(Vol.77 No.11 November 2002) <1> Kekkaku Vol.77,No.11:703-708,2002 Original Article MANAGEMENT OF TUBERCULOSIS DIRING PREGNANCY AND PUERPERIUM 1Emiko TOYOTA, 2Shigeki MINOURA, and 3Hirofumi MIYAZAWA Abstract We reported 22 cases with tuberculosis in pregnancy and puerperium, who were treated in our hospital from 1993 to 2001. Nine out of 22 cases were foreign women and the onset of tuberculosis was not clear and the diagnosis tended to be delayed in most cases. In the reports from industrial countries, most of those patients are foreign bone and the delay in diagnosis is common because symptoms are apt to be mixed up those for pregnancy and puerperium. In 10 of 22 cases, extrapulmonary lesions were noted. Most of our cases were treated with INH, RFP and EB, and in some severer cases PZA was added. WHO and BTS recommend standard therapy with PZA but ATS recommends INH, RFP and EB without PZA. Generally SM is contraindicated because of adverse effect of hearing loss for all pregnant periods, and the data for PZA and other second line drugs are insufficient. Our cases and their neonates showed normal course and no malformation nor congenital tuberculosis. 2 cases could not keep adherence for drugs and 2 babies got active tuberculosis. Precaution for infection is one of most important problem to deal with cases with tuberculosis during pregnancy and postpartum in the hospital. If she is still infectious on delivery, we should consider prevention for transmission and manage her in isolated manner. CDC recommends not to treat for latent tuberculosis during pregnancy because of high frequency of hepatic damage due to INH. It is the best way to check and treat latent tuberculosis before gestation if she is at high risk with tuberculosis. Key words:Pregnancy, Delivery, Puerperium, Tuberculosis, Neonate, Precaution Department of 1Respiratory Disease, 2Obstetrics, and 3Pediatrics, International Medical Center of Japan Correspondence to:Emiko Toyota, Department of Respiratory Disease, International Medical Center of Japan, 1-21-1, Toyama-cho, Shinjuku-ku, Tokyo 162-8655 Japan. (E-mail:etoyota@imcj.hosp.go.jp) <2> Kekkaku Vol.77,No.11:709-716,2002 Original Article A CLINICAL STUDY OF DECEASED CASES OF PULMONARY M.AVIUM COMPLEX(MAC) DISEASE -In Contrast with Survived Cases Followed-up for 5 Years or Longer- Susumu HARADA, Yasuko HARADA, Sanae OCHIAI, Mikiko EMORI, Akira KAJIKI, Yoshiya KITAHARA, Masahiro TAKAMOTO, and Tsuneo ISHIBASHI Abstract We performed a clinical study of pulmonary M.avium complex(MAC) disease comparing deceased cases and survived cases followed-up for 5 years or longer. The results were as follows: 1.At the time of starting the initial medical treatment for pulmonary MAC disease, the deceased cases were older than the survived cases, and the deceased cases were severer than the survived cases in clinical conditions. The spread of the lesions was more extensive and cavities were more frequently observed in the deceased cases than in the survived cases. 2.We classified the clinical pattern of pulmonary MAC disease into a primary infection type and a secondary infection type. Then, we subclassified the primary infection type into a localized type, which contained a tuberculosis-like type and middle, lingular or other lobar pneumonia type, and a diffuse type. The secondary infection type was more frequent in the deceased cases than in the survived cases, and any middle, lingular or other lobar pneumonia type was not observed in the deceased cases. 3.We classified the mode of progression of pulmonary MAC disease in the deceased cases into a tuberculosis-like progression and a diffuse progression. The tuberculosis- like type and the secondary infection type frequently showed the tuberculosis-like progression and the diffuse type frequently showed the diffuse progression. The patients who showed the tuberculosis-like progression were frequently sputum culture positive for MAC, while all patients showing the diffuse progression were culture negative at the time of death. An interval from the estimated onset of the disease to death was shorter in the tuberculosis-like progression type than in the diffuse progression type. Key words:M.avium complex, Deceased case, Prognostic factor, Mode of progression Department of Internal Medicine, National Ohmuta Hospital Correspondence to:Susumu Harada, Department of Internal