Cost-consequence analysis of ambulatory clinic- and home-based multidrug-resistant tuberculosis management models in Eswatini.

BACKGROUND: We compared the cost-consequence of a home-based multidrug-resistant tuberculosis (MDR-TB) model of care, based on task-shifting of directly observed therapy (DOT) and MDR-TB injection administration to lay health workers, to a routine clinic-based strategy within an established national TB programme in Eswatini. METHODS: Data on costs and effects of the two ambulatory models of MDR-TB care was collected using documentary data and interviews in the Lubombo and Shiselweni regions of Eswatini. Health system, patient and caregiver costs were assessed in 2014 in US$ using standard methods. Cost-consequence was calculated as the cost per patient successfully treated. RESULTS: In the clinic-based and home-based models of care, respectively, a total of 96 and 106 MDR-TB patients were enrolled in 2014, with treatment success rates of 67.8% and 82.1%. Health system costs per patient treated were slightly lower in the home-based strategy (US$19 598) compared to the clinic-based model (US$20 007). The largest costs in both models were for inpatient care, administration of DOT and injectable treatment, and drugs. Costs incurred by patients and caregivers were considerably higher in the clinic-based model of care due to the higher direct travel costs to the nearest clinic to receive DOT and injections daily. In total, MDR patients in the clinic-based strategy incurred average costs of US$670 compared to US$275 for MDR-TB patients in the home-based model. MDR-TB patients in the home-based programme, where DOT and injections was provided in their homes, only incurred out-of-pocket travel expenses for monthly outpatient treatment monitoring visits averaging US$100. The cost per successfully treated patient was US$31 106 and US$24 157 in the clinic-based and home-based models of care, respectively. The analysis showed that, in addition to the health benefits, direct and indirect costs for patients and their caregivers were lower in the home-based care model. CONCLUSION: The home-based strategy used less resources and generated substantial health and economic benefits, particularly for patients and their caregivers, and decision makers can consider this approach as an alternative to expand and optimise MDR-TB control in resource-limited settings. Further research to understand the appropriate mix of treatment support components that are most important for optimal clinical and public health outcomes in the ambulatory home-based model of MDR-TB care is necessary.

Tuberculosis in people of Ukrainian origin in the European Union and the European Economic Area, 2019 to 2022.

Approximately five million Ukrainians were displaced to the EU/EEA following the Russian invasion of Ukraine. While tuberculosis (TB) notification rates per 100,000 Ukrainians in the EU/EEA remained stable, the number of notified TB cases in Ukrainians increased almost fourfold (mean 2019-2021: 201; 2022: 780). In 2022, 71% cases were notified in three countries, and almost 20% of drug-resistant TB cases were of Ukrainian origin. Targeted healthcare services for Ukrainians are vital for early diagnosis and treatment, and preventing transmission.

Multidrug-resistant tuberculosis: latest opinions on epidemiology, rapid diagnosis and management.

PURPOSE OF REVIEW: This review addresses the escalating global challenge of multidrug-resistant tuberculosis (MDR-TB) in Sub-Saharan Africa, with a focus on its complex comorbidity with HIV/AIDS. Emphasizing the urgency of the issue, the review aims to shed light on the unique healthcare landscape shaped by the convergence of high prevalence rates and intersecting complexities with HIV/AIDS in the region. RECENT FINDINGS: A notable increase in MDR-TB cases across Sub-Saharan Africa is attributed to challenges in timely diagnoses, treatment initiation, and patient treatment defaulting. The literature underscores the critical need for proactive measures to address diagnostic and treatment gaps associated with MDR-TB, particularly concerning its comorbidity with HIV/AIDS. SUMMARY: To effectively manage MDR-TB and its co-morbidity with HIV/AIDS, proactive screening programs are imperative. The review highlights the necessity of active follow-up strategies to ensure treatment adherence and reduce default rates, offering evidence-based insights for improved disease management in the region.

Global burden of MDR-TB and XDR-TB attributable to high fasting plasma glucose from 1990 to 2019: a retrospective analysis based on the global burden of disease study 2019.

