Nowadays, methods of the diagnosis in infants with suspected tuberculosis and of the treatment are definitely established in Japan, where a number of childhood tuberculosis has been falling down (the incidence is less than 2 per 100, 000). Still, infants less than one year are considered to be at high risk against tuberculosis. Actually, the number of tuberculosis among them is three times larger than those of one or two years old children. One of major reasons of difficulties in the treatment is the rapid progress of the disease because of underdeveloped cell-mediated immunity among them. Alveolar macrophage and lymphocyte and their cooperation in immunological functions do not develop enough to kill or confine Mycobacterium tuberculosis. As a result, the infection may progress to disease quickly, and then may spread systemically before the starting treatment. Anatomical underdevelopment of cranial arteries and narrow cerebrospinal passages easily cause cerebral infarction and hydrocephalus following meningeal inflammation due to tuberculosis. These neurological disorders may result in poor prognosis despite of administration of effective antituberculosis medicines. Delay in the diagnosis also makes the treatment difficult in some infants whose tuberculin skin test shows false negative and radiographic manifestation of chest is not clear. During the treat-ment, systemic and enteric viral infections occur frequently among infants with tuberculosis, and liver functional disorders caused by these infections sometimes disturbs the treatment for tuberculosis. Recurrence of tuberculosis is very rare among infants who complete the full treatment at the age of more than one year. Finally, it is important for the early start of treatment for tuberculosis to recognize both susceptibility to tuberculosis and difficulties in the diagnosis in some infants less than one year.

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The incidence rate of “active” pulmonary tuberculosis (TB) cases with bacteriological confirmation or cavitary lesions on chest radiographs was studied among population screened with mass miniature radiography in Funai-Gun, Kyoto Prefecture from 1982 to 1993. The results were as follows: Among population of 40 and over, prevalence rate of all fibrotic lesions on chest radiographs among male (8.3%) was twice as high as that of female (3.8%). The rate of moderate or extensive fibrotic lesions among male (3.3%) was three times as high as that of female (1%). The higher the age of the population, the higher the prevalence rate of radiologi-cal fibrotic lesions both in male and female. In male, in particular, prevalence rate of moderate or extensive fibrotic lesions started to rise after 40 years of age, became much higher after 70 years of age and reached8.1% after 80 years of age. In female, however, it started to rise at 50s (0.3%) gradually and reached only2.3% after 80 years of age. The incidence rate of “active” pulmonary TB among male of 40 years and over with moderate or extensive fibrotic lesions (4.2 per 1000person-years) was16 times as high as male of 40 years and over with normal chest X-ray finding (0.26 per 1000 person-years). Similarly, the incidence rate of “active” pulmonary TB in female of 40 years and over with moderate or extensive fibro-tic lesions was 24 times as high as among female with normal finding, and the difference was statistically significant (p<0.001). From the data obtained and bibliographical review, benefits of INH prophylaxis were discussed.

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In cases in which hepatotoxicity developed during anti-tuberculosis chemotherapy, the rapid recovery of liver function is essential for the completion of the anti-tuberculosis chemotherapy protocol. Glycyrrhizin (Stronger Neo-Minophagen C: SNMC) is widely used in Japan for the treatment of patients with drug eruption or chronic hepatitis. However, a consensus on the clinical effects of glycyrrhizin for the treatment of anti-tuberculosis druginduced hepatitis has not yet been reached. We studied 24 cases who showed abnormal liver function test results while undergoing anti-tuberculosis chemotherapy and who were treated with or without glycyrrhizin. We then compared recovery periods of liver function among both groups. The time required for liver function normalization in the patients who received glycyrrhizin (SNMC, 40 ml daily, intravenously) was 15.1±4.5 days and the time required for normalization in the non-glycyrrhizin group was 15.2 5.2 days. The difference was not significant and the fact indicated that glycyrrhizin is not useful for the treatment of anti-tuberculosis drug-induced hepatitis.

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Notification of TB cases was introduced since 1947 in Japan, and statistics on notified TB cases by sex and age groups was available since 1949. Sex and age specific TB notification rates per 100, 000 from 1949 to 2001 were tabulated together with the number of notified TB cases since 1969.

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A 90-year old man was admitted to a hospital because of consciousness loss with hyponatremia. Although his symptom promptly improved with Na supply, his chest X-ray film showed pulmonary infiltration and direct microscopy of sputum smear was positive for acid-fast bacilli, then he was referred our hospital and was admitted. We made a clinical diagnosis of pulmonary tuberculosis with SIADH based on detailed examinations. But he should neither respiratory symptoms nor fever. He was medicated with the standard antituberculosis drugs with fluid restriction, and his tuberculo-sis and hyponatremia were improved gradually.
We should be more careful about pulmonary tuberculosis irrespective of its severity as a cause of SIADH.

