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Nontuberculous mycobacterial pulmonary disease (NTM-PD) prevalence is a rising public health concern. We assessed the long-term healthcare systems perspective of costs incurred by 147 NTM-PD patients at a tertiary hospital in South Korea. Median cumulative total medical cost in managing NTM-PD patients was US $5,044 (interquartile range US $3,586–$9,680) over 49.7 months (interquartile range 33.0–68.2 months) of follow-up. The major cost drivers were diagnostic testing and medication, accounting for 59.6% of total costs. Higher costs were associated with hospitalization for Mycobacterium abscessus infection and pulmonary comorbidities. Of the total medical care costs, 50.2% were patient co-payments resulting from limited national health insurance coverage. As South Korea faces significant problems of poverty during old age and increasing NTM-PD prevalence, the financial and socio-economic burden of NTM-PD may become a major public health concern that should be considered with regard to adequate strategies for NTM-PD patients.

Abstract Background In Vietnam and other global settings, men who have sex with men (MSM) have become the population at greatest risk of HIV infection. Although HIV pre-exposure prophylaxis (PrEP) has been implemented as a prevention strategy, PrEP outcomes may be affected by low persistence and adherence among MSM with unhealthy alcohol use. MSM have a high prevalence of unhealthy alcohol use in Vietnam, which may affect PrEP outcomes. Methods Design: We will conduct a two-arm hybrid type 1 effectiveness-implementation randomized controlled trial of a brief alcohol intervention (BAI) compared to the standard of care (SOC) at the Sexual Health Promotion (SHP) clinic Hanoi, Vietnam. Participants: Sexually active MSM (n=564) who are newly initiating PrEP or re-initiating PrEP and have unhealthy alcohol use will be recruited and randomized 1:1 to the SOC or BAI arm. A subgroup of participants (n=20) in each arm will be selected for longitudinal qualitative interviews; an additional subset (n=48) in the BAI arm will complete brief quantitative and qualitative interviews after completion of the BAI to assess the acceptability of the intervention. Additional implementation outcomes will be assessed through interviews with clinic staff and stakeholders (n=35). Intervention: Study participants in both arms will receive standard care for PrEP clients. In the BAI arm, each participant will receive two face-to-face intervention sessions and two brief booster phone sessions, based on cognitive behavioral therapy and delivered in motivational interviewing informed style, to address their unhealthy alcohol use. Outcomes: Effectiveness (PrEP and alcohol use) and cost-effectiveness outcomes will be compared between the two arms. Intervention implementation outcomes (acceptability, feasibility, adoption) will be assessed among MSM participants, clinic staff, and stakeholders. Discussion This proposed trial will assess an alcohol intervention for MSM with unhealthy alcohol use who initiate or re-initiate PrEP, while simultaneously preparing for subsequent implementation. The study will measure the effectiveness of the BAI for increasing PrEP persistence through reducing unhealthy alcohol use in a setting where excessive alcohol consumption is a normative behavior. If effective, implementation-focused results will inform future scale-up of the BAI in similar settings. Trial registration NCT06094634 on clinicaltrials.gov. Registered 16 October 2023.

Background Despite the global increase in nontuberculous mycobacterial pulmonary disease (NTM-PD), clinical characteristics show geographical variations. We investigated the clinical characteristics of patients with NTM-PD in South Korea. Methods We systematically reviewed articles concerning patients with NTM-PD in South Korea until February 2022. Individual participant data, regardless of treatment, were collected using a standard case report form. Results Data of 6,489 patients from 11 hospitals between 2002 and 2019 were analyzed. The mean age was 61.5±11.7 years, of whom 57.7% were women. Mycobacterium avium (41.4%) and Mycobacterium intracellulare (38.4%) comprised most of the causative species, followed by Mycobacterium abscessus subspecies abscessus (8.6%) and M. abscessus subspecies massiliense (7.8%). Bronchiectasis (59.4%) was the most common pulmonary comorbidity. Although reported cases of NTM-PD increased over the years, the proportions of causative species and radiologic forms remained similar. Distinct clinical characteristics were observed according to age and sex. Men were older at the time of diagnosis (median 63.8 years vs. 59.9 years, p

Abstract Background Evidence-based interventions (EBIs) often address normative behaviors. If a behavior is also common among clinicians, they may be skeptical about the necessity or effectiveness of an EBI. Alternatively, clinicians’ attitudes and behaviors may be misaligned, or they may lack the knowledge and self-efficacy to deliver the EBI. Several EBIs address unhealthy alcohol use, a common and often culturally acceptable behavior. But unhealthy alcohol use may be particularly harmful to people with HIV (PWH). Here, we present an implementation trial using an experiential implementation strategy to address clinicians’ knowledge, attitudes, and behaviors. Clinicians receive the experiential intervention before they begin delivering an evidence-based brief alcohol intervention (BAI) to PWH with unhealthy alcohol use. Methods Design: In this hybrid type 3 implementation-effectiveness cluster randomized controlled trial, ART clinics (n = 30) will be randomized 1:1 to facilitation, a flexible strategy to address implementation barriers, or facilitation plus the experiential brief alcohol intervention (EBAI). In the EBAI arm, clinicians, irrespective of their alcohol use, will be offered the BAI as experiential learning. EBAI will address clinicians’ alcohol-related attitudes and behaviors and increase their knowledge and confidence to deliver the BAI. Participants: ART clinic staff will be enrolled and assessed at pre-BAI training, post-BAI training, 3, 12, and 24 months. All PWH at the ART clinics who screen positive for unhealthy alcohol use will be offered the BAI. A subset of PWH (n = 810) will be enrolled and assessed at baseline, 3, and 12 months. Outcomes: We will compare implementation outcomes (acceptability, fidelity, penetration, costs, and sustainability) and effectiveness outcomes (viral suppression and alcohol use) between the two arms. We will assess the impact of site-level characteristics on scaling-up the BAI. We will also evaluate how experiencing the BAI affected clinical staff’s alcohol use and clinic-level alcohol expectations in the EBAI arm. Discussion This trial contributes to implementation science by testing a novel strategy to implement a behavior change intervention in a setting in which clinicians themselves may engage in the behavior. Experiential learning may be useful to address normative and difficult to change lifestyle behaviors that contribute to chronic diseases. Trial Registration NCT06358885 (04/10/2024), https://clinicaltrials.gov/study/NCT06358885 .