PURPOSE: High fasting plasma glucose (HFPG) has been identified as a risk factor for drug-resistant tuberculosis incidence and mortality. However, the epidemic characteristics of HFPG-attributable multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) remain unclear. We aimed to analyze the global spatial patterns and temporal trends of HFPG-attributable MDR-TB and XDR-TB from 1990 to 2019. METHODS: Utilizing data from the Global Burden of Disease 2019 project, annual deaths and disability-adjusted life years (DALYs) of HFPG-attributable MDR-TB and XDR-TB were conducted from 1990 to 2019. Joinpoint regression was employed to quantify trends over time. RESULTS: From 1990 to 2019, the deaths and DALYs due to HFPG-attributable MDR-TB and XDR-TB globally showed an overall increasing trend, with a significant increase until 2003 to 2004, followed by a gradual decline or stability thereafter. The low sociodemographic index (SDI) region experienced the most significant increase over the past 30 years. Regionally, Sub-Saharan Africa, Central Asia and Oceania remained the highest burden. Furthermore, there was a sex and age disparity in the burden of HFPG-attributable MDR-TB and XDR-TB, with young males in the 25-34 age group experiencing higher mortality, DALYs burden and a faster increasing trend than females. Interestingly, an increasing trend followed by a stable or decreasing pattern was observed in the ASMR and ASDR of HFPG-attributable MDR-TB and XDR-TB with SDI increasing. CONCLUSION: The burden of HFPG-attributable MDR-TB and XDR-TB rose worldwide from 1990 to 2019. These findings emphasize the importance of routine bi-directional screening and integrated management for drug-resistant TB and diabetes.

Unsuccessful tuberculosis treatment outcomes across Brazil's geographical landscape before and during the COVID-19 pandemic: are we truly advancing toward the sustainable development/end TB goal?

BACKGROUND: Tuberculosis is one of the most significant infectious diseases for global public health. The reallocation of healthcare resources and the restrictions imposed by the COVID-19 pandemic have hindered access to TB diagnosis and treatment. Increases in unfavorable outcomes of the disease have been observed in Brazil. The objective of this study was to analyze the spatial distribution of unfavorable TB treatment outcomes in Brazil before and during the pandemic. METHODS: An ecological study with spatial analysis was conducted with all 5569 municipalities in Brazil. All reported cases of tuberculosis between January 2010 and December 2021, as well as reported cases of COVID-19 from February 2020 to December 2021, were included. The outcomes studied encompass loss to follow-up, drug-resistant tuberculosis, and death. The Getis Ord GI* technique was employed to assess spatial association, and the Kernel density estimator was used to identify areas with concentrated increases or decreases in outcomes. Bivariate Local Moran's I was used to examine the spatial association between outcomes and COVID-19 incidence. The study was approved by the Research Ethics Committee of Ribeirão Preto Nursing School, University of São Paulo. RESULTS: There were 134,394 cases of loss to follow-up, 10,270 cases of drug resistance, and 37,863 deaths. Clusters of high and low values were identified for all three outcomes, indicating significant changes in the spatial distribution patterns. Increases in concentrations were observed for lost to follow-up cases in the Southeast, while reductions occurred in the Northeast, South, and Midwest. Drug-resistant tuberculosis experienced an increase in the Southern and Southeastern regions and a decrease in the Northeast and South. TB-related deaths showed notable concentrations in the Midwest, Northeast, South, and Southeast. There was an increase in high occurrence clusters for deaths after 2020 and 2021 in the Northeast. CONCLUSIONS: The pandemic has brought additional challenges, emphasizing the importance of enhancing efforts and disease control strategies, prioritizing early identification, treatment adherence, and follow-up. This commitment is vital for achieving the goal of tuberculosis elimination.

Time to sputum culture conversion and its associated factors among drug-resistant tuberculosis patients: a systematic review and meta-analysis.

