OBJECTIVES:A pooled testing algorithm for tuberculosis (TB), in which sputum specimens from multiple individuals are tested in pools with individual testing of positive pools, can optimize diagnostic resources. This study evaluated the diagnostic accuracy and cartridge savings of pooled testing with the Xpert MTB/RIF Ultra assay (Xpert-Ultra) versus individual Xpert-Ultra testing. METHODS:We conducted a cross-sectional study among 2396 adults (≥15 years) with presumptive TB enrolled between July 2024 and February 2025, through facility-based case finding (FBCF) and community-based case finding (CBCF). Participants submitted two sputum specimens. The first underwent individual Xpert-Ultra testing; remnant specimens were combined into 4-specimen pools (0.5 mL per specimen; total 2 mL) and retested using Xpert-Ultra. The second specimen was used to inoculate liquid culture (BACTEC MGIT). Data were used to simulate an upfront pooled testing strategy; sensitivity and specificity were estimated against culture, and cartridge use was compared with individual Xpert-Ultra testing. RESULTS:Of 2396 participants, 395 (16.5%) had a positive Xpert-Ultra and/or culture, including 360 of 912 (39.5%) in FBCF and 35 of 1484 (2.4%) in CBCF. The pooled testing approach had sensitivity of 82.4% (95% confidence interval [CI], 77.9-86.3) and specificity of 98.5% (97.8-99.0) compared with culture, with lower sensitivity than individual Xpert-Ultra testing (86.5%, 82.4-89.9) but high specificity (98.1%, 97.4-98.7). Sensitivity of pooled testing was lower in CBCF (59.1%, 36.4-79.3) than in FBCF (84.0%, 79.5-87), whereas cartridge savings were greater in CBCF (69.1% vs. 9.6%). The pooling strategy reduced Xpert-Ultra cartridge use by 46.5%, saving USD 14 447. CONCLUSIONS:Pooled Xpert-Ultra testing among adults appears resource-efficient for TB screening in Vietnam. As sensitivity is lower than individual Xpert-Ultra testing, particularly for paucibacillary disease, these losses should be carefully weighed against gains in affordability and expanded access to molecular testing. Careful, context-specific implementation is essential to maximize programmatic benefit while minimizing missed persons with TB.

