Cost-effectiveness of latent tuberculosis infection testing and treatment with 6-week regimen among key population in rural communities in China: a decision analysis study.

PURPOSE: Several model studies suggested the implementation of latent tuberculosis infection (LTBI) testing and treatment could greatly reduce the incidence of tuberculosis (TB) and achieve the 2035 target of the "End TB" Strategy in China. The present study aimed to evaluate the cost-effectiveness of LTBI testing and TB preventive treatment among key population (≥ 50 years old) susceptible to TB at community level in China. METHODS: A Markov model was developed to investigate the cost-effectiveness of LTBI testing using interferon gamma release assay (IGRA) and subsequent treatment with 6-month daily isoniazid regimen (6H) (as a standard regimen for comparison) or 6-week twice-weekly rifapentine and isoniazid regimen (6-week H2P2) in a cohort of 10,000 adults with an average initial age of 50 years. RESULTS: In the base-case analysis, LTBI testing and treatment with 6H was dominated (i.e., more expensive with a lower quality-adjusted life year (QALY)) by LTBI testing and treatment with 6-week H2P2. LTBI testing and treatment with 6-week H2P2 was more effective than no intervention at a cost of $20,943.81 per QALY gained, which was below the willingness-to-pay (WTP) threshold of $24,211.84 per QALY gained in China. The one-way sensitivity analysis showed the change of LTBI prevalence was the parameter that most influenced the results of the incremental cost-effectiveness ratios (ICERs). CONCLUSION: As estimated by a Markov model, LTBI testing and treatment with 6-week H2P2 was cost-saving compared with LTBI testing and treatment with 6H, and it was considered to be a cost-effective option for TB control in rural China.

Modeling the Cost-Effectiveness of Latent Tuberculosis Screening and Treatment Strategies in Recent Migrants to a Low-Incidence Setting.

Many tuberculosis (TB) cases in low-incidence settings are attributed to reactivation of latent TB infection (LTBI) acquired overseas. We assessed the cost-effectiveness of community-based LTBI screening and treatment strategies in recent migrants to a low-incidence setting (Australia). A decision-analytical Markov model was developed that cycled 1 migrant cohort (≥11-year-olds) annually over a lifetime from 2020. Postmigration/onshore and offshore (screening during visa application) strategies were compared with existing policy (chest x-ray during visa application). Outcomes included TB cases averted and discounted cost per quality-adjusted life-year (QALY) gained from a health-sector perspective. Most recent migrants are young adults and cost-effectiveness is limited by their relatively low LTBI prevalence, low TB mortality risks, and high emigration probability. Onshore strategies cost at least $203,188 (Australian) per QALY gained, preventing approximately 2.3%-7.0% of TB cases in the cohort. Offshore strategies (screening costs incurred by migrants) cost at least $13,907 per QALY gained, preventing 5.5%-16.9% of cases. Findings were most sensitive to the LTBI treatment quality-of-life decrement (further to severe adverse events); with a minimal decrement, all strategies caused more ill health than they prevented. Additional LTBI strategies in recent migrants could only marginally contribute to TB elimination and are unlikely to be cost-effective unless screening costs are borne by migrants and potential LTBI treatment quality-of-life decrements are ignored.

Health System Costs of Treating Latent Tuberculosis Infection With Four Months of Rifampin Versus Nine Months of Isoniazid in Different Settings.