OBJECTIVE: We aimed to evaluate the sputum culture conversion time of DR-TB patients and its related factors. METHODS: PubMed, The Cochrane Library, Embase, CINAHL, Web of Science, CNKI, Wan Fang, CBM and VIP databases were electronically searched to collect studies on sputum culture conversion time in patients with DR-TB. Meta-analysis was performed by using the R 4.3.0 version and Stata 16 software. RESULTS: A total of 45 studies involving 17373 patients were included. Meta-analysis results showed that the pooled median time to sputum culture conversion was 68.57 days (IQR 61.01,76.12). The median time of sputum culture conversion in patients with drug-resistant tuberculosis was different in different WHO regions, countries with different levels of development and different treatment schemes. And female (aHR = 0.59,95%CI: s0.46,0.76), alcohol history (aHR = 0.70,95%CI:0.50,0.98), smoking history (aHR = 0.58,95%CI:0.38,0.88), history of SLD use (aHR = 0.64,95%CI:0.47,0.87), BMI < 18.5 kg/m2 (aHR = 0.69,95%CI:0.60,0.80), lung cavity (aHR = 0.70,95%CI:0.52,0.94), sputum smear grading at baseline (Positive) (aHR = 0.56,95%CI:0.36,0.87), (grade 1+) (aHR = 0.87,95%CI:0.77,0.99), (grade 2+) (aHR = 0.81,95%CI:0.69,0.95), (grade 3+) (aHR = 0.71,95%CI:0.61,0.84) were the related factor of sputum culture conversion time in patients with DR-TB. CONCLUSION: Patients with DR-TB in Europe or countries with high level of economic development have earlier sputum culture conversion, and the application of bedaquiline can make patients have shorter sputum culture conversion time. Female, alcohol history, smoking history, history of SLD use, BMI < 18.5 kg/m2, lung cavity, sputum smear grading at baseline (Positive, grade 1+, grade 2+, grade 3+) may be risk factors for longer sputum culture conversion time. This systematic review has been registered in PROSPERO, the registration number is CRD42023438746.

Global prevalence and burden of multidrug-resistant tuberculosis from 1990 to 2019.

BACKGROUND: Tuberculosis(TB) remains a pressing public health challenge, with multidrug-resistant tuberculosis (MDR-TB) emerging as a major threat. And healthcare authorities require reliable epidemiological evidence as a crucial reference to address this issue effectively. The aim was to offer a comprehensive epidemiological assessment of the global prevalence and burden of MDR-TB from 1990 to 2019. METHODS: Estimates and 95% uncertainty intervals (UIs) for the age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), age-standardized disability-adjusted life years rate (ASR of DALYs), and age-standardized death rate (ASDR) of MDR-TB were obtained from the Global Burden of Disease (GBD) 2019 database. The prevalence and burden of MDR-TB in 2019 were illustrated in the population and regional distribution. Temporal trends were analyzed by using Joinpoint regression analysis to calculate the annual percentage change (APC), average annual percentage change (AAPC) and its 95% confidence interval(CI). RESULTS: The estimates of the number of cases were 687,839(95% UIs: 365,512 to 1223,262), the ASPR were 8.26 per 100,000 (95%UIs: 4.61 to 15.20), the ASR of DALYs were 52.38 per 100,000 (95%UIs: 22.64 to 97.60) and the ASDR were 1.36 per 100,000 (95%UIs: 0.54 to 2.59) of MDR-TB at global in 2019. Substantial burden was observed in Africa and Southeast Asia. Males exhibited higher ASPR, ASR of DALYs, and ASDR than females across most age groups, with the burden of MDR-TB increasing with age. Additionally, significant increases were observed globally in the ASIR (AAPC = 5.8; 95%CI: 5.4 to 6.1; P < 0.001), ASPR (AAPC = 5.9; 95%CI: 5.4 to 6.4; P < 0.001), ASR of DALYs (AAPC = 4.6; 95%CI: 4.2 to 5.0; P < 0.001) and ASDR (AAPC = 4.4; 95%CI: 4.0 to 4.8; P < 0.001) of MDR-TB from 1990 to 2019. CONCLUSIONS: This study underscored the persistent threat of drug-resistant tuberculosis to public health. It is imperative that countries and organizations worldwide take immediate and concerted action to implement measures aimed at significantly reducing the burden of TB.

