Engagement of private health care facilities in TB management in Lusaka district of Zambia: lessons learned and achievements.

BACKGROUND: Globally, at least 3 million TB patients are missed every year. In Zambia, the TB treatment coverage increased from 66% in 2020 to 92% in 2022. Involvement of all levels of health care service delivery is critical to finding all the missing TB patients. METHODS: A survey was undertaken in 15 private facilities in Lusaka district of Zambia using a structured tool administered by project team and a district health team member. Data collected during the survey was analysed and results were used to determine the type of TB services that were offered as well as barriers and enablers to TB service provision. This was followed by a set of interventions that included; training and mentorship on active case finding and systematic TB screening, increased diagnostic capacity, provision of national recording and reporting tools and provision of TB medication through linkage with the National TB program (NTP). We report findings from the baseline survey and changes in presumptive TB identification and notification following interventions. RESULTS: Major barriers to TB service delivery were the high cost of TB diagnostic testing and treatment in facilities where services were not supported by the National TB program; the mean cost was 33 (SD 33) and 93 (SD 148) for GeneXpert testing and a full course of treatment respectively. Pre-intervention, presumptive TB identification appeared to increase monthly by 4 (P = 0.000, CI=[3.00-5.00]). The monthly trends of presumptive TB identification during the intervention period increased by 5.32 (P = 0.000, [CI 4.31-6.33. Pre-intervention, the notification of TB appeared to decrease every month by -4.0 (P = 0.114, CI=[-9.00-0.10]) followed by an immediate increase in notifications of 13.94 TB patients (P = 0.001, CI [6.51, 21.36] in the first month on intervention. The monthly trends of notification during the intervention period changed by 0.34 (P = 0.000 [CI 0.19-0.48]). Private facility contribution to TB notification increased from 3 to 7%. CONCLUSION: Engagement and inclusion of private health facilities in TB service provision through a systems strengthening approach can increase contribution to TB notification by private health facilities.

Quantifying gaps in the tuberculosis care cascade in Brazil: A mathematical model study using national program data.

BACKGROUND: In Brazil, many individuals with tuberculosis (TB) do not receive appropriate care due to delayed or missed diagnosis, ineffective treatment regimens, or loss-to-follow-up. This study aimed to estimate the health losses and TB program costs attributable to each gap in the care cascade for TB disease in Brazil. METHODS AND FINDINGS: We constructed a Markov model simulating the TB care cascade and lifetime health outcomes (e.g., death, cure, postinfectious sequelae) for individuals developing TB disease in Brazil. We stratified the model by age, human immunodeficiency virus (HIV) status, drug resistance, state of residence, and disease severity, and developed a parallel model for individuals without TB that receive a false-positive TB diagnosis. Models were fit to data (adult and pediatric) from Brazil's Notifiable Diseases Information System (SINAN) and Mortality Information System (SIM) for 2018. Using these models, we assessed current program performance and simulated hypothetical scenarios that eliminated specific gaps in the care cascade, in order to quantify incremental health losses and TB diagnosis and treatment costs along the care cascade. TB-attributable disability-adjusted life years (DALYs) were calculated by comparing changes in survival and nonfatal disability to a no-TB counterfactual scenario. We estimated that 90.0% (95% uncertainty interval [UI]: 85.2 to 93.4) of individuals with TB disease initiated treatment and 10.0% (95% UI: 7.6 to 12.5) died with TB. The average number of TB-attributable DALYs per incident TB case varied across Brazil, ranging from 2.9 (95% UI: 2.3 to 3.6) DALYs in Acre to 4.0 (95% UI: 3.3 to 4.7) DALYs in Rio Grande do Sul (national average 3.5 [95% UI: 2.8 to 4.1]). Delayed diagnosis contributed the largest health losses along the care cascade, followed by post-TB sequelae and loss to follow up from TB treatment, with TB DALYs reduced by 71% (95% UI: 65 to 76), 41% (95% UI: 36 to 49), and 10% (95% UI: 7 to 16), respectively, when these factors were eliminated. Total health system costs were largely unaffected by improvements in the care cascade, with elimination of treatment failure reducing attributable costs by 3.1% (95% UI: 1.5 to 5.4). TB diagnosis and treatment of false-positive individuals accounted for 10.2% (95% UI: 3.9 to 21.7) of total programmatic costs but contributed minimally to health losses. Several assumptions were required to interpret programmatic data for the analysis, and we were unable to estimate the contribution of social factors to care cascade outcomes. CONCLUSIONS: In this study, we observed that delays to diagnosis, post-disease sequelae and treatment loss to follow-up were primary contributors to the TB burden of disease in Brazil. Reducing delays to diagnosis, improving healthcare after TB cure, and reducing treatment loss to follow-up should be prioritized to improve the burden of TB disease in Brazil.

