Quantifying the potential effects of air pollution reduction on population health and health expenditure in Taiwan.

Air pollution, particularly ambient fine particulate matter (PM2.5) pollution, poses a significant risk to public health, underscoring the importance of comprehending the long-term impact on health burden and expenditure at national and subnational levels. Therefore, this study aims to quantify the disease burden and healthcare expenditure associated with PM2.5 exposure in Taiwan and assess the potential benefits of reducing pollution levels. Using a comparative risk assessment framework that integrates an auto-aggressive integrated moving average model, we evaluated the avoidable burden of cardiopulmonary diseases (including ischemic heart disease, stroke, chronic obstructive pulmonary disease, lung cancer, and diabetes mellitus) and related healthcare expenditure under different air quality target scenarios, including status quo and target scenarios of 15, 10, and 5 µg/m3 reduction in PM2.5 concentration. Our findings indicate that reducing PM2.5 exposure has the potential to significantly alleviate the burden of multiple diseases. Comparing the estimated attributable disease burden and healthcare expenditure between reference and target scenarios from 2022 to 2050, the avoidable disability-adjusted life years were 0.61, 1.83, and 3.19 million for the 15, 10, and 5 µg/m3 target scenarios, respectively. Correspondingly, avoidable healthcare expenditure ranged from US$ 0.63 to 3.67 billion. We also highlighted the unequal allocation of resources and the need for policy interventions to address health disparities due to air pollution. Notably, in the 5 µg/m3 target scenario, Kaohsiung City stands to benefit the most, with 527,368 disability-adjusted life years avoided and US$ 0.53 billion saved from 2022 to 2050. Our findings suggest that adopting stricter emission targets can effectively reduce the health burden and associated healthcare expenditure in Taiwan. Overall, this study provides policymakers in Taiwan with valuable insights for mitigating the negative effects of air pollution by establishing a comprehensive framework for evaluating the co-benefits of air pollution reduction on healthcare expenditure and disease burden.

Mortality, morbidity, and risk factors in Taiwan, 1990-2017: findings from the Global Burden of Disease Study 2017.

BACKGROUND: Taiwan has implemented a national health insurance system since 1995 with high coverage and utilization rate. However, the health care system in Taiwan is facing immense challenges due to rapid population ageing. We have evaluated the landscape of population health by revisiting the results of GBD 2017 study. METHODS: Taiwan vital registration data (1980-2016) and Taiwan national health insurance database (2016) were used. We also conducted benchmarking comparisons with selected countries in East Asia from 1990 to 2017. RESULTS: The age-standardized disability-adjusted life-year (DALY) rates decreased by one-quarter from 1990 to 2017; however, progress was relatively slow compared to the comparator countries and has been stagnant recently. The Social-demographic Index (SDI) level in Taiwan in 2017 was 0.86, which is similar to Japan, Singapore, and South Korea in 2017, while the SDI level of China in 2017 was similar to that of Taiwan (0.69) in 1990. Although Taiwan's SDI reached the same level as those in Japan, Singapore, and South Korea in 2017, modifiable risk factors still contributed to nearly half of Taiwan's total disease burden. Five leading risk factors (high fasting plasma glucose, high body-mass index, alcohol use, illicit drug use, and impaired kidney function) accounted for a higher DALY rate in Taiwan than comparator countries in 2017. CONCLUSION: Taiwan made marked progress in health from 1990 to 2017. However, interventions targeted on major modifiable disease risk factors should be prioritized to realize the full potential of heath improvement in the process of rapid socioeconomic development.

Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset.

