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

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

Economic evaluation of short treatment for multidrug-resistant tuberculosis, Ethiopia and South Africa: the STREAM trial.

OBJECTIVE: To investigate cost changes for health systems and participants, resulting from switching to short treatment regimens for multidrug-resistant (MDR) tuberculosis. METHODS: We compared the costs to health systems and participants of long (20 to 22 months) and short (9 to 11 months) MDR tuberculosis regimens in Ethiopia and South Africa. Cost data were collected from participants in the STREAM phase-III randomized controlled trial and we estimated health-system costs using bottom-up and top-down approaches. A cost-effectiveness analysis was performed by calculating the incremental cost per unfavourable outcome avoided. FINDINGS: Health-care costs per participant in South Africa were 8340.7 United States dollars (US$) with the long and US$ 6618.0 with the short regimen; in Ethiopia, they were US$ 6096.6 and US$ 4552.3, respectively. The largest component of the saving was medication costs in South Africa (67%; US$ 1157.0 of total US$ 1722.8) and social support costs in Ethiopia (35%, US$ 545.2 of total US$ 1544.3). In Ethiopia, trial participants on the short regimen reported lower expenditure for supplementary food (mean reduction per participant: US$ 225.5) and increased working hours (i.e. 667 additional hours over 132 weeks). The probability that the short regimen was cost-effective was greater than 95% when the value placed on avoiding an unfavourable outcome was less than US$ 19 000 in Ethiopia and less than US$ 14 500 in South Africa. CONCLUSION: The short MDR tuberculosis treatment regimen was associated with a substantial reduction in health-system costs and a lower financial burden for participants.

Direct and indirect patient costs of tuberculosis care in India.

OBJECTIVE: To synthesise the evidence for estimating the direct and indirect patient costs of drug-sensitive and drug-resistant tuberculosis care in India. METHOD: PubMed, Embase, Web of Science, IndMED and Google Scholar were searched for studies conducted in India between 2000 and 2018 and published in English. The search terms were "tuberculosis" AND "costs" (cost Analysis, economics, cost of illness, health care costs, health expenditures, direct service costs, catastrophic cost) AND "India". The cost of TB care was from the patient's perspective. Data regarding costs were extracted, indexed to the year 2018 using cumulative inflation rate and converted to US dollars at the exchange rate of 2018. RESULTS: Thirteen studies were included in this review. The mean (unweighted) total cost incurred by patients being treated for drug-sensitive TB in a public health facility was $ 235.00 (SD- 222.10), and the median of means was $ 170.60 (range - 43.70-718.40). The mean direct cost was 45.5% of the total cost. Only one study, which was conducted in a private facility, reported the mean total cost for drug-resistant TB as $ 7778.04. Catastrophic cost (total cost ≥ 20% of the total annual household income) was experienced by 7% to 32.4% of drug-sensitive TB patients and by 68% of drug-resistant TB patients. CONCLUSION: Despite free diagnostic and treatment services provided under the Revised National Tuberculosis Control Programme, the patient cost of tuberculosis care is high. Relevant studies vary widely in methodology and cost reporting.