Background: Vietnam is a top 20 burden country for multi-drug resistant/rifampicin-resistant tuberculosis (MDR/RR-TB), with nearly 10,000 cases a year. With the emergence of new diagnostic assays for M. tuberculosis and resistance, along with new drugs for both treatment and prevention, we sought to better understand the molecular epidemiology of RR-TB in this high-burden setting, through the study of clinical trial isolates from the VQUIN MDR trial. Methods: We assembled a sample of cultured isolates, collected from patients with confirmed RR-M. tuberculosis within 10 provinces, enriching for isolates from outside of the 2 major cities, Hanoi and Ho Chi Minh City. We subjected these isolates whole genome sequencing (WGS) and bioinformatic analysis, with a subset subject to phenotypic drug susceptibility testing to evaluate phenotypic/genotypic concordance. New genome sequences were phylogenetically contextualised to publicly-available M. tuberculosis genome sequences sampled in Vietnam from National Center for Biotechnology Information (NCBI) Sequence Read Archives (SRA). Results: Isolates from 252 RR-TB cases passed quality controls and were available for analysis. Xpert MTB/RIF had a high concordance with WGS-based rifampicin-resistance prediction (PPV=96.8%). Of the 244 isolates confirmed to be rifampicin resistant, a high proportion (235/244 = 96.3%) had mutations associated with resistance to at least one other first- or second-line antibiotic. Phenotypic drug susceptibility testing (DST) for rifampicin, isoniazid, and levofloxacin was completed for 77 isolates with a high concordance demonstrated between DST and genomic-based resistance predictions (67/77, 87.0% RIF; 76/77, 98.7% INH; 73/77, 94.8%LFX). High concordance was also observed with new and repurposed antibiotics linezolid (100%, 60/60), pretomanid (100%, 60/60), and bedaquiline (56/60, 93.3%). Rifampicin-resistant strains were more likely to be lineage 2.2.1, compared to rifampicin-susceptible M. tuberculosis strains in Vietnam, particularly in the major cities. Conclusions: The high prevalence of secondary drug-resistance beyond RIF and INH, along with the dominance of one major lineage across geographic regions, provides insights on the spread of MDR/RR-TB in Vietnam and reinforces the importance of prompt and broad detection of drug-resistance to inform the timely initiation of effective drug regimens. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial CTRN12616000215426 ### Funding Statement This project was funded by a National Health and Medical Research Council (NHMRC) Project Grant (1081443) to GJF and a Foundation Grant from the Canadian Institutes for Health research (CIHR) to MAB (FDN 148362). GJF was supported by a NHMRC Leadership Fellowship (2007920). ELM was supported by a CIHR Fellowship (472823). MAB was supported by a Tier 1 Canada Research Chair. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics for our study was provided by the research institute of the McGill University Health Centre Institutional Review Board (2021-7242) Ethics for the VQUIN clinical trial was provided by Australia New Zealand Clinical Trials Registry number (CTRN12616000215426). HREC approval was from Human Research Ethics Committee of the University of Sydney (2014/929) Institutional Review Board at the Ministry of Health Vietnam (4040/QD-BYT). The VQUIN follow-up study was added as an amendment to USYD HREC (2014/929), as well as Institutional Review Board at the Ministry of Health of Vietnam (4640/QD-BYT and 94/CN-HDDD). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Background: Mobile health has been increasingly integrated into tuberculosis care to support patient education, communication, and treatment engagement. However, evidence remains limited regarding whether positive engagement with mHealth is associated with knowledge, attitudes, and practices among patients with multidrug-resistant tuberculosis. This study aimed to examine the association between positive mHealth engagement and knowledge, attitude, practice, and total KAP among patients with multidrug-resistant tuberculosis, and to evaluate the psychometric properties of the engagement score used as the primary exposure variable. Methods: A cross-sectional study was conducted among patients with multidrug-resistant tuberculosis. A positive mHealth engagement score was constructed from 12 mHealth-related items after harmonizing item directionality so that higher scores indicated more favorable engagement. The 12 items reflected five behavioural domains: intensity of use, ease and acceptability of use, functional engagement (communication with providers, access to health information, and perceived benefit for disease self-management), continuity of use, and barriers to sustained engagement. The composite score was computed as the mean of the 12 standardised items, with higher values indicating more positive engagement. Internal consistency was assessed using Cronbach's alpha and corrected item-total correlations, and structural validity was explored using principal component analysis. Adjusted linear regression models were used to examine associations between the engagement score and Knowledge, Attitude, Practice, and total KAP scores, controlling for age, sex, and occupation. Sensitivity analyses were performed after excluding a poorly performing item, and tertile analyses were used to assess dose-response patterns. Results: The positive mHealth engagement score showed good internal consistency, with a Cronbach's alpha of 0.852. One item demonstrated poor psychometric performance, and Cronbach's alpha increased to 0.864 after its exclusion. The data were suitable for dimensionality assessment, with a Kaiser-Meyer-Olkin value of 0.870 and a significant Bartlett's test. Principal component analysis identified a dominant first component explaining 43.29% of the total variance. Using the refined score, higher positive mHealth engagement was significantly associated with higher Knowledge scores (β = 2.06; 95% CI: 1.28-2.85; p < 0.001), higher Attitude scores (β = 4.68; 95% CI: 3.30-6.06; p < 0.001), and higher total KAP scores (β = 6.68; 95% CI: 4.62-8.74; p < 0.001), whereas no significant association was observed for the Practice score (β = -0.07; 95% CI: -0.63 to 0.49; p = 0.804). In tertile analyses, Knowledge, Attitude, and total KAP scores increased significantly across engagement levels, while Practice scores did not. Conclusions: Positive mHealth engagement was associated with better knowledge, attitudes, and overall KAP among patients with multidrug-resistant tuberculosis, but not with practice. These findings are associative; the cross-sectional design does not permit causal conclusions. The engagement score demonstrated good reliability and acceptable structural validity and may be a useful summary measure for evaluating patient interaction with mHealth interventions in tuberculosis care. Integrated strategies combining mHealth with clinical follow-up, adherence counseling, and structural support may be needed to translate informational and attitudinal gains into practice change.

