Ambient air pollution and risk of tuberculosis: a cohort study.

OBJECTIVES: Several respirable hazards, including smoking and indoor air pollution from biomass, were suggested to increase the risk of tuberculosis. Few studies have been conducted on ambient air pollution and tuberculosis. We investigated the association between exposure to ambient air pollution and incidence of active tuberculosis. METHODS: We conducted a cohort study using 106,678 participants of a community-based screening service in Taiwan, 2005-2012. We estimated individual exposure to air pollution using data from the nearest air quality monitoring station and the road intensity within a 500 m buffer zone. The incidence of tuberculosis was ascertained from the national tuberculosis registry. RESULTS: After a median follow-up of 6.7 years, 418 cases of tuberculosis occurred. Exposure to fine particulate matter (PM2.5) was associated with increased risk of active tuberculosis (adjusted HR: 1.39/10 µg/m3 (95% CI 0.95 to 2.03)). In addition, traffic-related air pollution including nitrogen dioxide (adjusted HR: 1.33/10 ppb; 95% CI 1.04 to 1.70), nitrogen oxides (adjusted HR: 1.21/10 ppb; 95% CI 1.04 to 1.41) and carbon monoxide (adjusted HR: 1.89/ppm; 95% CI 0.78 to 4.58) was associated with tuberculosis risk. There was a non-significant trend between the length of major roads in the neighbourhood and culture-confirmed tuberculosis (adjusted HR: 1.04/km; 95% CI 0.995 to 1.09). CONCLUSIONS: Our study revealed a possible link between ambient air pollution and risk of active tuberculosis. Since people from developing countries continue to be exposed to high levels of ambient air pollution and to experience high rates of tuberculosis, the impact of worsening air pollution on global tuberculosis control warrants further investigation.

Surveillance of Tuberculosis in Taipei: The Influence of Nontuberculous Mycobacteria.

BACKGROUND: Notification of tuberculosis (TB) but not nontuberculous mycobacteria (NTM) is mandatory in Taiwan. Partly due to the strict regulation on TB notification, several patients infected with NTM were notified as TB cases. Notification of patients infected with NTM as TB cases can trigger public health actions and impose additional burdens on the public health system. We conducted a study to assess the influence of NTM infection on surveillance of TB in Taipei. METHODOLOGY/PRINCIPAL FINDINGS: The study population included all individuals with a positive culture for Mycobacterium who were citizens of Taipei City and notified as TB cases in the calendar years 2007-2010. Of the 4216 notified culture-positive tuberculosis (TB) cases, 894 (21.2%) were infected with NTM. The average annual reported case rate of infection with NTM was 8.6 (95% confidence interval 7.7-9.4) per 100,000 people. The reported case rate of NTM increased with age in both males and females. The proportion of reported TB cases infected with NTM was significantly higher in females than in males (27.6% vs 17.8%, adjusted OR (adjOR) 1.93, 95% confidence interval (CI) 1.63-2.28); in smear-positive than in smear-negative (23.1% vs 19.2%, adjOR 1.26, 95% CI 1.08-1.47); and in previously treated cases than in new cases (35.7% vs 19.1%, adjOR 2.30, 95% CI 1.88-2.82). The most frequent species was M. avium complex (32.4%), followed by M. chelonae complex (17.6%), M. fortuitum complex (17.0%) and M. kansasii (9.8%). Of the 890 notified NTM cases assessed, 703 (79.0%) were treated with anti-TB drugs, and 730 (82.0%) were de-notified. CONCLUSIONS/SIGNIFICANCE: The influence of NTM on surveillance of TB in Taipei was substantial. Health authorities should take action to ensure that nucleic acid amplification tests are performed in all smear-positive cases in a timely manner to reduce the misdiagnosis of patients infected with NTM as TB cases.

Using financial incentives to improve the care of tuberculosis patients.

