Is convenience really king? Comparative evaluation of catastrophic costs due to tuberculosis in the public and private healthcare sectors of Viet Nam: a longitudinal patient cost study.

BACKGROUND: In Viet Nam, tuberculosis (TB) represents a devastating life-event with an exorbitant price tag, partly due to lost income from daily directly observed therapy in public sector care. Thus, persons with TB may seek care in the private sector for its flexibility, convenience, and privacy. Our study aimed to measure income changes, costs and catastrophic cost incurrence among TB-affected households in the public and private sector. METHODS: Between October 2020 and March 2022, we conducted 110 longitudinal patient cost interviews, among 50 patients privately treated for TB and 60 TB patients treated by the National TB Program (NTP) in Ha Noi, Hai Phong and Ho Chi Minh City, Viet Nam. Using a local adaptation of the WHO TB patient cost survey tool, participants were interviewed during the intensive phase, continuation phase and post-treatment. We compared income levels, direct and indirect treatment costs, catastrophic costs using Wilcoxon rank-sum and chi-squared tests and associated risk factors between the two cohorts using multivariate regression. RESULTS: The pre-treatment median monthly household income was significantly higher in the private sector versus NTP cohort (USD 868 vs USD 578; P = 0.010). However, private sector treatment was also significantly costlier (USD 2075 vs USD 1313; P = 0.005), driven by direct medical costs which were 4.6 times higher than costs reported by NTP participants (USD 754 vs USD 164; P < 0.001). This resulted in no significant difference in catastrophic costs between the two cohorts (Private: 55% vs NTP: 52%; P = 0.675). Factors associated with catastrophic cost included being a single-person household [adjusted odds ratio (aOR = 13.71; 95% confidence interval (CI): 1.36-138.14; P = 0.026], unemployment during treatment (aOR = 10.86; 95% CI: 2.64-44.60; P < 0.001) and experiencing TB-related stigma (aOR = 37.90; 95% CI: 1.72-831.73; P = 0.021). CONCLUSIONS: Persons with TB in Viet Nam face similarly high risk of catastrophic costs whether treated in the public or private sector. Patient costs could be reduced through expanded insurance reimbursement to minimize direct medical costs in the private sector, use of remote monitoring and multi-week/month dosing strategies to avert economic costs in the public sector and greater access to social protection mechanism in general.

Active case-finding of tuberculosis compared with symptom-driven standard of care: a modelling analysis.

BACKGROUND: In settings with large case detection gaps, active case-finding (ACF) may play a critical role in the uberculosis (TB) response. However, ACF is resource intensive, and its effectiveness depends on whether people detected with TB through ACF might otherwise spontaneously resolve or be diagnosed through routine care. We analysed the potential effectiveness of ACF for TB relative to the counterfactual scenario of routine care alone. METHODS: We constructed a Markov simulation model of TB natural history, diagnosis, symptoms, ACF and treatment, using a hypothetical reference setting using data from South East Asian countries. We calibrated the model to empirical data using Bayesian methods, and simulated potential 5-year outcomes with an 'aspirational' ACF intervention (reflecting maximum possible effectiveness) compared with the standard-of-care outcomes. RESULTS: Under the standard of care, 51% (95% credible interval, CrI: 31%, 75%) of people with prevalent TB at baseline were estimated to be diagnosed and linked to care over 5 years. With aspirational ACF, this increased to 88% (95% CrI: 84%, 94%). Most of this difference represented people who were diagnosed and treated through ACF but experienced spontaneous resolution under standard-of-care. Aspirational ACF was projected to reduce the average duration of TB disease by 12 months (95% CrI: 6%, 18%) and TB-associated disability-adjusted life-years by 71% (95% CrI: 67%, 76%). CONCLUSION: These data illustrate the importance of considering outcomes in a counterfactual standard of care scenario, as well as trade-offs between overdiagnosis and averted morbidity through earlier diagnosis-not just for TB, but for any disease in which population-based screening is recommended.

Implementation of large-scale pooled testing to increase rapid molecular diagnostic test coverage for tuberculosis: a retrospective evaluation.

