Effectiveness and cost-effectiveness of community-based directly observed treatment (DOT) versus health facility-based DOT of tuberculosis in Africa: protocol for a systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) remains a significant global health challenge, especially prevalent in the WHO African region. The WHO's End TB Strategy emphasises effective treatment approaches such as directly observed therapy (DOT), yet the optimal implementation of DOT, whether through health facility-based (HF DOT) or community-based (CB DOT) approaches, remains uncertain. OBJECTIVE: To conduct a systematic comparison of the effectiveness and cost-effectiveness of Community-Based Directly Observed Treatment (CB DOT) versus Health Facility-Based Directly Observed Treatment (HF DOT) for tuberculosis (TB) treatment in African settings. METHODS: We will conduct a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search PubMed, Embase, Web of Science, Scopus and the Cochrane Library for articles published up to 30 March 2023, without date restrictions. Eligible studies must be full economic evaluations conducted in African countries, comparing CB DOT to HF DOT regarding treatment outcomes and costs. Exclusion criteria include non-English, non-peer-reviewed or studies lacking caregiver involvement in CB DOT, health facility-based DOT comparison, direct comparability between CB DOT and HF DOT, significant selection bias or non-economic evaluations. Data extraction will be performed independently by reviewers, and meta-analyses will use STATA software. To pool the data, a random-effect model will be applied, and quality assessment of the studies will be conducted. ETHICS AND DISSEMINATION: Ethical approval is not required as the study will use previously published articles available publicly. Findings will be presented at international and national conferences and published in open-access, peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42023443260.

Impact of an innovative bundled payment to TB health care providers in China: an economic simulation analysis.

BACKGROUND: Tuberculosis is the second most deadly infectious disease after COVID-19 and the 13th leading cause of death worldwide. Among the 30 countries with a high burden of TB, China ranks third in the estimated number of TB cases. China is in the top four of 75 countries with a deficit in funding for TB strategic plans. To reduce costs and improve the effectiveness of TB treatment in China, the NHSA developed an innovative BP method. This study aimed to simulate the effects of this payment approach on different stakeholders, reduce the economic burden on TB patients, improve the quality of medical services, facilitate policy optimization, and offer a model for health care payment reforms that can be referenced by other regions throughout the world. METHODS: We developed a simulation model based on a decision tree analysis to project the expected effects of the payment method on the potential financial impacts on different stakeholders. Our analysis mainly focused on comparing changes in health care costs before and after receiving BPs for TB patients with Medicare in the pilot areas. The data that were used for the analysis included the TB service claim records for 2019-2021 from the health insurance agency, TB prevalence data from the local Centre for Disease Control, and health care facilities' revenue and expenditure data from the Statistic Yearbook. A Monte Carlo randomized simulation model was used to estimate the results. RESULTS: After adopting the innovative BP method, for each TB patient per year, the total annual expenditure was estimated to decrease from $2,523.28 to $2,088.89, which is a reduction of $434.39 (17.22%). The TB patient out-of-pocket expenditure was expected to decrease from $1,249.02 to $1,034.00, which is a reduction of $215.02 (17.22%). The health care provider's revenue decreased from $2,523.28 to $2,308.26, but the health care provider/institution's revenue-expenditure ratio increased from -6.09% to 9.50%. CONCLUSIONS: This study highlights the potential of BPs to improve medical outcomes and control the costs associated with TB treatment. It demonstrates its feasibility and advantages in enhancing the coordination and sustainability of medical services, thus offering valuable insights for global health care payment reform.

Economic implications of novel regimens for tuberculosis treatment in three high-burden countries: a modelling analysis.

