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Objective: To determine the characteristics associated with mortality in patients with culture-positive pulmonary tuberculosis (PTB) in Airin, Osaka City, Japan. Methods: The characteristics of patients with culture-positive PTB registered between 2015 and 2018 in Airin, Osaka City, Japan, were compared between those who died of all causes before or during treatment and those who completed treatment. Results: Of the 241 culture-positive PTB patients eligible for this study, 170 completed treatment, with negative sputum culture tests, and 62 died. The all-cause case fatality rate was 26.7% (62/232). Multivariate analysis showed that mortality was associated with age >70 years, having a positive sputum smear, a body mass index of

Objective This study aimed to evaluate the treatment outcome of latent tuberculosis infection (LTBI) in persons with fibrotic pulmonary lesions, treated with isoniazid (INH) or rifampicin (RFP) in Nishinari Ward, Osaka City.Methods As part of a tuberculosis screening program by chest X-ray (CXR), we selected persons who met the following four criteria for initiation of LTBI treatment:①Anti-tuberculosis treatment has not been performed for more than one month in the past. ②CXR shows fibrotic pulmonary lesions.③Fibrotic pulmonary lesions with CXR have not changed for more than one year.④QuantiFERON TB Gold-in-tube (QFT) shows positive values (≥0.35 IU/mL). Before treatment, the blood samples were within the standard values for aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, and serum creatinine. Treatment with INH was stopped when AST or ALT levels were elevated to more than 150 IU/L, or symptoms of liver dysfunction appeared even when AST or ALT levels were less than 150 IU/L. After liver dysfunction improved, treatment with RFP was started. Treatment completion was defined as being dispensed with INH for ≥180 days or RFP for ≥120 days.Results The 27 participants were all male and their age was 68.4±6.6 years. Of the 27 participants, 14 (51.9%) completed treatment with INH. Of the remaining 13 persons, nine (69.2%) stopped treatment with INH because of liver dysfunction. Nine restarted RFP treatment and all participants completed the treatment without interruption by liver dysfunction. In total, 23 (85.2%) completed the treatment.Conclusion LTBI treatment with INH in persons with fibrotic pulmonary lesions in the area where people in financial need live was stopped because of liver dysfunction; however, changes from INH to RFP could improve treatment outcomes.

Objective: To identify individual characteristics related to the development of pulmonary tuberculosis (PTB) among residents in the Airin area (Airin), Osaka City, Japan. Methods: We conducted a retrospective case-control study of individual characteristics potentially related to the development of PTB by comparing PTB patients and residents without tuberculosis (TB) in Airin. The following binominal data of characteristics were compared: age (65); body mass index (BMI) (18.5);diabetes mellitus (diagnosed or not diagnosed); smoking (currently smoking any amount or not smoking); and alcohol use (currently drinking any amount or not drinking). Results: We compared the individual characteristics of 192 PTB patients notified from January 2015 to December 2018 and 190 residents of supportive houses who attended a health education programme from April 2016 to March 2018. Univariable analysis showed that the following characteristics were significantly related with PTB: BMI

[Objective] To contribute to countermeasures against pulmonary tuberculosis in patients with HIV infection through analyzing and evaluating its treatment outcomes and patient management. [Methods] The 'subjects were pulmonary tuberculosis patients newly registered between 2008 and 2014 in whom concomitant HIV infection was detected. For the control, sex- and generation-matched pulmonary tuberculosis patients newly registered in Osaka City -between 2012 and 2014 were adopted. On analysis, the X² test and Fisher's exact test were used, and a significance level below 5% was regarded as significant. [Results] 1) There were 25 pulmonary tuberculosis patients complicated by HIV. All were male -and the mean age was 43.2 years old. 2) The sputum smear positivity rate was 76.0% in the pulmonary tuberculosis patients complicated by HIV and 50.8 % in 250 control pulmonary tuberculosis patients, showing a significantly higher rate in the former. 3) Risk factors for the discontinuation of medication for tuberculosis: In the patients complicated by HIV, the follow- ing risks of the discontinuation of medication were noted in the order of a decreasing frequency: 'Lack of medication helpers' in 68.0%, 'Side effects' in 48.0%, 'Financial prob- lems' in 32.0%, and 'Liver damage' in 28.0%. Those in the control pulmonary tuberculosis patients were 33.2%, 22.8 %, 16.0%, and 11.6%, respectively, showing a significant difference in each factor. 4) The DOTS executing rates were 68.0% and 94.8% in the patients complicated by HIV and control patients, respectively, showing that it was significantly lower in the patients complicated by HIV. On comparison of the treatment outcomes excluding died, on treatment, transferred out, not evaluated, treatment succeeded in 72.7% in the patients complicated by HIV and 92.9% in the control patients, showing a significantly lower success rate in the patients complicated by HIV. The numbers of risk factors of discon- tinuation in. 16 and 6 patients complicated by HIV in whom treatment succeeded and treatment failed/defaulted were 3.8 and 2.8, respectively, showing that the number was higher in patients with successful treatment, and the DOTS execution rates were 75.0% and 33.3%, respectively, showing a higher rate in the successful treatment cases. [Conclusion] The treatment outcome was significantly poorer in pulmonary tuberculosis patients complicated by HIV than in the control pulmonary tuberculosis patients. More risk factors for the discontinuation of medication were observed and the DOTS execution rate was lower in the patients complicated by HIV, suggesting that risk assess- fient for the discontinuation of medication should be appro- priately performed, and support for medication should be strengthened.

Tuberculosis (TB) is a severe and wide-spread infectious disease worldwide. The modern Beijing subfamily, one lineage of M. tuberculosis, reportedly has high pathogenicity and transmissibility. This study used a molecular epidemiological approach to investigate the transmissibility of the modern Beijing subfamily in the Airin area of Osaka City, Japan. During 2006–2016, we collected 596 M. tuberculosis clinical isolates in the Airin area, Osaka city, Japan. We analyzed the 24-locus variable number of tandem repeats typing optimized for the Beijing family of isolates, M. tuberculosis lineage, and patient epidemiological data. The proportion of the modern Beijing subfamily was significantly higher not only than previously obtained data for the Airin area: it was also higher than the nationwide in Japan. The rate of recent clusters, defined as a variable number of tandem repeats profile identified within two years, of the modern Beijing subfamily was significantly higher than that the rate of recent clusters of the ancient Beijing subfamily. Results suggest that TB control measures formulated with attention to the modern Beijing subfamily might be an important benchmark to understanding recent TB transmission in the area.

QuantiFERON® TB-Gold In-Tube (3G) testing was performed on tuberculosis-positive index cases and their contacts. The purpose of this study was to evaluate the relationship between 3G test results and the subsequent development of tuberculosis, and to identify effective strategies to prevent the onset of tuberculosis.Index cases and their contacts were subjected to 3G testing in a contact investigation in Osaka City in 2011-2012. For index cases, sputum smears were tested, and the infecting organism was identified. For the contacts, the following information was collected: age, results of 3G testing, presence or absence of latent tuberculosis infection (LTBI) treatment, and onset of tuberculosis disease within 2 years of follow-up from the last contact with the index cases.(1) There were 830 index cases, including 774 subjects with pulmonary tuberculosis (93.3%) and 3 with laryngeal tuberculosis (0.4%). From sputum smear tests, 726 patients (87.5%) were determined to be 3G positive, and 83 (10.0%) were determined to be 3G negative. (2) In total, 2,644 contacts were subjected to 3G testing. Of these, 2,072 patients (78.4%) tested negative, 196 (7.4%) showed an equivocal result, and 375 (14.2%) tested positive. Their mean ages were 33.7, 38.0, and 38.8 years, respectively, showing significant differences in tuberculosis status according to age (P0.001). (3) Among the 2,072 3G-negative contacts, tuberculosis developed in 2 (0.1%) of 2063. None of these contacts was treated for LTBI. Among the 375 3G-positive contacts, tuberculosis developed in 36 (36.0%) of 100 subjects that were not LTBI treated, while tuberculosis developed in 3 (1.1 %) of 275 subjects that were LTBI treated. A significant difference in the incidence of tuberculosis between treated and untreated 3G-positive contacts was observed (P0.001).Tuberculosis developed in a high proportion of 3G-positive contacts that were not LTBI treated, suggesting the need for preventive management of 3G-positive contacts.

