Chronic Lung Allograft Dysfunction Is Associated with Significant Disability after Lung Transplantation-A Burden of Disease Analysis in 1025 Cases.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the leading cause of death after the first postoperative years of lung transplantation (LTx). OBJECTIVE: To assess the number of disability-adjusted life years (DALYs) per patient with severe CLAD. METHODS: The clinical and demographic data of patients who received their lung transplantation between 2010 and 2020 in the Hanover Medical School (Germany) were evaluated. RESULTS: A total of 1025 lung transplant patients were followed for a median of 51 months (4.25 years); the median age at transplantation was 52.8 (interquartile range (IQR) 19) years. More than a quarter of transplant patients (271/1025 or 26.4%) developed CLAD, mostly (60%) of the bronchiolitis obliterans syndrome (BOS) phenotype. Of the CLAD patients, 99, or 36.5%, suffered from significant disability, which on average occurred after 2 years (IQR 2.55). The survival of CLAD patients with disability after transplantation was significantly lower compared to that of patients without CLAD (median 4.04 versus 5.41 years). Adjusted to the DALY estimation approach, CLAD patients lost 1.29 life years (YLL) and lived for 0.8 years with their disability (YLD), adding up to 2.09 DALYs (range 1.99-2.72) per patient. CONCLUSIONS: CLAD after lung transplantation is a major public health problem and is associated with substantial disability and costs. Further work is needed to develop therapeutic interventions that reduce its development.

Cost-Benefit of Real-Time Multiplex PCR Testing of SARS-CoV-2 in German Hospitals.

BACKGROUND: The current Omicron COVID-19 pandemic has significant morbidity worldwide. OBJECTIVE: Assess the cost-benefit relation of implementing PCR point-of-care (POCT) COVID-19 testing in the emergency rooms (ERs) of German hospitals and in the case of inpatient admission due to other acute illnesses. METHODS: A deterministic decision-analytic model simulated the incremental costs of using the Savanna® Multiplex RT-PCR test compared to using clinical judgement alone to confirm or exclude COVID-19 in adult patients in German ERs prior to hospitalization or just prior to discharge. Direct and indirect costs were evaluated from the hospital perspective. Nasal or nasopharyngeal swabs of patients suspected to have COVID-19 by clinical judgement, but without POCT, were sent to external labs for RT-PCR testing. RESULTS: In probabilistic sensitivity analysis, assuming a COVID-19 prevalence ranging between 15.6-41.2% and a hospitalization rate between 4.3-64.3%, implementing the Savanna® test saved, on average, €107 as compared to applying the clinical-judgement-only strategy. A revenue loss of €735 can be avoided when SARS-CoV-2 infection in patients coming unplanned to the hospital due to other acute illnesses are excluded immediately by POCT. CONCLUSIONS: Using highly sensitive and specific PCR-POCT in patients suspected of COVID-19 infection at German ERs may significantly reduce hospital expenditures.

Point-of-Care COVID-19 Antigen Testing in Exposed German Healthcare Workers-A Cost Model.