Abstract Background Each year, 1 million children develop TB resulting in over 200,000 child deaths. TB preventive treatment (TPT) is highly effective in preventing TB but remains poorly implemented for household child contacts. Home-based child contact management and TPT services may improve access to care. In this study, we aim to evaluate the effectiveness and cost-effectiveness of home-based contact management with TPT initiation in two TB high-burden African countries, Ethiopia and South Africa. Methods This pragmatic cluster randomized trial compares home-based versus facility-based care delivery models for contact management. Thirty-six clinics with decentralized TB services (18 in Ethiopia and 18 in South Africa) were randomized in a 1:1 ratio to conduct either home-based or facility-based contact management. The study will attempt to enroll all eligible close child contacts of infectious drug-sensitive TB index patients diagnosed and treated for TB by one of the study clinics. Child TB contact management, including contact tracing, child evaluation, and TPT initiation and follow-up, will take place in the child’s home for the intervention arm and at the clinic for the control arm. The primary outcome is the cluster-level ratio of the number of household child contacts less than 15 years of age in Ethiopia and less than 5 years of age in South Africa initiated on TPT per index patient, comparing the intervention to the control arm. Secondary outcomes include child contact identification and the TB prevention continuum of care. Other implementation outcomes include acceptability, feasibility, fidelity, cost, and cost-effectiveness of the intervention. Discussion This implementation research trial will determine whether home-based contact management identifies and initiates more household child contacts on TPT than facility-based contact management. Trial registration NCT04369326 . Registered on April 30, 2020.

Background The fixed-dose combination (FDC) for first-line antituberculosis (TB) treatment has long been a standard practice worldwide; however, there is limited evidence on whether the use of FDC improves long-term treatment outcomes in the real-world setting.Methods We identified 32 239 newly diagnosed patients with drug-susceptible (DS) TB in 2015 and 2016 who had been prescribed FDC or non-FDC TB treatment from a multiyear (2013–2018) national TB cohort database that linked the Korean National Tuberculosis Surveillance System, the National Health Insurance Database and the Health Insurance Review and Assessment Service database. Inverse probability of treatment weighting (IPTW) with a propensity score was used to control for differences in patient characteristics between 5926 patients with TB treated with FDC and 26 313 patients with non-FDC. Multivariable logistic regression analyses were performed to assess for the factors influencing treatment outcomes between the two groups.Results After IPTW, new patients with DS-TB treated with FDC had higher treatment completion rate (83.9% vs 78.9%, p

Abstract Background Countries with high TB burden have expanded access to molecular diagnostic tests. However, their impact on reducing delays in TB diagnosis and treatment has not been assessed. Our primary aim was to summarize the quantitative evidence on the impact of nucleic acid amplification tests (NAAT) on diagnostic and treatment delays compared to that of the standard of care for drug-sensitive and drug-resistant tuberculosis (DS-TB and DR-TB). Methods We searched MEDLINE, EMBASE, Web of Science, and the Global Health databases (from their inception to October 12, 2020) and extracted time delay data for each test. We then analysed the diagnostic and treatment initiation delay separately for DS-TB and DR-TB by comparing smear vs Xpert for DS-TB and culture drug sensitivity testing (DST) vs line probe assay (LPA) for DR-TB. We conducted random effects meta-analyses of differences of the medians to quantify the difference in diagnostic and treatment initiation delay, and we investigated heterogeneity in effect estimates based on the period the test was used in, empiric treatment rate, HIV prevalence, healthcare level, and study design. We also evaluated methodological differences in assessing time delays. Results A total of 45 studies were included in this review (DS = 26; DR = 20). We found considerable heterogeneity in the definition and reporting of time delays across the studies. For DS-TB, the use of Xpert reduced diagnostic delay by 1.79 days (95% CI − 0.27 to 3.85) and treatment initiation delay by 2.55 days (95% CI 0.54–4.56) in comparison to sputum microscopy. For DR-TB, use of LPAs reduced diagnostic delay by 40.09 days (95% CI 26.82–53.37) and treatment initiation delay by 45.32 days (95% CI 30.27–60.37) in comparison to any culture DST methods. Conclusions Our findings indicate that the use of World Health Organization recommended diagnostics for TB reduced delays in diagnosing and initiating TB treatment. Future studies evaluating performance and impact of diagnostics should consider reporting time delay estimates based on the standardized reporting framework.

Abstract Background Historically, the focus of cost-effectiveness analyses has been on the costs to operate and deliver interventions after their initial design and launch. The costs related to design and implementation of interventions have often been omitted. Ignoring these costs leads to an underestimation of the true price of interventions and biases economic analyses toward favoring new interventions. This is especially true in low- and middle-income countries (LMICs), where implementation may require substantial up-front investment. This scoping review was conducted to explore the topics, depth, and availability of scientific literature on integrating implementation science into economic evaluations of health interventions in LMICs. Methods We searched Web of Science and PubMed for papers published between January 1, 2010, and December 31, 2021, that included components of both implementation science and economic evaluation. Studies from LMICs were prioritized for review, but papers from high-income countries were included if their methodology/findings were relevant to LMIC settings. Results Six thousand nine hundred eighty-six studies were screened, of which 55 were included in full-text review and 23 selected for inclusion and data extraction. Most papers were theoretical, though some focused on a single disease or disease subset, including: mental health (n = 5), HIV (n = 3), tuberculosis (n = 3), and diabetes (n = 2). Manuscripts included a mix of methodology papers, empirical studies, and other (e.g., narrative) reviews. Authorship of the included literature was skewed toward high-income settings, with 22 of the 23 papers featuring first and senior authors from high-income countries. Of nine empirical studies included, no consistent implementation cost outcomes were measured, and only four could be mapped to an existing costing or implementation framework. There was also substantial heterogeneity across studies in how implementation costs were defined, and the methods used to collect them. Conclusion A sparse but growing literature explores the intersection of implementation science and economic evaluation. Key needs include more research in LMICs, greater consensus on the definition of implementation costs, standardized methods to collect such costs, and identifying outcomes of greatest relevance. Addressing these gaps will result in stronger links between implementation science and economic evaluation and will create more robust and accurate estimates of intervention costs. Trial registration The protocol for this manuscript was published on the Open Science Framework. It is available at: https://osf.io/ms5fa/ (DOI: 10.17605/OSF.IO/32EPJ).