OBJECTIVES: Tuberculosis (TB) is a serious public health concern, and Taiwan has implemented a pay-for-performance (P4P) program to incentivize healthcare professionals to provide comprehensive care to TB patients. This study aims to examine the effects of the TB P4P program on treatment outcomes and related expenses. STUDY DESIGN: A population-based natural experimental design with intervention and comparison groups. METHODS: Propensity score matching was conducted to increase the comparability between the P4P and non-P4P group. A total of 12,018 subjects were included in the analysis, with 6009 cases in each group. Generalized linear models and multinomial logistic regression were employed to examine the effects of the P4P program. RESULTS: The regression models indicated that patients enrolled in the P4P program had 14% more ambulatory visits than non-P4P patients (P < .001), but there were no differences in hospitalization rates. On average, P4P enrollees spent $215 (4.6%) less on TB-related expenses than their counterparts. In addition, P4P enrollees had a higher likelihood of being successfully treated (odds ratio, 1.56; P < .001) and were less likely to die compared with nonenrollees. CONCLUSIONS: Patients in the P4P program were less likely to die, were more likely to be treated successfully, and incurred lower costs. Providing financial incentives to healthcare institutions could be a feasible model for better TB control.

Comparing the factors correlated with tuberculosis-specific and non-tuberculosis-specific deaths in different age groups among tuberculosis-related deaths in Taiwan.

BACKGROUND: Nearly 20% of tuberculosis (TB) patients die within one year, and TB-related mortality rates remain high in Taiwan. The study aimed to identify factors correlated with TB-specific deaths versus non-TB-specific deaths in different age groups among TB-related mortalities. METHODS: A retrospective cohort study was conducted from 2006-2008 with newly registered TB patients receiving follow-up for 1 year. The national TB database from the Taiwan-CDC was linked with the National Vital Registry System and the National Health Insurance database. A chi-squared test and logistic regression were used to analyse the correlated factors related to TB-specific and non-TB-specific deaths in different age groups. RESULTS: Elderly age (odds ratio [OR] 2.68-8.09), Eastern residence (OR 2.01), positive sputum bacteriology (OR 2.54), abnormal chest X-ray (OR 2.28), and comorbidity with chronic kidney disease (OR 2.35), stroke (OR 1.74) or chronic liver disease (OR 1.29) were most likely to be the cause of TB-specific deaths, whereas cancer (OR 0.79) was less likely to be implicated. For non-TB-specific deaths in patients younger than 65 years of age, male sex (OR 2.04) and comorbidity with HIV (OR 5.92), chronic kidney disease (OR 8.02), stroke (OR 3.75), cancer (OR 9.79), chronic liver disease (OR 2.71) or diabetes mellitus (OR 1.38) were risk factors. CONCLUSIONS: Different factors correlated with TB-specific deaths compared with non-TB-specific deaths, and the impact of comorbidities gradually decreased as age increased. To reduce TB-specific mortality, special consideration for TB patients with old age, Eastern residence, positive sputum bacteriology and comorbidity with chronic kidney disease or stroke is crucial. In particular, Eastern residence increased the risk of TB-specific death in all age groups. In terms of TB deaths among patients younger than 65 years of age, patients with HIV, chronic kidney disease or cancer had a 6-10 times increased risk of non-TB-specific deaths.

Risk factors associated with death in a 12-month cohort analysis of tuberculosis patients: 12-month follow-up after registration.

The aim of the study was to investigate the risk of death for 12 months follow-up after registration of tuberculosis (TB), using a nationwide population-based retrospective cohort study. A total of 33851 new TB cases were enrolled from 2006 to 2008. Of these, 5584 (16.5%) patients died during the follow-up period because of TB, and 4224 (12.5%) patients died because of other causes. Multivariate survival analysis revealed that age, HIV, chronic kidney disease, stroke, cancer, and chronic liver disease and cirrhosis were significant risk factors associated with death. Patients of age 0 to 64 years with HIV, chronic kidney disease, cancer, stroke, chronic liver disease and cirrhosis, or diabetes had a higher risk of death than those without these comorbidities. The majority of the TB patients in Taiwan died because of causes other than TB, and death often occurred in the first 2 months after TB registration. Therefore, medical care and case management for those with comorbidities are advised to prevent death during TB treatment.