BACKGROUND: Four months of rifampin treatment for latent tuberculosis infection is safer, has superior treatment completion rates, and is as effective as 9 months of isoniazid. However, daily medication costs are higher for a 4-month rifampin regimen than a 9-month isoniazid regimen. OBJECTIVE: To compare health care use and associated costs of 4 months of rifampin and 9 months of isoniazid. DESIGN: Health system cost comparison using all health care activities recorded during 2 randomized clinical trials. (ClinicalTrials.gov: NCT00931736 and NCT00170209). SETTING: High-income countries (Australia, Canada, Saudi Arabia, and South Korea), middle-income countries (Brazil and Indonesia), and African countries (Benin, Ghana, and Guinea). PARTICIPANTS: Adults and children with clinical or epidemiologic factors associated with increased risk for developing tuberculosis that warranted treatment for latent tuberculosis infection. MEASUREMENTS: Health system costs per participant. RESULTS: A total of 6012 adults and 829 children were included. In both adults and children, greater health system use and higher costs were observed with 9 months of isoniazid than with 4 months of rifampin. In adults, the ratios of costs of 4 months of rifampin versus 9 months of isoniazid were 0.76 (95% CI, 0.70 to 0.82) in high-income countries, 0.90 (CI, 0.85 to 0.96) in middle-income countries, and 0.80 (CI, 0.78 to 0.81) in African countries. Similar findings were observed in the pediatric population. LIMITATION: Costs may have been overestimated because the trial protocol required a minimum number of follow-up visits, although fewer than recommended by many authoritative guidelines. CONCLUSION: A 4-month rifampin regimen was safer and less expensive than 9 months of isoniazid in all settings. This regimen could be adopted by tuberculosis programs in many countries as first-line therapy for latent tuberculosis infection. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Solutions to improve the latent tuberculosis Cascade of Care in Ghana: a longitudinal impact assessment.

BACKGROUND: Loss of patients in the latent tuberculosis infection (LTBI) cascade of care is a major barrier to LTBI management. We evaluated the impact and acceptability of local solutions implemented to strengthen LTBI management of household contacts (HHCs) at an outpatient clinic in Ghana. METHODS: Local solutions to improve LTBI management were informed by a baseline evaluation of the LTBI cascade and questionnaires administered to index patients, HHCs, and health care workers at the study site in Offinso, Ghana. Solutions aimed to reduce patient costs and improve knowledge. We evaluated the impact and acceptability of the solutions. Specific objectives were to: 1) Compare the proportion of eligible HHCs completing each step in the LTBI cascade of care before and after solution implementation; 2) Compare knowledge, attitude, and practices (KAP) before and after solution implementation, based on responses of patients and health care workers (HCW) to structured questionnaires; 3) Evaluate patient and HCW acceptability of solutions using information obtained from these questionnaires. RESULTS: Pre and Post-Solution LTBI Cascades included 58 and 125 HHCs, respectively. Before implementation, 39% of expected < 5-year-old HHCs and 66% of ≥5-year-old HHCs were identified. None completed any further cascade steps. Post implementation, the proportion of eligible HHCs who completed identification, assessment, evaluation, and treatment initiation increased for HHCs < 5 to 94, 100, 82, 100%, respectively, and for HHCs ≥5 to 96, 69, 67, 100%, respectively. Pre and Post-Solutions questionnaires were completed by 80 and 95 respondents, respectively. Study participants most frequently mentioned financial support and education as the solutions that supported LTBI management. CONCLUSION: Implementation of locally selected solutions was associated with an increase in the proportion of HHCs completing all steps in the LTBI cascade. Tuberculosis programs should consider prioritizing financial support, such as payment for chest x-rays, to support LTBI cascade completion.

Cost-effectiveness of 3 months of weekly rifapentine and isoniazid compared with other standard treatment regimens for latent tuberculosis infection: a decision analysis study.

Background: Latent tuberculosis infection (LTBI) is a critical driver of the global burden of active TB, and therefore LTBI treatment is key for TB elimination. Treatment regimens for LTBI include self-administered daily isoniazid for 6 (6H) or 9 (9H) months, self-administered daily rifampicin plus isoniazid for 3 months (3RH), self-administered daily rifampicin for 4 months (4R) and weekly rifapentine plus isoniazid for 3 months self-administered (3HP-SAT) or administered by a healthcare worker as directly observed therapy (3HP-DOT). Data on the relative cost-effectiveness of these regimens are needed to assist policymakers and clinicians in selecting an LTBI regimen. Objectives: To evaluate the cost-effectiveness of all regimens for treating LTBI. Methods: We developed a Markov model to investigate the cost-effectiveness of 3HP-DOT, 3HP-SAT, 4R, 3RH, 9H and 6H for LTBI treatment in a cohort of 10000 adults with LTBI. Cost-effectiveness was evaluated from a health system perspective over a 20 year time horizon. Results: Compared with no preventive treatment, 3HP-DOT, 3HP-SAT, 4R, 3RH, 9H and 6H prevented 496, 470, 442, 418, 370 and 276 additional cases of active TB per 10000 patients, respectively. All regimens reduced costs and increased QALYs compared with no preventive treatment. 3HP was more cost-effective under DOT than under SAT at a cost of US$27948 per QALY gained. Conclusions: Three months of weekly rifapentine plus isoniazid is more cost-effective than other regimens. Greater recognition of the benefits of short-course regimens can contribute to the scale-up of prevention and achieving the 'End TB' targets.

