(Vol.77 No.12 December 2002) <1> Kekkaku Vol.77,No.12:771-775, 2002 Original Article CLINICAL EVALUATION OF THE CAUSE OF DEATH IN PATIENTS WITH ACTIVE PULMONARY TUBERCULOSIS 1Yoshihiro KOBASHI, 1Toshiharu MATSUSHIMA, 2Niro OKIMOTO, and 3Yoshihito HARA Abstract We made a clinical analysis of the cause of death of forty deceased patients with active pulmonary tuberculosis who were admitted to Kawasaki Medical School Hospital, Kawasaki Medical School Kawasaki Hospital, and Asahigaoka Hospital during the period from January 1996 to December 2001. The age of 40 deceased patients (29 males/11 females) ranged from 55 to 93 years old, and were mostly bedridden. Underlying diseases existed in all except one case, and they were respiratory diseases in 9 patients and non-respiratory diseases in 34 patients. Laboratory findings revealed poor nutritional conditions. The diagnosis of pulmonary tuberculosis was established within one month from the appearance of symptoms in over half of these patients because most of them were smear positive for Mycobacterium tuberculosis. None of the strains of Mycobacterium tuberculosis isolated from these patients were multidrug resistant for antituberculous drugs and only one strain was completely resistant for Rifampicin. Radiological findings of the tuberculosis were bilateral in 30 patients. Consolidation shadows without cavity were noted in 22 patients, and extension within the unilateral lung field was observed in 24 patients. Regarding the cause of death, advanced pulmonary tuberculosis was the cause in 17 patients and non- tuberculous diseases were the cause in 23 patients. There were 15 patients with bacterial super infections such as bacterial pneumonia, 4 with malignancy, and 4 with other disease. The number of pulmonary tuberculosis patients in poor general and nutritional condition has been increasing with the aging of the Japanese population. Treatment for pulmonary tuberculosis has been successful in most cases, however, the number of the deaths unrelated to tuberculosis including those due to bacterial super infection has been increasing. Therefore, treatment should be considered against resistant microorganisms such as MRSA. Key words:Active pulmonary tuberculosis, Bacterial super infection, MRSA, Antituberculous drug 1Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, 2Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School Kawasaki Hospital. 3Department of Internal Medicine, Asahigaoka Hospital Correspondence to:Yoshihiro Kobashi, Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, 577, Matsushima, Kurashiki-shi, Okayama 701-0192 Japan. (E-mail:resp@med.kawasaki-m.ac.jp) <2> Kekkaku Vol.77,No.12:777-782, 2002 Original Article SMEAR-POSITIVE PULMONARY TUBERCULOSIS DIAGNOSED IN A GENERAL HOSPITAL Shin SASAKI, Yoshirou MOCHIZUKI, Yasuharu NAKAHARA, Akira TANAKA, and Tetsuji KAWAMURA Abstract In Japan, patients with smear-positive pulmonary tuberculosis (SPTB) are hospitalized in a sanatorium because of the law for the prevention of tuberculosis, and not in a general hospital. According to our experience, however, some of the patients with SPTB are hospitalized in a general hospital. In order to study if it is possible to prevent the admission of patients with SPTB to a general hospital, we retrospectively reviewed and compared the medical records of pulmonary TB patients whose sputum was smear-positive for Mycobacterium tuberculosis at our outpatient clinic (Group B; n=61), and patients whose sputum was smear-positive after the admission to our hospital(Group A; n=17). The Group A patients were significantly older than the Group B patients [mean age, Group A, 67 years vs Group B, 56 years;(p=0.01)]. Compared with the Group B patients, the Group A patients more often suffered from underlying diseases [percentage of patients with underlying disease, Group A, 88.2% vs Group B, 37.7%; p<0.001];more often showed atypical infiltrative patterns of pulmonary tuberculosis [percentage of cases showing atypical chest