the second months after starting chemotherapy was 95.7%, which was significantly higher than that in cases treated with the SM·INH·RFP regimen as previously reported (Fig. 1).
The difference in the results was particularly remarkable in cases with large amount of bacilli discharge at the start of treatment; the negative conversion rate was 94.1% in PZA containing group and 78.6% in SM·INH·REP group. (Table 3)
As shown in table 4, 19 out of 70 cases were dropped out from the follow-up study, and in 31% of the remaining 51 cases, a further radiographic improvement was seen after completing chemotherapy.
Only one case (2%) showed radiographic and bateriological relapse at the 4th months after completing chemotherapy. (Table 5, 6)
In 47% cases using PZA, serum uric acid concentration was elevated during the period of treatment, but no correlation was found between subjective arthralgia and elevation of serumuric acid level.
The above mentioned experience showed that the higher and faster sputum negative conversion with less chance of relapse was obtained by the initial intensive chemotherapy with SM·INH·REP adding PZA for the first two months.
Moreover, the regimen containing pyrazinamide did not produce undue toxicity.
This regimen might be successful even for cases with primary resistance to INH.

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Background factors of seven patients with lung tuberculosis, who died suddenly by massive hemoptysis (more than 1, 000ml) were as follows:
1) The age of the patients was 32 to 78 (average 51 years);
2) Duration of lung tuberculosis until death was more than 10 years;
3) All patients, except for one, showed tubercle bacilli both on smear and culture with multiple drug-resistance;
4) All patients showed one or more large cavities (more than 5cm in long size) at least in one lung.
The above findings indicated the presence of large cavities with active tuberculous process. It has been suggested that the fatal massive hemoptysis occurs due to rupture of arteria pulmonaris remaining in an old, large cavity by invasive tuberculous process. The patients with the above conditions should be subjected to careful observation in a hospital.

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Thirty years have passed since the epoch-making report of the disease caused by atypical acid-fast bacilli presented by Pollak and Buhler in the beginning of the 1950s. During these three decades, the epidemiology, and the clinical features of the diseases caused by so called atypical mycobacteria have been elucidated by many investigators, who have been supported by a remarkable advance in the field of the classification of mycobacteria.
Many problems are still unsolved, however, and the urgent problems to be solved exist in the treatment of Mycobacterium avium-M. intracellulare complex (M. intracellulare) infection, which is now the most prevalent disease among atypical mycobacterial infections in Japan. Because of lack of susceptibilities of M. intracellulare against various antimicrobial substances, in vitro and in vivo energetic investigations are still of paramount importance. In this lecture, the author intended to discuss the present status of experimental studies from the point of clinical mycobacteriology with intentional references to our recent studies.
(1) In vitro studies: Many clinical investigators have suggested the benefits of using multidrug regimens in the treatment of M. intracellulare infections. Our in vitro studies demon strated the potentiations of the bacteriostatic effects against M. intracellulare in various 3- antituberculous drug regimens, and possibly in some 5-drug regimens on solid medium. However, the results were rather unpredictable, and the elucidation of the fundamental mechanisms of the drug resistance of M. intracellulare are urgently needed. In the study of different colony formers [thin-transparent colony-formers (T-formers), opaque dome-shaped colony-formers (D (O) formers), intermediate colony-formers (IM-formers), rough colony-formers (R-formers)], marked differences between D (O) formers and the other colony-formers were demonstrated. The D (O) formers tended to be far less resistant to a number of drugs than the others. Relative prevalences of these different colony-formers in an individual strain, especially in stock cultures, are diverse, and any evaluation of in vitro susceptibilities of stock cultures should have areference to colony morphology.
(2) In vivo studies: The efforts of making a suitable animal model for experimental chemo therapy of M. intracellulare infection have been hampered by the lack of or low pathogenicity (virulence) to experimental animals of M. intracellulare. A few investigators have reported, however, reasonably virulent strains for mice, which has encouraged our efforts to select avirulent strain for mice. Our systematic search for a mouse (ddY) virulent strain was based on the following observations; that T-formers were more virulent for mice than the other colony-formers, that T-formers tended to be dysgonic on Ogawa medium, and that stock cultures for long periods of time should be avoided.

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