Evaluating the potential costs and impact of digital health technologies for tuberculosis treatment support.

Ensuring adherence and support during treatment of tuberculosis (TB) is a major public health challenge. Digital health technologies could help improve treatment outcomes. We considered their potential cost and impact on treatment for active or latent TB in Brazil.Decision analysis models simulated two adult cohorts with 1) drug-susceptible active TB, and 2) multidrug-resistant TB, and two cohorts treated with isoniazid for latent TB infection (LTBI): 1) close contacts of persons with active TB, and 2) others newly diagnosed with LTBI. We evaluated four digital support strategies: two different medication monitors, synchronous video-observed therapy (VOT), and two-way short message service (SMS). Comparators were standard directly observed treatment for active TB and self-administered treatment for LTBI. Projected outcomes included costs (2016 US dollars), plus active TB cases and disability-adjusted life years averted among persons with LTBI.For individuals with active TB, medication monitors and VOT are projected to lead to substantial (up to 58%) cost savings, in addition to alleviating inconvenience and cost to patients of supervised treatment visits. For LTBI treatment, SMS and medication monitors are projected to be the most cost-effective interventions. However, all projections are limited by the scarcity of published estimates of clinical effect for the digital technologies.

Economic burden of HIV and TB/HIV coinfection in a middle-income country: a costing analysis alongside a pragmatic clinical trial in Brazil.

OBJECTIVE: The objective of this study was to measure the costs of people living with HIV (PLHIV) as well as active tuberculosis (TB/HIV), latent tuberculosis infection (LTBI/HIV) or without TB (HIV/AIDS). METHODS: We analysed the costs through the entire pathway of care during the prediagnosis and treatment periods from the Brazilian public health system perspective. We applied a combination of bottom-up and top-down approaches to capture and estimate direct medical and non-medical costs. We measured the mean cost per patient per type of care (inpatient, outpatient and emergency care) and disease category (HIV/AIDS, HIV/AIDS death, TB/HIV, TB/HIV death and LTBI/HIV). RESULTS: Between March 2014 and March 2016 we recruited 239 PLHIV. During the follow-up 26 patients were diagnosed and treated for TB and 5 received chemoprophylaxis for LTBI. During the prediagnosis and treatment period, the mean total costs for HIV or AIDS and AIDS death categories were US$1558 and US$2828, respectively. The mean total costs for TB/HIV and TB/HIV death categories were US$5289.0 and US$8281, respectively. The mean total cost for the LTBI/HIV category was US$882. CONCLUSIONS: Patients with TB/HIV impose a higher economic burden on the health system than HIV/AIDS and LTBI/HIV. Patients with LTBI/HIV were the lowest cost group among all disease categories, indicating that preventive TB treatment can avoid the further costs treating active TB. TRIAL REGISTRATION NUMBER: RBR-22t943, Results.

Treatment completion for latent tuberculosis infection in Norway: a prospective cohort study.