roentgenograms, 70.6% vs 19.7%; p<0.001]; and were in a more serious condition [percentage of deaths during treatment, 47.1% vs 1.7%; p<0.001]. We conclude that hospitalization of SPTB patients in general hospitals is inevitable, because SPTB can not always be accurately diagnosed before admission, and because it is sometimes difficult to send severely ill SPTB patients to a sanatorium which is inconveniently located in the country-side. We propose to provide facilities for the treatment of SPTB at all general hospitals in Japan. Key words:Pulmonary tuberculosis, Positive sputum smear, Infectious tuberculous patients, General hospital, Sanatorium Department of Internal Medicine, National Himeji Hospital Correspondence to:Shin Sasaki, Department of Internal Medicine, National Himeji Hospital, 68 Honmachi, Himeji-shi, Hyogo 670-8520 Japan. (E-mail:sasakis@hmj.hosp.go.jp) <3> Kekkaku Vol.77,No.12:783-788, 2002 Original Article MOLECULAR EPIDEMIOLOGIC STUDY OF TUBERCULOSIS -A Study on Isolates of M.tuberculosis in Southern Half of Osaka Prefecture- Hiromi ANO, Yoshio MORIYAMA, Tomoshige MATSUMOTO, Nobuko TANIGAWA, Hirokazu TOBA, Tetsuya TAKASHIMA, Masanori KIKUI, and Izuo TSUYUGUCHI Abstract Restriction fragment length polymorphism, RFLP of DNA fingerprinting technique provides a very useful tool for the study of epidemiology of tuberculosis transmission in human. We performed RFLP analysis with the IS6110 insertion sequence of the organisms isolated from culture-positive patients who visited our Hospital during the period from January to December 2001. Our Hospital covers patients living in southern half of Osaka Prefecture including a part of Osaka City, which is the highest TB prevalence area in Japan. The number of copies of IS6110 per isolate ranged from 1 to 21. Most isolates (67%) carried 10 to 15 copies. Of 410 available isolates during the year of 2001, 131(32%) belonged to a cluster and 279(68%) did not. The clusters comprised one matching isolate in minimum to 13 isolates in maximum and had a total of 49 distinct RFLP patterns. The average age of the clustered cases was 52.1 years and 64% cases belonged to patients with ages younger than 60 years. Above findings suggest that many cases of tuberculosis in southern part of Osaka Prefecture result from recent transmission. It remains to be elucidated, however, how and where these recent infections occurred in these clustered cases. Key words:RFLP typing, Molecular epidemiologic study, Tuberculosis Osaka Prefectural Habikino Hospital Correspondence to:Hiromi Ano, Osaka Prefectural Habikino Hospital, 3-7-1, Habikino, Habikino-shi, Osaka 583-8588 Japan. (E-mail:ano@zeus.eonet.ne.jp) <4> Kekkaku Vol.77,No.12:789-793, 2002 Report and Information A STUDY ON LOW PERFORMANCE STATUS CASES OF PULMONARY TUBERCULOSIS IN THE ELDERLY 1Fuminobu KURODA, 2Fumio YAMAGISHI, 2Yuka SASAKI, 2Takenori YAGI, 2Tomoko HAMAOKA, and 1Hiromi HIGURASHI Abstract The subjects consisted of 42 patients aged over 60 years, whose performance status (PS) was grade 3 or 4, and who had been admitted for pulmonary tuberculosis at National Chiba- Higashi Hospital between 1997 and 1998. The average age (}SD) of the 34 men and 8 women was 77.6 (}8.5) years (range, 60-91 years). The mean stay in the hospital of the improved patients was 166.6 days (range, 57-303 days), and the mean survival period from admission to death was 43.4 days (range, 2-179 days in died patients). On admission to our hospital, 26 cases were sputum smear positive, 8 cases were smear negative and culture positive, and 8 were negative both on smear and culture. The cavity was observed in 30 cases (71.4%) on the chest X-ray. The laboratory data on admission revealed low nutritional condition. The mean serum total protein, albumin, and cholesterol level on admission were 6.2 (}0.82) g/dl, 2.7(}0.62) g/dl, and 143.0(}41.9) mg/dl. Most of the patients had a difficulty in taking foods, and 20 cases (47.6%) were performed parenteral nutrition by central venous catheter. 