[RISK GROUPS FOR TUBERCULOSIS IN JAPAN: ANALYSIS OF RELATIVE RISK AND POPULATION ATTRIBUTABLE FRACTION].

OBJECTIVE: Despite the decreasing trend in tuberculosis (TB) cases reported within the general population, TB incidence remains high in certain high-risk groups in Japan. Many of the previous discussions and studies have concentrated mainly on the elderly and those with clinical risks; however, no comprehensive evaluation has been conducted to date. Our study thus sought to estimate the relative risk (RR) and the population attributable fraction (PAF) of selected risk groups in Japan and discuss their relevance to programming future research needs and policies. METHOD: PAF and RR were calculated for patients with human immunodeficiency virus infection, diabetes, rheumatoid arthritis, those on dialysis, the elderly, health care workers, the homeless, people receiving public assistance, foreigners, prisoners, smokers, and those with alcohol problems, and were grouped into "high PAF" (PAF ≥ 5%), "middle PAF" (5% > PAF ≥ 1%), and "low PAF" (PAF < 1%) groups. RESULTS: The elderly and patients with diabetes showed the highest PAF and RR and should thus be prioritized for policies.

[EFFECT OF EDUCATIONAL LEAFLETS ON KNOWLEDGE AND ATTITUDE TO TUBERCULOSIS AMONG HOMELESS PERSONS IN TOKYO, JAPAN].

SETTING: Delay in seeking care is one of the critical issues in tuberculosis (TB) control among homeless persons in Japan. Yet knowledge of and attitude towards TB among homeless persons have remained unclear and limited efforts have been made to disseminate information related to TB among homeless persons. OBJECTIVE: To evaluate the effect of TB leaflets, produced and distributed to homeless persons by a group of ex-homeless TB patients, and to understand what homeless persons know about TB. DESIGN: Self-administered questionnaire was conducted among homeless persons before and after distribution of the TB leaflets. Changes in the responses to each question were also subjected to principal component analysis to group questions into types according to response patterns and identify constructs of TB-related knowledge. RESULTS: Results of 88 participants were analyzed. TB knowledge score related to risks and symptoms significantly improved after the intervention (from 54.3% to 70.6%, p < 0.05), while knowledge on treatment cost did not. Two components were identified, namely, the "improvement in TB impression" and "improvement in TB knowledge". CONCLUSION: TB leaflets were effective in improving certain aspects of TB knowledge. However, its effect on knowledge regarding treatment cost, which may be crucial in improving delay, was limited and thus the messages need to be revised.

[Socio-economic factors that influence tuberculosis death among the youth and middle-aged population: a systematic review].

OBJECTIVE AND METHOD: The number of tuberculosis (TB) deaths in Japan has decreased by 9% in the past 10 years. As of 2012, the death rate was 1.7 per 100,000 populations. Many studies have reported on the clinical factors associated with the number of TB deaths in Japan, and have identified aging to be a major cause of death among patients with TB. However, death among younger patients with TB is also a serious concern, and although several socio-economic factors have been suggested in the past, these studies have varied in methods and results. Therefore, we conducted a systematic review of previous studies that have focused on the association between TB death and socio-economic factors. RESULTS: Our results revealed unemployment, education, history of homelessness, substance and alcohol abuse, and nationality to be risk factors for TB death. CONCLUSION: Many of these factors are markers of poverty, and in Japan too, various markers of socio-economic vulnerability have been suggested to have an influence on TB death. These factors negatively affect patients' health-seeking behavior and thereby increase the risk of death. It is therefore necessary to encourage persons at risk of TB to seek early care by collaborating not only with public health and medical institutions, but also with welfare services, employment support services, and alcohol and drug support groups.

[On-the-street DOTS for a homeless tuberculosis patient--case report of a patient who had difficulties with TB treatment adherence].

PURPOSE: A homeless patient with tuberculosis (TB), who had often quit his TB treatment in mid-course and then gone homeless again, succeeded in completing his treatment for over 10 months through on-the-street DOTS ("Bluesky DOTS" is another expression). Based on the analysis of this case, we have discussed how to provide effective countermeasures to non-compliant TB patients. METHOD: An episode of a successful on-the-street DOTS for a 70-year-old homeless man with sputum smear positive pulmonary TB was qualitatively analyzed, with a view toward patient's empowerment. RESULT: The patient had had human-relations problems in his life, and trouble with medical and welfare service staff. During his hospital admissions, he repeatedly self-discharged or was forced to discharge due to violent behavior against staff. Public health nurses at Shinjuku public health center visited the patient frequently at the hospital, and tried to build a good relationship with the patient from the beginning of the treatment. Following a two and half month interruption of the TB treatment after he disappeared from the hospital, he was discovered staying outside at a canal side in the area, and on-the-street TB treatment was carried out, with good cooperation with the hospital and social welfare office. Directly observed TB medication was given to him by a public health nurse and another health center staff member for 293 days, at the park near his living place. The patient often rejected the medication, particularly when he was hungry, but offering lunch to him was a very effective incentive. Through comprehensive supports to the patient, he gradually changed his attitude, and on his own came to consider his health and his future. DISCUSSION: We have analyzed a successfully treated case of a homeless TB patient who had difficulties in maintaining a social life and had not been cooperative in complying with the medication. The level of independence improved during the course of on-the-street DOTS with incentive and other supports. He became receptive to TB treatment and became self-supportive during the course of DOTS, with food as an incentive. This indicates that on-the-street DOTS was successful not only for the treatment completion but also contributed to empowering the TB patient. This approach of adjusting the service to the patient's needs fostered a positive relationship with all stakeholders.