Financial burden of tuberculosis diagnosis and treatment for patients in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Despite the diagnosis and treatment of tuberculosis (TB) given free of charge in many high-burden countries, the costs that patients face in the cascade of care remain a major concern. Here, we aimed to investigate the financial burden of TB diagnosis and treatment for people with TB in Ethiopia. METHOD: For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase, and Cochrane Center for Clinical Trials from December 1 2022 to 31 June 2023 for articles reporting the cost of diagnosis and treatment for patients regardless of their age with all forms of TB in Ethiopia. Major study outcomes were catastrophic costs, direct (out-of-pocket) pre-diagnosis, medical cost, and post-diagnosis costs, indirect (income loss) costs, coping costs, and total costs. We have used a threshold of 20% to define catastrophic costs. We used random-effects meta-analyses to calculate summary estimates of costs. R-studio software was used for analysis. The study is registered with PROSPERO: CRD42023387687. RESULT: Twelve studies, with a total of 4792 patients with TB, were included in our analysis. At the 20% threshold of total expenses, 51% of patients (2301 participants from 5 studies, 95% CI: 36-65%, I2 = 97%) faced catastrophic costs due to bacteriologically confirmed drug-sensitive pulmonary TB. Private facility diagnosis, drug-resistance TB, TB-HIV co-infection, hospitalization, and occupation were found to be associated with catastrophic costs. Reduction in the total cost spent by the patients was associated with digital adherence interventions, community-based direct observed therapy, short-course MDR-TB treatment regimens, and active case-finding. Pre-diagnosis costs had a positive correlation with diagnosis delays and the number of facilities visited until diagnosis. Post-diagnosis costs had a positive correlation with rural residence and inpatient treatments. CONCLUSION: Irrespective of a national policy of free TB service, more than half of TB patients are suffering catastrophic costs due to drug-sensitive pulmonary TB in Ethiopia and most of the patients spend a lot of money during the pre-diagnosis period and intensive phase, but declined drastically over time. Active case-finding, digital adherence interventions, community-based treatment, and comprehensive health insurance coverage have the potential to minimize the financial burden of TB diagnosis and treatment.

Cost-effectiveness of improving patients' adherence to tuberculosis treatment in South Korea using discrete event simulation.

BACKGROUND: Poor adherence to tuberculosis (TB) treatment is an obstacle to controlling the disease. The Korean government's national TB control plan includes a program on adherence to TB treatment to manage patients with TB. This study aimed to assess the cost-effectiveness of a national TB program for improving patient adherence. METHODS: A discrete event simulation (DES) model was developed to estimate the costs and quality-adjusted life-years (QALYs) of adherent and non-adherent patients. In this model, we considered treatment completion, loss to follow-up, recurrence, death, and treatment changes from drug-susceptible to multidrug-resistant TB as clinical events. We obtained input parameters such as costs, probability of events, and time distributions for each event from the Korean National Health Insurance claims data. We estimated the costs and QALYs before implementation of the program (adherence rate = 79%) and at present (current adherence rate = 94%). The incremental cost-effectiveness ratio (ICER) was used to evaluate whether the program was cost-effective given the willingness-to-pay threshold. RESULTS: In the simulation, the program increasing the proportion of adherent patients gained 0.018 QALY/patient while spending $162/patient. The ICER of the TB program was $8790/QALY. Given a willingness-to-pay threshold of $20,000, the national TB program was considered cost-effective. CONCLUSION: Improvements in adherence to TB treatment through the current TB program were cost-effective. The DES model accurately reflected the real world. Commitment programs to improve patient adherence may help manage TB nationwide.

Treatment outcomes and risk factors for an unsuccessful outcome among patients with highly drug-resistant tuberculosis in Ukraine.

OBJECTIVES: To describe demographics, clinical features, and treatment outcomes of patients with highly drug-resistant tuberculosis (TB) in Ukraine, and to evaluate risk factors for an unsuccessful outcome. METHODS: Data from patients with multi-, pre-extensively, or extensively drug-resistant TB were collected prospectively from TB dispensaries in 15 out of 24 Ukrainian oblasts (regions) from 2020 to 2021. Treatment outcomes were evaluated using WHO definitions. Risk factors for an unsuccessful outcome were identified using a multivariable logistic regression model. RESULTS: Among 1748 patients, the overall proportion of successful outcomes was 58% (95% confidence interval [95% CI] 56-60) (n = 1015/1748), ranging from 65% (95% CI: 62-69) (n = 531/814) for multidrug-resistant TB to 54% (95% CI: 49-58) (n = 301/563) for pre-extensively drug-resistant TB and 49% (95% CI: 44-55) (n = 183/371) for extensively drug-resistant TB. Results were similar across oblasts, with few exceptions. The strongest risk factors for an unsuccessful outcome were extensively drug-resistant TB (adjusted OR [aOR] 3.23; 95% CI: 1.88-5.53), total serum protein below 62 g/L in adults and below 57 g/L for children and adolescents (aOR 2.79; 95% CI: 1.93-4.04), psychiatric illness (aOR 2.79; 95% CI: 1.46-5.33), age at TB diagnosis >65 years (aOR 2.50; 95% CI: 1.42-4.42), and alcohol misuse (aOR 2.48; 95% CI: 1.89-3.26). DISCUSSION: The overall proportion of successful outcomes among Ukrainians treated for highly drug-resistant TB was 58%, notably better compared with previous years, but still low for extensively drug-resistant TB. Risk factors for unsuccessful outcomes highlight that addressing socioeconomic factors in TB management is crucial. Efforts in maintaining TB dispensaries during and following the ongoing war are highly warranted.