23 cases (54.8%) received oxygen therapy by facial mask or nasal tube. The most common cause of low PS on admission was pulmonary tuberculosis in 14 cases (33.3%), followed by cerebrovascular diseases in 11 cases, and orthopedic disease in 8 cases. The proportion of patients whose cause of low PS was not due to lung tuberculosis increased with age. Observing the mortality by the route of administration of antituberculosis medications on admission, 19 (55.9%) of 34 cases who could take drugs per oral route died. One (50.0%) of 2 cases who were administered drugs through gastric tube died, and all (100.0%) of 5 cases who could not take drugs per oral route and were injected isoniazid and streptomycin died. One case who could not administer any drug died. 16 cases improved and 26 cases died, of whom the most common cause of death was pulmonary tuberculosis in 11 cases (42.3%), followed by bacterial pneumonia in 5 cases, and cerebrovascular disease in 3 cases. The mortality by the PS on admission were as follows: 10 (47.6%) of 21 cases with PS 3 died. 16 (76.2%) of 21 cases with PS 4 died. 16 (6.4%) of 249 cases aged over 60 years with PS 0, 1 or 2, and were admitted for pulmonary tuberculosis at the same hospital during the same period died. This study confirms that the prognosis of low performance status patients of pulmonary tuberculosis in the elderly was significantly poor. We have to detect tuberculosis patients in the early stage, and give them antituberculosis medications per oral route as far as possible. Key words:Pulmonary tuberculosis, Elderly, Performance status, Mortality rate, Cause of death, Route of administration 1Department of Chest Medicine, School of Medicine, Chiba University, 2Division of Thoracic Disease, National Chiba-Higashi Hospital Correspondence to:Fuminobu Kuroda, Department of Chest Medicine, School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677 Japan. (E-mail:fkuroda@insei.m.chiba-u.ac.jp) <5> Kekkaku Vol.77,No.12:795-798, 2002 Case Report A CASE OF PNEUMOCYSTIS CARINII PNEUMONIA DURING TREATMENT FOR MILIARY TUBERCULOSIS 1Shinichi MATSUNAGA, 2Hideaki NAGAI, 2Shinobu AKAGAWA, 2Atsuyuki KURASHIMA, 2Hideki YOTSUMOTO, 2Masashi MORI, and 3Akira HEBISAWA Abstract A 30-year old man of Myanmar origin was admitted to our hospital because of productive cough, anorexia, weight loss and fever. Sputum smear was strongly positive for M. tuberculosis (Gaffky 6) and sputum culture proved M.tuberculosis. Caseous necrosis with Langhans giant cells was observed in the biopsied specimens of the liver and bone marrow. He was diagnosed as miliary tuberculosis. Treatment with combined use of isoniazid, rifampicin, ethambutol and streptomycin was started. After one month, his cough resolved, fever subsided and chest X-ray findings improved. Two months later, non-productive cough and fever recurred. Chest radiograph and computed tomographic scan of the chest revealed diffuse ground-glass opacity. Specimens taken by transbronchial biopsy showed pneumocystis carinii in alveoli. Pulsed use of methyprednisolone with Trimethoprim-sulfamethoxazole was started. The symptoms and chest X-ray findings disappeared and he recovered uneventfully. Tests for HIV infection were negative. Anti-HTLV antibody was negative. There were no other suggestive evidences of immune suppression. CD4+T cell count was low, when Pneumocystis carinii pneumonia occurred. The relation between miliary tuberculosis, Pneumocystis carinii pneumonia and CD4-T lymphocytopenia has remained unelucidated. Key words:Miliary tuberculosis, Pneumocystis carinii, CD4+T cell 1Department of Internal Medicine, Nakano Kyouritsu Hospital, 2Deprtment of Respiratory Medicine, 3Clinical Laboratory, National Sanatorium Tokyo Hospital Correspondence to:Shinichi Matsunaga, Department of Internal Medicine, Nakano Kyouritsu Hospital, 5-44-7, Nakano, Nakano-ku, Tokyo 164-0001 Japan. (E-mail:m-siniti@mb.kcom.ne.jp) <6> Kekkaku Vol.77,No.12:799-804, 2002 The 77th Annual Meeting Lunch-Time Lecture MEDICAL RISK