Importance: The dynamics of coronavirus disease 2019 (COVID-19) transmissibility are yet to be fully understood. Better understanding of the transmission dynamics is important for the development and evaluation of effective control policies. Objective: To delineate the transmission dynamics of COVID-19 and evaluate the transmission risk at different exposure window periods before and after symptom onset. Design, Setting, and Participants: This prospective case-ascertained study in Taiwan included laboratory-confirmed cases of COVID-19 and their contacts. The study period was from January 15 to March 18, 2020. All close contacts were quarantined at home for 14 days after their last exposure to the index case. During the quarantine period, any relevant symptoms (fever, cough, or other respiratory symptoms) of contacts triggered a COVID-19 test. The final follow-up date was April 2, 2020. Main Outcomes and Measures: Secondary clinical attack rate (considering symptomatic cases only) for different exposure time windows of the index cases and for different exposure settings (such as household, family, and health care). Results: We enrolled 100 confirmed patients, with a median age of 44 years (range, 11-88 years), including 44 men and 56 women. Among their 2761 close contacts, there were 22 paired index-secondary cases. The overall secondary clinical attack rate was 0.7% (95% CI, 0.4%-1.0%). The attack rate was higher among the 1818 contacts whose exposure to index cases started within 5 days of symptom onset (1.0% [95% CI, 0.6%-1.6%]) compared with those who were exposed later (0 cases from 852 contacts; 95% CI, 0%-0.4%). The 299 contacts with exclusive presymptomatic exposures were also at risk (attack rate, 0.7% [95% CI, 0.2%-2.4%]). The attack rate was higher among household (4.6% [95% CI, 2.3%-9.3%]) and nonhousehold (5.3% [95% CI, 2.1%-12.8%]) family contacts than that in health care or other settings. The attack rates were higher among those aged 40 to 59 years (1.1% [95% CI, 0.6%-2.1%]) and those aged 60 years and older (0.9% [95% CI, 0.3%-2.6%]). Conclusions and Relevance: In this study, high transmissibility of COVID-19 before and immediately after symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized measures may be required, such as social distancing.

Explaining age disparities in tuberculosis burden in Taiwan: a modelling study.

BACKGROUND: Tuberculosis (TB) burden shows wide disparities across ages in Taiwan. In 2016, the age-specific notification rate in those older than 65 years old was about 100 times as much as in those younger than 15 years old (185.0 vs 1.6 per 100,000 population). Similar patterns are observed in other intermediate TB burden settings. However, driving mechanisms for such age disparities are not clear and may have importance for TB control efforts. METHODS: We hypothesised three mechanisms for the age disparity in TB burden: (i) older age groups bear a higher risk of TB progression due to immune senescence, (ii) elderly cases acquired TB infection during a past period of high transmission, which has since rapidly declined and thus contributes to little recent infections, and (iii) assortative mixing by age allows elders to maintain a higher risk of TB infection, while limiting spillover transmission to younger age groups. We developed a series of dynamic compartmental models to incorporate these mechanisms, individually and in combination. The models were calibrated to the TB notification rates in Taiwan over 1997-2016 and evaluated by goodness-of-fit to the age disparities and the temporal trend in the TB burden, as well as the deviance information criterion (DIC). According to the model performance, we compared contributions of the hypothesised mechanisms. RESULTS: The 'full' model including all the three hypothesised mechanisms best captured the age disparities and temporal trend of the TB notification rates. However, dropping individual mechanisms from the full model in turn, we found that excluding the mechanism of assortative mixing yielded the least change in goodness-of-fit. In terms of their influence on the TB dynamics, the major contribution of the 'immune senescence' and 'assortative mixing' mechanisms was to create disparate burden among age groups, while the 'declining transmission' mechanism served to capture the temporal trend of notification rates. CONCLUSIONS: In settings such as Taiwan, the current TB burden in the elderly may be impacted more by prevention of active disease following latent infection, than by case-finding for blocking transmission. Further studies on these mechanisms are needed to disentangle their impacts on the TB epidemic and develop corresponding control strategies.

Health impact assessment of PM2.5 from a planned coal-fired power plant in Taiwan.

PURPOSE: To investigate the impact of a planned coal-fired power plant (CFPPT) in Shenao on air quality and health at subnational levels in Taiwan. METHODS: We applied the Gaussian trajectory transfer-coefficient (GTx) model to estimate annual average PM2.5 (particulate matter with aerodynamic diameter less than 2.5 µm) increments in 19 Taiwanese cities and counties caused by CFPPT operation. A population health risk assessment was performed by incorporating evidence of the health effects of PM2.5 provided by prospective studies and estimating long-term PM2.5 exposure. Additionally, we considered ischemic heart disease, stroke, lung cancer, and chronic obstruct pulmonary disease as the primary outcomes. The population-attributable fraction was used to estimate the county-level mortality burden attributable to CFPPT-generated PM2.5 in 2025. RESULTS: The estimated annual PM2.5 increments ranged from 0.004 µg/m3 (Taitung County) to 0.28 µg/m3 (Hsinchu County) due to the Shenao CFPPT. The total and premature deaths attributable to PM2.5 from Shenao CFPPT operation in Taiwan during 2025-2040 would be 576 (95% confidence interval [CI]: 537-619) and 145 (95% CI: 136-155), respectively. Notably, we estimated 198 (95% CI: 169-234) deaths and 58 (95% CI: 51-66) premature deaths, respectively, in New Taipei City, which accounted for over a quarter of the total deaths. Overall, the mortality rate attributable to the Shenao CFPPT in Taiwan was 6 per 10,000. CONCLUSION: A scientific approach should be adopted for assessing the impacts of CFPPT operation on population health, which can serve as a valuable policymaking reference for the government.