In 2021, only 6.4 million of the 10.6 million people with tuberculosis (TB) were diagnosed and treated for the disease. Although the World Health Organization recommends initial diagnostic testing using a rapid sensitive molecular assay, only 38% of people diagnosed with TB benefited from these, due to barriers including the high cost of available assays. Pooled testing has been used as an approach to increase testing efficiency in many resource-constrained situations, such as the COVID-19 pandemic, but it has not yet been widely adopted for TB diagnostic testing. Here we report a retrospective analysis of routine pooled testing of 10,117 sputum specimens using the Xpert MTB/RIF and Xpert MTB/RIF Ultra assays that was performed from July 2020 to February 2022. Pooled testing saved 48% of assays and enabled rapid molecular testing for 4156 additional people as compared to individual testing, with 6.6% of specimens positive for TB. From an in silico analysis, the positive percent agreement of pooled testing in pools of 3 as compared with individual testing for the Xpert MTB/RIF Ultra assay was estimated as 99.4% (95% CI, 96.6% to 100%). These results support the scale-up of pooled testing for efficient TB diagnosis.

Comparing Catastrophic Costs: Active vs. Passive Tuberculosis Case Finding in Urban Vietnam.

Active case finding (ACF) is a strategy that aims to identify people with tuberculosis (TB) earlier in their disease. This outreach approach may lead to a reduction in catastrophic cost incurrence (costs exceeding 20% of annual household income), a main target of WHO's End TB Strategy. Our study assessed the socio-economic impact of ACF by comparing patient costs in actively and passively detected people with TB. Longitudinal patient cost surveys were prospectively fielded for people with drug-sensitive pulmonary TB, with 105 detected through ACF and 107 passively detected. Data were collected in four Vietnamese cities between October 2020 and March 2022. ACF reduced pre-treatment (USD 10 vs. 101, p < 0.001) and treatment costs (USD 888 vs. 1213, p < 0.001) in TB-affected individuals. Furthermore, it reduced the occurrence of job loss (15.2% vs. 35.5%, p = 0.001) and use of coping strategies (28.6% vs. 45.7%, p = 0.004). However, catastrophic cost incurrence was high at 52.8% and did not differ between cohorts. ACF did not significantly decrease indirect costs, the largest contributor to catastrophic costs. ACF reduces costs but cannot sufficiently reduce the risk of catastrophic costs. As income loss is the largest driver of costs during TB treatment, social protection schemes need to be expanded.

What matters most? A qualitative study exploring priorities for supportive interventions for people with tuberculosis in urban Viet Nam.

INTRODUCTION: The health and economic burden of tuberculosis (TB) in urban Viet Nam is high. Social protection and support interventions can improve treatment outcomes and reduce costs. However, evidence regarding optimal strategies in this context is lacking. This study aimed to increase understanding of what people with TB and healthcare providers (HCPs) perceive as important to improve TB treatment outcomes and reduce costs. METHODS: We conducted qualitative focus group discussions (seven groups, n=30) and key informant interviews (n=4) with people with drug-susceptible and multidrug-resistant TB and HCPs in Ha Noi and Ho Chi Minh City. Topic guides covered perspectives on and prioritisation of different forms of social protection and support. Data were analysed using reflexive thematic analysis and interpreted using a Framework for Transformative Social Protection. RESULTS: We identified three themes and seven subthemes. The first theme, 'Existing financial safety nets are essential, but could go further to support people affected by TB', highlights that support to meet the medical costs of TB treatment and flexible cash transfers are a priority for people with TB and HCPs. The second, 'It is important to promote "physical and spiritual health" during TB treatment', demonstrates that extended psychosocial and nutritional support would encourage people with TB during their treatment. The third, 'Accessibility and acceptability are critical in designing social support interventions for people with TB', shows the importance of ensuring that support is accessible and proportional to the needs of people with TB and their families. CONCLUSIONS: Accessible interventions that incorporate financial risk protection, nutritional and psychosocial support matter most to people with TB and HCPs in urban Viet Nam to improve their treatment outcomes and reduce catastrophic costs. This study can inform the design of stronger person-centred interventions to advance progress towards the goals of the WHO's End TB Strategy.

Enhancing the reliability and accuracy of AI-enabled diagnosis via complementarity-driven deferral to clinicians.