BACKGROUND: With numerous trials investigating novel drug combinations to treat tuberculosis, we aimed to evaluate the extent to which future improvements in tuberculosis treatment regimens could offset potential increases in drug costs. METHODS: In this modelling analysis, we used an ingredients-based approach to estimate prices at which novel regimens for rifampin-susceptible and rifampin-resistant tuberculosis treatment would be cost-neutral or cost-effective compared with standards of care in India, the Philippines, and South Africa. We modelled regimens meeting targets set in the WHO's 2023 Target Regimen Profiles (TRPs). Our decision-analytical model tracked cohorts of adults initiating rifampin-susceptible or rifampin-resistant tuberculosis treatment, simulating their health outcomes and costs accumulated during and following treatment under standard-of-care and novel regimen scenarios. Price thresholds included short-term cost-neutrality (considering only savings accrued during treatment), medium-term cost-neutrality (additionally considering savings from averted retreatments and secondary cases), and cost-effectiveness (incorporating willingness-to-pay for improved health outcomes). FINDINGS: Total medium-term costs per person treated using standard-of-care regimens were estimated at US$450 (95% uncertainty interval 310-630) in India, $560 (350-860) in the Philippines, and $730 (530-1090) in South Africa for rifampin-susceptible tuberculosis (current drug costs $46) and $2100 (1590-2810) in India, $2610 (2090-3280) in the Philippines, and $3790 (3090-4630) in South Africa for rifampin-resistant tuberculosis (current drug costs $432). A rifampin-susceptible tuberculosis regimen meeting the optimal targets defined in the TRPs could be cost-neutral in the short term at drug costs of $140 (90-210) per full course in India, $230 (130-380) in the Philippines, and $280 (180-460) in South Africa. For rifampin-resistant tuberculosis, short-term cost-neutral thresholds were higher with $930 (720-1230) in India, $1180 (980-1430) in the Philippines, and $1480 (1230-1780) in South Africa. Medium-term cost-neutral prices were approximately $50-100 higher than short-term cost-neutral prices for rifampin-susceptible tuberculosis and $250-550 higher for rifampin-resistant tuberculosis. Health system cost-neutral prices that excluded patient-borne costs were 45-70% lower (rifampin-susceptible regimens) and 15-50% lower (rifampin-resistant regimens) than the cost-neutral prices that included patient costs. Cost-effective prices were substantially higher. Shorter duration was the most important driver of medium-term savings with novel regimens, followed by ease of adherence. INTERPRETATION: Improved tuberculosis regimens, particularly shorter regimens or those that facilitate better adherence, could reduce overall costs, potentially offsetting higher prices. FUNDING: WHO.

Catastrophic costs incurred by tuberculosis affected households from Thailand's first national tuberculosis patient cost survey.

Tuberculosis (TB) causes an economic impact on the patients and their households. Although Thailand has expanded the national health benefit package for TB treatment, there was no data on out-of-pocket payments and income losses due to TB from patients and their household perspectives. This national TB patient cost survey was conducted to examine the TB-related economic burden, and assess the proportion of TB patients and their households facing catastrophic total costs because of TB disease. A cross-sectional TB patient cost survey was employed following WHO methods. Structured interviews with a paper-based questionnaire were conducted from October 2019 to July 2021. Both direct and indirect costs incurred from the patient and their household perspective were valued in 2021 and estimated throughout pre- and post-TB diagnosis episodes. We assessed the proportion of TB-affected households facing costs > 20% of household expenditure due to TB. We analyzed 1400 patients including 1382 TB (first-line treatment) and 18 drug-resistant TB patients (DR-TB). The mean total costs per TB episode for all study participants were 903 USD (95% confident interval; CI 771-1034 USD). Of these, total direct non-medical costs were the highest costs (mean, 402 USD, and 95%CI 334-470 USD) incurred per TB-affected household followed by total indirect costs (mean, 393 USD, and 95%CI 315-472 USD) and total direct medical costs (mean, 107 USD, and 95%CI 81-133 USD, respectively. The proportion of TB-affected households facing catastrophic costs was 29.5% (95%CI 25.1-34.0%) for TB (first-line), 61.1% (95%CI 29.6-88.1%) for DR-TB and 29.9% (95%CI 25.6-34.4%) overall. This first national survey highlighted the economic burden on TB-affected households. Travel, food/nutritional supplementation, and indirect costs contribute to a high proportion of catastrophic total costs. These suggest the need to enhance financial and social protection mechanisms to mitigate the financial burden of TB-affected households.

