(Vol.75 No.12 December 2000) <1> Kekkaku Vol.75,No.12:685-690, 2000 LIVER TRANSPLANTATION AND TUBERCULOSIS 1,2*Tetsuya KIUCHI 1Department of Transplantation and Immunology, Kyoto University Faculty of Medicine, 2*Department of Transplant Surgery, Kyoto University Hospital Although liver transplantation in Japan has rapidly expanded its indication to adult patients, our experience and measures in posttransplant tuberculosis is still limited. Early posttransplant patients under immunosuppressants generally have a higher risk for tuber- culosis and the risk in liver recipients follows that in lung recipients. Rejection treatment is one of the risk factors for infection, dissemination, and mortality of tuberculosis. Drug-induced liver injury by anti-tuberculotic drugs and their interaction with immuno- suppressants, combined infection, and increased susceptibility to rejection in posttrans- plant tuberculosis are major obstacles in the treatment. Evidence-based consensus in the diagnosis and treatment of posttransplant tuberculosis, as well as establishment of speedy and reliable screening method in potential organ donors, are in a pressing need. Key words:Tuberculosis, Organ transplantation, Liver transplantation, Immunosuppressant, Rejection *54, Kawara-cho, Shogoin, Sakyo-ku, Kyoto-shi, Kyoto 606-8507 Japan. (Received 10 Aug. 2000/Accepted 6 Sep. 2000) <2> Kekkaku Vol.75,No.12:691-697, 2000 LIMITS OF NUCLEIC ACID AMPLIFICATION TESTS FOR DIAGNOSIS OF SMEAR NEGATIVE PULMONARY TUBERCULOSIS 1*Kunihiko ITO, 1Takashi YOSHIYAMA, 2Tomoaki NAKAZONO 2Hideo OGATA, 1Masako WADA, and 2Seiji MIZUTANI 1*Research Institute of Tuberculosis, Japan Anti-tuberculosis Assosiation, 2Fukujuji Hospital, Japan Anti-tuberculosis Assosiation Study objectives:To assess the usefulness of commercial kits of nucleic acid amplifi- cation test (NAAT) for diagnosis of smear negative (SN) pulmonary tuberculosis. Design and patients:Retrospective study of patients who were diagnosed as, or sus- pected of pulmonary tuberculosis during 3 years from January 1996 to December 1998 in Fukujuji Hospital which has 100 beds for tuberculosis patients. Measurements and Results:145 smear negative culture-positive pulmonary tuberculo- sis patients are entered to our analysis. The DNA-based amplification test kit (Amplicor Mycobacterium Tuberculosis Test (AMPL), Roche Diagnostic Systems, Basel, Switzerland) detected 39.2% (20/51, 95% confidence interval (CI):25.8-52.6%) of smear-negative cul- ture-positive (SNCP) pulmonary tuberculosis cases. The RNA-based amplification test kit (Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (AMTDT), Gen-Probe Inc., San Diego, Calif., USA) detected 40.5% (15/37, 95% CI:24.7-56.3%) of SNCP pulmonary tuberculosis cases. For both NAATs (AMPL and AMTDT), between two groups with and without the NAAT at diagnosis of SNCP pulmonary tuberculosis, there was statisti- cal difference in culture-positive rate (proportion of positivity in sputum culture test at diagnosis), but no statistical difference in maximum number of colony of Mycobacterium tuberculosis (MTB). When stratified for the culture positive rate, adjusted sensitivity for SNCP patients was 44.2% (AMLP) and 40.4% (AMTDT) respectively. On the other hand, among 245 patients with sputum AMPL positive results during the 3 years, 8 were smear-negative culture-negative (SNCN), only out of these 8 cases was judged as true ac- tive tuberculosis without treatment. Among 89 patients with sputum AMTDT positive results, 7 were SNCN, and 3 out of them were judged as true active tuberculosis without treatment. Conclusion:Usefulness of commercial NAAT kits (AMPL and AMTDT) to diagnosis SN pulmonary tuberculosis is limited in the point of sensitivity. Key words:Nucleic acid amplification test, Amplicor Mycobacterium Tuberculosis Test, Amplicor Mycobacterium Tuberculosis Direct Test, Smear negative, Plmonary tuberculosis, Pseudo-positive *3-1-24, Matsuyama, Kiyose-shi, Tokyo 204-8533 Japan. (Received 3 Aug. 2000/Accepted 21 Sep. 2000) <3> Kekkaku Vol.75,No.12:699-704, 2000 DESENSITIZATION THERAPY FOR ALLERGIC REACTIONS OF ANTITUBERCULOUS DRUGS -Evaluation of Desensitization Therapy According to the Guideline of the Japanese Society for Tuberculosis 1*Yoshihiro KOBASHI, 1Niro OKIMOTO, 2Toshiharu MATSUSHIMA, 3Takahiro ABE, 3Kazutaka NISHIMURA, 4Shinji SHISHIDO, 5Shin KAWAHARA, 6Eriko SHIGETO, 7Hiroyasu TAKEYAMA, and 8Toshihiko KURAOKA 1*Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School Kawasaki Hospital, 2Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, 3Division of Respiratory Diseases, Department of Medicine, National Ehime Hospital, 4Department of Respiratory Diseases, National