OBJECTIF: Synthétiser les données probantes permettant d'estimer les coûts directs et indirects des soins anti-TB pour les patients avec une TB sensible ou résistante aux médicaments en Inde. MÉTHODE: PubMed, Embase, Web of Science, IndMED et Google Scholar ont été recherchés pour des études menées en Inde entre 2000 et 2018 et publiées en anglais. Les termes de recherche étaient 'tuberculose' ET 'coûts' (analyse des coûts, économie, coût de la maladie, coûts des soins de santé, dépenses de santé, coûts directs des services, coût catastrophique) ET 'Inde'. Le coût des soins anti-TB était du point de vue du patient. Les données concernant les coûts ont été extraites, indexées pour l'année 2018 en utilisant le taux d'inflation cumulé et converties en dollars US au taux de change de 2018. RÉSULTATS: Treize études ont été incluses dans cette revue. Le coût total moyen (non pondéré) encouru par les patients traités pour une TB sensible aux médicaments dans un établissement de santé public était de 235,00 USD (SD-222,10), et la médiane des moyennes était de 170,60 USD (intervalle - 43,70 - 718,40). Le coût direct moyen était de 45,5% du coût total. Une seule étude, qui a été menée dans un établissement privé, a rapporté le coût moyen total pour la TB résistante aux médicaments équivalent à 7.778,04 USD. Des coûts catastrophiques (coût total ≥ 20% du revenu annuel total du ménage ) ont été subis par 7% à 32,4% des patients avec une TB sensible aux médicaments et par 68% des patients avec une TB résistante aux médicaments. CONCLUSION: Malgré les services gratuits de diagnostic et de traitement fournis dans le cadre du Programme National Révisé de Lutte contre la TB, le coût des soins anti-TB pour les patients est élevé. Les études pertinentes varient considérablement dans la méthodologie et la communication des coûts.

What causes high costs for rural tuberculosis inpatients? Evidence from five counties in China.

BACKGROUND: Tuberculosis (TB) still causes high economic burden on patients in China, especially for rural patients. Our study aims to explore the risk factors associated with the high costs for TB inpatients in rural China from the aspects of inpatients' socio-demographic and institutional attributes. METHODS: Generalized linear models were utilized to investigate the factors associated with TB inpatients' total costs and out-of-pocket (OOP) expenditures. Quantile regression (QR) models were applied to explore the effect of each factor across the different costs range and identify the risk factors of high costs. RESULTS: TB inpatients with long length of stay and who receive hospitalization services cross provincially, in tertiary and specialized hospitals were likely to face high total costs and OOP expenditures. QR models showed that high total costs occurred in Dingyuan and Funan Counties, but they were not accompanied by high OOP expenditures. CONCLUSIONS: Early diagnosis, standard treatment and control of drug-resistant TB are still awaiting for more efforts from the government. TB inpatients should obtain medical services from appropriate hospitals. The diagnosis and treatment process of TB should be standardized across all designated medical institutions. Furthermore, the reimbursement policy for migrant workers who suffered from TB should be ameliorated.

Cost of three models of care for drug-resistant tuberculosis patients in Nigeria.

BACKGROUND: Nigeria accounts for a significant proportion of the global drug-resistant tuberculosis (DR-TB) burden, a large proportion of which goes untreated. Different models for managing DR-TB treatment with varying levels of hospitalization are in use across Nigeria, however costing evidence is required to guide the scale up of DR-TB care. We aimed to estimate and compare the costs of different DR-TB treatment and care models in Nigeria. METHODS: We estimated the costs associated with three models of DR-TB treatment and care: Model (A) patients are hospitalized throughout the 8-month intensive phase, Model (B) patients are partially hospitalized during the intensive phase and Model (C) is entirely ambulatory. Costs of treatment, in-patient and outpatient care and diagnostic and monitoring tests were collected using a standardized data collection sheet from six sites through an ingredient's approach and cost models were based on the Nigerian National Tuberculosis, Leprosy and Buruli Ulcer Guideline - Sixth Edition (2014) and Guideline for programmatic and clinical management of drug-resistant tuberculosis in Nigeria (2015). RESULTS: Assuming adherence to the Nigerian DR-TB guidelines, the per patient cost of Model A was $18,528 USD, Model B $15,159 USD and Model C $9425 USD. Major drivers of cost included hospitalization (Models A and B) and costs of out-patient consultations and supervision (Model C). CONCLUSION: Utilizing a decentralized ambulatory model, is a more economically viable approach for the expansion of DR-TB care in Nigeria, given that patient beds for DR-TB treatment and care are limited and costs of hospitalized treatment are considerably more expensive than ambulatory models. Scale-up of less expensive ambulatory care models should be carefully considered in particular, when treatment efficacy is demonstrated to be similar across the different models to allow for patients not requiring hospitalization to be cared for in the least expensive way.