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There has not yet been systematic studies which attempt to elucidate detailed profiles of the interaction between antimicrobial drugs and macrophage microbicidal mechanisms. We examined the effects of antisense oligo DNAs (AsDNAs) against oxyR and ahpC on the susceptibility of Mycobacterium avium complex (MAC) to the H₂O₂-halogenation system and combined antimycobacterial drugs [Cclarithromycin (CAM) + rifampicin (RFP)], both separate-ly and in combination. It was found that AsDNA treatment of MAC did not affect the susceptibility of the organisms to any of the antimicrobial systems tested. Since the present AsDNAs did not efficiently reduce the expression of AhpC mRNA, attempts to increase bacterial uptake of AsDNAs are necessary to achieve significant increase in the drug susceptibility of MAC organisms due to AsDNA treatment.

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The unprecedented and rapid changes at the global level posed a big challenge to public health. The tuberculosis disease as one of major health problems today should be viewed from this context. These global challenges include 1) population issue particularly on growth and ageing; 2) epidemiological issue such as health transition; and, 3) social and environmental issues such as rapid urbanization and global warming. Furthermore, we should also take into account other changes such as the role of the government in the health service delivery, clinical or cure-oriented approach to prevention, increasing consumer demand and health financing.
The burden of tuberculosis is devastating. Everyday in the Western Pacific Region (WPR), about 1000 people lose their life due to tuberculosis. Most of them are between the ages 14-54, which are the socalled economically productive age group. The economic impact, therefore, is significant. In addition TB is a disease of poverty of which the risk of getting TB is higer in poor who have less access to TB services due to financial barrier and lack of knowledge. Despite this devastating situation, TB has a significant and cost effective tool called DOTS. WPRO put highest priority in TB control programme not only because of the facts mentioned above but I also consider TB as an agenda carried over from the last century. I would like, then, to commit myself to this cause for the betterment of the future of the next generation.

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The number of people infected with human immunodeficiency virus (HIV) is gradually increasing in Japan, and the morbidity rate from tuberculosis in the Japanese people is high. Accordingly, the number of cases with both infections is considered to increase in the future. Our hospital has already encountered 31 cases of HIV associated tuberculosis.
HIV infects mainly CD4-positive cells. The extreme decrease in the cell count results in serious cellular immunological disorder. CD4-positive cell disorder induces disorders of B lymphocytes, cytotoxic T cells, natural killer cells, and macrophage functions. These destructive conditions show the state of immunodeficiency including macrophage that are most important for defense of acid-fast bacterial infection. Migration and activation of macrophages with cytokines derived from T cells are impaired to induce the following phenomena: hypo-plasia of granuloma, failure of tubercule bacillus suppression, the spread to regional lymph nodes (hilar or mediastinal lymph nodes), and hematogenous dissemination. On this occasion, caseous necrosis and cavitation are unlikely to occur, and false-negative tuberculin reaction is often observed.
The incidence of severe cases, which include miliary tuberculosis, tuberculous meningitis, etc., and extrapulmonary tuberculosis, are high among acquired immunodeficiency syndrome (AIDS)-associated tuberculosis cases. HIV-infected tuberculosis cases are generally regarded as endogenous exacerbation, but they include primary infection and reinfection as well. Even during the treatment for drugsensitive strains particularly, some cases may have reinfection with multidrug-resistant bacteria, suggesting that caution should be taken against this point. Conversely, the association of tuberculosis is a factor for the poor prognosis of HIV infection, since it facilitates the development of HIV infection. If the bacteria belong to a drug-sensitive strain, the infection with them responds well to antituberculous drugs, the same as in tuber-culosis cases without HIV infection, showing a favorable prognosis. However, the mortality rate of infection with multidrug-resistant tuberculosis is extremely high.
The combined use of a protease inhibitor, i.e., anti-HIV drug, with rifampicin is regarded as contraindication for the treatment because rifampicin strongly induces hepatic cytochrome P-450 and increases the metabolism of protease inhibitors and nonnucleoside reverse transcriptases to markedly decrease the blood concentrations. Accordingly, the treatmentfor tuberculosis should take priority over that for HIV infection in HIV-infected tuberculosis, and highly active antiretroviral therapy (HAART) may be administered after the treatment of tuberculosis. When HAART is necessary for the treatment during the tuberculosis treatment, rifampicin had better be exchanged to rifabutin because the effect of rifabutin to induce cytochrome P-450 is less potent than that of rifam-picin.

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