Matsue Hospital, 5Department of Medicine, National Minami-Okayama Hospital, 6Department of Respiratory Diseases, National Hiroshima Hospital, 7Department of Medicine, National Sanyo Hospital, 8Department of Medicine, Yoshijima Hospital We prospectively evaluated the effectiveness of desensitization therapy for cases showing side-effects to antituberculous drugs(Isoniazid and Rifampicin) according to the guideline proposed by the Treatment Committee of the Japanese Society for Tuberculosis. Nineteen patients (28-88 years old, male 9, female 10) who had experienced adverse effects after receiving antituberculous drugs and underwent desensitization therapy between August 1998 and March 2000 were studied. Underlying diseases were 14 cases of pulmonary tuberculo- sis, 2 cases of cervical tuberculous lymphadenitis, 1 case of pulmonary atypical myco- bacteriosis, 1 case of pulmonary tuberculosis and tuberculous pleuritis, 1 case of pulmo- nary tuberculosis and tuberculous lymphadenitis. The regimens of treatment for tuberculo- sis were INH+RFP+EB in 8 cases, INH+RFP+EB+PZA in 7 cases, INH+RFP+SM in 2 cases, INH+RFP+SM+PZA in 1 case, and INH+RFP in 1 case. Adverse reactions were 8 cases of eruption, 7 cases of drug fever, 3 cases of drug fever and eruption, and 1 case of drug fever and cervical lymphadenopathy. The causative drugs suggested from DLST or the clinical course were RFP in 17 cases and INH in 8 cases. The clinical effect of desensitization therapy for these antituberculous drugs was good in 14 out of the 17 cases (82%) for RFP, and in 6 out of 8 cases (75%) for INH. The effectiveness rate of the present desensitization therapy according to the guideline of the Japanese Society for Tuberculosis was almost equal to that of previous desensiti- zation therapy, and the clinical results were almost same in present and previous studies despite the different methods of administration of the antituberculous drugs. Key words:Antituberculous drugs, Desensitizatiton therapy, Protocol, Effectiveness *2-1-80, Nakasange, Okayama-shi, Okayama 700-8505 Japan. (Received 22 Jun. 2000/Accepted 25 Sep. 2000) <4> Kekkaku Vol.75,No.12:705-709, 2000 A CASE OF PULMONARY TUBERCULOSIS DIAGNOSED BY DNA AMPLIFICATION METHODS FROM TRANSBRONCHIAL LUNG BIOPSY MATERIALS *Yoshiyuki ABE, Tadahiko FUJINO, Toshinori HASHIZUME, Kuninori SUZUKI, and Keiichi KIKUCHI *Department of Respiratory Disease, National Sanatorium Kanagawa Hospital The hybridization assay using polymerase chain reaction (PCR) is useful for rapid detection of Mycobacterium tuberculosis (M.tuberculosis). A 77-year old female was admitted to our hospital complaining of cough, and examination of the sputum culture showed M.tuberculosis. Her chest X-ray showed a variety of abnormal shadows, such as a cavity lesion, multiple coin lesions, and infiltrates. Malignant disease was also suspected to be involved, with the complication of pulmonary tuberculosis. Specimens were obtained by transbronchial lung biopsy (TBLB) from coin lesions. The hybridization assay using PCR on the TBLB specimens showed M.tuberculosis gene expression. She was treated with anti-tuberculous drugs. All shadows in her chest X-ray were improved six months after admission. She was remained well without recurrence for more than two years after admission. The hybridization assay using PCR with TBLB specimens is useful for the detection of M.tuberculosis. Key words:Pulmonary tuberculosis, Polymerase chain reaction (PCR), Transbronchial lung biopsy (TBLB), DNA *666-1, Ochiai, Hadano-shi, Kanagawa 259-8585 Japan. (Received 17 Jul. 2000/Accepted 19 Sep. 2000) <5> Kekkaku Vol.75,No.12:711-715, 2000 PULMONARY MYCOBACTERIUM GORDONAE INFECTION TREATED WITH CLARITHROMYCIN 1*Tomonobu KOIZUMI, 1Yoshitaka YAMAZAKI, 1Keishi KUBO, 2Yuuji YAGUCHI, 2Hideji YANAGISAWA, and 3Kazuyoshi YAMAUCHI 1*First Department of Medicine and 3Central Laboratory in Shinshu University School of Medicine, 2MIROKU Medical Laboratory We reported a case of 51-year-old female immunocompetent patient with pulmonary Mycobacterium gordonae infection. The patient complained persistent cough and sputum and occasionally hemosputum. Chest radiograph and computed tomography (CT) of the lung showed bronchiectasis and small nodules in middle lobe. Bronchofiberscopy was per- formed twice, and bronchial washing specimen repeatedly revealed acid-fast bacilli. The organism was identified as Mycobacterium gordonae by biochemical tests and direct sequence method. She was treated with clarithromycin (400mg/day) over 6 months and the chest CT findings showed improvement. The case was considered to be sensitive to clarithromycin in vitro drug susceptibility test. The case