BACKGROUND: Hospital staffing shortages are again (mid-year 2021) becoming a significant problem as the number of positive COVID-19 cases continues to increase worldwide. OBJECTIVE: To assess the costs of sending HCW into quarantine (Scenario 1) from the hospital's and the taxpayer's perspective versus the costs arising from implementing point-of-care COVID-19 antigen testing (POCT) for those staff members who, despite learning that they have been exposed to hospital patients later found to be infected with COVID-19, continue to report to work (Scenario 2). METHODS: A mathematical model was built to calculate the costs of a sample-and-stay strategy for exposed healthcare workers (HCW) in Germany by utilizing a high-quality antigen fluorescent immunoassay (FIA), compared to the costs of quarantine. Direct costs and wage costs were evaluated from the hospital as well as from the taxpayer perspective assuming a SARS-CoV-2 infection prevalence of 10%. RESULTS: Serial POCT testing of exposed HCW in Germany (Scenario 2) who do not go into quarantine but continue to work during a post-exposure period of 14 days at their working place raises costs of EUR 289 (±20%: EUR 231 to EUR 346, rounded) per HCW at the expense of the employing hospital while the extra-costs to the taxpayer per exposed HCW are limited to EUR 16 (±20%: EUR 13 to EUR 19). In contrast, sending HCW into quarantine (Scenario 1) would result in costs of EUR 111 (±20%: EUR 89 to EUR 133) per exposed HCW for the hospital but EUR 2235 (±20%: EUR 1744 to EUR 2727) per HCW at the expense of the taxpayer. CONCLUSIONS: Monitoring exposed HCW who continued working by sequential POCT may considerably reduce costs from the perspective of the taxpayer and help mitigate personnel shortages in hospitals during pandemic COVID-19 waves.

Predictive modeling of nontuberculous mycobacterial pulmonary disease epidemiology using German health claims data.

OBJECTIVES: Administrative claims data are prone to underestimate the burden of non-tuberculous mycobacterial pulmonary disease (NTM-PD). METHODS: We developed machine learning-based algorithms using historical claims data from cases with NTM-PD to predict patients with a high probability of having previously undiagnosed NTM-PD and to assess actual prevalence and incidence. Adults with incident NTM-PD were classified from a representative 5% sample of the German population covered by statutory health insurance during 2011-2016 by the International Classification of Diseases, 10th revision code A31.0. Pre-diagnosis characteristics (patient demographics, comorbidities, diagnostic and therapeutic procedures, and medications) were extracted and compared to that of a control group without NTM-PD to identify risk factors. RESULTS: Applying a random forest model (area under the curve 0.847; total error 19.4%) and a risk threshold of >99%, prevalence and incidence rates in 2016 increased 5-fold and 9-fold to 19 and 15 cases/100,000 population, respectively, for both coded and non-coded vs. coded cases alone. CONCLUSIONS: The use of a machine learning-based algorithm applied to German statutory health insurance claims data predicted a considerable number of previously unreported NTM-PD cases with high probabilty.

Cost of illness of non-multidrug-resistant tuberculosis in Germany: an update.

BACKGROUND: A total of 5429 new cases of tuberculosis (TB) were reported in Germany in 2018; out of the 3780 TB cases for whom drug susceptibility testing was available, the proportion of multidrug-resistant TB (MDR-TB) cases was only 3.1% (118 cases). METHODS: On the basis of the current therapy guidelines of the German Central Committee against Tuberculosis, this study estimates the mean direct outpatient and combined in- and outpatient costs per non-MDR-TB patient from the perspective of the German statutory health insurance (SHI) system, together with costs arising from productivity losses and costs due to public health screening for TB in close contacts. RESULTS: From the insurance perspective, the mean outpatient costs (rounded) per case were €1628 for adults and €1179 for children for standard therapy; the mean cost of inpatient treatment amounted to €8626. The mean combined inpatient/outpatient cost was €8756 for adults and €8512 for children. As 95% of all TB patients were adults, the weighted treatment cost per patient in Germany in 2018 was €8746. These are in addition to the mean cost arising from productivity losses (€1839) and, weighted by pulmonary infectivity, cost of contact investigations (€368), coming to a total of €10 953. CONCLUSION: Given the clear increase in the number of non-MDR-TB cases since 2015, TB is still a disease of significant economic impact in Germany.

Intersectoral Cost of Treating Pulmonary Non-Tuberculosis Mycobacterial Disease (NTM-PD) in Germany-A Change of Perspective in Disease Management.