Modelling the effect of discontinuing universal Bacillus Calmette-Guérin vaccination in an intermediate tuberculosis burden setting.

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination is a widely-used public health intervention for tuberculosis (TB) control. In Taiwan, like other intermediate TB burden settings, steadily declining TB incidence raises important questions on whether universal BCG vaccination should be discontinued. Recent surveys on adverse events following immunisation, such as BCG-induced osteomyelitis/osteitis, also suggest a need to re-evaluate the vaccination programme. METHODS: We developed an age-structured transmission dynamic model, calibrated to population demography and age-specific TB notification rates in Taiwan. We adopted 'weak-protection' and 'strong-protection' scenarios, representing a range of characteristics including the duration of BCG protection and vaccine efficacies against TB infection and progression. We estimated averted disability-adjusted life years (DALYs) and incremental costs over 10 years after discontinuing universal BCG vaccination in 2018, 2035, and 2050. We also examined the potential impact of 'surveillance-guided' discontinuation, triggered once notification rates fall to a given threshold. RESULTS: In the weak-protection scenario, discontinuing BCG would result in 2.8 (95% uncertainty range: 2.3, 3.1) additional notified TB cases and -4.1 (-7.7, 0.8) net averted DALYs over 2018-2027. In the strong-protection scenario, 82.9 (72.6, 91.6) additional cases and -402.7 (-506.6, -301.2) averted DALYs would be reported, suggesting a robustly negative health impact. However, in this vaccine scenario, there could be an overall health benefit if BCG is discontinued once TB notification falls below 5 per 100,000 population. The most influential vaccine characteristic for the net health impact is the vaccine efficacy against progression to pulmonary TB. In financial terms, the eliminated cost of the vaccination programme substantially outweighed the incremental cost for TB treatment regardless of BCG protection. CONCLUSIONS: BCG discontinuation may be warranted in intermediate burden settings, depending on the quality of vaccine protection, and the potential for refocusing on other TB control activities for earlier detection and treatment.

Adult mortality of diseases and injuries attributable to selected metabolic, lifestyle, environmental, and infectious risk factors in Taiwan: a comparative risk assessment.

BACKGROUND: To facilitate priority-setting in health policymaking, we compiled the best available information to estimate the adult mortality (>30 years) burden attributable to 13 metabolic, lifestyle, infectious, and environmental risk factors in Taiwan. METHODS: We obtained data on risk factor exposure from nationally representative health surveys, cause-specific mortality from the National Death Registry, and relative risks from epidemiological studies and meta-analyses. We applied the comparative risk assessment framework to estimate mortality burden attributable to individual risk factors or risk factor clusters. RESULTS: In 2009, high blood glucose accounted for 14,900 deaths (95% UI: 11,850-17,960), or 10.4% of all deaths in that year. It was followed by tobacco smoking (13,340 deaths, 95% UI: 10,330-16,450), high blood pressure (11,190 deaths, 95% UI: 8,190-14,190), ambient particulate matter pollution (8,600 deaths, 95% UI: 7,370-9,840), and dietary risks (high sodium intake and low intake of fruits and vegetables, 7,890 deaths, 95% UI: 5,970-9,810). Overweight-obesity and physical inactivity accounted for 7,620 deaths (95% UI: 6,040-9,190), and 7,400 deaths (95% UI: 6,670-8,130), respectively. The cardiometabolic risk factors of high blood pressure, high blood glucose, high cholesterol, and overweight-obesity jointly accounted for 12,120 deaths (95% UI: 11,220-13,020) from cardiovascular diseases. For domestic risk factors, infections from hepatitis B virus (HBV) and hepatitis C virus (HCV) were responsible for 6,300 deaths (95% UI: 5,610-6,980) and 3,170 deaths (95% UI: 1,860-4,490), respectively, and betel nut use was associated with 1,780 deaths from oral, laryngeal, and esophageal cancer (95% UI: 1,190-2,360). The leading risk factors for years of life lost were similar, but the impact of tobacco smoking and alcohol use became larger because the attributable deaths from these risk factors occurred among young adults aged less than 60 years. CONCLUSIONS: High blood glucose, tobacco smoking, and high blood pressure are the major risk factors for deaths from diseases and injuries among Taiwanese adults. A large number of years of life would be gained if the 13 modifiable risk factors could be removed or reduced to the optimal level.

