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Objective: To investigate the prevalence of non‐communicable diseases among household contacts of people with tuberculosis. Methods: We conducted a systematic review and individual participant data meta‐analysis. We searched Medline, Embase and the Global Index Medicus from inception to 16 May 2023. We included studies that assessed for at least one non‐communicable disease among household contacts of people with clinical tuberculosis. We estimated the non‐communicable disease prevalence through mixed effects logistic regression for studies providing individual participant data, and compared it with estimates from aggregated data meta‐analyses. Furthermore, we compared age and sex‐standardised non‐communicable disease prevalence with national‐level estimates standardised for age and sex. Results: We identified 39 eligible studies, of which 14 provided individual participant data (29,194 contacts). Of the remaining 25 studies, 18 studies reported aggregated data suitable for aggregated data meta‐analysis. In individual participant data analysis, the pooled prevalence of diabetes in studies that undertook biochemical testing was 8.8% (95% confidence interval [CI], 5.1%–14.9%, four studies). Age‐and sex‐standardised prevalence was higher in two studies (10.4% vs. 6.9% and 11.5% vs. 8.4%) than the corresponding national estimates and similar in two studies. Prevalence of diabetes mellitus based on self‐report or medical records was 3.4% (95% CI 2.6%–4.6%, 14 studies). Prevalence did not significantly differ compared to estimates from aggregated data meta‐analysis. There were limited data for other non‐communicable diseases. Conclusion: The prevalence of diabetes mellitus among household contacts was high while that of known diabetes was substantially lower, suggesting the underdiagnosis. tuberculosis household contact investigation offers opportunities to deliver multifaceted interventions to identify tuberculosis infection and disease, screen for non‐communicable diseases and address shared risk factors. [ABSTRACT FROM AUTHOR]

Background: In 2022, fewer than half of persons with tuberculosis (TB) had access to molecular diagnostic tests for TB due to their high costs. Studies have found that the use of artificial intelligence (AI) software for chest X-ray (CXR) interpretation and sputum specimen pooling can each reduce the cost of testing. We modeled the combination of both strategies to estimate potential savings in consumables that could be used to expand access to molecular diagnostics. Methods: We obtained Xpert testing and positivity data segmented into deciles by AI probability scores for TB from the community- and healthcare facility-based active case finding conducted in Bangladesh, Nigeria, Viet Nam, and Zambia. AI scores in the model were based on CAD4TB version 7 (Zambia) and qXR (all other countries). We modeled four ordinal screening and testing approaches involving AI-aided CXR interpretation to indicate individual and pooled testing. Setting a false negative rate of 5%, for each approach we calculated additional and cumulative savings over the baseline of universal Xpert testing, as well as the theoretical expansion in diagnostic coverage. Results: In each country, the optimal screening and testing approach was to use AI to rule out testing in deciles with low AI scores and to guide pooled vs individual testing in persons with moderate and high AI scores, respectively. This approach yielded cumulative savings in Xpert tests over baseline ranging from 50.8% in Zambia to 57.5% in Nigeria and 61.5% in Bangladesh and Viet Nam. Using these savings, diagnostic coverage theoretically could be expanded by 34% to 160% across the different approaches and countries. Conclusions: Using AI software data generated during CXR interpretation to inform a differentiated pooled testing strategy may optimize TB diagnostic test use, and could extend molecular tests to more people who need them. The optimal AI thresholds and pooled testing strategy varied across countries, which suggests that bespoke screening and testing approaches may be needed for differing populations and settings. [ABSTRACT FROM AUTHOR]

Current strategies to promptly, effectively, and equitably screen people with tuberculosis (TB) and link them to diagnosis and care are insufficient; new approaches are required to find the millions of people around the world with TB who are missed each year. Interventions also need to be designed considering how people interact with health care facilities and where appropriate should be suitable for use in the community. Here, the historical, new, and reemerging technologies that are being utilised for TB diagnosis globally are discussed, whilst highlighting that how we use and evaluate tests is just as important as the tests themselves. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Despite 30 years as a public health emergency, tuberculosis (TB) remains one of the world's deadliest diseases. Most deaths are among persons with TB who are not reached with diagnosis and treatment. Thus, timely screening and accurate detection of TB, particularly using sensitive tools such as chest radiography, is crucial for reducing the global burden of this disease. However, lack of qualified human resources represents a common limiting factor in many high TB-burden countries. Artificial intelligence (AI) has emerged as a powerful complement in many facets of life, including for the interpretation of chest X-ray images. However, while AI may serve as a viable alternative to human radiographers and radiologists, there is a high likelihood that those suffering from TB will not reap the benefits of this technological advance without appropriate, clinically effective use and cost-conscious deployment. The World Health Organization recommended the use of AI for TB screening in 2021, and early adopters of the technology have been using the technology in many ways. In this manuscript, we present a compilation of early user experiences from nine high TB-burden countries focused on practical considerations and best practices related to deployment, threshold and use case selection, and scale-up. While we offer technical and operational guidance on the use of AI for interpreting chest X-ray images for TB detection, our aim remains to maximize the benefit that programs, implementers, and ultimately TB-affected individuals can derive from this innovative technology. [ABSTRACT FROM AUTHOR]