FACTORS OF TUBERCULOSIS AND COUNTERMEASURES Fumio YAMAGISHI Abstract We describe the actual situation of and measures for medical risk factors of tuberculosis in compromised hosts and elderly people. Cases of diabetes mellitus, collagen disease and lung cancer administered corticosteroid preparation are taken up as compromised hosts. The frequency of TB patients having diabetes mellitus concurrently tends to increase, and the relative risk of diabetics developing tuberculosis is also high. Physicians giving diagnosis and treatment of diabetes mellitus should understand that diabetics belong to the high risk group of developing tuberculosis and perform chest X-ray examination periodically. In order to prevent the development of tuberculosis from diabetics, it is considered preferable to give chemoprophylaxis where there is no history of TB treatment and healing of TB has been found on the chest X-ray films. Where corticosteroid preparation, more than 10mg in terms of prednisolone is administered over a long period of time for collagen diseases except rheumatoid arthritis and lung cancer, chemoprophylaxis is considered desirable. As for the present situation of the elderly TB patients among in-patients at our hospital, the elderly often had serious complications, their prognosis was poor and they often died of the diseases other than tuberculosis. To strengthen the measures to deal with tuberculosis in the elderly, early discovery and prophylaxis of pulmonary tuberculosis are considered. For the early discovery when the patients is symptomatic, the examination of sputum along with chest X-ray examination is important. As for the periodical health examination, the patients with the risk of infection to those around them being high need to undergo the health examination for sure. As the prophylactic measures, chemoprophylaxis is recommended where there is no history of TB treatment and healing of tuberculosis has been found on chest X-ray films. Key words:Pulmonary tuberculosis, Diabetes mellitus, Collagen disease, Lung cancer, Corticosteroid, Elderly patients Department of Respiratory Diseases, National Chiba-Higashi Hospital Correspondence to:Fumio Yamagishi, Department of Respiratory Diseases, National Chiba-Higashi Hospital, 673, Nitona-cho, Chuo-ku, Chiba-shi, Chiba 260-8712 Japan. (E-mail:yamagisf@chibae.hosp.go.jp) <7> Kekkaku Vol.77,No.12:805-813, 2002 The 77th Annual Meeting Educational Lecture TREATMENT FOR MULTIDRUG-RESISTANT TUBERCULOSIS IN JAPAN Yutsuki NAKAJIMA Abstract Introduction:Multidrug-resistant(MDR) tuberculosis is now refractory against standard chemotherapy for tuberculosis. The curability of medical treatments for it has been up to 50`75%. In Japan several hundreds new MDR tuberculosis cases are supposed to occur every year. This review is the outline of Japanese preliminary guideline of treatment for MDR tuberculosis. Drug susceptibility test:One of the most important points to manage MDR tuberculosis is the drug usages according to drug susceptibility. Recently some susceptibility tests with liquid media were introduced in our country, but Japanese new standard test of Ogawa method (using absolute concentration with proportion method) is still important from point of true evaluation of susceptibility. Medical chemotherapy:In MDR tuberculosis one-half of two-third cases are cured by suitable resume of anti-tuberculosis chemotherapy. If patients would prove to be suffered from MDR tuberculosis, chemotherapy resume must be changed from standard resume to special one, that are made from effective and stronger four or five (at least three) anti-tuberculosis drugs including new quinolones. Those drugs should be changed at the same time, not one by one. Although CPM and Tb1 cannot be available in Japan, but sometimes we have to try administrations of those drugs, -lactam antibiotics, interferon. The duration of treatment will be 18-24 months usually. If decreasing of tuberculosis bacilli in sputa is failed under new effective resume through four months treatment, surgical treatment may be indicated. Surgical treatment:(1) In Fukujuji Hospital, Japan Anti-Tuberculosis Association, surgical treatments for seventy four cases of MDR tuberculosis were undergone from 1983 to 2001 March. 