Exposure to secondhand smoke and risk of tuberculosis: prospective cohort study.

BACKGROUND: Prospective evidence on the association between secondhand-smoke exposure and tuberculosis is limited. METHODS: We included 23,827 never smokers from two rounds (2001 and 2005) of Taiwan National Health Interview Survey. Information on exposure to secondhand smoke at home as well as other sociodemographic and behavioral factors was collected through in-person interview. The participants were prospectively followed for incidence of tuberculosis through cross-matching the survey database to the national tuberculosis registry of Taiwan. RESULTS: A total of 85 cases of active tuberculosis were identified after a median follow-up of 7.0 years. The prevalence of exposure to secondhand smoke at home was 41.8% in the study population. In the multivariable Cox proportional hazards analysis, secondhand smoke was not associated with active tuberculosis (adjusted hazard ratio [HR], 1.03; 95% CI, 0.64 to 1.64). In the subgroup analysis, the association between secondhand smoke and tuberculosis decreased with increasing age; the adjusted HR for those <18, > = 18 and <40, > = 40 and <60, and > = 60 years old was 8.48 (0.77 to 93.56), 2.29 (0.75 to 7.01), 1.33 (0.58 to 3.01), and 0.66 (0.35 to 1.23) respectively. Results from extensive sensitivity analyses suggested that potential misclassification of secondhand-smoke exposure would not substantially affect the observed associations. CONCLUSIONS: The results from this prospective cohort study did not support an overall association between secondhand smoke and tuberculosis. However, the finding that adolescents might be particularly susceptible to secondhand smoke's effect warrants further investigation.

Improved consistency in dosing anti-tuberculosis drugs in Taipei, Taiwan.

BACKGROUND: It was reported that 35.5% of tuberculosis (TB) cases reported in 2003 in Taipei City had no recorded pre-treatment body weight and that among those who had, inconsistent dosing of anti-TB drugs was frequent. Taiwan Centers for Disease Control (CDC) have taken actions to strengthen dosing of anti-TB drugs among general practitioners. Prescribing practices of anti-TB drugs in Taipei City in 2007-2010 were investigated to assess whether interventions on dosing were effective. METHODOLOGY/PRINCIPAL FINDINGS: Lists of all notified culture positive TB cases in 2007-2010 were obtained from National TB Registry at Taiwan CDC. A medical audit of TB case management files was performed to collect pretreatment body weight and regimens prescribed at commencement of treatment. Dosages prescribed were compared with dosages recommended. The proportion of patients with recorded pre-treatment body weight was 64.5% in 2003, which increased to 96.5% in 2007-2010 (p<0.001). The proportion of patients treated with consistent dosing of a 3-drug fixed-dose combination (FDC) increased from 73.9% in 2003 to 87.7% in 2007-2010 (p<0.001), and that for 2-drug FDC from 76.0% to 86.1% (p = 0.024), for rifampicin (RMP) from 62.8% to 85.5% (p<0.001), and for isoniazid from 87.8% to 95.3% (p<0.001). In 2007-2010, among 2917 patients treated with either FDCs or RMP in single-drug preparation, the dosage of RMP was adequate (8-12 mg/kg) in 2571(88.1%) patients, too high in 282(9.7%), too low in 64(2.2%). In multinomial logistic regression models, factors significantly associated with adequate dosage of RMP were body weight and preparations of RMP. Patients weighting <40 kg (relative risk ratio (rrr) 6010.5, 95% CI 781.1-46249.7) and patients weighting 40-49 kg (rrr 1495.3, 95% CI 200.6-11144.6) were more likely to receive higher-than-recommended dose of RMP. CONCLUSIONS/SIGNIFICANCE: Prescribing practice in the treatment of TB in Taipei City has remarkably improved after health authorities implemented a series of interventions.

