[Treatment outcome of latent tuberculosis infection in persons with fibrotic pulmonary lesions].

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.

[TREATMENT SUPPORT AND TREATMENT QUTCOMES OF PULMONARY TUBERCULOSIS IN PATIENTS WITH HIV INFECTION IN OSAKA CITY].

[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.

[USE OF QuantiFERON® TB-GOLD IN-TUBE IN A CONTACT INVESTIGATION TO DETERMINE THE ONSET OF TUBERCULOSIS WITH OR WITHOUT LATENT TUBERCULOSIS INFECTION TREATMENT].

PURPOSE: 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. METHODS: 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. RESULTS: (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 (P < 0.001). (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 (P < 0.001). DISCUSSION: 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.

[TUBERCULOSIS SCREENING BY CHEST RADIOGRAPHY AMONG INTERNATIONAL STUDENTS AT JAPANESE LANGUAGE SCHOOLS IN OSAKA CITY].

PURPOSE: 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. METHODS: 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. RESULTS: 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 (P<0.001), 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. DISCUSSION: 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.

[PULMONARY TUBERCULOSIS TREATMENT OUTCOME AMONG FOREIGN NATIONALS RESIDING IN OSAKA CITY].

UNLABELLED: Abstract PURPOSE: In this study, we analyzed pulmonary tuberculosis treatment outcomes among foreign nationals of different backgrounds. METHODS: 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. RESULTS: (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%; P < 0.05). (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%; P < 0.01). (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%; P < 0.01). The rate of transfer out among foreign nationals with pulmonary tuberculosis was 19.1%, also significantly higher than that of Japanese patients (5.3%; P < 0.001). DISCUSSION: 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.

[RATES OF COMPLETION AND TREATMENT OUTCOMES FOR TYPE OF COMMUNITY DOTS].

AIM: 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. METHODS AND SUBJECTS: 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. RESULTS: 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 (P < 0.001). 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 (P < 0.001). 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 (P < 0.00 1). Among the visiting, HWC, and P DOTS groups, the completion of DOTS resulted in a high treatment success rate. DISCUSSION: 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.

[EXAMINATION OF TUBERCULOSIS OUTBREAK INDEX CASES IN OSAKA CITY].

OBJECTIVE: To analyze tuberculosis outbreak index cases in order to improve preventative measures. METHODS: 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. RESULTS: 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 (p < 0.001). 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 (p < 0.001). 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 (p < 0.001). DISCUSSION: 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.

[Tuberculosis contact investigation in hospitals].

OBJECTIVE: To contribute to measures against hospital-acquired infections by analyzing and evaluating tuberculosis contact investigations in hospitals. METHODS: 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. RESULTS: 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" (P < 0.05). DISCUSSION: Our results suggest that early diagnosis and appropriate responses during high-risk procedures may be necessary measures to prevent hospital-acquired infections.

[Evaluation of risk factors for failed/defaulted on treatment outcomes of pulmonary tuberculosis in Osaka City].

OBJECTIVE: In this study, we analyzed the relationship between the risk of discontinuing medication and patient outcomes. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

[Interpreting "equivocal" results obtained from the QuantiFERON-TB Gold In-Tube test in contact investigations].

OBJECTIVE: In this study, we demonstrate the interpretation of "equivocal" results by the QuantiFERON"-TB Gold In-Tube (QFT-GIT) test in contact investigations. METHODS: 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. 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). CONCLUSIONS: 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.

[Medication support and treatment outcome in homeless patients with tuberculosis].

PURPOSE: We conducted a study on factors related to treatment outcome and medication support in homeless patients with tuberculosis. METHODS: 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. RESULTS: 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%; P < 0.001). 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 (P < 0.01). CONCLUSION: 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.

[Evaluation of the effect of DOTS on treatment outcomes in patients with smear-positive pulmonary tuberculosis in Osaka City].

PURPOSE: 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. METHODS: 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. RESULTS: (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 (P<0.01). (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. CONCLUSION: 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 background of drug-resistant tuberculosis patients on the basis of the annual report database for 2007-2009 in Japan].

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, p < 0.001, 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, p < 0.001, 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, p < 0.001, 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, p < 0.001) and foreigners who had entered Japan within the last 5 years (odds ratio = 1.8, 95% CI: 1.3-2.5, p < 0.001); 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.