BACKGROUND: In line with its increasing prevalence, pulmonary Mycobacterium avium complex (MAC) disease (MAC-PD) gives rise to substantial healthcare costs. However, there is only limited information on the costs of intersectoral reimbursement. OBJECTIVES: Inpatient and outpatient costs for diagnosing and treating pulmonary MAC-PD in Germany in accordance with standard international guidelines were calculated and their potential effects on MAC disease management in Germany were determined. METHODS: Hospitalization costs were calculated by using the German diagnosis related group (G-DRG) browser, with and without inclusion of the diseases most often associated with M. avium. Separated by drug macrolide susceptibility and severity of MAC-PD, the direct medical costs of suitable therapies in the outpatient setting were determined by Monte-Carlo simulation, including all conceivable options. RESULTS: According to our simulation, the weighted mean cost of outpatient treatment over 14 or 18 months, in either case followed by a post-treatment monitoring over 12 months, amounts to €8675.22 (95% confidence interval [CI] €8616.17 to €8734.27). Of that amount, the revenue for outpatient doctors´ services, dependent on treatment duration, is low, ranging between €894.79 (10.3%) and €979.42 (11.3%), accordingly. Mean drug costs for MAC-PD patients amount to €6130.25 [95% CI €6073.52 to €6186.98], i.e., more than two third (70.7%) of the total outpatient costs. In contrast, the non-surgical reimbursement for a hospital stay of up to 14 days is €3321.64. Hospital reimbursement does not increase in cases of complications (a higher number and/or challenging type of associated diseases), but it is fully paid even in cases that require as few as 2 days of hospitalization. CONCLUSION: The imbalance between well-rewarded hospital care and the low reimbursement for long-term treatment of MAC-PD outpatients may induce inappropriate disease management. In order to arrive at properly integrated care of MAC-PD patients in Germany, measures such as better incentives for physicians in the outpatient setting and a targeted use of resources in hospitals are required. Reimbursed, periodic case conferences between outpatient physicians and experts in hospitals as well as preventive short-term checks of MAC-PD patients in specialty clinics may promote cross-sector cooperation and improve overall treatment quality. Nationwide pilot studies are required to gain evidence on the effectiveness of the new approach.

Cost-Benefit Analysis of Real-Time Influenza Testing for Patients in German Emergency Rooms.

BACKGROUND: Seasonal influenza causes significant morbidity worldwide and has a substantial economic impact on the healthcare system. OBJECTIVE: To assess the cost-benefit relation of implementing a real-time influenza test in emergency rooms (ER) of German hospitals. METHODS: A deterministic decision-analytic model was developed simulating the incremental costs of using the Solana® Influenza A+B test, compared to those of using conventional clinical judgement alone to confirm or exclude influenza in adult ILI (influenza-like illness) patients, in German ER, prior to hospitalization. Direct costs were evaluated from the hospital perspective, considering resource use directly related to influenza testing and treatment, as well as indirect costs incurred by nosocomial influenza transmission. RESULTS: Through base-case analysis and assuming an influenza prevalence of 42.6%, real-time testing with Solana® reduced average costs of hospitalized ILI patients by €132.61, per tested patient. Moreover, the Solana® saved €6.9 per tested patient in favor of the hospital. In probabilistic sensitivity analysis, under all reasonable assumptions, implementing the Solana® saved on average €144.13 as compared to applying the clinical-judgement-only strategy, thus, it was found to be constantly less expensive. CONCLUSIONS: Using highly sensitive and specific real-time influenza tests in ILI patients at German ER might significantly reduce hospital expenditures.

The economic burden of bronchiectasis - known and unknown: a systematic review.

