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 female 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 extrapulmoanry tuberculosis.
(2) Results
In tuberculosis of all forms, the number of observed patients (0) 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 tuberculosis was made, and it is needed to improve such a situation in the future.
The prognosis of tuberculosis undergoing haemodialysis was poor. Three out of 43 patients with PTB and 2 out of 13 tuberculosis 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 required to restudy the measures to prevent development of tuberculosis, management and treatment in the future.

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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 evaluation, 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 log2 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.

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A 46-year-old man complained fever, headache, and vertigo after he was given steroid for sudden deafness. He was diagnosed as miliary 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 CSF, was added. At present (2 yrs after beginning the therapy), lesions in the brain and spinal cord improved but remain with the sequelae.

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A 80-year-old male visited an outpatient department of a nearby hospital complaining of fever, cough, and poor appetite on June 2000. The patient 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 positive 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 c erebrospinal 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.

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Mizutani estimated three therapeutic guidlines in US, UK and Japan. (1) MAC infection: In USA, CAM and AZM are the essential drugs and combination therapy with EB, RFP/RBT and SM were recommended by ATS in 1997. In UK, the administration of CAM and AZM are restricted to the cases of treatment failure or the relapsed cases. In Japan, though the efficacy of CAM and AZM have been well understood, these drugs are officially not recommended as key drugs yet, because recommended dosage of such medications by ATS are not covered by medical health insurance. In Japan and USA, one year is estimated enough to finish the treatment with the regimens include CAM or AZM. In UK, two years are recommended for treatment period. The New-Quinolons and TH are listed as the other drugs for medications, but all guidlines stated that these drugs are not so useful. (2) M kansasii infection: The all guidlines stated that RFP has an excellent activity against M kansasii. The usefulness of INH is disputable, therefore ATS recommended the regimen with HRE (INH, EB and RFP). It comes to the same recommendation in Japan, but BTS recommend the prescription with RFP and EB. (3) The rapid growers: The anti-tuberculous drugs are recommended for these species in UK, but the ATS guidline stated that anti-tuberculous drugs have no effect for such species.
Harada evaluated the usefulness of the Japanese guideline of treatment for non-tuberculous mycobacteriosis (NTM), studying the outcome of treatment and the prognosis of pulmonary MAC disease for 50 cases of long term follow-up and 33 dead cases in his hospital. The results were as follows: (1) The dead cases were older and severer on chest X-ray features at starting of initial treatment, comparing survived cases which were observed for more than 5 years. In clinical patterns, a tuberculosis-like pattern of primary infection type and secondary infection type were more frequent in dead cases than in survived cases. (2) Among dead cases, the cases of tuberculosis-like pattern died earlier than the cases of diffuse bronchiectatic pattern, inclining to be in persistent bacillipositive condition. (3) In the long survivors more than 5 years, the rate of persistent bacilli-positive cases was 40%, but the rate of worsened cases on chest X-ray was 54%. (4) In long survivors, bacteriological prognoses are not correlative with the courses of chest X-ray features. (5) The bacteriological prognoses in 1-2 years of primarily treated cases following the Japanese guidline were better than the prognoses of other treated cases. These results showed that the prognoses of MAC patients were strongly affected by clinical features before treatment, and the Japanese guidline is useful for the treatment of pulmonary MAC disease.

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In ordinary general hospitals lacking a ward to use exclusively for T. B., technicians in charge of acid-fast bacteria test are working without the aid of special doctors for T. B. However, the technicians often discover a patient positive for smear test for the first, because such patient is apt to visit hospital with suspect of some disease other than T.B. Therefore, they are required to quickly produce reliable and accurate results of the smears test for acid-fast bacteria from a doctor in charge. Recently, the test procedures for acid-fast bacteria have been markedly progressed as seen in gene analysis, use of liquid culture medium and automatic culture system and knowledge necessary to perform the test are much increased. In facilities lacking a special and/or leader doctor for T. B., laboratory technicians are racking to prepare a routine manual for the test suitable for each facility. In last year, a new guideline for T.B. test has been introduced under such circumferences after 20 years from the last revision. Here, we described the present status and problems in acid-fast bacteria test in general hospitals lacking T. B. ward for exclusive use, aiming to inform the specialists in the academic field of T. B. and make clear what laboratory technicians should do. It seems necessary to clarify the practical procedures and range of our works according to the procedures defined by the guideline. Thus, it would be easy to realize the purpose of guideline in the routine test of our general hospitals. Furthermore, we proposed some problems to put it in practice as daily procedures, especially in hospital with no special ward for T. B. We hope that the opinions of laboratory technicians in charge of the test are reflected to the revision of guideline in future.
We thanks to, Drs. T. Abe and H. Saito for their valuable advice to hold this symposium

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