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis.

Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis). This poses several challenges similar to those encountered in the pre-chemotherapy era, including the inability to cure tuberculosis, high mortality, and the need for alternative methods to prevent disease transmission. This phenomenon mirrors the worldwide increase in antimicrobial resistance and the emergence of other MDR pathogens, such as malaria, HIV, and Gram-negative bacteria. MDR and XDR tuberculosis are associated with high morbidity and substantial mortality, are a threat to health-care workers, prohibitively expensive to treat, and are therefore a serious public health problem. In this Commission, we examine several aspects of drug-resistant tuberculosis. The traditional view that acquired resistance to antituberculous drugs is driven by poor compliance and programmatic failure is now being questioned, and several lines of evidence suggest that alternative mechanisms-including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions-are likely crucial to the pathogenesis of drug-resistant tuberculosis. These factors have implications for the design of new interventions, drug delivery and dosing mechanisms, and public health policy. We discuss epidemiology and transmission dynamics, including new insights into the fundamental biology of transmission, and we review the utility of newer diagnostic tools, including molecular tests and next-generation whole-genome sequencing, and their potential for clinical effectiveness. Relevant research priorities are highlighted, including optimal medical and surgical management, the role of newer and repurposed drugs (including bedaquiline, delamanid, and linezolid), pharmacokinetic and pharmacodynamic considerations, preventive strategies (such as prophylaxis in MDR and XDR contacts), palliative and patient-orientated care aspects, and medicolegal and ethical issues.

Burden of disease attributable to ambient fine particulate matter exposure in Taiwan.

BACKGROUND/PURPOSE: There is compelling epidemiological evidence that links air pollution to increased risk of mortality from cardiopulmonary disease and lung cancer. We quantified the burden of mortality attributable to ambient fine particulate matter (PM2.5) among the Taiwanese population in 2014 at the national and subnational levels. METHODS: Subnational PM2.5 exposure levels were obtained from Taiwan Air Quality Monitoring Network. Relative risks were derived from a previously developed exposure-response model. Population attributable fraction for cause-specific mortality was estimated at the county level using the estimated ambient PM2.5 concentrations and the relative risk functions. RESULTS: In 2014, PM2.5 accounted for 6282 deaths [95% confidence interval (CI), 5716-6847], from ischemic heart disease (2244 deaths; 95% CI, 2015-2473), stroke (2140 deaths; 95% CI, 1760-2520), lung cancer (1252 deaths; 95% CI, 995-1509), and chronic obstructive pulmonary disease (645 deaths; 95% CI, 418-872). Nationally, the population attributable mortality fraction of PM2.5 for the four disease causes was 18.6% (95% CI, 16.9-20.3%). Substantial geographic variation in PM2.5 attributable mortality fraction was found; the percentage of deaths attributable to PM2.5 ranged from 8.7% in Hualian County to 21.8% in Yunlin County. In terms of absolute number of deaths, New Taipei and Kaohsiung cities had the largest number of deaths associated with PM2.5 (874 and 829 deaths, respectively) among all cities and counties. CONCLUSION: Ambient PM2.5 pollution is a major mortality risk factor in Taiwan. Aggressive and multisectorial intervention strategies are urgently needed to bring down the impact of air pollution on environment and health.

Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models.

BACKGROUND: The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. METHODS: We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016-35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice. FINDINGS: Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective. INTERPRETATION: Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary. FUNDING: Bill & Melinda Gates Foundation.

Health system delay among patients with tuberculosis in Taiwan: 2003-2010.