Tuberculosis in people of Ukrainian origin in the European Union and the European Economic Area, 2019 to 2022.

Approximately five million Ukrainians were displaced to the EU/EEA following the Russian invasion of Ukraine. While tuberculosis (TB) notification rates per 100,000 Ukrainians in the EU/EEA remained stable, the number of notified TB cases in Ukrainians increased almost fourfold (mean 2019-2021: 201; 2022: 780). In 2022, 71% cases were notified in three countries, and almost 20% of drug-resistant TB cases were of Ukrainian origin. Targeted healthcare services for Ukrainians are vital for early diagnosis and treatment, and preventing transmission.

Cost-effectiveness of active tuberculosis screening among high-risk populations in low tuberculosis incidence countries: a systematic review, 2008 to 2023.

BackgroundIn countries with a low TB incidence (≤ 10 cases/100,000 population), active pulmonary tuberculosis (PTB) mostly affects vulnerable populations with limited access to healthcare. Thus, passive case-finding systems may not be successful in detecting and treating cases and preventing further transmission. Active and cost-effective search strategies can overcome this problem.AimWe aimed to review the evidence on the cost-effectiveness (C-E) of active PTB screening programmes among high-risk populations in low TB incidence countries.MethodsWe performed a systematic literature search covering 2008-2023 on PubMed, Embase, Center for Reviews and Dissemination, including Database of Abstracts of Reviews of Effects (DARE), National Health Services Economic Evaluation Database (NHS EED), Global Index Medicus and Cochrane Central Register of Controlled Trials (CENTRAL).ResultsWe retrieved 6,318 articles and included nine in this review. All included studies had an active case-finding approach and used chest X-ray, tuberculin skin test, interferon-gamma release assay and a symptoms questionnaire for screening. The results indicate that screening immigrants from countries with a TB incidence > 40 cases per 100,000 population and other vulnerable populations as individuals from isolated communities, people experiencing homelessness, those accessing drug treatment services and contacts, is cost-effective in low-incidence countries.ConclusionIn low-incidence countries, targeting high-risk groups is C-E. However, due to the data heterogenicity, we were unable to compare C-E. Harmonisation of the methods for C-E analysis is needed and would facilitate comparisons. To outline comprehensive screening and its subsequent C-E analysis, researchers should consider multiple factors influencing screening methods and outcomes.

Inventory study on completeness of tuberculosis case notifications in Poland in 2018.

BackgroundEvaluating tuberculosis (TB) notification completeness is important for monitoring TB surveillance systems, while estimating the TB disease burden is crucial for control strategies.AimWe conducted an inventory study to assess TB reporting completeness in Poland in 2018.MethodsUsing a double-pronged inventory approach, we compared notifications of culture-positive TB cases in the National TB Register to records of diagnostic laboratories. We calculated under-reporting both with observed and capture-recapture (CRC)-estimated case numbers. We further compared the notifications by region (i.e. voivodship), sex, and age to aggregated data from hospitalised TB patients, which provided an independent estimate of reporting completeness.ResultsIn 2018, 4,075 culture-positive TB cases were notified in Poland, with 3,789 linked to laboratory records. Laboratories reported further 534 TB patients, of whom 456 were linked to notifications from 2017 or 2019. Thus, 78 (534 - 456) cases were missing in the National TB Register, yielding an observed TB under-reporting of 1.9% (78/(4,075 + 78) × 100). CRC-modelled total number of cases in 2018 was 4,176, corresponding to 2.4% ((4,176 - 4,075)/4,176 × 100) under-reporting. Based on aggregated hospitalisation data from 13 of 16 total voivodeships, under-reporting was 5.1% (3,482/(3,670 - 3,482) × 100), similar in both sexes but varying between voivodeships and age groups.ConclusionsOur results suggest that the surveillance system captures ≥ 90% of estimated TB cases in Poland; thus, the notification rate is a good proxy for the diagnosed TB incidence in Poland. Reporting delays causing discrepancies between data sources could be improved by the planned change from a paper-based to a digital reporting system.

