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.

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.

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.

Factors associated with catastrophic total costs due to tuberculosis under a designated hospital service model: a cross-sectional study in China.

BACKGROUND: Certain districts and counties in China designated local general hospital as the designated hospital for tuberculosis (TB) management after the promulgation of the Law of Practicing Physicians in 2009. To our knowledge, there is limited research on catastrophic payments of TB patients under this service model, often with inconsistent conclusions. In addition, there has been no published studies from China using the updated 2018 World Health Organization (WHO) definition of catastrophic total costs due to TB. This study used the latest criterion recommended by the WHO to analyze the incidence of catastrophic total costs for households affected by TB under the designated hospital model and explore its influencing factors. METHODS: A cross-sectional analysis was carried out in all ten designated hospitals in Ningbo, China. Eligible pulmonary TB cases confirmed by sputum culture of Mycobacterium tuberculosis were recruited and surveyed from September 2018 to October 2018. We evaluated catastrophic total costs using total costs for TB treatment exceeding 20% of the household's annual pre-TB income. A sensitivity analysis was performed while varying the thresholds. The least absolute shrinkage and selection operator (LASSO) regression were applied to select variables, and multiple logistic regression analysis were used to identify the determinants of catastrophic total costs. RESULTS: A total of 672 patients were included, with a median age of 41 years old. The rate of catastrophic total costs of surveyed households was 37.1%, and that of households affected by MDR was 69.6%. Medical cost accounted for more than 60% of the total cost. 57.7% cases were hospitalized. The hospitalization rates of patients with no comorbidities, no severe adverse drug reactions, and rifampin-sensitive TB were 53.9, 54.9, and 55.3%, respectively. Patients in the poorest households had the highest hospitalization rates (Q1:54.8%, Q2:61.4%, Q3:52.2%, Q4:49.5%, Q5:69.7%, P = 0.011) and the highest incidence of severe adverse drug reactions (Q1:29.6%, Q2:19.6%, Q3:28.0%, Q4:33.7%, Q5:35.3%, P = 0.034). Factors such as elderly, minimum living security, unemployed before or after illness, poor economic status, seeking medical care outside the city, hospitalization, absence of local basic medical insurance coverage and MDR were positively associated with catastrophic costs. CONCLUSION: Substantial proportions of patients and households affected by pulmonary TB faced catastrophic economic risks in Ningbo, China. The existing policies that focus on expanding the coverage of basic medical insurance and economic protection measures (such as cash transfers to compensate low-income households for direct non-medical costs and income loss) might be insufficient. Tailored program that mitigate inappropriate healthcare and address equity of care delivery are worthy of attention.

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.

Cost-effectiveness of Preventive Therapy for Tuberculosis With Isoniazid and Rifapentine Versus Isoniazid Alone in High-Burden Settings.

Background: A short-course regimen of 3 months of weekly rifapentine and isoniazid (3HP) has recently been recommended by the World Health Organization as an alternative to at least 6 months of daily isoniazid (isoniazid preventive therapy [IPT]) for prevention of tuberculosis (TB). The contexts in which 3HP may be cost-effective compared to IPT among people living with human immunodeficiency virus are unknown. Methods: We used a Markov state transition model to estimate the incremental cost-effectiveness of 3HP relative to IPT in high-burden settings, using a cohort of 1000 patients in a Ugandan HIV clinic as an emblematic scenario. Cost-effectiveness was expressed as 2017 US dollars per disability-adjusted life year (DALY) averted from a healthcare perspective over a 20-year time horizon. We explored the conditions under which 3HP would be considered cost-effective relative to IPT. Results: Per 1000 individuals on antiretroviral therapy in the reference scenario, treatment with 3HP rather than IPT was estimated to avert 9 cases of TB and 1 death, costing $9402 per DALY averted relative to IPT. Cost-effectiveness depended strongly on the price of rifapentine, completion of 3HP, and prevalence of latent TB. At a willingness to pay of $1000 per DALY averted, 3HP is likely to be cost-effective relative to IPT only if the price of rifapentine can be greatly reduced (to approximately $20 per course) and high treatment completion (85%) can be achieved. Conclusions: 3HP may be a cost-effective alternative to IPT in high-burden settings, but cost-effectiveness depends on the price of rifapentine, achievable completion rates, and local willingness to pay.

