(Vol.75 No.10 October 2000) <1> Kekkaku Vol.75, No.10:569-573,2000 A CLINICAL STUDY IN THE COLLAGEN DISEASE PATIENTS DEVELOPED PULMONARY TUBERCULOSIS DURING CORTICOSTEROID ADMINISTRATION *Yuka SASAKI, Fumio YAMAGISHI, Takenori YAGI, Hideki YAMATANI, Fuminobu KURODA, and Hideaki SHODA *Division of Thoracic Disease, National Chiba Higashi Hospital The study subjects consisted of 14 pulmonary tuberculosis (PTB) patients with collagen disease. They are under corticosteroid treatment and the mean age is 56.4 years. The length of time from the development of collagen disease to the development of PTB averaged 4.1 years. The breakdown of collagen disease are SLE (6 patients), MCTD (3 patients), PN (2 patients), and PSS, PM, Sjogren syndrome (1 case, each). Thirteen cases were bacilli positive by the sputum examination on admission to our hospital. Chest X-ray findings on admission revealed cavitation in 3 cases and non- cavitation in 11 cases, of which 5 cases had miliary tuberculosis. Corticosteroid prepara- tion had been administered to all of the 14 cases for more than one year. The mean dose of corticosteroid preparation administered when PTB developed was 13.9mg (predonisolone) and it was more than 20mg in 8 cases. The median duration from the start of the respi- ratory symptoms to diagnosis was 39.2 days. The delay in the discovery exceeding 1 month were seen in 9 cases. In the cases of collagen disease, when the disease course extends over a long period of time, and even when the dose of corticosteroid preparations are decreased, there is a need to be note on the risk of developing PTB. There are many non-cavitary cases with spu- tum smear positive. The fact suggested that an appropriate diagnosis is need so that the discovery of PTB should not be delayed. Key words:Compromised host, Corticosteroid, Opportunistic infection, Pulmonary tuberculosis, Doctor's delay *673, Nitona-cho, Chuo-ku, Chiba-shi, Chiba 260-8712 Japan. (Received 2 Mar. 2000/Accepted 19 Jun. 2000) <2> Kekkaku Vol.75, No.10:575-581,2000 DETECTION OF RIFAMPIN-RESISTANT MYCOBACTERIUM TUBERCULOSIS BY LINE PROBE ASSAY (LiPA) 1*Chiyoji ABE, 2Hideo OGATA, 3Kanemitsu KAWATA, 4Toru HIRAGA, 5Tetsuya TAKASHIMA, and 6Toshinori SUETAKE 1*Research Institute of Tuberculosis and 2Fukujuji Hospital, Japan Anti-Tuberculosis Association, 3National Minami-Yokohama Hospital, 4Toneyama National Hospital, 5Osaka Prefectural Habikino Hospital, 6Nissho Corporation A recently described reverse hybridization-based line probe assay is used for the rapid detection of the mutations in the rpoB genes of rifampin-resistant Mycobacterium tuber- culosis and for the identification of the M.tuberculosis complex. A multicenter study that included 5 laboratories was performed to evaluate the line probe assay in compari- son with the in vitro susceptibility test. A total of 406 mycobacteria isolates which were composed of 103 rifampin-resistant and 230 rifampin-susceptible M.tuberculosis isolates, and 73 mycobacteria other than tubercle bacilli (MOTT), were subjected to this study. All 333 M.tuberculosis isolates were discriminated correctly from MOTT bacilli by a line probe assay. Concordance rates with sequencing results for five wild-type probes (S probes) and four specific mutations (R probes) for detecting the mutations in the rpoB genes were both 100%. The overall concordance rate with the in vitro susceptibility test- ing results was 98.5% (328 of 333 isolates). These results indicate that a line probe assay kit may be useful for the rapid diagnosis of rifampin-resistant tuberculosis. Key words:Mycobacterium tuberculosis, rpoB gene, Rifampin resistance, Line probe assay *3-1-24, Matsuyama, Kiyose-shi, Tokyo 204-8533 Japan. (Received 5 Jun. 2000/Accepted 21 Jun. 2000) <3> Kekkaku Vol.75, No.10:583-588,2000 COMPARISON OF CHEST CT FINDINGS BETWEEN SUSPECTED AND DEFINITE CASES OF PRIMARY PULMONARY M.AVIUM COMPLEX INFECTION *Susumu HARADA, Yasuko HARADA, Sanae OCHIAI, Yukari IKEDOH, Yoshiya KITAHARA, Akira KAJIKI, Masahiro TAKAMOTO, and Tsuneo ISHIBASHI *Ohmuta National Sanatorium It is very difficult to treat pulmonary infection with MAC, because we have few effec- tive drugs against this organism. In this situation, an early diagnosis and treatment are very important to manage this disease. We evaluated chest CT scans of the primary pulmonary MAC infection which had no underlying lung diseases and no immuno- compromised diseases such as HIV infection. We difined suspected cases of pulmonary MAC infection as cases in which abnormal features of chest CT scans were recognized but frequency of detection of organisms of MAC did not fulfil the diagnostic criteria for atypical mycobacteriosis according to Japanese Mycobacteriosis Research Group of the National Chest Hospitals. CT scans of suspected cases were compared with the definite cases. Results obtained were as follows: 1. In classification by CT scans of primary pulmonary MAC infection, the proportion of localized type and diffuse type was the same both in suspected and definite cases. In localized type, more tuberculosis-like pattern was seen in definite cases. 