Cost-effectiveness of interferon-γ release assay for screening of latent tuberculosis infection in individuals with schizophrenia.

Schizophrenia is recognized as a significant risk factor for tuberculosis (TB). This study aimed to evaluate the effectiveness and cost-effectiveness of interferon-γ release assay (IGRA) with preventive treatment for screening of latent tuberculosis infection (LTBI) in individuals with schizophrenia. A state transition model was developed from a healthcare payer perspective on a lifetime horizon. Ten strategies were compared by combining two different tests for LTBI, i.e. IGRA and tuberculin skin test (TST), and five different preventive treatments, i.e. 9-month isoniazid (9H), 3-month isoniazid and rifapentine (3HP) by directly observed therapy, 3HP by self-administered therapy, 3-month isoniazid and rifampin (3RH), and 4-month rifampin (4R). The main outcomes were costs, quality-adjusted life-years (QALYs), life expectancy life-years (LYs), incremental cost-effectiveness ratios, drug-sensitive tuberculosis (DS-TB) cases, and TB-related deaths. For both bacillus Calmette-Guérin (BCG)-vaccinated and non-BCG-vaccinated individuals, IGRA with 4R was the most cost-effective and TST with 3RH was the least effective. Among schizophrenic individuals in Japan, IGRA with 4R saved US$17.8 million, increased 58,981 QALYs and 935 LYs, and prevented 222 DS-TB cases and 75 TB-related deaths compared with TST with 3RH. In individuals with schizophrenia, IGRA with 4R is recommended for LTBI screening with preventive treatment to reduce costs, morbidity, and mortality from TB.

Cost-effectiveness of Low-complexity Screening Tests in Community-based Case-finding for Tuberculosis.

INTRODUCTION: In high-burden settings, low-complexity screening tests for tuberculosis (TB) could expand the reach of community-based case-finding efforts. The potential costs and cost-effectiveness of approaches incorporating these tests are poorly understood. METHODS: We developed a microsimulation model assessing 3 approaches to community-based case-finding in hypothetical populations (India-, South Africa-, The Philippines-, Uganda-, and Vietnam-like settings) with TB prevalence 4 times that of national estimates: (1) screening with a point-of-care C-reactive protein (CRP) test, (2) screening with a more sensitive "Hypothetical Screening test" (95% sensitive for Xpert Ultra-positive TB, 70% specificity; equipment/labor costs similar to Xpert Ultra, but using a $2 cartridge) followed by sputum Xpert Ultra if positive, or (3) testing all individuals with sputum Xpert Ultra. Costs are expressed in 2023 US dollars and include treatment costs. RESULTS: Universal Xpert Ultra was estimated to cost a mean $4.0 million (95% uncertainty range: $3.5 to $4.6 million) and avert 3200 (2600 to 3900) TB-related disability-adjusted life years (DALYs) per 100 000 people screened ($670 [The Philippines] to $2000 [Vietnam] per DALY averted). CRP was projected to cost $550 (The Philippines) to $1500 (Vietnam) per DALY averted but with 44% fewer DALYs averted. The Hypothetical Screening test showed minimal benefit compared to universal Xpert Ultra, but if specificity were improved to 95% and per-test cost to $4.5 (all-inclusive), this strategy could cost $390 (The Philippines) to $940 (Vietnam) per DALY averted. CONCLUSIONS: Screening tests can meaningfully improve the cost-effectiveness of community-based case-finding for TB but only if they are sensitive, specific, and inexpensive.

Ethambutol and visual assessment in England: current practice and recommendations.

BACKGROUND: Standard treatment for tuberculosis (TB) in children and adults includes an initial two-month course of ethambutol, a drug that in rare cases can cause optic neuropathy and irreversible vision loss. There is a lack of clear guidance on what vision assessments are needed before and during treatment with ethambutol, with the Royal College of Ophthalmologists, National Institute for Health and Care Excellence, British National Formulary and British Thoracic Society offering different guidance. We aimed to assess how vision is routinely tested in patients treated with ethambutol in TB services across England. METHODS: An online survey developed by Public Health England was sent to all TB services in England in 2018 to assess current practice and inform the development of best practice recommendations for visual assessment of patients treated with ethambutol for TB. RESULTS: Sixty-six TB professionals from across England responded, a response rate of 54%. The results showed variations in practice, including when to omit ethambutol from treatment, the timing and frequency of visual assessment, the type of visual assessment, referral processes and management of visual changes. CONCLUSION: This national survey highlights the need for clear guidelines on the testing of vision for patients taking ethambutol at recommended doses, before and during treatment. We suggest a pragmatic approach to visual assessment to reduce variation in practice, proposing a stepwise pathway for patients on standard TB treatment for local adaptation.

