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Abstract 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 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

Abstract 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.

COVID-19 significantly disrupted tuberculosis (TB) services in Vietnam. In response, the National TB Program (NTP) integrated TB screening using mobile chest X-rays into COVID-19 vaccination events. This prospective cohort study evaluated the integrated model’s yield, treatment outcomes, and costs. We further fitted regressions to identify risk factors and conduct interrupted time-series analyses in the study area, Vietnam’s eight economic regions, and at the national level. At 115 events, we conducted 48,758 X-ray screens and detected 174 individuals with TB. We linked 89.7% to care, while 92.9% successfully completed treatment. The mean costs per person diagnosed with TB was $547. TB risk factors included male sex (aOR = 6.44, p < 0.001), age of 45–59 years (aOR = 1.81, p = 0.006) and ≥60 years (aOR = 1.99, p = 0.002), a history of TB (aOR = 7.96, p < 0.001), prior exposure to TB (aOR = 3.90, p = 0.001), and symptomatic presentation (aOR = 2.75, p < 0.001). There was a significant decline in TB notifications during the Delta wave and significant increases immediately after lockdowns were lifted (IRR(γ1) = 5.00; 95%CI: (2.86, 8.73); p < 0.001) with a continuous upward trend thereafter (IRR(γ2) = 1.39; 95%CI: (1.22, 1.38); p < 0.001). Similar patterns were observed at the national level and in all regions but the northeast region. The NTP’s swift actions and policy decisions ensured continuity of care and led to the rapid recovery of TB notifications, which may serve as blueprint for future pandemics.

Abstract Background Many tuberculosis (TB) patients incur catastrophic costs. Active case finding (ACF) may have socio-protective properties that could contribute to the WHO End TB Strategy target of zero TB-affected families suffering catastrophic costs, but available evidence remains limited. This study measured catastrophic cost incurrence and socioeconomic impact of an episode of TB and compared those socioeconomic burdens in patients detected by ACF versus passive case finding (PCF). Methods This cross-sectional study fielded a longitudinal adaptation of the WHO TB patient cost survey alongside an ACF intervention from March 2018 to March 2019. The study was conducted in six intervention (ACF) districts and six comparison (PCF) districts of Ho Chi Minh City, Viet Nam. Fifty-two TB patients detected through ACF and 46 TB patients in the PCF cohort were surveyed within two weeks of treatment initiation, at the end of the intensive phase of treatment, and after treatment concluded. The survey measured income, direct and indirect costs, and socioeconomic impact based on which we calculated catastrophic cost as the primary outcome. Local currency was converted into US$ using the average exchange rates reported by OANDA for the study period (VNĐ1 = US$0.0000436, 2018–2019). We fitted logistic regressions for comparisons between the ACF and PCF cohorts as the primary exposures and used generalized estimating equations to adjust for autocorrelation. Results ACF patients were poorer than PCF patients (multidimensional poverty ratio: 16 % vs. 7 %; p = 0.033), but incurred lower median pre-treatment costs (US$18 vs. US$80; p