BACKGROUND: Taiwan has integrated the previous vertical tuberculosis (TB) control system into the general health care system. With the phase out of the specialized TB care system and the declining TB incidence, it is likely that clinical workers become less familiar with the presentation of TB, resulting in delay in TB diagnosis and treatment. METHODS: We used the detailed information of health care visits in the Taiwan National Health Insurance database to analyze the temporal pattern of the health system delay (HSD) among 3,117 patients with TB between 2003 and 2010. RESULTS: The median HSD was 29 days (interquartile range 5-73 days), and the median delay increased from 26 days in 2003 to 33.5 days in 2008, thereafter slightly decreased to 32 days in 2010. Patient factors associated with a longer HSD included: aged 45-64 and ≧65 years (as compared to aged <30 years); females (as compared to males); an initial visit as an outpatient (as compared to an inpatient). Provider factors were an initial visit to a provider not specialized in TB (as compared to a TB-related provider), to a primary care clinic or to a medical center (as compared to a district hospital), and in Central region, Northern region, KaoPing region, Southern region and Taipei region (as compared to in Eastern region). Longer distances from the point of initial visit to that of treatment were associated with longer HSD. Patients who switched among different levels or different types of medical care services during their illness exhibited the longest HSD. CONCLUSIONS: In countries where the TB care systems are being restructured from a vertical to a horizontal system, it is critical to monitor HSD and be aware of its increase. The potential increase in the HSD from 2003 to 2008 observed in this study is concerning and the decline of HSD after 2008 might be attributed to the launch of contact investigation. Our results call for actions to improve the efficiency of TB diagnosis in the health care system and to increase the awareness of TB among physicians and the general public.

Impact of active screening for methicillin-resistant Staphylococcus aureus (MRSA) and decolonization on MRSA infections, mortality and medical cost: a quasi-experimental study in surgical intensive care unit.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading pathogen of healthcare-associated infections in intensive care units (ICUs). Prior studies have shown that decolonization of MRSA carriers is an effective method to reduce MRSA infections in ICU patients. However, there is currently a lack of data on its effect on mortality and medical cost. METHODS: Using a quasi-experimental, interrupted time-series design with re-introduction of intervention, we evaluated the impact of active screening and decolonization on MRSA infections, mortality and medical costs in the surgical ICU of a university hospital in Taiwan. Regression models were used to adjust for effects of confounding variables. RESULTS: MRSA infection rate decreased from 3.58 (baseline) to 0.42‰ (intervention period) (P <0.05), re-surged to 2.21‰ (interruption period) and decreased to 0.18‰ (re-introduction of intervention period) (P <0.05). Patients admitted to the surgical ICU during the intervention periods had a lower in-hospital mortality (13.5% (155 out of 1,147) versus 16.6% (203 out of 1,226), P = 0.038). After adjusting for effects of confounding variables, the active screening and decolonization program was independently associated with a decrease in in-hospital MRSA infections (adjusted odds ratio: 0.3; 95% CI: 0.1 to 0.8) and 90-day mortality (adjusted hazard ratio: 0.8; 95% CI: 0.7 to 0.99). Cost analysis showed that $22 medical costs can be saved for every $1 spent on the intervention. CONCLUSIONS: Active screening for MRSA and decolonization in ICU settings is associated with a decrease in MRSA infections, mortality and medical cost.

Assessment of the patient, health system, and population effects of Xpert MTB/RIF and alternative diagnostics for tuberculosis in Tanzania: an integrated modelling approach.

BACKGROUND: Several promising new diagnostic methods and algorithms for tuberculosis have been endorsed by WHO. National tuberculosis programmes now face the decision on which methods to implement and where to place them in the diagnostic algorithm. METHODS: We used an integrated model to assess the effects of different algorithms of Xpert MTB/RIF and light-emitting diode (LED) fluorescence microscopy in Tanzania. To understand the effects of new diagnostics from the patient, health system, and population perspective, the model incorporated and linked a detailed operational component and a transmission component. The model was designed to represent the operational and epidemiological context of Tanzania and was used to compare the effects and cost-effectiveness of different diagnostic options. FINDINGS: Among the diagnostic options considered, we identified three strategies as cost effective in Tanzania. Full scale-up of Xpert would have the greatest population-level effect with the highest incremental cost: 346 000 disability-adjusted life-years (DALYs) averted with an additional cost of US$36·9 million over 10 years. The incremental cost-effectiveness ratio (ICER) of Xpert scale-up ($169 per DALY averted, 95% credible interval [CrI] 104-265) is below the willingness-to-pay threshold ($599) for Tanzania. Same-day LED fluorescence microscopy is the next most effective strategy with an ICER of $45 (95% CrI 25-74), followed by LED fluorescence microscopy with an ICER of $29 (6-59). Compared with same-day LED fluorescence microscopy and Xpert full rollout, targeted use of Xpert in presumptive tuberculosis cases with HIV infection, either as an initial diagnostic test or as a follow-on test to microscopy, would produce DALY gains at a higher incremental cost and therefore is dominated in the context of Tanzania. INTERPRETATION: For Tanzania, this integrated modelling approach predicts that full rollout of Xpert is a cost-effective option for tuberculosis diagnosis and has the potential to substantially reduce the national tuberculosis burden. It also estimates the substantial level of funding that will need to be mobilised to translate this into clinical practice. This approach could be adapted and replicated in other developing countries to inform rational health policy formulation.