Assessing tuberculosis in the skeleton with the use of decision tree analysis.

Diagnosis of specific infectious diseases in the skeleton is often difficult and relies on expert opinion. Statistics is not often used as a tool to assist in such diagnoses, and therefore this study aimed at employing data mining and machine learning in the form of decision tree analysis to aid in recognizing tuberculosis (TB) in skeletal remains and find patterns of skeletal involvement. The sample included 387 modern South African individuals (n = 207 individuals known to have died of TB and n = 180 as a control group) which were scored for the presence or absence of 21 skeletal lesions documented to be associated with TB. A pruned decision tree classification analysis was done to detect significant patterns and associations between variables which produced a model with a moderate classification rate based on four of the variables. As expected, vertebral changes were selected first, followed by rib, acetabular and lastly cranial changes. As a proof of concept, it was shown that machine learning was able to identify patterns of changes in TB skeletons versus a control group. However, further investigation into the use of machine learning in assessing skeletal changes associated with specific diseases is needed.

A retrospective cohort analysis of treatment outcomes of patients with tuberculosis who used substances in Tel Aviv, Israel.

AIMS: To outline the demographic, clinical, laboratory characteristics, and treatment outcomes of tuberculosis (TB) patients who used substances. METHODS: This retrospective cohort study compared 50 TB patients who used substances with a matched random sample of 100 TB patients who did not use substances between 2007 and 2017. Treatment failure was defined as a sputum smear or culture that tested positive after 5 months of treatment, loss to follow-up, unevaluated patients, or death. RESULTS: TB patients who used substances were typically younger, experienced homelessness, smokers, and had fewer chronic diseases than those who did not use substances. They also were hospitalized for longer periods, their treatment durations were longer, had higher rates of multidrug resistant strains, increased rates of treatment failure, and higher mortality. Individuals whose treatment failed predominantly originated from the former Soviet Union, experienced homelessness, and had chronic diseases compared with those whose treatment was successful. In the multivariate analysis, homelessness [odds ratios (OR) = 6.7], chronic diseases (OR = 12.4), and substance use (OR = 4.0) were predictors of treatment failures. CONCLUSIONS: TB patients who used substances were more likely to have treatment failure. Targeted interventions, including early diagnosis and enhanced support during treatment, are essential to achieve treatment success in this vulnerable population, in addition to TB-alcohol/drug collaborative activities.

Label-Free Citrate-Stabilized Silver Nanoparticles-Based, Highly Sensitive, Cost-Effective, and Rapid Visual Method for the Differential Detection of Mycobacterium tuberculosis and Mycobacterium bovis.

Tuberculosis poses a global health challenge, and it demands improved diagnostics and therapies. Distinguishing between Mycobacterium tuberculosis (M. tb) and Mycobacterium bovis (M. bovis) infections holds critical "One Health" significance due to the zoonotic nature of these infections and inherent resistance of M. bovis to pyrazinamide, a key part of the directly observed treatment, short-course (DOTS) regimen. Furthermore, most of the currently used molecular detection methods fail to distinguish between the two species. To address this, our study presents an innovative molecular-biosensing strategy. We developed a label-free citrate-stabilized silver nanoparticle aggregation assay that offers sensitive, cost-effective, and swift detection. For molecular detection, genomic markers unique to M. tb and M. bovis were targeted using species-specific primers. In addition to amplifying species-specific regions, these primers also aid the detection of characteristic deletions in each of the mycobacterial species. Post polymerase chain reaction (PCR), we compared two highly sensitive visual detection methods with respect to the traditional agarose gel electrophoresis. The paramagnetic bead-based bridging flocculation assay successfully discriminates M. tb from M. bovis with a sensitivity of ∼40 bacilli. The second strategy exploits citrate-stabilized silver nanoparticles, which aggregate in the absence of amplified dsDNA on the addition of sodium chloride (NaCl). This technique enables the precise, sensitive, and differential detection of as few as ∼4 bacilli. Our study hence advances tuberculosis detection, overcoming the challenges of M. tb and M. bovis differentiation and offering a quicker alternative to time-consuming methods.