With a broader aim of controlling pulmonary tuberculosis (TB) among foreigners, here, we have reported the findings of chest radiography screening for TB among international students at Japanese language schools in Osaka city.Between April 2011 and December 2013, 4,529 international students from 19 Japanese language schools in Osaka city underwent chest radiography for TB screening. The chest radiographs were studied in reference to the student's sex, age, nationality, and date of entry to Japan as well as any health conditions present at the time of screening. We further analyzed the bacterial information and pulmonary TB classification based on chest radiography findings of students who were identified to be positive for TB. Information on the implementation of health education was also gathered.The results revealed that 52.5% of the students who underwent chest radiography came from China, 20.3 % from South Korea, and 16.3% from Vietnam. Of the students, 52.9% were male and 47.1% were female. The median age of students was 23 years (range: 14-70 years). The median number of days from the first date of entry to Japan up until the radiography screening was 63 days. Based on the chest radiography findings, 71 students (1.6%) were suspected to have TB; however, further detailed examination confirmed that 19 students (0.4%) had active TB. This percentage is significantly higher than the 0.1% TB identification rate among residents in Osaka city of the same time period (P0.001), which was also determined by chest radiography. The median age of the 19 TB positive patients was 23 years. Among them, 14 (73.7%) were male. The median time from the date of entry to Japan to the date of the chest radiography screening was 137 days. For 16 of those students, the entry to Japan was within 1 year of the radiography. Of the 19 TB positive patients, 16 (84.2%) did not have respiratory symptoms, 15 (79.0%) had sputum smear negative results, and 17 (89.5%) had no cavity. Health education was conducted in 11 schools (for a total of 12 times) in the 3-year period. A total of 257 language school staff and students attended the health education seminars.The identification rate of TB positive students in Japanese language schools was higher than that of the general residents in Osaka city. In addition, most of these students came to Japan within 1 year. It is also important to note that the majority of TB positive students had sputum smear negative results. This study proves that medical examination after entry to Japan would be useful for early detection of TB positive patients. Furthermore, it would be beneficial to conduct chest radiography screenings among students at language schools on a continuous basis. It is also necessary to provide health education to the staff and students in Japanese language schools. Effective methods of disseminating health education, especially on the topic of TB, should be considered.

小児結核患者数が減少しており, 小児結核対策は集団的・一律的対策よりも個別的・重点的対策に比重を移していくべきである。そこで, 大阪地区では「医療機関・保健所の合同症例検討会」を2003年度より連続4年間実施している。その年度に登録された小児結核患者症例を, 医療機関と保健所が一堂に会して検討することにより, その予防, 治療支援, 患者背景などに関して共通の理解を得, また共同していく基盤を確立し, 実際に小児結核患者の治療支援や発生予防に活かしてきた。4年間で参加者の人数は増加傾向にあり, 医師・保健師・看護師のみならず多職種の参加が見られてきた。全国的に見ると, 小児結核患者の発生は, 都市部に多く見られており, この検討会方式の対策は, 今後全国の都市部における結核対策への拡大が可能であり今後の行政施策に大きく貢献できる可能性がある。

To analyze tuberculosis outbreak index cases in order to improve preventative measures.Outbreaks reported in Osaka City between 2008 and 2014 were investigated. The index cases were examined according to category group, sex, age, chest radiograph findings, sputum smear examination, patient delay, doctor delay, total delay in case finding, and adherence to regular health examinations. As controls, 467 patients in Osaka City with newly registered sputum smear-positive pulmonary tuberculosis in 2011 were included.Thirteen outbreaks occurred. The group categories included enterprises (9 outbreaks), preparatory schools (2), a junior high school (1), and other (1). The group of index cases consisted of 12 men (92.3%) and one woman (7.7%), with a mean age of 39.1 years; 11 (84.6%) were 30 to 50 years of age. Their ages ranged from 15 to 54 years. Of the control group of patients with sputum smear-positive pulmonary tuberculosis, 69.2% were 60 years or older, with a mean age of 65.4 years. These results suggest that the index case group was significantly younger (p0.001). There were ten cases (76.9%) of patient delay (initial visit 2 months or more after onset), and 8 (61.5%) of total delay (diagnosed 3 months or more after onset). These rates were significantly higher than those in the control group (p0.001). There were regular health examinations in four cases; among those, one did not see a doctor and another did not receive further examination. Chest radiographs revealed cavities in 12 cases (92.3%). All sputum smears were positive, with grades of 1 + in one case (7.7%), 2 + in two cases (15.4%), and 3 + in 10 cases (76.9%). These cases had a significantly higher rate of smear positivity than those in the control group (p0.001).The index cases were predominantly male, in their prime, and had higher infectivity rates. These findings suggest the importance of preventing delays in case findings and receiving regular and adequate health examinations.

To investigate the relationship between completion rates for community directly observed treatment short-course (DOTS) and treatment outcomes, according to implementation tactics, to improve the treatment outcomes.We evaluated 529 newly registered patients with smear-positive pulmonary tuberculosis who underwent community DOTS (checking medication at least once per week) during 2010 and 2011 in Osaka City. DOTS completion was defined as checking medication 3 times or more per month, with checking medication missed less than 3 consecutive times. DOTS was implemented using the following 4 tactics: healthcare staff visited the patients' home or workplace (visiting type), the patients visited a health and welfare center (HWC type), the patients visited a pharmacy (P type), or the patients visited an outpatient department at a medical center (MC type). Regarding treatment outcomes, resolution of the tuberculosis or treatment completion was defined as "successful treatment", and treatment failure or default was defined as "unsuccessful treatment". We then analyzed the DOTS completion rate for each DOTS implementation tactic.DOTS was completed in 417 (78.8%) of the 529 patients. The completion rates were 79.7%, 75.4%, 75.9%, and 81.3% for patients who underwent visiting (n= 394), HWC (n = 61), P (n = 58), and MC (n = 16) DOTS, respectively; no significant difference was observed. The mean ages for each group were 62.8 years, 53.6 years, 45.0 years, and 56.6 years for patients who underwent visiting, HWC, P, and MC DOTS, respectively; patients who underwent P DOTS were significantly younger (P0.001). Among the 4 groups, the visiting DOTS group had the lowest percentage of full-time employees (16.2%) and the highest percentage of unemployed individuals (67.3%). In contrast, the percentage of full-time employees was 63.8% and 50.0% in the P and MC DOTS groups, respectively. The P DOTS group had the lowest unemployment percentage (19.0%) among the 4 groups. Thus, a significant correlation existed between the DOTS implementation tactics and the presence/ absence of the patients' occupations (P0.001). Among the 417 patients who completed DOTS, 99.8% achieved successful treatment. Among the 112 patients who did not complete DOTS, 89.3% achieved successful treatment, and this success rate was significantly lower than that for the group who completed DOTS (P0.00 1). Among the visiting, HWC, and P DOTS groups, the completion of DOTS resulted in a high treatment success rate.Patients who completed DOTS achieved better treatment outcomes; therefore, it is important to provide patients with medication support until their tuberculosis is resolved. The P DOTS group contained a higher percentage of full-time employees and had a significantly lower mean age; this was likely because pharmacies are accessible at night and during the weekend. There was no significant difference in the DOTS completion rates according to implementation tactic, which suggests that it is important to assist patients with their medication according to their needs.