Predictive artificial intelligence (AI) systems based on deep learning have been shown to achieve expert-level identification of diseases in multiple medical imaging settings, but can make errors in cases accurately diagnosed by clinicians and vice versa. We developed Complementarity-Driven Deferral to Clinical Workflow (CoDoC), a system that can learn to decide between the opinion of a predictive AI model and a clinical workflow. CoDoC enhances accuracy relative to clinician-only or AI-only baselines in clinical workflows that screen for breast cancer or tuberculosis (TB). For breast cancer screening, compared to double reading with arbitration in a screening program in the UK, CoDoC reduced false positives by 25% at the same false-negative rate, while achieving a 66% reduction in clinician workload. For TB triaging, compared to standalone AI and clinical workflows, CoDoC achieved a 5-15% reduction in false positives at the same false-negative rate for three of five commercially available predictive AI systems. To facilitate the deployment of CoDoC in novel futuristic clinical settings, we present results showing that CoDoC's performance gains are sustained across several axes of variation (imaging modality, clinical setting and predictive AI system) and discuss the limitations of our evaluation and where further validation would be needed. We provide an open-source implementation to encourage further research and application.

Pooling sputum testing to diagnose tuberculosis using xpert MTB/RIF and xpert ultra: a cost-effectiveness analysis.

BACKGROUND: The World Health Organization (WHO) recommends the diagnosis of tuberculosis (TB) using molecular tests, such as Xpert MTB/RIF (MTB/RIF) or Xpert Ultra (Ultra). These tests are expensive and resource-consuming, and cost-effective approaches are needed for greater coverage. METHODS: We evaluated the cost-effectiveness of pooling sputum samples for TB testing by using a fixed amount of 1,000 MTB/RIF or Ultra cartridges. We used the number of people with TB detected as the indicator for cost-effectiveness. Cost-minimization analysis was conducted from the healthcare system perspective and included the costs to the healthcare system using pooled and individual testing. RESULTS: There was no significant difference in the overall performance of the pooled testing using MTB/RIF or Ultra (sensitivity, 93.9% vs. 97.6%, specificity 98% vs. 97%, p-value > 0.1 for both). The mean unit cost across all studies to test one person was 34.10 international dollars for the individual testing and 21.95 international dollars for the pooled testing, resulting in a savings of 12.15 international dollars per test performed (35.6% decrease). The mean unit cost per bacteriologically confirmed TB case was 249.64 international dollars for the individual testing and 162.44 international dollars for the pooled testing (34.9% decrease). Cost-minimization analysis indicates savings are directly associated with the proportion of samples that are positive. If the TB prevalence is ≥ 30%, pooled testing is not cost-effective. CONCLUSION: Pooled sputum testing can be a cost-effective strategy for diagnosis of TB, resulting in significant resource savings. This approach could increase testing capacity and affordability in resource-limited settings and support increased testing towards achievement of WHO End TB strategy.

Economic evaluation of a community health worker model for tuberculosis care in Ho Chi Minh City, Viet Nam: a mixed-methods Social Return on Investment Analysis.

BACKGROUND: There is extensive evidence for the cost-effectiveness of programmatic and additional tuberculosis (TB) interventions, but no studies have employed the social return on investment (SROI) methodology. We conducted a SROI analysis to measure the benefits of a community health worker (CHW) model for active TB case finding and patient-centered care. METHODS: This mixed-method study took place alongside a TB intervention implemented in Ho Chi Minh City, Viet Nam, between October-2017 - September-2019. The valuation encompassed beneficiary, health system and societal perspectives over a 5-year time-horizon. We conducted a rapid literature review, two focus group discussions and 14 in-depth interviews to identify and validate pertinent stakeholders and material value drivers. We compiled quantitative data from the TB program's and the intervention's surveillance systems, ecological databases, scientific publications, project accounts and 11 beneficiary surveys. We mapped, quantified and monetized value drivers to derive a crude financial benefit, which was adjusted for four counterfactuals. We calculated a SROI based on the net present value (NPV) of benefits and investments using a discounted cash flow model with a discount rate of 3.5%. A scenario analysis assessed SROI at varying discount rates of 0-10%. RESULTS: The mathematical model yielded NPVs of US$235,511 in investments and US$8,497,183 in benefits. This suggested a return of US$36.08 for each dollar invested, ranging from US$31.66-US39.00 for varying discount rate scenarios. CONCLUSIONS: The evaluated CHW-based TB intervention generated substantial individual and societal benefits. The SROI methodology may be an alternative for the economic evaluation of healthcare interventions.

Sensitivity and specificity of CRP and symptom screening as tuberculosis screening tools among HIV-positive and negative outpatients at a primary healthcare facility in Lusaka, Zambia: a prospective cross-sectional study.