Cost-effectiveness of treating multidrug- and extensively drug-resistant tuberculosis: A systematic review.

OBJECTIVE: Tuberculosis (TB), along with the human immunodeficiency virus, is one of the leading causes of death from infectious diseases. Its prevalence has rendered the treatment of drug-resistant TB a major public health problem that threatens the progress made in TB care and control worldwide. Our objectives were to conduct a systematic review of the cost-effectiveness of treatment for multidrug-resistant and extensively drug-resistant TB (MDR-TB/XDR-TB) and to synthesise available data from scientific research. METHODS: Using English keywords, we searched for papers over reputable databases, such as Scopus, PubMed, Cochrane and Google Scholar, from Jan. 23 to Mar. 23, 2019. RESULTS: The search and screening yielded 13 articles, whose results were extracted and reviewed to draw conclusions on the cost-effectiveness of MDR-TB/XDR-TB treatment. The data extraction table used to cull and categorise the results comprised the characteristics of a given study, as well as its objectives, the perspectives used to guide the investigation, methods and results (outcome, sensitivity analysis). The measured outcome was the incremental cost-effectiveness ratio. CONCLUSIONS: The review indicated that MDR -TB/XDR-TB treatment can be very cost-effective in countries with low to high incomes, regardless of whether minimal or considerable disease burdens exist.

How affordable is TB care? Findings from a nationwide TB patient cost survey in Ghana.

OBJECTIVES: Tuberculosis (TB) is known as a disease of the poor. Despite TB diagnosis and care usually being offered for free, TB patients can still face substantial costs, especially in the context of multi-drug resistance (MDR). The End TB Strategy calls for zero TB-affected families incurring 'catastrophic' costs due to TB by 2025. This paper examines, by MDR status, the level and composition of costs incurred by TB-affected households during care seeking and treatment; assesses the affordability of TB care using catastrophic and impoverishment measures; and describes coping strategies used by TB-affected households to pay for TB care. METHODS: A nationally representative survey of TB patients at public health facilities across Ghana. RESULTS: We enrolled 691 patients (66 MDR). The median expenditure for non-MDR TB was US$429.6 during treatment, vs. US$659.0 for MDR patients (P-value = 0.001). Catastrophic costs affected 64.1% of patients. MDR patients were pushed significantly further over the threshold for catastrophic payments than DS patients. Payments for TB care led to a significant increase in the proportion of households in the study sample that live below the poverty line at the time of survey compared to pre-TB diagnosis. Over half of patients undertook coping strategies. CONCLUSION: TB patients in Ghana incur substantial costs, despite free diagnosis and treatment. High rates of catastrophic costs and coping strategies in both non-MDR and MDR patients show that new policies are urgently needed to ensure TB care is actually affordable for TB patients.

Household contact non-attendance of clinical evaluation for tuberculosis: a pilot study in a high burden district in South Africa.