Background: Ultra-portable X-ray devices with artificial intelligence (AI) are increasingly used to screen for tuberculosis (TB). Few studies have documented their performance. We aimed to evaluate the performance of chest X-ray (CXR) and symptom screening for active case finding of TB among remote populations using ultra-portable X-ray and AI. Methods: We organized screening camps in rural northeast Nigeria, and all consenting individuals ≥ 15 years were screened for TB symptoms (cough, fever, night sweats, and weight loss) and received a CXR. We used a MinXray Impact system interpreted by AI (qXR V3), which is a wireless setup and can be run without electricity. We collected sputum samples from individuals with an qXR abnormality score of 0.30 or higher or if they reported any TB symptoms. Samples were tested with Xpert MTB/RIF. We documented the TB screening cascade and evaluated the performance of screening with different combinations of symptoms and CXR interpreted by AI. Results: We screened 5297 individuals during 66 camps: 2684 (51%) were females, and 2613 (49%) were males. Using ≥ 2 weeks of cough to define presumptive TB, 1056 people (20%) would be identified. If a cough of any duration was used, the number with presumptive TB increased to 1889 (36%) and to 3083 (58%) if any of the four symptoms were used. Overall, 769 (14.5%) had abnormality scores of 0.3 or higher, and 447 (8.4%) had a score of 0.5 or higher. We collected 1021 samples for Xpert testing and detected 85 (8%) individuals with TB. Screening for prolonged cough only identified 40% of people with TB. Any symptom detected 90.6% of people with TB, but specificity was 11.4%. Using an AI abnormality score of 0.50 identified 89.4% of people with TB with a specificity of 62.8%. Conclusions: Ultra-portable CXR can be used to provide more efficient TB screening in hard-to-reach areas. Symptom screening missed large proportions of people with bacteriologically confirmed TB. Employing AI to read CXR can improve triaging when human readers are unavailable and can save expensive diagnostic testing costs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In the field of tuberculosis (TB), Community Healthcare Workers (CHWs) have been engaged for advocacy, case detection, and patient support in a wide range of settings. Estimates predict large-scale shortfalls of healthcare workers in low- and middle-income settings by 2030 and strategies are needed to optimize the health workforce to achieve universal availability and accessibility of healthcare. In 2018, the World Health Organization (WHO) published guidelines on best practices for CHW engagement, and identified remaining knowledge gaps. Stop TB Partnership's TB REACH initiative has supported interventions using CHWs to deliver TB care in over 30 countries, and utilized the same primary indicator to measure project impact at the population-level for all TB active case finding projects, which makes the results comparable across multiple settings. This study compiled 10 years of implementation data from the initiative's grantee network to begin to address key knowledge gaps in CHW networks.Methods: We conducted a cross-sectional study analyzing the TB REACH data repository (n = 123) and primary survey responses (n = 50) of project implementers. We designed a survey based on WHO guidelines to understand projects' practices on CHW recruitment, training, activities, supervision, compensation, and sustainability. We segmented projects by TB notification impact and fitted linear random-effect regression models to identify practices associated with higher changes in notifications.Results: Most projects employed CHWs for advocacy alongside case finding and holding activities. Model characteristics associated with higher project impact included incorporating e-learning in training and having the prospect of CHWs continuing their responsibilities at the close of a project. Factors that trended towards being associated with higher impact were community-based training, differentiated contracts, and non-monetary incentives.Conclusion: In line with WHO guidelines, our findings emphasize that successful implementation approaches provide CHWs with comprehensive training, continuous supervision, fair compensation, and are integrated within the existing primary healthcare system. However, we encountered a great degree of heterogeneity in CHW engagement models, resulting in few practices clearly associated with higher notifications. [ABSTRACT FROM AUTHOR]

Background: TB REACH is a grant-making initiative launched by the Stop TB Partnership in January 2010 to support innovative approaches and technologies to find and treat people with active TB disease, drugresistant TB, or TB infection. Since then, TB REACH has launched eight Waves of funding to pilot untested, but promising technologies, tools, and approaches. The objective of this paper was to review the grants implemented in Pakistan in the decade since TB REACH's inception and to summarize the approaches used, document the results, and assess the impact of these projects on local and international policy. Methods: We searched the TB REACH's Grant Management System (GMS), which is a database for information on all grants awarded through the initiative, for recipient organisations in Pakistan from 2010 until June 2020. Data was abstracted for the following topic areas: type of grant, focus of work, case finding strategies, risk groups screened and impact on case finding. Results: Through eight waves of funding, TB REACH has supported 28 grants for 21 different interventions in Pakistan worth a total of USD 13.4 million. Overall, 19 of these projects aimed to improve detection, linkage to treatment and reporting of TB and two were product innovation grants for developing resources and materials to aide TB service delivery. Conclusion: TB REACH support has facilitated the introduction of new technologies, establishment of innovative processes in both public and private sector and approaches for addressing TB in key populations. The TB response in Pakistan and globally will continue to require innovation and disruption of 'business as usual' approaches if we are to End TB. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recently recommended Video Observed Therapy (VOT) as one option for monitoring tuberculosis (TB) treatment adherence. There is evidence that private sector TB treatment has substandard treatment follow-up, which could be improved using VOT. However, acceptability of VOT in the private sector has not yet been evaluated. Methods: We conducted a cross-sectional survey employing a theoretical framework for healthcare intervention acceptability to measure private provider perceptions of VOT across seven constructs in three cities of Viet Nam: Ha Noi, Ho Chi Minh City, and Hai Phong. We investigated the differences in private providers' attitudes and perceptions of VOT using mixed ordinal models to test for significant differences in responses between groups of providers stratified by their willingness to use VOT. Results: A total of 79 private providers completed the survey. Sixty-two providers (75%) indicated they would use VOT if given the opportunity. Between private providers who would and would not use VOT, there were statistically significant differences (p≤0.001) in the providers' beliefs that VOT would help identify side effects faster and in their confidence to monitor treatment and provide differentiated care with VOT. There were also significant differences in providers' beliefs that VOT would save them time and money, address problems faced by their patients, benefit their practice and patients, and be relevant for all their patients. Conclusion: Private providers who completed the survey have positive views towards using VOT and specific subpopulations acknowledge the value of integrating VOT into their practice. Future VOT implementation in the private sector should focus on emphasizing the benefits and relevance of VOT during recruitment and provide programmatic support for implementing differentiated care with the technology. [ABSTRACT FROM AUTHOR]

