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Background: Shorter, safer, and cheaper tuberculosis (TB) preventive treatment (TPT) regimens will enhance uptake and effectiveness. WHO developed target product profiles describing minimum requirements and optimal targets for key attributes of novel TPT regimens. We performed a cost-effectiveness analysis addressing the scale-up of regimens meeting these criteria in Brazil, a setting with relatively low transmission and low HIV and rifampicin-resistant TB (RR-TB) prevalence, and South Africa, a setting with higher transmission and higher HIV and RR-TB prevalence.Methods and Findings: We used outputs from a model simulating scale-up of TPT regimens meeting minimal and optimal criteria. We assumed that drug costs for minimal and optimal regimens were identical to 6 months of daily isoniazid (6H). The minimal regimen lasted 3 months, with 70% completion and 80% efficacy; the optimal regimen lasted 1 month, with 90% completion and 100% efficacy. Target groups were people living with HIV (PLHIV) on antiretroviral treatment and household contacts (HHCs) of identified TB patients. The status quo was 6H at 2019 coverage levels for PLHIV and HHCs. We projected TB cases and deaths, TB-associated disability-adjusted life years (DALYs), and costs (in 2020 US dollars) associated with TB from a TB services perspective from 2020 to 2035, with 3% annual discounting. We estimated the expected costs and outcomes of scaling up 6H, the minimal TPT regimen, or the optimal TPT regimen to reach all eligible PLHIV and HHCs by 2023, compared to the status quo. Maintaining current 6H coverage in Brazil (0% of HHCs and 30% of PLHIV treated) would be associated with 1.1 (95% uncertainty range [UR] 1.1-1.2) million TB cases, 123,000 (115,000-132,000) deaths, and 2.5 (2.1-3.1) million DALYs and would cost $1.1 ($1.0-$1.3) billion during 2020-2035. Expanding the 6H, minimal, or optimal regimen to 100% coverage among eligible groups would reduce DALYs by 0.5% (95% UR 1.2% reduction, 0.4% increase), 2.5% (1.8%-3.0%), and 9.0% (6.5%-11.0%), respectively, with additional costs of $107 ($95-$117) million and $51 ($41-$60) million and savings of $36 ($14-$58) million, respectively. Compared to the status quo, costs per DALY averted were $7,608 and $808 for scaling up the 6H and minimal regimens, respectively, while the optimal regimen was dominant (cost savings, reduced DALYs). In South Africa, maintaining current 6H coverage (0% of HHCs and 69% of PLHIV treated) would be associated with 3.6 (95% UR 3.0-4.3) million TB cases, 843,000 (598,000-1,201,000) deaths, and 36.7 (19.5-58.0) million DALYs and would cost $2.5 ($1.8-$3.6) billion. Expanding coverage with the 6H, minimal, or optimal regimen would reduce DALYs by 6.9% (95% UR 4.3%-95%), 15.5% (11.8%-18.9%), and 38.0% (32.7%-43.0%), respectively, with additional costs of $79 (-$7, $151) million and $40 (-$52, $140) million and savings of $608 ($443-$832) million, respectively. Compared to the status quo, estimated costs per DALY averted were $31 and $7 for scaling up the 6H and minimal regimens, while the optimal regimen was dominant. Study limitations included the focus on 2 countries, and no explicit consideration of costs incurred before the decision to prescribe TPT.Conclusions: Our findings suggest that scale-up of TPT regimens meeting minimum or optimal requirements would likely have important impacts on TB-associated outcomes and would likely be cost-effective or cost saving. [ABSTRACT FROM AUTHOR]