BACKGROUND: Successful treatment of latent tuberculosis infection (LTBI) is essential to reduce tuberculosis (TB) incidence rates in low-burden countries. This study measures treatment completion and determinants of non-completion of LTBI treatment in Norway in 2016. METHODS: This prospective cohort study included all individuals notified with LTBI treatment to the Norwegian Surveillance System for Infectious Diseases (MSIS) in 2016. We obtained data from MSIS and from a standardized form that was sent to health care providers at the time of patient notification to MSIS. We determined completion rates. Pearson's chi squared test was used to study associations between pairs of categorical variables and separate crude and multivariable logistic regression models were used to identify factors associated with treatment completion and adverse drug effects. RESULTS: We obtained information on treatment completion from 719 of the 726 individuals notified for LTBI treatment in 2016. Overall, 91% completed treatment. Treatment completion was highest in the foreign-born group [foreign-born, n = 562 (92%) vs Norwegian-born, n = 115 (85%), p = 0.007]. Treatment completion did not differ significantly between prescribed regimens (p = 0.124). Adverse events were the most common reason for incomplete treatment. We found no significant differences in adverse events when comparing weekly rifapentine (3RPH) with three months daily isoniazid and rifampicin (3RH). However, there were significantly fewer adverse events with 3RPH compared to other regimens (p = 0.037). Age over 35 years was significantly associated with adverse events irrespective of regimen (p = 0.024), whereas immunosuppression was not significantly associated with adverse events after adjusting for other variables (p = 0.306). Treatment under direct observation had a significant effect on treatment completion for foreign-born (multivariate Wald p-value = 0.017), but not for Norwegian-born (multivariate Wald p-value = 0.408) individuals. CONCLUSIONS: We report a very high treatment completion rate, especially among individuals from countries with high TB incidence. The follow-up from tuberculosis-coordinators and the frequent use of directly observed treatment probably contributes to this. Few severe adverse events were reported, even with increased age and in individuals that are more susceptible. While these results are promising, issues of cost-effectiveness and targeting treatment to individuals at highest risk of TB are important components of public health impact.

The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA: a systematic review.

BackgroundMigrants account for a large and growing proportion of tuberculosis (TB) cases in low-incidence countries in the European Union/European Economic Area (EU/EEA) which are primarily due to reactivation of latent TB infection (LTBI). Addressing LTBI among migrants will be critical to achieve TB elimination. Methods: We conducted a systematic review to determine effectiveness (performance of diagnostic tests, efficacy of treatment, uptake and completion of screening and treatment) and a second systematic review on cost-effectiveness of LTBI screening programmes for migrants living in the EU/EEA. Results: We identified seven systematic reviews and 16 individual studies that addressed our aims. Tuberculin skin tests and interferon gamma release assays had high sensitivity (79%) but when positive, both tests poorly predicted the development of active TB (incidence rate ratio: 2.07 and 2.40, respectively). Different LTBI treatment regimens had low to moderate efficacy but were equivalent in preventing active TB. Rifampicin-based regimens may be preferred because of lower hepatotoxicity (risk ratio = 0.15) and higher completion rates (82% vs 69%) compared with isoniazid. Only 14.3% of migrants eligible for screening completed treatment because of losses along all steps of the LTBI care cascade. Limited economic analyses suggest that the most cost-effective approach may be targeting young migrants from high TB incidence countries. Discussion: The effectiveness of LTBI programmes is limited by the large pool of migrants with LTBI, poorly predictive tests, long treatments and a weak care cascade. Targeted LTBI programmes that ensure high screening uptake and treatment completion will have greatest individual and public health benefit.

The economic burden of tuberculosis and latent tuberculosis in people living with HIV in Brazil: a cost study from the patient perspective.

OBJECTIVE: The objective of this study was to evaluate the direct and indirect costs of tuberculosis (TB) (active and latent TB [LTB]) and HIV co-infection from the patient perspective. STUDY DESIGN: Costing study conducted alongside a pragmatic clinical trial. METHODS: The study was conducted in Brazil in a referral service for HIV/AIDS. We applied a standardised questionnaire to collect data about out-of-pocket expenses and indirect cost. The questionnaire was applied at every patient's appointment in the referral service after TB or LTB diagnosis. We followed all patients' pathways during the prediagnosis period and treatment period. For patients on sickness benefit due to TB/HIV, income loss was calculated as the difference between an employee's wages forgone and the sickness benefit received. The monetary value of the time loss was calculated based on the Brazilian minimum wage/2015. RESULTS: Among 239 people living with HIV recruited in the first year of the trial, 31 patients were included into the costing study, 26 patients who were diagnosed and treated for TB/HIV and five patients who were diagnosed and treated for LTB/HIV. TB/HIV patients incurred higher total costs than LTB/HIV (US$ 1,429 vs US$ 166). The main cost component for TB/HIV was indirect costs, especially income loss (US$ 749). CONCLUSIONS: Public health policies may address ways to prevent high patients' costs through the introduction of more accurate algorithms for TB diagnosis to prevent delays in the diagnosis and treatment.