BACKGROUND: In 2012, the World Health Organization launched guidelines for systematically investigating contacts of persons with infectious tuberculosis (TB) in low- and middle-income countries. As such, it is necessary to understand factors that would influence successful scale-up. This study targeted household contacts of newly-diagnosed infectious TB patients in the Mangaung Metropolitan district to explore factors associated with non-attendance of clinical evaluation. METHOD: In September-October 2016, a pilot study of household contacts was conducted. At each of the 40 primary health care (PHC) facilities in the district, at least one out of four types of TB index cases were purposefully selected. These included children <5 years, smear-positive cases, HIV co-infected cases, and multidrug-resistant TB (MDR-TB) cases. Trained fieldworkers administered questionnaires and screened contacts for TB symptoms. Those with TB symptoms as well as children <5 years were referred for clinical evaluation at the nearest PHC facility. Contacts' socio-demographic and clinical characteristics, TB knowledge and perception about TB-related discrimination are described. Logistic regression analysis was used to investigate factors associated with non-attendance of clinical evaluation. RESULTS: Out of the 259 participants, approximately three in every five (59.5%) were female. The median age was 20 (interquartile range: 8-41) years. While the large majority (87.3%) of adult contacts correctly described TB aetiology, almost three in every five (59.9%) thought that it was hereditary, and almost two-thirds (65.5%) believed that it could be cured by herbal medicine. About one-fifth (22.9%) of contacts believed that TB patients were subjected to discrimination. Two in every five (39.4%) contacts were referred for clinical evaluation of whom more than half (52.9%) did not attend the clinic. Non-attendance was significantly associated with inter alia male gender (AOR: 3.4; CI: 1.11-10.24), prior TB diagnosis (AOR: 5.6; CI: 1.13-27.90) and sharing of a bedroom with the index case (AOR: 3.4: CI: 1.07-10.59). CONCLUSION: The pilot study identified gaps in household contacts' knowledge of TB. Further research on important individual, clinical and structural factors that can influence and should be considered in the planning, implementation and scale-up of household contact TB investigation is warranted.

Implementing the End TB Strategy in the Western Pacific Region: Translating vision into reality.

The End TB Strategy aims to end the global tuberculosis (TB) epidemic by 2035 in line with the sustainable development goals targets and has been implemented in the World Health Organization (WHO) Western Pacific Region since 2015. Significant progress has been made in implementing this strategy. However, several challenges still remain. In 2016, an estimated 1.8 million people developed TB in the region, and of these about 20% were missed by national TB programmes. The gap in diagnosis and enrolment as well as treatment completion is greater with drug-resistant TB. Many TB-affected families face catastrophic costs due to the disease. Sustaining financing for TB care is a long-term challenge in many countries. This article emphasizes targeted interventions in high-risk populations, including systematic screening and patient-centred TB care. Several other approaches including improving TB diagnostic tools and algorithm, and engaging all care providers are suggested to find missing TB patients. Drug-resistant TB requires additional resourcing for laboratories, enrolment and patient support. Specific measures are required at different levels to mitigate financial burden due to TB including linking TB to overall social protection schemes. The Moscow Ministerial conference in 2017 and upcoming United Nations (UN) 2018 high-level meeting provide an opportunity to raise TB higher on the global agenda, forge partnerships and move towards universal health coverage.

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.

Estimated generic prices for novel treatments for drug-resistant tuberculosis.

Background: The estimated worldwide annual incidence of MDR-TB is 480 000, representing 5% of TB incidence, but 20% of mortality. Multiple drugs have recently been developed or repurposed for the treatment of MDR-TB. Currently, treatment for MDR-TB costs thousands of dollars per course. Objectives: To estimate generic prices for novel TB drugs that would be achievable given large-scale competitive manufacture. Methods: Prices for linezolid, moxifloxacin and clofazimine were estimated based on per-kilogram prices of the active pharmaceutical ingredient (API). Other costs were added, including formulation, packaging and a profit margin. The projected costs for sutezolid were estimated to be equivalent to those for linezolid, based on chemical similarity. Generic prices for bedaquiline, delamanid and pretomanid were estimated by assessing routes of synthesis, costs/kg of chemical reagents, routes of synthesis and per-step yields. Costing algorithms reflected variable regulatory requirements and efficiency of scale based on demand, and were validated by testing predictive ability against widely available TB medicines. Results: Estimated generic prices were US$8-$17/month for bedaquiline, $5-$16/month for delamanid, $11-$34/month for pretomanid, $4-$9/month for linezolid, $4-$9/month for sutezolid, $4-$11/month for clofazimine and $4-$8/month for moxifloxacin. The estimated generic prices were 87%-94% lower than the current lowest available prices for bedaquiline, 95%-98% for delamanid and 94%-97% for linezolid. Estimated generic prices were $168-$395 per course for the STREAM trial modified Bangladesh regimens (current costs $734-$1799), $53-$276 for pretomanid-based three-drug regimens and $238-$507 for a delamanid-based four-drug regimen. Conclusions: Competitive large-scale generic manufacture could allow supplies of treatment for 5-10 times more MDR-TB cases within current procurement budgets.