GeneXpert-based testing with Xpert MTB/RIF or Ultra assays is essential for tuberculosis diagnosis. However, testing may be affected by cartridge and staff shortages. More efficient testing strategies could help, especially during the coronavirus disease pandemic. We searched the literature to systematically review whether GeneXpert-based testing of pooled sputum samples achieves sensitivity and specificity similar to testing individual samples; this method could potentially save time and preserve the limited supply of cartridges. From 6 publications, we found 2-sample pools using Xpert MTB/RIF had 87.5% and 96.0% sensitivity (average sensitivity 94%; 95% CI 89.0%-98.0%) (2 studies). Four-sample pools averaged 91% sensitivity with Xpert MTB/RIF (2 studies) and 98% with Ultra (2 studies); combining >4 samples resulted in lower sensitivity. Two studies reported that pooling achieved 99%-100% specificity and 27%-31% in cartridge savings. Our results show that pooling may improve efficiency of GeneXpert-based testing. [ABSTRACT FROM AUTHOR]

Background: In Bangladesh, about 80% of healthcare is provided by the private sector. Although free diagnosis and care is offered in the public sector, only half of the estimated number of people with tuberculosis are diagnosed, treated, and notified to the national program. Private sector engagement strategies often have been small scale and time limited. We evaluated a Social Enterprise Model combining external funding and income generation at three tuberculosis screening centres across the Dhaka Metropolitan Area for diagnosing and treating tuberculosis. Methods and findings: The model established three tuberculosis screening centres across Dhaka Metropolitan Area that carried the icddr,b brand and offered free Xpert MTB/RIF tests to patients visiting the screening centres for subsidized, digital chest radiographs from April 2014 to December 2017. A network of private and public health care providers, and community recommendation was formed for patient referral. No financial incentives were offered to physicians for referrals. Revenues from radiography were used to support screening centres' operation. Tuberculosis patients could choose to receive treatment from the private or public sector. Between 2014 and 2017, 1,032 private facilities networked with 8,466 private providers were mapped within the Dhaka Metropolitan Area. 64, 031 patients with TB symptoms were referred by the private providers, public sector and community residents to the three screening centres with 80% coming from private providers. 4,270 private providers made at least one referral. Overall, 10,288 pulmonary and extra-pulmonary tuberculosis cases were detected and 7,695 were bacteriologically positive by Xpert, corresponding to 28% of the total notifications in Dhaka Metropolitan Area. Conclusion: The model established a network of private providers who referred individuals with presumptive tuberculosis without financial incentives to icddr,b's screening centres, facilitating a quarter of total tuberculosis notifications in Dhaka Metropolitan Area. Scaling up this approach may enhance national and international tuberculosis response. [ABSTRACT FROM AUTHOR]

Tuberculosis prevalence surveys have demonstrated the benefit of screening with chest x-ray (CXR) and sensitive diagnostic tests compared to symptoms and smear microscopy. However, in programmatic practice there is little evidence on the yield of different algorithms. We implemented contact tracing in Chennai, India for adult sputum-positive TB patients registered from January 2015 to March 2016. Patients with symptoms or abnormal X-ray findings further underwent testing using Xpert MTB/RIF (Xpert) and smear microscopy. A retrospective cohort study was done to summarize the key findings. We verbally screened 5553 contacts for symptoms, CXR through private sector collaboration, Xpert, and smear microscopy. Overall, 1312 (23.6%) contacts screened positive. CXR alone identified 531 (40.5%) of them, 679 (51.8%) were symptom-positive only, while 102 (7.8%) were positive on both the symptom and CXR screen. Overall, 35 bacteriologically positive cases were identified (0.7%). A standard approach of symptoms screening followed by microscopy identified only 9 (25.7%) of the total number of bacteriologically positive cases, whereas the combination of a CRX screening followed by microscopy identified 13 (37.1%) of the cases. The algorithm of symptoms screening followed by Xpert testing, detected 20 cases, whereas the combination of symptoms and CXR followed by Xpert increased this number to 35 (75% increase compared to symptoms and Xpert). Optimal use of more sensitive screening tests, better diagnostic tests, and novel private sector engagement can improve diagnostic yield in a programmatic setting. [ABSTRACT FROM AUTHOR]