Systematic Review, Meta-analysis, and Cost-effectiveness of Treatment of Latent Tuberculosis to Reduce Progression to Multidrug-Resistant Tuberculosis.

BACKGROUND.: Evidence-based recommendations for treating persons having presumed latent tuberculosis (LTBI) after contact to infectious multidrug-resistant (MDR) tuberculosis (TB) are lacking because published data consist of small observational studies. Tuberculosis incidence in persons treated for latent MDR -TB infection is unknown. METHODS.: We conducted a systematic review of studies published 1 January 1994-31 December 2014 to analyze TB incidence, treatment completion and discontinuation, and cost-effectiveness. We considered contacts with LTBI effectively treated if they were on ≥1 medication to which their MDR-TB strain was likely susceptible. We selected studies that compared treatment vs nontreatment outcomes and performed a meta-analysis to estimate the relative risk of TB incidence and its 95% confidence interval. RESULTS.: We abstracted data from 21 articles that met inclusion criteria. Six articles presented outcomes for contacts who were treated compared with those not treated for MDR-LTBI; 10 presented outcomes only for treated contacts, and 5 presented outcomes only for untreated contacts. The estimated MDR-TB incidence reduction was 90% (9%-99%) using data from 5 comparison studies. We also found high treatment discontinuation rates due to adverse effects in persons taking pyrazinamide-containing regimens. Cost-effectiveness was greatest using a fluoroquinolone/ethambutol combination regimen. CONCLUSIONS.: Few studies met inclusion criteria, therefore results should be cautiously interpreted. We found a reduced risk of TB incidence with treatment for MDR-LTBI, suggesting effectiveness in prevention of progression to MDR-TB, and confirmed cost-effectiveness. However, we found that pyrazinamide-containing MDR-LTBI regimens often resulted in treatment discontinuation due to adverse effects.

Revisiting annual screening for latent tuberculosis infection in healthcare workers: a cost-effectiveness analysis.

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.

SIRCLE: a randomised controlled cost comparison of self-administered short-course isoniazid and rifapentine for cost-effective latent tuberculosis eradication.

BACKGROUND: Currently, treatment of latent tuberculosis infection (LTBI) in Australia consists most commonly of a 9-month course of isoniazid (9H). A 3-month course of weekly isoniazid and rifapentine (3HP) has been shown to be as effective as 9 months of daily isoniazid, and associated with less hepatotoxicity; however, rifapentine is not currently available in Australia. Introduction of this regimen would have apparent advantages for people with LTBI in Victoria by safely shortening duration of LTBI therapy. However, the cost benefit of this new therapeutic approach is uncertain. AIM: Cost-analysis of standard and short-course therapy for LTBI in an Australian context. METHODS: Single-centre randomised controlled trial conducted between December 2013-March 2016. Participants underwent 1:1 randomisation to either a 9-month course of daily isoniazid or a 12-week course of weekly isoniazid and rifapentine. The primary outcome measure was total healthcare system costs (in Australian dollars; AUD) per completed course of LTBI therapy. Secondary cost analyses were performed to consider varying assumptions regarding commercial cost of rifapentine. RESULTS: Overall, 34 of 40 (85%) participants in the 9H group and 36/40 (90%) in the 3HR group completed therapy. One patient in the 3HP group was hospitalised for a febrile illness; no hospitalisations were recorded in the 9H group. The cost per completed course of 9H was 601 AUD, while that of 3HP was significantly lower at 511 AUD (P < 0.01). CONCLUSIONS: This study provides cost analysis evidence to support the use of 3HP for the treatment of LTBI in Australia.

How much does tuberculosis cost? An Australian healthcare perspective analysis.

Tuberculosis (TB) remains a disease of high morbidity in Australia, with implications for both public health and the individual. Cost analyses is relevant for programmatic evaluation of TB. There is minimal published TB cost data in the Australian setting. Patients with drug sensitive active pulmonary TB (DS-PTB) and latent TB (LTBI) were enrolled in a single tertiary referral centre to evaluate healthcare provider costs. The median cost of treating drug susceptible pulmonary TB in this case series was 11,538 AUD. Approximately 50% of total costs is derived from inpatient hospitalisation bed days. In comparison, the average cost of managing latent TB was 582 AUD per completed course. We find the median provider cost of our DS-PTB treatment group comparable to costs from other regions globally with similar economic profiles. A program designed to detect and treat LTBI to prevent subsequent disease may be cost effective in appropriately selected patients and warrants further study.