Financial barriers and coping strategies: a qualitative study of accessing multidrug-resistant tuberculosis and tuberculosis care in Yunnan, China.

BACKGROUND: Tuberculosis (TB) and multidrug-resistance tuberculosis (MDR-TB) pose serious challenges to global health, particularly in China, which has the second highest case burden in the world. Disparities in access to care for the poorest, rural TB patients may be exacerbated for MDR-TB patients, although this has not been investigated widely. We examine whether certain patient groups experience different barriers to accessing TB services, whether there are added challenges for patients with MDR-TB, and how patients and health providers cope in Yunnan, a mountainous province in China with a largely rural population and high TB burden. METHODS: Using a qualitative study design, we conducted five focus group discussions and 47 in-depth interviews with purposively sampled TB and MDR-TB patients and healthcare providers in Mandarin, between August 2014 and May 2015. Field-notes and interview transcripts were analysed via a combination of open and thematic coding. RESULTS: Patients and healthcare providers consistently cited financial constraints as the most common barriers to accessing care. Rural residents, farmers and ethnic minorities were the most vulnerable to these barriers, and patients with MDR-TB reported a higher financial burden owing to the centralisation and longer duration of treatment. Support in the form of free or subsidised treatment and medical insurance, was deemed essential but inadequate for alleviating financial barriers to patients. Most patients coped by selling their assets or borrowing money from family members, which often strained relationships. Notably, some healthcare providers themselves reported making financial and other contributions to assist patients, but recognised these practices as unsustainable. CONCLUSIONS: Financial constraints were identified by TB and MDR-TB patients and health care professionals as the most pervasive barrier to care. Barriers appeared to be magnified for ethnic minorities and patients coming from rural areas, especially those with MDR-TB. To reduce financial barriers and improve treatment outcomes, there is a need for further research into the total costs of seeking and accessing TB and MDR-TB care. This will enable better assessment and targeting of appropriate financial support for identified vulnerable groups and geographic development of relevant services.

Cost-effectiveness of adding novel or group 5 interventions to a background regimen for the treatment of multidrug-resistant tuberculosis in Germany.

BACKGROUND: Treatment of multidrug-resistant tuberculosis (MDR-TB) is complex, lengthy, and involves a minimum of four drugs termed a background regimen (BR), that have not previously been prescribed or that have proven susceptible to patient sputum culture isolates. In recent years, promising new treatment options have emerged as add-on therapies to a BR. The aim of this study was to evaluate the long-term costs and effectiveness of adding the novel or group 5 interventions bedaquiline, delamanid, and linezolid to a background regimen (BR) of drugs for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis (MDR-TB), within their marketing authorisations, from a German healthcare cost-effectiveness perspective. METHODS: A cohort-based Markov model was developed to simulate the incremental cost-effectiveness ratio of bedaquiline plus BR, delamanid plus BR, or linezolid plus BR versus BR alone in the treatment of MDR-TB, over a 10-year time horizon. Effectiveness of treatment was evaluated in Quality-Adjusted Life-Years (QALYs) and Life-Years Gained (LYG), using inputs from clinical trials for bedaquiline and delamanid and from a German observational study for linezolid. Cost data were obtained from German Drug Directory costs (€/2015), published literature, and expert opinion. A 3% yearly discount rate was applied. Probabilistic and deterministic sensitivity analyses were conducted. RESULTS: The total discounted costs per-patient were €85,575 for bedaquiline plus BR, €81,079 for delamanid plus BR, and €80,460 for linezolid plus BR, compared with a cost of €60,962 for BR alone. The total discounted QALYs per-patient were 5.95 for bedaquiline plus BR, 5.36 for delamanid plus BR, and 3.91 for linezolid plus BR, compared with 3.68 for BR alone. All interventions were therefore associated with higher QALYs and higher costs than BR alone, with incremental costs per QALY gained of €22,238 for bedaquiline, €38,703 for delamanid, and €87,484 for linezolid, versus BR alone. In a fully incremental analysis, bedaquiline plus BR was the most cost-effective treatment option at thresholds greater than €22,000 per QALY gained. In probabilistic analyses, the probability that bedaquiline plus BR was the most cost-effective treatment strategy at a willingness-to-pay threshold of €30,000 was 54.5%, compared with 22.9% for BR alone, 18.2% for delamanid plus BR, and 4.4% for linezolid. CONCLUSIONS: In Germany, the addition of bedaquiline, delamanid, or linezolid to a BR would result in QALY gains over BR alone. Based on this analysis, bedaquiline is likely to be the most cost-effective intervention for the treatment of MDR-TB, when added to a BR regimen at thresholds greater than €22,000 per QALY.