In this study, we analyzed pulmonary tuberculosis treatment outcomes among foreign nationals of different backgrounds.The research was conducted between January 2006 and December 2011. One hundred fifty nine foreign nationals residing in Osaka city had pulmonary tuberculosis during this period. Patients were grouped according to treatment outcomes. We conducted three different types of comparisons. First, we compared backgrounds of patients with treatment success or default. Second, backgrounds of patients who continued treatment in Japan or who moved overseas (transfer out) were compared. Third, treatment outcomes of foreign nationals between 20 and 39 years of age were compared with those of age-matched Japanese patients registered between 2010 and 2011.(1) The treatment outcomes were as follows: cured, 53 cases (33.3%); treatment completed, 55 cases (34.6 %); treatment failure, 0 cases (0.0%); treatment default, 14 cases (8.8%); moved overseas, 17 cases (10.7%); moved to another location inside Japan, 13 cases (8.2%); died, 6 cases (3.8%); and under treatment, 1 case (0.6%). (2) Comparison of treatment success and default among foreign nationals with pulmonary tuberculosis revealed a default rate among smear-negative cases of 14.5%, significantly higher than in smear-positive cases (2.1%; P0.05). (3) We compared backgrounds between foreign nationals with pulmonary tuberculosis who continued taking treatment in Japan and those who moved abroad (transfer out). The rate of overseas transfer out (44.4%) was higher among patients not covered by health insurance. This was significantly higher than among patients covered by public insurance or assistance (9.0%; P0.01). (4) Comparison of foreign and Japanese nationals between 20 and 39 years of age revealed a default rate in foreign nationals with pulmonary tuberculosis of 13.6%. This was significantly higher than that of Japanese patients (4.0%; P0.01). The rate of transfer out among foreign nationals with pulmonary tuberculosis was 19.1%, also significantly higher than that of Japanese patients (5.3%; P0.001).The rates of treatment default and transfer out among patients between 20 to 39 years of age were significantly higher among foreign nationals than in Japanese patients. Lack of knowledge about treatment and language problems may contribute to this finding. This suggests that adequate support and definitive directly observed treatment short-course programs are needed for foreign nationals. Patients who moved abroad (overseas transfer out) may also be ultimately categorized as treatment default. However, it is difficult to determine final treatment outcomes of patients who moved abroad. Further measures are needed to ensure that foreign nationals continue to receive treatment when they transfer overseas.

The tuberculosis (TB) notification in Osaka City has been persistently high compared with other urban areas in Japan. Although the TB notification in Greater London has kept much lower level compared with that in Osaka City, it has been also persistently high compared with other urban areas in the UK. Nonetheless, the contexts of the two cities relating TB control programme as well as the epidemiological situation greatly vary; there must be some lessons to be learnt from each other to improve each TB control programme to tackle against TB more effectively. Comparing the epidemiological situation of TB in both cities, it is obvious that Osaka City suffers TB more than Greater London in terms of the TB notification rate. Concerning the context of the TB control programme, Osaka City has centralised approach with strong local government commitment; Greater London, on the other hand, has an approach that is greatly fragmented but coordinated through voluntary TB Networks. This paper aims to draw some constructive and practical lessons from Greater London TB control management for further improvement of Osaka City TB control management through literature review and interview to health professionals. TB epidemiology in Greater London shows distinct features in the extent of TB in new entrants and TB co-infected with HIV in comparison with those in Osaka City. TB epidemiology in Osaka City is to a great extent specifically related to homeless people whereas in Greater London, this relationship occurs to a lesser extent. Both areas have relatively high TB-notification rates compared with national figures, and they have "TB hot spots" where remarkably high TB-notification rates exist. TB control in Greater London is characterised with decentralised and devolved services to local government health authorities supplemented with co-ordinating bodies across sectors as well as across Greater London. Sector-wide TB Network as well as London TB Group (LTBG) and London TB Nurses Network are major key functioning bodies to involve relevant professionals as wide as possible. The specialist TB nurses play key roles for TB case management across Greater London, while in Osaka City, TB control is characterised with strong leadership and commitment of Osaka City Government for the TB control programme. The Osaka City Public Health Centre (PHC) takes initiatives to expand "Cohort Analysis and Case Management Conferences" at each of the 24 Ward Health and Welfare Centres as well as "DOTS Conferences" at hospitals for improvement of case management by physicians and nurses at hospitals as well as by the health centre staff. Public health nurses (PHNs) play very important roles for TB case management as frontline in Osaka City. Comparing the TB control in both cities, the following suggested recommendations are made to both cities for further improvement. Four suggested recommendations to Osaka City are: more resource re-allocation to community-based TB care than to hospital-based TB care should be done; Cohort Analysis and Case Management Conferences should be strengthened through involving more multi-disciplinary sectors; specialist TB PHN at each of the 24 Ward Health and Welfare Centres should be assigned in order to concentrate more on TB control activities; and accessibility to laboratory data such as drug susceptibility test for health centre staff should be improved. Two suggested recommendations to Greater London are: screening for TB high-risk group like homeless people should be strengthened, and regular sector-wide multi-disciplinary case conferences for proper case management should be strengthened.

In this study, we analyzed the relationship between the risk of discontinuing medication and patient outcomes.Newly registered patients with pulmonary tuberculosis from Osaka City who required outpatient treatment in 2011 were included in the study. We assessed the number of patient cures and the number of patients who completed medication as outcomes for successful treatment and the number of failed treatments and the number of treatments that were discontinued by patients as outcomes for failed and discontinued treatments. As related factors, we examined the risk of discontinuing medication, implementation of directly observed treatments, short course (DOTS), and planned duration of treatment. To assess the risk of discontinuing medication, we examined the following medical risk factors: (1) drug resistance to isoniazid or rifampicin, (2) diabetes, (3) use of immunosuppressive/anticancer drugs, (4) use of adrenal corticosteroid, (5) artificial dialysis, (6) human immunodeficiency virus infection/acquired immunodeficiency syndrome, (7) liver damage, and (8) side effects. The social risk factors were (1) being without a fixed address at the time of registration, (2) a history of discontinuing treatment, (3) lack of assistance with medication, (4) being elderly and requiring nursing care, (5) alcohol/drug dependence, (6) serious mental disease, (7) financial problems, (8) lack of the awareness of being ill, (9) keeping irregular hours, and (10) others.We identified 568 cases of successful treatment and 41 cases of failed and discontinued treatment. Multiple logistic regression analysis was performed, with successful treatment considered as the dependent variable 0 and failed and discontinued treatment considered as the dependent variable 1. The medical/social risk factors, positive/negative sputum smear test results, the planned duration of treatment (6 months/9 months or more), and the implementation of B type or higher DOTS were included as independent variables. The significant medical risk factors were drug resistance to isoniazid or rifampicin, the use of immunosuppressive/anticancer drugs, and side effects, with odds ratios of 4.55, 4.68, and 2.68, respectively. Further, a planned duration of treatment of 9 months or more and the implementation of B type or higher DOTS were associated with odd ratios of 4.51 and 0.35, respectively.These results highlight the need to assess risk factors for discontinuing treatment and to adopt measures to overcome these factors, such as the type of DOTS being implemented, in each case.

To contribute to measures against hospital-acquired infections by analyzing and evaluating tuberculosis contact investigations in hospitals.This study included 202 tuberculosis cases between January 2010 and September 2011 in which contact investigations were requested from the Public Health Office in Osaka City.1) To assess the necessity for contact investigation and the demographics of index cases, contact investigations were conducted for 66 of the 202 cases. Index cases with higher rates of contact investigation included those with "higher degree of sputum smear positivity," "respiratory symptoms," "period from hospitalization to tuberculosis diagnosis of 8 days or longer," and "high-risk procedures (including endotracheal intubation, endotracheal aspiration, and bronchofiberscopy)." 2) A total of 632 contact persons from the following professions underwent QuantiFERON-TB (QFT) testing: 59 doctors, 492 nurses, 60 other hospital staff members, and 21 patients, and the positive QFT rates were 18.6, 10.8, 13.3, and 14.3%, respectively. 3) Among the 66 index cases for which contact investigations were conducted, there were 0 QFT-positive contact persons in 37 cases (56.1%), 1 or more in 29 (43.9%), and 2 or more in 18 cases (27.3%). Assuming the dependent variable to be 0 and 1, respectively, for index cases with 0 and 2 or more QFT-positive contact persons, we performed a multiple logistic regression analysis with independent variables that included the presence or absence of high-risk procedures, period from hospitalization to diagnosis either within 7 days or 8 or more days, presence or absence of cough and cavity, and the degree of sputum smear positivity (1+/2+/3+). Among these variables, those significantly associated with cases with 1 and 2 or more QFT-positive persons included the "presence of high-risk procedures" and "period from hospitalization to diagnosis of 8 days or longer" (P0.05).Our results suggest that early diagnosis and appropriate responses during high-risk procedures may be necessary measures to prevent hospital-acquired infections.