[Tuberculosis care and new horizon of Japanese society].

Current tuberculosis (TB) problems are reflections of Japanese society. Living or dying alone among the elderly, difficulty in finding jobs or withdrawal into themselves among the youths are features of modem society. The future needs for TB care were discussed on specific topics of TB among the elderly, foreigners and the homeless. Presenters showed the importance of the patient-centered care in collaboration with public health and welfare services. Both patients and staffs will see others shining, as they touch each other in the deep part of human existence. A diabetic ex-TB patient talked his experience in his treatment. His window of mind was gradually opened from inside with the continuous support in DOTS by the staff of the public health center. To accumulate these experiences of a heartwarming atmosphere will have the effective power on establishment of social supporting systems. This symposium can be a step towards humanized society or a new horizon of public health which can answer to another need of inner cry of a sick people particularly among the socially disadvantaged who are the victims of the weakness of society. 1. Current situation and issues of elderly tuberculosis patients: Eriko SHIGETO (NHO Higashihiroshima Medical Center). By the analysis of 102 tuberculosis patients of 70 years old and above who were registered at Hiroshima Prefectural Health Center in 2009, 41 patients had severe complications such as diabetes mellitus, renal insufficiency, malignancy or cerebrovascular disorder. Their prognosis was rather poor and the ADL tended to be worsened during hospitalization. Though 16 of the 34 deaths were caused with non-tuberculosis diseases, the ratio of the tuberculosis deaths was higher (4/17) among the patients living alone. Sufficient care of the elderly for early diagnosis, care system to treat various complications and patient support are required. 2. Provision of medical interpreters to help foreigners with tuberculosis in Tokyo: Takashi SAWADA (Services for Health in Asian & African Regions (SHARE)). In 2006, Tokyo Metropolitan Government started to dispatch interpreters for foreigners to strengthen DOTS program. Collaboration with NGOs made it possible to train 37 volunteer interpreters, and to provide services in 13 languages, as of 2010. In Japan, the treatment defaulter rate among non-Japanese tuberculosis patients had been remarkably high. But with having the assistance of interpreters, the treatment completion rate has become higher than 80%. It is recommended to expand a similar system to other part of Japan, as the proportion of foreigners among total tuberculosis cases keeps on increasing nationwide. 3. Tuberculosis problems in Japan from the view point of homelessness-through the activities of a NPO supporting the homeless in collaboration with a public health center: Sadako KANAZAWA (Volunteer, NPO Medical Care Team of Shinjuku Renraku-Kai). It has been 20 years since the issue of homelessness emerged in Japanese society. The people with a history of both tuberculosis and experience of homelessness tend to show a poor prognosis. Our team has played an active role, working with Shinjuku Public Health Center for conducting a screening for tuberculosis every year. It seems that the screening service itself does not make a fundamental solution for homeless people with tuberculosis. Developing a more basic system of 'from street to apartment' is more essential. We believe that understanding the importance of the system is most essential to the people who are involved in health and medical care. 4. What we have learned from DOTS--Toward care by cuddling the patient's mind: Kazuyo ARIMA (PHN, Osaka City Public Health Center). Osaka City has achieved the goals of DOTS set up by the City's TB Control Guidelines since 2001 such as 80% DOTS implementation rate, halving the defaulter rate and incidence rate. It was shown by analysis that the treatment success depends on 'patient's awareness of the disease', 'appropriate DOTS method for each patient', 'existence of side effects', or 'the relationship between treatment supporters'. Through working for the patients whose treatment management was difficult, we have learned that our attitude towards the patients is a most important first step to build a good relationship and mutual trust with the patients, and DOT is an important tool. For treatment supporters,'the patient-centered care', 'care by staying close to the patients' or 'cuddling the patient' s mind' is most necessary to lead the patients to cure. 5. Patient's view: Through DOTS, my life has been renewed: Kuniyoshi MAEDA (Himawari no kai; Ex-homeless TB patients self-help group). It is an unforgettable memory that I was hospitalized due to TB back in 2009. I was seriously ill with also diabetes mellitus. Because I had lost everything due to my friend's cheating, I could not trust anyone before the TB treatment. But I learned how to think of others through the daily communication with doctors, nurses, other staff at the hospital, and Public Health Center. They encouraged me every day and I came to desire to answer to their expectations. Public health nurses taught me that building the reliable relationship is so essential for humans, and I may not have realized this importance if I had not been treated for TB, or treated outside Shinjuku. I would rather say that I was lucky to have got TB, as I have become able to trust other people through DOTS TB care. DOTS is not only for medication, but also general health care and counseling. I hope that as many as poor people, especially homeless can have a similar experience by knowing more about TB and using a health service. I would like to cooperate with TB services if I can be useful. health: Toshio TAKATORIGE (Graduate School of Safety Science, Kansai University). Tuberculosis was ever the biggest health problem in Japan. Ministry of Health and Welfare and Public Health Centers were founded to push forward tuberculosis control. Local governments, companies and people had to follow the national tuberculosis control program uniformly without exception. Currently a new stream of tuberculosis control has been started by DOTS strategy. The aim of DOTS has made all patients take medicine regardless of their social conditions until cure. Every patient is snuggled up and supported whether he is homeless, criminal or a foreigner. The patients also participate in the program actively. The DOTS may be a new public health movement. The strong public health infrastructure is necessary to maintain tuberculosis control towards the low incidence situation. The role of the local government should be more important. This symposium has also shown that the tuberculosis services must be patients-centered and supported by the people, addressing a new horizon of public health in Japan through tuberculosis control.