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.

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.

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-effectiveness of rifampin for 4 months and isoniazid for 9 months in the treatment of tuberculosis infection.

The purpose of this study was to evaluate the cost-effectiveness of the strategy of controlling the contacts of tuberculosis patients with latent tuberculosis infection by means of treatment with rifampin for 4 months or isoniazid for 9 months. The cost was the sum of the cost of treating latent tuberculosis infection in all contacts plus the cost of treating tuberculosis in whom the disease was not avoided. The effectiveness was expressed as cases avoided. The efficacy adopted was 90 % for rifampin for 4 months and 93 % for isoniazid for 9 months. We carried out a sensitivity analysis for efficacies of rifampin for 4 months of 80 %, 75 %, 69 % and 65 %. Of the 1,002 patients studied, 139 were treated with rifampin for 4 months and 863 were treated with isoniazid for 9 months. The cost-effectiveness was 436,842.83/50 cases avoided with rifampin for 4 months and 692,164.42/40 cases avoided with isoniazid for 9 months. Rifampin for 4 months was dominant. In the sensitivity analysis, rifampin for 4 months was dominant for efficacies of 75 % or greater. The cost-effectiveness analysis favoured the use of rifampin for 4 months when its efficacy was 75 % or greater.

The impact and cost-effectiveness of strategies to detect drug-resistant tuberculosis.

Drug-resistant tuberculosis (TB) is a serious emerging problem in many low-resource countries. TB control programmes are uncertain of which drug susceptibility tests (DSTs) to use and when to test patients. We predicted the potential cost-effectiveness of different DST strategies, in settings with varying prevalence of drug resistance. Using decision analysis, we assessed the cost-effectiveness of conventional and rapid DSTs for previously diagnosed smear-positive TB cases. Five different time-points were considered for administering DSTs. Different initial drug resistance and HIV scenarios were also considered. All DST scenarios in the wide range of settings considered were found to be cost-effective. The strategy of performing a rapid DST that detects any form of isoniazid (INH) and rifampicin (RIF) resistance for all patients before the initiation of treatment was predicted to be the most cost-effective strategy. In a setting with moderate drug resistance, the cost per disability-adjusted life year gained was as low as US$744. Our findings support the roll-out of rapid drug susceptibility testing at the moment of diagnosis to detect any form of INH and RIF resistance in all countries with moderate or greater burdens of drug-resistant TB.

Why Do We Use 600 mg of Rifampicin in Tuberculosis Treatment?

The 600-mg once daily dose of rifampicin plays a key role in tuberculosis treatment. The evidence underpinning this dose is scant. A review of the historical literature identified 3 strands of reasoning. The first is the pharmacokinetic argument: The 600-mg dose yields serum drug concentrations well above the minimum inhibitory concentration of rifampicin against Mycobacterium tuberculosis. The second is the argument that adverse events may be dose related. The third is the economic argument: Rifampicin was prohibitively expensive at the time of its introduction. Recent in vitro, animal, and early bactericidal activity studies suggest that the 600-mg once daily dose is at the lower end of the dose-response curve, refuting the pharmacokinetic argument. The reduced cost and the lack of evidence of toxicity at higher daily doses remove the other arguments. To optimize tuberculosis treatment, the clinical value of higher doses of rifampicin should be tested in clinical trials.

Impact of treatment completion, intolerance and adverse events on health system costs in a randomised trial of 4 months rifampin or 9 months isoniazid for latent TB.

RATIONALE: Treatment 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. OBJECTIVES: To compare the health system costs of 4RIF and 9INH. METHODS: In 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. RESULTS: Total 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%. CONCLUSIONS: The 4RIF regimen was significantly cheaper per patient completing treatment because of better completion and fewer adverse events.

Costs and cost-effectiveness of four treatment regimens for latent tuberculosis infection.

