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Mycobacterium xenopi is very rare pathogen in Japan. We reported herein four cases of M. xenopi pulmonary disease. These patients were all male and their ages ranged from 53 to 72. They all had past history of pulmonary tuberculosis, including two cases who had been also treated for Mycobacterium kansasii pulmonary disease later. The bacilli could be cultured in Mycobacteria Growth Indicator Tube (MGIT) system from 10 sputum samples, but they could not be cultured on Ogawa egg media except for two samples. All four cases fulfilled the criteria for the diagnosis of nontuberculous mycobacteria pulmonary disease proposed by the Japanese Society for Tuberculosis. Combination chemotherapy including isoniazid, rifampicin, and ethambutol was started in all four cases when mycobacteria were detected under tentative diagnosis of the relapse of tuberculosis or Mycobacterium kansasii disease. Sputum converted to culture negative by the chemotherapy in two cases. In one case, the chemotherapeutic regimen was changed to rifampicin, ethambutol, and clarithromycin after the bacteriological identification of M. xenopi, and the new regimen was found to be effective. In the final case, both of the regimens were finally ineffective.
Principles of antituberculosis chemotherapy and the present situation of the drug susceptibility testing in Japan were reviewed. There are three types of the bacteria in patients with tuberculosis: 1) actively replicating bacteria in cavities, 2) slowly replicating bacteria in caseous necrosis, and 3) fully dormant bacteria. The type 1) bacteria are the most vulnerable to all antituberculosis drugs, particularly INH, while the type 2) bacteria are susceptible to either RFP or PZA alone. In Japan, the drug susceptibility testing have been done by the absolute concentration method using Ogawa egg slants. However, there are many drawbacks pointed out in the system. Therefore, the Japanese society for tuberculosis has recommended a new testing system using the proportion method with the Ogawa medium since 1997.
We investigated the serum level of IL-8 and TNF-alpha using ELISA in 16 patients with active pulmonary tuberculosis before administration of antituberculous drugs and in age-, smoking habit-matched 20 healthy controls. The mean level of serum IL-8 in patients with active pulmonary tuberculosis was significantly higher than that in healthy controls (P < 0.001). The mean level of serum TNF-alpha in tuberculosis patients was also high, while TNF-alpha was not detectable in the sera of healthy controls. We also examined the relationship between clinical pictures mainly defined by radiographic findings and the serum levels of IL-8 and TNF-alpha. The serum IL-8 level of 9 patients with tuberculous cavity is significantly higher than that of 7 patients without cavity. (P < 0.05) We classified the patients with cavities into two subgroups according to the radiographic classification of the Japanese Society of Tuberculosis. Four patients with advanced lesions on chest X-ray showed higher serum IL-8 level than 5 patients with moderate lesions (P < 0.05). On the other hand, there was no correlation between serum TNF-alpha level and radiographic findings. These results suggest that IL-8 appears to be involved in the formation of tuberculous cavitary lesion.
The 1951 Tuberculosis Control Law of Japan is now faced with tremendous changes that have occurred during the last 50 years in tuberculosis epidemiology and in the environment in tuberculosis control implementation. The law is also challenged with the shift of the paradigm for the National Tuberculosis (TB) Programme. In order to respond properly to these changes, the Tuberculosis Panel of the Health Science Council of the Ministry of Health, Labor and Welfare submitted its report for the amendment of the law in March 2002. Based on this report, a new Tuberculosis Control Law was passed in Parliament last June, and related decrees of the Cabinet and the Ministry are now being revised in preparation for it's enactment in April 2005. In this special lecture, the main points and framework of the revisions were discussed with the perspective of the development of new technical innovations relevant to each area of the revised TB control legislation. 1. Case detection. There will be a shift from the current "indiscriminate" screening scheme to a selective one regarding periodic mass health examination. Only subjects aged 65 or older will be eligible for the screening, supplemented with selected occupational groups who are considered to be at a higher risk of TB, or may be a danger to others if they develop TB, such as health-care providers and school teachers. In addition, local autonomies are responsible for offering screening to the socio-economic high-risk populations, such as homeless people, slum residents, day laborers, and/or workers in small businesses. This means that the efforts of the autonomies are critical for the new system to be effective. The extra-ordinary examination will be limited to only the patient's contacts, and will be mandatory for those contacts so they cannot refuse to be examined by the Health Center. The public services used in the contact investigations will be greatly facilitated by such new technologies as DNA fingerprinting of TB bacilli and a new diagnostic of TB infection using whole-blood interferon-gamma determination (QuantiFERON). The quality of clinical diagnosis and monitoring of treatment should also be improved by introducing an external quality assurance system of commercial laboratory services. 