Cost-effectiveness study of the microbiological diagnosis of tuberculosis using geneXpert MTB/RIF®. / Estudio de coste-efectividad del diagnóstico microbiológico de tuberculosis mediante geneXpert MTB/RIF®.

INTRODUCTION/OBJECTIVE: To perform a cost-effectiveness analysis of a molecular biology technique for the diagnosis of tuberculosis compared to the classical diagnostic alternative. METHODS: A cost-effectiveness analysis was performed to evaluate the theoretical implementation of a molecular biology method including two alternative techniques for early detection of Mycobacterium tuberculosis Complex, and resistance to rifampicin (alternative1: one determination in selected patients; alternative2: two determinations in all the patients). Both alternatives were compared with the usual procedure for microbiological diagnosis of tuberculosis (staining and microbiological culture), and was accomplished on 1,972 patients in the period in 2008-2012. The effectiveness was measured in QALYs, and the uncertainty was assessed by univariate, multivariate and probabilistic analysis of sensitivity. RESULTS: A value of €8,588/QALYs was obtained by the usual method. Total expenditure with the alternative1 was €8,487/QALYs, whereas with alternative2, the cost-effectiveness ratio amounted to €2,960/QALYs. Greater diagnostic efficiency was observed by applying the alternative2, reaching a 75% reduction in the number of days that a patient with tuberculosis remains without an adequate treatment, and a 70% reduction in the number of days that a patient without tuberculosis remains in hospital. CONCLUSION: The implementation of a molecular microbiological technique in the diagnosis of tuberculosis is extremely cost-effective compared to the usual method. Its introduction into the routine diagnostic procedure could lead to an improvement in quality care for patients, given that it would avoid both unnecessary hospitalisations and treatments, and reflected in economic savings to the hospital.

Scenario Analysis for Programmatic Tuberculosis Control in Western Province, Papua New Guinea.

Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) are major health problems in Western Province, Papua New Guinea. While comprehensive expansion of TB control programs is desirable, logistical challenges are considerable, and there is substantial uncertainty regarding the true disease burden. We parameterized our previously described mathematical model of Mycobacterium tuberculosis dynamics in Western Province, following an epidemiologic assessment. Five hypothetical scenarios representing alternative programmatic approaches during the period from 2013 to 2023 were developed with local staff. Bayesian uncertainty analyses were undertaken to explicitly acknowledge the uncertainty around key epidemiologic parameters, and an economic evaluation was performed. With continuation of existing programmatic strategies, overall TB incidence remained stable at 555 cases per 100,000 population per year (95% simulation interval (SI): 420, 807), but the proportion of incident cases attributable to MDR-TB increased from 16% to 35%. Comprehensive, provincewide strengthening of existing programs reduced incidence to 353 cases per 100,000 population per year (95% SI: 246, 558), with 46% being cases of MDR-TB, while incorporating programmatic management of MDR-TB into these programs reduced incidence to 233 cases per 100,000 population per year (95% SI: 198, 269) with 14% MDR-TB. Most economic costs were due to hospitalization during the intensive treatment phase. Broad scale-up of TB control activities in Western Province with incorporation of programmatic management of MDR-TB is vital if control is to be achieved. Community-based treatment approaches are important to reduce the associated economic costs.