The cost-effectiveness of migrant tuberculosis prevention programs is highly relevant to many countries with low tuberculosis incidence as they attempt to eliminate the disease. Dale et al. (Am J Epidemiol. 2022;191(2):255–270) evaluated strategies for tuberculosis infection screening and treatment among new migrants to Australia. Screening for infection before migration, and then administering preventive treatment after arrival, was more cost-effective than performing both screening and treatment after arrival. From the Australian health payer perspective, the improved cost-effectiveness of premigration screening partly reflected the shift of screening costs to migrants, which may raise ethical concerns. Key sensitivity analyses highlighted the influence of health disutility associated with tuberculosis preventive treatment, and of posttreatment sequelae of tuberculosis disease. Both considerations warrant greater attention in future research. For all strategies, the impact on tuberculosis incidence among migrants was modest (<15%), suggesting enhanced migrant screening will not achieve tuberculosis elimination in low-incidence settings. This emphasizes the need to increase investment and effort in global tuberculosis prevention and care, which will ultimately reduce the prevalence of tuberculosis infection and therefore the risk of tuberculosis disease among migrants. Such efforts will benefit high and low tuberculosis incidence countries alike, and advance all countries further toward tuberculosis elimination. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In North America, tuberculosis incidence is now very low and risk to healthcare workers has fallen. Indeed, recent cohort data question routine annual tuberculosis screening in this context. We compared the cost-effectiveness of three potential strategies for ongoing screening of North American healthcare workers at risk of exposure. The analysis did not evaluate the cost-effectiveness of screening at hiring, and considered only workers with negative baseline tests.Methods: A decision analysis model simulated a hypothetical cohort of 1000 workers following negative baseline tests, considering duties, tuberculosis exposure, testing and treatment. Two tests were modelled, the tuberculin skin test (TST) and QuantiFERON®-TB-Gold In-Tube (QFT). Three screening strategies were compared: (1) annual screening, where workers were tested yearly; (2) targeted screening, where workers with high-risk duties (e.g. respiratory therapy) were tested yearly and other workers only after recognised exposure; and (3) post exposure-only screening, where all workers were tested only after recognised exposure. Workers with high-risk duties had 1% annual risk of infection, while workers with standard patient care duties had 0.3%. In an alternate higher-risk scenario, the corresponding annual risks of infection were 3% and 1%, respectively. We projected costs, morbidity, quality-adjusted survival and mortality over 20 years after hiring. The analysis used the healthcare system perspective and a 3% annual discount rate.Results: Over 20 years, annual screening with TST yielded an expected 2.68 active tuberculosis cases/1000 workers, versus 2.83 for targeted screening and 3.03 for post-exposure screening only. In all cases, annual screening was associated with poorer quality-adjusted survival, i.e. lost quality-adjusted life years, compared to targeted or post-exposure screening only. The annual TST screening strategy yielded an incremental cost estimate of $1,717,539 per additional case prevented versus targeted TST screening, which in turn cost an incremental $426,678 per additional case prevented versus post-exposure TST screening only. With the alternate "higher-risk" scenario, the annual TST strategy cost an estimated $426,678 per additional case prevented versus the targeted TST strategy, which cost an estimated $52,552 per additional case prevented versus post-exposure TST screening only. In all cases, QFT was more expensive than TST, with no or limited added benefit. Sensitivity analysis suggested that, even with limited exposure recognition, annual screening was poorly cost-effective.Conclusions: For most North American healthcare workers, annual tuberculosis screening appears poorly cost-effective. Reconsideration of screening practices is warranted. [ABSTRACT FROM AUTHOR]

Novel tuberculosis vaccines are in varying stages of pre-clinical and clinical development. This study seeks to estimate the potential cost-effectiveness of a BCG booster vaccine, while accounting for costs of large-scale clinical trials, using the MVA85A vaccine as a case study for estimating potential costs. We conducted a decision analysis from the societal perspective, using a 10-year time frame and a 3% discount rate. We predicted active tuberculosis cases and tuberculosis-related costs for a hypothetical cohort of 960,763 South African newborns (total born in 2009). We compared neonatal vaccination with bacille Calmette-Guérin alone to vaccination with bacille Calmette-Guérin plus a booster vaccine at 4 months. We considered booster efficacy estimates ranging from 40% to 70%, relative to bacille Calmette-Guérin alone. We accounted for the costs of Phase III clinical trials. The booster vaccine was assumed to prevent progression to active tuberculosis after childhood infection, with protection decreasing linearly over 10 years. Trial costs were prorated to South Africa's global share of bacille Calmette-Guérin vaccination. Vaccination with bacille Calmette-Guérin alone resulted in estimated tuberculosis-related costs of $89.91 million 2012 USD, and 13,610 tuberculosis cases in the birth cohort, over the 10 years. Addition of the booster resulted in estimated cost savings of $7.69–$16.68 million USD, and 2,800–4,160 cases averted, for assumed efficacy values ranging from 40%–70%. A booster tuberculosis vaccine in infancy may result in net societal cost savings as well as fewer active tuberculosis cases, even if efficacy is relatively modest and large scale Phase III studies are required. [ABSTRACT FROM AUTHOR]