Cost-effectiveness of a decentralized care model for managing multi-drug-resistant tuberculosis in low- and middle-income countries: a systematic review protocol.

OBJECTIVE: The purpose of this systematic review is to assess the available economic evidence of a decentralized care model compared to a centralized model for treating multi-drug-resistant tuberculosis (MDR-TB) in low- and middle-income countries (LMICs). INTRODUCTION: Diseases that affect physiological health create a burden on human livelihoods and the economy. There is a lack of studies examining the economic evaluation of MDR-TB across different countries. A preliminary search identified no published or ongoing reviews on MDR-TB in LMICs. INCLUSION CRITERIA: Studies will be eligible if they include both patients receiving centralized care (ie, care provided by specialist centers through inpatient or outpatient services) and patients receiving decentralized care (ie, care provided by grassroots community workers in peripheral facilities or in the patients' residence) for MDR-TB in LMICs. Eligible studies will report economic evaluations of treatment for MDR-TB. METHODS: A preliminary search of MEDLINE (PubMed) was undertaken using MeSH terms, such as MDR-TB, economic evaluation, therapeutics, LMICs . Two reviewers will independently screen the titles, abstracts, and full text against the inclusion criteria. Disagreements will be resolved through discussion or with a third reviewer. The JBI checklist for economic evaluations will be utilized to evaluate the methodological quality. Data will be extracted using a modified JBI data extraction form for economic evaluations. The Dominance Ranking Matrix, developed by JBI for economic evaluations, will be used to summarize and compare the results of different types of economic evaluations (cost-effectiveness, cost-benefit analysis, cost-utility analysis, or cost-minimization analysis). Cost per quality-adjusted life year gained and cost per disability-adjusted life year averted will be measures for economic evaluation. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach will be used to assess the certainty of economic evidence. REVIEW REGISTRATION: PROSPERO CRD42022368696.

Determinants of catastrophic costs among households affected by multi-drug resistant tuberculosis in Ho Chi Minh City, Viet Nam: a prospective cohort study.

BACKGROUND: Globally, most people with multidrug-resistant tuberculosis (MDR-TB) and their households experience catastrophic costs of illness, diagnosis, and care. However, the factors associated with experiencing catastrophic costs are poorly understood. This study aimed to identify risk factors associated with catastrophic costs incurrence among MDR-TB-affected households in Ho Chi Minh City (HCMC), Viet Nam. METHODS: Between October 2020 and April 2022, data were collected using a locally-adapted, longitudinal WHO TB Patient Cost Survey in ten districts of HCMC. Ninety-four people with MDR-TB being treated with a nine-month TB regimen were surveyed at three time points: after two weeks of treatment initiation, completion of the intensive phase and the end of the treatment (approximately five and 10 months post-treatment initiation respectively). The catastrophic costs threshold was defined as total TB-related costs exceeding 20% of annual pre-TB household income. Logistic regression was used to identify variables associated with experiencing catastrophic costs. A sensitivity analysis examined the prevalence of catastrophic costs using alternative thresholds and cost estimation approaches. RESULTS: Most participants (81/93 [87%]) experienced catastrophic costs despite the majority 86/93 (93%) receiving economic support through existing social protection schemes. Among participant households experiencing and not experiencing catastrophic costs, median household income was similar before MDR-TB treatment. However, by the end of MDR-TB treatment, median household income was lower (258 [IQR: 0-516] USD vs. 656 [IQR: 462-989] USD; p = 0.003), and median income loss was higher (2838 [IQR: 1548-5418] USD vs. 301 [IQR: 0-824] USD; p < 0.001) amongst the participant households who experienced catastrophic costs. Being the household's primary income earner before MDR-TB treatment (aOR = 11.2 [95% CI: 1.6-80.5]), having a lower educational level (aOR = 22.3 [95% CI: 1.5-344.1]) and becoming unemployed at the beginning of MDR-TB treatment (aOR = 35.6 [95% CI: 2.7-470.3]) were associated with experiencing catastrophic costs. CONCLUSION: Despite good social protection coverage, most people with MDR-TB in HCMC experienced catastrophic costs. Incurrence of catastrophic costs was independently associated with being the household's primary income earner or being unemployed. Revision and expansion of strategies to mitigate TB-related catastrophic costs, in particular avoiding unemployment and income loss, are urgently required.