BackgroundMobile health (mHealth) interventions have shown promise in supporting tuberculosis care, but their association with patient knowledge, attitudes, and practices (KAP) among people with multidrug-resistant tuberculosis (MDR-TB) remains poorly evaluated in high-burden, programmatic settings. We assessed the association between a smartphone-based mHealth application and KAP regarding treatment adherence and adverse events within the V-SMART randomised controlled trial in Vietnam.MethodsThis nested cross-sectional study included 528 patients with MDR-TB (278 intervention, 250 control) enrolled across seven provinces in Vietnam between 2023 and 2025. KAP was measured using a validated questionnaire (Knowledge 0–17, Attitude 0–44, Practice 0–19, total 0–80). Multivariable linear regression adjusted for age, sex, province, education, time on treatment, PHQ-9, stigma, and social support. Dose-response relationships with self-reported app usage were examined in the intervention arm.ResultsThe mHealth intervention was associated with higher total KAP scores (adjusted mean difference 5.0 points, 95% CI 3.3–6.7, p<0.001), with largest gains in practice (+2.2 points) and knowledge (+1.1 points). Clear dose-response relationships were observed: each additional month of app use was associated with a 0.81-point increase in total KAP score (p<0.001).ConclusionThe smartphone-based mHealth intervention was associated with meaningfully higher KAP scores among MDR-TB patients in Vietnam. These findings support integration of mHealth tools into routine programmatic management of drug-resistant tuberculosis in high-burden settings.

Tuberculosis remains a leading public health and socioeconomic challenge in low- and middle-income countries such as Vietnam. Affected households often experience financial hardship, stigma, and psychological distress. Social protection interventions that integrate financial and psychosocial support may address these intersecting challenges. This study will evaluate the effectiveness and implementation of a psycho-socioeconomic support intervention combining conditional cash transfers with peer-led support groups (clubs) to improve tuberculosis treatment outcomes and reduce catastrophic costs. A hybrid type II effectiveness-implementation randomized controlled trial will be conducted in 12 districts across northern, central, and southern Vietnam. Adults with drug-sensitive pulmonary tuberculosis will be individually randomized 1:1 to receive standard of care or the intervention. Data will be collected at the individual, household, and club levels. The co-primary outcomes will include individual-level treatment success and household-level catastrophic cost incurrence. The primary implementation outcome will be club-level fidelity, measured through a composite adherence score. Secondary outcomes will be health-related quality of life, tuberculosis-related stigma, depression, sustainable livelihoods, uptake of tuberculosis-related healthcare services and social health insurance. A mixed-method process evaluation will assess acceptability, participation, quality, and contextual influences. Cost-effectiveness will be assessed. Developed through a people-centered design process, the intervention will target socioeconomic and psychosocial determinants of tuberculosis care. By combining cash transfers and peer support, it will seek to enhance treatment engagement, financial resilience, and equity. Findings will aim to generate actionable evidence for national scale-up in Vietnam and inform policies in other high-burden settings.

Tóm tắt Mục tiêu: Tổng hợp và chia sẻ các phương pháp và bài học cốt lõi có tính nhân rộng trong xây dựng và triển khai Hệ thống điện tử của Quỹ Hỗ trợ Người bệnh Chiến thắng Bệnh lao. Kết quả: Hệ thống điện tử được xây dựng qua các chu kỳ lặp lại gồm thu thập ý kiến người dùng, xây dựng, thử nghiệm bản mẫu với người dùng, phát triển phần mềm, và thí điểm. Chúng tôi đưa ra 4 đề xuất có khả năng nhân rộng với các dự án chuyển đổi số (CĐS) khác trong lĩnh vực y tế: (1) áp dụng phương pháp thiết kế lấy con người làm trung tâm (TKLCNLTT) trong quá trình phát triển công cụ số và xác định rõ “bài toán” công cụ số sẽ giải quyết, (2) đảm bảo công cụ số được phát triển theo định hướng chung của quốc gia, (3) phân tích và điều chỉnh quy trình làm việc để phát huy tối đa hiệu quả của công cụ, (4) tham khảo và vận dụng các hướng dẫn và tiêu chuẩn toàn cầu trong triển khai y tế số. Kết luận: CĐS trong lĩnh vực y tế nên ưu tiên TKLCNLTT trong suốt quá trình xây dựng và triển khai. Các hoạt động xây dựng công cụ số nên cân nhắc từ sớm và áp dụng các nguyên tắc TKLCNLTT để có thể tạo ra các sản phẩm mang tính bền vững và hữu ích cho người dùng.

