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Objectives: In California, about 80% of tuberculosis disease is caused by untreated latent tuberculosis infection (LTBI), and the rate of LTBI is higher among incarcerated persons (16%) than among nonincarcerated persons (6%). We compared 2 regimens to treat LTBI in an adult prison population in California: 9 months of twice-weekly isoniazid (9H; previous standard of care) and 12 once-weekly doses of isoniazid and rifapentine (3HP; introduced in 2011). Methods: We evaluated the rates of completion and discontinuation caused by hepatotoxicity among randomly selected patients with LTBI prescribed the 9H regimen in 2011 and among patients with LTBI prescribed the 3HP regimen who entered California prisons during September 2013–March 2014. We compared the cost per fully treated patient for the 2 regimens. Results: Of 92 patients treated with the 9H regimen, the treatment completion rate was 42% and discontinuation due to hepatotoxicity was 14%. Of 122 patients who accepted the 3HP regimen, the completion rate was 90% and discontinuation due to hepatotoxicity was 2%. The cost per fully treated patient for the 9H regimen was $981 and for 3HP was $652. Conclusions: In an incarcerated population, the 3HP regimen had a higher completion rate, lower hepatotoxicity, and lower cost per fully treated patient than the 9H regimen. If coupled with a high treatment initiation rate, the high rate of LTBI treatment completion with 3HP may contribute to reducing tuberculosis morbidity in California.

ObjectiveThe 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).MethodsWe 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).ResultsBetween 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.ConclusionsPatients 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 numberRBR-22t943, Results.

RationaleTreatment for latent tuberculosis infection with isoniazid for 9 months (9INH) has poor completion and serious adverse events, while treatment for 4 months with daily rifampin (4RIF) has significantly higher completion and fewer adverse events.ObjectivesTo compare the health system costs of 4RIF and 9INH.MethodsIn a randomised trial conducted in five Canadian centres, one Brazilian and one Saudi Arabian centre, consenting subjects were randomised to receive 4RIF or 9INH. Health system costs were estimated from healthcare utilisation including scheduled and unscheduled visits, investigations and drugs. All activities for all subjects were evaluated using financial information from 2007 from the Montreal Chest Institute. Costs were expressed in Canadian dollars.ResultsTotal health system cost per patient allocated to 4RIF was $854 compared with $970 for 9INH (p<0.0001). The average cost per patient for the 328 of 420 (78%) who completed 4RIF therapy was $1094 compared with $1625 for the 254 of 427 (60%) completing 9INH (p<0.0001). Costs were modestly increased in patients with minor intolerance and substantially increased if the treating physician stopped treatment because of possible adverse events. Total costs related to management of adverse events with 9INH were $48 142 compared with $25 684 for 4RIF (p=0.008). Using these data, incremental cost-effectiveness analyses showed that 4RIF would be cost saving and prevent more cases within 2 years if efficacy exceeded 74%, and cost saving if efficacy exceeded 65%.ConclusionsThe 4RIF regimen was significantly cheaper per patient completing treatment because of better completion and fewer adverse events.RCT registration numberNCT00170209.

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.

Migrants from high to low tuberculosis (TB) incidence countries may benefit from screening for latent TB infection (LTBI), but the optimal approaches and effectiveness are not well described. Our primary objective was to synthesise evidence for cost-effectiveness, and barriers and facilitators to successful implementation, of LTBI screening programmes for migrants entering high income, low TB burden countries. Evidence was synthesised using rapid review methodologies. 41 studies (including 2 reviews) were included, covering the European region and national programmes. Main settings of LTBI screening were primary care, new arrivals clinics, and schools. The most frequently cited facilitator was structural cohesiveness (integration of health care services, collaboration with community partnerships, and co-ordination of care with social workers or accommodation staff). The most frequently cited barrier was lack of understanding and misconceptions of service users. Economic evaluations consistently demonstrated long term cost-savings for LTBI programmes. Screening migrants from countries of origin of the highest TB burden is more cost-effective but less likely to identify all TB and ultimately eliminate TB compared to screening at a lower TB burden threshold. We found consistent evidence that LTBI screening programmes for migrants from high to low tuberculosis TB incidence countries can be effective and cost-saving in a variety of settings. A co-ordinated, integrated approach is a key programme facilitator.

Background Expanding tuberculosis preventive treatment (TPT) for high-risk populations with latent tuberculosis infection (LTBI) is a key component of the End TB Strategy. However, the high-risk population size is small, which may have limited impact on reducing TB incidence. We aimed to evaluate the health impact and cost-effectiveness of expanding TPT to key community-level population Methods We developed a dynamic transmission model incorporating the effect of TPT and seasonal variations in TB incidence. The model was calibrated by monthly pulmonary tuberculosis (PTB) case data during 2011–2018 from Shaanxi province, China, and validated by data in 2019. We first assessed the TB epidemic trend for seven expanding TPT strategies and sought the optimal TPT strategy that can reach the target of the End TB Strategy by 2035. Then, we calculated the incremental cost-effectiveness ratios (ICER) of this optimal TPT strategy with five TPT regimens (isoniazid monotherapy with two different durations, rifampin monotherapy, and combinations of isoniazid with rifampin or rifapentine) over 2025–2050, compared with no TPT, from a health system perspective. A willingness-to-pay threshold of US $36,378 (three times the per-capita gross domestic product of Shaanxi province in 2023) was used. Results The optimal TPT strategy is implementing TPT for all WHO-recommended populations and individuals with LTBI aged ≥ 50 at the community level (starting in 2025 with full coverage within 1 year), which could reduce the PTB incidence rate to 1.83/100,000 by 2035, meeting the WHO target of a 90% reduction (5.64/100,000) compared with 2015. This strategy with five TPT regimens was all cost-effective compared with no TPT, with ICER ranging from US $154 (3 months of daily rifampicin plus isoniazid, 3HR) to US $910 (9 months of daily isoniazid monotherapy, 9H) per quality-adjusted life-year (QALY) gained. Conclusions Rapid TPT implementation for all WHO-recommended populations and individuals with LTBI aged ≥ 50 at the community level is critical to achieving TB elimination by 2035. The 3HR regimen, widely performed in clinical practice in China, offers the greatest cost-effectiveness, which provides health economic evidence to expand this regimen further.