Completeness and timeliness of tuberculosis notification in Taiwan.

UNLABELLED: Tuberculosis (TB) is a notifiable disease by the Communicable Disease Control Law in Taiwan. Several measures have been undertaken to improve reporting of TB but the completeness and timeliness of TB notification in Taiwan has not yet been systemically evaluated. METHODS: To assess completeness and timeliness of TB notification, potential TB cases diagnosed by health care facilities in the year 2005-2007 were identified using the reimbursement database of national health insurance (NHI), which has 99% population coverage in Taiwan. Potential TB patients required notification were defined as those who have TB-related ICD-9 codes (010-018) in the NHI reimbursement database in 2005-2007, who were not diagnosed with TB in previous year, and who have been prescribed with 2 or more types of anti-TB drugs. Each potential TB case was matched to the national TB registry maintained at Taiwan Centers for Disease Control (CDC) by using national identity number or, if non-citizen, passport number to determine whether the patients had been notified to local public health authorities and Taiwan CDC. The difference in the number of days between date of anti-tuberculosis treatment and date of notification was calculated to determine the timeliness of TB reporting. RESULTS: Of the 57,405 TB patients who were prescribed with 2 or more anti-tuberculosis drugs, 55,291 (96.3%) were notified to National TB Registry and 2,114 (3.7%) were not. Of the 55,291 notified cases, 45,250 (81.8%) were notified within 7 days of anti-tuberculosis treatment (timely reporting) and 10,041(18.2%) after 7 days (delayed reporting). Factors significantly associated with failure of notification are younger age, previously notified cases, foreigner, those who visited clinics and those who visited health care facilities only once or twice in 6 months. CONCLUSION: A small proportion of TB cases were not notified and a substantial proportion of notified TB cases had delayed reporting, findings with implication for strengthening surveillance of tuberculosis in Taiwan. Countries where the completeness and timeliness of TB notification has not yet been evaluated should take similar action to strengthen surveillance of TB.

Trends in tuberculosis in Taiwan, 2002-2008.

BACKGROUND/PURPOSE: Tuberculosis (TB) remains an important infectious disease in Taiwan. To control TB effectively, the Taiwan Centers for Disease Control implemented the National Tuberculosis Program (NTP) in 2006, modeled on the World Health Organization global TB control program. The goal of the program was to reduce the number of TB cases by half within a decade. This study was designed to describe the epidemiology of TB in Taiwan, and to evaluate the preliminary effectiveness of the NTP. METHODS: We conducted a retrospective study of data from the National Tuberculosis Registry System collected between 2002 and 2008. Demographics, geographic distribution of disease, and change in rates of TB incidence and mortality were analyzed. RESULTS: From 2002 to 2008, new TB cases declined from 16,758 to 14,265, and incidence decreased from 75 per 100,000 population to 62 per 100,000 population. More than 50% of new cases occurred among elderly adults. Over the study period, TB mortality decreased from 5.7 per 100,000 population to 3.3 per 100,000 population, with over half of TB deaths occurring among patients aged ≥ 65 years. Since the NTP was implemented, from 2005 to 2008, TB incidence and mortality declined by 14% and 23%, respectively. CONCLUSION: TB-associated incidence and mortality decreased over the course of the study. Nevertheless, there continue to be high-incidence areas that show the opposite trend; these areas should strive to improve case management and consultation. In the most populous districts, rigorous surveillance is necessary to track incidence and mortality rate fluctuations.

Impact of HAART therapy on co-infection of tuberculosis and HIV cases for 9 years in Taiwan.