Abstract Background Vietnam has a high burden of undetected tuberculosis (TB). The Vietnamese National TB Strategic Plan highlights active case-finding (ACF) as one strategy to find people with TB who are currently unreached by the existing government health services. The IMPACT TB (Implementing proven community-based active TB case-finding intervention) project was implemented across six districts of Ho Chi Minh City, 2017–2019. We aimed to explore the facilitators and barriers for ACF implementation during the IMPACT TB project to understand how and why the intervention achieved high yields. Methods This was an exploratory qualitative study based on 39 semi-structured key-informant interviews with TB patients who were diagnosed through ACF, employees and volunteers who implemented ACF, and leaders from district, national, or international institutions and organizations in Vietnam. Thematic analysis was applied, using an implementation science framework by Grol and Wensing. Results We generated three main themes: (1) the studied ACF model used in Vietnam provided a conducive social and organizational context for ACF implementation with areas for improvement, including communication and awareness-raising, preparation and logistics, data systems and processes, and incentives; (2) employees and volunteers capitalized on their strengths to facilitate ACF implementation, e.g., experience, skills, and communication; and (3) employees and volunteers were in a position to address patient-level barriers to ACF implementation, e.g., stigma, discrimination, and mistrust. These themes covered a variety of facilitators and barriers, which we divided into 17 categories. All categories were mentioned by employees and volunteers, except the category of having a network that facilitates ACF implementation, which was only mentioned by volunteers. This study also highlighted examples and ideas of how to address facilitators and barriers. Conclusions IMPACT TB provided a favorable social and organizational context for ACF implementation. Individual employees and volunteers still determined the success of the project, as they had to be able to capitalize on their own strengths and address patient-level barriers. Volunteers especially used their networks to facilitate ACF. Knowledge of both facilitators and barriers, and how to address them can inform the planning and implementation ACF in Vietnam and similar contexts across low- and middle-income countries worldwide.

Abstract Background In order to end tuberculosis (TB), it is necessary to expand coverage of TB care services, including systematic screening initiatives. However, more evidence is needed for groups among whom systematic screening is only conditionally recommended by the World Health Organization. This study evaluated concurrent screening in multiple target groups using community health workers (CHW). Methods In our two-year intervention study lasting from October 2017 to September 2019, CHWs in six districts of Ho Chi Minh City, Viet Nam verbally screened three urban priority groups: (1) household TB contacts; (2) close TB contacts; and (3) residents of urban priority areas without clear documented exposure to TB including hotspots, boarding homes and urban slums. Eligible persons were referred for further screening with chest radiography and follow-on testing with the Xpert MTB/RIF assay. Symptomatic individuals with normal or without radiography results were tested on smear microscopy. We described the TB care cascade and characteristics for each priority group, and calculated yield and number needed to screen. Subsequently, we fitted a mixed-effect logistic regression to identify the association of these target groups and secondary patient covariates with TB treatment initiation. Results We verbally screened 321 020 people including 24 232 household contacts, 3182 social and close contacts and 293 606 residents of urban priority areas. This resulted in 1138 persons treated for TB, of whom 85 were household contacts, 39 were close contacts and 1014 belonged to urban priority area residents. The yield of active TB in these groups was 351, 1226 and 345 per 100 000, respectively, corresponding to numbers needed to screen of 285, 82 and 290. The fitted model showed that close contacts [adjusted odds ratio (aOR) = 2.07; 95% CI: 1.38–3.11; P

Abstract Background To achieve the WHO End TB Strategy targets, it is necessary to detect and treat more people with active TB early. Scale–up of active case finding (ACF) may be one strategy to achieve that goal. Given human resource constraints in the health systems of most high TB burden countries, volunteer community health workers (CHW) have been widely used to economically scale up TB ACF. However, more evidence is needed on the most cost-effective compensation models for these CHWs and their potential impact on case finding to inform optimal scale-up policies. Methods We conducted a two-year, controlled intervention study in 12 districts of Ho Chi Minh City, Viet Nam. We engaged CHWs as salaried employees (3 districts) or incentivized volunteers (3 districts) to conduct ACF among contacts of people with TB and urban priority groups. Eligible persons were asked to attend health services for radiographic screening and rapid molecular diagnosis or smear microscopy. Individuals diagnosed with TB were linked to appropriate care. Six districts providing routine NTP care served as control area. We evaluated additional cases notified and conducted comparative interrupted time series (ITS) analyses to assess the impact of ACF by human resource model on TB case notifications. Results We verbally screened 321,020 persons in the community, of whom 70,439 were eligible for testing and 1138 of them started TB treatment. ACF activities resulted in a + 15.9% [95% CI: + 15.0%, + 16.7%] rise in All Forms TB notifications in the intervention areas compared to control areas. The ITS analyses detected significant positive post-intervention trend differences in All Forms TB notification rates between the intervention and control areas (p = 0.001), as well as between the employee and volunteer human resource models (p = 0.021). Conclusions Both salaried and volunteer CHW human resource models demonstrated additionality in case notifications compared to routine case finding by the government TB program. The salaried employee CHW model achieved a greater impact on notifications and should be prioritized for scale-up, given sufficient resources.