BACKGROUND: The increasing prevalence and recognition of bronchiectasis in clinical practice necessitates a better understanding of the economic disease burden to improve the management and achieve better clinical and economic outcomes. This study aimed to assess the economic burden of bronchiectasis based on a review of published literature. METHODS: A systematic literature review was conducted using MEDLINE, Embase, EconLit and Cochrane databases to identify publications (1 January 2001 to 31 December 2016) on the economic burden of bronchiectasis in adults. RESULTS: A total of 26 publications were identified that reported resource use and costs associated with management of bronchiectasis. Two US studies reported annual incremental costs of bronchiectasis versus matched controls of US$5681 and US$2319 per patient. Twenty-four studies reported on hospitalization rates or duration of hospitalization for patients with bronchiectasis. Mean annual hospitalization rates per patient, reported in six studies, ranged from 0.3-1.3, while mean annual age-adjusted hospitalization rates, reported in four studies, ranged from 1.8-25.7 per 100,000 population. The average duration of hospitalization, reported in 12 studies, ranged from 2 to 17 days. Eight publications reported management costs of bronchiectasis. Total annual management costs of €3515 and €4672 per patient were reported in two Spanish studies. Two US studies reported total costs of approximately US$26,000 in patients without exacerbations, increasing to US$36,00-37,000 in patients with exacerbations. Similarly, a Spanish study reported higher total annual costs for patients with > 2 exacerbations per year (€7520) compared with those without exacerbations (€3892). P. aeruginosa infection increased management costs by US$31,551 to US$56,499, as reported in two US studies, with hospitalization being the main cost driver. CONCLUSIONS: The current literature suggests that the economic burden of bronchiectasis in society is significant. Hospitalization costs are the major driver behind these costs, especially in patients with frequent exacerbations. However, the true economic burden of bronchiectasis is likely to be underestimated because most studies were retrospective, used ICD-9-CM coding to identify patients, and often ignored outpatient burden and cost. We present a conceptual framework to facilitate a more comprehensive assessment of the true burden of bronchiectasis for individuals, healthcare systems and society.

Cost-benefit analysis of VKA versus NOAC treatment in German patients with atrial fibrillation utilizing patient self-testing.

BACKGROUND: Clinical complications of long-term anticoagulation in patients with atrial fibrillation cause significant morbidity and have a substantial economic impact on the healthcare system. OBJECTIVE: To assess the cost-benefit by implementing patient self-testing (PST) in German patients anticoagulated with vitamin K antagonists (VKA) compared to treatment with the new oral anticoagulant drugs (NOAC) apixaban, dabigatran, edoxaban, and rivaroxaban. METHODS: A deterministic decision-analytic model was developed simulating the number of major bleedings, ischemic strokes, and hemorrhagic strokes and their associated costs by utilizing PST compared to those of treatment with NOAC. Data on the rates of these adverse events in both groups during the 1st year of treatment was taken from the NOAC approval studies. Direct costs were evaluated from the perspective of the Statutory Health Insurance (SHI) considering the use of resources directly related to PST testing and costs incurred by hospital treatment of the adverse events. Univariate sensitivity analysis was performed to examine the extent to which our calculations were affected by varying the parameters considered in our model within plausible extremes. To capture the interactions between multiple inputs, we also provided a probabilistic sensitivity analysis (PSA). RESULTS: When achieving an average time in therapeutic range (TTR) of 78%, implementing PST in VKA patients reduces cost per patient compared to NOAC treatment between €603.38 [USD 681.52] (edoxaban) and €762.64 [USD 861.40] (rivaroxaban) during the 1-year observation period. In line with the TTR increase, the initially higher number of adverse events per VKA patient compared to NOACtreated patients in the approval studies becomes largely aligned; the difference in associated hospital costs per patient in the NOAC groups is then only €1.03 [USD 1.16] (in favor of dabigatran), €23.41 [USD 26.44] (in favor of apixaban), €0.53 [USD 0.60] (in favor of edoxaban) and €52.62 [USD 59.43] (in favor of VKA anticoagulation in the rivaroxaban group).In PSA, implementation of self-management results on average in a cost saving between €619.20 [USD 699.39] and €785.24 [USD 886.93] per VKA patient in favor of the SHI. Under all reasonable assumptions, PST remains constantly less expensive irrespective of which NOAC is administered. CONCLUSION: Implementing PST in German VKA patients may significantly reduce SHI expenditures compared to utilizing NOAC.