A systematic review of economic evaluations of pharmacological treatments for active tuberculosis.

Objectives: The continuing spread of tuberculosis (TB) worldwide, especially drug-resistant TB, poses a major challenge to healthcare systems globally. Addressing this requires appraising the cost effectiveness of existing pharmacological interventions against TB to identify key drivers of cost effectiveness and value and guide pharmaceutical innovation and novel drug regimen development. Methods: Studies were identified from a search of six database: MEDLINE MEDLINE-In Process, MEDLINE Epub Ahead of Print, EMBASE, Cochrane Database of Systematic Reviews, and Econlit in July 2022. Two reviewers independently assessed all identified studies and reports using pre-defined inclusion/exclusion criteria. Study methodological quality was assessed, data were extracted in standard tables, and results were narratively synthesized. Results: Overall, 991 studies and 53 HTA reports were identified with 20 studies and 3 HTA reports meeting the inclusion criteria. Quality assessment of the 20 studies identified 4 with minor limitations, while the remainder were assessed as having potentially or very serious limitations. Sixteen studies conducted cost-utility analyses, 6 conducted cost-effectiveness analyses, and 2 conducted cost-comparison analyses with some studies performing multiple analyses. The majority (n = 16) were model-based. Eleven studies analyzed the cost-effectiveness of bedaquiline, 6 compared shorter to longer/standard duration regimens, 2 assessed ethambutol, and 1 assessed delamanid. Key drivers of cost effectiveness were drug costs, the number of TB cases, the portion of cases with sputum culture conversion, treatment delivery costs, and treatment efficacy. Common value elements considered included adverse events, drug resistance, and improving treatment adherence. Conclusion: Our results suggest that out of the pharmacological treatments assessed, bedaquiline is likely a cost-effective addition to existing treatment regimens/background treatment regimens, while ethambutol is not likely to be. Newer shorter regimens, even if more costly, seem to be more cost-effective compared to longer regimens. These results illustrate the limited number of novel cost-effective pharmacological interventions and highlight a need to develop new drugs/regimens against TB to overcome resistance, taking into account the key drivers of cost effectiveness and other value attributes identified from this review.

Analysis of Health-Related Quality of Life and Incurred Costs Among Human Immunodeficiency Virus, Tuberculosis, and Tuberculosis/HIV Coinfected Outpatients in Indonesia.

OBJECTIVES: A growing interest in healthcare costs and patients' health-related quality of life (HRQoL) exists in the context of the increasing importance of health technology assessment in countries with high numbers of the HIV and tuberculosis (TB) patient populations, such as Indonesia. This study aimed to analyze the HRQoL and out-of-pocket (OOP) costs of HIV, TB, and TB/HIV coinfected participants in a city in Indonesia with a high prevalence of HIV and TB. METHODS: A cross-sectional survey was conducted in the voluntary counseling and testing and lung clinics of Bekasi City Public Hospital (Indonesia) from January to March 2018. Patients' HRQoL was measured using the EQ-5D-5L questionnaire, whereas OOP costs were extracted from a semistructured questionnaire. RESULTS: Of the 460 eligible participants, 82% resided in the city, 48% of them were married, and their median age was 34 years. Less than half were insured, and more than half had no source of income. The median values of health utilities for participants with HIV, TB, and TB/HIV were perceived as potentially high (1.0, 0.9, and 0.8, respectively). The TB/HIV coinfected outpatients had the highest OOP costs (US$94.5), with the largest contribution coming from direct medical OOP expenditures. Taking loans from family members was adopted as a financial strategy to overcome inadequate household incomes and high treatment costs. CONCLUSION: This study suggests that TB/HIV coinfection potentially lowers HRQoL and increases healthcare costs and the need for economic analysis to underpin cost-effective treatment in such patients.