Abstract Background Tuberculosis (TB) remains a major cause of avoidable deaths. Economic migrants represent a vulnerable population due to their exposure to medical and social risk factors. These factors expose them to higher risks for TB incidence and poor treatment outcomes. Methods This cross-sectional study evaluated WHO-defined TB treatment outcomes among economic migrants in an urban district of Ho Chi Minh City, Viet Nam. We measured the association of a patient’s government-defined residency status with treatment success and loss to follow-up categories at baseline and performed a comparative interrupted time series (ITS) analysis to assess the impact of community-based adherence support on treatment outcomes. Key measures of interest of the ITS were the differences in step change (β6) and post-intervention trend (β7). Results Short-term, inter-province migrants experienced lower treatment success (aRR = 0.95 [95% CI: 0.92–0.99], p = 0.010) and higher loss to follow-up (aOR = 1.98 [95% CI: 1.44–2.72], p 55 years of age (aRR = 0.93 [95% CI: 0.89–0.96], p

BackgroundIn the last decade, active case finding (ACF) strategies for tuberculosis (TB) have been implemented in many diverse settings, with some showing large increases in case detection and reporting at the sub-national level. There have also been several studies which seek to provide evidence for the benefits of ACF to individuals and communities in the broader context. However, there remains no quantification of the impact of ACF with regards to reducing the burden of transmission. We sought to address this knowledge gap and quantify the potential impact of active case finding on reducing transmission of TB at the national scale and further, to determine the intensification of intervention efforts required to bring the reproduction number (R0) below 1 for TB.MethodsWe adopt a dynamic transmission model that incorporates heterogeneity in risk to TB to assess the impact of an ACF programme (IMPACT TB) on reducing TB incidence in Vietnam and Nepal. We fit the models to country-level incidence data using a Bayesian Markov Chain Monte Carlo approach. We assess the impact of ACF using a parameter in our model, which we term the treatment success rate. Using programmatic data, we estimate how much this parameter has increased as a result of IMPACT TB in the implementation districts of Vietnam and Nepal and quantify additional efforts needed to eliminate transmission of TB in these countries by 2035.ResultsExtending the IMPACT TB programme to national coverage would lead to moderate decreases in TB incidence and would not be enough to interrupt transmission by 2035. Decreasing transmission sufficiently to bring the reproduction number (R0) below 1, would require a further intensification of current efforts, even at the sub-national level.ConclusionsActive case finding programmes are effective in reducing TB in the short term. However, interruption of transmission in high-burden countries, like Vietnam and Nepal, will require comprehensive incremental efforts. Complementary measures to reduce progression from infection to disease, and reactivation of latent infection, are needed to meet the WHO End TB incidence targets.

BackgroundThe 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.MethodsWe 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.ResultsA 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.ConclusionPrivate 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.