2. In suspected cases, characteristic features of CT scans of primary pulmonary MAC infection were recognized in the same frequency as in definite cases. 3. In pulmonary tuberculosis-like type, difinite cases showed more cavitary lesions than suspected cases. These results showed that a careful long term follw-up of suspected cases with fre- quent bacteriological tests of sputum and chest CT scannings was important for early diagnosis of primary pulmonary MAC infection. Key words:Mycobacterium avium complex(MAC), Primary pulmonary MAC disease, Chest CT scan *1044-1, Tachibana, Omuta-shi, Fukuoka 837-0911 Japan. (Received 7 Jun. 2000/Accepted 19 Jul. 2000) <4> Kekkaku Vol.75, No.10:589-593,2000 A CASE OF TUBERCULOSIS ANEURYSM OF THE AORTA 1*Toshio SUGANE, 1Noriaki TAKAHASHI, 1Toshiya KOURA, 1Kouichi ICHIMURA, 1Yoshiaki KOYA, 1Tsuneto AKASHIBA, 1Takashi HORIE, 2Kazuo KITAMURA, and 2Kazumitsu OOMORI 1*First Department of Internal Medicine, Nihon University School of Medicine, 2Second Department of Surgery, Nihon University School of Medicine We reported a rare case of tuberculous aneurysm of the aorta managed successfully with urgent surgical therapy. A 35-year-old woman was admitted to our hospital com- plaining of fatigue and hemoptysis. Laboratory tests showed severe anemia, slight liver dysfunction, elevated level of C-reactive protein, and negative syphilis serologies. The chest roentgenogram revealed widening of right upper mediastinum, two nodular shadows in right middle lobe, and left-sided infiltration shadow with pleural effusion. The pleural effusion was bloody and its level of adenosine deaminase was normal. Culture of pleural effusion specimen remained negative. A computed tomography scans of the chest revealed an aortic aneurysm on the aortic hiatus. Rapid increase in pleural effusion was followed by hemothorax a few hours later. After operation, she received antituberculosis therapy. Histopathologically, the rasected lung showed inflammatory process including granulation of giant cells and epithelioid cells. The specimens of the aortic aneurysm revealed rupture of whole layer of aortic wall and inflammatory cell infiltrations. These findings suggested that the case to be a tuberculous aneurysm of the aorta. Therefore, we diag- nosed the case as the rupture of tuberculous aneurysm of the aorta. Key words:Tuberculous aneurysm of the aorta, Hemoptysis, Hemothorax, Pulmo- nary tuberculosis, Surgical treatment *30-1, Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610 Japan. (Received 5 Apr. 2000/Accepted 17 Jul. 2000) <5> Kekkaku Vol.75, No.10:595-598,2000 The 75th Annual Meeting Opening Lecture IMMUNOLOGY IN THE 20TH CENTURY -Progress Made in Research on Infectious and Immunological Diseases- *Tadamitsu KISHIMOTO *Osaka University The new era of the modern medicine was opened 100 years ago by Robert Koch and Louis Pasteur who demonstrated that various infectious diseases were caused by their respective microbes. Koch discovered Mycobacterium tuberculosis, the causative agent of tuberculosis. The first breakthrough in the modern medicine to combat against infectious diseases was the discovery of anti-diphtheria toxin antibody by E.A. von Behring and S.Kitasato. The concept of immunity-immune from disease-has thus been established. The immune response between antigen and antibody sometimes provides the host with a harmful effect. The concept of allergy was introduced by Richet and later by Prausnitz and Kustner. Why the same immune response leads to the different outcome, immunity or allergy had not been made clear until the discovery of IgE by Drs. Kimishige and Teruko Ishizaka in 1968:The IgG antibody plays a role in immunity whereas IgE anti- body is involved in allergy. Tuberculin skin reaction which is well known as the diagnostic tool for mycobacterial infection was studied by M. Chase in 1945 demonstrating that it was able to be transferred to the healthy individual by immune cells but not by antibody. The immune response is now categorized into two;soluble immunity-immediate type allergy and cell-mediated immunity-delayed type allergy. The rapid progress in the molecular biology in the past decades has also accerelated the progress in immunology, several of which include discovery of two types of lymphocytes;T and B cells;concept of two T cells, Th1 and Th2 cells;and the discovery of cytokines which regulate immune cell responses. The mechanism of the