Background Tuberculosis-related stigma remains a substantial psychosocial burden among patients with multidrug-resistant tuberculosis, particularly in resource-constrained settings where prolonged treatment, social vulnerability, and barriers to care may further compromise well-being and engagement with health services. Stigma may adversely affect patients’ treatment experience, healthcare-seeking behavior, and continuity of care. This study aimed to assess perceived stigma and examine its association with tuberculosis-related knowledge, attitudes, and practices among patients with multidrug-resistant tuberculosis in Vietnam. Methods We conducted a cross-sectional study among 528 patients with multidrug-resistant tuberculosis in Vietnam. Perceived stigma was assessed using the Van Rie tuberculosis stigma scale. Knowledge, attitude, and practice scores were derived from structured questionnaire items. Spearman correlation analysis was used to assess bivariate associations between stigma and the knowledge, attitude, and practice domains. Multivariable linear regression was performed to identify factors independently associated with stigma. Results The mean age of participants was 42.61 years (standard deviation, 13.62), and 68.8% were male. The mean stigma score was 23.68 (standard deviation, 4.30), with a median of 24.0 and an interquartile range of 21.0-27.0, indicating a considerable burden of perceived stigma. In bivariate analysis, stigma was inversely correlated with knowledge score (rho = -0.095, p = 0.030), attitude score (rho = -0.270, p < 0.001), and total knowledge-attitude-practice score (rho = -0.192, p < 0.001), while the correlation with practice score was not statistically significant (rho = 0.081, p = 0.064). In multivariable analysis, a higher attitude score remained independently associated with lower stigma (beta = -0.229, 95% confidence interval: -0.306 to -0.153, p < 0.001), whereas knowledge and practice scores were not independently associated with stigma. Being on treatment was also associated with lower stigma (beta = -1.966, 95% confidence interval: -2.716 to -1.216, p < 0.001). Conclusions Patients with multidrug-resistant tuberculosis in Vietnam experienced a considerable burden of perceived stigma. More favorable tuberculosis-related attitudes were independently associated with lower stigma, underscoring the importance of integrating stigma reduction, psychosocial support, and patient-centered educational interventions into multidrug-resistant tuberculosis care. Such approaches may help improve treatment experience and strengthen sustained engagement in care, particularly in settings facing persistent social and health-system challenges.

Abstract Background Tuberculosis (TB) remains the leading cause of death from an infectious disease globally, yet financing for the TB response continues to fall far short of identified needs. Decisions about how resources are allocated are often made with limited engagement of people directly affected by TB, potentially overlooking lived experiences and community-defined priorities. This study was implemented in Viet Nam to align future TB investments with community-defined priorities and programmatic feasibility. This paper describes the process and its application to priority setting and intervention selection alongside national planning processes. Methods This was a participatory co-design study guided by a people-centered design framework. The process integrated qualitative data collection and deliberative stakeholder engagement across three phases: Discover (qualitative interviews and focus groups to identify challenges), Define (stakeholder workshops to prioritize challenges and co-develop an evaluation framework), and Develop (structured prioritization assessment and selection of an intervention). In the Discover phase, 88 participants identified challenges across the TB care cascade. In the Define and Develop phases, decision-making was overseen by a diverse 21-member Leadership Group. Participants co-developed an evaluation framework across three domains (fit and desirability, potential impact, and feasibility), which was used to assess and rank potential investment opportunities. Facilitation strategies, including equal voting rights and anonymous ranking, were applied to promote equitable participation. Results In the Discover phase, 15 key challenges across the TB care cascade were identified and reframed as opportunities for improvement. In the Define phase, stakeholders applied the evaluation framework to assess 19 innovation categories. Three intervention areas were shortlisted for detailed consideration: computer-aided detection software for chest X-ray interpretation, paper-free data systems, and social and financial protection. In the Develop phase, structured scoring and deliberation, including consideration of feasibility and the existing funding landscape, led to the selection of social and financial protection as the intervention for near-term investment and implementation. Conclusions Participatory co-design enabled TB-affected people and health system stakeholders to directly contribute to early-stage investment prioritization within Viet Nam’s TB response. The selection of social and financial protection reflects both lived economic challenges and system-level considerations, highlighting the value of participatory approaches in identifying locally relevant priorities that may be underemphasized in conventional funding processes.