Background: A decade of Boko Haram insurgency brought conflict, mass displacement, and the destruction of basic infrastructure to Northeast Nigeria. Over 2 million internally displaced persons (IDPs) suffering from lack of basic hygienic conditions, malnutrition, and disease live in camps or are hosted by communities in the region, where the conflict has contributed to a massive destruction of health facilities. Infectious diseases like tuberculosis (TB) and HIV are especially difficult to address under such conditions, and IDPs are vulnerable to both. Although international investment supports some health interventions among IDPs, locally sourced solutions are lacking.Methods and Findings: We evaluated the impact of an active case finding (ACF) intervention for TB and testing for HIV in IDP communities and provided linkages to treatment in 3 states in Northeast Nigeria: Adamawa, Gombe, and Yobe. The ACF was a component of a multistakeholder collaboration between government, civil society, and IDP community partners, which also included mapping of IDP populations and health services, supporting existing health facilities, developing a sample transport network, and organizing community outreach to support ACF. Between July 1, 2017, and June 30, 2018, ACF was conducted in 26 IDP camps and 963 host communities in 12 local government areas (LGAs) with another 12 LGAs serving as a control population. Outreach efforts resulted in 283,556 screening encounters. We screened 13,316 children and 270,239 adults including 150,303 (55.6%) adult women and 119,936 (44.4%) men. We tested 17,134 people for TB and 58,976 for HIV. We detected 1,423 people with TB and 874 people living with HIV. We linked 1,419 people to anti-TB treatment and 874 people with HIV to antiretroviral treatment sites. We evaluated additional TB cases notified and conducted comparative interrupted time series (ITS) analyses to assess the impact of ACF on TB case notifications. Through our efforts, bacteriologically confirmed TB notifications increased by 847 (45.1%) during the intervention period, with IDPs accounting for 46% of these notifications. The ITS analyses detected significant positive postintervention trend differences in TB notification rates between the intervention and control areas in all forms TB (incidence rate ratio [IRR] = 1.136 [1.072, 1.204]; p ≤ 0.001) and bacteriologically positive TB (IRR = 1.141 [1.058, 1.229]; p = 0.001). The TB prevalence (502 cases per 100,000 screening encounters) was 10 times the national notification rates and 2.3 times the estimated national incidence. Rates of HIV infection (1.8%) were higher than HIV prevalence estimates in the 3 states. Our study was limited by the nonrandom selection of LGAs. Furthermore, we did not use sensitive screening tools like chest X-ray and likely missed people with TB.Conclusions: In this study, we observed a burden of TB in IDP populations of Northeast Nigeria many times higher than national rates and HIV rates higher than state level estimates. The impact of the intervention showed that ACF can greatly increase TB case notifications. Engaging IDP communities, local governments, and civil society organizations is essential to ensuring the success of interventions targeting TB and HIV, and such approaches can provide sustained solutions to these and other health crises among vulnerable populations. [ABSTRACT FROM AUTHOR]

Pakistan ranks fifth among high tuberculosis (TB) burden countries and also has seventh highest burden for diabetes mellitus (DM). DM increases the risk of developing TB and contributes to adverse TB treatment outcomes hence screening and integrated management for both diseases in high burden countries is suggested. Computer-Aided Detection for TB (CAD4TB) can potentially be used as triage tool in low resource settings to pre-screen individuals for Xpert MTB/RIF testing. The aim of this study was to evaluate the diagnostic accuracy and performance of CAD4TB software in people with diabetes (PWD) enrolled in a TB screening program in Karachi, Pakistan. A total of 694 individuals with a diagnosis of DM (of whom 31.1% were newly diagnosed) were screened with CAD4TB and simultaneously provided sputum for Xpert MTB/RIF testing. Of the 74 (10.7%) participants who had bacteriologically positive (MTB+) results on Xpert testing, 54 (73%) had a CAD4TB score >70; and 155 (25%) participants who tested MTB-negative had scores >70. The area under the receiver operator curve was 0.78 (95% CI: 0.77–0.80). Our study findings indicate that CAD4TB offers good diagnostic accuracy as a triage test for TB screening among PWD using Xpert MTB/RIF as the reference standard. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Multidrug-resistant tuberculosis (MDR-TB) jeopardizes global TB control. The prevalence and predictors of Rifampicin-resistant (RR) TB, a proxy for MDR-TB, and the treatment outcomes with standard and shortened regimens have not been assessed in post-conflict regions, such as the South Kivu province in the eastern Democratic Republic of the Congo (DRC). We aimed to fill this knowledge gap and to inform the DRC National TB Program. Methods of adults and children evaluated for pulmonary TB by sputum smear microscopy and Xpert MTB/RIF (Xpert) from February 2012 to June 2017. Multivariable logistic regression, Kaplan–Meier estimates, and multivariable Cox regression were used to assess independent predictors of RR-TB and treatment failure/death. Results Of 1535 patients Xpert-positive for TB, 11% had RR-TB. Independent predictors of RR-TB were a positive sputum smear (adjusted odds ratio [aOR] 2.42, 95% confidence interval [CI] 1.63–3.59), retreatment of TB (aOR 4.92, 95% CI 2.31–10.45), and one or more prior TB episodes (aOR 1.77 per episode, 95% CI 1.01–3.10). Over 45% of RR-TB patients had no prior TB history or treatment. The median time from Xpert diagnosis to RR-TB treatment initiation was 12 days (interquartile range 3–60.2). Cures were achieved in 30/36 (83%) and 84/114 (74%) of patients on 9- vs 20/24-month MDR-TB regimens, respectively (P =.06). Predictors of treatment failure/death were the absence of directly observed therapy (DOT; adjusted hazard ratio [aHR] 2.77, 95% CI 1.2–6.66) and any serious adverse drug event (aHR 4.28, 95% CI 1.88–9.71). Conclusions Favorable RR-TB cure rates are achievable in this post-conflict setting with a high RR-TB prevalence. An expanded Xpert scale-up; the prompt initiation of shorter, safer, highly effective MDR-TB regimens; and treatment adherence support are critically needed to optimize outcomes. [ABSTRACT FROM AUTHOR]

