[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.

[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.

[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.

[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.

Influence of the 2009 financial crisis on detection of advanced pulmonary tuberculosis in Osaka city, Japan: a cross-sectional study.

OBJECTIVE: To investigate the association between the economic recession and the detection of advanced cases of pulmonary tuberculosis in Osaka city from 2007 to 2009. DESIGN: A repeated cross-sectional study. SETTING: Osaka city has been the highest tuberculosis burden area in Japan. After the previous global financial crisis, the unemployment rate in Osaka prefecture has deteriorated from 5.3% in 2008 to 6.6% in 2009. PARTICIPANTS: During the study period, 3406 pulmonary tuberculosis cases were enrolled: 2530 males and 876 females; 1546 elderly cases (65 years and above) and 1860 young cases (under 65 years); 417 homeless cases and 2989 non-homeless cases. OUTCOME MEASURES: Patients' information included the sex, age, registry, health insurances, places of detection, sputum smear test results, patients' delay, doctors' delay and the grade of chest x-ray findings. They were statistically analysed between 2007 and 2008, two years before and just before the financial crisis, and between 2008 and 2009, just before and after the financial crisis. RESULTS: The total numbers of pulmonary tuberculosis cases were 1172 in 2007, 1083 in 2008 and 1151 in 2009. In health examinations for non-homeless people, higher number of cases in 2009 were sputum smear positive, had respiratory symptoms and showed advanced disease in chest x-rays than those in 2008, with a longer patients' delay. On the contrary, in health examination for homeless people, fewer cases of advanced pulmonary tuberculosis were found in 2009 than in 2008, with a shorter patients' delay. In clinical examinations, there was no trend towards a difference between non-homeless and homeless people. CONCLUSIONS: Although homeless people might be protected by public assistance, tuberculosis prevention and control need to be reinforced for the non-homeless population after the financial crisis.

[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.

[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.

[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.