(Vol.77 No.2 February 2002) <1>Kekkaku Vol.77 No.2:51-59,2002 Original Article TUBERCULOSIS IN THE PATIENTS UNDERGOING HAEMODIALYSIS IN JAPAN, 1996 1Yuka SASAKI, 1Fumio YAMAGISHI, and 2Toru MORI Abstract We conducted a questionnaire survey on patients undergoing haemodialysis about the present situation of tuberculous incidence. They are immunocompromised hosts and are said to be at high risk of developing tuberculosis in many reports. (1) Design Of the 167,192 patients on haemodialysis registered on December 31, 1996 in Japan, 71,411 patients were available for the questionnaire survey. Of the 2,893 hospitals used as the study subjects, 1,108 hospitals gave satisfactory replies. Of them, 141 hospitals reported that they had patients with tuberculosis in 1996, and 79 cases were collected by the detailed survey on tuberculosis patients conducted later. They included 45 male cases, 34 female cases for tuberculosis of all forms, 28 male cases, 15 femal cases for pulmonary tuberculosis (PTB), 13 male cases, 4 female cases for tuberculosis bacilli positive pulmonary tuberculosis (TB positive PTB), and 17 male cases, 19 female cases for extrapulmonary tuberculosis. (2)Results In tuberculosis of all forms, the number of observed patients (O) against the number of patients expected (E) was calculated, and the standardized patients ratio (O/E ratio) was computed. It was 1.55 for male, 2.79 for female and 1.99 for total. The incidence of tuberculosis haemodialysis patients was significantly higher compared with the general population (p<0.01). As to PTB, the O/E ratio was 1.01 for male, 1.40 for female and 1.16 for total;the incidence of PTB was not significantly higher compared with the general population. With TB positive PTB, the O/E ratio was 0.96 for male, 0.80 for female and 0.97 for total, and no significant difference was found. As for extrapulmonary tuberculosis, the O/E ratio was 13.45 for male, 13.07 for female and 12.97 for total;the incidence of extrapulmonary tuberculosis in haemodialysis patients was significantly higher (p<0.01), but it was lower than these reported in the past literature. The seventy nine cases consisted of 52 primary treatment cases, 23 retreatment cases, and 4 unknown cases. Out of 79 cases, 36 cases developed tuberculosis almost at the same time or within 1 year after undergoing haemodialysis, and thereafter it decreased gradually. Underlying diseases for haemodialysis were mainly glomerulonephritis and diabetic nephropathy. There were many patients who failed to notify to the public health centers after the diagnosis of tuberuclosis was made, and it is needed to improve such a situation in the future. The prognosis of tuberuclosis undergoing haemodialysis was poor. Three out of 43 patients with PTB and 2 out of 13 tuberuclosis pleurisy cases died. (3)Conclusion The risk of developing PTB in patients undergoing haemodialysis was not high compared with the general population, however, the risk was much higher for extrapulmonary tuberculosis, Moreover, the treatment outcome was not satisfactory in patients with PTB and pleurisy. As patients undergoing haemodialysis have the factors which suppress the cell-mediated immunity, it is requied to restudy the measures to prevent development of tuberculosis, management and tratment in the future. Key words:Haemodialysis, Tuberculosis, Immunocompromised host 1Division of Thoracic disease, National Chiba HIgashi Hospital, 2Research Institute of Tuberculosis, Japan anti-Tuberculosis Association Correspondence to:Yuka Sasaki, Division of Thoracic disease, National Chiba Higashi Hospital, 673, Nitona-cho, Chuo-ku, Chiba-shi, Chiba 260-8712 Japan.(E-mail:sasakiy@chibae.hosp.go.jp) <2>Kekkaku Vol.77 No.2:61-66,2002 Original Article INTERPRETIVE COMPATIBILITY OF ANTIMYCOBACTERIAL SUSCEPTIBILITY FOR MYCOBACTERIUM TUBERCULOSIS DETERMINED BY PROPORTION TEST METHOD ON EGG-BASED OGAWA MEDIA AND BROTH MICRODILUTION TEST, BrothMIC MTB 1Miyako HIGA, 2Hiroshi SAITOH, 3Nobuhisa YAMANE, 1Isamu NAKASONE, and 3Chika MIYAGI Abstract The antimycobacterial susceptibility test method newly proposed by the Japanese Society for Tuberculosis, a proportion method on egg-based Ogawa media, was evaluated in comparison with microdilution test for Mycobacterium tuberculosis complex, BrothMIC MTB-1(Kyokuto Pharmaceutical Inc., Tokyo). In the evaluatin, five antimicrobial