Assessment of the Global Fund-supported procurement and supply chain reforms at the Ethiopian Pharmaceuticals Supply Agency: a mixed-methods study.

OBJECTIVE: The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund) partnered with the Ethiopian Pharmaceutical Supply Agency (EPSA) in 2018-2019 to reform procurement and supply chain management (PSCM) procedures within the Ethiopian healthcare system. This assessment sought to determine the impact of the reforms and document the lessons learnt. DESIGN: Mixed-methods study incorporating qualitative and quantitative analysis. Purposive and snowballing sampling techniques were applied for the qualitative methods, and the data collected was transcribed in full and subjected to thematic content analysis. Descriptive analysis was applied to quantitative data. SETTING: The study was based in Ethiopia and focused on the EPSA operations nationally between 2017 and 2021. PARTICIPANTS: Twenty-five Ethiopian healthcare decision-makers and health workers. INTERVENTION: Global Fund training programme for health workers and infrastructural improvements OUTCOMES: Operational and financial measures for healthcare PSCM. RESULTS: The availability of antiretrovirals, tuberculosis and malaria medicines, and other related commodities, remained consistently high. Line fill rate and forecast accuracy were average. Between 2018 and 2021, procurement lead times for HIV and malaria-related orders reduced by 43.0% relative to other commodities that reported an increase. Many interview respondents recognised the important role of the Global Fund support in improving the performance of EPSA and provided specific attributions to the observed successes. However, they were also clear that more needs to be done in specific critical areas such as financing, strategic reorganisation, data and information management systems. CONCLUSION: The Global Fund-supported initiatives led to improvements in the EPSA performance, despite several persistent challenges. To sustain and secure the gains achieved so far through Global Fund support and make progress, it is important that various stakeholders, including the government and the donor community, work together to support EPSA in delivering on its core mandate within the Ethiopian health system.

A spatial analysis of TB cases and abnormal X-rays detected through active case-finding in Karachi, Pakistan.

Tuberculosis (TB) is the leading cause of avoidable deaths from an infectious disease globally and a large of number of people who develop TB each year remain undiagnosed. Active case-finding has been recommended by the World Health Organization to bridge the case-detection gap for TB in high burden countries. However, concerns remain regarding their yield and cost-effectiveness. Data from mobile chest X-ray (CXR) supported active case-finding community camps conducted in Karachi, Pakistan from July 2018 to March 2020 was retrospectively analyzed. Frequency analysis was carried out at the camp-level and outcomes of interest for the spatial analyses were mycobacterium TB positivity (MTB+) and X-ray abnormality rates. The Global Moran's I statistic was used to test for spatial autocorrelation for MTB+ and abnormal X-rays within Union Councils (UCs) in Karachi. A total of 1161 (78.1%) camps yielded no MTB+ cases, 246 (16.5%) camps yielded 1 MTB+, 52 (3.5%) camps yielded 2 MTB+ and 27 (1.8%) yielded 3 or more MTB+. A total of 79 (5.3%) camps accounted for 193 (44.0%) of MTB+ cases detected. Statistically significant clustering for MTB positivity (Global Moran's I: 0.09) and abnormal chest X-rays (Global Moran's I: 0.36) rates was identified within UCs in Karachi. Clustering of UCs with high MTB positivity were identified in Karachi West district. Statistically significant spatial variation was identified in yield of bacteriologically positive TB cases and in abnormal CXR through active case-finding in Karachi. Cost-effectiveness of active case-finding programs can be improved by identifying and focusing interventions in hotspots and avoiding locations with no known TB cases reported through routine surveillance.

Cost of TB services: approach and summary findings of a multi-country study (Value TB).