Methods Used in Economic Evaluations of Tuberculin Skin Tests and Interferon Gamma Release Assays for the Screening of Latent Tuberculosis Infection: A Systematic Review.

BACKGROUND: Latent tuberculosis infection (LTBI) provides a constant pool of new active tuberculosis cases; a third of the earth's population is estimated to be infected with LTBI. OBJECTIVE: The objective of this systematic review was to assess the quality and summarize the available evidence from published economic evaluations reporting on the cost-effectiveness of tuberculin skin tests (TSTs) compared with interferon gamma release assays (IGRAs) for the screening of LTBI. METHODS: An extensive systematic review of the published literature was conducted. A two-step process was adopted to identify relevant articles: information was extracted into evidence tables and then analyzed. The quality of the publications was assessed using a 10-item checklist specific for economic evaluations. RESULTS: Twenty-eight studies were identified for inclusion in this review. Most of the studies found IGRAs to be more cost-effective than TSTs; however, the conclusions from the studies varied significantly. Most studies scored highly on the checklist although only one fulfilled all the stipulated criteria. A wide variety of methodological approaches were documented; identified differences included the type of economic evaluation and model, time horizon, perspective, and outcomes measures. CONCLUSIONS: The lack of consistent methods across studies makes it difficult to draw any firm conclusions about the most cost-effective option between TSTs and IGRAs. This problem can be solved by improving the quality of economic evaluation studies in the field of LTBI screening, through adherence to quality checklists.

Decreasing cost effectiveness of testing for latent TB in HIV in a low TB incidence area.

Testing for latent tuberculosis infection (LTBI) in HIV-infected persons in low tuberculosis (TB) incidence areas is often recommended. Using contemporary, clinical data, we report the yield and cost-effectiveness of testing all HIV attendees, two current UK strategies and no LTBI testing. Economic modelling was performed utilising 10-year follow up data from a large HIV clinical cohort. Outcomes were numbers of cases of active TB and incremental cost per quality-adjusted life year (QALY) gained. Between 2000 and 2010, 256 people were treated for TB/HIV co-infection. 72 (28%) occurred ≥3 months after HIV diagnosis and may have been prevented by LTBI testing. Between 2000 and 2005, the incremental cost per QALY gained for the British HIV Association (BHIVA) and UK National Institute of Care Excellence (NICE) strategies, and testing all clinic attendees was €6270, €6998 and €33,473, respectively. These rose to €9332, €32,564 and €74,067, respectively, between 2005 and 2010. Probabilistic sensitivity analysis suggested that at a threshold of €24,000 per additional QALY, the most cost-effective strategies would be NICE or testing all in 2000-2005 and BHIVA during 2005-2010. Both UK testing regimens missed cases but are cost-effective compared with no testing. Using recent data, they all became more expensive, suggesting that alternative or more targeted TB testing strategies must be considered.

A cost-benefit analysis of a proposed overseas refugee latent tuberculosis infection screening and treatment program.

BACKGROUND: This study explored the effect of screening and treatment of refugees for latent tuberculosis infection (LTBI) before entrance to the United States as a strategy for reducing active tuberculosis (TB). The purpose of this study was to estimate the costs and benefits of LTBI screening and treatment in United States bound refugees prior to arrival. METHODS: Costs were included for foreign and domestic LTBI screening and treatment and the domestic treatment of active TB. A decision tree with multiple Markov nodes was developed to determine the total costs and number of active TB cases that occurred in refugee populations that tested 55, 35, and 20 % tuberculin skin test positive under two models: no overseas LTBI screening and overseas LTBI screening and treatment. For this analysis, refugees that tested 55, 35, and 20 % tuberculin skin test positive were divided into high, moderate, and low LTBI prevalence categories to denote their prevalence of LTBI relative to other refugee populations. RESULTS: For a hypothetical 1-year cohort of 100,000 refugees arriving in the United States from regions with high, moderate, and low LTBI prevalence, implementation of overseas screening would be expected to prevent 440, 220, and 57 active TB cases in the United States during the first 20 years after arrival. The cost savings associated with treatment of these averted cases would offset the cost of LTBI screening and treatment for refugees from countries with high (net cost-saving: $4.9 million) and moderate (net cost-saving: $1.6 million) LTBI prevalence. For low LTBI prevalence populations, LTBI screening and treatment exceed expected future TB treatment cost savings (net cost of $780,000). CONCLUSIONS: Implementing LTBI screening and treatment for United States bound refugees from countries with high or moderate LTBI prevalence would potentially save millions of dollars and contribute to United States TB elimination goals. These estimates are conservative since secondary transmission from tuberculosis cases in the United States was not considered in the model.