85 surgical interventions for them were performed in 71 pulmonary resections (pneumonectomy in 20, lobectomy in 44, segmentectomy in 7) for 64 cases, 8 thoracoplasties alone for 8 cases, 5 cavernostomies for 5 cases, 1phrenic nerve avulsion for 1. The result of pulmonary resections was as follows;early negative conversion rate of tuberculosis expectorations was 97.2%, reexpectoration rate of sputa tuberculosis bacilli was 13.8%, final success rate of pulmonary resections was 91.7%. The factors significantly correlated to reexpectoration of tuberculosis bacilli were preoperative positive bacilli in sputa, few sensitive drugs, other cavitary lesions remained, postoperative prolonged bronchopleural fistula. The result of thoracoplasty alone revealed 75% success rate. In postoperative complications of 85 interventions, there was no operative deaths, prolonged bronchopleural fistula in 17.6%, respiratory failure in 8.7%, pyothorax in 5.9%. (2) Recently results of surgical treatment for MDR tuberculosis were reported in several literatures. Those success rates were almost same 85`95% as our result. They seemed to be very excellent for refractory cases against vigorous medical treatments. So any surgical treatment for MDR tuberculosis should be indicated more constructively in its earlier course. (3) Indication of surgical treatment is as follows;Main target lesions that should be removed are cavitary ones in pulmonary or pleural foci. And any capsulated localized tuberculosis foci more than 2 cm in diameter is better to be resected because of the possibility of later cavitation. Surgically it is the best that all tuberculosis foci are within a resected lobe, effective drugs remained as many as possible and no cardiopulmonary risk. But even if patient's state are over those criteria, resections of more extended pulmonary foci including in opposite sides can be tried within tolerable cardiopulmonary function. Other comments:Treatment for HIV-positive MDR tuberculosis and protection for nosocomial transmission of MDR tuberculosis are discussed briefly in this article. Preventive therapy for newly infected persons with MDR tuberculosis is controversial. At this time just in MDR tuberculosis cases no preventive therapy, careful following up, and drastic treatment with remained effective drugs after developing of disease will be recommended. Key words:Multidrug tuberculosis, Drug susceptibility, Medical treatment, Surgical treatment, Indication for surgery Department of Chest Surgery, Fukujuji Hospital, Japan Anti- Tuberculosis Association Correspondence to:Yutsuki Nakajima, Department of Chest Surgery, Fukujuji Hospital, Japan Anti-Tuberculosis Association, 3-1-24, Matsuyama, Kiyose-shi, Tokyo 204-8522 Japan. (E-mail:yutsuki_@ka2.so-net.ne.jp) <8> Kekkaku Vol.77,No.12:815-821, 2002 The 77th Annual Meeting Educational Lecture DIAGNOSIS AND TREATMENT OF PULMONARY NONTUBERCULOSIS MYCOBACTERIOSIS Atsuyuki KURASHIMA Abstract Pulmonary non-tuberculous mycobacteriosis in Japan occurs more than about 5,000 cases annually. Among them, about 70% are occupied by Mycobacterium avium complex (MAC) infection. Considering the frequency and the difficulty of treatment, we discuss mainly on pulmonary MAC infection on this report. At National Tokyo hospital, secondary MAC infection after tuberculosis sequelae were 46.5% out of 170 pulmonary MAC cases since 1969 to 1985, but it decreased to 19.4% out of 268 cases since 1986 to 2000. In this same period, a type of MAC infection like middle lobe syndrome without recognizing preceding pulmonary disease, increased to 69.8% out of all pulmonary MAC cases (Fig.1). Recently, this type of pulmonary MAC infection, which consists with scattered nodular lesion and local bronchiectasis in middle