OBJECTIVES: To evaluate the performance of point-of-care C-reactive protein (CRP) as a screening tool for tuberculosis (TB) using a threshold of 10 mg/L in both people living with HIV (PLHIV) and HIV-negative individuals and compare it to symptom screening using a composite reference for bacteriological confirmation of TB. METHODS: Prospective cross-sectional study. SETTING: A primary healthcare facility in Lusaka, Zambia. PARTICIPANTS: Consecutive adults (≥18 years) presenting for routine outpatient healthcare were enrolled. Of the 816 individuals approached to participate in the study, 804 eligible consenting adults were enrolled into the study, of which 783 were included in the analysis. PRIMARY OUTCOME MEASURES: Sensitivity, specificity, positive predictive value and negative predictive value (NPV) of CRP and symptom screening. RESULTS: Overall, sensitivity of WHO-recommended four-symptom screen (W4SS) and CRP were 87.2% (80.0-92.5) and 86.6% (79.6-91.8) while specificity was 30.3% (26.7-34.1) and 34.8% (31.2-38.6), respectively. Among PLHIV, sensitivity of W4SS and CRP was 92.2% (81.1-97.8) and 94.8% (85.6-98.9) while specificity was 37.0% (31.3-43.0) and 27.5% (22.4-33.1), respectively. Among those with CD4≥350, the NPV for CRP was 100% (92.9-100). In the HIV negative, sensitivity of W4SS and CRP was 83.8% (73.4-91.3) and 80.3% (69.5-88.5) while specificity was 25.4% (20.9-30.2) and 40.5% (35.3-45.6), respectively. Parallel use of CRP and W4SS yielded a sensitivity and NPV of 100% (93.8-100) and 100% (91.6-100) among PLHIV and 93.3% (85.1-97.8) and 90.0% (78.2-96.7) among the HIV negatives, respectively. CONCLUSION: Sensitivity and specificity of CRP were similar to symptom screening in HIV-positive outpatients. Independent use of CRP offered limited additional benefit in the HIV negative. CRP can independently accurately rule out TB in PLHIV with CD4≥350. Parallel use of CRP and W4SS improves sensitivity irrespective of HIV status and can accurately rule out TB in PLHIV, irrespective of CD4 count.

Results of community-based TB and HIV screening among transgender women and male sex workers in Pakistan.

In Pakistan and globally, a large proportion of people with TB who are not receiving treatment are key populations with poor access to diagnosis and care. Transgender women and male sex workers (MSW) are heavily stigmatized and marginalized groups. While HIV rates are well documented among these key populations, little such data exists for TB. We engaged local organizations working with transgender women and MSW communities in Karachi and five urban cities in Sindh Province. People from the communities served as screening facilitators and treatment supporters. Verbal screening was followed by testing with Xpert MTB/RIF and HIV testing was offered. People with TB were supported through treatment. We screened 18,272 transgender women and 24,253 MSW. 8,921 (21.0%) individuals had presumptive TB and 7,472 (83.8%) provided sputum samples. We detected 438 (5.9%) people with positive results including 140 transgender women and 298 MSW. Including people diagnosed clinically, 625 people with TB were identified and 98.1% initiated treatment. Overall, 1.5% of people screened had TB, 1.7% among MSW and 1.1% among transgender women. Of 1,508 people tested for HIV, 243 had HIV infection (HIV+). The rates of TB among HIV+ transgender women (8.8%) were slightly lower than among MSW (10.3%). Previously, few attempts have been made to address TB in transgender women and MSW. Our work shows that these groups carry a significant burden of both TB and HIV in Pakistan and do not regularly access services. Effective interventions should include the engagement of community leaders and peers.

Early user experience and lessons learned using ultra-portable digital X-ray with computer-aided detection (DXR-CAD) products: A qualitative study from the perspective of healthcare providers.