agents, streptomycin, ethambutol, Kanamycin, isoniazid and rifampicin were included. Through repeated testings of the three reference strains against five antimicrobial agents, both test methods were found to be highly precise. All the minimum inhibitory concentrations (MICs) determined by BrothMIC MTB fell within 3 log(2) dilutions, however a total of 11 MICs resulted in indeterminate (I) interpretations. Whereas, all the test results by a proportion method on Ogawa media were comparable to the expected interpretations. However, three of 48 testings resulted in undeterminable interpretations due to insufficient growth on the growth control media. A total of 127 clinical isolates of M. tuberculosis complex were tested by both methods, and 89 to 90% of the test results were comparable with each other in category interpretations. However, 7.1 to 9.4% of MICs determined by BrothMIC MTB resulted in indeterminate (I), and 0.8 to 3.1% of discrepant interpretations were observed. In conclusion, both test methods were highly precise and comparable in determining antimycobacterial susceptibility for M. tuberculosis complex. Several advantages and disadvantages in each test method were discussed. Key words:Antimycobacterial susceptibility test, Interpretive compatibility, Proportion test method on Ogawa media, Microdilution susceptibility test, BrothMIC MTB 1Clinical Laboratories, University Hospital School of Medicine, University of the Ryukyus, 2Clinical Research Laboratories, National Miyakonojo Hospital, 3Department of Laboratory Medicine, Faculty of Medicine, University of the Ryukyus Correspondence to: Miyako HIGA, Clinical Laboratories, University Hospital School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Nakagami-gum, Okinawa 903-0215 Japan. (E-mail:miyako-ryk@umin.ac.jp) <3>Kekkaku Vol.77 No.2:67-72,2002 Case Report A CASE OF MILIARY TUBERCULOSIS COMPLICATED WITH SIADH, BRAIN TUBERCULOMA, AND TUBERCULOUS MENINGITIS Makoto TAKAHARA Abstract A 46-year old man complained fever, headache, and vertigo after he was given steroid for sudden deafness. He was diagnosed as mieiary tuberculosis by his chest CT findings. After admission, 4 anti-tuberculous drugs (INH, RFP, SM, and PZA) were prescribed but his laboratory findings showed SIADH, which was difficult to treat, and steroid was readministered. Brain MRI, examined 2 months after admission, showed brain tuberculomas, and examination of cerebrospinal fluid revealed a diagnosis of tuberculous meningitis. Three months later, meningitis deteriorated transiently, however symptoms and findings improved by increasing steroid. Later, miliary tuberculosis and SIADH were cured, however, some tuberculomas grew larger gradually on brain MRI, and spinal MRI showed tuberculomas in the spinal cord. LVFX, high concentration in CFS, was added. At present (2 yrs after begining the therapy), lesions in the brain and spinal cord improved but remain with the sequelae. Key words:Miliary tuberculosis, SIADH, MRI, Brain tuberculoma, Tuberculous meningitis Department of Internal Medicine, National NIshi-Kofu Hospital Correspondence to: Makoto Takahara, Department of Internal Medicine, National Nishi-Kofu Hospital, 3368, Yamamiya, Kofu-shi, Yamanashi, 400-0075 Japan. (E-mail:takahara@wkoufu.hosp.go.jp) <4>Kekkaku Vol.77 No.2:73-77,2002 Case Report A CASE OF DISSEMINATED TUBERCULOSIS REQUIRING EXTENDED PERIOD FOR THE IDENTIFICATION OF MYCOBACTERIUM TUBERCULOSIS ON CULTURE 1Junko ASHINO, 1Isao OHNO, 1Shinji OKADE, 1Yuji NISHIMAKI, 2Yoshihiko SAITO, 3Mareyuki ENDO, 2Mitsuo KAKU, 3Hironobu SASANO, and 1Toshio HATTORI Abstract A 80-year-old male visited an outpatient department of a nearby hospital complaining of fever, cough, and poor appetite on June 2000. The patinet was diagnosed as bacterial pneumonia and was treated with antibiotics although specific cause could not be identified. After one month, he was hospitalized due to lack of improvement. After admission, acid-fast bacilli (AFB) was found from the bronchial washing. The patient was then transferred to our hospital. Upon admission, sputum smear examination was potitive for AFB and MTB was confirmed by PCR. Therapy was initiated with INH 300 mg, RFP 450 mg, EB 1000 mg, and PZA 1000 mg, orally daily. However, on the day following the admission, he became unconscious. Brain MRI showed several small granulomas on the cortex of the bilateral anterior and temporal brain. Although