The economic burden of households affected by tuberculosis in Brazil: First national survey results, 2019-2021.

BACKGROUND: One of the three main targets of the World Health Organization (WHO) End TB Strategy (2015-2035) is that no tuberculosis (TB) patients or their households face catastrophic costs (defined as exceeding 20% of the annual household income) because of the disease. Our study seeks to determine, as a baseline, the magnitude and main drivers of the costs associated with TB disease for patients and their households and to monitor the proportion of households experiencing catastrophic costs in Brazil. METHODS: A national cross-sectional cluster-based survey was conducted in Brazil in 2019-2021 following WHO methodology. TB patients of all ages and types of TB were eligible for the survey. Adult TB patients and guardians of minors (<18 years old) were interviewed once about costs, time loss, coping measures, income, household expenses, and asset ownership. Total costs, including indirect costs measured as reported household income change, were expressed as a percentage of annual household income. We used descriptive statistics to analyze the cost drivers and multivariate logistic regression to determine factors associated with catastrophic costs. RESULTS: We interviewed 603 patients, including 538 (89%) with drug-sensitive (DS) and 65 (11%) with drug-resistant (DR) TB. Of 603 affected households, 48.1% (95%CI: 43-53.2) experienced costs above 20% of their annual household income during their TB episode. The proportion was 44.4% and 78.5% among patients with DS- and DR-TB, respectively. On average, patients incurred costs of US$1573 (95%CI: 1361.8-1785.0) per TB episode, including pre-diagnosis and post-diagnosis expenses. Key cost drivers were post-diagnosis nutritional supplements (US$317.6, 95%CI: 232.7-402.6) followed by medical costs (US$85.5, 95%CI: 54.3-116.5) and costs of travel for clinic visits during treatment (US$79.2, 95%CI: 61.9-96.5). In multivariate analysis, predictors of catastrophic costs included positive HIV status (aOR = 3.0, 95%CI:1.1-8.6) and self-employment (aOR = 2.7, 95%CI:1.1-6.5); high education was a protective factor (aOR = 0.1, 95%CI:0.0-0.9). CONCLUSIONS: Although the services offered to patients with TB are free of charge in the Brazilian public health sector, the availability of free diagnosis and treatment services does not alleviate patients' financial burden related to accessing TB care. The study allowed us to identify the costs incurred by patients and suggest actions to mitigate their suffering. In addition, this study established a baseline for monitoring catastrophic costs and fostering a national policy to reduce the costs to patients for TB care in Brazil.

mHealth application for improving treatment outcomes for patients with multidrug-resistant tuberculosis in Vietnam: an economic evaluation protocol for the V-SMART trial.