Tuberculosis (TB) is the top killer of the productive age group in developing countries. More than half of cases in the world occur in Asia-Pacific region. The number of cases will increase in the next decades due to increase in urban poor population and HIV incidence, and poor access to health services and poor TB programme. The mainstay of effective strategy is to promote DOTS. DOTS population coverage is high, 58% in the Western Pacific Region but low; 29% in the southeast Asia region. Even among intermediate TB-burden countries in Asia, reduction of incidence has stagnated in recent years because of aging population, health problems in the urban poor population and influx of populations from high endemic areas. Indicators of successful TB programmes are high cure rate and low drug resistance rate. There is a strong correlation between the overall quality of TB control in the past and the current primary drug-resistant rate. To solve these problems, priority should be given to nationwide implementation of DOTS in high TB-burden countries with emphasis on ensuring availability of free anti-TB drugs and strengthening primary health care. General hospitals and private sector should be involved in control programmes to prevent drug resistant cases.

We conducted a study on factors related to treatment outcome and medication support in homeless patients with tuberculosis.Participants were 433 homeless patients with tuberculosis newly registered in Osaka City between 2007 and 2009. We investigated factors related to treatment outcome (e.g., length of hospital stay, scheduled duration of outpatient treatment, and type of DOTS). Controls were 3,047 non-homeless patients with pulmonary tuberculosis newly registered in Osaka City during the same period.Regarding medication support, 219 (70.4%) of the 311 patients with successful treatment received DOTS and completed the treatment during their hospital stay. Thirty-five (72.9%) of the forty-eight patients who did not complete treatment left the hospital at their own discretion, resulting in treatment failure/default. The rate of treatment failure/default in the homeless patients with pulmonary tuberculosis was 11.0%, significantly higher than that of non-homeless patients with pulmonary tuberculosis (6.5%; P0.001). Among the 102 patients receiving community DOTS, medication compliance occurred at least 5 days a week in 66 patients (64.7%) and treatments failed or were interrupted in 10 patients (9.8%). The mean hospital stay was 2.0 +/- 1.6 months in patients with failed/defaulted treatment and 4.4 +/- 2.5 months in those with successful treatment. The scheduled duration of outpatient treatment was 7.9 +/- 2.7 months in patients with failed/defaulted treatment and 3.6 +/- 2.1 months in those with successful treatment. Shorter length of hospital stay and longer scheduled duration of outpatient treatment were associated with a higher rate of treatment failure/default (P0.01).Homeless patients with tuberculosis had a higher rate of treatment failure/default, most likely due to leaving the hospital at their own discretion. Patients with successful treatment generally completed treatment during their hospital stay. In contrast, patients who received community DOTS after discharge from the hospital had a higher rate of treatment failure/default, despite receiving medication at least 5 days a week. This suggests the need for adequate support, particularly in patients with a shorter hospital stay and those with a longer scheduled duration of outpatient treatment.

Osaka City has the highest tuberculosis (TB) notification rates in Japan. In the period 1999–2003, the TB control programme was strengthened, and the Stop TB Strategy was implemented to reduce the number of notified cases. The objective of this study was to assess the effect of these control activities in Osaka City, including the implementation of directly observed treatment (DOT), by analysing TB surveillance and routinely collected data. We reviewed the surveillance data of all sputum smear-positive pulmonary tuberculosis (PTB) cases registered in the Osaka City Public Health Office from 2001 to 2008 and data collected from the routine TB programme. The DOT implementation rate increased from 0% in 2001 to 68% in 2008 for smear-positive PTB cases of the general public and to 61% for all PTB cases of the homeless. The proportion of smear-positive PTB cases that had treatment failure and default combined, declined from 8.0% (52 of 650) in 2001 to 3.6% (20 of 548) in 2006. The proportion of cases among the homeless with previous treatment declined from 28% in 2001 to 15% in 2008. The proportion of cases with multidrug resistant-TB (MDR-TB) among those without previous treatment declined from 1.7% in 2001 to 0.9% in 2008. It is logical that reduction in the failure and default rate would lead to the reduction of cases with previous treatment and TB transmission, including resistant TB, therefore to the reduction of MDR-TB rates.

In this study, we demonstrate the interpretation of "equivocal" results by the QuantiFERON"-TB Gold In-Tube (QFT-GIT) test in contact investigations.The participants of the contact examinations were assessed by the QFT-GIT test after 2 to 4 months from the last contact with smear-positive tuberculosis patients. The study was conducted between April 2011 and March 2012. We enrolled 79 contact participants whose QFT-GIT tests produced equivocal results.The average age of the enrolled contacts was 35.9 years and the average interval from the last contact to the first QFT-GIT test was 85.4 days (range 62-118 days). The second QFT-GIT test produced negative results in 42 (53%) participants, equivocal results in 28 (35%), and positive results in 9 (11%). These 9 positive contacts belonged to the group of contacts with an index case whose QFT-GIT positive rate was more than 15%. The contacts belonging to groups with a QFT positive rate higher than 15% in the initial test had significantly higher QFT positive rates in the follow-up test than those belonging to groups with lower initial QFT positive rates (p=0.011).After retesting contacts with initially equivocal QFT results, 65% demonstrated either negative or positive results. If a contact's second QFT-GIT test is positive, it is highly probable that he/she is infected with tuberculosis and adequate treatment for latent TB infection is indicated. Thus far, no guidelines have been established for the management of contacts with equivocal results by the QFT-GIT test; therefore, further investigations and discussions are mandatory.

To investigate the possibility of improving the results of therapy, we analyzed the association between the performance of directly observed treatment short course (DOTS) and treatment outcomes in patients with tuberculosis.Patients with sputum smear-positive pulmonary tuberculosis who were newly registered in Osaka City between 2007 and 2010 were included in the study. The patients' drug-taking was confirmed at least once a week during DOTS.(1) In total, 2,423 patients were enrolled in the study (676, 563, 631, and 553 in 2007, 2008, 2009, and 2010, respectively). Of these, patients who died, those who were transferred during treatment, and those who remained under treatment at the time of analysis, were excluded. In 2007, 2008, 2009, and 2010, 84.1%, 82.3%, 86.2%, and 92.0% of patients, respectively, underwent DOTS and 91.6%, 91.7%, 92.6%, and 95.1%, respectively, were considered to be cured or to have completed treatment, demonstrating increases in both the parameters. On the other hand, 8.4%, 8.3%, 7.4%, and 4.9% of patients, respectively, were considered to have failed to respond to treatment or defaulted, showing a decreasing trend. (2) We examined the results of treatment of the 2010 cohort of patients with respect to whether a patient was supported by the DOTS service. Four percent of the 377 patients who underwent DOTS failed or defaulted compared with 15.2% of the 33 patients who did not undergo DOTS, which was a significant difference (P0.01). (3) In total, 131 patients failed to respond to treatment or defaulted between 2007 and 2010, with reasons for such including abandonment of treatment, departure from the hospital, or refusal of treatment in 61 patients (46.6%); premature discontinuation of treatment due to physicians instructions in 33 (25.2%); and side effects in 22 (16.8%). The absence of a DOTS partner was considered a risk factor for discontinuation of treatment in 31 (56.4%) of the 55 patients who failed to respond to treatment or defaulted in 2009 and 2010.An increase in the coverage of DOTS may be important for improving treatment outcomes. The most common reasons for patients failing to respond to treatment or defaulting were abandonment of treatment, earlier departure from hospital, or refusal of treatment. The absence of a DOTS partner accounted for more than 50% of cases of premature discontinuation of treatment. Thus, it may be mandatory to adequately evaluate the risk of treatment discontinuation in individual patients and to take appropriate action against it.