Free highly active antiretroviral therapy (HAART) was made available by The Department of Health since April 1997. As a result, the incidence rate of tuberculosis (TB)/human immunodeficiency virus (HIV) co-infection among HIV cases rose from 1.90% to 3.82% during 1993 to 1998 and decreased from 3.82% to 0.94% during 1998 to 2006. The incidence rate of TB/HIV co-infection among HIV cases reached its peak in 1998 and then started to reverse, although the next year the TB disease burden (incidence rate: 62.7 cases per 100,000 persons) remained consistently high, and this continued in the following years. The survival rate of TB/HIV co-infection cases was 62.16% during the period 1993-1996 (pre-free HAART era) and increased to 86.60% during the period 1998-2006 (P < 0.0001) (post-free HAART era). Highly active antiretroviral therapy decreased the incidence rate of new TB/HIV co-infection cases among HIV cases and increased the survival rate of TB/HIV co-infection cases.

Assessing the quality of tuberculosis-related underlying cause of death assignment in Taiwan, 2001-2005.

BACKGROUND/PURPOSE: Assignment of underlying cause of death (UCOD) might be inconsistent among coders if physicians do not properly record cause of death on death certificates. This study aimed to assess the changes in the quality of tuberculosis-related UCOD assignment in Taiwan after interventions by the Center for Disease Control (CDC). METHODS: The reference (gold standard) we used to assess the quality of UCOD assignment by coders was the UCOD selected by the Automated Classification of Medical Entities (ACME) computer program. The agreement, over- and under-coding rates between coders and the reference were calculated by years before and after the CDC interventions. RESULTS: An abrupt decrease in tuberculosis death rates according to the UCOD assigned by coders was noted from 2003 to 2004, but no such decrease was noted according to the reference. The agreement in UCOD assignments between coders and ACME decreased from 0.75 in 2001 to 0.67 in 2005. We found a significant decrease in the over-coding rate from 0.21 in 2003 to 0.11 in 2004, and a prominent increase in under-coding rates from 0.08 in 2003 to 0.24 in 2004. CONCLUSION: The abrupt decrease in the official published tuberculosis mortality rate from 2003 to 2004 was due to significant changes in the practice of UCOD assignment of official coders, which might have been a response to interventions initiated by the CDC.

Screening for pulmonary tuberculosis among military conscripts in Taiwan.

BACKGROUND AND PURPOSE: Military service is obligatory for young men who are medically fit in Taiwan. Each year, all 19-year-old men are notified to undergo a required health check to determine their eligibility for military service. This study determined the prevalence of pulmonary tuberculosis (TB) among military conscripts in 1997 and 1998 and evaluated the effect of the mass radiographic screening program for military conscripts on the reported TB case rate. METHODS: During the annual health check, all 19-year-old men in Taiwan undergo miniature (70 x 70 mm) chest roentgenography (CXR). Those who have suspicious lesions on miniature films are notified to undergo follow-up CXR (14 x 14 inch) and sputum examinations. All these data for the period from 1997 to 1998 were analyzed to determine the prevalence of pulmonary TB. To evaluate the effect of the mass radiographic screening program among military conscripts on the reported TB case rates, annual data for newly diagnosed pulmonary TB in 1997 and 1998 were obtained from the National TB Register and analyzed by age and sex. RESULTS: A total of 305, 140 men eligible for military service underwent the required examination in 1997 and 1998. Pulmonary TB was diagnosed in 237 (0.08%) of these men, and 21 (6.9/100,000) had positive bacteriologic findings. In 1997 and 1998, the annual reported TB case rates for males and females were similar in both children and young adults, except for an early peak among men aged 19 years. CONCLUSION: The screening program resulted in a significant increase in the reported TB case rate among males aged 19 years. However, a low bacteriologic confirmation rate implies the possibility of over-diagnosis with CXR. Mass radiographic screening at the health check for military conscripts is inefficient in detecting bacteriologically confirmed TB, an observation with implications for screening policy development by the national TB program.