[Medical service systems for tuberculosis in low-incidence countries].

OBJECTIVES: Currently, Japan has a near low incidence of tuberculosis (TB); the incidence is below 20/100,000. Considering this incidence, the medical service provision system needs to be restructured and related policies need to be revised. The Revised National Guidelines for TB Control, issued in May 2011 by the Ministry of Health, Labour, and Welfare, provided the policy towards achieving a low incidence of TB. This study aims to provide suggestions for restructuring the medical service system in Japan by analyzing the systems in selected countries with low incidence. METHOD: Between 2004 and 2010, we conducted tours to study TB control and medical services in the UK, the USA, Germany, The Netherlands, and Norway. In these tours, we visited the medical facilities, agencies implementing preventive activities, health departments of central and local governments, reference laboratories, technical agencies, non-governmental organizations, and other organizations involved in TB control in these countries. In addition, we collected information from published papers and related documents through the internet. This paper reports the policies and strategies adopted in these low-incidence countries, especially pertaining to medical service systems, directly observed treatment, short-course (DOTS) services, hospital beds and facilities, objectives and duration of hospitalization, and mechanisms for maintaining quality medical services. RESULTS: In all the visited countries, except Germany, TB patients were diagnosed and treated, as well as provided support such as DOTS, by a single organization or agency. In the US and Norway, DOTs was provided to all TB patients at chest centers and/or health centers. On the other hand, in the UK, guidelines from the National Institute for Health and Clinical Excellence (NICE) stated that DOT is not necessary for managing most active TB cases. In these countries there were 3 modes of treating infectious patients: home isolation, hospitalization for the first 2 weeks after initiating treatment, and hospitalization until smear examination results are negative. None of the countries had official standards for hospitalization. Measures to maintain service quality were integrating service providers, strengthening technical support, training and/or educating experts, and networking of personnel in charge. DISCUSSION: The study tours were conducted over 6 years, but no follow-up surveys were conducted. In each visit, we visited only a limited number of medical facilities, which may not be representative of that country. Obviously, this report does not aim to be a comparative study but to provide useful information for discussing the future direction of the medical service system in Japan. In Japan, TB is diagnosed and treated in hospitals and clinics, but contact surveys and other preventive activities are conducted in health centers. In this regard, Japan seems to be unique in that the ways to achieve collaboration among hospitals, health centers, and related organizations are emphasized in the revised National Guidelines for TB Control. Regardless of the DOT target group of a patient, healthcare providers in Japan are expected to ensure patient's adherence through patient-centered support in order to achieve successful treatment. In Japan, the central Government is expected to take responsibility to prevent infection. We suggest that the standards for lengths of hospital stay of TB patients should be revised such that the lengths are based on each patient's bacteriological condition and social setting. The revised National Guidelines for TB Control provide frameworks for ensuring the quality of medical services, but further discussions are warranted in order to plan and implement an effective strategy.

Computerized surveillance system of tuberculosis in Japan: its evolution, achievement and challenges.

The nationwide computerized tuberculosis (TB) surveillance system was revised in 2007. It was developed to be user-friendly and to allow the evaluation of current TB problems and control issues in Japan. All public health centers in Japan (518 as of April 2007) have system terminals connected to a central computer, and the data entered at these terminals are sent to the online central computer excluding personal identification data. All the figures and tables in this paper were created using the annual report database which are compiled from this system. The revision in 2007 added many new functions to the system, such as a function for automatically sending data upon transfer. The monitoring information for assisting case management of TB patients by the DOTS was also enhanced. The algorithm for classifying treatment outcomes automatically based on data entered regarding cancellations from registration, bacteriological results and drug usage each month was revised. The proportion of "Failed" and "Defaulted" combined was 4.6% among new sputum smear positive pulmonary TB patients newly registered in 2009, while "Died" accounted for as high as 19.3%, due largely to a high percentage of the elderly. A new system for contact examination management is provided as a subsystem. Feedback of data analyses has been strengthened by various methods. This TB surveillance system is indispensable for implementing the evidence-based TB control program in Japan. An important role of the Research Institute of Tuberculosis is to support the planning and execution of TB control with provision of useful epidemiological information from the system.