The demographic transition theory that mortality reduction is followed by fertility reduction is challenged by reports that many developing countries are trapped in the stage of high fertility and lower mortality. We examined the extent to which reduced infant mortality lowers fertility both directly and indirectly relative to other determinants of fertility in developing countries. According to the available information, determinants of fertility were selected. Data from the United Nations on fertility and its determinants in 117 developing countries were analyzed. Remarkable fertility reduction started only when the infant mortality rate was reduced to a certain "threshold" level around 50-125 per 1000 live births. Fertility reduction is related to the level of infant mortality and other socioeconomic variables mainly indirectly through the increase in contraceptive prevalence. Thus, the demographic transition theory is still maintained. Even in the country group which was "trapped" in the stage of "low" mortality of around 125 and high fertility, fertility reduction seems to be possible by further reducing the infant mortality rate, e.g. to lower than 100, which helps increase family planning practices.

This study aimed to analyze and evaluate the association between tuberculosis (TB) and smoking in order to obtain basic information for the control of smoking.Of the 637 patients with sputum smear-positive pulmonary tuberculosis who were newly registered in Osaka City in 2009, 581 patients whose smoking status was identified were selected as study subjects. Data on the following were collected: patient characteristics, presence or absence of underlying conditions, patient's delay and doctor's delay in the diagnosis of TB, presence or absence of cavities, and degree of smear positivity. The patients were divided into the following three groups according to their smoking status: (1) never smokers (those who have never smoked), (2) former smokers (those who had smoked, but quitted), and (3) current smokers (those who smoke currently).(1) PATIENT CHARACTERISTICS: The subjects consisted of 413 males and 168 females, with mean ages of 65.7, 55.4, and 70.2 years for never smokers, current smokers, and former smokers, respectively. (2) Comparison with the national adult smoking rate (National health and nutrition survey 2009, Ministry of Health, Labour and Welfare): The prevalence of current smoking among male patients with sputum smear-positive pulmonary TB in Osaka was 62.4-82.4% among men in their 20s to 60s, and 27.5% among men in their 70s, which is higher than the national average. For female patients, the prevalence of current smoking was 46.2% among women in their 20s and 45.5% among women in their 30s, which is clearly higher than the national average. This was also true for those aged 40 years or older. (3) Severity of TB disease and smoking status: The presence of a cavity was significantly associated with being a male patient, being a current smoker, and longer patient's delay. Sputum smear grades (2+) and (3 +) were significantly correlated with being under 59 years old, being a current smoker, and longer patient's delay.The prevalence of current smokers was significantly higher among sputum smear-positive pulmonary TB patients in Osaka than the national average. More smokers had cavitary lesions and a high degree of smear positivity, which may lead to poorer treatment outcomes, and may also expose more surrounding people to infection.

In this study, the background of drug-resistant tuberculosis (TB) patients in Japan was analyzed using the annual report database for 2007-2009. The results of the drug susceptibility test of 15,425 patients who were diagnosed with pulmonary TB between 2007 and 2009 were obtained and analyzed. The chi-square test for independence between susceptibility test results and parameters (i.e., sex, age, nationality, etc.) was conducted. Logistic regression analysis was performed using the variables (20s, 30s, 40s ..., new treatment, retreatment, etc.) of parameters that were statistically significant by chi-square test. The risk of multi-drug resistance (MDR) among TB patients who underwent retreatment was significantly high (odds ratio = 11.3, 95% CI: 7.7-16.6, p0.001, reference = new treatment), and the risk of MDR among foreigners who had entered Japan within the last 5 years was also high (odds ratio = 9.5, 95% CI: 4.6-19.4, p0.001, reference = Japanese). Moreover, logistic regression analysis was performed for TB patients who had previously undergone treatment. The risk of MDR was higher among the patients treated after 1970 than those treated before 1970. Especially, the risk of MDR among the patients previously treated in 1990-1999 was extremely high (odds ratio = 20.8, 95% CI: 5.7-75.0, p0.001, reference = before 1970). The risk of MDR among previously treated foreigners who had entered Japan within the last 5 years was also high (odds ratio = 3.8, 95% CI: 1.1-13.2, p = 0.036). Similar to the results for MDR, the risk of resistance to one or more drugs was significantly high among TB patients who underwent retreatment for TB (odds ratio = 2.2, 95% CI: 1.9-2.6, p0.001) and foreigners who had entered Japan within the last 5 years (odds ratio = 1.8, 95% CI: 1.3-2.5, p0.001); however, their risk of resistance to one or more drugs was lower than that for MDR. In addition, the odds ratios of age groups younger than 80 years to those over 80 years were obtained. They were 2.1 (95% CI: 1.5-2.9) in 0-29 years, 2.2 (95% CI: 1.6-3.0) in 30-39 years, 2.2 (95% CI: 1.7-3.0) in 40-49 years, 2.1 (95% CI: 1.6-2.8) in 50-59 years, 1.9 (95% CI: 1.4-2.5) in 60-69 years, and 1.5 (95% CI: 1.2-1.8) in 70-79 years. With respect to the background of high MDR among TB patients who underwent retreatment and foreigners who have recently entered Japan, the usage of RFP and poor adherence to drugs and entry from high-prevalence countries with high MDR risk were suspected. Regarding the background of generational differences in resistance to one or more drugs, it was suspected that most people over 80 years of age had been infected with TB bacilli in the distant past, before anti-TB drugs were available, when drug-resistant bacilli had not yet emerged. However, the younger generations have become more susceptible to drug-resistant TB bacilli because anti-TB drugs were being widely used when they were born, and drug-resistant bacilli were prevalent in the world.

To analyze and evaluate onset cases of tuberculosis detected in contact investigations and to apply the results to future countermeasures.Index and secondary cases in contact investigations in which the secondary cases occurred in Osaka City between 2005 and 2008 were enrolled. The tuberculin skin test or QFT (QuantiFERON-TB Gold) was conducted to diagnose whether the contacts were infected with tuberculosis. X-ray examination of the chest was conducted to determine whether tuberculosis had developed, immediately or 6 months, 1 year or 2 years after the contact investigation.(1) Index cases: Index cases followed by secondary cases numbered 131 patients. Regarding the chest X-ray findings, a cavity was observed in 67.7% of the index cases, and a sputum smear of 3 + was observed in 51.5% of the index cases. A 3-month or longer delay in index case-finding was noted in 50.4% of the index cases. (2) Secondary cases: Secondary cases numbered 177 patients, consisting of 107 patients who showed an onset of less than 6 months after their last contact with index cases. Of 70 secondary cases in whom tuberculosis was detected in the investigation conducted 6 months to 2 years after the contact investigation, 50% of them were not tested for infection due to their older age, consisting of 11 patients in their 40's, 8 in their 50's, and 16 in their 60's or over, and 17.1% of them refused or discontinued the treatment for latent tuberculosis infection, leading to onset.Many secondary cases were detected immediately after the contact investigation, suggesting the importance of reducing the delay in index case-finding. Regarding the onset of secondary cases who showed an onset 6 months after the last contact with index cases, many cases showed an onset without being tested for infection due to their older age. More attention should be paid to the cases who refused or discontinued the treatment for latent tuberculosis infection, leading to onset.