Rapid Point-of-Care Influenza Testing for Patients in German Emergency Rooms - A Cost-Benefit Analysis.

BACKGROUND: Each year, influenza causes significant morbidity and death worldwide and produces significant economic losses at the expense of the healthcare system. OBJECTIVE: To assess the cost-benefit relationship of implementing a rapid point-of-care (POC) influenza test in emergency rooms (ERs) of German hospitals. METHODS: A deterministic decision-analytic model simulated the incremental costs of using the Sofia® Influenza A+B test compared to those of using clinical judgement alone to confirm or exclude influenza in adult ILI (influenza-like illness) patients in German ERs prior to hospitalization. Direct costs, with and without subsequent oseltamivir treatment, were evaluated from the hospital perspective as well as indirect costs incurred by nosocomial influenza transmission to hospital employees. RESULTS: In base-case analysis, taking the influenza prevalence of 25.9% in the season 2018/2019 and assuming a hospitalization rate among influenza suspects of 21.9%, rapid testing with the Sofia® followed by administering oseltamivir to patients testing positive reduced average costs of hospitalized ILI patients by €52.16 per tested patient. If oseltamivir was not offered, testing with the Sofia® reduced costs by €42.28 in favor of the hospital.In probabilistic sensitivity analysis, under all reasonable assumptions, implementing the Sofia® saved on average €119.89 as compared to applying the clinical-judgement-only strategy. The major part of the cost savings, €113.17 or 94.4%, was due to the POC test's high specificity, which led to 91% reduction in needless bed-blocking on the first day of hospitalization. However, as the sensitivity of 75.3% was only slightly higher than that of conventional clinical judgement, improved classification of patients with true influenza and a correspondingly lower rate of illness in hospital employees could not be achieved. CONCLUSIONS: Using highly specific rapid POC influenza tests in ILI patients at German ER, despite their sub-optimal sensitivity, may significantly reduce hospital expenditures.

Economic burden of bronchiectasis in Germany.

Estimates of healthcare costs for incident bronchiectasis patients are currently not available for any European country.Out of a sample of 4 859 013 persons covered by German statutory health insurance companies, 231 new bronchiectasis patients were identified in 2012. They were matched with 685 control patients by age, sex and Charlson Comorbidity Index, and followed for 3 years.The total direct expenditure during that period per insured bronchiectasis patient was EUR18 634.57 (95% CI EUR15 891.02-23 871.12), nearly one-third higher (ratio of mean 1.31, 95% CI 1.02-1.68) than for a matched control (p<0.001). Hospitalisation costs contributed to 35% of the total and were >50% higher in the bronchiectasis group (ratio of mean 1.56, 95% CI 1.20-3.01; p<0.001); on average, bronchiectasis patients spent 4.9 (95% CI 2.27-7.43) more days in hospital (p<0.001). Antibiotics expenditures per bronchiectasis outpatient (EUR413.81) were nearly 5 times higher than those for a matched control (ratio of mean 4.85, 95% CI 2.72-8.64). Each bronchiectasis patient had on average 40.5 (95% CI 17.1-43.5) sick-leave days and induced work-loss costs of EUR4230.49 (95% CI EUR2849.58-5611.20). The mortality rate for bronchiectasis and matched non-bronchiectasis patients after 3 years of follow-up was 26.4% and 10.5%, respectively (p<0.001). Mortality in the bronchiectasis group was higher among those who also had chronic obstructive lung disease than in patients with bronchiectasis alone (35.9% and 14.6%, respectively; p<0.001).Although bronchiectasis is considered underdiagnosed, the mortality and associated financial burden in Germany are substantial.

Pulmonary disease by non-tuberculous mycobacteria - clinical management, unmet needs and future perspectives.