[The use of nationwide tuberculosis surveillance system data to determine geographical differences in drug resistance--consideration of the representativeness of the drug resistance rate in Japan].

Annual reports of tuberculosis (TB) statistics have been compiled using a database built through the nationwide computerized TB surveillance system in Japan. Using the annual report database for 2007-2009, this study compared the drug resistance rates among eight geographical districts. The proportion of bacteriological test results obtained at public health centers, which enter data into their computers that can then be accessed by the central computer, improved greatly from 2007 to 2009. The proportion of initial culture test results obtained among pulmonary TB increased from 63.8% to 74.8% and the proportion of drug susceptibility test results obtained among culture-positive pulmonary TB cases increased from 41.8% to 63.5%. As a result, susceptibility test results among 15,425 (26.5%) of 58,198 newly notified pulmonary TB cases during the three-year study period were obtained. The proportion of multi-drug resistant (MDR) TB among new treatment patients was 0.6% in the whole country. Although there were no particular districts having a significantly high rate of MDR-TB, the Kinki district showed the highest rate at 0.8%. In the case of retreatment patients, the MDR-TB rate was 5.1% in the whole country and there was no statistical difference among the eight districts. The proportion having resistance to any INH among new treatment patients was 4.5% in the whole country, with the Kinki and Kanto districts showing significantly high rates of 5.3% and 5.2%, respectively. In the case of retreatment patients, the proportion having resistance to any INH was 13.3% in the whole country, and there was no district where the proportion was significantly high. The proportion having resistance to one or more drugs among new treatment patients was 12.7% in the whole country, with the Kinki district showing a significantly higher rate of 15.4%. In the case of retreatment patients, the proportion having resistance to one or more drugs was 22.2% in the whole country, and there was no district where the proportion was significantly high. It is important to monitor drug susceptibility results for a comprehensive TB control program. The results of drug susceptibility tests through the nationwide TB surveillance system revealed a tendency toward higher drug resistance in districts that included large cities. Although many problems remain to be solved in order to optimize the use of results from the nationwide computerized TB surveillance system to represent the drug resistance rates in Japan, this practice is expected to yield great benefits.

Promoting health equity in cities through evidence-based action.

The impact of the urban setting on health and, in particular, health inequities has been widely documented. However, only a few countries have examined their inter- or intra-city health inequalities, and few do so regularly. Information that shows the gaps between cities or within the same city is a crucial requirement to trigger appropriate local actions to promote health equity. To generate relevant evidence and take appropriate actions to tackle health inequities, local authorities need a variety of tools. In order to facilitate a comprehensive understanding of health systems performance, these tools should: (1) adopt a multi-sectorial approach; (2) link evidence to actions; (3) be simple and user-friendly; and (4) be operationally feasible and sustainable. In this paper we have illustrated the use of one such tool, The World Health Organization's Urban HEART, which guides users through a process to identify health inequities, focusing on health determinants and then developing actions based on the evidence generated. In a time of increasing financial constraints, there is a pressing need to allocate scarce resources more efficiently. Tools are needed to guide policy makers in their planning process to identify best-practice interventions that promote health equity in their cities.

[Recent case-finding activities of school children in Japan].

PURPOSE: The procedure for TB mass-screening of elementary and junior-high school students was revised in 2003 in Japan. An interview sheet with questions about the past history of TB, episodes of contact with TB patient, TB symptoms, and BCG vaccination history has been administered to all students to determine high-risk groups for TB infection or TB disease despite previous mass-screening with PPD testing for those in first grade. Our purpose in the present study was to evaluate the effects of revised case-finding activity for these school students. METHOD: We analyzed the case-finding activities for school students from 2003-2008 based on data from the national TB surveillance system and related ad-hoc surveys. RESULT: The total number of notified TB cases among these students was 295 out of which 156 were detected by contact survey, 110 by consultation at medical facilities with symptoms, 19 by mass-screening at schools, and the remaining 10 by other means. Although the contact investigation detected more than half of all cases, there were some more cases with a known source of infection among those who were detected in other modes; 28 cases were identified by consultation at medical facilities and 10 by school mass-screening. Case-finding activities by consultation at medical facilities detected 43 bacteriologically positive cases. There were 97 cases without a known source of infection. Most of the cases detected by school mass-examination had risk factors such as TB history in the family and/or a history of staying in TB-prevalent countries. The TB incidence in urban areas is higher than that in other areas for junior-high school students with known or unknown sources of infection. DISCUSSION: The effectiveness of the contact investigation could be enhanced by improving its way of implementation. Delay of diagnosis for infectious cases should be minimized as much as possible to prevent TB outbreaks among students. For that purpose, parents, school teachers, and school nurses should be aware to prevent a delay in seeking care for the patient. Because the efficiency of the current school mass-screening is quite low, revision of this program is necessary, taking into consideration the reinforcement of other case-finding activities. The difference between urban and other areas might be due to a higher infection risk in junior-high school students in urban areas who have higher social activity and may be exposed to higher TB infection risk due to casual contact.