We examined whether immunization coverage (IMC) is one of the predictors of infant mortality rate (IMR), as a single indicator representing the availability of primary health care (PHC) services in developing countries. Multiple regression analysis showed that partial correlation coefficients for IMR with immunization coverage (-0.224), logarithm of per capita GNP (-0.294), total fertility rate (0.269), and adult literacy rate (-0.325) were all statistically significant (p0.001) in 97 developing countries which make up more than 97% of the population in all the developing countries of the world. Multiple correlation coefficients of IMR with these four variables in 97 countries was 0.921. Thus, more than 80% of variation of IMR in developing countries were explained by the variation of the four variables. The study also showed that IMC was well correlated (simple correlation) with the four indicators of the availability of primary health care services; access to local care (0.730), care of pregnant women (0.603), delivery care (0.666), and infant care (0.553), all of which were statistically significant (p0.001) in the 48 developing countries which make up 42% of the population of all developing countries. Multiple correlation coefficients of these four variables was 0.787. About 60% of the variation of IMC will be explained by the variation of the four variables. Thus we conclude that immunization coverage is one of the main predictors of the infant mortality rate. It represents one of the health intervention components which can be used as a proxy indicator of the availability of PHC service in developing countries.Multivariate logistic regression analysis of data from 97 developing countries identified immunization coverage as a key predictor of the infant mortality rate and a reliable proxy indicator of the availability of primary health care services. The mean infant mortality rate in 1986-87 in the 97 developing countries was 78.6 (standard deviation, 42.8), while mean immunization coverage for diphtheria, tetanus, and pertussis and poliomyelitis was 52.9 (standard deviation, 23.9). Partial correlation coefficients for the infant mortality rate were -0.224 for immunization coverage, -0.325 for adult literacy rate, -0.294 for log per capita gross national product, and 0.269 for total fertility rate. All these values were statistically significant (p 0.001). Multiple correlation coefficients of infant mortality rate with these four variables was 0.921, indicating that they explained over 80% of the variance. In the 42 countries for which data were available, the simple correlation coefficients for immunization coverage were 0.730 for access to local health care, 0.603 for care for pregnant women, 0.666 for delivery care, and 0.553 for infant care. Again, all these values were significant (p 0.001). Multiple correlation coefficients of immunization coverage with these four indicators of primary health care services was 0.787, indicating that they explained about 60% of the variance in immunization coverage.

Reproducibility of results from a self-administered questionnaire on dietary habits (the frequency of taking various foods and eating habits), smoking and drinking was examined to study the reliability of the questionnaire, stability of lifestyle, and the validity of the questionnaire in assessing lifestyle as a risk factor in chronic diseases. The study sample included 120 males and 173 females in a rural town in Kyoto Prefecture, who participated in a series of three health examinations in 1988, 1989, and 1992. A survey using the same questionnaire was performed before each health examination. Reproducibility was assessed by correlation (Spearman's rank correlation coefficient or kappa coefficient), exact agreement of category answered, and comparison of mean frequency. An attempt was made to separate reliability and stability from reproducibility using the data from the questionnaire obtained in the three years. Good reproducibility for one-year and four-year intervals was found for foods taken habitually or often (boiled rice, cooked rice gruel with tea, milk, coffee, fruits and bread), and habits (eating breakfast, some eating habits, smoking and drinking). The same was also found for cigarette or alcohol consumption among current consumers except that cigarette consumption over a four-year interval was more likely to change. The reliability of the questionnaire and stability of these items were considered satisfactory, suggesting that the questionnaire was a valid method of assessing long-term lifestyle. Poor reproducibility of results regarding consumption of green-yellow and other vegetables indicated both poor reliability and a change in consumption over four years, and suggested poor validity. However, disagreement in more than one category of vegetables was not large and misclassification in assessing them as risk factors and changes in frequency of consumption may not be large either. Although correlation coefficients for the items of dairy food and eating snacks were fair, disagreement in more than one category was relatively large which may have caused misclassification. The mean frequency of consumption of pickles and fishpaste, ham or sausage significantly decreased over the four year interval. This may reflect the influence of health education on reducing salt intake.

Factors responsible for the premature self-discharge of homeless tuberculosis (TB) patients from the hospital and the association between the self-discharge and treatment interruption were assessed.A total of 205 homeless patients with TBs who were newly registered between January, 2007 and June, 2008 were evaluated. The subjects were divided into two groups (those who were discharged themselves from the hospital prematurely ["case" group] and those who were not [control group]), and the difference between the groups regarding the factors possibly responsible for the self-discharge was evaluated.i) Patient's characteristics: The subjects were all men; there were 45 in the "case" group and 160 in the control group. The proportion of subjects aged under 60 years was significantly higher in the "case" group (84.4%) than in the control group (52.5%). The proportion of subjects who consumed 360 mL or more of sake a day was significantly higher in the "case" group (64.4%) than in the control group (38.8%). ii) Questionnaire survey on admission: All of the patients were hospitalized for treatment of TB. In the interview on admission, more "case" group patients reported "I do not know much about TB" or "I am dissatisfied with my hospitalization", as shown by multiple logistic regression analysis. A review of troubles with inmates or healthcare workers over alcohol drinking or smoking showed that the proportion of subjects who had such troubles was significantly higher in the "case" group (55.6%) than in the control group (5.0%). iii) The association between the treatment outcomes and the self-discharge: The proportion of subjects with treatment outcomes of "cured" or "treatment completed" was significantly lower in the "case" group (46.7%) than in the control group (78.8%). The proportion of subjects with a treatment outcome of "defaulted" was significantly higher in the "case" group (42.2%) than in the control group (3.8%).The patients who were aged under 60 years or who consumed 360 mL or more of sake a day were shown to be significantly more likely to discharge themselves prematurely, which warrants a more careful handling of such problems. The poor understanding of disease necessitates more adequate explanation of TB, or education, considering each patient's level of understanding. In addition, the patients' dissatisfaction with their hospital stay, as seen in the case group, should be more carefully addressed in order to avoid the higher rate of trouble.

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.

We encountered a contact group investigation in which differences in environmental factors, including the ventilation frequency and the airflow, led to differences in the infection risk.The index case was diagnosed with tuberculosis after cough and sputum persisted for 9 months. The patient was an instructor working at vocational schools A and B. Sixty-six instructors/staff and 446 students had contact with this patient at the schools. The patient taught 24 regular courses and 21 short-term courses at the 2 schools after symptom onset through to the final day of work.In a contact investigation of instructors/staff, one person with latent tuberculosis infection (LTBI) was identified. Subsequently, 30 and 240 students with the closest contacts and those with 8-hour or longer contact with the index case, respectively, were examined. In School A, of the 162 students examined, one student developed tuberculosis, 7 were QFT-positive, one was QFT-doubtful, 147 were QFT-negative or judged as not infected (either QFT-negative, or a tuberculin skin test of erythema less than 20 mm, including past history of LTBI treatment or TB treatment), and 6 were not examined. In School B, of the 108 students examined, no one developed tuberculosis nor was QFT-positive, 4 were QFT-doubtful, 98 were either QFT-negative or judged as not infected, one was QFT-indeterminate, and 5 were not examined. Since the onset of tuberculosis and QFT-positivity occurred in only School A, the difference in the incidence of infection between the 2 schools, despite the levels of contact being similar, was assumed to be due to environmental factors. Thus, the ventilation frequency, which had been not reported initially, was reinvestigated. The frequency of air change was as low as 0.45-1/hour in School A, whereas it was better (3.57-7/hour) in School B. Moreover, the air flew from the instructor side toward students in School A, while it was reversed in School B.It was clarified that the ventilation frequency and airflow markedly influenced infection. It is important to investigate environmental factors on epidemiological investigations and to educate people regarding the importance of ventilation.