Cost-effectiveness analysis of adding tuberculosis household contact investigation on passive case-finding strategy in Southwestern Uganda.

INTRODUCTION: The standard passive case-finding strategy implemented by most developing countries is inadequate to detect new cases of Tuberculosis. A household contact investigation is an alternative approach. However, there is limited cost-effectiveness data to support planning and implementation in low and middle-income countries. The study aimed to evaluate the cost-effectiveness of adding household contact investigation (HCI) to the passive case-finding (PCF) strategy in the Tuberculosis control program in Southwestern Uganda. METHODS: We conducted an economic evaluation using a retrospective study approach and bottom-up costing (ingredients) techniques. It was a synthesis-based evaluation of existing data extracted from the District Health Information System (DHIS 2), TB registers, and a primary cost survey. The study compared two methods of Tuberculosis (TB) case finding (PCF and HCI) strategies. Regarding PCF, patients either self-reported their signs and symptoms or were prompted by healthcare workers. At the same time, HCI was done by home visiting and screening contacts of TB patients. Patients and household contacts presumed to have Tuberculosis were requested to produce samples for analysis. We applied a static decision-analytic modeling framework to examine both strategies' costs and effectiveness. The study relied on cost and probability estimates from National Tuberculosis (TB) program data, activity costs, and published literature. It was performed from the societal and provider perspectives over 1.5 years across 12 facilities in Ntungamo, Sheema, and Rwampara Districts. The primary effectiveness measure was the number of TB cases detected (yield) and the number needed to screen (NNS). The TB yield was calculated from the number of patients screened during the period under study. The incremental cost-effectiveness ratio (ICER) was expressed as cost in 2021 US$ per additional TB case detected. We did not apply a discount rate because of the short analytic time horizon. RESULTS: The unit costs of detecting a Tuberculosis case were US$ (United States dollar) 204.22 for PCF and US$ 315.07 for HCI. Patient and caregiver costs are five times more in PCF than in HCI [US$26.37 Vs. US$ 5.42]. The ICER was US$ 3,596.94 per additional TB case detected. The TB screening yields were 0.52% (1496/289140) for passive case finding and 5.8% (197/3414) for household contact investigation. Household contact investigation yield among children 0-14 Vs. 15+ years [6.2% Vs.5.4%] P = 0.04. The Yield among People living with HIV (PLHIV) Vs. HIV-negative [15.8% Vs.5.3%] P = 0.03 in HHCI. The PCF yield in men Vs. Women [1.12% Vs.0.28%] P<0.01. The NNS in PCF was 193 [95% CI: 186-294] and 17 [95% CI: 14-22] in HCI. CONCLUSION: Our baseline assumptions and the specific implementations of adding HCI to existing PCF programs in the context of rural African settings prove to be not cost-effective, rather than HCI as a strategy. HCI effectively identifies children and PLHIV with TB and should be prioritized. Meanwhile, the Passive case-finding strategy effectively finds men with TB and costs lower than household contact investigation.

Cost of inaction: a framework to estimate the economic cost of missing a patient with tuberculosis in the Indian context.

OBJECTIVES: To estimate the economic impact of failure to find and treat tuberculosis disease and prevent tuberculosis infection from progressing to active disease. DESIGN: Estimating the economic cost of not finding and treating a patient suffering from tuberculosis. SETTING: Estimation methodology is developed in the Indian context, as informed by local costs and reported tuberculosis epidemiology. PARTICIPANTS: No individual participants were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure is the total cost of patients with drug-susceptible and drug-resistant tuberculosis who are and are not found and treated by tuberculosis programmes, including costs for medications, lost productivity, healthcare services and furthered transmission. We calculate the economic burdens by varying the number of individuals a person sick with tuberculosis infects (10 or 15 people) and the risk of progression to tuberculosis disease if infected (5 or 8%). The secondary outcome measure is the amount saved by finding a patient early or who would not have otherwise been found. All costs are presented in US dollars (exchange rate: 72 Indian rupees/1 US$). RESULTS: By finding and treating a patient early before furthered transmission occurs-or stopping progression of tuberculosis infection to tuberculosis disease with preventive therapy-the Indian health system can save US$5502 to US$15 825 and US$5846 to US$25 575, for each individual with drug-susceptible and drug-resistant tuberculosis, respectively, across scenarios. CONCLUSIONS: These estimates provide crude, lower bounds for the potential costs of not appropriately diagnosing and treating a single patient with active tuberculosis in a timely manner, or preventing a patient with tuberculosis infection from progressing to active disease. The actual financial burden on society is far higher than estimated using this simple, short-term cost-effective analyses. Our results highlight the limitations of tuberculosis costing models to date, and demonstrate the importance of accounting for airborne transmission of tuberculosis.