Cost-optimization in the treatment of multidrug resistant tuberculosis in Nigeria.

OBJECTIVE: To compare the cost of facility-based MDR TB care (F) to home-based care (H) from the perspective of the Nigerian national health system. METHODS: We assessed the expected costs of the two MDR TB treatment approaches using a decision-analytic model with a follow-up of 6 months. MDR TB treatment outcomes were obtained from a systematic review of randomised clinical trials. The outcomes of interest included treatment success, treatment failure, treatment default and mortality and did not vary significantly between the two alternatives. Treatment costs included the cost of the following: drug therapy (F, H), hospital stay (F), nurse care (F, H), physician care (F), nursing facility (F) and transport to the healthcare provider (H). Finally, we estimated the potential cost savings associated with home-based treatment for all patients starting MDR TB treatment in Nigeria. RESULTS: The average expected total treatment cost for a Nigerian patient treated for MDR TB was estimated at US2095 for facility - based care and 1535 for home-based care, a potential saving of 25%. One of the major drivers of this difference is significantly more intensive, and therefore more costly, nursing care in hospitals. In 2013, a total of 426 patients were initiated on facility-based MDR TB treatment in Nigeria. Thus, the potential savings through home-based care are US$ 223 204 per year. CONCLUSION: In Nigeria, treatment of MDR TB using home-based care is expected to result in similar patient outcomes at markedly reduced public health costs as facility-based care.

The socioeconomic impact of multidrug resistant tuberculosis on patients: results from Ethiopia, Indonesia and Kazakhstan.

BACKGROUND: One of the main goals of the post-2015 global tuberculosis (TB) strategy is that no families affected by TB face catastrophic costs. We revised an existing TB patient cost measurement tool to specifically also measure multi-drug resistant (MDR) TB patients' costs and applied it in Ethiopia, Indonesia and Kazakhstan. METHODS: Through structured interviews with TB and MDR-TB patients in different stages of treatment, we collected data on the direct (out of pocket) and indirect (loss of income) costs of patients and their families related to the diagnosis and treatment of TB and MDR-TB. Direct costs included costs for hospitalization, follow-up tests, transport costs for health care visits, and food supplements. Calculation of indirect costs was based on time needed for diagnosis and treatment. Costs were extrapolated over the patient's total treatment phase. RESULTS: In total 406 MDR-TB patients and 197 other TB patients were included in the survey: 169 MDR-TB patients and 25 other TB patients in Ethiopia; 143 MDR-TB patients and 118 TB patients in Indonesia; and 94 MDR-TB patients and 54 other TB patients in Kazakhstan. Total costs for diagnosis and current treatment episode for TB patients were estimated to be USD 260 in Ethiopia, USD 169 in Indonesia, and USD 929 in Kazakhstan, compared to USD 1838, USD 2342, and USD 3125 for MDR-TB patients, respectively. These costs represented 0.82-4.6 months of pre-treatment household income for TB patients and 9.3-24.9 months for MDR-TB patients. Importantly, 38-92 % reported income loss and 26-76 % of TB patients lost their jobs due to (MDR) TB illness, further aggravating the financial burden. CONCLUSIONS: The financial burden of MDR-TB is alarming, although all TB patients experienced substantial socioeconomic impact of the disease. If the patient is the breadwinner of the family, the combination of lost income and extra costs is generally catastrophic. Therefore, it should be a priority of the government to relieve the financial burden based on the cost mitigation options identified.

