Sex differences in the global burden of multidrug- resistant tuberculosis without extensive drug resistance in the general population and people living with HIV/AIDS, 1990-2019.

OBJECTIVE: Currently, human immunodeficiency virus (HIV) and multi-drug resistant tuberculosis (MDR-TB) without extensive drug resistance (XDR) are significant challenges in terms of the global burden of disease. This study aimed to evaluate the trends of the global burden of MDR-TB without XDR and HIV/AIDS-MDR-TB without XDR, focusing on differences in socioeconomic status and sex for 204 countries and territories across periods from 1990 to 2019. MATERIALS AND METHODS: Data from the Global Burden of Disease (GBD) 2019 study were obtained to construct a separate index measuring the burden of MDR-TB without XDR and HIV/AIDS-MDR-TB without XDR. Incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated for each case and group. A population-attributable fraction approach was used to assess mortality and incidence of HIV/AIDS and MDR-TB coinfection. 95% uncertainty intervals (UIs) were presented for all measures. RESULTS: Our global estimates suggest that there were approximately 450,000 (95% UI 247,000-785,000) incident cases of MDR-TB without XDR and 109,000 (43,000-210,000) deaths caused by MDR-TB without XDR among individuals who were HIV-negative in 2019. For HIV-positive individuals, the corresponding figures were approximately 47,000 (33,000-67,000) incident cases of MDR-TB and 19,000 (8,000-36,000) deaths due to MDR-TB in the same year. In 2019, higher numbers of incident cases and deaths were observed in males compared to females among individuals who were HIV-negative. Conversely, for HIV-positive individuals, females had higher numbers of incident cases and deaths compared to males. Specifically, the estimated numbers for incident cases were 23,000 (15,000-33,000) for females and 24,000 (17,000-35,000) for males, while the estimated numbers for deaths were 9,600 (4,000-17,900) for females and 9,800 (4,100-18,500) for males. Male-to-female ratios have remained above 1.0 from 1990 to 2019 in both incident cases and number of deaths for HIV-negative individuals. However, for HIV and MDR-TB coinfection, both ratios were below 1.0 in most of the time series. CONCLUSIONS: Males had more cases and deaths due to MDR-TB without XDR than females in HIV-negative patients, while females faced a higher incidence and mortality in HIV/AIDS-MDR-TB without XDR. Interventions are needed to deal with such factors, which increase the burden of coinfection among females across the world.

Impact and cost-effectiveness of the 6-month BPaLM regimen for rifampicin-resistant tuberculosis in Moldova: A mathematical modeling analysis.

BACKGROUND: Emerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment (EOT) outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether fluoroquinolone resistance (FQ-R) was detected on drug susceptibility testing (DST). METHODS AND FINDINGS: The primary objective was to determine whether 6 months of BPaLM is a cost-effective treatment strategy for RR-TB. We used genomic and demographic data to parameterize a mathematical model estimating long-term health outcomes measured in quality-adjusted life years (QALYs) and lifetime costs in 2022 USD ($) for each treatment strategy for patients 15 years and older diagnosed with pulmonary RR-TB in Moldova, a country with a high burden of TB drug resistance. For each individual, we simulated the natural history of TB and associated treatment outcomes, as well as the process of acquiring resistance to each of 12 anti-TB drugs. Compared to the standard of care, 6 months of BPaLM was cost-effective. This strategy was estimated to reduce lifetime costs by $3,366 (95% UI: [1,465, 5,742] p < 0.001) per individual, with a nonsignificant change in QALYs (-0.06; 95% UI: [-0.49, 0.03] p = 0.790). For those stopping moxifloxacin under the BPaLM regimen, continuing with BPaL plus clofazimine (BPaLC) provided more QALYs at lower cost than continuing with BPaL alone. Strategies based on 6 months of BPaLM had at least a 93% chance of being cost-effective, so long as BPaLC was continued in the event of stopping moxifloxacin. BPaLM for 6 months also reduced the average time spent with TB resistant to amikacin, bedaquiline, clofazimine, cycloserine, moxifloxacin, and pyrazinamide, while it increased the average time spent with TB resistant to delamanid and pretomanid. Sensitivity analyses showed 6 months of BPaLM to be cost-effective across a broad range of values for the relative effectiveness of BPaLM, and the proportion of the cohort with FQ-R. Compared to the standard of care, 6 months of BPaLM would be expected to save Moldova's national TB program budget $7.1 million (95% UI: [1.3 million, 15.4 million] p = 0.002) over the 5-year period from implementation. Our analysis did not account for all possible interactions between specific drugs with regard to treatment outcomes, resistance acquisition, or the consequences of specific types of severe adverse events, nor did we model how the intervention may affect TB transmission dynamics. CONCLUSIONS: Compared to standard of care, longer regimens, the implementation of the 6-month BPaLM regimen could improve the cost-effectiveness of care for individuals diagnosed with RR-TB, particularly in settings with a high burden of drug-resistant TB. Further research may be warranted to explore the impact and cost-effectiveness of shorter RR-TB regimens across settings with varied drug-resistant TB burdens and national income levels.