Population health impact and cost-effectiveness of tuberculosis diagnosis with Xpert MTB/RIF: a dynamic simulation and economic evaluation.

BACKGROUND: The Xpert MTB/RIF test enables rapid detection of tuberculosis (TB) and rifampicin resistance. The World Health Organization recommends Xpert for initial diagnosis in individuals suspected of having multidrug-resistant TB (MDR-TB) or HIV-associated TB, and many countries are moving quickly toward adopting Xpert. As roll-out proceeds, it is essential to understand the potential health impact and cost-effectiveness of diagnostic strategies based on Xpert. METHODS AND FINDINGS: We evaluated potential health and economic consequences of implementing Xpert in five southern African countries--Botswana, Lesotho, Namibia, South Africa, and Swaziland--where drug resistance and TB-HIV coinfection are prevalent. Using a calibrated, dynamic mathematical model, we compared the status quo diagnostic algorithm, emphasizing sputum smear, against an algorithm incorporating Xpert for initial diagnosis. Results were projected over 10- and 20-y time periods starting from 2012. Compared to status quo, implementation of Xpert would avert 132,000 (95% CI: 55,000-284,000) TB cases and 182,000 (97,000-302,000) TB deaths in southern Africa over the 10 y following introduction, and would reduce prevalence by 28% (14%-40%) by 2022, with more modest reductions in incidence. Health system costs are projected to increase substantially with Xpert, by US$460 million (294-699 million) over 10 y. Antiretroviral therapy for HIV represents a substantial fraction of these additional costs, because of improved survival in TB/HIV-infected populations through better TB case-finding and treatment. Costs for treating MDR-TB are also expected to rise significantly with Xpert scale-up. Relative to status quo, Xpert has an estimated cost-effectiveness of US$959 (633-1,485) per disability-adjusted life-year averted over 10 y. Across countries, cost-effectiveness ratios ranged from US$792 (482-1,785) in Swaziland to US$1,257 (767-2,276) in Botswana. Assessing outcomes over a 10-y period focuses on the near-term consequences of Xpert adoption, but the cost-effectiveness results are conservative, with cost-effectiveness ratios assessed over a 20-y time horizon approximately 20% lower than the 10-y values. CONCLUSIONS: Introduction of Xpert could substantially change TB morbidity and mortality through improved case-finding and treatment, with more limited impact on long-term transmission dynamics. Despite extant uncertainty about TB natural history and intervention impact in southern Africa, adoption of Xpert evidently offers reasonable value for its cost, based on conventional benchmarks for cost-effectiveness. However, the additional financial burden would be substantial, including significant increases in costs for treating HIV and MDR-TB. Given the fundamental influence of HIV on TB dynamics and intervention costs, care should be taken when interpreting the results of this analysis outside of settings with high HIV prevalence.

Modelling the impacts of new diagnostic tools for tuberculosis in developing countries to enhance policy decisions.

The introduction and scale-up of new tools for the diagnosis of Tuberculosis (TB) in developing countries has the potential to make a huge difference to the lives of millions of people living in poverty. To achieve this, policy makers need the information to make the right decisions about which new tools to implement and where in the diagnostic algorithm to apply them most effectively. These decisions are difficult as the new tools are often expensive to implement and use, and the health system and patient impacts uncertain, particularly in developing countries where there is a high burden of TB. The authors demonstrate that a discrete event simulation model could play a significant part in improving and informing these decisions. The feasibility of linking the discrete event simulation to a dynamic epidemiology model is also explored in order to take account of longer term impacts on the incidence of TB. Results from two diagnostic districts in Tanzania are used to illustrate how the approach could be used to improve decisions.