To clarify factors involved in the refusal or discontinuation of treatment for latent tuberculosis infection (LTBI), we reviewed LTBI treatment.The subjects were 193 patients for whom LTBI treatment was indicated on a family contact investigation in 2006. We examined the subjects' backgrounds and reasons for treatment refusal or discontinuation. In addition, we investigated the incidence of the onset of tuberculosis within 2 years after the final contact with the source of infection.i) Patient background: The state of treatment could be evaluated in 185 patients. Of these, drug therapy was completed in 138 (75%), whereas 47 (25%) refused or discontinued treatment. The mean ages of the former and latter were 21.0 and 26.2 years, respectively, showing a significant difference. Concerning the state of contact, 9 (8%) of 114 patients who had lived with and 12 (17%) of 71 who had lived apart from the source of infection refused treatment, showing a significant difference. ii) Onset within 2 years: We analyzed 180 patients for whom follow-up was possible. Drug therapy was completed in 137 patients. No patient developed tuberculosis onset. On the other hand, drug therapy was not completed in 43 patients, and 6 (14%) developed tuberculosis onset. iii) The reasons were investigated in 47 patients who did not complete drug therapy. There were 15 episodes associated with side effects, followed by 14 related to personal circumstances, such as being busy, disliking medicines, and the absence of confidence regarding the completion of drug therapy, and 6 associated with either insufficient explanations regarding the diagnosis or an absence of symptoms.Treatment refusal/discontinuation was more frequent in the more advanced age groups and patients who had lived apart from the source of infection. It may therefore be necessary to more closely explain the importance of treatment to these patients. Most reasons for treatment refusal/discontinuation were associated with side effects or insufficient explanations, suggesting the necessity of providing sufficient information to aid in patient understanding.

Risk factors for tuberculosis transmission from patients to contacts were found to be younger age, presence of cavitary lesion in chest X-ray findings, shedding higher number of organisms, longer duration of respiratory symptoms, longer hours of contact, and smaller space of contact environment. It should be noted that even casual contacts identified by contact investigation developed tuberculosis later on. In the past contact investigation and subsequent latent TB infection (LTBI) treatment, preventive effects of tuberculosis was obvious, although there might be some over-diagnosis of LTBI with tuberculin skin testing (TST). Introduction of interferon-gamma release assay (IGRA) added to TST seems to increase specificity and reduce over-diagnosis of TB infection. However in case of outbreak investigation in schools, screening by TST is still effective and efficient. Only those case with 30mm or over of redness (equivalent of 15 mm of induration) of TST were tested with QFT, IGRA. If anyone shows positive QFT, test of QFT would be expanded to the contact with TST of less than 30 mm.

The global problem of tuberculosis (TB) is well recognized by the international community. As a result of promotion of Directly Observed Treatment, Short Course (DOTS), TB incidence has started to decline. Currently the STOP TB Partnership leads the initiative to resolve important issues such as TB/HIV, multi-drug resistant (MDR) TB, and strengthening of health systems through implementation of TB control.

The causes of delay in receiving medical examinations (for a period of more than 2 months between the appearance of tuberculosis symptoms and the first examination at a medical institution) were investigated.Interviews of 127 smear positive pulmonary tuberculosis patients (study period: June-December, 2008). Subjects were divided into 2 groups: those who showed delay in receiving medical examination (hereinafter referred to as "case") and those who did not show delay in receiving medical examination (hereinafter referred to as "control"), and the factors causing differences between the two groups were investigated.There were 44 case examples and 83 control examples. There were higher rates of "aged under 60", "employed" and "have no family doctor" among cases, however, none of them were statistically significant. The rate of smokers was significantly higher in cases. At the time of diagnosis, chest X-ray findings were significantly aggravated in cases and cases were also significantly higher in the degree of smear positivity. It was mostly cases that replied "they were not the symptoms of a serious illness" concerning the initial symptoms and, concerning the timing of medical examinations, the reply "I was busy at work and couldn't take time off" was significantly higher.It is considered that cases do not take symptoms seriously and that many of them do not receive medical examinations. Further, it is also considered necessary to carefully educate smokers in particular. There were many cases diagnosed as serious on chest X-ray findings and showed higher degree of smear positivity, so it is considered important to reduce delays in receiving medical examinations in order to treat patients early and prevent the spread of infection.

To evaluate tuberculosis index case, group contact investigation and usefulness of tuberculin skin test (TST) results.We analyzed data for 833 groups examined by contact investigation registered in 2003-2005 in 24 wards of Osaka City characteristics of their index cases, TST results, and follow-up outcome of radiograph screening up to 2 years.71.3% (7406/10378) of contacts completed 2 years follow-up radiograph screening. There were 54 secondary cases. Characteristics of 38 index cases of contact groups were compared by the rate of causing secondary cases. Results showed that the following characteristics were statistically significant in causing secondary cases: sex (male: 5.6%, female: 1.8%, chi2 test; p0.05), age (49 or less: 6.8%, 50-64: 5.7%, 65 or over: 0, p0.01), chest radiography (cavitary: 6.0%, non-cavitary: 2.0%, p0.05), initial AFB smear grade (G5 or over: 6.5%, G4 or less: 2.2%, p0.01), cough duration (2 months or more: 7.0%, less than 2 months: 2.8%, p0.01), transmission risk index (10 or over: 8.4%, 0.1-9.9: 3.4%, 0: 0, p0.001). As initial part of contact investigation, decision was made for each group whether TB secondary transmission was "likely" or "unlikely". If it was considered as "likely", TST was conducted for contacts. Incidence rate of secondary case was 0.44% in groups TST was conducted, and 0.09% in groups TST was not conducted. The difference was statistically significant (p0.05). According to tuberculin results, 760 persons in 215 groups were given LTBI treatment. Comparing the number of secondary cases in the age group of 10-39 eligible for LTBI treatment, 19 secondary cases were detected immediately or 2 months after the initial contact examination, and it was reduced to 7 cases after 6 months to 2 years. However in the age group of 40 and over not eligible of LTBI treatment, the number of secondary cases increased from 10 immediately or 2 months after the initial contact examination to 18 after 6 months to 2 years, and the difference was statistically significant (p0.01).Results of contact investigation and successive LTBI treatment showed that the prevention of secondary cases was effective, despite of some over-diagnosis of LTBI by TST.

Summary A population-based study of Mycobacterium tuberculosis isolated from homeless tuberculosis patients was performed during 2002–2004 in Osaka City, Japan. The data show that the ancient Beijing subfamily was predominant, whereas clustered isolates based on refined variable number of tandem repeats genotyping (19 loci) mainly belonged to the modern Beijing subfamily, suggesting its increased transmissibility.

To analyze conditions of developing TB among nurses and to discuss preventive measures.TB patient cards of nurses and other health workers registered in Osaka City from 1999 to 2003 were studied.Incidence rate of TB among female nurse/ assistant-nurse was 3.0 times higher than that of all female population. The route of case finding were as follows with descending order, visit to medical facilities with symptoms (55.8%), regular health check (35.8%), individual health check (5.8%), and contact examination (2.5%). Among risk factors related to the development of TB work in hospitals account for 55.0% in nurse patients of all ages, 72.5% in 20s, 47.4% in 30s, 37.5% in 40s, 36.4% in 50s and 0% in 60s. Individual risk factors were identified as follows in descending order, "TB patients diagnosed in the hospital." (10.0%), "examined at TB contact examination." (9.2%), "history of TB treatment at 18 years of age and over" (7.5%), "working experience in TB hospital/TB ward." (6.7%), "TB patients diagnosed among colleague." (5.0%), "increased reaction of tuberculin skin test after employment." (2.5%), "diagnosis of 'healed TB lesion" at regular health check." (1.7%), "default of chemoprophylaxis" (1.7%). Among various risk factors, "examined at TB contact examination" and "TB patients diagnosed in the hospital" are the two most common factors and occupied 38.8% in patients in 20s.Therefore it is important to promote further nosocomial TB infection control with a view to lower incidence rate of TB among nurses, which is 3 times higher than that of all female population.