immune response is now understood at the gene level. Several immunological diseases can now be successfully treated by controlling the levels of cytokines involves. For example, refractory rheuma- toid arthritis is now under control by the administration of recombinant soluble TNF receptor molecules to the patients. The complete human genome sequence is currently under investigation. We can now envisage the advent of the days when every disease can be diagnosed and intervened at the gene level. Key words:Immunity and allergy, T and B cells, Cytokines, Genomes *1-1, Yamadaoka, Suita-shi, Osaka 565-0871 Japan. (Received 6 Jul. 2000) <6> Kekkaku Vol.75, No.10:599-602,2000 The 75th Annual Meeting Special Lecture PROSPECT OF CHEMOTHERAPY IN THE 21ST CENTURY *Satoshi OMURA *The Kitasato Institute gGolden Era in Chemotherapyhhas begun with the discovery of penicillin in the early 1940's and lasted for two decades during which many antibiotics were discovered. How- ever, the once-believed bright prospect that every infectious disease could be eliminated on the earth by the discovery of antibiotics had to be canceled owing to the emerging of drug-resistant microbes. It was indeed a rat race. We are now at the point when we have to seek another way to combat infectious dis- eases:One possible way might be not to eradicate the microbes but to coexist with them so long as they do no harm to the human hosts. The first step of infection with patho- gens to the host is the adherence of the microbes to the surface of host cells. Therefore, the method how to inhibit this adhesion of microbes to the host cells may provide a new tool to prevent the development of infectious diseases without elimination of microbes from the host. This is just an example of strategy by which humans and pathogens co- exist at peace and should be taken into consideration for the development of new-type antibiotics or ganti-infective drugshin the 21st century. The analysis of genome sequences has been accelerated recently for various pathogenic bacteria one by one. New targets in the pathogenic microbes for the development of new antibiotics can, therefore, be determined from the genetic point of view. The discovery of antibiotics has indeed been the history of collection of innumerable species and/or strains of bacteria from the soils to search for the biologically active anti-pathogenic agents. The current progress in the technology of molecular genetics, however, will certainly make it possible to search for active molecules by DNA technology; bacterial DNA but not whole microorganisms from the soil is to be transformed into the conventional bacteria and searched for active molecules with combat against pathogens. Key words:Chemotherapy, Anti-infective drug, Coexistence of pathogen and host, Gene technology *5-9-1 Shirokane, Minato-ku, Tokyo 108-8642 Japan. (Received 24 Jul. 2000) <7> Kekkaku Vol.75, No.10:603-609,2000 The 75th Annual Meeting President Lecture RIDDLES IN HUMAN TUBERCULOUS INFECTION *Izuo TSUYUGUCHI *Osaka Prefectural Habikino Hospital Tuberculosis is indeed an infectious disease caused by Mycobacterium tuberculosis. How- ever, only a small percentage of individuals infected develops overt disease, tuberculosis whereas the infected bacilli persist alive years long within the vast majority of persons infected but remained healthy. There are several riddles or enigmas in the natural history of M.tuberculosis infection in humans. Some of them are as follows: 1. What is the virulence of M.tuberculosis? 2. How does M.tuberculosis persist dormant within the host? 3. What determines the development of disease from remaining healthy after infection with M.tuberculosis? 4. What is the mechanism ofgendogenous reactivationhof dormant M.tuberculosis within the host? 5. Can we expect more potent anti-TB vaccine than BCG in near future? Most of these issues cited above remain unsolved. What is urgently needed today to answer correctly to these questions is the production of appropriate animal model of tuberculosis infection which mimics human tuberculosis. Murine TB does not reflect' human TB at all. What characterizes the mycobacterial organism is its armour-plated unique cell wall structure which is rich in lipid and carbohydrate. Cord factor or trehalose dimycolate (TDM), the main component of cell wall, has once been regarded as the virulence factor of mycobacteria. Cord factor is responsible for the pathogenesis of TB and cachexia or even death of the patients infected. However, cord factor in itself is not toxic but exerts its detrimental effect to the host through the excessive stimulation of the host's immune system to produce abundant varied cytokines including TNF-ƒ¿. How to evade this embarrassing effect of mycobacterial cell wall