Transmission of specific genotype streptomycin resistant strains of Mycobacterium tuberculosis in the Tokyo Metropolitan Area in Japan.

BACKGROUND: From 2003 through to 2004, an outbreak of tuberculosis was identified at a university campus in Yokohama City, located in the southern part of the Tokyo Metropolitan Area (TMA). All Mycobacterium tuberculosis (M. tuberculosis) strains detected with regards to this outbreak turned out to be Streptomycin resistant with matched patterns of 14 IS6110 bands of Restriction Fragment Length Polymorphism (RFLP). The M. tuberculosis bacilli, which had the matched IS6110 band patterns with resistance to Streptomycin to those of bacilli isolated in the outbreak, were also concurrently detected through either the population-based or the hospital-based DNA fingerprinting surveillance of M. tuberculosis either in Shinjuku City or in Kawasaki City respectively. The aim of the present study is to describe the spread of the specific genotype strains of M. tuberculosis in the TMA as observed in the above incident, and to identify the possible transmission routes of the strains among people living in urban settings in Japan. METHODS: We applied Variable Numbers of Tandem Repeats (VNTR) analysis to all M. tuberculosis isolates which were resistant to Streptomycin with a matched IS6110-RFLP band pattern (M-strains). They were isolated either from cases related to the tuberculosis outbreak that happened at a university, or through DNA fingerprinting surveillance of M. tuberculosis both in Shinjuku City and in Kawasaki City. For VNTR analysis, 12MIRU loci, 4ETR loci, seven loci by Supply, four loci by Murase (QUB15, Mtub24, VNTR2372, VNTR3336) were selected. RESULTS: Out of a total of 664 isolates collected during the study period, 46 isolates (6.9%) were identified as M-strains. There was a tendency that there was a higher proportion of those patients whose isolates belonged to M4-substrains, with four copies of tandem repeat at the ETR-C locus, to have visited some of the internet-cafés in the TMA than those whose isolates belonged to M5-substrains, with five copies at the ETR-C locus, although statistically not significant (38.1% vs. 10.0%, Exact p = 0.150). CONCLUSION: Although firm conclusions could not be reached through the present study, it suggested that we have to take into consideration that tuberculosis can be transmitted in congregated facilities like internet cafés where tuberculosis high-risk people and general people share common spaces.

[Tuberculosis among the socially vulnerable populations; perspectives from human security concept].

Tuberculosis (TB) has been and will continue to be the disease of the poor and the socially vulnerable. Current TB epidemiology in Japan shows increasing proportion of TB among the economically and socially poor or vulnerable populations. Though there is no universally recognized set of the definitions, the economically poor who are covered under the social security services including the homeless, foreign migrants, or the aged over 80 years may be considered as consisting the "socially vulnerable population" for TB in Japan. TB among the socially vulnerable has several characteristics, for example, patients are often detected with severe conditions due to delayed diagnosis, and have high defaulter rate during treatment, which causes immature death, or drug-resistant disease. Stop TB Strategy by WHO, responding to the Millennium Development Goals, proposes a new approach which focuses on empowering the patients and the community. Observations from various studies show that DOTS contributes to empowering the patients and the communities. Further effort will be needed to reorient TB programs towards the perspective of patients' empowerment. Solely relying on static analyses of TB among the socially vulnerable has its limitations. Dynamic approach, which utilizes human security concepts such as empowerment and patients' perspective, will be required not only to control TB among the socially vulnerable population but also to holistically tackle the problem of TB for Japan.

[Problems in model-beds for tuberculosis patients].

PURPOSE: To investigate the possibility and obstacles to care tuberculosis patients in general hospitals. OBJECT & METHOD: Sending questionnaire to the general and psychiatric hospitals running the model-beds for tuberculosis patients care, which have been the project proposed by Ministry of Health, Labour and Welfare, and analyzing their answers. RESULT: Answer sheets were recovered from 43 of 75 (57%) hospitals which were the objects of this investigation. Situations of running the model-beds were highly diverse. 74% of the hospitals assumed that the general hospitals (if some conditions were satisfied) could care most of the tuberculosis patients. Problems in running the model-beds pointed by the hospitals were; HIC (hospital infection control) procedures pressing extra-workload (37%), low occupancy rate of the model-beds (30%), high cost of equipments for HIC (28%), high workload and high cost for tuberculosis patients care (21%), low fee for tuberculosis care (16%), difficulties of caring psychologically and/or physically unstable tuberculosis patients in rooms separate from the nurse station (16%), difficulties in long-term in-hospital care due to lack of sufficient amenities (14%), difficulties in accepting tuberculosis patients with short notice (12%), heavy burden for nurses who have to care for patients with associated conditions unfamiliar to them (12%), difficulties in maintaining quality of tuberculosis care (7%), risk of infection to the staffs and other patients (5%) and others miscellaneous problems (16%). CONCLUSION: Needs for tuberculosis patients' care in general hospitals are expected to further increase in the near future, but to cope with the above situation many problems are still to be solved. Hereafter we must expand the project of model-beds for tuberculosis care, and accumulate more experiences in tuberculosis patients' care in general hospitals.