The Osaka Socio-Medical Center Hospital is a medical care facility located in the Airin area of Osaka city where the prevalence of tuberculosis is high, and treats day laborers and homeless people mainly, either free of charge or with a small fee. To investigate whether this hospital can play a role to reduce the prevalence of tuberculosis in this area, we investigated the case rate of active tuberculosis in outpatients of the hospital.Of 1673 patients who first visited the Orthopaedic Outpatient Clinic between March 31, 2005 and June 15, 2006, 538 patients consented to undergo screening and underwent chest X-ray examination (screening group). We also analyzed chest X-ray examination in 2000 patients examined at the Department of Internal Medicine during the same period (control group).Of the 538 patients in the screening group (523 males and 15 females), 13 male patients (2.4%) requiring treatment were detected. Of the 2000 patients in the control group, 85 patients (84 males and 1 female) (4.3%) requiring treatment were detected.The tuberculosis case rate (2.4%) in the screening group was similar to that of tuberculosis screenings (1.1-1.8%) in the Airin area in 2004. The case rate in the control group was two times higher. Since the prevalence is very high in patients of this hospital, the hospital should play a significant role in the health care of tuberculosis patients in this community by reinforcing the screening system and enriching the outpatient clinic system.

To ascertain tuberculosis (TB) infection control measures and incidence of TB in nursing homes for elder.The questionnaire on TB infection control was distributed to all nursing homes in Osaka City in 2005.The questionnaire was returned from 197 (90%) out of 219 facilities. In more than half of facilities, infection control committee was organized (57%) and automated ventilation system was installed (59%). In almost all facilities, residents had annual chest X-ray screening (94%). Respiratory symptoms were checked for residents and "day service" users in majority of facilities. 100% of employees had annual chest X-ray screening. However TB education session for employees was held annually in only 40% of facilities. Education materials on TB were distributed in 19%. Tuberculin skin test (TST) was conducted for new employees in 31%. TB patients were diagnosed in 22% of facilities in the past 3 years from 2002 to 2004. Incidence rate of TB is 75.2 per 100,000 for residents and 24.1 per 100,000 for employees. Analysis showed that TB incidence rate is higher in facilities with larger number of residents and in facilities where infection control committee is organized, and facilities where TST is conducted for new employees.In Osaka City, TB infection control was more often implemented in facilities where TB patient was diagnosed. When age structure is taken into consideration, TB incidence rate of employees or residents was lower than general population. Nosocomial TB infection does not seem to be occurring in nursing homes. However, as TB patients were diagnosed occasionally, TB infection control measures should be strengthened in Osaka City.

To ascertain nosocomial tuberculosis (TB) infection control practice in hospitals in Osaka City.A questionnaire was distributed in the orientation meeting and collected at the occasion of medical inspection in all 196 hospitals in Osaka City in 2003.TB patients were diagnosed in about half of hospitals in the past 3 years. Basic TB infection control measures were taken in the majority of hospitals; such as chest X-ray screening for all inpatients, health check for employees, tuberculin skin test (TST) for newly employed staff, and nomination of a person in charge of TB infection control. Control measures were practiced more often in hospitals where TB patients were diagnosed, such as "fiberoptic bronchoscopy is to be conducted last in the working hours to avoid contamination of TB bacilli in a room," "TST (including two-step method) for all newly employed staff," "Staff wear N95 mask when they deal with TB patients/suspects," and the differences were statistically significant.It is necessary in hospitals in Osaka City to strengthen nosocomial TB infection control as TB patients were diagnosed in about half of hospitals in the past 3 years. Low cost infection control measures were undertaken more often among hospitals where TB patients were diagnosed. Introduction of high cost equipment or improvement of facilities should be considered in hospitals of high TB risk. Guidelines formulated based on analysis of the survey should facilitate all hospitals to introduce at least low cost effective tuberculosis infection control measures.

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 radiological 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 reached 8.1% after 80 years of age. In female, however, it started to rise at 50s (0.3%) gradually and reached only 2.3% 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 1000 person-years) was 16 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 fibrotic lesions was 24 times as high as among female with normal finding, and the difference was statistically significant (p0.001). From the data obtained and bibliographical review, benefits of INH prophylaxis were discussed.

The notification rate of tuberculosis in Japan was 31.0 per 100,000 in 2000. The rate was especially high among the elderly population, reaching 85.5 per 100,000 among those over 65 years of age. We conducted a study of preventive therapy in middle-aged and elderly persons selected from the population-based screening by the mass miniature radiography. The eligible criteria were 50-79 years of age, fibrous lesion which were compatible with healed tuberculosis and showed no change for at least one year, no previous treatment for tuberculosis, normal liver function tests, and no serious disease at the time of study. The eligible criteria for liver function tests in this study was less than 50 IU/L of AST and ALT value, and less than 1.5 mg/dl of T-bil level. A total of 13,219 people underwent TB screening in 4 cities in 1997 and 2 cities in 1998. Among them, 440 persons fulfilled the above criteria based on the screening records and chest X-ray films. The municipal offices sent letters to 418 people, except 22 whose addresses were unknown, to obtain permission to use their addresses and results of screening in our study. Permission was obtained from 137 persons and we sent them invitation letters for cost-free physical checkup service. Ninety-five persons visited us, and we offered them physical checkup and explained about our study. After obtaining the informed consent, we performed chest X-ray and sputum examination for 3 consecutive days. Finally 29 people were enrolled in the study. They were divided into 4 groups by sex and age, and were randomly assigned to one of two treatment groups. One group took 300 mg of INH per day for 6 months and the other group was only followed up by chest X-ray. Fourteen out of 29 persons began to take INH and received monthly liver function test. All the subjects were scheduled to follow by medical checkup every 6 months for 5 years. The proportion of taking INH tablets was estimated to range from 94% to 100%, based on the calendar for record of taking medication and the number of remaining tablets each month. Six (42.9%) of 14 persons reported adverse reactions. Two of 6 persons complained some of diarrhea, vomiting and gastrointestinal disturbance within 2 weeks, and discontinued taking INH, although none of them showed abnormal liver function tests. Two of 6 persons who reported some kinds of symptoms and 2 of 8 persons who did not complain of any symptoms showed abnormal liver function tests. The abnormal liver function tests had developed from 2 months after the beginning of INH taking in most of the persons and the abnormality improved after the completion of 6-month treatment. We have followed them for a maximum duration of 2.5 years, and 3 cases dropped out from the study. These defaulted cases had completed 6 months of INH. One person (69 y.o. male) was diagnosed as active TB by his chest X-ray film at the 6th month medical checkup, although it was not confirmed bacteriologically. One person (62 y.o. female) had the mastectomy for breast cancer 7 months before the entry to this study and relapsed at the 8th month after the entry. One person (73 y.o. female) was diagnosed as lung cancer at the medical checkup on 2.5 years. Besides them, 4 persons were suspected of worsening the abnormal shadows on chest X-ray films; one was from the INH group and three were from the follow-up group. However none of them was diagnosed clinically and bacteriologically as active tuberculosis.

To ascertain the extent of under-utilization and insufficiency or inappropriateness in provision of health services as one of the possible causes of high mortality from pediatric pneumonia in pilot areas in Vietnam.The household survey on morbidity and treatment of acute respiratory infections, simple cough, and cold and pneumonia, was conducted in two communities with 10% sampling of the child population.Both under-treatment of "fast breathing", a proxy for pneumonia, and over-treatment of simple cough and cold with antimicrobials by health workers, mothers, and private practitioners were common.A household survey on morbidity and treatment was found to be useful to clarify actual practices in the treatment of acute respiratory infections in the community, which cannot be obtained by mere interview with health workers or mothers. Since a change of knowledge did not automatically lead to change of practice, the training of health workers, health education of mothers and provision of antimicrobials at village health stations would not guarantee improved practice of health workers and mothers. Therefore, constant supervision for health workers, continued health education of mothers and involvement of private practitioners are needed to improve the situation.

This article summarizes the implementation and efficacy of the World Health Organization's standard case management program for pediatric pneumonia in three counties in China and in the Western Division of Fiji. The information provided through this program was simple enough to be understood by parents and health care workers with a basic educational background. The program reduced mortality from pneumonia even when implemented through the existing health care system in a relatively poor county in China. The factors important in the success of the program included improved recognition of the signs of childhood pneumonia by parents, earlier presentation of children with these signs to health care facilities, availability of antimicrobial agents at the primary health care level, and rational decisions by health care workers about the use of these agents.