RATIONALE: Isoniazid given daily for 9 months is the standard treatment for latent tuberculosis infection (LTBI), but its effectiveness is limited by poor completion rates. Shorter course regimens and regimens using directly observed therapy result in improved adherence but have higher upfront costs. OBJECTIVES: To evaluate the costs and cost-effectiveness of regimens for the treatment of LTBI. METHODS: We used a computerized Markov model to estimate total societal costs and benefits associated with four regimens for the treatment of LTBI: self-administered isoniazid daily for 9 months, directly observed isoniazid twice-weekly for 9 months, directly observed isoniazid plus rifapentine once weekly for 3 months, and self-administered rifampin daily for 4 months. In the base-case analysis, subjects were assumed to have newly positive tuberculin skin tests after recent exposure to infectious tuberculosis. MEASUREMENTS AND MAIN RESULTS: We determined the costs of treatment, quality-adjusted life-years gained, and cases of active tuberculosis prevented. In the base-case analysis, rifampin dominated (less costly with increased benefits) all other regimens except isoniazid plus rifapentine, which was more effective at a cost $48,997 per quality-adjusted life year gained. Isoniazid plus rifapentine dominated all regimens at a relative risk of disease 5.2 times the baseline estimate, or with completion rates less than 34% for isoniazid or 37% for rifampin. Rifampin could be 17% less efficacious than self-administered isoniazid and still be cost-saving compared with this regimen. CONCLUSIONS: In our model, rifampin is cost-saving compared with the standard therapy of self-administered isoniazid. Isoniazid plus rifapentine is cost-saving for extremely high-risk patients and is cost-effective for lower-risk patients.

Multi-drug resistant tuberculosis burden and risk factors: an update.

Multi-drug resistant (MDR) tuberculosis is defined as disease caused by Mycobacterium tuberculosis with resistance to at least two anti-tubercular drugs Isoniazid and Rifampicin. Recent surveillance data have revealed that prevalence of the drug resistant tuberculosis has risen to the highest rate ever recorded in the history. Drug resistant tuberculosis generally arises through the selection of mutated strains by inadequate therapy. The most powerful predictor of the presence of MDR-TB is a history of treatment of TB. Shortage of drugs has been one of the most common reasons for the inadequacy of the initial anti-TB regimen, especially in resource poor settings. Other major issues significantly contributing to the higher complexity of the treatment of MDR-TB is the increased cost of treatment. Other factors also play important role in the development of MDR-TB such as poor administrative control on purchase and distribution of the drugs with no proper mechanism on quality control and bioavailability tests. Tuberculosis control program implemented in past has also partially contributed to the development of drug resistance due to poor follow up and infrastructure. The association known for centuries between TB and poverty also applies to MDR-TB, a rather significant inverse association with MDR-TB. Various treatment strategies have been employed, including the use of standardised treatment regimens based upon representative local susceptibility patterns, empirical treatment based upon previous treatment history and local Drug Susceptibility Test (DST) patterns, and individualised treatment designed on the basis of individual DST results.Treatment outcomes among MDR-TB cases have varied widely; a recent survey of five Green Line Committee (GLC) approved sites in resource-limited countries found treatment success rates of 70%. Treatment continues to be limited in the resource poor countries where the demand is high. The ultimate strategy to control multidrug resistant tuberculosis is one that implements comprehensive approach incorporating treatment of multidrug-resistant tuberculosis based upon principles closely related to those of its general DOTS strategy for TB control: sustained political commitment; a rational case-finding strategy including accurate, timely diagnosis through quality assured culture and DST; appropriate treatment strategies that use second-line drugs under proper case management conditions; uninterrupted supply of quality-assured antituberculosis drugs; standardised recording and reporting system.

Leprosy post-exposure prophylaxis in the Indian health system: A cost-effectiveness analysis.