Medicine, National Ohmuta Hospital, 1044-1, Tachibana, Ohmuta-shi, Fukuoka 837-0911 Japan. (E-mail:haradas@oomuta.hosp.go.jp) <3> Kekkaku Vol.77,No.11:717-723,2002 Case Report PULMONARY MYCOBACTERIUM AVIUM COMPLEX DISEASE SHOWING NODULAR BRONCHIECTASIS -Pathological Findings in Two Cases- 1Masao OKUMURA, 2Kazuro IWAI, 1Hideo OGATA, 1Seiji MIZUTANI, 1Kouzou YOSHIMORI, 2Kunihiko ITHO, 3Yutuki NAKAJIMA and 4Shouji KUDOH Abstract Histopathological examinations were carried out on 2 cases of Mycobacterium avium complex (MAC) disease of nodular bronchiectasis (NB) type on radiograms. The removed lung specimens revealed histological findings of granulomatous bronchiolopneumonia, consisting of epithelioid cell granulomas with lymphocytic infiltrations without exudation in the alveolar areas surrounding the respiratory bronchiole. The central bronchiolar walls were also affected by epithelioid cell granulomas with lymphocytic infiltration, occasionally showing polypoid protrusion into the bronchiolar lumen accompanying emphysema in the peripheral alveolar area. Bronchial lesions seemed to progress from peripheral to central airway with consequent atrophy and disappearance of intramural smooth muscles, resulted in bronchioloectasis. These histological findings well correspond to radiographical 'nodular bronchiectasis'. Large histiocytic granulomas without caseous necrosis developed in some area, which are not usually found in tuberculosis lesions. Epithelioid cell granulomas were occasionally found in the hilar lymph nodes as well as in the walls of lymphatic vessel in the pulmonary interlobular tissues, indicating intrapulmonary lymphatic spread of the mycobacteria. Key words:Mycobacterium avium complex(MAC) disease, Nodular bronchiectasis, Epithelioid cell granulomas, Granulomatous bronchiolopneumonia Department of 1Respiratory Medicine, Fukujuji Hospital, Japan Anti- Tuberculosis Association, 2Research Institute of Tuberculosis, JATA, 3Thoracic Surgery, Fukujuji Hospital, JATA, 4The Fourth Department of Internal Medicine, Nippon Medical School Correspondence to:Masao Okumura, Department of Respiratory Medicine, Fukujuji Hospital, Japan Anti-Tuberculosis Association, 3-1-24, Matsuyama, Kiyose-shi, Tokyo 204-8522 Japan. (E-mail:masao-ok@zd5.so-net.ne.jp) <4> Kekkaku Vol.77,No.11:725-728,2002 Case Report A CASE OF MYCOBACTERIUM AVIUM PULMONARY DISEASE ACCOMPANIED WITH PLEURAL EFFUSION 1Kanako KOBAYASHI, 1Shuichi YANO, 1Kazuhiro KATO, 1Shinji SAITO, and 2Takeshi TOKUSHIMA Abstract Nontuberculous mycobacterial infection is seldom complicated with pleural involvement. We report a very rare case of M.avium pulmonary disease accompanied with pleural effusion. A 76-year-old man was admitted to our hospital because of cough and low-grade fever. A chest radiograph and computed tomograph showed centrilobular nodules in the right middle lobe and left lingula, and right pleural effusion. The patient had had a right spontaneous pneumothorax 50 days before his admission. The sputum smear was negative for acid fast bacilli. The smear of pleural effusion was positive for acid fast bacilli, the level of adenosine delaminate in the effusion was markedly elevated, and pleural effusion was positive for M.avium as assessed by polymerase chain reaction(PCR). The pleural biopsy specimen showed fibrous change without granuloma, while the transbronchial biopsy specimen showed noncaseous epithelioid granulomas. We considered that the pneumothorax was caused by the spread of pulmonary M.avium infection to the visceral pleura with its perforation. Key words:Mycobacterium avium pulmonary disease, Pleuritis Department of 1Pulmonary Medicine and 2Surgery, National Matsue Hospital Correspondence to:Kanako Kobayashi, Department of Pulmonary Medicine, National Matsue Hospital, 5-8-31, Agenogi, Matsue-shi, Shimane 690-8556 Japan <5> Kekkaku Vol.77,No.11:729-733,2002 Case Report A CASE OF MULTIDRUG-RESISTANT TUBERUCLOSIS (MDR-TB) IN YOUNG FEMALE COMPLICATED WITH ACUTE RESPIRATORY DISTRESS SYNDROME AND DEVELOPING MULTIPLE GIANT CYSTS AND PNEUMOTHORAX IN BOTH LUNG Yuko ITO, Noritaka YAMADA, Kunihiko GOTO, Takayuki ANDO, Kenji OGAWA, and Masao TANO Abstract A 20-year-old woman was admitted to our hospital because of cough and dyspnea in April 2001. On admission, laboratory data showed positive inflammatory signs. A chest roentogenogram revealed infiltrated shadow in