component on the host immune system seems very important for the future development of better TB vac- cine than the currently used BCG. Key words:Human TB, Natural history of TB infection, Endogenous reactivation *3-7-1, Habikino, Habikino-shi, Osaka 583-8588 Japan. (Received 12 Jul. 2000) <8> Kekkaku Vol.75, No.10:611-617,2000 The 75th Annual Meeting Symposium ‡W. TUBERCULOSIS CONTROL OF URBAN AREAS IN JAPAN Chairpersons:1*Toshio TAKATORIGE 2Tadayuki AHIKO 1*Department of School and Environmental Health, Osaka University Graduate School of Medicine, 2Yamagata Prefectural Murayama Public Health Center The rates of tuberculosis remain high in urban areas. The declining speed of tuberculo- sis incidence rate in urban areas has been slower than other areas. Efforts and resources to tuberculosis control must be concentrated on urban locations to eradicate tuberculosis in Japan. 1. Tuberculosis control in a public health center of urban area:Teru OGURA and Chiyo INOGUCHI(Toshima City, Ikebukuro Public Health Center, Tokyo Metropolitan) A wide range of TB control measures is implemented by public health centers, such as a patient registration, home-visit guidance, contact examination in urban areas. Direc- tors of every health center have the direct responsibility for tuberculosis control measures in their jurisdiction. Ikebukuro is urban areas where there are many offices, shopping and amusement facilities. Urban people is often on the move looking for job, so public health centers are often not easy to carry out contact examinations as planned. In recent years, homelessness has been recongnized as a growing urban social problem. Their incidence of tuberculosis is high. Special TB control program must be carried out in urban areas. 2. Tuberculosis Control in Tokyo Metropolitan:Kazumasa MATSUKI(Department of Infectious Diseases and Tuberculosis, Bureau of Public Health, Tokyo Metropolitan) There has been a steady decline in the TB wards. The beds for TB patients are running short and even smear positive TB cases cannot be put in a hospital without waiting several days. Staffs of an urban emergency department must protect tuberculosis infec- tion by environmental controls of emergency room. Tokyo Metropolitan government sup- ports the engineering improvements of emergency room to hospitals. Directly observed therapy for tuberculosis patients at a district has been implemented to complete their therapy. On DOT, a trained health worker observes the patient take anti-TB medication. 3. Usefulness of Molecular Epidemiologic approach on Tuberculosis Control:Atsushi HASE(Osaka City Institute Laboratory of Health and Environment) DNA fingerprinting establishes the genetic relatedness of Mycobacterium tuberculosis isolates and has become a powerful tool in tuberculosis epidemiology. To use DNA finger- printing to assess the efficacy of current tuberculosis infection-control practices. Com- bining conventional epidemioloigic techniques with DNA fingerprinting of M.tuberculosis can improve the understanding of how tuberculosis is transmitted. Patients were assigned to clusters based on mycobacterial isolates with identical DNA fingerprints. Clusters were assumed to have arisen from recent transmission. We analyzed M.tuberculosis isolates form patients reported to the tuberculosis registry by RFLP techniques. These results were interpreted along with demographic data. Patients infected with the same strains were identified according to their RFLP patterns, and patients with identical pat- terns were grouped in clusters. RFLP patterns of high incidence districts have more variations than other areas. This suggests that the source of tuberculosis infection are quite diverse and complicated. Tuberculosis patients may accumulate to high incidence districts from other places after infection. 4. Structure of High Incidence of Tuberculosis and Control Plan in Osaka City:Yoichi TATSUMI(Bureau of Infection Control, Osaka City Office) The case notification rate in Osaka City is the highest in Japan. That of all TB cases and smear positive TB cases was 1573 and 216 per 100,000 population in 1997 at Airin District in Osaka City. The main reason for this highest incidence rate is that there are many homeless people and it is a mobile population. Most of residents are daily laborers. They come from all over Japan and stay there, mainly in rented rooms, to look for jobs. Thousands of homeless people also live in tents on streets or in parks. We are making to new strategic plan to intensify tuberculosis control measures throughout the city. Osaka city government has set one major goal by the year 2010, i.e., to achieve the tuberculosis incidence below national average. 