Cost-effectiveness analysis of optimal control measures for tuberculosis.

We propose and analyze an optimal control problem where the control system is a mathematical model for tuberculosis that considers reinfection. The control functions represent the fraction of early latent and persistent latent individuals that are treated. Our aim was to study how these control measures should be implemented, for a certain time period, in order to reduce the number of active infected individuals, while minimizing the interventions implementation costs. The optimal intervention is compared along different epidemiological scenarios, by varying the transmission coefficient. The impact of variation of the risk of reinfection, as a result of acquired immunity to a previous infection for treated individuals on the optimal controls and associated solutions, is analyzed. A cost-effectiveness analysis is done, to compare the application of each one of the control measures, separately or in combination.

Optimizing screening for tuberculosis and hepatitis B prior to starting tumor necrosis factor-α inhibitors in Crohn's disease.

BACKGROUND AND AIMS: Treatment with tumor necrosis factor-α (TNF-α) inhibitors in patients with Crohn's disease (CD) is associated with potentially serious infections, including tuberculosis (TB) and hepatitis B virus (HBV). We assessed the cost-effectiveness of extensive TB screening and HBV screening prior to initiating TNF-α inhibitors in CD. METHODS: We constructed two Markov models: (1) comparing tuberculin skin test (TST) combined with chest X-ray (conventional TB screening) versus TST and chest X-ray followed by the interferon-gamma release assay (extensive TB screening) in diagnosing TB; and (2) HBV screening versus no HBV screening. Our base-case included an adult CD patient starting with infliximab treatment. Input parameters were extracted from the literature. Direct medical costs were assessed and discounted following a third-party payer perspective. The main outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity and Monte Carlo analyses were performed over wide ranges of probability and cost estimates. RESULTS: At base-case, the ICERs of extensive screening and HBV screening were €64,340 and €75,760 respectively to gain one quality-adjusted life year. Sensitivity analyses concluded that extensive TB screening was a cost-effective strategy if the latent TB prevalence is more than 12 % or if the false positivity rate of TST is more than 20 %. HBV screening became cost-effective if HBV reactivation or HBV-related mortality is higher than 37 and 62 %, respectively. CONCLUSIONS: Extensive TB screening and HBV screening are not cost-effective compared with conventional TB screening and no HBV screening, respectively. However, when targeted at high-risk patient groups, these screening strategies are likely to become cost-effective.

Current treatment options for latent tuberculosis infection.

Treatment of latent tuberculosis infection (LTBI) is a key component in TB control strategies worldwide. However, as people with LTBI are neither symptomatic nor contagious, any screening decision should be weighed carefully against the potential benefit of preventing active disease in those who are known to be at higher risk and are willing to accept therapy for LTBI. This means that a targeted approach is desirable to maximize cost effectiveness and to guarantee patient adherence. We focus on LTBI treatment strategies in patient populations at increased risk of developing active TB, including candidates for treatment with tumor necrosis factor-α blockers. In the last 40 years, isoniazid (INH) has represented the keystone of LTBI therapy across the world. Although INH remains the first therapeutic option, alternative treatments that are effective and associated with increased adherence and economic savings are available. Current recommendations, toxicity, compliance, and cost issues are discussed in detail in this review. A balanced relationship between the patient and healthcare provider could increase adherence, while cost-saving treatment strategies with higher effectiveness, fewer side effects, and of shorter duration should be offered as preferred.