the bilateral lung fields. Sputum smear examination showed acid-fast bacilli identified as Mycobacterium tuberculosis by DNA- DNA PCR method. Four days after admission, she had an acute respiratory distress syndrome (ARDS) and serious liver dysfunction. Moreover, drug sensitivity test revealed that this case was multidrug-resistant tuberculosis (MDR-TB), and she was treated with sensitive anti-tuberculous drugs (PZA, SM, LVFX). Three months later, her sputa converted to negative for tubercle bacillis, however, a chest computed tomogram (CT) revealed multiple giant cysts in the bilateral lung fields, which developed during treatment. Pneumothorax of both sides was repeatedly observed, and it was difficult to treat. At present (1 year after admission), multiple giant cysts stopped its progression and treatment for tuberculosis is being continued. Key words:Young adult, Multidrug-resistant tuberculosis, ARDS, Cystic change, Pneumothorax Department of Respiratory Diseases, National Higashi-Nagoya Hospital Correspondence to:Yuko Ito, Department of Respiratory Diseases, National Higashi-Nagoya Hospital, 5-101, Umemorizaka, Meito-ku, Nagoya-shi, Aichi 465-8620 Japan <6> Kekkaku Vol.77,No.11:735-740,2002 The 77th Annual Meeting Invited Lecture CURRENT PROBLEMS OF DRUG-RESISTANT TUBERCULOSIS AND ITS CONTROL Sang Jae Kim Drug resistance emerges wherever and whenever the microbial environment favors the selective growth of drug-resistant mutants. The programmatic errors that lead to the development of durg resistance are inappropriate regimens,non-adherence to therapy by the patients, the sale and availability of over-the-counter drugs, an interruption in the drug supply, and the unavailability of free diagnosis and treatment. As a result, drug-resistant organisms are spread in the community, generating secondary cases with primary drug resistance, which in turn can spread and generate further cases. The uninterrupted cycle of creation and spreading is responsible for increases in DR. According to global data on anti-tuberculosis drug resistance appearing in the WHO monographs, drug resistance is so ubiquitous as to be encountered in every countyr. Anti-TB DR among previously treated cases was found to be very high in some countries, while it remained relatively low in others. The median of at least one drug resistance among four major drugs tested, was 25.2%(ranging from 8.3 to 68.5%), and the median MDR-TB was 8.7%(ranging from 0 to 48.2%) among those previously treated patients. Drug resistance among new cases infected with drug-resistant organisms from patients with acquired or primary drug resistance was found to be higher in some areas than in others. The median of at least one drug resistance was 10.9%(ranging from 1.7 to 40.6%) and MDR-TB of 1.1%(ranging from 0 to 14.1%). Twelve geographic areas had levels of 3% or more of MDR-TB among new cases. The majority of MDR-TB cases end up as incurable and spread these deadly organismas in the community, as indicated by several outbreaks in certain areas. Increased MDR-TB will seriously threaten TB control programs in the future. We must therefore exert our best efforts to prevent the further generation of such cases by improving the cure rate of newly diagnosed cases, and by aggressively intervening to identify and remove MDR-TB cases as soon as possible. Key words:Tuberculosis, Drug resistance, Development, Control, Surveillance Korean Institute of Tuberculosis, Korean National Tuberculosis Association, Seoul, Korea Correspondence to:Sang Jae Kim, Tuberculosis Strategy & Operations, Stop TB Department, World Health Organization, 20 Avenue Appia, CH-1211 Geneva, Switzerland (E-mail:Kims@who.int) <7> Kekkaku Vol.77,No.11:741-752,2002 The 77th Annual Meeting Special Lecture MOLECULAR EPIDEMIOLOGY OF MYCOBACTERIUM TUBERCULOSIS: ITS ACCOMPLISHMENT AND FUTURE PERSPECTIVE Mitsuyoshi TAKAHASHI Abstract In the traditional study of tuberculosis epidemiology, information about social contact of persons and patient's illness history used to be an only relevant basis for elucidating transmission of tuberculosis infection. Therefore, it was very difficult to give a clear conclusion of whether isolates from different patients derived from a common source of infection or not. Recently, the subspecies typing of M.tuberculosis strains has become possible, based on the visualization of multiple