5. Medical Care of tuberculosis patients in Osaka City:Kayo MUI(Osaka City Public Health Center) A large proportion of the new cases of homeless went to the private hospitals serving the indigent and working poor. Almost homeless patients received medical care by admis- sion. We will require careful attention to diagnosis and treatment procedures in these hospital for homeless TB. The ultimate control of TB will continue to depend on the coordinated efforts between health care facilities and public health center. The hospital medical staffs and public health nurses had important and defined roles in case treat- ment. We need to establish methods of communication between clinic, hospital and health department. An ongoing health care community collaborative effort may successfully reduce tuberculosis case in a homeless population. Outreach and case management are thought to be critical components of improved access to health care for homeless people. 6. New Policy to Health and Medical Care System Against Tuberculosis in Japan: Toshinobu SATO(Department of Tuberculosis and Infectious Diseases, Bureau of Health Service, Ministry of Health and Welfare) It has now become apparent that, after many years of steady decline, the number of new cases reported in 1997 marked the first increase in 38 years, while the morbidity rate increased for the first time in 43 years. There is a clear danger that these figures will continue to move upward in the years ahead. Conditions in Japan may be at a critical turning point in its fight against tuberculosis. The Ministry of Health and Welfare is hereby declaring a state of emergency concerning tuberculosis. The Ministry will work to implement countermeasures, such as medical examinations, provided for under the Tuber- culosis Prevention Law, and to actively conduct surveys of the occurrence of tuberculosis and promote special anti-tuberculosis programs. Tuberculosis is drifting to the lower socio-economic population such as homeless persons, day laborers and lower-income peo- ple in urban areas. The tuberculosis control system need be reformed against this situa- tion. The cooperation between medical facilities and public health centers must be strengthened. The TB policies according to regional characteristics will be needed. Key words:Urban area, Tuberculosis control, DOT, RFLP, Public health center *2-2, Yamadaoka, Suita-shi, Osaka, 565-0871 Japan. (Received 17 Jul. 2000) <9> Kekkaku Vol.75, No.10:619-623,2000 The 75th Annual Meeting Symposium ‡T. TUBERCULOUS INFECTION AND PREVENTION Chairpersons:1*Yoshihiro NAMBU 2Takashi OGURA 1*Department of Respiratory Medicine, Kanazawa Medical University, 2National Sanatorium Toneyama Hospital In Japan, the number of tuberculosis infected patients has been increasing again, espe- cially in the elderly. the incidence of newly registered tuberculosis patients who are over 70 years is 34%. The outbreak of tuberculosis also has been increasing, and has become a serious social problem. The elderly have a high risk of developing tuberculosis because of their immunosuppressed condition due to underlying disease and aging. Elderly active tuberculous people also confer a risk of tuberculosis infection to the non-tuberculosis infected young generation. In this symposium, we discussed about 1) the tuberculosis out- break related to the strategy for tuberculous prevention, 2) the health examination to detect tuberculous people in the middle-aged and elderly, 3) the nosocomial transmission of tuberculosis in the hospital, 4) the nutritional damage and immunosuppressive state in elderly people related to developing active tuberculosis in latent tuberculous infection, and 5) the organ transplantation and tuberculosis focusing on living related liver transplantation. Seven cases of tuberculosis outbreak were reported in Osaka from 1989 to 1998, 2 cases in the hospital and 5 in others. Tuberculouos infection index (maximum sputum Gaffky score multiplied by the number of months of persisted cough) was 8 and 15 in the hospital, 3, 0, 84, 14, and 27 in others. Three cases (43%) were observed in persons with less than 10 of this index. It is essential to evaluate carefully for tuberculosis outbreak in extraordinary examination, if the tuberculous infectious index is low. There are various immunosuppressive patients with malignancy and other underlying disease in the hospital, so we have to pay careful attention for tuberculous outbreak when there is an active tuberculous patient. In these seven cases of extraordinary examination for tuberculous epidemic, only one (0.4%) of 241 cases who received isoniazide prophylactic therapy developed active tuberculosis. Isoniazide prophylactic therapy was an important strategy for the prevention of tuberculous outbreak. (Isamu TAKAMATSU, Osaka Prefectural Habikino Hospital, Osaka) It is essential