BACKGROUND: There are currently large gaps in unit cost data for TB, and substantial variation in the quality and methods of unit cost estimates. Uncertainties remain about sample size, range and comprehensiveness of cost data collection for different purposes. We present the methods and results of a project implemented in Kenya, Ethiopia, India, The Philippines and Georgia to estimate unit costs of TB services, focusing on findings most relevant to these remaining methodological challenges.METHODS: We estimated financial and economic unit costs, in close collaboration with national TB programmes. Gold standard methods included both top-down and bottom-up approaches to resource use measurement. Costs are presented in 2018 USD and local currency unit.RESULTS: Cost drivers of outputs varied by service and across countries, as did levels of capacity inefficiency. There was substantial variation in unit cost estimates for some interventions and high overhead costs were observed. Estimates were subject to sampling uncertainty, and some data gaps remain.CONCLUSION: This paper describes detailed methods for the largest TB costing effort to date, to inform prioritisation and planning for TB services. This study provides a strong baseline and some cost estimates may be extrapolated from this data; however, regular further studies of similar quality are needed to add estimates for remaining gaps, or to add new or changing services and interventions. Further research is needed on the best approach to extrapolation of cost data. Costing studies are best implemented as partnerships with policy makers to generate a community of mutual learning and capacity development.

How much does TB screening cost? A systematic review of economic evaluations.

BACKGROUND: Systematic screening for TB has been recommended as a method to control TB on a global level; however, this involves significant costs that place a burden on the health system.METHODS: We conducted a systematic review of the existing economic literature on systematic screening for TB to summarise costs, cost-effectiveness and affordability, and the key factors that influence costs and cost-effectiveness. Specific populations of interest included the general population, children and close contacts of TB patients.RESULTS: We identified 21 studies that provided both cost and outcome data on TB screening among the populations of interest. All were from low- and middle-income settings. Studies were heterogenous in the intervention, and included costs and reported outcomes. The incremental cost-effectiveness ratio (ICER) estimates ranged from USD281 to USD698 per disability-adjusted life-year (DALY) averted among the general population, USD619/DALY averted among children and USD372-3,718/DALY averted among close contacts.CONCLUSION: Prevalence of TB among targeted high-risk groups was identified across the majority of studies as a driver of cost-effectiveness. The heterogeneity of the included costs and outcomes across the economic literature for systematic screening suggests a need for standardisation of included cost components and key economic evaluation methods to improve comparability and generalisability of results.

Cost of TB services in the public and private sectors in Georgia (No 2).

BACKGROUND: Patient-centred care along with optimal financing of inpatient and outpatient services are the main priorities of the Georgia National TB Programme (NTP). This paper presents TB diagnostics and treatment unit cost, their comparison with NTP tariffs and how the study findings informed TB financing policy.METHODS: Top-down (TD) and bottom-up (BU) mean unit costs for TB interventions by episode of care were calculated. TD costs were compared with NTP tariffs, and variations in these and the unit costs cost composition between public and private facilities was assessed.RESULTS: Outpatient interventions costs exceeded NTP tariffs. Unit costs in private facilities were higher compared with public providers. There was very little difference between per-day costs for drug-susceptible treatment and NTP tariffs in case of inpatient services. Treatment day financing exceeded actual costs in the capital (public facility) for drug-resistant TB, and this was lower in the regions.CONCLUSION: Use of reliable unit costs for TB services at policy discussions led to a shift from per-day payment to a diagnosis-related group model in TB inpatient financing in 2020. A next step will be informing policy decisions on outpatient TB care financing to reduce the existing gap between funding and costs.

Cost of TB services in healthcare facilities in Kenya (No 3).