A costing framework to compare tuberculosis infection tests.

OBJECTIVE: To develop a framework to estimate the practical costs incurred from, and programmatic impact related to, tuberculosis (TB) infection testing-tuberculin skin tests (TST) versus interferon gamma release assay (IGRA)-in a densely populated high-burden TB area. METHODS: We developed a seven-step framework that can be tailored to individual TB programmes seeking to compare TB infection (TBI) diagnostics to inform decision-making. We present methodology to estimate (1) the prevalence of TBI, (2) true and false positives and negatives for each test, (3) the cost of test administration, (4) the cost of false negatives, (5) the cost of treating all that test positive, (6) the per-test cost incurred due to treatment and misdiagnosis and (7) the threshold at which laboratory infrastructure investments for IGRA are outweighed by system-wide savings incurred due to IGRA utilisation. We then applied this framework in a densely populated, peri-urban district in Lima, Peru with high rates of Bacillus Calmette-Guérin (BCG) vaccination. FINDINGS: The lower sensitivity of TST compared with IGRA is a major cost driver, leading to health system and societal costs due to misdiagnosis. Additionally, patient and staff productivity costs were greater for TST because it requires two patient visits compared with only one for IGRA testing. When the framework was applied to the Lima setting, we estimate that IGRA-associated benefits outweigh infrastructural costs after performing 672 tests. CONCLUSIONS: Given global shortages of TST and concerns about costs of IGRA testing and laboratory capacity building, this costing framework can provide public health officials and TB programmes guidance for decision-making about TBI testing locally. This framework was designed to be adaptable for use in different settings with available data. Diagnostics that increase accuracy or mitigate time to treatment should be thought of as an investment instead of an expenditure.

Financing for tuberculosis prevention, diagnosis and treatment services in the Western Pacific Region in 2005-2020.

Objective: This paper provides an overview of financing for tuberculosis (TB) prevention, diagnostic and treatment services in the World Health Organization (WHO) Western Pacific Region during 2005-2020. Methods: This analysis uses the WHO global TB finance database to describe TB funding during 2005-2020 in 18 low- and middle-income countries (LMICs) in the Western Pacific Region, with additional country-level data and analysis for seven priority countries: Cambodia, China, the Lao People's Democratic Republic, Mongolia, Papua New Guinea, the Philippines and Viet Nam. Results: Funding for the provision of TB prevention, diagnostic and treatment services in the 18 LMICs tripled fromUS$ 358 million in 2005 to US$ 1061 million in 2020, driven largely by increases in domestic funding, which rose from US$ 325 million to US$ 939 million over the same period. In the seven priority countries, TB investments also tripled, from US$ 340 million in 2005 to US$ 1020 million in 2020. China alone accounted for much of this growth, increasing its financing for TB programmes and services fivefold, from US$ 160 million to US$ 784 million. The latest country forecasts estimate that US$ 3.8 billion will be required to fight TB in the seven priority countries by 2025, which means that unless additional funding is mobilized, the funding gap will increase from US$ 326 million in 2020 to US$ 830 million by 2025. Discussion: Increases in domestic funding over the past 15 years reflect a firm political commitment to ending TB. However, current funding levels do not meet the required needs to finance the national TB strategic plans in the priority countries. An urgent step-up of public financing efforts is required to reduce the burden of TB in the Western Pacific Region.

Cost-effectiveness of community-based household tuberculosis contact management for children in Cameroon and Uganda: a modelling analysis of a cluster-randomised trial.