Tuberculosis cost in tunisia.

BACKGROUND: Tuberculosis (TB) infects one third of the world population. Its economic impact is important, affecting the global economy in the World. OBJECTIVE: To determine the economic costs related to tuberculosis in Tunisia. METHODS: Calculations were made for the reference year 2013; we covered all cost components of the disease, which are related to program management, BCG vaccination, health workers training, social mobilization, screening, chemoprophylaxis, and tuberculosis care. With the exception of costs related to care, which were the subject of a specific survey, the costs of other categories were obtained from the National TB Control Program. RESULTS: The cost of the different components related to the management, prevention, screening and tuberculosis care in 2013 amounted 504688,000DT. The cost of care represented 80.0% of total costs (6807 808,000DT) ; cost related to program  management represented 13.2% (1 121 580,00 DT) and the BCG vaccination  6.0% e (512 300,00DT) The average cost per patient was 1447,360 DTin 2013. CONCLUSION: Reducing the cost of tuberculosis, would involve reducing diagnostic delay. It is also recommended to reduce hospitalization recourse, and prevent multidrug resistance which lead to additional expenditures.

Availability, price and affordability of anti-tuberculosis drugs in Europe: a TBNET survey.

Data on availability and cost of anti-tuberculosis (TB) drugs in relation to affordability at national level are scarce. We performed a cross-sectional study on availability and cost of anti-TB drugs at major TB-reference centres in 37 European countries. Costs of standardised treatment regimens used for pan-sensitive TB, multidrug-resistant (MDR) TB, pre-extensively drug-resistant (XDR) TB, and XDR-TB were compared using a purchasing power analysis. Affordability was evaluated in relation to monthly national gross domestic products per capita (GDP). At least one second-line injectable and either moxifloxacin or levofloxacin were available in all countries. Linezolid and clofazimine were available in 79% and 46% of the countries, respectively. Drug cost for XDR-TB was three-times more expensive than those for MDR-TB. The average price of treatment for pan-sensitive TB represented a maximum of 8.5% of the monthly GDP across countries, while for standard MDR-TB treatment this was <30% in only six countries and more than 100% in four countries. Treatment of XDR-TB represented more than 100% of a month's GDP in all countries where the regimen was available. High cost and limited availability of drugs for treatment of drug-resistant TB, particularly beyond resistance to first-line drugs, are a major impediment to successful TB control in Europe.

Cost-effectiveness of a comprehensive programme for drug-resistant tuberculosis in China.

OBJECTIVE: To investigate the cost-effectiveness of a comprehensive programme for drug-resistant tuberculosis launched in four sites in China in 2011. METHODS: In 2011-2012, we reviewed the records of 172 patients with drug-resistant tuberculosis who enrolled in the comprehensive programme and we collected relevant administrative data from hospitals and China's public health agency. For comparison, we examined a cohort of 81 patients who were treated for drug-resistant tuberculosis in 2006-2009. We performed a cost-effectiveness analysis, from a societal perspective, that included probabilistic uncertainty. We measured early treatment outcomes based on three-month culture results and modelled longer-term outcomes to facilitate estimation of the comprehensive programme's cost per disability-adjusted life-year (DALY) averted. FINDINGS: The comprehensive programme cost 8837 United States dollars (US$) per patient treated. Low enrolment rates meant that some fixed costs were higher, per patient, than expected. Although the comprehensive programme appeared 30 times more costly than the previous one, it resulted in greater health benefits. The comprehensive programme, which cost US$ 639 (95% credible interval: 112 to 1322) per DALY averted, satisfied the World Health Organization's criterion for a very cost-effective intervention. CONCLUSION: The comprehensive programme, which included rapid screening, standardized care and financial protection, improved individual outcomes for MDR tuberculosis in a cost-effective manner. To support post-2015 global heath targets, the comprehensive programme should be expanded to non-residents and other areas of China.