Patient knowledge is a key component of multidrug-resistant tuberculosis (MDR-TB) care, particularly forunderstanding treatment duration and recognizing adverse effects. However, evidence on treatment-related knowledgeamong patients with MDR-TB in Vietnam remains limited. We assessed item-level knowledge and explored demographicfactors related to selected knowledge outcomes among patients receiving MDR-TB care in Vietnam during 2023-2024.In this cross-sectional study, 250 patients completed a 17-item knowledge questionnaire covering disease definition,treatment adherence and adverse effects. Item-level performance was summarized using the proportion of correctresponses, and logistic regression was used to examine associations between demographic characteristics and selectedlow-performing items, as well as an overall binary good knowledge outcome. Knowledge varied across domains. Higherproportions of correct responses were observed for items related to disease transmission, treatment failure, and someadverse effects, including digestive, ocular, and auditory symptoms. Lower performance was found for the definition ofMDR-TB and for selected treatment toxicity items, particularly peripheral neuropathy and musculoskeletal side effects.In exploratory regression analyses, female participants had higher estimated odds of correct responses on selected itemsand of good overall knowledge than male participants, although these differences were not statistically significant. Inthe adjusted model, participants aged 30–60 years had significantly lower estimated odds of good knowledge comparedto those under 30 years (OR = 0.3, 95% CI: (0.12–0.90), p = 0.030). These findings highlight core disease concepts andtreatment-related adverse effects as priority topics for patient counseling in MDR-TB care

BACKGROUND:High-dose rifampicin could potentially shorten tuberculosis preventive therapy (TPT) and improve outcomes. We aimed to characterize population pharmacokinetics of standard- and high-dose rifampicin for TPT among individuals with tuberculosis infection. METHODS:Intensive and sparse pharmacokinetic substudies were conducted in Indonesia, Canada, and Vietnam within the 2R2 randomized trial, which compared 2 months of high-dose rifampicin at 20 mg/kg/day (2R20) or 30 mg/kg/day (2R30) with 4 months of standard-dose rifampicin at 10 mg/kg/day (4R10) in adults and adolescents aged ≥ 10 years. Venous blood samples were collected after 4 weeks of treatment. Rifampicin pharmacokinetics were analyzed using nonlinear mixed-effects modeling in NONMEM. RESULTS:Among 1368 trial participants, 440 were included in model development (51 intensive and 389 sparse sampling), with 191 (43%) assigned to 4R10, 159 (36%) to 2R20, and 90 (20%) to 2R30. A 1-compartment model with saturable hepatic extraction and transit-compartment absorption best described rifampicin pharmacokinetics. All disposition parameters were allometrically scaled using fat-free mass. Country-specific differences, particularly variation in drug formulation, were associated with lower bioavailability in Canada {-21.8% (95% confidence interval [CI] -27.9 to -18.0%)} and Vietnam (-12.3% [95% CI -17.7 to -7.9%]) compared with Indonesia. The 24-hour area under the concentration-time curve increased more than proportionally with dose and was higher across treatment arms in Indonesia, followed by Vietnam and Canada. CONCLUSIONS:High-dose rifampicin for TPT resulted in greater-than-proportional increases in exposure due to nonlinear clearance at higher doses. Substantial between-country variability in exposure was observed, which may have been due to multiple factors, including differences in country-specific formulations, fat-free mass, and unmeasured confounders.

The health-related quality of life (QoL) assessed by the 12-item Short Form (SF-12) offers a time-efficient alternative to the 36-item version 2 (SF-36 v2). This study aimed to compare the performance of SF-12 and SF-36 v2 among patients with rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) in Vietnam. A cross-sectional survey was conducted among RR/MDR-TB patients treated in seven provinces between October 2020 and March 2023. Participants completed the SF-36 v2 questionnaire at enrollment. Physical (PCS) and mental component summary (MCS) scores were compared between SF-12 and SF-36 v2. Linear regression assessed the ability of PCS-12 and MCS-12 to predict PCS-36 and MCS-36. Discriminative ability was assessed via receiver operating characteristic (ROC) curves. This study included 565 participants with a median age of 45.4 years (IQR 44.2–46.5) and a male proportion of 71.7