Background: Cambodia has one of the highest tuberculosis (TB) prevalence rates in the world. People aged 55 years and over account for an estimated 50% of the country's TB burden, yet this group has a low notification rate owing to specific barriers in accessing health services. One-off active case finding (ACF) days with mobile GeneXpert and X-ray systems were organized at 75 government health facilities in four operational districts. Symptomatic community members with an abnormal chest X-ray were tested using the Xpert MTB/RIF assay. People with TB were then treated at health facilities after screening services moved onto the next site. Methods: De-identified project data were analysed to produce descriptive statistics about the people tested on Xpert and those diagnosed with TB. A linear regression was fit through the 12 quarters of National TB Program (NTP) TB case notification data immediately prior to ACF. The regression was used to calculate trend-expected notifications during and after the ACF quarters. Notifications from the ACF quarters were then compared to actual notifications from the previous year and to the trend-expected notifications during the ACF quarter by age group and type of TB. Finally, NTP TB treatment outcomes for the patients started on treatment during the ACF quarter were compared to those from a year prior. Results: 2068 individuals submitted sputum for Xpert MTB/RIF testing, resulting in the identification of 319 (15.4%) bacteriologically-positive TB patients and an additional 574 people who were clinically diagnosed with TB. In the ACF quarters, new bacteriologically-positive notifications increased +119.2% for all ages and +262.7% for people aged 55 and over compared with trend-expected notifications. Treatment initiation figures remained above trend-expected notifications for three full quarters after ACF. The treatment success rate across all operational districts was significantly higher for patients detected in the ACF quarters (88.8% vs 94.5%, p = 0.012). Conclusion: A series of roving, one-off ACF days at government health facilities were able to increase TB diagnosis, treatment initiation and treatment outcomes in a key population with high TB prevalence. Targeted ACF interventions such as this could be used to reduce a backlog of untreated, prevalent TB. Keywords: Tuberculosis, Active case finding, Elderly, Chest X-ray, Xpert, GeneXpert

To accelerate the reduction in tuberculosis (TB) incidence, it is necessary to optimize the use of innovative tools and approaches available within a local context. This study evaluated the use of an existing network of community health workers (CHW) for active case finding, in combination with mobile chest X-ray (CXR) screening events and the expansion of Xpert MTB/RIF testing eligibility, in order to reach people with TB who had been missed by the current system. A controlled intervention study was conducted from January 2018 to March 2019 in five intervention and four control districts of two low to medium TB burden cities in Viet Nam. CHWs screened and referred eligible persons for CXR to TB care facilities or mobile screening events in the community. The initial diagnostic test was Xpert MTB/RIF for persons with parenchymal abnormalities suggestive of TB on CXR or otherwise on smear microscopy. We analyzed the TB care cascade by calculating the yield and number needed to screen (NNS), estimated the impact on TB notifications and conducted a pre-/postintervention comparison of TB notification rates using controlled, interrupted time series (ITS) analyses. We screened 30,336 individuals in both cities to detect and treat 243 individuals with TB, 88.9% of whom completed treatment successfully. All forms of TB notifications rose by +18.3% (95% CI: +15.8%, +20.8%). The ITS detected a significant postintervention step-increase in the intervention area for all-form TB notification rates (IRR(β6) = 1.221 (95% CI: 1.011, 1.475); p = 0.038). The combined use of CHWs for active case findings and mobile CXR screening expanded the access to and uptake of Xpert MTB/RIF testing and resulted in a significant increase in TB notifications. This model could serve as a blueprint for expansion throughout Vietnam. Moreover, the results demonstrate the need to optimize the use of the best available tools and approaches in order to end TB.

Under-detection and -reporting in the private sector constitute a major barrier in Viet Nam’s fight to end tuberculosis (TB). Effective private-sector engagement requires innovative approaches. We established an intermediary agency that incentivized private providers in two districts of Ho Chi Minh City to refer persons with presumptive TB and share data of unreported TB treatment from July 2017 to March 2019. We subsidized chest x-ray screening and Xpert MTB/RIF testing, and supported test logistics, recording, and reporting. Among 393 participating private providers, 32.1% (126/393) referred at least one symptomatic person, and 3.6% (14/393) reported TB patients treated in their practice. In total, the study identified 1203 people with TB through private provider engagement. Of these, 7.6% (91/1203) were referred for treatment in government facilities. The referrals led to a post-intervention increase of +8.5% in All Forms TB notifications in the intervention districts. The remaining 92.4% (1112/1203) of identified people with TB elected private-sector treatment and were not notified to the NTP. Had this private TB treatment been included in official notifications, the increase in All Forms TB notifications would have been +68.3%. Our evaluation showed that an intermediary agency model can potentially engage private providers in Viet Nam to notify many people with TB who are not being captured by the current system. This could have a substantial impact on transparency into disease burden and contribute significantly to the progress towards ending TB.