Background: The development of a successful new tuberculosis (TB) vaccine would circumvent many limitations of current diagnostic and treatment practices. However, vaccine development is complex and costly. We aimed to assess the potential cost effectiveness of novel vaccines for TB control in a sub-Saharan African country - Zambia - relative to the existing strategy of directly observed treatment, short course (DOTS) and current level of bacille Calmette-Guérin (BCG) vaccination coverage. Methods: We conducted a decision analysis model-based simulation from the societal perspective, with a 3% discount rate and all costs expressed in 2007 US dollars. Health outcomes and costs were projected over a 30-year period, for persons born in Zambia (population 11,478,000 in 2005) in year 1. Initial development costs for single vaccination and prime-boost strategies were prorated to the Zambian share (0.398%) of global BCG vaccine coverage for newborns. Main outcome measures were TB-related morbidity, mortality, and costs over a range of potential scenarios for vaccine efficacy. Results: Relative to the status quo strategy, a BCG replacement vaccine administered at birth, with 70% efficacy in preventing rapid progression to TB disease after initial infection, is estimated to avert 932 TB cases and 422 TBrelated deaths (prevention of 199 cases/100,000 vaccinated, and 90 deaths/100,000 vaccinated). This would result in estimated net savings of $3.6 million over 30 years for 468,073 Zambians born in year 1 of the simulation. The addition of a booster at age 10 results in estimated savings of $5.6 million compared to the status quo, averting 1,863 TB cases and 1,011 TB-related deaths (prevention of 398 cases/100,000 vaccinated, and of 216 deaths/100,000 vaccinated). With vaccination at birth alone, net savings would be realized within 1 year, whereas the prime-boost strategy would require an additional 5 years to realize savings, reflecting a greater initial development cost. Conclusions: Investment in an improved TB vaccine is predicted to result in considerable cost savings, as well as a reduction in TB morbidity and TB-related mortality, when added to existing control strategies. For a vaccine with waning efficacy, a prime-boost strategy is more cost-effective in the long term. [ABSTRACT FROM AUTHOR]

Objective: To assess the cost-effectiveness of spiral CT for the diagnosis of acute pulmonary embolism. Design: Computer-based cost-effectiveness analysis. Patients: Simulated cohort of 1,000 patients with suspected acute pulmonary embolism (PE), with a prevalence of 28.4%, as in the Prospective Investigation of Pulmonary Embolism Diagnosis study. Interventions: Using a decision-analysis model, seven diagnostic strategies were compared, which incorporated combinations of ventilation-perfusion (V/Q) scans, duplex ultrasound of the legs, spiral CT, and conventional pulmonary angiography. Measurements and results: Expected survival and cost (in Canadian dollars) at 3 months were estimated. Four of the strategies yielded poorer survival at higher cost. The three remaining strategies were as follows: (1) V/Q ± leg ultrasound ± spiral CT, with an expected survival of 953.4 per 1,000 patients and a cost of $1,391 per patient; (2) V/Q ± leg ultrasound ± pulmonary angiography (the "traditional" algorithm), with an expected survival of 953.7 per 1,000 patients and a cost of $1,416 per patient; and (3) spiral CT ± leg ultrasound, with an expected survival of 958.2 per 1,000 patients and a cost of $1,751 per patient. The traditional algorithm was then excluded by extended dominance. The cost per additional life saved was $70,833 for spiral CT ± leg ultrasound relative to V/Q ± leg ultrasound ± spiral CT. Conclusions: Spiral CT can replace pulmonary angiography in patients with nondiagnostic V/Q scan and negative leg ultrasound findings. This approach is likely as effective as—and possibly less expensive than—the current algorithm for diagnosis of acute PE. When spiral CT is the initial diagnostic test, followed by leg ultrasound, expected survival improves but costs are also considerably higher. These findings were robust to variations in the assumed sensitivity and specificity of spiral CT. [ABSTRACT FROM AUTHOR]

Background:Immigrants have increased mortality from hepatocellular carcinoma as compared to the host populations, primarily due to undetected chronic hepatitis B virus (HBV) infection. Despite this, there are no systematic programs in most immigrant-receiving countries to screen for chronic HBV infection and immigrants are not routinely offered HBV vaccination outside of the universal childhood vaccination program. Methods and findings:A cost-effective analysis was performed to compare four HBV screening and vaccination strategies with no intervention in a hypothetical cohort of newly-arriving adult Canadian immigrants. The strategies considered were a) universal vaccination, b) screening for prior immunity and vaccination, c) chronic HBV screening and treatment, and d) combined screening for chronic HBV and prior immunity, treatment and vaccination. The analysis was performed from a societal perspective, using a Markov model. Seroprevalence estimates, annual transition probabilities, health-care costs (in Canadian dollars), and utilities were obtained from the published literature. Acute HBV infection, mortality from chronic HBV, quality-adjusted life years (QALYs), and costs were modeled over the lifetime of the cohort of immigrants. Costs and QALYs were discounted at a rate of 3% per year. Screening for chronic HBV infection, and offering treatment if indicated, was found to be the most cost-effective intervention and was estimated to cost $40,880 per additional QALY gained, relative to no intervention. This strategy was most cost-effective for immigrants < 55 years of age and would cost < $50,000 per additional QALY gained for immigrants from areas where HBV seroprevalence is ≥ 3%. Strategies that included HBV vaccination were either prohibitively expensive or dominated by the chronic HBV screening strategy. Conclusions:Screening for chronic HBV infection from regions where most Canadian immigrants originate, except for Latin America and the Middle East, was found to be reasonably cost-effective and has the potential to reduce HBV-associated morbidity and mortality. [ABSTRACT FROM AUTHOR]