Background: Most studies evaluate active case findings (ACF) for bacteriologically confirmed TB. Adapted diagnostic approaches are needed to identify cases with lower bacillary loads. Objectives: To assess the likelihood of diagnosing all forms of TB, including clinically diagnosed pulmonary and extra-pulmonary TB, using different ACF algorithms in Cambodia. Methods: Clients were stratified into 'high-risk' (presumptive TB plus TB contact, or history of TB, or presumptive HIV infection; n = 12,337) and 'moderate-risk' groups (presumptive TB; n = 28,804). Sputum samples were examined by sputum smear microscopy (SSM) or Xpert MTB/RIF (Xpert). Initially, chest X-ray using a mobile radiography unit was a follow-up test after a negative sputum examination [algorithms A (Xpert/X-ray) and B (SSM/X-ray)]. Subsequently, all clients received an X-ray [algorithms C (X-ray+Xpert) and D (Xray+SSM/Xpert)]. X-rays were interpreted on the spot. Results: Between 25 August 2014 and 31 March 2016, 2217 (5.4%) cases with all forms of TB cases were diagnosed among 41,141 adults. The majority of TB cases (1488; 67.1%) were diagnosed using X-ray. When X-rays were taken and interpreted the same day the sputum was collected, same-day diagnosis more than doubled. Overall, the number needed to test (NNT) to diagnose one case was 18.6 (95%CI:17.9–19.2). In the high-risk group the NNT was lower [algorithm D: NNT = 17.3(15.9–18.9)] compared with the 'moderate-risk group' [algorithm D: NNT = 20.8(19.6–22.2)]. In the high-risk group the NNT was lower when using Xpert as an initial test [algorithm A: NNT = 12.2(10.8–13.9) or algorithm C: NNT = 11.2(9.6–13.0)] compared with Xpert as a follow-up test [algorithm D: NNT = 17.3(15.9–18.9)]. Conclusion: To diagnose all TB forms, X-ray should be part of the diagnostic algorithm. The combination of X-ray and Xpert testing for high-risk clients was the most effective ACF approach in this setting. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is the deadliest infectious disease globally. Current case finding approaches may miss many people with TB or detect them too late. Data and methods: This study was a retrospective, spatial analysis of routine TB surveillance and cadastral data in Go Vap district, Ho Chi Minh City. We geocoded TB notifications from 2011 to 2015 and calculated theoretical yields of simulated door-to-door screening in three concentric catchment areas (50m, 100m, 200m) and three notification window scenarios (one, two and four quarters) for each index case. We calculated average yields, compared them to published reference values and fit a GEE (Generalized Estimating Equation) linear regression model onto the data. Results: The sample included 3,046 TB patients. Adjusted theoretical yields in 50m, 100m and 200m catchment areas were 0.32% (95%CI: 0.27,0.37), 0.21% (95%CI: 0.14,0.29) and 0.17% (95%CI: 0.09,0.25), respectively, in the baseline notification window scenario. Theoretical yields in the 50m-catchment area for all notification window scenarios were significantly higher than a reference yield from literature. Yield was positively associated with treatment failure index cases (beta = 0.12, p = 0.001) and short-term inter-province migrants (beta = 0.06, p = 0.022), while greater distance to the DTU (beta = -0.02, p<0.001) was associated with lower yield. Conclusions: This study is an example of inter-departmental collaboration and application of repurposed cadastral data to progress towards the end TB objectives. The results from Go Vap showed that the use of spatial analysis may be able to identify areas where targeted active case finding in Vietnam can help improve TB case detection. [ABSTRACT FROM AUTHOR]

Background: Currently, only 62% of incident tuberculosis (TB) cases are reported to the national programme in Pakistan. Several innovative interventions are being recommended to detect the remaining ‘missed’ TB cases. One such intervention involved expanding contact investigation to the community using the Xpert MTB/RIF test. Methods: This was a before and after intervention study involving retrospective record review. Passive case finding and household contact investigation was routinely done in the pre-intervention period July 2011-June 2013. Four districts with a high concentration of slums were selected as intervention areas; Lahore, Rawalpindi, Faisalabad and Islamabad. Here, in the intervention period, July 2013-June 2015, contact investigation beyond household was conducted: all people staying within a radius of 50 metres (using Geographical Information System) from the household of smear positive TB patients were screened for tuberculosis. Those with presumptive TB were investigated using smear microscopy and the Xpert MTB/RIF test was performed on smear negative patients. All the diagnosed TB patients were linked to TB treatment and care. Results: A total of 783043 contacts were screened for tuberculosis: 23741(3.0%) presumptive TB patients were identified of whom, 4710 (19.8%) all forms and 4084(17.2%) bacteriologically confirmed TB patients were detected. The contribution of Xpert MTB/RIF to bacteriologically confirmed TB patients was 7.6%. The yield among investigated presumptive child TB patients was 5.1%. The overall yield of all forms TB patients among investigated was 22.3% among household and 19.1% in close community. The intervention contributed an increase of case detection of bacteriologically confirmed tuberculosis by 6.8% and all forms TB patients by 7.9%. Conclusion: Community contact investigation beyond household not only detected additional TB patients but also increased TB case detection. However, further long term assessments and cost-effectiveness studies are required before national scale-up. [ABSTRACT FROM AUTHOR]

Background: Screening of household contacts of tuberculosis (TB) patients is a recommended strategy to improve early case detection. While it has been widely implemented in low prevalence countries, the most optimal protocols for contact investigation in high prevalence, low resource settings is yet to be determined. This study evaluated contact investigation interventions in eleven lower and middle income countries and reviewed the association between context or program-related factors and the yield of cases among contacts. Methods: We reviewed data from nineteen first wave TB REACH funded projects piloting innovations to improve case detection. These nineteen had fulfilled the eligibility criteria: contact investigation implementation and complete data reporting. We performed a cross-sectional analysis of the percentage yield and case notifications for each project. Implementation strategies were delineated and the association between independent variables and yield was analyzed by fitting a random effects logistic regression. Findings: Overall, the nineteen interventions screened 139,052 household contacts, showing great heterogeneity in the percentage yield of microscopy confirmed cases (SS+), ranging from 0.1% to 6.2%). Compared to the most restrictive testing criteria (at least two weeks of cough) the aOR’s for lesser (any TB related symptom) and least (all contacts) restrictive testing criteria were 1.71 (95%CI 0.94−3.13) and 6.90 (95% CI 3.42−13.93) respectively. The aOR for inclusion of SS- and extra-pulmonary TB was 0.31 (95% CI 0.15−0.62) compared to restricting index cases to SS+ TB. Contact investigation contributed between <1% and 14% to all SS+ cases diagnosed in the intervention areas. Conclusions: This study confirms that high numbers of active TB cases can be identified through contact investigation in a variety of contexts. However, design and program implementation factors appear to influence the yield of contact investigation and its concomitant contribution to TB case detection. [ABSTRACT FROM AUTHOR]