BACKGROUND:Existing rates of death and recurrent tuberculosis (TB) among people treated for rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB) are likely underestimates. We determined long-term disease outcomes among a cohort of people treated for RR/MDR-TB. METHODS:We conducted a prospective cohort study among patients treated by the National TB Program (NTP) in 10 provinces of Vietnam. Individuals with confirmed RR/MDR-TB starting World Health Organization-recommended regimens were followed up for ≥32 months. After this period, we surveyed the cohort to measure vital status and subsequent TB episodes. Family members completed verbal autopsies for deceased participants. We calculated rates of mortality and TB re-occurrence, and standardized mortality ratio (SMR) using participants' household contacts as a reference population. RESULTS:Between March 2016 and July 2020, 1755 patients were enrolled, of whom we assessed 1364 (77.7%) at final follow-up. Median follow-up time was 4.3 years. Successful treatment outcomes were reported for 1357/1755 (77.3%) individuals. From enrollment until end of follow-up, 289 participants died (16.5%; mortality rate, 42.6/1000 person-years); overall SMR was 5.6 and post-treatment SMR was 3.0. Tuberculosis was the probable or confirmed cause of death in 96 deceased participants. Many (71/165; 43.0%) deaths occurring on-treatment were not reported to the NTP. The rate of subsequent TB episodes among all participants, regardless of treatment outcome, was 10.3/1000 person-years. CONCLUSIONS:RR/MDR-TB survivors have high risks of mortality and re-occurring TB. Programmatic reports underestimate the true mortality rate both during and after treatment. Interventions are urgently needed to strengthen programmatic follow-up, improve treatment outcomes, and monitor for TB recurrence.

BACKGROUND:Tuberculosis (TB) infection is a driver of the global TB epidemic. Accurate, affordable, and simpler diagnostics are crucial for identifying people for preventive therapy. We evaluated the diagnostic performance of the STANDARD F TB-Feron FIA (TB-Feron), a near-point-of-care (POC) assay for detecting TB infection. METHODS:From June to December 2024, we conducted a cross-sectional study at the Vietnam National Lung Hospital, enrolling 352 participants, including 345 eligible participants: 95 with microbiologically confirmed pulmonary TB (Group 1), 200 household contacts of people with pulmonary TB (Group 2), and 50 with a recent history of a negative QFT-Plus result and no known TB exposure (Group 3). Participants were tested with TB-Feron and the reference standard, QuantiFERON TB Gold Plus (QFT-Plus). Results were compared for sensitivity and specificity (primary endpoints), with inter-test agreement (Cohen's κ) and reproducibility (Bland-Altman analysis) as secondary outcomes. RESULTS:Among 345 eligible participants, TB-Feron sensitivity was 88.4% (95% confidence interval [CI] 80.2-94.1) in Group 1, and specificity was 70.0% (55.4-82.1) in Group 3. In Group 2, positive and negative agreements with QFT-Plus were 89.2% (79.8-95.2%) and 75.4% (66.9-82.6), respectively, with inter-test agreement of 80.5% (Cohen's κ=0.6069, P < .0001). Intra-test reproducibility showed no significant differences in IFN-γ levels (mean difference = 2.08 IU/mL, 95% CI -1.28 to 5.44, P = .206). CONCLUSIONS:With high sensitivity, the TB-Feron assay is a potential near-POC alternative to the QFT-Plus assay for diagnosing TB infection, but requires consideration of its suboptimal specificity.