BACKGROUND: WHO recommends household contact management (HCM) including contact screening and tuberculosis-preventive treatment (TPT) for eligible children. The CONTACT trial found increased TPT initiation and completion rates when community health workers were used for HCM in Cameroon and Uganda. METHODS: We did a cost-utility analysis of the CONTACT trial using a health-system perspective to estimate the health impact, health-system costs, and cost-effectiveness of community-based versus facility-based HCM models of care. A decision-analytical modelling approach was used to evaluate the cost-effectiveness of the intervention compared with the standard of care using trial data on cascade of care, intervention effects, and resource use. Health outcomes were based on modelled progression to tuberculosis, mortality, and discounted disability-adjusted life-years (DALYs) averted. Health-care resource use, outcomes, costs (2021 US$), and cost-effectiveness are presented. FINDINGS: For every 1000 index patients diagnosed with tuberculosis, the intervention increased the number of TPT courses by 1110 (95% uncertainty interval 894 to 1227) in Cameroon and by 1078 (796 to 1220) in Uganda compared with the control model. The intervention prevented 15 (-3 to 49) tuberculosis deaths in Cameroon and 10 (-20 to 33) in Uganda. The incremental cost-effectiveness ratio was $620 per DALY averted in Cameroon and $970 per DALY averted in Uganda. INTERPRETATION: Community-based HCM approaches can substantially reduce child tuberculosis deaths and in our case would be considered cost-effective at willingness-to-pay thresholds of $1000 per DALY averted. Their impact and cost-effectiveness are likely to be greatest where baseline HCM coverage is lowest. FUNDING: Unitaid and UK Medical Research Council.

Development and validation of assessment instrument for the perception and attitude toward tuberculosis among the general population in Indonesia: a Rasch analysis of psychometric properties.

Introduction: Tuberculosis (TB)-related knowledge is an important evaluation metric for health education interventions. Factor analysis is limited when used on ordinal scales and does not provide in-depth item function examinations, whereas Rasch analysis addresses these limitations and offers potential advantages such as generalizability, testing of unidimensionality, producing an ordered set of items, and identifying poorly functioning items. Therefore, this research aims to develop a reliable and valid measure of perception and attitude toward TB (PATT) for public application use Rasch Analysis. Methods: A questionnaire-based survey was conducted on the Indonesian general population using the Google Form platform. Rasch analysis was then employed to examine the psychometric properties and develop the final items of PATT. Results: Experts from across the TB community participated in the PATT development, producing an initial scale of 16 items. Up to 1,616 participants completed the PATT questionnaire, where 74.8% were female, and 5% had a TB history. The final unidimensional 16-item scale has an item reliability of 1.00 for the two components (perception and attitude), a person reliability index of 0.87 and 0.60, as well as a Cronbach's test reliability of 0.88 and 0.88 for perception and attitude, respectively. Conclusion: The PATT is a unidimensional scale with good construct validity and internal consistency. It has the potential to be useful for the assessment of TB perception and attitude in research and clinical practice.

Assessment and validation of enrichment and target capture approaches to improve Mycobacterium tuberculosis WGS from direct patient samples.

Within-host Mycobacterium tuberculosis (Mtb) diversity may detect antibiotic resistance or predict tuberculosis treatment failure and is best captured through sequencing directly from sputum. Here, we compared three sample pre-processing steps for DNA decontamination and studied the yield of a new target enrichment protocol for optimal whole-genome sequencing (WGS) from direct patient samples. Mtb-positive NALC-NaOH-treated patient sputum sediments were pooled, and heat inactivated, split in replicates, and treated by either a wash, DNase I, or benzonase digestion. Levels of contaminating host DNA and target Mtb DNA were assessed by quantitative PCR (qPCR), followed by WGS with and without custom dsDNA target enrichment. The pre-treatment sample has a high host-to-target ratio of DNA (6,168 ± 1,638 host copies/ng to 212.3 ± 59.4 Mtb copies/ng) that significantly decreased with all three treatments. Benzonase treatment resulted in the highest enrichment of Mtb DNA at 100-fold compared with control (3,422 ± 2,162 host copies/ng to 11,721 ± 7,096 Mtb copies/ng). The custom dsDNA probe panel successfully enriched libraries from as little as 0.45 pg of Mtb DNA (100 genome copies). Applied to direct sputum the dsDNA target enrichment panel increased the percent of sequencing reads mapping to the Mtb target for all three pre-processing methods. Comparing the results of the benzonase sample sequenced both with and without enrichment, the percent of sequencing reads mapping to the Mtb increased to 90.95% from 1.18%. We demonstrate a low limit of detection for a new custom dsDNA Mtb target enrichment panel that has a favorable cost profile. The results also demonstrate that pre-processing to remove contaminating extracellular DNA prior to cell lysis and DNA extraction improves the host-to-Mtb DNA ratio but is not adequate to support average coverage WGS without target capture.

Cost-effectiveness analysis of interventions to improve diagnosis and preventive therapy for paediatric tuberculosis in 9 sub-Saharan African countries: A modelling study.