The inability to detect all individuals with active tuberculosis has led to a growing interest in new approaches to improve case detection. Policy makers and program staff face important challenges measuring effectiveness of newly introduced interventions and reviewing feasibility of scaling-up successful approaches. While robust research will continue to be needed to document impact and influence policy, it may not always be feasible for all interventions and programmatic evidence is also critical to understand what can be expected in routine settings. The effects of interventions on early and improved tuberculosis detection can be documented through well-designed program evaluations. We present a pragmatic framework for evaluating and measuring the effect of improved case detection strategies using systematically collected intervention data in combination with routine tuberculosis notification data applying historical and contemporary controls. Standardized process evaluation and systematic documentation of program implementation design, cost and context will contribute to explaining observed levels of success and may help to identify conditions needed for success. Findings can then guide decisions on scale-up and replication in different target populations and settings. [ABSTRACT FROM AUTHOR]

Background: Globally, TB notifications have stagnated since 2007, and sputum smear positive notifications have been declining despite policies to improve case detection. We evaluate results of 28 interventions focused on improving TB case detection. Methods: We measured additional sputum smear positive cases treated, defined as the intervention area's increase in case notification during the project compared to the previous year. Projects were encouraged to select control areas and collect historical notification data. We used time series negative binomial regression for over-dispersed cross-sectional data accounting for fixed and random effects to test the individual projects' effects on TB notification while controlling for trend and control populations. Results: Twenty-eight projects, 19 with control populations, completed at least four quarters of case finding activities, covering a population of 89.2 million. Among all projects sputum smear positive (SS+) TB notifications increased 24.9% and annualized notification rates increased from 69.1 to 86.2/100,000 (p = 0.0209) during interventions. Among the 19 projects with control populations, SS+TB case notifications increased 36.9% increase while in the control populations a 3.6% decrease was observed. Fourteen (74%) of the 19 projects' SS+TB notification rates in intervention areas increased from the baseline to intervention period when controlling for historical trends and notifications in control areas. Conclusions: Interventions were associated with large increases in TB notifications across many settings, using an array of interventions. Many people with TB are not reached using current approaches. Different methods and interventions tailored to local realities are urgently needed. [ABSTRACT FROM AUTHOR]

Background: In Pakistan, like many Asian countries, a large proportion of healthcare is provided through the private sector. We evaluated a systematic screening strategy to identify people with tuberculosis in private facilities in Karachi and assessed the approaches' ability to diagnose patients earlier in their disease progression. Methods and Findings: Lay workers at 89 private clinics and a large hospital outpatient department screened all attendees for tuberculosis using a mobile phone-based questionnaire during one year. The number needed to screen to detect a case of tuberculosis was calculated. To evaluate early diagnosis, we tested for differences in cough duration and smear grading by screening facility. 529,447 people were screened, 1,010 smear-positive tuberculosis cases were detected and 942 (93.3%) started treatment, representing 58.7% of all smear-positive cases notified in the intervention area. The number needed to screen to detect a smear-positive case was 124 (prevalence 806/100,000) at the hospital and 763 (prevalence 131/100,000) at the clinics; however, ten times the number of individuals were screened in clinics. People with smear-positive TB detected at the hospital were less likely to report cough lasting 2–3 weeks (RR 0.66 95%CI [0.49–0.90]) and more likely to report cough duration >3 weeks (RR 1.10 95%CI [1.03–1.18]). Smear-positive cases at the clinics were less likely to have a +3 grade (RR 0.76 95%CI [0.63–0.92]) and more likely to have +1 smear grade (RR 1.24 95%CI [1.02–1.51]). Conclusions: Tuberculosis screening at private facilities is acceptable and can yield large numbers of previously undiagnosed cases. Screening at general practitioner clinics may find cases earlier than at hospitals although more people must be screened to identify a case of tuberculosis. Limitations include lack of culture testing, therefore underestimating true TB prevalence. Using more sensitive and specific screening and diagnostic tests such as chest x-ray and Xpert MTB/RIF may improve results. [ABSTRACT FROM AUTHOR]