loci of an insertion sequence (IS6110) that is a relatively stable gene fragment existing in a specific region of the genome. The variability of the number of copies and locations of this IS6110 in a genome is the basis that enables this technique to be used for the above purpose, which is a unique tool applicable to the analysis of M.tuberculosis. Generally, this technique, i.e., restriction fragment length polymorphism (RFLP) analysis, depends on the diversity of pattern of any polymorphic marker found in a genome of a strain. Among various markers so far developed and examined, IS6110 has been proved most appropriate for the purpose of typing strains of M.tuberculosis complex, especially in such circumstances as in Japan where isolated strains' RFLP patterns are similar each with others so that finer sub typing is needed. In this lecture, I would like to review the following topics based on the world literature of molecular epidemiology and the findings of our own that we have achieved during 1992 through 2001 in our Institute;1)typing of the isolates for the identification of the infection source, 2)pathogenesis of tuberculosis under low incidence situation, 3)predominance of certain genotypes endemic in an area, 4)cross-contamination of isolates in the laboratory, 5)the stability of IS6110 patterns, 6)phylogeny of M.tuberculosis complex, and 7)differentiation between M.tuberculosis and M.bovis BCG. Key words:Molecular epidemiology, IS6110, M.tuberculosis Department of Bacteriology, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Correspondence to:Mitsuyoshi Takahashi, Department of Bacteriology, Research Institute of Tuberculosis, JATA, 3-1-24, Matsuyama, Kiyose-shi, Tokyo 204-8533 Japan. (E-mail:tak@jata.or.jp) <8> Kekkaku Vol.77,No.11:753-757,2002 The 77th Annual Meeting Educational Lecture TUBERCULOSIS CONTROL AND TECHNOLOGY ASSESSMENT IN JAPAN WITH SPECIAL REFERENCE TO CANCER CONTROL Akira OSHIMA Abstract Tuberculosis morbidity and mortality statistics show that tuberculosis control efforts in Japan have recently borne little fruit. Almost a similar situation has occurred in cancer control efforts in Japan. To overcome these difficulties, we should introduce the principles of evidence-based healthcare into control activities and each activity of tuberculosis control and cancer control should be evaluated strictly by technology assessment. The most important issue to be discussed is that screening programs for tuberculosis and various cancers have been eagerly conducted in Japan as a public health policy since 1951 and 1961 and there has been no change of "Early diagnosis / early treatment is best" policy although many changes have occurred around the diseases and the society since then. From the viewpoint of a cancer epidemiologist, the significance of screening tests for tuberculosis, the completeness of tuberculosis registries, the significance of tuberculosis registries as a monitoring system for tuberculosis treatment and the role of health centers in the new programs of tuberculosis control are discussed. Key words:Technology assessment, Evidence-based healthcare, Efficacy, Effectiveness, Efficiency Department of Cancer Control and Statistics, Osaka Medical Center for Cancer and Cardiovascular Diseases Correspondence to:Akira Oshima, Department of Cancer Control and Statistics, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka-shi, Osaka 537-8511 Japan (E-mail:oosima-ak@mc.pref.osaka.jp) <9> Kekkaku Vol.77,No.11:759-761,2002 The 77th Annual Meeting Symposium TREATMENT FOR TUBERCULOSIS IN DIFFICULT SITUATIONS Chairpersons:1Toru RIKIMARU and 2Takeo KAWASHIRO Abstract Many patients with tuberculosis have complications and concern with underlying diseases. Those statuses make us difficult to treat the patients with tuberculosis. We presented the therapy of senile and infant tuberculosis and tuberculosis of patients with hemodialysis, diabetes mellitus, liver dysfunction, pregnancy, and puerperium in this symposium. We discussed about further issues with audiences. Symposium Topics and Presenters: 1.Treatment for senile tuberculosis and tuberculosis associated with hemodialysis: Toshinobu YOKOYAMA(Department of Internal Medicine, Kurume University School of Medicine) 2.Treatment for tuberculosis associated with diabetes mellitus:Fumio YAMAGISHI (Department of Respiratory, National Chiba-Higashi