Pharmacokinetics and 48-week efficacy of nevirapine: 400 mg versus 600 mg per day in HIV-tuberculosis coinfection receiving rifampicin.

BACKGROUND: We aim here to determine the appropriate dose of nevirapine (NVP) in Thai HIV-tuberculosis (TB)-coinfected patients receiving rifampicin. METHODS: Thirty-two HIV-infected adults with CD4+ T-cell counts <200 cells/mm3 and active TB, receiving rifampicin for 2-6 weeks were randomized to receive either NVP 400 mg (NVP400) or 600 mg (NVP600) per day plus two nucleoside reverse transcriptase inhibitors; a 2-week NVP lead-in was performed at 200 mg once daily (OD) and 200 mg twice daily, respectively. Plasma NVP levels were determined at weeks 2, 4 and 12. Twelve-hour pharmacokinetics (PK) were obtained (n=20) at week 4. RESULTS: Baseline body weight was comparable. There were more patients with NVP plasma concentration at 12 h (C12) <3.1 mg/l at week 2 in NVP400 than in NVP600 (79% versus 19%, respectively; P=0.002). However, the proportions were comparable at weeks 4 and 12. From week 4, 12 h PK studies showed that NVP400 had lower median NVP area under the plasma concentration-0-12 h (AUC0-12 h, maximum concentration in plasma (Cmax) and C12 than NVP600 (P<0.05). Four patients in NVP600 developed NVP hypersensitivity. At week 48, the median CD4+ T-cell count rise and proportion with viral load <50 copies/ml (intention-to-treat analysis 56% versus 50% and as-treated analysis 75% versus 89%) were comparable. CONCLUSIONS: In rifampicin-treated patients, 200 mg NVP OD lead-in led to a significant short-term suboptimal NVP C12 level, while NVP 400 mg lead-in then 600 mg/day was associated with a high rate of NVP hypersensitivity. Forty-eight week efficacy was comparable. Thus, NVP 600 mg/day in rifampicin-treated patients is not recommended.

[Estimation of the future epidemiological situation of tuberculosis in Japan].

OBJECTIVE: To estimate the future trends of all forms of tuberculosis (TB) and sputum smear positive pulmonary TB in order to consider the emerging issues of TB control and eliminating TB in Japan. MATERIALS AND METHODS] Annual reports of TB registrations were used for observing past trends of TB, and predictions were then made assuming that past trends would continue. At first, to obtain the number of TB patients by sex and age-group, sex-age-specific incidence rates were estimated for the years 2010, 2015, 2020, 2025 and 2030, and then applied to a sex-age-specific population which was projected by the National Institution of Population and Social Security Research. According to the different methods used to calculate the reduction rates of incidence, we adopted model A and model B. In model A, the reduction rate was calculated by using two groups of the same age group but different members by calendar year. In model B, the reduction rate was calculated by using the same birth cohort but different age by calendar year. We also adopted two sub-models by the observation period of past trends. The incidence rates for the period from 1987 to 2005 were used in model 1 and the incidence rates for the period from 1998 to 2005 were used in model 2. The incidence rate in 1999 was excluded from both model 1 and 2, because the TB incidence rate increased abnormally due to the declaration of a state of emergency concerning tuberculosis in 1999. The speed of decline among particular several sex-age-groups was weighted taking into account the influence of foreign, homeless and elderly cases. The future number of sex-age-specific sputum smear positive pulmonary patients was estimated by applying various parameters, i.e. pulmonary TB rate, sputum smear positive rate and its trend, to the estimated future number of TB incidence. RESULTS: The TB incidence rate, which was 22.2 per 100,000 population as of 2005, would reach 9.8 in model A-1, 5.4 in model A-2, 7.5 in model B-1 and 3.2 in model B-2 by 2030. On the other hand, the sputum smear positive pulmonary incidence rate, which was 8.9 per 100,000 population as of 2005, would decline to 5.5 in model A-1, 3.0 in model A-2, 4.2 in model B-1 and 1.7 in model B-2 by 2030. The future number of TB patients and incidence rates by sex and age were discussed based on a mixed model which used the middle series of estimates, and was obtained by combining model A-2 and model B-1. The number of TB patients by the mixed model will become about 12 thousand with 10.1 per 100,000 population in 2020, and about 7.4 thousand with 6.5 per 100,000 population in 2030. From 2005 to 2020, the age composition of TB patients will change from 0.4% to 0.2% at 0-14 years old, 4% to 4% at 15-24 years old, from 10% to 11% at 25-34 years old, 8% to 11% at 35-44 years old, from 9% to 12% at 45-54 years old, from 15% to 10% at 55-64 years old, 18% to 15% at 64-74 years old, from 24% to 17% at 75-84 years old, and from 11% to 20% at 85 years of age or older. Although the proportion of the elderly aged 65 years or higher will not be so different, the proportion of TB patients aged 85 years or older will almost double. CONCLUSION: The year when the TB incidence rate will reach the level of low-incidence countries, which is defined as a country with a TB incidence rate of less than 10 per 100,000 population, might be around 2020 in Japan. At that time, the age composition of TB patients will tend to be very old patients, and the young adult and middle-aged patients. Problems such as delay in diagnosis and difficulty of treatment are expected among very old patients.