BACKGROUND: The reduction of Kenya´s TB burden requires improving resource allocation both to and within the National TB, Leprosy and Lung Disease Program (NTLD-P). We aimed to estimate the unit costs of TB services for budgeting by NTLD-P, and allocative efficiency analyses for future National Strategic Plan (NSP) costing.METHODS: We estimated costs of all TB interventions in a sample of 20 public and private health facilities from eight counties. We calculated national-level unit costs from a health provider´s perspective using bottom-up (BU) and top-down (TD) approaches for the financial year 2017-2018 using Microsoft Excel and STATA v16.RESULTS: The mean unit cost for passive case-finding (PCF) was respectively US$38 and US$60 using the BU and TD approaches. The unit BU and TD costs of a 6-month first-line treatment (FLT) course, including monitoring tests, was respectively US$135 and US$160, while those for adult drug-resistant TB (DR-TB) treatment was respectively US$3,230.28 and US$3,926.52 for the 9-month short regimen. Intervention costs highlighted variations between BU and TD approaches. Overall, TD costs were higher than BU, as these are able to capture more costs due to inefficiency (breaks/downtime/leave).CONCLUSION: The activity-based TB unit costs form a comprehensive cost database, and the costing process has built-in capacity within the NTLD-P and international TB research networks, which will inform future TB budgeting processes.

Active screening for tuberculosis in high-incidence Inuit communities in Canada: a cost-effectiveness analysis.

BACKGROUND: Active screening for tuberculosis (TB) involves systematic detection of previously undiagnosed TB disease or latent TB infection (LTBI). It may be an important step toward elimination of TB among Inuit in Canada. We aimed to evaluate the cost-effectiveness of community-wide active screening for TB infection and disease in 2 Inuit communities in Nunavik. METHODS: We incorporated screening data from the 2 communities into a decision analysis model. We predicted TB-related health outcomes over a 20-year time frame, beginning in 2019. We assessed the cost-effectiveness of active screening in the presence of varying outbreak frequency and intensity. We also considered scenarios involving variation in timing, impact and uptake of screening programs. RESULTS: Given a single large outbreak in 2019, we estimated that 1 round of active screening reduced TB disease by 13% (95% uncertainty range -3% to 27%) and was cost saving compared with no screening, over 20 years. In the presence of simulated large outbreaks every 3 years thereafter, a single round of active screening was cost saving, as was biennial active screening. Compared with a single round, we also determined that biennial active screening reduced TB disease by 59% (95% uncertainty range 52% to 63%) and was estimated to cost Can$6430 (95% uncertainty range -$29 131 to $13 658 in 2019 Can$) per additional active TB case prevented. With smaller outbreaks or improved rates of treatment initiation and completion for people with LTBI, we determined that biennial active screening remained reasonably cost-effective compared with no active screening. INTERPRETATION: Active screening is a potentially cost-saving approach to reducing disease burden in Inuit communities that have frequent TB outbreaks.

Health-Related Quality of Life of Tuberculosis Patients and the Role of Socioeconomic Factors: A Mixed-Method Study.

This study aims to assess tuberculosis (TB) patients' health-related quality of life (HRQoL) and to determine the relationship between HRQoL and the socioeconomic and health characteristics of patients. A mixed-method approach of explanatory sequential design is used in this study. Data were collected at 11 TB centers and two private clinics in Khyber Pakhtunkhwa, Pakistan. Quantitative data were collected through a standardized questionnaire (SF-36) of RAND organization from 269 pulmonary TB patients. Qualitative data were collected through 20 in-depth interviews, 15 Key Informant interviews, and a focus group discussion. The maximum score of SF-36 is 100, however, different aspects of HRQoL indicated that patients scored lowest in the role limitation physical (10.3) and emotional (11.2) categories, while the highest remained in the mental health (45.3) category. Patients of higher age, being female, low household income, and comorbidity decreased the HRQoL. Qualitative findings show that TB affected the patients' social functioning, vitality, and emotions. Moreover, poverty and low income, people living in Kacha Houses, family support, and the hate from family members and community are related to low HRQoL. In summary, TB has affected the Patients' HRQoL. TB program managers should pay attention to the nonmedication aspects of TB management. Financial support should be extended TB patients. This study calls for the urgent attention of the National Tuberculosis Program and policymakers, for an increased focus on patients' welfare programs.