BACKGROUND: Recent technological and radiological advances have renewed interest in using X-rays to screen and triage people with tuberculosis (TB). The miniaturization of digital X-ray (DXR), combined with automatic interpretation using computer-aided detection (CAD) software can extend the reach of DXR screening interventions for TB. This qualitative study assessed early implementers' experiences and lessons learned when using ultra-portable (UP) DXR systems integrated with CAD software to screen and triage TB. METHODS: Semi-structured interviews were conducted with project staff and healthcare workers at six pilot sites. Transcripts were coded and analyzed using a framework approach. The themes that emerged were subsequently organized and presented using the Consolidated Framework for Implementation Research (CFIR). RESULTS: There were 26 interviewees with varying roles: supervisory, clinicians, radiographers, and radiologists. Participants recognized the portability as the main advantage, but criticize that it involves several compromises on throughput, internet dependence, manoeuvrability, and stability, as well as suitability for patients with larger body sizes. Furthermore, compared to using hardware and software from the same supplier and without digital health information systems, complexity increases with interoperability between hardware and software, and between different electronic health information systems. Currently, there is a limited capacity to implement these technologies, especially due to the need for threshold selection, and lack of guidance on radiation protection suitable for UP DXR machines. Finally, the respondents stressed the importance of having protected means of sharing patient medical data, as well as comprehensive support and warranty plans. CONCLUSION: Study findings suggest that UP DXR with CAD was overall well received to decentralize radiological assessment for TB, however, the improved portability involved programmatic compromises. The main barriers to uptake included insufficient capacity and lack of guidance on radiation protection suitable for UP DXR.

Optimising diagnosis and treatment of tuberculosis infection in community and primary care settings in two urban provinces of Viet Nam: a cohort study.

OBJECTIVES: To end tuberculosis (TB), the vast reservoir of 1.7-2.3 billion TB infections (TBIs) must be addressed, but achieving global TB preventive therapy (TPT) targets seems unlikely. This study assessed the feasibility of using interferon-γ release assays (IGRAs) at lower healthcare levels and the comparative performance of 3-month and 9-month daily TPT regimens (3HR/9H). DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This cohort study was implemented in two provinces of Viet Nam from May 2019 to September 2020. Participants included household contacts (HHCs), vulnerable community members and healthcare workers (HCWs) recruited at community-based TB screening events or HHC investigations at primary care centres, who were followed up throughout TPT. PRIMARY AND SECONDARY OUTCOMES: We constructed TBI care cascades describing indeterminate and positivity rates to assess feasibility, and initiation and completion rates to assess performance. We fitted mixed-effects logistic and stratified Cox models to identify factors associated with IGRA positivity and loss to follow-up (LTFU). RESULTS: Among 5837 participants, the indeterminate rate was 0.8%, and 30.7% were IGRA positive. TPT initiation and completion rates were 63.3% (3HR=61.2% vs 9H=63.6%; p=0.147) and 80.6% (3HR=85.7% vs 9H=80.0%; p=0.522), respectively. Being male (adjusted OR=1.51; 95% CI: 1.28 to 1.78; p<0.001), aged 45-59 years (1.30; 1.05 to 1.60; p=0.018) and exhibiting TB-related abnormalities on X-ray (2.23; 1.38 to 3.61; p=0.001) were associated with positive IGRA results. Risk of IGRA positivity was lower in periurban districts (0.55; 0.36 to 0.85; p=0.007), aged <15 years (0.18; 0.13 to 0.26; p<0.001), aged 15-29 years (0.56; 0.42 to 0.75; p<0.001) and HCWs (0.34; 0.24 to 0.48; p<0.001). The 3HR regimen (adjusted HR=3.83; 1.49 to 9.84; p=0.005) and HCWs (1.38; 1.25 to 1.53; p<0.001) showed higher hazards of LTFU. CONCLUSION: Providing IGRAs at lower healthcare levels is feasible and along with shorter regimens may expand access and uptake towards meeting TPT targets, but scale-up may require complementary advocacy and education for beneficiaries and providers.

Pooling of sputum samples to increase tuberculosis diagnostic capacity in Brazil during the COVID-19 pandemic.

OBJECTIVES: We assessed whether combining (pooling) four individual's samples and testing with Xpert Ultra has the same accuracy as testing samples individually as a more efficient testing method. METHODS: We conducted a cross-sectional study of individuals with presumptive tuberculosis attending primary health care or general hospital facilities in Alagoas, Brazil. The sputum samples of four consecutive individuals were pooled and the pool and individual samples were tested with Xpert Ultra. The agreement of the tests was compared using kappa statistics. We estimated the sensitivity and specificity of pooling using the individual test as the reference standard and potential cartridge savings. RESULTS: A total of 396 participants were tested. A total of 95 (24.0%) individual samples were Mycobacterium tuberculosis (MTB)-positive, 300 (75.8%) "MTB not detected", including 20 "MTB trace", and one reported an error. A total of 99 pools of four samples were tested, of which 62 (62.6%) had MTB detected and 37 (37.4%) MTB not detected, including six (6.1%) with MTB trace. The agreement between individual and pooled testing was 96.0%. Pooling had a sensitivity of 95.0% (95% confidence interval 86.9-99%), specificity of 97.1% (95% confidence interval 85.1-99.9%), and kappa of 0.913. The method saved 12.4% of cartridge costs. CONCLUSION: The pooled testing of specimens had a high level of agreement with individual testing. The pooling of samples for testing improves the efficiency of testing, potentially enabling the screening and testing of larger numbers of individuals more cost-effectively.