[What is needed to prevent defaulting from tuberculosis treatment?].

PURPOSE: To investigate the factors relating to defaulting from tuberculosis treatment in Japan, and clarify what is needed to prevent defaulting. OBJECT: Tuberculosis patients who were registered at public health centers (PHCs), and interrupted treatment for more than 2 months without the doctors' direction at the end of December 2005. METHOD: Investigation by questionaire sent by post-mail to all public health centers (608 PHCs) in Japan. RESULT: The valid answers was obtained from 89.0% (541/ 608) of PHCs. Tuberculosis patients who had interrupted treatment, but could be contacted by PHCs' staff were 137, and for those patients the factors relating to defaulting from treatment were analyzed. The factors were classified into 7 categories (there may be more than one factors in one patients); factors related to disbelief and/or prejudice for diagnosis and/or treatment (except factors related to drug adverse effects) were observed in 51.8%, factors related to economical problem in 24.1%, factors related to job or studies in 23.4%, factors related to drug adverse effects in 22.6%, factors related to visiting out-patients departments in 6.6%, psychiatric disease and/or drug abuse in 4.4%, others in 9.5%. CONCLUSION: It is needed to prevent defaulting, first, to improve the quality of tuberculosis medical care and services including good and sufficient explanations on TB and how to cure it to patients, and proper managements for drug adverse effects, and then to expand public economical support for the costs of medicine and travel expenses to medical facilities and to make accessible time and place of the tuberculosis outpatient clinic more convenient and flexible for patients.

[Tuberculosis control in Shinjuku Ward, Tokyo--promoting the DOTS program and its outcome].

OBJECTIVES: The objectives were to report how to promote tuberculosis (TB) control including DOTS (Directly Observed Treatment, Short-course) programs, and to evaluate the results of TB control programs in Shinjuku Ward (Shinjuku-ku). SETTING AND CHARACTERISTICS: Inhabitants and TB patients in Shinjuku Ward. Shinjuku Ward is located in the center of metropolitan Tokyo and has typical urban TB problems, such as high incidence rate and TB among foreigners and the homeless. The TB incidence rates in Shinjuku Ward decreased from 83.9 per 100,000 population in 1999 to 42.5 per 100,000 population in 2006, however, the rates were still two times higher than the national average. Therefore, one of the important TB programs in Shinjuku has been to actively detect cases among high-risk groups such as foreigners and the homeless. METHODS: We observed the trend of case detection rates by health examination with chest X-ray among different high-risk groups, and compared the treatment outcomes before and after DOTS program execution. We also reviewed the changes of re-treatment rates and drug resistance rates. RESULTS: The case detection rates of TB by health examinations of foreign students at Japanese language schools decreased from 0.49% in 1996 to 0.13% in 2006 (p = 0.021). Although the case detection rates decreased, they were still about 26 times higher than those of Japanese students. While, the case detection rates among the homeless remained high with 4.7%, 3.3%, 4.5% and 3.6% in 1999-2002, respectively, since 2003, however, they had decreased and no TB cases were detected in 2005-2006. The DOTS program for homeless TB patients has been carried out since 2000 and that for the foreigners since 2003. The rates of defaulting during treatment before DOTS were very high among both homeless patients (21.4%) and foreigners (29.8%) in 1998-1999. However, after the introduction of DOTS program, those rates declined to 10.4% (p = 0.014) among the homeless and 7.8% (p = 0.002) among foreigners in 2002-2004. The proportion of newly notified patients with previous TB treatment and those with multi-drug resistant TB (MDR-TB) have also decreased after the introduction of DOTS programs. From 2000-2002 to 2003-2006, the re-treatment rates decreased from 19.4% to 10.0% (p < 0.001) and MDR-TB rates decreased from 1.6% to 0.2% (p = 0.042), respectively. DISCUSSION: The key points of TB control in Shinjuku Ward are to detect TB cases early especially among the high-risk groups, and to assist all TB patients to complete their treatment. In order to expand this strategy, besides promoting active case findings among high-risk groups, we have developed many types of DOTS programs, considering each patient's lifestyle and cooperating with school teachers at schools, pharmacists at pharmacies, home-care specialists at homes or facilities for the elderly, and so on. Among others, a major premise for the homeless and some other socially disadvantaged patients was to guarantee the provision of medicine and living by introducing social welfare services, before starting DOTS programs. This approach might have helped to reduce the defaulting rate, relapse rate and MDR-TB rate.

[Implementation and evaluation by a population-based RFLP analysis in an urban area, Shinjuku city, Tokyo--the possibility of application for contact investigations].