Hospital) 3.Clinical investigation of patients with pulmonary tuberculosis associated with liver disorder:Tetsuya SHIOMI(Department of Internal Medicine, National Higashi-Saitama Hospital) 4.Treatment for tuberculosis associated with pregnancy and puerperium:Emiko TOYOTA(1), Shigeki MINOURA(2), Hirofumi MIYAZAWA(3), (Department of (1)Respiratory, (2)Gynecology, (3)Pediatrics, International Medical Center) 5.Treating infants, especially 12 month-old or less, for tuberculosis:Shinya KONDO, Masaki ITOH (Division of Respiratory Disease, Tokyo Metropolitan Children's Hospital) Main issue of this symposium was treatment for tuberculosis in difficult situations. At first, we decided what were difficult situations. There were so many personal and social problems to treat patients for tuberculosis. We focused personal and popular issues, such as senile and infantile tuberculosis and tuberculosis associated with hemodialysis, diabetes mellitus, liver disorder, pregnancy and puerperium. Dr. Yokoyama reported as for tuberculous patients with dialysis and elder patients with pulmonary tuberculosis. He described that those patients were treated successfully although both states were immunosuppressive. Treatment for patients with hemodialysis was problem in care and management, not in therapeutic. Dr. Yamagishi strongly described that patinets with diabetes mellitus were one of the high risk groups of developing pulmonary tuberculosis and they had to undergo chest X-ray examination periodically. He revealed that many physicians treating for diabetes mellitus had little concern with tuberculosis, thus the retraining of physicians dealing with diabetics on tuberculosis is considered to be necessary. We discussed with the duration of treating patients for tuberculosis associated with diabetes mellitus. Thus far, the duration was controversial. Dr. Shiomi presented about clinical investigation of pulmonary tuberculosis with liver disorder. He described that patients with liver disorder needed to discontinue the use of the medicine. Duration of smear positive in the patients, however, had no significant difference compared with patients without liver disorder. Dr. Toyota reported 22 cases with tuberculosis associated with pregnancy and puerperium. 10 cases out of all had extra pulmonary lesions and 9 cases were foreign women. It was difficult to diagnose the patient's illness as tuberculosis because pregnancy and puerperium hid symptoms of tuberculosis. A long time was needed to diagnose the pregnant patients as tuberculosis. WHO and BTS recommended standard four drugs regimen:INH, RFP, EB, and PZA, for these patients. On the other hand, ATS suggested three drugs regimen without PZA due to less data of adverse reaction of PZA in patients with pregnancy and puerperium. All guidelines recommended that SM was not suitable for patients with pregnancy and puerperium because of the adverse reaction as hearing loss. Dr. Kondo revealed that the number of tuberculosis infants less than one year were considered to be risky against tuberculosis. One of major reasons of difficulties in treatments is the rapid progress of the disease because of underdevelopment of cell- mediated immunity among them. Anatomical underdevelopment of cranial arteries and narrow cerebrospinal passages easily cause cerebral infarction and hydrocephalus following meningeal inflammation of tuberculosis. A belated diagnosis also makes the treatment difficult in some infants whose tuberculin skin test shows false negative and radiographic manifestation of chest is unwarranted. During the treatment, systemic and enteric viral infections occur frequently among infants with tuberculosis, and liver functional disorders caused by these infections sometimes prevent the treatment. It is important to treat tuberculosis as soon as possible and to recognize both susceptibilities to tuberculosis and difficulties in diagnosis in some infants less than one year. We appreciate all of participants in this symposium. Key words:Treatment for tuberculosis, Complications, Senile tuberculosis, Pregnancy, Infant tuberculosis (1)Internal Medicine, Kurume University School of Medicine, (2)Department of Internal Medicine, National Higashi-Saitama Hospital Correspondence to:Toru Rikimaru, Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume-shi, Fukuoka 830-0011 Japan. (E-mail:riki@med.kurume-u.ac.jp)