A spatial analysis of TB cases and abnormal X-rays detected through active case-finding in Karachi, Pakistan.

Tuberculosis (TB) is the leading cause of avoidable deaths from an infectious disease globally and a large of number of people who develop TB each year remain undiagnosed. Active case-finding has been recommended by the World Health Organization to bridge the case-detection gap for TB in high burden countries. However, concerns remain regarding their yield and cost-effectiveness. Data from mobile chest X-ray (CXR) supported active case-finding community camps conducted in Karachi, Pakistan from July 2018 to March 2020 was retrospectively analyzed. Frequency analysis was carried out at the camp-level and outcomes of interest for the spatial analyses were mycobacterium TB positivity (MTB+) and X-ray abnormality rates. The Global Moran's I statistic was used to test for spatial autocorrelation for MTB+ and abnormal X-rays within Union Councils (UCs) in Karachi. A total of 1161 (78.1%) camps yielded no MTB+ cases, 246 (16.5%) camps yielded 1 MTB+, 52 (3.5%) camps yielded 2 MTB+ and 27 (1.8%) yielded 3 or more MTB+. A total of 79 (5.3%) camps accounted for 193 (44.0%) of MTB+ cases detected. Statistically significant clustering for MTB positivity (Global Moran's I: 0.09) and abnormal chest X-rays (Global Moran's I: 0.36) rates was identified within UCs in Karachi. Clustering of UCs with high MTB positivity were identified in Karachi West district. Statistically significant spatial variation was identified in yield of bacteriologically positive TB cases and in abnormal CXR through active case-finding in Karachi. Cost-effectiveness of active case-finding programs can be improved by identifying and focusing interventions in hotspots and avoiding locations with no known TB cases reported through routine surveillance.

Improving Tuberculosis Case Detection in Children: Summary of Innovations and Findings From 18 Countries.

Despite a growing focus on the plight of tuberculosis (TB) among children, 56% of the 1.2 million children who develop TB annually are not detected and notified. TB REACH is a platform of the Stop TB Partnership that supports innovative interventions to improve TB case detection and preventative treatment. We present summary findings from 27 TB REACH-supported projects in 18 countries. Interventions were designed around intensified case-finding approaches (facility-based systematic screening and contact investigation), capacity building (including decentralized care delivery and supported decision-making), and improving diagnostic methods (ie, introduction of alternative respiratory specimens and new tools to aid the diagnosis). These interventions were evaluated on how they worked to identify children with TB, prevent further transmission of TB among children, and strengthen the health system involved with childhood TB care. Overall, 13 715 children were detected with TB, improving case notifications by 34%. In addition, nearly 5000 eligible contacts were enrolled on TB preventive treatment through these interventions. Focusing efforts and funding on childhood TB can produce marked improvements in case detection.

Pooling samples to increase testing capacity with Xpert Xpress SARS-CoV-2 during the Covid-19 pandemic in Lao People's Democratic Republic.

The COVID-19 pandemic created the need for large-scale testing of populations. However, most laboratories do not have sufficient testing capacity for mass screening. We evaluated pooled testing of samples, as a strategy to increase testing capacity in Lao PDR. Samples of consecutive patients were tested in pools of four using the Xpert Xpress SARS CoV-2 assay. Positive pools were confirmed by individual testing, and we describe the performance of the test and savings achieved. We also diluted selected positive samples to describe its effect on the assays CT values. 1,568 patients were tested in 392 pools of four. 361 (92.1%) pools were negative and 31 (7.9%) positive. 29/31 (93.5% (95%CI 77-99%) positive pools were confirmed by individual testing of the samples but, in 2/31 (6.5%) the four individual samples were negative, suggesting contamination. Pools with only one positive sample had higher CT values (lower RNA concentrations) than the respective individual samples, indicating a dilution effect, which suggested an increased risk of false negative results with dilutions >1:10. However, this risk may be low if the prevalence of infection is high, when pools are more likely to contain more than one positive sample. Pooling saved 67% of cartridges and substantially increased testing capacity. Pooling samples increased SARS-CoV-2 testing capacity and resulted in considerable cartridge savings. Given the need for high-volume testing, countries may consider implementation of pooling for SARS-CoV-2 screening.