OBJECTIVES: The objectives were to examine Mycobacterium tuberculosis transmission patterns by RFLP analysis in Shinjuku city, and to elucidate more effective methods of contact investigations. METHODS: We applied RFLP analysis to 389 M. tuberculosis isolates from 402 TB patients registered in Shinjuku city from September 2002 though August 2006. RESULTS: Forty-six clusters consisting of 155 TB patients (average 3.4 people per cluster) were identified (proportion of clustering: 39.8%). The clustering rates were 34.5% among general patients, and 57.8% among homeless patients, and the latter was higher than that of non-homeless patients (odds ratio: 2.6, 95% CI; 1.6-4.1, p < 0.001). On the other hand, the clustering rates were only 19.4% among foreigners (odds ratio: 0.5, 95% CI; 0.2-1.2, p = 0.090). Twenty-eight of 46 clusters (60.9%) were consisted of mixture of general patients, homeless patients and foreigner patients. Thus, RFLP analysis can detect the transmission route which can not be identified by the routine contact examination, thus enabling contact investigations extended to the appropriate persons. DISCUSSION: The homeless clustering rate was significantly high. This suggests that the proportion of transmission among the homeless patients might be high. However, many clusters were composed of a mixture of homeless patients and non-homeless patients, so transmission patterns are not easy to identify. It is not always true that transmission of tuberculosis to non-homeless patients took place from homeless patients. Clustering rates among homeless patients are high, therefore taking countermeasures for the homeless patients is an effective way to prevent the spread of tuberculosis. Introduction of RFLP analysis is a practical epidemiological methodology to investigate the source of infection and transmission route of infection, and can be applied to contact investigations. If RFLP analysis can be applied in a larger area, yearly changes of notification rates and molecular epidemiological clustering rates will provide indices for preventive measures against tuberculosis.

The profile of prisoners with tuberculosis in Japan.

Purpose Although globally, prisoners are considered one of the vulnerable groups to tuberculosis (TB), little is known about the situation of TB in prison setting in Japan. The purpose of this paper is to examine the characteristics of TB among prisoners in Japan. Design/methodology/approach Records of TB patients from one medical prison were analyzed in terms of general demographic characteristics, clinical manifestations, risk factors and delay in diagnosis and in initiating treatment, and compared with data from the national TB surveillance and other published data on health of inmates, where appropriate. Continuous variables were compared using student independent samples t-test. Proportions were compared using χ2 or Fisher exact test as appropriate. Kaplan-Meier survival analysis was conducted to determine the time from entry to prison institution to diagnosis of TB. Findings A total of 49 patients were analyzed. The mean age was 49.5 (±14.3) and 69.4 percent were males. Being unemployed and homeless prior to incarceration, and several co-morbidities were potential risk factors for TB ( p<0.01). Analysis of diagnosis and treatment delay showed that 16.1 percent of smear positive patients took more than a week to be placed on treatment after being diagnosed of TB. Approximately 50 percent of the patients were diagnosed within four months of entering the prison institution. Practical implications Several potential risk factors identified suggest the need to strengthen screening for specific sub-groups within the prison population, such as those with poor socio-economic status and co-morbidities, as well as to consider the possible role of systematic screening for latent TB infection. Originality/value This study presents some important data to help understand the profile of TB patients in prisons in Japan, as well as showing that a detailed epidemiological analysis of existing records can provide useful insight.

[Frequency of MDR-TB/XDR-TB strains isolated from chronic pulmonary tuberculosis patients in Japan].

PURPOSE: To observe the frequency of MDR-TB/XDR-TB strains isolated from chronic pulmonary tuberculosis patients in Japan. OBJECT: Ad hoc National Tuberculosis Survey 2000 on frequency of MDR-TB and XDR-TB strains. MATERIALS AND METHOD: Four hundred and thirty four clinical isolates were collected by the Ad hoc National Tuberculosis Survey 2000, the drug susceptibility testings (proportion method, MGIT Middlebrook, and BrothMIC NTM) were conducted on these strains. These clinical isolates were obtained from patients registered at Health Centers in Japan by the end of 1999 who were culture-positive in 1999 and were registered before January 1st, 1998. The isolates used in this study were selected from patients who were culture-positive at shortest 2 years after the registration. RESULT: The clinical isolates resistant to both INH and RFP were 321 out of 434 (74.0%). The 180 MDR-resistant clinical isolates were also resistant to levofloxacin and amikacin and/or kanamycin. These phenotypes are XDR-TB. No previously registered cases were 165, and previously registered cases were 143 and unknown cases were 13 out of 321 MDR-TB. In 180 XDR-TB cases, no previously registered cases were 95, previously registered cases were 78 and unknown cases were 7. In no previously registered cases, more than 50% cases started treatment in 1990s. Approximately 50% of previously registered patients started treatment in 1960s and 1970s. CONCLUSION: We performed drug susceptibility testing for 434 clinical isolates which were culture-positive at shortest 2 years after registration. No. of MDR-TB patients was 321 and that of XDR-TB patients was 180. The treatment outcome of these patients have to be followed up carefully at Health Centers. The frequency of amikacin resistance was relatively high. This may be due to either common use of amikacin or cross-resistance against streptomycin and kanamycin.