to prevent tuberculosis in the elderly to achieve tuberculosis control in public health. The health examination was an important strategy for the detection of tuberculosis in the middle-aged and elderly. The incidence of tuberculosis detection is only 9.3% by the health examination at this age. However, the health examination has well detected active tuberculosis patients in elderly (34.5%), and also 16.8% in smear positive cases with pulmonary cavitary formation. The early detection of persons with active tuberculosis is essential, and further discussion regarding cost-performance and accuracy of the health examination for tuberculosis should also be essential. Prophylactic therapy of isoniazide also might be considered for the high risk middle-aged and elderly people with underlying diseases. (Masako OMORI et al., Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo) The cases of nosocomial transmission of tuberculosis in the hospital have been increas- ing. In younger persons, the incidence of tuberculosis infected nurses and doctors is relatively higher than healthy control. The transmission of tuberculosis from elder active tuberculosis patients to healthy non-tuberculosis infected medical workers has been well recognized. It is very essential to follow guidelines for the prevention of tuberculous transmission in the hospital from the Japan Tuberculosis Society including routine tuberculin skin test for fresh medial workers. Primary education for tuberculosis in medical and nursing school is also an important strategy. Further discussion might be essential that BCG could prevent tuberculosis transmission in tuberculin skin test nega- tive adults. (Masanori SAKATANI, National Kinki Central Hospital, Osaka) It is estimated that approximately 10% of individuals who acquire tuberculosis infection and are not given preventive therapy will develop active tuberculosis. In this development of active tuberculosis from latent tuberculosis, cellular immunity including T lymphocytes and natural killer cells plays important roles. The nutritional state and activity of cellular immunity are impaired in the elderly, so they have a greater risk to develop active tuberculosis. In the elderly, malnutrition of decreased albumin induces damage of Interleukin-12 and natural killer cell activity system. The induction of Interleukin-12 and Interferon-ƒÁ production was decreased, by the stimulation of monocytes from elderly tuberculosis patients by BCG solution. It is essential to evaluate the mechanism of developing active tuberculosis related to nutritional damage and cellular immuno suppression. (Takahiro YONEDA et al., Nara Medical University, Nara) In organ transplantation therapy, immunosuppressive therapy consisting of tacrolimus, cyclosporine and glucocorticosteroid is administered to prevent rejection. Such therapy interferes with cellular immunity that plays an important role in tuberculosis infection. The incidence of tuberculosis infection related to organ transplantation therapy has been reported as 0.3-15%. In Japan, only 1 case of tuberculosis infection has been reported in over 500 cases of living related liver transplantation (Department of Transplantation Surgery, Kyoto University). Most living related liver transplantation involves younger patients, and faster reduction of immunosuppressive therapy might affect the lower incidence of tuberculosis. The cases of organ transplantation should increase, because especially organ transplantation is now available from brain dead donors. The precise guideline for the prevention and therapy of tuberculosis in organ transplantation is appraisal. (Tetsuya KIUCHI, Kyoto University, Kyoto) Summary, 1)Careful attention for the outbreak of tuberculosis at the extraordinary examination should be paid and prophylactic isoniazide therapy is recommended. 2) The early detection of active tuberculosis in middle-aged and elderly people is important and isoniazide prophylactic therapy for elderly persons with underlying diseases might be con- sidered. 3) Following the guideline for the prevention of tuberculosis transmission in the hospital of the Japan Tuberculosis Society is essential to prevent tuberculosis transmis- sion in the hospital. 4) T lymphocytes, IL-12 and INF-ƒÁ play an important role in the process of developing active tuberculosis in previously tuberculosis infected individuals. 5) Attention to tuberculous infection in organ transplantation should be more important in the future because of the increasing number of transplanted patients. Key words:Tuberculous outbreak, Tuberculosis in the elderly, Nosocomial transmission, Cellular immunosuppression, Organ transplantation *1-1, Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293 Japan. (Received 31 Jul. 2000)