Comparative assessment of the cost-effectiveness of Tuberculosis (TB) active case-finding interventions: A systematic analysis of TB REACH wave 5 projects.

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.

Diagnostic Accuracy of the Truenat MTB Plus Assay and Comparison with the Xpert MTB/RIF Assay to Detect Tuberculosis among Hospital Outpatients in Cameroon.

The Truenat MTB Plus assay is a rapid molecular test that has been recommended by the World Health Organization since 2020 as an initial test to detect tuberculosis (TB). The WHO highlighted the need to further evaluate assay performance to inform future recommendations, including in people living with HIV and compared to the Xpert MTB/RIF assay. We conducted a prospective evaluation of the diagnostic accuracy of the Truenat assay in Cameroon, a country with a high burden of HIV/TB. Adult outpatients were recruited at four hospitals; demographic information and medical history were collected, and participants produced two sputum specimens. Truenat and Xpert testing was performed on the same specimen, and performance was compared to TB culture as the reference standard. From November 2019 to December 2020, 945 participants were enrolled and included in the analysis. Among 251 participants with culture-positive TB, the sensitivity of Truenat MTB Plus was 91% (95% confidence interval [CI], 86 to 94%), similar to Xpert (90%; 95% CI, 86 to 93%). Among 74 HIV-positive participants with culture-positive TB, the sensitivity of Truenat MTB Plus was 85% (95% CI, 75 to 92%) compared to 81% for Xpert (95% CI, 70 to 89%). Among 47 participants with smear-negative TB, the sensitivity of Truenat MTB Plus was 55% (95% CI, 40 to 70%), similar to Xpert (53%; 95% CI, 38 to 68%). The specificity of Truenat MTB Plus was 96% (95% CI, 94 to 97%) compared to 99% (95% CI, 97 to 99%) for Xpert. For TB detection compared to the reference standard of TB culture, the performance of the Truenat MTB Plus assay was similar to that of Xpert in this population, including among people living with HIV.

Effectiveness of women-led community interventions in improving tuberculosis preventive treatment in children: results from a comparative, before-after study in Ethiopia.

OBJECTIVES: Our objective was to evaluate the impact of a service delivery model led by membership-based associations called Iddirs formed by women on tuberculosis preventive treatment (TPT) initiation and completion rates among children. DESIGN: Comparative, before-and-after study design. SETTING: Three intervention and two control districts in Ethiopia. PARTICIPANTS: Children who had a history of close contact with adults with infectious forms of tuberculosis (TB). Child contacts in whom active TB and contraindications to TPT regimens were excluded were considered eligible for TPT. INTERVENTIONS: Between July 2020 and June 2021, trained women Iddir members visited households of index TB patients, screened child household contacts for TB, provided education and information on the benefits of TPT, linked them to the nearby health centre and followed them at home for TPT adherence and side effects. Two control zones received the standard of care, which comprised of facility-based provision of TPT to children. We analysed quarterly TPT data for treatment initiation and completion and compared intervention and control zones before and after the interventions and tested for statistical significance using Poisson regression. PRIMARY AND SECONDARY OUTCOME MEASURES: There were two primary outcome measures: proportion of eligible children initiated TPT and proportion completed treatment out of those eligible. RESULTS: TPT initiation rate among eligible under-15-year-old children (U15C) increased from 28.7% to 63.5% in the intervention zones, while it increased from 34.6% to 43.2% in the control zones, and the difference was statistically significant (p<0.001). TPT initiation rate for U5C increased from 13% (17 out of 131) to 93% (937 out of 1010). Of the U5C initiated, 99% completed treatment; two discontinued due to side effects; three parents refused to continue; and one child was lost to follow-up. CONCLUSION: Women-led Iddirs contributed to significant increase in TPT initiation and completion rates. The model of TPT delivery should be scaled-up.