Objective:To determine tuberculosis prevalence among health-care facility patients and to assess the effectiveness of chest radiography in facility-based tuberculosis screening. Methods:Our cross-sectional analysis used individual-level data collected during 2020-2023 from adults presenting at 796 health-care facilities participating in a public-private partnership in 15 provinces of Viet Nam. We constructed tuberculosis care cascades stratified by symptomatic presentation according to the World Health Organization (WHO) four-symptom screening and chest radiography. We reported diagnostic yield, number needed to screen and positivity. Findings:Among 1 423 818 participants, 22 598 had bacteriologically confirmed tuberculosis. Diagnostic yields were 2.2% (19 289/892 894) among symptomatic individuals with cough, 1.0% (1869/191 677) among symptomatic individuals without cough and 0.4% (1440/339 247) among asymptomatic individuals. Tuberculosis-suggestive chest radiograph results compared with normal results increased bacteriologically confirmed positivity by 9.4 percentage points in symptomatic individuals with cough (17.3%; 18 746/108 650 versus 7.9%; 543/6851), by 4.6 percentage points in symptomatic individuals without cough (12.6%; 1748/13 831 versus 8.0%; 121/1515) and by 7.6 percentage points in asymptomatic individuals (15.0%; 1328/8862 versus 7.4%; 112/1511). Without chest radiography, the number of individuals requiring testing to detect tuberculosis among symptomatic individuals with cough and without a cough would have been 6.5 (1 084 571/165 679) and 5.4 (892 894/165 679) times higher, respectively. Conclusion:Chest radiograph screening can reduce the number of expensive molecular tests used in symptomatic patients and enable tuberculosis diagnosis in asymptomatic patients. Future research should analyse cost and cost-effectiveness of using chest radiography in active and intensified case finding.

Abstract Background Tuberculosis (TB) is the archetypal disease of poverty, driven by social determinants and causing catastrophic costs. A 2023 United Nations General Assembly resolution called for all TB-affected people to receive a social benefits package by 2027. Cash transfers have been shown to improve health outcomes; however, operational evidence on their implementation and effectiveness in reducing catastrophic costs due to TB is limited. This pilot study sought to assess the feasibility of delivering cash transfers to people affected by drug-susceptible TB to inform the design of a future trial. Methods A longitudinal, non-randomized cohort study was conducted in Ho Chi Minh City, Vietnam. Half of the participants received unconditional cash transfers (UCTs) while the other half received conditional cash transfers (CCTs) after monthly appointment attendance and completion of 85% of scheduled doses. We analyzed pilot data to assess rates of participant enrollment, adherence and retention in the intervention, TB treatment success, and catastrophic cost incurrence. A 22-day time and motion study quantified the distribution of time pilot staff spent administering the cash transfer intervention by cohort. Results Delivering cash transfers was feasible, with 60/70 (85.7%) and 60/66 (90.9%) of eligible individuals in the CCT and UCT cohorts agreeing to participate, respectively. Only 12.3% of CCT participants had one or more transfers withheld and 5.8% of the total expected CCTs were withheld. Delivering CCTs in the observation period took twice as much time as UCTs (32.4 hours for 43 CCT participants vs. 16.0 hours for 47 UCT participants). There were no significant differences in TB treatment success rates between the cohorts (91.7% CCT vs. 93.3% UCT). Cash transfers caused catastrophic cost incurrence to decline by 12.9% in the CCT cohort (44.2% to 38.5%) and 26.9% in the UCT cohort (26.8% to 19.6%). Conclusions Cash transfers are a feasible way to mitigate the economic burden of TB in Vietnam. The conditionality assessed was not associated with any quantifiable benefits to TB-affected people, and required more effort to implement. A larger trial utilizing similar methods and outcomes is warranted. Our findings inform the design of a slightly modified approach of cash transfer delivery for the larger trial.

OBJECTIVES:Vietnam is a high tuberculosis (TB) and rifampicin-resistant TB (RR-TB) burden country. Different new RR-TB regimens were recommended in recent years. Locally-generated evidence about nationwide implementation of different RR-TB regimens is essential to inform national treatment guidelines. METHODS:A retrospective cohort study of all patients with RR-TB treated nationwide in Vietnam from 2021 to 2022. Short treatment regimens (STR) were 9-11-month standardized 7-drug regimens with either bedaquiline (BDQ_STR) or an injectable drug (inj_STR), and a modified 9-11-month 5-drug regimen (m_STR). Long regimens were 18-20-month regimens for fluoroquinolone-susceptible RR-TB (long RR-TB) or fluoroquinolone-resistant RR-TB (long pre-extensively drug-resistant TB). With logistic regression we estimated predictors of unfavorable outcome. RESULTS:Of 4814 patients with RR-TB, 71.2% had end-of-treatment success. Failure, death, lost-to-follow-up (LTFU) and not evaluated accounted for 3.6%, 7.8%, 13.3%, and 4.2%, respectively. Long RR-TB regimen had significantly higher unfavorable outcomes as compared to BDQ_STR (adjusted odds ratio [95% confidence interval] = 1.56 [1.32-1.84]). Among STR, inj_STR had the lowest success rate (71.8%) in comparison to BDQ_STR (76.2%) (adjusted odds ratio [95% confidence interval] = 1.23 [1.04-1.45]). However, the LTFU rate is still high in both BDQ_STR and inj_STR. Treatment with inj_STR or long RR-TB regimen, retreatment after LTFU, being male and aged ≥50 years were predictors of unfavorable RR-TB treatment outcomes. CONCLUSIONS:During the transition from injectable-containing to all-oral short regimens, nationwide data showed 71.2% RR-TB treatment success in Vietnam. The wider use of STRs and addressing LTFU may further improve outcomes. More robust and better managed long regimens are needed for those not eligible for any STR.