INTRODUCTION: The Strengthen the Management of Multidrug-Resistant Tuberculosis in Vietnam (V-SMART) trial is a randomised controlled trial of using mobile health (mHealth) technologies to improve adherence to medications and management of adverse events (AEs) in people with multidrug-resistant tuberculosis (MDR-TB) undergoing treatment in Vietnam. This economic evaluation seeks to quantify the cost-effectiveness of this mHealth intervention from a healthcare provider and societal perspective. METHODS AND ANALYSIS: The V-SMART trial will recruit 902 patients treated for MDR-TB across seven participating provinces in Vietnam. Participants in both intervention and control groups will receive standard community-based therapy for MDR-TB. Participants in the intervention group will also have a purpose-designed App installed on their smartphones to report AEs to health workers and to facilitate timely management of AEs. This economic evaluation will compare the costs and health outcomes between the intervention group (mHealth) and the control group (standard of care). Costs associated with delivering the intervention and health service utilisation will be recorded, as well as patient out-of-pocket costs. The health-related quality of life (HRQoL) of study participants will be captured using the 36-Item Short Form Survey (SF-36) questionnaire and used to calculate quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratios (ICERs) will be based on the primary outcome (proportion of patients with treatment success after 24 months) and QALYs gained. Sensitivity analysis will be conducted to test the robustness of the ICERs. A budget impact analysis will be conducted from a payer perspective to provide an estimate of the total budget required to scale-up delivery of the intervention. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by the University of Sydney Human Research Ethics Committee (2019/676), the Scientific Committee of the Ministry of Science and Technology, Vietnam (08/QD-HDQL-NAFOSTED) and the Institutional Review Board of the National Lung Hospital, Vietnam (13/19/CT-HDDD). Study findings will be published in peer-reviewed journals and conference proceedings. TRIAL REGISTRATION NUMBER: ACTRN12620000681954.

Economic burden of multidrug-resistant tuberculosis on patients and households: a global systematic review and meta-analysis.

Multidrug-resistant tuberculosis (MDR-TB) is a major health threat worldwide, causing a significant economic burden to patients and their families. Due to the longer duration of treatment and expensive second-line medicine, the economic burden of MDR-TB is assumed to be higher than drug-susceptible TB. However, the costs associated with MDR-TB are yet to be comprehensively quantified. We conducted this systematic review and meta-analysis to determine the global burden of catastrophic costs associated with MDR-TB on patients and their households. We systematically searched five databases (CINHAL, MEDLINE, Embase, Scopus, and Web of Science) from inception to 2 September 2022 for studies reporting catastrophic costs on patients and affected families of MDR-TB. The primary outcome of our study was the proportion of patients and households with catastrophic costs. Costs were considered catastrophic when a patient spends 20% or more of their annual household income on their MDR-TB diagnosis and care. The pooled proportion of catastrophic cost was determined using a random-effects meta-analysis. Publication bias was assessed using visualization of the funnel plots and the Egger regression test. Heterogeneity was assessed using I2, and sub-group analysis was conducted using study covariates as stratification variables. Finally, we used the Preferred Reporting Items for Reporting Systematic Review and Meta-Analysis-20 (PRISMA-20). The research protocol was registered in PROSPERO (CRD42021250909). Our search identified 6635 studies, of which 11 were included after the screening. MDR-TB patients incurred total costs ranging from $USD 650 to $USD 8266 during treatment. The mean direct cost and indirect cost incurred by MDR-TB patients were $USD 1936.25 (SD ± $USD 1897.03) and $USD 1200.35 (SD ± $USD 489.76), respectively. The overall burden of catastrophic cost among MDR-TB patients and households was 81.58% (95% Confidence Interval (CI) 74.13-89.04%). The catastrophic costs incurred by MDR-TB patients were significantly higher than previously reported for DS-TB patients. MDR-TB patients incurred more expenditure for direct costs than indirect costs. Social protection and financial support for patients and affected families are needed to mitigate the catastrophic economic consequences of MDR-TB.

Cost of inaction: a framework to estimate the economic cost of missing a patient with tuberculosis in the Indian context.

OBJECTIVES: To estimate the economic impact of failure to find and treat tuberculosis disease and prevent tuberculosis infection from progressing to active disease. DESIGN: Estimating the economic cost of not finding and treating a patient suffering from tuberculosis. SETTING: Estimation methodology is developed in the Indian context, as informed by local costs and reported tuberculosis epidemiology. PARTICIPANTS: No individual participants were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure is the total cost of patients with drug-susceptible and drug-resistant tuberculosis who are and are not found and treated by tuberculosis programmes, including costs for medications, lost productivity, healthcare services and furthered transmission. We calculate the economic burdens by varying the number of individuals a person sick with tuberculosis infects (10 or 15 people) and the risk of progression to tuberculosis disease if infected (5 or 8%). The secondary outcome measure is the amount saved by finding a patient early or who would not have otherwise been found. All costs are presented in US dollars (exchange rate: 72 Indian rupees/1 US$). RESULTS: By finding and treating a patient early before furthered transmission occurs-or stopping progression of tuberculosis infection to tuberculosis disease with preventive therapy-the Indian health system can save US$5502 to US$15 825 and US$5846 to US$25 575, for each individual with drug-susceptible and drug-resistant tuberculosis, respectively, across scenarios. CONCLUSIONS: These estimates provide crude, lower bounds for the potential costs of not appropriately diagnosing and treating a single patient with active tuberculosis in a timely manner, or preventing a patient with tuberculosis infection from progressing to active disease. The actual financial burden on society is far higher than estimated using this simple, short-term cost-effective analyses. Our results highlight the limitations of tuberculosis costing models to date, and demonstrate the importance of accounting for airborne transmission of tuberculosis.