Economic and modeling evidence for tuberculosis preventive therapy among people living with HIV: A systematic review and meta-analysis.

BACKGROUND: Human immunodeficiency virus (HIV) is the strongest known risk factor for tuberculosis (TB) through its impairment of T-cell immunity. Tuberculosis preventive treatment (TPT) is recommended for people living with HIV (PLHIV) by the World Health Organization, as it significantly reduces the risk of developing TB disease. We conducted a systematic review and meta-analysis of modeling studies to summarize projected costs, risks, benefits, and impacts of TPT use among PLHIV on TB-related outcomes. METHODS AND FINDINGS: We searched MEDLINE, Embase, and Web of Science from inception until December 31, 2020. Two reviewers independently screened titles, abstracts, and full texts; extracted data; and assessed quality. Extracted data were summarized using descriptive analysis. We performed quantile regression and random effects meta-analysis to describe trends in cost, effectiveness, and cost-effectiveness outcomes across studies and identified key determinants of these outcomes. Our search identified 6,615 titles; 61 full texts were included in the final review. Of the 61 included studies, 31 reported both cost and effectiveness outcomes. A total of 41 were set in low- and middle-income countries (LMICs), while 12 were set in high-income countries (HICs); 2 were set in both. Most studies considered isoniazid (INH)-based regimens 6 to 2 months long (n = 45), or longer than 12 months (n = 11). Model parameters and assumptions varied widely between studies. Despite this, all studies found that providing TPT to PLHIV was predicted to be effective at averting TB disease. No TPT regimen was substantially more effective at averting TB disease than any other. The cost of providing TPT and subsequent downstream costs (e.g. post-TPT health systems costs) were estimated to be less than $1,500 (2020 USD) per person in 85% of studies that reported cost outcomes (n = 36), regardless of study setting. All cost-effectiveness analyses concluded that providing TPT to PLHIV was potentially cost-effective compared to not providing TPT. In quantitative analyses, country income classification, consideration of antiretroviral therapy (ART) use, and TPT regimen use significantly impacted cost-effectiveness. Studies evaluating TPT in HICs suggested that TPT may be more effective at preventing TB disease than studies evaluating TPT in LMICs; pooled incremental net monetary benefit, given a willingness-to-pay threshold of country-level per capita gross domestic product (GDP), was $271 in LMICs (95% confidence interval [CI] -$81 to $622, p = 0.12) and was $2,568 in HICs (-$32,115 to $37,251, p = 0.52). Similarly, TPT appeared to be more effective at averting TB disease in HICs; pooled percent reduction in active TB incidence was 20% (13% to 27%, p < 0.001) in LMICs and 37% (-34% to 100%, p = 0.13) in HICs. Key limitations of this review included the heterogeneity of input parameters and assumptions from included studies, which limited pooling of effect estimates, inconsistent reporting of model parameters, which limited sample sizes of quantitative analyses, and database bias toward English publications. CONCLUSIONS: The body of literature related to modeling TPT among PLHIV is large and heterogeneous, making comparisons across studies difficult. Despite this variability, all studies in all settings concluded that providing TPT to PLHIV is potentially effective and cost-effective for preventing TB disease.

Costs and cost-effectiveness of a comprehensive tuberculosis case finding strategy in Zambia.