AFB was not detected from the cerebrospinal fluid, tuberculous meningitis was suspected and steroid was given. Nine days after admission, the patient died due to tuberculous meningitis. The isolation of MTB had been attempted on Ogawa culture medium using patient's sputum and liquor, and it took 14 weeks to find colony growth both from sputum and liquor. In the autopsy, numerous granulomas were detected in his lung, liver, kidney, and pancreas. These findings indicate that disseminated growth of MTB occurred in vivo in spite of very slow growth of MTB in vitro. Key words:Miliary tuberculosis, Tuberculous meningitis, Virulence, Culture, Anti TBGL (tuberculous glycolipid) antibody 1Department of Respiratory & Infection Diseases, 2Clinical Laboratory, 3Pathology Laboratory, Tohoku University Hospital Correspondence to:Junko Ashino, Department of Respiratory & Infection Diseases, Tohoku Universtiy Hospital, 1-1, Seiryo-cho, Aoba-ku, Sendai-shi, Miyagi 980-8574 Japan. (E-mail:ashino@intl.med.tohoku.ac.jp) <5>Kekkaku Vol.77 No.2:79-86,2002 The 76th Annual Meeting Educational Lecture CT DIAGNOSIS OF PULMONARY INFECTIOUS DISEASES Sadayuki MURAYAMA Abstract Generally, the patient's inflammatory reaction is obvious, and the characteristic infiltrative shadow as pneumonia in the chest radiograph is recognized, no more imaging study is needed. However, when (1) radiographic finding is uncommon as a pneumonia; (2) antimicrobial drug treatment is ineffective;or (3) stenosis of central bronchi causing pneumonia by lung cancer and so on is suspicious, more precise imaging information of computed tomography (CT) is necessary. Recently, high resolution CT of lung disease as a new diagnostic method has been introduced, and diagnostic efficacy of CT has markedly advanced. Although the high resolution CT diagnosis based on the minute anatomy of the lung is also applied for the pulmonary infectious disease, their analysis and arrangement is not yet established since a large number of pathogens and various images exist. In reading CT films, it is necessary to consider patient's immune status. Infectiostiy and size of the pathogen must be also considered. In this manuscript, CT imaging characteristics of lung infectious diseases are clarified by taking these points into account. Key words:CT, high resolution CT, Pulmonary infection, Community-acquired pneumonia, Hospital-acquired pneumonia Department of Radiology, School of Medicine, Universtiy of the Ryukyus Correspondence to: Sadayuki MURAKAMI, Department of Radiology, School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Nakagami-gun, Okinawa 903-0215 Japan. (E-mail:sadayuki@med.u-ryukyu.ac.jp) <6>Kekkaku Vol.77 No.2:87-93,2002 The 76th Annual Meeting Educational Lecture REGULATION OF Th1 AND Th2 IMMUNE RESPONSES BY IL-18 Kenji NAKANISHI Abstract IL-18, which requires cleavage with caspase-1 to become active, was originally discovered as a factor that enhances IFN-ƒÁ production from Th1 cells in the presence of anti-CD3 or anti-TcR Ab. However, it was later shown that IL-12 and IL-18 without TcR engagement can induce IFN-ƒÁ in Th1 cells and nonpolarized T cells. Additional TcR engagement has no effect on this TFN-ƒÁ response. Furthermore, a combination of IL-12 and IL-18 acts on B cells, NK cells, macrophages and dendritic cells to produce IFN-ƒÁ. In contrast, IL-18 without help from IL-12 induces Th2 cytokines in T cells and NK cells. Moreover, IL-18 directly stimulates basophils and mast cells to produce Th2 cytokines and histamine independently of IgE. Most surprisingly, IL-18 causes high-level IgE production when administered to normal mice by causing CD4(+) T cells to produce IL-4 and to express CD 40 ligand. We established skin-specific caspase-1 transgenic mice with elevated levels of IL-18 in their sera. We found high serum level of IgE, which is entirely dependent on stat6 in these transgenic mice. These results indicate that caspase1/IL-18 may be critically involved in regulation of IgE production in vivo, providing a potential therapeutic target for allergic disorders. Key words:IL-18, Th1 immune response, Th2 immune response, Allergic diseases Department of Immunology and Medical Zoology, Hyogo College of Medicine Correspondence to: Kenji Nakanishi, Department of Immunology and Medical Zoology, Hyogo College of Medicine, 1-1, Nukogawa-cho, Nishinomiya-shi, Hyogo 663-8501 Japan.