Abstract Background Approximately 7% of all reported tuberculosis (TB) cases each year are recurrent, occurring among people who have had TB in the recent or distant past. TB recurrence is particularly common in India, which has the largest TB burden worldwide. Although patients recently treated for TB are at high risk of developing TB again, evidence around effective active case finding (ACF) strategies in this population is scarce. We will conduct a hybrid type I effectiveness-implementation non-inferiority randomized trial to compare the effectiveness, cost-effectiveness, and feasibility of two ACF strategies among individuals who have completed TB treatment and their household contacts (HHCs). Methods We will enroll 1076 adults (≥ 18 years) who have completed TB treatment at a public TB unit (TU) in Pune, India, along with their HHCs (averaging two per patient, n = 2152). Participants will undergo symptom-based ACF by existing healthcare workers (HCWs) at 6-month intervals and will be randomized to either home-based ACF (HACF) or telephonic ACF (TACF). Symptomatic participants will undergo microbiologic testing through the program. Asymptomatic HHCs will be referred for TB preventive treatment (TPT) per national guidelines. The primary outcome is rate per 100 person-years of people diagnosed with new or recurrent TB by study arm, within 12 months following treatment completion. The secondary outcome is proportion of HHCs

BackgroundAccess to drug resistant testing for tuberculosis (TB) remains a challenge in high burden countries. Recently, the World Health Organization approved the use of several moderate complexity automated nucleic acid amplification tests (MC-NAAT) that have performance profiles suitable for placement in a range of TB laboratory tiers to improve drug susceptibility tests (DST) coverage.MethodsWe conducted cost analysis of two MC-NAATs with different testing throughput: Lower Throughput (LT, < 24 tests per run) and Higher Throughput (HT, upto 90+ tests per run) for placement in a hypothetical laboratory in a resource limited setting. We used per-test cost as the main indicator to assess 1) drivers of cost by resource types and 2) optimized levels of annual testing volumes for the respective MC-NAATs.ResultsThe base-case per test cost of $18.52 (range: $13.79 - $40.70) for LT test and $15.37 (range: $9.61 - $37.40) for HT test. Per test cost estimates were most sensitive to the number of testing days per week, followed by equipment costs and TB-specific workloads. In general, HT NAATs were cheaper at all testing volume levels, but at lower testing volumes (less than 2,000 per year) LT tests can be cheaper if the durability of the testing system is markedly better and/or procured equipment costs are lower than that of HT NAAT.ConclusionAssuming equivalent performance and infrastructural needs, placement strategies for MC-NAATs need to be prioritized by laboratory system's operational factors, testing demands, and costs.

IntroductionIn South Africa, Community Caregivers (CCGs) visit households to provide basic healthcare services including those for tuberculosis and HIV. However, CCG workloads, costs, and time burden are largely unknown. Our objective was to assess the workloads and operational costs for CCG teams operating in different settings in South Africa.MethodsBetween March and October 2018, we collected standardized self-reported activity time forms from 11 CCG pairs working at two public health clinics in Ekurhuleni district, South Africa. CCG workloads were assessed based on activity unit times, per-household visit time, and mean daily number of successful household visits. Using activity-based times and CCG operating cost data, we assessed CCG annual and per-household visit costs (USD 2019) from the health system perspective.ResultsCCGs in clinic 1 (peri-urban, 7 CCG pairs) and 2 (urban, informal settlement; 4 CCG pairs) served an area of 3.1 km2 and 0.6 km2 with 8,035 and 5,200 registered households, respectively. CCG pairs spent a median 236 minutes per day conducting field activities at clinic 1 versus 235 minutes at clinic 2. CCG pairs at clinic 1 spent 49.5% of this time at households (versus traveling), compared to 35.0% at clinic 2. On average, CCG pairs successfully visited 9.5 vs 6.7 households per day for clinics 1 and 2, respectively. At clinic 1, 2.7% of household visits were unsuccessful, versus 28.5% at clinic 2. Total annual operating costs were higher in clinic 1 ($71,780 vs $49,097) but cost per successful visit was lower ($3.58) than clinic 2 ($5.85).ConclusionsCCG home visits were more frequent, successful, and less costly in clinic 1, which served a larger and more formalized settlement. The variability in workload and cost observed across pairs and clinics suggests that circumstantial factors and CCG needs must be carefully assessed for optimized CCG outreach operations.

Background and objective: The global prevalence and incidence of nontuberculous mycobacterial (NTM) infections are increasing; however, population-level data on healthcare use and medical costs for people with NTM infections are limited. Thus, we investigated the rates of healthcare use and medical costs of people with NTM infections in South Korea using the National Health Insurance Service-National Sample Cohort from 2002 to 2015. Methods: In this cohort study, people with and without NTM infection aged 20–89 years were matched 1 to 4 by sex, age, Charlson comorbidity index, and year of diagnosis. The overall and annual average healthcare use and medical costs were calculated. In addition, trends in healthcare use and medical costs for each of the 3 years before and after NTM diagnosis were investigated for people diagnosed with NTM infection. Results: A total of 798 individuals (336 men and 462 women) diagnosed with NTM infection and 3192 controls were included in the study. NTM-infected patients had significantly higher rates of healthcare use and medical costs than those in the control group ( p

Abstract Background Failing to account for the resources required to successfully implement public health interventions can lead to an underestimation of costs and budget impact, optimistic cost-effectiveness estimates, and ultimately a disconnect between published evidence and public health decision-making. Methods We developed a conceptual framework for assessing implementation costs. We illustrate the use of this framework with case studies involving interventions for tuberculosis and HIV/AIDS in resource-limited settings. Results Costs of implementing public health interventions may be conceptualized as occurring across three phases: design, initiation, and maintenance. In the design phase, activities include developing intervention components and establishing necessary infrastructure (e.g., technology, standard operating procedures). Initiation phase activities include training, initiation of supply chains and quality assurance procedures, and installation of equipment. Implementation costs in the maintenance phase include ongoing technical support, monitoring and evaluation, and troubleshooting unexpected obstacles. Within each phase, implementation costs can be incurred at the site of delivery (“site-specific” costs) or more centrally (“above-service” or “central” costs). For interventions evaluated in the context of research studies, implementation costs should be classified as programmatic, research-related, or shared research/program costs. Purely research-related costs are often excluded from analysis of programmatic implementation. Conclusions In evaluating public health interventions in resource-limited settings, accounting for implementation costs enables more realistic estimates of budget impact and cost-effectiveness and provides important insights into program feasibility, scale-up, and sustainability. Assessment of implementation costs should be planned prospectively and performed in a standardized manner to ensure generalizability.