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.

Effectiveness, cost, and safety of four regimens recommended by WHO for RR/MDR-TB treatment: a cohort study in Eastern China.

BACKGROUND: To compare the effectiveness, cost, and safety of four regimens recommended by the World Health Organization (WHO) for rifampicin resistance/multidrug-resistance tuberculosis (RR/MDR-TB) Treatment in Eastern China. METHODS: We performed a cohort study among patients with RR/MDR between 2020 and 2022 in Jiangsu Province. The treatment success rate, cost, and drug adverse reaction rate were compared. RESULTS: Between 2020 and 2022, 253 RR/MDR-TB patients were enrolled in the study. 37 (14.62%), 76 (30.04%), 74 (29.25%), and 66 (26.09%) patients had the short-term regimens, the new long-term oral regimens, the new long-term injectable regimens, and the traditional long-term regimens, respectively. The treatment success rate was the highest among patients treated with the short-term regimen (75.68%) and was the lowest among patients treated with the traditional long-term regimens (60.61%). The estimated mean cost per favorable outcome was 142.61 thousand Chinese Yuan (CNY), and the short-term regimens showed the lowest cost in the four regimes (88.51 thousand CNY vs. 174.24 thousand CNY, 144.00 thousand CNY, and 134.98 thousand CNY). Incremental cost-effectiveness ratios of the short-term regimens, the new long-term oral regimen, and the new long-term injectable regimens were -3083.04, 6040.09, and 819.68 CNY compared to the traditional long-term regimens. CONCLUSIONS: For RR/MDR-TB patients in China who meet the criteria for short-term regimens, the short-term regimens were proven to be the most cost-effective of the four regimens recommended by WHO. For RR/MDR-TB patients in China who don't meet the criteria for short-term regimens, the new long-term injectable regimens are more cost-effective than the remaining two regimens.

This is the first study to evaluate the effectiveness, cost, and safety of four regimens recommended by the WHO for RR/MDR-TB treatment in China.For RR/MDR-TB patients in China who meet the criteria for the short-term regimens, the short-term regimens were proven to be the most cost-effective of the four regimens recommended by WHO.

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.

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.

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.

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.

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.

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.

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.

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.

Global burden of disease due to rifampicin-resistant tuberculosis: a mathematical modeling analysis.

In 2020, almost half a million individuals developed rifampicin-resistant tuberculosis (RR-TB). We estimated the global burden of RR-TB over the lifetime of affected individuals. We synthesized data on incidence, case detection, and treatment outcomes in 192 countries (99.99% of global tuberculosis). Using a mathematical model, we projected disability-adjusted life years (DALYs) over the lifetime for individuals developing tuberculosis in 2020 stratified by country, age, sex, HIV, and rifampicin resistance. Here we show that incident RR-TB in 2020 was responsible for an estimated 6.9 (95% uncertainty interval: 5.5, 8.5) million DALYs, 44% (31, 54) of which accrued among TB survivors. We estimated an average of 17 (14, 21) DALYs per person developing RR-TB, 34% (12, 56) greater than for rifampicin-susceptible tuberculosis. RR-TB burden per 100,000 was highest in former Soviet Union countries and southern African countries. While RR-TB causes substantial short-term morbidity and mortality, nearly half of the overall disease burden of RR-TB accrues among tuberculosis survivors. The substantial long-term health impacts among those surviving RR-TB disease suggest the need for improved post-treatment care and further justify increased health expenditures to prevent RR-TB transmission.