2. Chemoprophylaxis. Although not explicitly defined in the new legislation, the expansion and improvement of chemoprophylaxis to cover anyone with any risk of clinical development of TB would have a tremendous effect in Japan, especially since 90% of patients who developed TB were infected tens of years ago. These technical innovations in diagnosis of TB infection will be very helpful. Development of new drug regimens for the preventive treatment is also badly needed. 3. Immunization. Prior to the amendment of the Law, the BCG vaccination of students entering primary and junior high schools has been already abandoned. In order to encourage the early primary vaccination for infants, the new Law will adopt the direct vaccination scheme in which babies will be given the BCG vaccine without tuberculin testing. This program will be implemented safely, only if it is given to young babies, e.g., less than one year old, as defined by the decree. It is essential to maintain the high level of vaccination coverage under the new program. The autonomy may encounter difficulty mobilizing client babies shortly after their birth (only one year, as compared with the current four years). To avoid the possible, though very rare, adverse health effects due to the vaccination of infected babies, careful questioning should be conducted regarding the risk of exposure to infection prior to vaccination. A ready course of treatment and examinations for abnormal reactions after vaccination (Koch's phenomenon) is also warranted. 4. Treatment and patient care: The revised Law clearly states the governmental responsibility for treating TB patients in close cooperation with a doctor. This is an important legal basis for the expansion of the DOTS Japan version. While the development of new anti-tuberculosis drugs will be realized in the near future, Japan still has to overcome the issue of improper practice of treatment, as well as the government's slow process for approving new drugs to be used for multi-drug resistant TB and non-tuberculous mycobacterioses. 5. Prefectural TB Control Plan: In order to resolve the problems specific to the respective prefectures in terms of epidemiological parameters or available resources, the new Law requests every prefecture to develop its own TB control plan. In order for the new TB Control Law to be effective, strong government commitment supported by technological innovation is mandatory. It is for that reason that the Japanese Society of Tuberculosis should aggressively join the global movement to stop TB along with the general public of Japan.
The year 1918 marked a juncture in the development of social work in health sare. During that year, the fledgling group of hospital social workers responded to needs created by World War I, the influenza pandemic, and epidemics of tuberculosis and venereal disease. At the same time, in order to meet these needs and to professionalize their services, they formed a professional organization, published two new journals, and expanded opportunities for professional education. Examination of these matters helps to explain the place and direction of hospital social work exactly 60 years ago.
Health care-almost exclusively a private affair in earlier times-is now more and more influenced by public administration. The role of the private organizations and with it the role of the health leagues has changed, but their importance remains. Motivation is stronger among volunteers, and services are more easily adapted to specific needs. Personal-also financial-engagement is a needed basis for many preventive actions, and public interventions should ideally be kept to a necessary minimum. Finally, private organizations are more ready and able to try new approaches and respond to changing needs. Their potential for innovation and flexibility will guarantee the persistence of their action within the Swiss health system, also in a future characterized by increasingly rapid change.
The cantonal associations against tuberculosis and lung disease, rheumatism and cardiovascular disease have joined in the "Fédération Vaudoise des Ligues de la Santé". Associations of diabetes, dialysis, mucoviscidosis and M. Bechterew collaborate in the local sections for assistance to patients and their relatives, early diagnosis, prevention and information of the public. Efficiency of the work and contacts with the authorities and the populations could be enhanced by this collaboration which still preserves the dynamism of the individual associations.
Together with the Cantonal League against Tuberculosis and Lung Diseases of Zurich, the Association "Das Band" has organized a first course for parents of children with asthma. The course is a component of the associations new "Prophylaxis Program for Children with Asthma and Their Parents". By exchanging ideas, the parents should become able to reflect their situation, characterized by excessive protectionism, aggressiveness, and guiltiness, and they also should learn to accept the disease as a part of their daily life. The first course, which meanwhile is followed by a second one, provided a first base for the solution of the many problems.