Abstract Background Delays in diagnosis and treatment of tuberculosis (TB) remain common in high-burden countries. To improve case detection, substantial investments have been made to scale-up Xpert MTB/RIF (Xpert), a cartridge-based nucleic acid amplification test that can detect TB within 2 hours, as a replacement for sputum smear microscopy. However, the optimal strategy for implementation of Xpert testing remains unclear. Methods The Xpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) trial uses an ultra-pragmatic, hybrid type II effectiveness-implementation design to assess the effectiveness and implementation of a streamlined strategy for delivery of Xpert testing in real-world settings. Twenty health centers with TB microscopy units were selected to participate in the trial, with ten health centers randomized to the intervention strategy (onsite molecular testing using GeneXpert Edge, process redesign to facilitate same-day TB diagnosis and treatment, and performance feedback) or routine care (onsite sputum smear microscopy plus referral of sputum samples to Xpert testing sites). The primary outcome is the number of patients with microbiologically confirmed TB who were initiated on treatment within 14 days of presentation to the health center, which reflects successful completion of the TB diagnostic evaluation process. Secondary outcomes include health outcomes (6-month vital status), as well as measures of the reach, adoption, and implementation of the intervention strategy. Discussion The design elements and implementation approach for the XPEL-TB trial were intentionally selected to minimize disruptions to routine care procedures, with the goal of limiting their influence on key primary and secondary outcomes. Trial findings may result in increased support and funding for rapid, onsite molecular testing as the standard-of-care for all patients being evaluated for TB. Trial registration US National Institutes of Health’s ClinicalTrials.gov, NCT03044158 . Registered 06 February 2017. Pan African Clinical Trials Registry, PACTR201610001763265 . Registered 03 September 2016.

Fast Track models-in which patients coming to facility to pick up medications minimize waiting times through foregoing clinical review and collecting pre-packaged medications-present a potential strategy to reduce the burden of treatment. We examine effects of a Fast Track model (FT) in a real-world clinical HIV treatment program on retention to care comparing two clinics initiating FT care to five similar (in size and health care level), standard of care clinics in Zambia. Within each clinic, we selected a systematic sample of patients meeting FT eligibility to follow prospectively for retention using both electronic medical records as well as targeted chart review. We used a variety of methods including Kaplan Meier (KM) stratified by FT, to compare time to first late pick up, exploring late thresholds at >7, >14 and >28 days, Cox proportional hazards to describe associations between FT and late pick up, and linear mixed effects regression to assess the association of FT with medication possession ratio. A total of 905 participants were enrolled with a median age of 40 years (interquartile range [IQR]: 34-46 years), 67.1% were female, median CD4 count was 499 cells/mm3 (IQR: 354-691), and median time on ART was 5 years (IQR: 3-7). During the one-year follow-up period FT participants had a significantly reduced cumulative incidence of being >7 days late for ART pick-up (0.36, 95% confidence interval [CI]: 0.31-0.41) compared to control participants (0.66; 95% CI: 0.57-0.65). This trend held for >28 days late for ART pick-up appointments, at 23% (95% CI: 18%-28%) among intervention participants and 54% (95% CI: 47%-61%) among control participants. FT models significantly improved timely ART pick up among study participants. The apparent synergistic relationship between refill time and other elements of the FT suggest that FT may enhance the effects of extending visit spacing/multi-month scripting alone. ClinicalTrials.gov Identifier: NCT02776254 https://clinicaltrials.gov/ct2/show/NCT02776254.

IntroductionMobile health (mHealth) applications may improve timely access to health services and improve patient-provider communication, but the upfront costs of implementation may be prohibitive, especially in resource-limited settings.MethodsWe measured the costs of developing and implementing an mHealth-facilitated, home-based strategy for tuberculosis (TB) contact investigation in Kampala, Uganda, between February 2014 and July 2017. We compared routine implementation involving community health workers (CHWs) screening and referring household contacts to clinics for TB evaluation to home-based HIV testing and sputum collection and transport with test results delivered by automated short messaging services (SMS). We carried out key informant interviews with CHWs and asked them to complete time-and-motion surveys. We estimated program costs from the perspective of the Ugandan health system, using top-down and bottom-up (components-based) approaches. We estimated total costs per contact investigated and per TB-positive contact identified in 2018 US dollars, one and five years after program implementation.ResultsThe total top-down cost was $472,327, including $358,504 (76%) for program development and $108,584 (24%) for program implementation. This corresponded to $320-$348 per household contact investigated and $8,873-$9,652 per contact diagnosed with active TB over a 5-year period. CHW time was spent primarily evaluating household contacts who returned to the clinic for evaluation (median 30 minutes per contact investigated, interquartile range [IQR]: 30-70), collecting sputum samples (median 29 minutes, IQR: 25-30) and offering HIV testing services (median 28 minutes, IQR: 17-43). Cost estimates were sensitive to infrastructural capacity needs, program reach, and the epidemiological yield of contact investigation.ConclusionOver 75% of all costs of the mHealth-facilitated TB contact investigation strategy were dedicated to establishing mHealth infrastructure and capacity. Implementing the mHealth strategy at scale and maintaining it over a longer time horizon could help decrease development costs as a proportion of total costs.

Purpose Interventions that can help streamline and reduce gaps in the tuberculosis (TB) care cascade can play crucial roles in TB prevention and care, but are often operationally complex and resource intensive, given the heterogenous settings in which they are implemented. In this study, we present a comparative analysis on cost-effectiveness of TB REACH Wave 5 projects with diverse programmatic objectives to inform future decisions regarding funding, strategic adoption, and scale-up. Methods We comprehensively reviewed project reports and financial statements from TB REACH Wave 5, a funding mechanism for interventions that aimed to strengthen the TB care cascade in diverse settings. Two independent reviewers abstracted cost (in 2017 US dollars) and key programmatic data, including project type (case-finding only; case-finding and linkage-to-care; or case-finding, linkage-to-care and patient support), operational setting (urban or rural), and project outputs (numbers of people with TB diagnosed, started on treatment, and successfully completing treatment). Cost-effectiveness ratios for each project were calculated as ratios of apportioned programmatic expenditures to corresponding project outputs. Results Of 32 case finding and patient support projects funded through TB REACH Wave 5, 29 were included for analysis (11 case-finding only; 9 case-finding and linkage-to-care; and 9 case-finding, linkage-to-care and patient support). 21 projects (72%) were implemented in either Africa or Southeast Asia, and 19 (66%) focused on serving urban areas. Average cost-effectiveness was $184 per case diagnosed (range: $30-$10,497), $332 per diagnosis and treatment initiation ($123-$10,608), and $40 per patient treatment supported ($8-$160). Cost per case diagnosed was lower for case-finding-only projects ($132) than projects including linkage-to-care ($342) or linkage-to-care and patient support ($254), and generally increased with the corresponding country’s per-capita GDP ($543 per $1000 increase, 95% confidence interval: -$53, $1138). Conclusion The costs and cost-effectiveness of interventions to strengthen the TB care cascade were heterogenous, reflecting differences in context and programmatic objective. Nevertheless, many such interventions are likely to offer good value for money. Systematic collection and analysis of cost-effectiveness data can help improve comparability, monitoring, and evaluation.