Analysis of catastrophic costs incurred by patients with multidrug-resistant tuberculosis in an outpatient clinic in the state of Rio de Janeiro.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a serious global public health concern associated with social vulnerability. In Brazil, the Unified Health System (SUS, Portuguese) provides free diagnosis and treatment for MDR-TB; however, other expenses may still be incurred for patients and their families which, according to the World Health Organization (WHO), can be catastrophic when these costs surpass 20.0% of the annual household income. This study aimed to assess the extent of catastrophic costs related to the diagnostic and therapeutic aspects of MDR-TB among patients receiving care at an outpatient clinic in Rio de Janeiro. METHODS: This prospective study used convenience sampling from July 2019 to June 2021. Data regarding direct and indirect costs were collected using a standardized questionnaire endorsed by the WHO. To analyze any impoverishment occurred from MDR-TB, a threshold established by the Brazilian Institute of Geography and Statistics for 2019 and 2020 of US$ 79,562 and US$ 94,5273, respectively, was applied. Descriptive statistics were used for data analysis, including mean; standard deviation; variation coefficient; median; and maximum, minimum, and interquartile ranges. RESULTS: A total of 65 patients were interviewed. Among the participants, 73.8% experienced catastrophic costs, with indirect costs exerting the most significant impact (median: US$ 3,825.9), in contrast to direct costs (median: US$ 542.7). When comparing the periods before and after diagnosis, the prevalence of poverty increased from 12.0% to 28.0%. CONCLUSIONS: Despite the support from the SUS in Brazil, diagnostic and therapeutic cascades incur additional costs, exacerbating social vulnerability among patients with MDR-TB.

Cost of digital technologies and family-observed DOT for a shorter MDR-TB regimen: a modelling study in Ethiopia, India and Uganda.

BACKGROUND: In 2017, the WHO recommended the use of digital technologies, such as medication monitors and video observed treatment (VOT), for directly observed treatment (DOT) of drug-susceptible TB. The WHO's 2020 guidelines extended these recommendations to multidrug-resistant tuberculosis (MDR-TB), based on low evidence. The impact of COVID on health systems and patients underscored the need to use digital technologies in the management of MDR-TB. METHODS: A decision-tree model was developed to explore the costs of several potential DOT alternatives: VOT, 99DOTS (Directly-observed Treatment, Short-course) and family-observed DOT. Assuming a 9-month, all-oral regimen (as evaluated within the STREAM trial), we constructed base-case cost models for the standard-of-care DOTs in Ethiopia, India, and Uganda, as well as for the three alternative DOT approaches. The models were populated with STREAM Stage 2 clinical trial outcome and cost data, supplemented with market prices data for the digital DOT strategies. Sensitivity analyses were conducted on key parameters. RESULTS: Modelling suggested that the standard-of-care DOT approach is the most expensive DOT strategy from a societal perspective in all three countries evaluated (Ethiopia, India, Uganda), with considerable direct- and indirect-costs incurred by patients. The second most expensive DOT approach is VOT, with high health-system costs, largely caused by up-front technology expenditure. Each of VOT, 99DOTS and family-observed DOT would reduce by more than 90% patients' direct and indirect costs compared to standard of care DOT. Results were robust to the sensitivity analyses. CONCLUSIONS: While data on the costs and efficacy of alternative DOT approaches in the context of shorter MDR-TB treatment is limited, our modelling suggests alternative DOT approaches can significantly reduce patient costs in all three countries. Health system costs are higher for VOT and lower for 99DOTS and family-observed therapy when compared to standard of care DOT, as low smartphone penetration and internet availability requires the VOT health system to fund the cost of making them available to patients.