INTRODUCTION: The number of patients with pulmonary disease caused by non-tuberculous mycobacteria (NTM) is increasing globally. Poor resistance against infections, for example, due to pre-existing lung diseases, immune deficiency and immune-modulating treatment, predisposes the population to developing pulmonary NTM disease. The incidence of pre-existing lung diseases such as chronic obstructive pulmonary disease and bronchiectasis has also increased. NTM disease diagnosis is often delayed due to non-specific symptoms. The therapeutic arsenal is limited and adherence to treatment guidelines is often low since the treatment regimens are complex, lengthy and side effects are common. Thus, current disease management is far from satisfactory and needs to be improved. Areas covered: This review provides an overview of the current knowledge of NTM infections and includes pathogenesis, disease patterns, epidemiology, disease management, unmet needs and future perspectives. Expert commentary: NTM disease is becoming more prevalent, in part with our increased awareness and improved diagnostic methods. However, our understanding of the disease pathogenesis is limited and treatment decisions are challenging, with difficult to employ drug regimens. Optimal management requires collaboration between healthcare providers, patients and expert centers.

Burden of non-tuberculous mycobacterial pulmonary disease in Germany.

The objective of this study was to estimate the burden of disease in incident patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD).A sample of 7 073 357 anonymised persons covered by German public statutory health insurances was used to identify patients with NTM-PD. In total, 125 patients with newly diagnosed NTM-PD in 2010 and 2011 were matched with 1250 control patients by age, sex and Charlson Comorbidity Index, and followed for 39 months.The incidence rate for NTM-PD was 2.6 per 100 000 insured persons (95% CI 2.2-3.1). The mortality rate for patients with NTM-PD and the control group in the observational period was 22.4% and 6%, respectively (p<0.001). Mean direct expenditure per NTM-PD patient was €39 559.60 (95% CI 26 916.49-52 202.71), nearly 4-fold (3.95, 95% CI 3.73-4.19) that for a matched control (€10 006.71, 95% CI 8907.24-11 106.17). Hospitalisations were three times higher in the NTM-PD group and accounted for 63% of the total costs. Attributable annual direct costs and indirect work-loss costs in NTM-PD patients were €9093.20 and €1221.05 per control patient, respectively. Only 74% of NTM-PD patients received antibiotics and nearly 12% were prescribed macrolide monotherapy.Although NTM-PD is considered rare, the attributable mortality and financial burden in Germany are high. Efforts to heighten awareness of appropriate therapy are urgently needed.

Cost-benefit analysis of Xpert MTB/RIF for tuberculosis suspects in German hospitals.

Our objective was to assess the cost-benefit of enhancing or replacing the conventional sputum smear with the real-time PCR Xpert MTB/RIF method in the inpatient diagnostic schema for tuberculosis (TB).Recent data from published per-case cost studies for TB/multidrug-resistant (MDR)-TB and from comparative analyses of sputum microscopy, mycobacterial culture, Xpert MTB/RIF and drug susceptibility testing, performed at the German National Reference Center for Mycobacteria, were used. Potential cost savings of Xpert MTB/RIF, based on test accuracy and multiple cost drivers, were calculated for diagnosing TB/MDR-TB suspects from the hospital perspective.Implementing Xpert MTB/RIF as an add-on in smear-positive and smear-negative TB suspects saves on average €48.72 and €503, respectively, per admitted patient as compared with the conventional approach. In smear-positive and smear-negative MDR-TB suspects, cost savings amount to €189.56 and €515.25 per person, respectively. Full replacement of microscopy by Xpert MTB/RIF saves €449.98. In probabilistic Monte-Carlo simulation, adding Xpert MTB/RIF is less costly in 46.4% and 76.2% of smear-positive TB and MDR-TB suspects, respectively, but 100% less expensive in all smear-negative suspects. Full replacement by Xpert MTB/RIF is also consistently cost-saving.Using Xpert MTB/RIF as an add-on to and even as a replacement for sputum smear examination may significantly reduce expenditures in TB suspects.