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We aimed to investigate the transitional pattern of the clinical features of pulmonary Mycobacterium-avium complex (MAC) disease, especially with regard to the clinical effect of treatment, in patients treated before and after the implementation of the 1998 guidelines of the Japanese Society for Tuberculosis for combined chemotherapy for pulmonary MAC disease. The clinical findings and treatments of 220 patients with pulmonary MAC disease during the past 10 years were compared by dividing the patients into two groups, each encompassing a 5-year period. During the past 5 years, we have carried out combined chemotherapy with rifampicin, ethambutol, an aminoglycoside (streptomycin or kanamycin), and clarithromycin (CAM) following the guidelines for the treatment of pulmonary MAC disease proposed in 1998, and we have achieved positive results; both the sputum conversion rate and clinical improvement of the outcome in patients with primary infectious type rose significantly. Although there were no significant differences in the background or in microbiological and radiological findings in the two groups, significant improvement was seen in the sputum conversion rate and in improvement of the clinical effect of treatment. The results of this combined chemotherapy were unsatisfactory, however, when compared with its clinical effect on pulmonary tuberculosis. Therefore, we anticipate the development of new companion drugs for pulmonary MAC disease that are as active as CAM.
A prospective study of the clinical efficacy of an aminoglycoside antibiotic (streptomycin, SM) for the treatment of pulmonary Mycobacterium avium complex (MAC) disease was carried out. In a multicenter trial, patients with pulmonary MAC disease received protocol-guided combined chemotherapy with or without SM. SM was given to the patients intramuscularly 15 mg/kg three times per week for the initial 3 months and three other antibiotics (rifampicin, ethambutol, and clarithromycin) were added and administered for over 24 months after the conversion of MAC strains. From April 1998 to December 2004, 160 HIV-negative patients were enrolled in this trial. Fourteen patients were found to be ineligible because they could not continue the treatment, and they were excluded from the analysis after randomization. Seventy-three patients were assigned to receive combined chemotherapy with SM (group A) and 73 were assigned to receive combined chemotherapy without SM (group B). The median durations of treatment were 27.6 months in group A and 28.4 months in group B. The difference in the backgrounds of the groups was not statistically significant. There were no differences in microbiological and radiological findings between the groups, but the sputum conversion rate for pulmonary MAC disease at the completion of treatment was significantly higher in group A than that in group B. Although, there were no significant differences in the sputum relapse rate and clinical improvement including both clinical symptoms and radiological findings, group A showed better initial microbiological response than group B. As for adverse reactions and abnormal laboratory findings, there were no significant differences between the groups. Based on the results of this double-blind randomized study, we support treatment including SM according to both the American Thoracic Society (ATS) and the Japanese Society for Tuberculosis (JST) guidelines for patients with pulmonary MAC disease without HIV infection.
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BACKGROUND: The difficulty of treatment for pulmonary Mycobacterium avium complex (MAC) in Japan. OBJECTIVES: To investigate the clinical and microbiological effects of treatment according to the guidelines proposed by the American Thoracic Society and the Japanese Society for Tuberculosis and prospective follow-up studies after the completion of treatment of patients with pulmonary MAC disease. METHODS: Analysis of the microbiological effects with regard to sputum conversion rate and the sputum relapsing rate and the clinical effects with regard to clinical symptoms and radiological findings for patients with pulmonary MAC disease treated with a regimen consisting of rifampicin, ethambutol, streptomycin, and clarithromycin over 24 months and follow-up over 12 months. RESULTS: Sixty-five patients with pulmonary MAC disease were enrolled in this trial. In 39 patients, negative sputum conversion was observed within 6 months after the initiation of this regimen, 16 relapsed, and 20 experienced clinical worsening within 1 year after the completion of treatment. Although retreatment with the same regimen or a regimen including new quinolones was carried out for these patients, we could not achieve negative sputum conversion and/or clinical improvement. CONCLUSIONS: We believe that the dose of clarithromycin for pulmonary MAC disease may be increased and recommend surgery for patients with a localized lesion at early-stage MAC disease to prevent a high rate of relapse.
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