BackgroundPublic-private mix (PPM) programs on tuberculosis (TB) have a critical role in engaging and integrating the private sector into the national TB control efforts in order to meet the End TB Strategy targets. South Korea's PPM program can provide important insights on the long-term impact and policy gaps in the development and expansion of PPM as a nationwide program.Methods and findingsHealthcare is privatized in South Korea, and a majority (80.3% in 2009) of TB patients sought care in the private sector. Since 2009, South Korea has rapidly expanded its PPM program coverage under the National Health Insurance (NHI) scheme as a formal national program with dedicated PPM nurses managing TB patients in both the private and public sectors. Using the difference in differences (DID) analytic framework, we compared relative changes in TB treatment outcomes-treatment success (TS) and loss to follow-up (LTFU)-in the private and public sector between the 2009 and 2014 TB patient cohorts. Propensity score matching (PSM) using the kernel method was done to adjust for imbalances in the covariates between the 2 population cohorts. The 2009 cohort included 6,195 (63.0% male, 37.0% female; mean age: 42.1) and 27,396 (56.1% male, 43.9% female; mean age: 45.7) TB patients in the public and private sectors, respectively. The 2014 cohort included 2,803 (63.2% male, 36.8% female; mean age: 50.1) and 29,988 (56.5% male, 43.5% female; mean age: 54.7) patients. In both the private and public sectors, the proportion of patients with transfer history decreased (public: 23.8% to 21.7% and private: 20.8% to 17.6%), and bacteriological confirmed disease increased (public: 48.9% to 62.3% and private: 48.8% to 58.1%) in 2014 compared to 2009. After expanding nationwide PPM, absolute TS rates improved by 9.10% (87.5% to 93.4%) and by 13.6% (from 70.3% to 83.9%) in the public and private sectors. Relative to the public, the private saw 4.1% (95% confidence interval [CI] 2.9% to 5.3%, p-value < 0.001) and -8.7% (95% CI -9.7% to -7.7%, p-value ConclusionsWe found that the nationwide scale-up of the PPM program was associated with improvements in TB treatment outcomes in the private sector in South Korea. Centralized financial governance and regulatory mechanisms were integral in facilitating the integration of highly diverse South Korean private sector into the national TB control program and scaling up of the PPM intervention nationwide. However, TB care gaps continued to exist for patients who transferred at least once during their treatment. These programmatic gaps may be improved through reducing administrative hurdles and making programmatic amendments that can help facilitate management TB patients between institutions and healthcare sectors, as well as across administrative regions.

Abstract Background India and many other high-burden countries have committed to providing universal access to high-quality diagnosis and drug susceptibility testing (DST) for tuberculosis (TB), but the most cost-effective approach to achieve this goal remains uncertain. Centralized testing at district-level hub facilities with a supporting sample transport network can generate economies of scale, but decentralization to the peripheral level may provide faster diagnosis and reduce losses to follow-up (LTFU). Methods We generated functions to evaluate the costs of centralized and decentralized molecular testing for tuberculosis with Xpert MTB/RIF (Xpert), a WHO-endorsed test which can be performed at centralized and decentralized levels. We merged the cost estimates with an agent-based simulation of TB transmission in a hypothetical representative region in India to assess the impact and cost-effectiveness of each strategy. Results Compared against centralized Xpert testing, decentralization was most favorable when testing volume at decentralized facilities and pre-treatment LTFU were high, and specimen transport network was exclusively established for TB. Assuming equal quality of centralized and decentralized testing, decentralization was cost-saving, saving a median $338,000 (interquartile simulation range [IQR] − $222,000; $889,000) per 20 million people over 10 years, in the most cost-favorable scenario. In the most cost-unfavorable scenario, decentralized testing would cost a median $3161 [IQR $2412; $4731] per disability-adjusted life year averted relative to centralized testing. Conclusions Decentralization of Xpert testing is likely to be cost-saving or cost-effective in most settings to which these simulation results might generalize. More decentralized testing is more cost-effective in settings with moderate-to-high peripheral testing volumes, high existing clinical LTFU, inability to share specimen transport costs with other disease entities, and ability to ensure high-quality peripheral Xpert testing. Decision-makers should assess these factors when deciding whether to decentralize molecular testing for tuberculosis.

Abstract Background The mass scale-up of antiretroviral therapy (ART) in Zambia has taken place in the context of limited infrastructure and human resources resulting in many operational side-effects. In this study, we aimed to empirically measure current workload of ART clinic staff and patient wait times and service utilization. Methods We conducted time and motion (TAM) studies from both the healthcare worker (HCW) and patient perspectives at 10 ART clinics throughout Zambia. Trained personnel recorded times for consecutive discrete activities based on direct observation of clinical and non-clinical activities performed by counselors, clinical officers, nurses, and pharmacy technicians. For patient TAM, we recruited consenting patients and recorded times of arrival and departure and major ART services utilized. Data from 10 clinics were pooled to evaluate median time per patient spent for each activity and patient duration of stay in the clinic. Results The percentage of observed clinical time for direct patient interaction (median time per patient encounter) was 43.1% for ART counselors (4 min, interquartile range [IQR] 2–7), 46.1% for nurses (3 min, IQR 2–4), 57.2% for pharmacy technicians (2 min, IQR 1–2), and 78.5% for clinical officers (3 min, IQR 2–5). Patient workloads for HCWs were heaviest between 8 AM and 12 PM with few clinical activities observed after 2 PM. The length of patient visits was inversely associated with arrival time – patients arriving prior to 8 AM spent 61% longer at the clinic than those arriving after 8 AM (277 vs. 171 min). Overall, patients spent 219 min on average for non-clinical visits, and 244 min for clinical visits, but this difference was not significant in rural clinics. In comparison, total time patients spent directly with clinic staff were 9 and 12 min on average for non-clinical and clinical visits. Conclusion Current Zambian ART clinic operations include substantial inefficiencies for both patients and HCWs, with workloads heavily concentrated in the first few hours of clinic opening, limiting HCW and patient interaction time. Use of a differentiated care model may help to redistribute workloads during operational hours and prevent backlogs of patients waiting for hours before clinic opening, which may substantially improve ART delivery in the Zambian context.