Background The Xpert MTB/RIF assay has garnered significant interest as a sensitive and rapid diagnostic tool to improve detection of sensitive and drug resistant tuberculosis. However, most existing literature has described the performance of MTB/RIF testing only in study conditions; little information is available on its use in routine case finding. TB REACH is a multi-country initiative focusing on innovative ways to improve case notification. Methods We selected a convenience sample of nine TB REACH projects for inclusion to cover a range of implementers, regions and approaches. Standard quarterly reports and machine data from the first 12 months of MTB/RIF implementation in each project were utilized to analyze patient yields, rifampicin resistance, and failed tests. Data was collected from September 2011 to March 2013. A questionnaire was implemented and semi-structured interviews with project staff were conducted to gather information on user experiences and challenges. Results All projects used MTB/RIF testing for people with suspected TB, as opposed to testing for drug resistance among already diagnosed patients. The projects placed 65 machines (196 modules) in a variety of facilities and employed numerous case-finding strategies and testing algorithms. The projects consumed 47,973 MTB/RIF tests. Of valid tests, 7,195 (16.6%) were positive for MTB. A total of 982 rifampicin resistant results were found (13.6% of positive tests). Of all tests conducted, 10.6% failed. The need for continuous power supply was noted by all projects and most used locally procured solutions. There was considerable heterogeneity in how results were reported and recorded, reflecting the lack of standardized guidance in some countries. Conclusions The findings of this study begin to fill the gaps among guidelines, research findings, and realworld implementation of MTB/RIF testing. Testing with Xpert MTB/RIF detected a large number of people with TB that routine services failed to detect. The study demonstrates the versatility and impact of the technology, but also outlines various surmountable barriers to implementation. The study is not representative of all early implementer experiences with MTB/RIF testing but rather provides an overview of the shared issues as well as the many different approaches to programmatic MTB/RIF implementation. [ABSTRACT FROM AUTHOR]

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Objective This cross-sectional study investigates HIV, other sexually transmitted infections (STI), and risk behaviours among men who have sex with men (MSM) in two cities in El Salvador. Methods Respondent-driven sampling (RDS) was used to recruit MSM in the cities of San Salvador and San Miguel, El Salvador. Participants responded to questions about HIV risk behaviours; and blood, urine and anal swabs were collected. Blood samples were tested for herpes simplex type 2, syphilis and HIV infection. Urine and anal samples were tested by polymerase chain reaction (PCR) for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium. HIV-positive samples were tested with the BED capture enzyme immunoassay to distinguish recent from longstanding HIV infection. We estimated population-adjusted prevalence of behavioural variables, STI and HIV, and identified risk factors for HIV . Results The final sample included 596 and 195 MSM in San Salvador and San Miguel, respectively. Consistent condom use was low across all partner types as was recent HIV testing. RDS-adjusted HIV prevalence was 10.8% (95% CI 7.4% to 14.7%) in San Salvador, and 8.8% (95% CI 4.2% to 14.5%) in San Miguel. The proportion of recent testing among HIV-positive samples was 20%. Prevalence of any bacterial STI by PRC testing was 12.7% (95% CI 8.2% to 17.5%) in San Salvador, and 9.6% (95% CI 4.9% to 15.4%) in San Miguel. Conclusions We found a high prevalence of HIV, high levels of recent infection, and low condom usage. In El Salvador, targeted interventions towards MSM are needed to promote condom use, as well as to diagnose, treat and prevent HIV and other STIs. [ABSTRACT FROM AUTHOR]

There is a need for diagnostics for tuberculosis (TB) that are easy to use, able to screen non-sputum samples, and able to provide rapid results for the management of both immunocompromised and immunocompetent individuals. The Fujifilm SILVAMP TB LAM (FujiLAM) assay, a new non-sputum based point of need test for the diagnosis of TB, could potentially address most of these needs. We evaluated the performance of FujiLAM in HIV positive and HIV negative patients with presumptive TB attending three district hospitals in Nigeria. Consecutive patients were asked to provide urine samples on the spot, which were tested with FujiLAM. The results were compared against a positive culture and/or Xpert MTB/RIF as the reference standard. Forty-five patients had bacteriologically confirmed TB, and 159 had negative culture and Xpert MTB/RIF (no TB). The FujiLAM test was positive in 23 (sensitivity 65.7%, 95% CI = 48–80) HIV negative and seven (70%, 95% CI = 35–92) HIV positive patients with bacteriological confirmation of TB. FujiLAM was negative in 97 (specificity 99.0%, 95% CI = 94–100) HIV negative and 56 (93.3%, 95% CI = 83–98) HIV positive patients without TB. The FujiLAM test has good diagnostic accuracy for considering its application in both HIV positive and HIV negative patients with TB. [ABSTRACT FROM AUTHOR]

Current diagnostics for tuberculosis (TB) only manage to confirm a small proportion of children with TB and require respiratory samples, which are difficult to obtain. There is a need for non-invasive biomarker-based tests as an alternative to sputum testing. Fujifilm SILVAMP TB lipoarabinomannan (FujiLAM), a lateral-flow test to detect lipoarabinomannan in urine, is a novel non-sputum-based point-of-care diagnostic reported to have increased sensitivity for the diagnosis of TB among human immunodeficiency virus (HIV)-infected adults. We evaluate the performance of FujiLAM in children with presumptive TB. Fifty-nine children attending a paediatric hospital in Haiti with compatible signs and symptoms of TB were examined using Xpert MTB/RIF, smear microscopy and X-rays, and classified according to the certainty of diagnosis into bacteriologically confirmed TB (n = 5), unconfirmed TB (bacteriologically negative, n = 50) and unlikely TB (n = 4). Healthy children (n = 20) were enrolled as controls. FujiLAM sensitivity and specificity were 60% and 95% among children with confirmed TB. FujiLAM's high specificity and its characteristics as a point-of-care indicate the test has a good potential for the diagnosis of TB in children. [ABSTRACT FROM AUTHOR]