India has the highest burden of leprosy in the world. Following a recent WHO guideline, the Indian National Leprosy Programme is introducing post-exposure prophylaxis with single-dose rifampicin (SDR-PEP) in all high-endemic districts of the country. The aim of this study is to estimate the long-term cost-effectiveness of SDR-PEP in different leprosy disability burden situations. We used a stochastic individual-based model (SIMCOLEP) to simulate the leprosy new case detection rate trend and the impact of implementing contact screening and SDR-PEP from 2016 to 2040 (25 years) in the Union Territory of Dadra Nagar Haveli (DNH) in India. Effects of the intervention were expressed as disability adjusted life years (DALY) averted under three assumption of disability prevention: 1) all grade 1 disability (G1D) cases prevented; 2) G1D cases prevented in PB cases only; 3) no disability prevented. Costs were US$ 2.9 per contact. Costs and effects were discounted at 3%. The incremental cost per DALY averted by SDR-PEP was US$ 210, US$ 447, and US$ 5,673 in the 25th year under assumption 1, 2, and 3, respectively. If prevention of G1D was assumed, the probability of cost-effectiveness was 1.0 at the threshold of US$ 2,000, which is equivalent to the GDP per capita of India. The probability of cost-effectiveness was 0.6, if no disability prevention was assumed. The cost per new leprosy case averted was US$ 2,873. Contact listing, screening and the provision of SDR-PEP is a cost-effective strategy in leprosy control in both the short (5 years) and long term (25 years). The cost-effectiveness depends on the extent to which disability can be prevented. As the intervention becomes increasingly cost-effective in the long term, we recommend a long-term commitment for its implementation.

4 months of rifampin compared with 9 months of isoniazid for the management of latent tuberculosis infection: a meta-analysis and cost-effectiveness study that focuses on compliance and liver toxicity.

BACKGROUND: One-third of the world's population is infected with tuberculosis, and 9 months of isoniazid monotherapy is the treatment of choice for latent tuberculosis infection. However, this approach has been associated with hepatotoxicity and poor compliance. A shorter (4-month) rifampin regimen has been evaluated in recent clinical trials. METHODS: We performed a meta-analysis of the published studies to compare compliance, toxicity, and cost-effectiveness between the 2 strategies. Pooled effects were calculated as risk ratios (RRs) by means of random-effects and fixed-effects models. RESULTS: Pooled data from 3586 patients suggested that 4-month rifampin therapy was associated with a significant reduction in the risk of noncompletion (RR for random-effects model, 0.53; 95% confidence interval [CI], 0.44-0.63). Noncompletion rates were lower among patients who received 4-month rifampin therapy (range, 8.6%-28.4%), compared with noncompletion rates among patients who received 9-month isoniazid therapy (range, 24.1%-47.4%). Also, rates of hepatotoxicity (defined as grade 3 or 4 liver failure leading to drug discontinuation) were lower for patients who received 4-month rifampin therapy (range, 0%-0.7%), compared with the corresponding rates for patients who received 9-month isoniazid therapy (range, 1.4%-5.2%), and rifampin was associated with significant reduction in the risk of hepatotoxicity (RR for fixed-effects model, 0.12; 95% CI, 0.05-0.30). Notably, with the data from our meta-analysis, we calculated that the 4-month rifampin strategy is also cost-effective and results in $213 savings per patient treated ($90/patient when doctor fees are not included). CONCLUSIONS: The improved compliance, safety, and cost associated with the 4-month rifampin therapy suggest that the efficacy of this approach needs to be evaluated in detail. An extended posttreatment follow-up in future studies will clarify the unresolved issue of tuberculosis reactivation rates.

A retrospective evaluation of completion rates, total cost, and adverse effects for treatment of latent tuberculosis infection in a public health clinic in central massachusetts.

Completion rates, total cost, and adverse effects were compared for patients in central Massachusetts treated for latent tuberculosis infection with 9 months of isoniazid or 4 months of rifampin. Although the adverse effects were similar between the 2 groups, 4 months of rifampin was associated with significantly better completion rates and less hepatotoxicity yet higher total cost.

Completion Rates, Adverse Effects, and Costs of a 3-Month and 9-Month Treatment Regimen for Latent Tuberculosis Infection in California Inmates, 2011-2014.

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.