[The association between smoking and sputum smear-positive pulmonary tuberculosis in Osaka City].

PURPOSE: 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. METHODS: 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). RESULTS: (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. CONCLUSION: 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.

[Examination of onset cases in contact investigation].

OBJECTIVES: To analyze and evaluate onset cases of tuberculosis detected in contact investigations and to apply the results to future countermeasures. METHODS: 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. RESULTS: (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. DISCUSSION: 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.

Tuberculosis infection among homeless persons and caregivers in a high-tuberculosis-prevalence area in Japan: a cross-sectional study.

BACKGROUND: Tuberculosis (TB) is a major public health problem. The Airin district of Osaka City has a large population of homeless persons and caregivers and is estimated to be the largest TB-endemic area in the intermediate-prevalence country, Japan. However, there have been few studies of homeless persons and caregivers. The objective of this study is to detect active TB and to assess the prevalence and risk factors for latent TB infection among homeless persons and caregivers. METHODS: We conducted a cross-sectional study for screening TB infection (active and latent TB infections) using questionnaire, chest X-ray (CXR), newly available assay for latent TB infection (QuantiFERON-TB Gold In-Tube; QFT) and clinical evaluation by physicians at the Osaka Socio-Medical Center Hospital between July 2007 and March 2008. Homeless persons and caregivers, aged 30-74 years old, who had not received CXR examination within one year, were recruited. As for risk factors of latent TB infection, the odds ratios (OR) and 95% confidence intervals (95% CI) for QFT-positivity were calculated using logistic regression model. RESULTS: Complete responses were available from 436 individuals (263 homeless persons and 173 caregivers). Four active TB cases (1.5%) among homeless persons were found, while there were no cases among caregivers. Out of these four, three had positive QFT results. One hundred and thirty-three (50.6%) homeless persons and 42 (24.3%) caregivers had positive QFT results. In multivariate analysis, QFT-positivity was independently associated with a long time spent in the Airin district: ≥10 years versus <10 years for homeless (OR = 2.53; 95% CI, 1.39-4.61) and for caregivers (OR = 2.32; 95% CI, 1.05-5.13), and the past exposure to TB patients for caregivers (OR = 3.21; 95% CI, 1.30-7.91) but not for homeless persons (OR = 1.51; 95% CI, 0.71-3.21). CONCLUSIONS: Although no active TB was found for caregivers, one-quarter of them had latent TB infection. In addition to homeless persons, caregivers need examinations for latent TB infection as well as active TB and careful follow-up, especially when they have spent a long time in a TB-endemic area and/or have been exposed to TB patients.

[An outbreak of tuberculosis in which environmental factors influenced tuberculosis infection].

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. DISCUSSION: 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.

[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.

[Assessment of self-discharge of homeless patients with tuberculosis].

OBJECTIVES: 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. METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

[Comparative performance of tuberculin skin test and QuantiFERON TB-gold in contact investigations for tuberculosis].

OBJECTIVES: To evaluate the performances of the QuantiFERON TB-Gold assay (QFT) and tuberculin skin test (TST) and to examine how a latent tuberculosis infection (LTBI) should be diagnosed in contact investigations of children aged 6 to 17 years. METHODS: A total of 232 boys and girls aged 6 to 17 years who were in contact with 134 culture-confirmed pulmonary tuberculosis patients (index cases) were examined both with QFT and TST. Factors influencing the results of the tests and their interactions were evaluated with multivariate analyses. RESULTS: Two variables (whether household contact and with/without contact with a cavitary disease patient) were found to significantly predict a positive QFT result. Positive TST defined with erythema being either greater than 20 mm or 30mm correlated significantly with two variables (whether household contact and with/without contact with a smear positive patient). There was moderate agreement between QFT and TST (positivity defined as with erythema greater than 30mm), with kappa=0.49, for contacts aged 6 to 11 years. Among contacts aged 6 to 11 years, 14 had a negative QFT result and TST with erythema greater than 30 mm. Of these 14, 7 contacts (50%) of smear positive index case were not indicated for LTBI treatment. CONCLUSIONS: When diagnosing LTBI among contacts aged 6 to 11 years who show negative QFT and strong TST reactions, we should take into consideration the factors related with a higher probability to the risk of infection. Because a history of past BCG vaccination is more likely to affect TST results in those aged 12 to 17 years than in younger subjects, greater care must be taken when evaluating the TST of these contacts.