BACKGROUND: Over 1 million children aged 0 to 14 years were estimated to develop tuberculosis in 2021, resulting in over 200,000 deaths. Practical interventions are urgently needed to improve diagnosis and antituberculosis treatment (ATT) initiation in children aged 0 to 14 years and to increase coverage of tuberculosis preventive therapy (TPT) in children at high risk of developing tuberculosis disease. The multicountry CaP-TB intervention scaled up facility-based intensified case finding and strengthened household contact management and TPT provision at HIV clinics. To add to the limited health-economic evidence on interventions to improve ATT and TPT in children, we evaluated the cost-effectiveness of the CaP-TB intervention. METHODS AND FINDINGS: We analysed clinic-level pre/post data to quantify the impact of the CaP-TB intervention on ATT and TPT initiation across 9 sub-Saharan African countries. Data on tuberculosis diagnosis and ATT/TPT initiation counts with corresponding follow-up time were available for 146 sites across the 9 countries prior to and post project implementation, stratified by 0 to 4 and 5 to 14 year age-groups. Preintervention data were retrospectively collected from facility registers for a 12-month period, and intervention data were prospectively collected from December 2018 to June 2021 using project-specific forms. Bayesian generalised linear mixed-effects models were used to estimate country-level rate ratios for tuberculosis diagnosis and ATT/TPT initiation. We analysed project expenditure and cascade data to determine unit costs of intervention components and used mathematical modelling to project health impact, health system costs, and cost-effectiveness. Overall, ATT and TPT initiation increased, with country-level incidence rate ratios varying between 0.8 (95% uncertainty interval [UI], 0.7 to 1.0) and 2.9 (95% UI, 2.3 to 3.6) for ATT and between 1.6 (95% UI, 1.5 to 1.8) and 9.8 (95% UI, 8.1 to 11.8) for TPT. We projected that for every 100 children starting either ATT or TPT at baseline, the intervention package translated to between 1 (95% UI, -1 to 3) and 38 (95% UI, 24 to 58) deaths averted, with a median incremental cost-effectiveness ratio (ICER) of US$634 per disability-adjusted life year (DALY) averted. ICERs ranged between US$135/DALY averted in Democratic of the Congo and US$6,804/DALY averted in Cameroon. The main limitation of our study is that the impact is based on pre/post comparisons, which could be confounded. CONCLUSIONS: In most countries, the CaP-TB intervention package improved tuberculosis treatment and prevention services for children aged under 15 years, but large variation in estimated impact and ICERs highlights the importance of local context. TRIAL REGISTRATION: This evaluation is part of the TIPPI study, registered with ClinicalTrials.gov (NCT03948698).

Alternativas de procesos para la búsqueda de casos de tuberculosis bajo condiciones económicas limitadas. Cuba 2022-2025 / Process Alternatives for the Tuberculosis Case Finding under Limited Economic Conditions. Cuba 2022-2025

Ejecutar procesos efectivos de búsqueda de casos de tuberculosis es crucial para acele-rar el paso hacia su eliminación. El empeoramiento de las condiciones económicas mun-diales y nacionales no nos permite aplicar extensivamente las tecnologías rápidas mo-leculares idóneas de diagnóstico. Consideramos sensato entonces aplicar algoritmos alternativos que satisfagan las necesidades nacionales presentes hasta que las condi-ciones permitan la cobertura completa de las tecnologías moleculares recomendadas. Sugerimos introducir la radiografía digital para todos los algoritmos, utilizar mejor la microscopía de fluorescencia LED y la óptica convencional ya probadas. En conclusión, es preciso que este enfoque de trabajo, que procura optimizar la efectividad y eficiencia del programa, se introduzca en la práctica cotidiana hasta que lo idóneo sea permisible

Executing effective tuberculosis case-finding processes is crucial to accelerate the path towards elimination of the disease. The worsening of global and national economic conditions do not allow us to extensively apply rapid molecular diagnostic technolo-gies. We consider it sensible and necessary to apply alternative algorithms that meet the current national needs, until conditions allow full coverage of the recommended molecular technologies. We suggest introducing digital X-rays for all algorithms, bet-ter use of LED fluorescence microscopy and conventional optics already appropriate-ly tested. In conclusion, it is necessary that this approach that seeks to optimize the effectiveness and efficiency of the Cuban program be introduced into daily practice until the ideal is permissible