INTRODUCTION: Active-case finding (ACF) programs have an important role in addressing case detection gaps and halting tuberculosis (TB) transmission. Evidence is limited on the cost-effectiveness of ACF interventions, particularly on how their value is impacted by different operational, epidemiological and patient care-seeking patterns. METHODS: We evaluated the costs and cost-effectiveness of a combined facility and community-based ACF intervention in Zambia that utilized mobile chest X-ray with computer-aided reading/interpretation software and laboratory-based Xpert MTB/RIF testing. Programmatic costs (in 2018 US dollars) were assessed from the health system perspective using prospectively collected cost and operational data. Cost-effectiveness of the ACF intervention was assessed as the incremental cost per TB death averted over a five-year time horizon using a multi-stage Markov state-transition model reflecting patient symptom-associated care-seeking and TB care under ACF compared to passive care. RESULTS: Over 18 months of field operations, the ACF intervention costed $435 to diagnose and initiate treatment for one person with TB. After accounting for patient symptom-associated care-seeking patterns in Zambia, we estimate that this one-time ACF intervention would incrementally diagnose 407 (7,207 versus 6,800) TB patients and avert 502 (611 versus 1,113) TB-associated deaths compared to the status quo (passive case finding), at an incremental cost of $2,284 per death averted over the next five-year period. HIV/TB mortality rate, patient symptom-associated care-seeking probabilities in the absence of ACF, and the costs of ACF patient screening were key drivers of cost-effectiveness. CONCLUSIONS: A one-time comprehensive ACF intervention simultaneously operating in public health clinics and corresponding catchment communities can have important medium-term impact on case-finding and be cost-effective in Zambia. The value of such interventions increases if targeted to populations with high HIV/TB mortality, substantial barriers (both behavioral and physical) to care-seeking exist, and when ACF interventions can optimize screening by achieving operational efficiency.

Economic impact of tuberculosis mortality in 120 countries and the cost of not achieving the Sustainable Development Goals tuberculosis targets: a full-income analysis.

BACKGROUND: The tuberculosis targets for the UN Sustainable Development Goals (SDGs) call for a 90% reduction in tuberculosis deaths by 2030, compared with 2015, but meeting this target now seems highly improbable. To assess the economic impact of not meeting the target until 2045, we estimated full-income losses in 120 countries, including those due to excess deaths resulting from COVID-19-related disruptions to tuberculosis services, for the period 2020-50. METHODS: Annual mortality risk changes at each age in each year from 2020 to 2050 were estimated for 120 countries. This risk change was then converted to full-income risk by calculating a population-level mortality risk change and multiplying it by the value of a statistical life-year in each country and year. As a comparator, we assumed that current rates of tuberculosis continue to decline through the period of analysis. We calculated the full-income losses, and mean life expectancy losses per person, at birth and at age 35 years, under scenarios in which the SDG targets are met in 2030 and in 2045. We defined the cost of inaction as the difference in full-income losses and tuberculosis mortality between these two scenarios. FINDINGS: From 2020 to 2050, based on the current annual decrease in tuberculosis deaths of 2%, 31·8 million tuberculosis deaths (95% uncertainty interval 25·2 million-39·5 million) are estimated to occur, corresponding to an economic loss of US$17·5 trillion (14·9 trillion-20·4 trillion). If the SDG tuberculosis mortality target is met in 2030, 23·8 million tuberculosis deaths (18·9 million-29·5 million) and $13·1 trillion (11·2 trillion-15·3 trillion) in economic losses can be avoided. If the target is met in 2045, 18·1 million tuberculosis deaths (14·3 million-22·4 million) and $10·2 trillion (8·7 trillion-11·8 trillion) can be avoided. The cost of inaction of not meeting the SDG tuberculosis mortality target until 2045 (vs 2030) is, therefore, 5·7 million tuberculosis deaths (5·1 million-8·1 million) and $3·0 trillion (2·5 trillion-3·5 trillion) in economic losses. COVID-19-related disruptions add $290·3 billion (260·2 billion-570·1 billion) to this cost. INTERPRETATION: Failure to achieve the SDG tuberculosis mortality target by 2030 will lead to profound economic and health losses. The effects of delay will be greatest in sub-Saharan Africa. Affected countries, donor nations, and the private sector should redouble efforts to finance tuberculosis programmes and research because the economic dividend of such strategies is likely to be substantial. FUNDING: None.