IntroductionActive-case finding (ACF) programs have an important role in addressing case detection gaps and halting tuberculosis (TB) transmission. Evidence is limited on the cost-effectiveness of ACF interventions, particularly on how their value is impacted by different operational, epidemiological and patient care-seeking patterns.MethodsWe evaluated the costs and cost-effectiveness of a combined facility and community-based ACF intervention in Zambia that utilized mobile chest X-ray with computer-aided reading/interpretation software and laboratory-based Xpert MTB/RIF testing. Programmatic costs (in 2018 US dollars) were assessed from the health system perspective using prospectively collected cost and operational data. Cost-effectiveness of the ACF intervention was assessed as the incremental cost per TB death averted over a five-year time horizon using a multi-stage Markov state-transition model reflecting patient symptom-associated care-seeking and TB care under ACF compared to passive care.ResultsOver 18 months of field operations, the ACF intervention costed $435 to diagnose and initiate treatment for one person with TB. After accounting for patient symptom-associated care-seeking patterns in Zambia, we estimate that this one-time ACF intervention would incrementally diagnose 407 (7,207 versus 6,800) TB patients and avert 502 (611 versus 1,113) TB-associated deaths compared to the status quo (passive case finding), at an incremental cost of $2,284 per death averted over the next five-year period. HIV/TB mortality rate, patient symptom-associated care-seeking probabilities in the absence of ACF, and the costs of ACF patient screening were key drivers of cost-effectiveness.ConclusionsA one-time comprehensive ACF intervention simultaneously operating in public health clinics and corresponding catchment communities can have important medium-term impact on case-finding and be cost-effective in Zambia. The value of such interventions increases if targeted to populations with high HIV/TB mortality, substantial barriers (both behavioral and physical) to care-seeking exist, and when ACF interventions can optimize screening by achieving operational efficiency.

INTRODUCTION:Over the years, technological and process innovations enabled active case finding (ACF) programs to expand their capacities and scope to have evolved to close gaps in missing TB patients globally. However, with increased ACF program's operational complexity and a need for significant resource commitments, a comprehensive, transparent, and standardized approach in evaluating costs of ACF programs is needed to properly determine costs and value of ACF programs. METHODS:Based on reviews of program activity and financial reports, multiple interviews with program managers of two TB REACH funded ACF programs deployed in Cambodia and Tajikistan, we first identified common program components, which formed the basis of the cost data collection, analysis, reporting framework. Within each program component and sub-activity group, cost data were collected and organized by relevant resource types (human resource, capital, recurrent, and overhead costs). Total shared, indirect and overhead costs were apportioned into each activity category based on direct human resource contribution (e.g. a number of staff and their relative level of effort dedicated to each program component). Capital assets were assessed specific to program components and were annualized based on their expected useful life and a 3% discount rate. All costs were assessed based on the service provider perspective and expressed in 2015 USD. RESULTS:Over the two program years (April 2013 to December 2015), the Cambodia and Tajikistan ACF programs cumulated a total cost of $336,951 and $771,429 to screen 68,846 and 1,980,516 target population, bacteriologically test 4,589 and 19,764 presumptive TB, diagnose 731 and 2,246 TB patients in the respective programs. Recurrent costs were the largest cost components (54% and 34%) of the total costs for the respective programs and Xpert MTB/RIF (Xpert) testing incurred largest program component/activity cost for both programs. Cost per screening was $0.63 and $0.10 and cost per Xpert test was $25 and $18; Cost per TB case detected (Xpert) was $373 and $343 in Cambodia and Tajikistan. CONCLUSIONS:Results from two contextually and programmatically different multi-component ACF programs demonstrate that our tool is fully capable of comprehensively and transparently evaluating and comparing costs of various ACF programs.

Summary: Background: Rapid on-site diagnosis facilitates tuberculosis control. Performing Xpert MTB/RIF (Xpert) at point of care is feasible, even when performed by minimally trained health-care workers, and when compared with point-of-care smear microscopy, reduces time to diagnosis and pretreatment loss to follow-up. However, whether Xpert is cost-effective at point of care remains unclear. Methods: We empirically collected cost (US$, 2014) and clinical outcome data from participants presenting to primary health-care facilities in four African countries (South Africa, Zambia, Zimbabwe, and Tanzania) during the TB-NEAT trial. Costs were determined using an bottom-up ingredients approach. Effectiveness measures from the trial included number of cases diagnosed, initiated on treatment, and completing treatment. The primary outcome was the incremental cost-effectiveness of point-of-care Xpert relative to smear microscopy. The study was performed from the perspective of the health-care provider. Findings: Using data from 1502 patients, we calculated that the mean Xpert unit cost was lower when performed at a centralised laboratory (Lab Xpert) rather than at point of care ($23·00 [95% CI 22·12–23·88] vs $28·03 [26·19–29·87]). Per 1000 patients screened, and relative to smear microscopy, point-of-care Xpert cost an additional $35 529 (27 054–40 025) and was associated with an additional 24·3 treatment initiations ([–20·0 to 68·5]; $1464 per treatment), 63·4 same-day treatment initiations ([27·3–99·4]; $511 per same-day treatment), and 29·4 treatment completions ([–6·9 to 65·6]; $1211 per completion). Xpert costs were most sensitive to test volume, whereas incremental outcomes were most sensitive to the number of patients initiating and completing treatment. The probability of point-of-care Xpert being cost-effective was 90% at a willingness to pay of $3820 per treatment completion. Interpretation: In southern Africa, although point-of-care Xpert unit cost is higher than Lab Xpert, it is likely to offer good value for money relative to smear microscopy. With the current availability of point-of-care nucleic acid amplification platforms (eg, Xpert Edge), these data inform much needed investment and resource allocation strategies in tuberculosis endemic settings. Funding: European Union European and Developing Countries Clinical Trials Partnership.