Currently, interferon-gamma release assay (IGRA) is costly and not included as latent tuberculosis infection (LTBI) screening test strategy in Thailand’s Universal Coverage Scheme (UCS) benefit package. The objective of this study was to assess the cost-utility of LTBI screening strategies among tuberculosis (TB) contacts in Thailand. A hybrid decision tree and Markov model was developed to compare the lifetime costs and health outcomes of tuberculin skin test (TST) and IGRA, in comparison to no screening, based on a societal perspective. Health outcomes were the total number of TB cases averted and quality-adjusted life years (QALYs), with results presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to explore uncertainties in all parameters. The ICER of TST compared with no screening was 27,645 baht per QALY gained, while that of IGRA compared to TST was 851,030 baht per QALY gained. In a cohort of 1000 TB contacts, both TST and IGRA strategies could avert 282 and 283 TB cases, respectively. At the Thai societal willingness-to-pay threshold of 160,000 baht per QALY gained, TST was deemed cost-effective, whereas IGRA would not be cost-effective, unless the cost of IGRA was reduced to 1,434 baht per test.

Host-response-based transcriptional signatures (HrTS) have been developed to identify \"incipient tuberculosis (TB)\". No study has reported the cost-effectiveness of HrTS for post-arrival migrant screening programs in low-incidence countries. The aim of this study was to assess the potential health impact and cost-effectiveness of HrTS for post-arrival TB infection screening among new migrants in the United States. We used a discrete-event simulation model to compare four strategies: (1) no screening for TB infection or incipient TB; (2) 'IGRA-only', screen all with interferon-gamma release assay (IGRA), provide TB preventive treatment for IGRA-positives; (3) 'IGRA-HrTS', screen all with IGRA followed by HrTS for IGRA-positives, provide incipient TB treatment for individuals testing positive with both tests; and (4) 'HrTS-only', screen all with HrTS, provide incipient TB treatment for HrTS-positives. We assessed outcomes over the lifetime of migrants entering the United Stataes (U.S.) in 2019, assuming HrTS met WHO Target Product Profile (TPP) optimal criteria. We conducted sensitivity analyses to evaluate the robustness of results. Our findings show that at a willingness-to-pay threshold of $150,000 per quality-adjusted life-year (QALY) gained, the IGRA-only strategy was the optimal strategy under both healthcare sector and societal perspectives, with an incremental cost-effectiveness ratio (ICER) of $104,138 and $143,103 per QALY gained, respectively. At a willingness-to-pay of $100,000 per QALY gained the IGRA-HrTS strategy appeared optimal. When the cohort was stratified by TB incidence in the country-of-origin, the IGRA-only strategy was optimal for country-of-origin incidence [Formula: see text]100 per 100,000, and the no-screening strategy was optimal for country-of-origin incidence <10 per 100,000. The IGRA-HrTS strategy was potentially cost-effective with country-of-origin incidence of 10-100 per 100,000, though this result had substantial uncertainty. Results were sensitive to time trends in TB progression risk after U.S. entry. An HrTS test meeting WHO TPP optimal criteria would be potentially cost-effective for post-arrival screening among a subset of U.S. migrants, but this result was sensitive to multiple factors.

Continuing rises in tuberculosis notifications in the UK are attributable to cases in foreign-born immigrants. National guidance for immigrant screening is hampered by a lack of data about the prevalence of, and risk factors for, latent tuberculosis infection in immigrants. We aimed to determine the prevalence of latent infection in immigrants to the UK to define which groups should be screened and to quantify cost-effectiveness. In our multicentre cohort study and cost-effectiveness analysis we analysed demographic and test results from three centres in the UK (from 2008 to 2010) that used interferon-γ release-assay (IGRA) to screen immigrants aged 35 years or younger for latent tuberculosis infection. We assessed factors associated with latent infection by use of logistic regression and calculated the yields and cost-effectiveness of screening at different levels of tuberculosis incidence in immigrants' countries of origin with a decision analysis model. Results for IGRA-based screening were positive in 245 of 1229 immigrants (20%), negative in 982 (80%), and indeterminate in two (0·2%). Positive results were independently associated with increases in tuberculosis incidence in immigrants' countries of origin (p=0·0006), male sex (p=0·046), and age (p<0·0001). National policy thus far would fail to detect 71% of individuals with latent infection. The two most cost-effective strategies were to screen individuals from countries with a tuberculosis incidence of more than 250 cases per 100 000 (incremental cost-effectiveness ratio [ICER] was £17 956 [£1=US$1·60] per prevented case of tuberculosis) and at more than 150 cases per 100 000 (including immigrants from the Indian subcontinent), which identified 92% of infected immigrants and prevented an additional 29 cases at an ICER of £20 819 per additional case averted. Screening for latent infection can be implemented cost-effectively at a level of incidence that identifies most immigrants with latent tuberculosis, thereby preventing substantial numbers of future cases of active tuberculosis. Medical Research Council and Wellcome Trust.

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.