lobe or lingula, attracts attention. Why is there much frequency in women? Why does it originate from middle lobe or lingula? Although, it shows a characteristic X-ray pattern, ant it is still an interesting problem, the origin of the disease cannot be clarified. First diagnostic standard of nontuberculous mycobacteriosis in Japan was submitted in 1967, and the current diagnostic standard was made in 1985, through several times improvements. These contents are almost similar to that of American diagnostic standard in 1997, but the new revision that reflected chest CT findings and bronchoscopic sampling etc, is pressed now. In the treatment, INH or PZA, which is a key drug in tuberculous chemotherapy, is not a key drug in MAC chemotherapy. MAC chemotherapy is multidrugs combination chemotherapy including EB, CAM, RFP, and amino glycosides. However, it is difficult to achieve complete regression whit current drugs combinations, and an early surgical resection is the most effective in case of localized MAC lesion. We propose a guidance of treatment selection with age and disease severity (Table). Fig2 shows survival curves of 104 cases pulmonary MAC infection at National Tokyo Hospital. Key words:Nontuberculous mycobacteriosis, Pulmonary MAC infection, Tuberculosis sequelae, Middle lobe syndrome, Diagnostic standard, Chemotherapy, Surgical treatment Clinical Research Division, National Tokyo Hospital Correspondence to:Atsuyuki Kurashima, Clinical Research Division, National Tokyo Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo 204-8585 Japan. (E-mail:krsm@tokyo.hosp.go.jp) <9> Kekkaku Vol.77,No.12:823-826, 2002 The 77th Annual Meeting Symposium NEW DIAGNOSTIC METHODS FOR TUBERCULOSIS AND THEIR CLINICAL UTILITIES Chairpersons:1Chiyoji ABE and 2Tetsuya TAKASHIMA Topics of symposium and Presenters: 1. Result of questionnaire survey on the laboratory diagnostic methods for tuberculosis: Atsuyuki KURASHIMA (National Tokyo Hospital) 2. Key point of quality control of the diagnostic methods for tuberculosis: Takeshi HIGUCHI (Osaka Hospital, Japan Anti-Tuberculosis Association) 3. Usefulness and problems of liquid medium and solid medium in mycobacterium culture: Yoshiko KAWABE (National Tokyo Hospital) 4. Usefulness and problems of Mycobacteria identification kit using anti-MPB64 monoclonal antibodies, "Capilia TB":Naoki HASEGAWA (Keio University School of Medicine) 5. Rapid drug susceptibility testing using BCTEC MGIT 960:Akio AONO (Fukujuji Hospital, Japan Anti-Tuberculosis Association) 6. Clinical utility of nucleic acid amplification assay:Tetsuya TAKASHIMA (Osaka Prefectural Habikino Hospital) Abstract The clinical utilities of new diagnostic methods for Mycobacterium tuberculosis, such as primary isolation and drug susceptibility testing using MGIT, identification using anti- MPB 64 monoclonal antibodies and nucleic acid amplification assay, were studied. It was shown that these new diagnostic methods were more rapid and more accurate than currently available approaches and useful for the early and aggressive case findings. Questionnaire survey indicated that most of the laboratories had been ready to introduce these new diagnostic methods. Thus, the diagnosis for active tuberculosis along the "CDC recommendation in 1993" has become realizable in Japan. Now, Japanese TB control program is under revision due to the current stagnation of the decline in notification rates. The importance of rapid and accurate diagnosis of active tuberculosis should be declared in the new Japanese TB control program by indicating the guideline of rapid diagnostic methods for Mycobacterium tuberculosis. Key words:New diagnostic methods, Questionnaire survey, Quality control, MGIT, Capilia TB, Nucleic acid amplification assay 1Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, 2Osaka Prefectural Habikino Hospital Correspondence to:Tetsuya Takashima, Osaka Prefectural Habikino Hospital, 3-7-1, Habikino, Habikino-shi, Osaka 583-8588 Japan. (E-mail:tetsuya@hbk.pref.osaka.jp)