Cost effectiveness of treating multi-drug resistant tuberculosis by adding Deltyba™ to background regimens in Germany.

OBJECTIVE: To assess the cost-effectiveness of adding delamanid (Deltyba™) to a background regimen (BR) for treating multidrug-resistant tuberculosis (MDR-TB) in Germany. METHODS: The incremental cost-effectiveness of treating a cohort of MDR-TB patients, 38-years old on average, with Deltyba™ plus BR versus a five drug- BR regimen alone was compared in a Markov model over a period of 10 years. Cost per quality-adjusted life year (QALY) and disability-adjusted life years (DALY) were determined from a societal perspective. Recent data from a German cost calculation on MDR-TB were applied to the 24-month outcome results of patients participating in the placebo-controlled, phase II Otsuka's Trial 204. Costs and effectiveness were discounted at a rate of 3% and subjected to deterministic as well as probabilistic sensitivity analysis in a Monte Carlo simulation. RESULTS: Based on the current market prices the total discounted cost per patient on BR plus Deltyba™ was €142,732 compared to €150,909 for BR alone. The total discounted QALYs per patient were 8.47 for Deltyba™ versus 6.13 for BR alone. Accordingly, the addition of Deltyba™ proved to be dominant over the BR alone-strategy by simultaneously saving €8177 and gaining 2.34 QALYs. Deltyba™ was cost saving in 73% of probabilistic sensitivity analyses compared to BR alone and 100% cost effective at a willingness-to-pay (WTP) threshold of €10,000. CONCLUSIONS: Under conditions prevalent in Germany, Deltyba™ added to a five drug BR regimen is likely to be cost-saving compared to BR alone under a wide range of assumptions. Adding delamanid remained cost-effective when costs due to loss of productivity were excluded as the QALYs gained by lower lethality and a higher proportion of successfully treated patients outweighed the delamanid drug costs. These results strongly support the application of Deltyba™ in treating MDR-TB patients.

Towards tuberculosis elimination: an action framework for low-incidence countries.

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.

Cost Effectiveness of Preventive Treatment for Tuberculosis in Special High-Risk Populations.

OBJECTIVE: In view of the goal of eliminating tuberculosis (TB) by 2050, economic evaluations of interventions against the development of TB are increasingly requested. Little research has been published on the incremental cost effectiveness of preventative therapy (PT) in groups at high risk for progression from latent TB infection (LTBI) with Mycobacterium TB (MTB) to active disease. A systematic review of studies with a primary focus on model-driving inputs and methodological differences was conducted. METHODS: A search of MEDLINE, the Cochrane Library and EMBASE to July 2014 was undertaken, and reference lists of eligible articles and relevant reviews were examined. RESULTS: A total of 876 citations were retrieved, with a total of 24 studies being eligible for inclusion, addressing six high-risk groups other than contact persons. Results varied considerably between studies and countries, and also over time. Although the selected studies generally demonstrated cost effectiveness for PT in HIV-infected subjects and healthcare workers (HCWs), the outcome of these analyses can be questioned in light of recent epidemiologic data. For immigrants from high TB-burden countries, patients with end-stage renal disease, and the immunosuppressed, now defined as further vulnerable groups, no consistent recommendation can be taken from the literature with respect to cost effectiveness of screening and treating LTBI. When the concept of a fixed willingness-to-pay (WTP) threshold as a prerequisite for final categorization was used, the sums ranged between 'no specification' and US$100,000 per quality-adjusted life-year. CONCLUSIONS: To date, incremental cost-effectiveness analyses on PT in groups at high risk for TB progression, other than contacts, are surprisingly scarce. The variation found between studies likely reflects variations in the major epidemiologic factors, particularly in the estimates on the accuracy of the tuberculin skin test (TST) and interferon-gamma release assays (IGRA) as screening methods used before considering PT. Further research, including explicit evaluation of local epidemiological conditions, test accuracy, and methodology of WTP thresholds, is needed.