BACKGROUND:Outreach and promotion programs are essential to ensuring uptake of new public health interventions and guidelines. We assessed the costs and operation dynamics of outreach and promotion efforts for up front Xpert MTB/RIF (Xpert) testing for pediatric presumptive tuberculosis (TB) patients in four major Indian cities. METHODS:Xpert test costs were assessed as weighted average per-test costs based on the daily workload dynamics matched by test volume specific Xpert unit cost at each study site. Costs of outreach programs to recruit health providers to refer pediatric patients for Xpert testing were assessed as cost per referral for each quarter based on total program costs and referral data. All costs were assessed in the health service provider's perspective and expressed in 2015 USD. RESULTS:Weighted average per-test costs ranged from $14.71 to $17.81 at the four laboratories assessed. Differences between laboratories were associated with unused testing capacity and/or frequencies of overtime work to cope with increasing demand and same-day testing requirements. Outreach activities generated between 825 and 2,065 Xpert testing referrals on average each quarter across the four study sites, translating into $0.63 to $2.55 per patient referred. Overall outreach costs per referral decreased with time, stabilizing at an average cost of $1.10, and demonstrated a clear association with increased referrals. CONCLUSIONS:Xpert test and outreach program costs within and across study sites were mainly driven by the dynamics of Xpert testing demand resulting from the combined outreach activities. However, these increases in demand required considerable overtime work resulting in additional costs and operational challenges at the study laboratories. Therefore, careful laboratory operational adjustment should be evaluated at target areas in parallel to the anticipated demand from the Xpert referral outreach program scale-up in other Indian regions.

Background: Xpert® MTB/RIF, a rapid tuberculosis (TB) molecular test, was endorsed by the World Health Organization in 2010. Since then, 34.4 million cartridges have been procured under concessional pricing. Although the roll out of this diagnostic is promising, previous studies showed low market penetration. Methods: To assess 3-year trends of market penetration of Xpert MTB/RIF in the public sector, smear and Xpert MTB/RIF volumes for the year 2016 were evaluated and policies from 2014-2016 within 22 high-burden countries (HBCs) were studied. A structured questionnaire was sent to representatives of 22 HBCs. The questionnaires assessed the total smear and Xpert MTB/RIF volumes, number of modules and days of operation of GeneXpert machines in National TB Programs (NTPs). Data regarding the use of NTP GeneXpert machines for other diseases and GeneXpert procurement by other disease control programs were collected. Market penetration was estimated by the ratio of total sputum smear volume for initial diagnosis divided by the number of Xpert MTB/RIF tests procured in the public sector. Results: The survey response rate was 21/22 (95%). Smear/Xpert ratios decreased in 17/21 countries and increased in four countries, since 2014. The median ratio decreased from 32.6 (IQR: 44.6) in 2014 to 6.0 (IQR: 15.4) in 2016. In 2016, the median GeneXpert utilization was 20%, however seven countries (7/19; 37%) were running tests for other diseases on their NTP-procured GeneXpert systems in 2017, such as HIV, hepatitis-C virus (HCV), Chlamydia trachomatis, and Neisseria gonorrhoeae. Five (5/15; 33%) countries reported GeneXpert procurement by HIV or HCV programs in 2016 and/or 2017. Conclusions: Our results show a positive trend for Xpert MTB/RIF market penetration in 21 HBC public sectors. However, GeneXpert machines were under-utilized for TB, and inadequately exploited as a multi disease technology.

Background: Xpert® MTB/RIF, a rapid tuberculosis (TB) molecular test, was endorsed by the World Health Organization in 2010. Since then, 34.4 million cartridges have been procured under concessional pricing. Although the roll out of this diagnostic is promising, previous studies showed low market penetration. Methods: To assess 3-year trends of market penetration of Xpert MTB/RIF in the public sector, smear and Xpert MTB/RIF volumes for the year 2016 were assessed and policies from 2014-2016 within 22 high-burden countries (HBCs) were studied. A structured questionnaire was sent to representatives of 22 HBCs. The questionnaires assessed the total smear and Xpert MTB/RIF volumes, number of modules and days of operation of GeneXpert machines in National TB Programs (NTPs). Data regarding the use of NTP GeneXpert machines for other diseases and GeneXpert procurement by other disease control programs were collected. Market penetration was estimated by the ratio of total sputum smear volume for initial diagnosis divided by the number of Xpert MTB/RIF tests procured in the public sector. Results: The survey response rate was 21/22 (95%). Smear/Xpert ratios decreased in 17/21 countries and increased in four countries, since 2014. The median ratio decreased from 32.6 (Q1:14.3, Q3: 58.9) in 2014 to 6.0 (Q1: 1.6, Q3: 17.0) in 2016. Nineteen countries (19/19; 100%) were not using GeneXpert machines to their full capacity, however seven countries (7/19; 37%) were running tests for other diseases on their NTP-procured GeneXpert systems in 2017, such as HIV, hepatitis-C virus (HCV), Chlamydia trachomatis, and Neisseria gonorrhoeae. Five (5/15; 33%) countries reported GeneXpert procurement by HIV or HCV programs in 2016 and/or 2017. Conclusions: Our results show a positive trend for Xpert MTB/RIF market penetration in 21 HBC public sectors. However, GeneXpert machines were under-utilized for TB, and inadequately exploited as a multi disease technology.

BACKGROUND:Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence. OBJECTIVE:To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy. METHODS:Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated. RESULTS:Of 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65). CONCLUSION:The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis.

BACKGROUND:Several reviews on the accuracy of Tuberculosis (TB) Nucleic Acid Amplification Tests (NAATs) have been performed but the evidence on their impact on patient-important outcomes has not been systematically reviewed. Given the recent increase in research evaluating such outcomes and the growing list of TB NAATs that will reach the market over the coming years, there is a need to bring together the existing evidence on impact, rather than accuracy. We aimed to assess the approaches that have been employed to measure the impact of TB NAATs on patient-important outcomes in adults with possible pulmonary TB and/or drug-resistant TB. METHODS:We first develop a conceptual framework to clarify through which mechanisms the improved technical performance of a novel TB test may lead to improved patient outcomes and outline which designs may be used to measure them. We then systematically review the literature on studies attempting to assess the impact of molecular TB diagnostics on such outcomes and provide a narrative synthesis of designs used, outcomes assessed and risk of bias across different study designs. RESULTS:We found 25 eligible studies that assessed a wide range of outcomes and utilized a variety of experimental and observational study designs. Many potentially strong design options have never been used. We found that much of the available evidence on patient-important outcomes comes from a small number of settings with particular epidemiological and operational context and that confounding, time trends and incomplete outcome data receive insufficient attention. CONCLUSIONS:A broader range of designs should be considered when designing studies to assess the impact of TB diagnostics on patient outcomes and more attention needs to be paid to the analysis as concerns about confounding and selection bias become relevant in addition to those on measurement that are of greatest concern in accuracy studies.