suggested that clarithromycin was a useful therapeutic agent to Mycobacterium gordonae infection. Key words:Mycobacterium gordonae, Non- tuberculous mycobacteriosis, Clarithromycin, Polymerase chain reaction assay *3-1-1, Asahi, Matsumoto-shi, Nagano 390-8621 Japan. (Received 29 Jun. 2000/Accepted 22 Sep. 2000) <6> Kekkaku Vol.75,No.12:717-724, 2000 THINKING ABOUT TUBEERCULOSIS IN OSAKA-CITY *Kazuhiko KAMEDA *Osaka-Prefectural Branch, Japan Anti-Tuberculosis Association The incidence rate of tuberculosis in Osaka City (104.2 per 100,000 population) is extremely high, namely 3 times higher than the national average. Why the tuberculosis situation of Osaka City is so bad? The reason could be summarized as follows:Before the end of the World War ‡U (1945), it was the sequelae of high prevalence observed in the era of Meiji, Taisho and early years of Showa. However, after the World War ‡U, especially from the Heisei era (1989`), it is deeply affected by the influence of socio-economic background in Japan. Osaka City is characterized as the city of merchants and small enterprises. And there- fore, the city substantially has the nature of the locality that brings in or produces some kinds of social vulnerability such as temporary laborers and homeless people. Of the tuberculosis patients in Osaka City, about 20% are homeless. In addition, patients of the smear positive infectious tuberculosis are often discovered among temporary laborers who change their residences and job sites from place to place and contact widely with citizens. These two are the most difficult problems in tuberculo- sis control program of Osaka City. In the meantime, there are many citizens who are careless of their health and do not follow the law or social rule, and this has apparently no direct connection with the prob- lems of tuberculosis. However, it might be one of the factors of an undesirable trend of tuberculosis in Osaka City. In order to improve such a unfavorable tuberculosis situation in Osaka City, effective and strong supporting activities to the tuberculosis program are essentially needed. And these activities must be done from the standpoint of health-promotion, namely, health education for citizens and improvement of social environmental conditions to maintain healthy and cultural life. Key words:Tuberculosis in Osaka City, Reason for tuberculosis situation in Osaka City is bad, Homeless, Health-promotion *4-6-5, Dosho-machi, Chuo-ku, Osaka-shi, Osaka 541-0045 Japan. (Received 14 Aug. 2000/Accepted 14 Sep. 2000) <7> Kekkaku Vol.75,No.12:725-728, 2000 The 75th Annual Meeting Symposium MOLECULAR GENETIC APPROACHES TO MYCOBACTERIUM TUBERCULOSIS 1*Yoshinori HASEGAWA, 2Chiyoji ABE, 3Yoshitsugu IINUMA, 4Yasuhiko SUZUKI, 2Mitsuyoshi TAKAHASHI, and 5Yasuo MIZUGUCHI 1First Department of Internal Medicine, Nagoya University School of Medicine, 2Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 3Department of Clinical Laboratory Medicine, Nagoya University Hospital, 4Department of Pathology, Osaka Prefectural Institute of Public Health, 5Chiba Prefectutal Institute of Public Health Recent progress of molecular genetics has been providing tools for new approaches to disease treatment and diagnosis of Mycobacterium tuberculosis. In 1998, Cole et al. reported the complete genome sequence of Mycobacterium tuberculosis. The new informa- tion will provide us the knowledge and understanding of the biology of Mycobacterium tuberculosis. Further, it will provide us new conception of diagnosis and treatment of the disease. Four topics were selected in this symposium. Dr. Iinuma reviewed and prospected the clinical utility of nucleic acid amplification methods of Mycobacterium tuberculosis. Dr. Suzuki reviewed the molecular mechanism of acquired resistance to anti-TB drugs and reported the early detection of genetic mutation by new designed DNA tip method. Dr. Takahashi reviewed the method of molecular epidemiology and genetic elements as a tool for strain differentiation of tuberculosis. Dr. Mizuguchi interpreted the essential feature of mycobacterial genome maps, and genes and their biological activity. He also reviewed the importance and the utility of the complete genome sequence of tuberculosis in asso- ciation with pathogenecity. These topics were summarized in this report, based on the symposium of gMolecular genetic approaches to Mycobacterium tuberculosishin the 75th annual meeting of the Japanese Society for Tuberculosis. Key words:Mycobacterium tuberculosis, Molecular genetics, Gene amplification, Drug resistant gene, Molecular epidemiology, Genome sequence *65, Tsurumai-cho, Showa-ku, Nagoya-shi, Aichi 466-8550 Japan. (Received 23 Oct. 2000)