Background: Xpert MTB/RIF (GX) for tuberculosis (TB) diagnosis is often located in reference laboratories, and sputum needs to be transported using a cold chain. Transport media to preserve sputum are available, but performance data under programmatic conditions are limited. Methods: Sputum samples were collected from patients with presumptive TB in Nigeria. One sputum was transported in a cold chain, tested immediately with GX and cultured. One sputum was swabbed and stored in PrimeStore-Molecular-Transport-Medium (Primestore), and the remainder was stored in OMNIGene-sputum (Omnigene), kept for seven days and tested with GX. Results: Of 248 patients, 63 were fresh-sputum culture-positive and 56 GX-positive (sensitivity 88.9%, 95% CI: 78.4–95.4%). Four of 185 culture-negative patients were GX-positive (specificity 97.8%, 94.6–99.4%). Omnigene GX and Primestore GX were positive in 56/62 (90.3%, 80.1–96.4%) and 49/62 (79.0%, 66.8–88.3%) culture-positive, respectively, and 1/185 (99.5%, 97.0–100.0%) and 3/185 (98.4%, 95.3–99.7%) were culture-negative patients. 14 Human Immunodeficiency Virus (HIV)-infected and 44 HIV-uninfected patients were culture-positive. Omnigene and Primestore detected 12/14 (85.7%, 57.2–98.2%) and 5/14 (35.7%, 12.8–64.9%) HIV-infected and 41/44 (93.2%, 81.3–98.6%) HIV-uninfected culture-positive patients. Interpretation: Omnigene stored and fresh sputum samples had similar GX results. The GX results of Primestore-stored samples were similar to those found in the fresh sputum of non-HIV infected patients, but GX-positivity was lower in HIV-infected patients. This was likely due to the lower amount of bacilli collected by the swab and transferred to PrimeStore. [ABSTRACT FROM AUTHOR]

In the original publication of this article [1], an author's name needs to be revised from Jacob Creswel to Jacob Creswell. [ABSTRACT FROM AUTHOR]

Deep learning (DL) neural networks have only recently been employed to interpret chest radiography (CXR) to screen and triage people for pulmonary tuberculosis (TB). No published studies have compared multiple DL systems and populations. We conducted a retrospective evaluation of three DL systems (CAD4TB, Lunit INSIGHT, and qXR) for detecting TB-associated abnormalities in chest radiographs from outpatients in Nepal and Cameroon. All 1196 individuals received a Xpert MTB/RIF assay and a CXR read by two groups of radiologists and the DL systems. Xpert was used as the reference standard. The area under the curve of the three systems was similar: Lunit (0.94, 95% CI: 0.93–0.96), qXR (0.94, 95% CI: 0.92–0.97) and CAD4TB (0.92, 95% CI: 0.90–0.95). When matching the sensitivity of the radiologists, the specificities of the DL systems were significantly higher except for one. Using DL systems to read CXRs could reduce the number of Xpert MTB/RIF tests needed by 66% while maintaining sensitivity at 95% or better. Using a universal cutoff score resulted different performance in each site, highlighting the need to select scores based on the population screened. These DL systems should be considered by TB programs where human resources are constrained, and automated technology is available. [ABSTRACT FROM AUTHOR]

Background: In Asia, over 50% of patients with symptoms of tuberculosis (TB) access health care from private providers. These patients are usually not notified to the National TB Control Programs, which contributes to low notification rates in many countries.Methods: From January 1, 2011 to December 31, 2012, Karachi's Indus Hospital - a private sector partner to the National TB Programme - engaged 80 private family clinics in its catchment area in active case finding using health worker incentives to increase notification of TB disease. The costs incurred were estimated from the perspective of patients, health facility and the program providing TB services. A Markov decision tree model was developed to calculate the cost-effectiveness of the active case finding as compared to case detection through the routine passive TB centers. Pakistan has a large private health sector, which can be mobilized for TB screening using an incentivized active case finding strategy. Currently, TB screening is largely performed in specialist public TB centers through passive case finding. Active and passive case finding strategies are assumed to operate independently from each other.Results: The incentive-based active case finding program costed USD 223 per patient treated. In contrast, the center based non-incentive arm was 23.4% cheaper, costing USD 171 per patient treated. Cost-effectiveness analysis showed that the incentive-based active case finding program was more effective and less expensive per DALY averted when compared to the baseline passive case finding as it averts an additional 0.01966 DALYs and saved 15.74 US$ per patient treated.Conclusion: Both screening strategies appear to be cost-effective in an urban Pakistan context. Incentive driven active case findings of TB in the private sector costs less and averts more DALYs per health seeker than passive case finding, when both alternatives are compared to a common baseline situation of no screening. [ABSTRACT FROM AUTHOR]

Background:The potential population-level impact of private-sector initiatives for tuberculosis (TB) case finding in Southeast Asia remains uncertain. In 2011, the Indus Hospital TB Control Program in Karachi, Pakistan, undertook an aggressive case-finding campaign that doubled notification rates, providing an opportunity to investigate potential population-level effects. Methods:We constructed an age-structured compartmental model of TB in the intervention area. We fit the model using field and literature data, assuming that TB incidence equaled the estimated nationwide incidence in Pakistan (primary analysis), or 1.5 times greater (high-incidence scenario). We modeled the intervention as an increase in the rate of formal-sector TB diagnosis and evaluated the potential impact of sustaining this rate for five years. Results:In the primary analysis, the five-year intervention averted 24% (95% uncertainty range, UR: 18-30%) of five-year cumulative TB cases and 52% (95% UR: 45-57%) of cumulative TB deaths. Corresponding reductions in the high-incidence scenario were 12% (95% UR: 8-17%) and 27% (95% UR: 21-34%), although the absolute number of lives saved was higher. At the end of five years, TB notification rates in the primary analysis were below their 2010 baseline, incidence had dropped by 45%, and annual mortality had fallen by 72%. About half of the cumulative impact on incidence and mortality could be achieved with a one-year intervention. Conclusions:Sustained, multifaceted, and innovative approaches to TB case-finding in Asian megacities can have substantial community-wide epidemiological impact. [ABSTRACT FROM AUTHOR]