BACKGROUND: Genechip (CapitalBio, Beijing, China) is a system for diagnosing resistance to rifampin and isoniazid, which shows high efficiency in detecting drug-resistant tuberculosis. Here, we firstly evaluated the costs of Genechip for detecting the drug susceptibility of Mycobacterium tuberculosis, compared to conventional drug susceptibility test (DST) in laboratories in China. METHODOLOGY/PRINCIPAL FINDINGS: Data on the costs of the two tests were collected at four hospitals. Costs were calculated using the essential factor cost calculation method. The costs of diagnosing a single case of multidrug-resistant tuberculosis (MDR-TB) using Genechip and DST were US$22.38 and $53.03, respectively. Taking into account the effect on costs from failure of a certain number of tests to accurately diagnose MDR-TB, the costs of Genechip and DST increased by 17.65% and 5.22%, respectively. The cost of both tests decreased with the increasing prevalence of MDR-TB disease, and the cost of Genechip at a sensitivity of more than 50% was lower than that of DST. When price of Genechip was varied to 50%, 80%, 150%, and 200% of the original price, the cost of Genechip at sensitivities of more than 30%, 40%, 60%, and 70%, respectively, was also lower than that of DST. CONCLUSIONS/SIGNIFICANCE: This study showed that Genechip was a more cost-effective method of diagnosing MDR-TB compared to conventional DST.

BackgroundXpert MTB/RIF (Xpert) is a promising new rapid diagnostic technology for tuberculosis (TB) that has characteristics that suggest large-scale roll-out. However, because the test is expensive, there are concerns among TB program managers and policy makers regarding its affordability for low- and middle-income settings.Methods and findingsWe estimate the impact of the introduction of Xpert on the costs and cost-effectiveness of TB care using decision analytic modelling, comparing the introduction of Xpert to a base case of smear microscopy and clinical diagnosis in India, South Africa, and Uganda. The introduction of Xpert increases TB case finding in all three settings; from 72%-85% to 95%-99% of the cohort of individuals with suspected TB, compared to the base case. Diagnostic costs (including the costs of testing all individuals with suspected TB) also increase: from US$28-US$49 to US$133-US$146 and US$137-US$151 per TB case detected when Xpert is used "in addition to" and "as a replacement of" smear microscopy, respectively. The incremental cost effectiveness ratios (ICERs) for using Xpert "in addition to" smear microscopy, compared to the base case, range from US$41-$110 per disability adjusted life year (DALY) averted. Likewise the ICERS for using Xpert "as a replacement of" smear microscopy range from US$52-$138 per DALY averted. These ICERs are below the World Health Organization (WHO) willingness to pay threshold.ConclusionsOur results suggest that Xpert is a cost-effective method of TB diagnosis, compared to a base case of smear microscopy and clinical diagnosis of smear-negative TB in low- and middle-income settings where, with its ability to substantially increase case finding, it has important potential for improving TB diagnosis and control. The extent of cost-effectiveness gain to TB programmes from deploying Xpert is primarily dependent on current TB diagnostic practices. Further work is required during scale-up to validate these findings.

ObjectiveTo analyse the feasibility, cost and performance of rapid tuberculosis (TB) molecular and culture systems, in a high multidrug-resistant TB (MDR TB) middle-income region (Samara, Russia) and provide evidence for WHO policy change.MethodsPerformance and cost evaluation was conducted to compare the BACTEC MGIT 960 system for culture and drug susceptibility testing (DST) and molecular systems for TB diagnosis, resistance to isoniazid and rifampin, and MDR TB identification compared to conventional Lowenstein-Jensen culture assays.Findings698 consecutive patients (2487 sputum samples) with risk factors for drug-resistant tuberculosis were recruited. Overall M. tuberculosis complex culture positivity rates were 31.6% (787/2487) in MGIT and 27.1% (675/2487) in LJ (90.5% and 83.2% for smear-positive specimens). In total, 809 cultures of M. tuberculosis complex were isolated by any method. Median time to detection was 14 days for MGIT and 36 days for LJ (10 and 33 days for smear positive specimens) and indirect DST in MGIT took 9 days compared to 21 days on LJ. There was good concordance between DST on LJ and MGIT (96.8% for rifampin and 95.6% for isoniazid). Both molecular hybridization assay results correlated well with MGIT DST results, although molecular assays generally yielded higher rates of resistance (by approximately 3% for both isoniazid and rifampin).ConclusionWith effective planning and logistics, the MGIT 960 and molecular based methodologies can be successfully introduced into a reference laboratory setting in a middle incidence country. High rates of MDR TB in the Russian Federation make the introduction of such assays particularly useful.

Objective: To analyse the feasibility, cost and performance of rapid tuberculosis (TB) molecular and culture systems, in a high multidrug-resistant TB (MDR TB) middle-income region (Samara, Russia) and provide evidence for WHO policy change. Methods: Performance and cost evaluation was conducted to compare the BACTEC™ MGIT™ 960 system for culture and drug susceptibility testing (DST) and molecular systems for TB diagnosis, resistance to isoniazid and rifampin, and MDR TB identification compared to conventional Lowenstein-Jensen culture assays. Findings: 698 consecutive patients (2487 sputum samples) with risk factors for drug-resistant tuberculosis were recruited. Overall M. tuberculosis complex culture positivity rates were 31.6% (787/2487) in MGIT and 27.1% (675/2487) in LJ (90.5% and 83.2% for smear-positive specimens). In total, 809 cultures of M. tuberculosis complex were isolated by any method. Median time to detection was 14 days for MGIT and 36 days for LJ (10 and 33 days for smear positive specimens) and indirect DST in MGIT took 9 days compared to 21 days on LJ. There was good concordance between DST on LJ and MGIT (96.8% for rifampin and 95.6% for isoniazid). Both molecular hybridization assay results correlated well with MGIT DST results, although molecular assays generally yielded higher rates of resistance (by approximately 3% for both isoniazid and rifampin). Conclusion: With effective planning and logistics, the MGIT 960 and molecular based methodologies can be successfully introduced into a reference laboratory setting in a middle incidence country. High rates of MDR TB in the Russian Federation make the introduction of such assays particularly useful. [ABSTRACT FROM AUTHOR]