Population-wide screening may accelerate the decline of tuberculosis (TB) incidence, but the optimal screening algorithm and duration must weigh resource considerations. We calibrated a deterministic transmission model to TB epidemiology in Viet Nam. We simulated three population-wide screening algorithms from 2025: sputum nucleic acid amplification tests (NAAT, Xpert MTB/RIF Ultra) only; chest radiography (CXR) followed by NAAT; and CXR-only without microbiological confirmation. We determined the annual screening rounds required to reduce pulmonary TB prevalence below 50 per 100,000 people. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs), representing the additional costs (in US$) per disability-adjusted life year (DALY) averted compared to business-as-usual by 2050. Additionally, we evaluated the impact of NAAT cartridges costing US$1 each. NAAT-based algorithms required at least six rounds to reach the prevalence threshold, while CXR-only required three. NAAT-only achieved a prevalence reduction consistent with the ACT3 trial after three rounds. The CXR+NAAT algorithm averted 4.29m DALYs (95%UI:2.86-6.14) at US$225 (95%UI:85-520) per DALY averted compared with business-as-usual. The front-loaded investment of US$161m (95%UI:111-224) annually during the intervention resulted in average annual cost savings of US$12.7m (95%UI:6.7-21.4) up to 2050 compared to the business-as-usual counterfactual. Reducing the cost of NAAT to US$1 led to a 50% and 15% reduction in budget impact and a 63% and 26% reduction in the estimated ICER for the NAAT-only and CXR+NAAT algorithms, respectively. In Viet Nam, population-wide screening could achieve ambitious policy goals. Substantial front-loaded investment is immediately followed by persistent cost savings and could be further offset by more affordable NAATs.

Individuals exposed to a person with infectious multidrug-resistant or rifampicin-resistant (MDR-RR) tuberculosis are at risk of developing tuberculosis disease. Historically, insufficient empirical evidence for preventive treatment in this group has permitted inadequate guidance for clinical decision making. However, several high-quality studies have been published detailing preventive treatment options for these contacts at high risk. In this Review, we discuss the management of individuals exposed to patients with infectious MDR-RR tuberculosis. We pay particular attention to the entire spectrum of clinical care for this population, including baseline assessment, possible preventive treatments, follow-up, and shared decision making. We discuss the available evidence, the rationales for different management strategies, and the interactions with (and implications of) secondary comorbidities such as HIV or malnutrition.

BACKGROUND:The optimal dosing strategy of linezolid for treating multidrug-resistant and rifampicin-resistant tuberculosis remains unclear. We conducted an individual patient data meta-analysis to determine the optimal linezolid dosing strategy. METHODS:We searched for randomised controlled trials and prospective cohort studies on short-course all‑oral regimens containing linezolid for treating multidrug-resistant and rifampicin-resistant tuberculosis in PubMed, Embase and Scopus up to 31 August 2023. Patients were grouped according to linezolid dosing patterns. Time to treatment success and adverse events of grade 3 and higher were analysed using the Fine-Gray sub-distribution hazard model. RESULTS:Of 12 eligible studies, eight (four randomised controlled trials, four prospective studies) were included. Overall, 945 patients were grouped as follows: group 1 (600 mg·day-1 linezolid for 8 weeks), group 2 (600 mg·day-1 for 16 weeks, then 300 mg·day-1 for 8 weeks), group 3 (600 mg·day-1 for 39 weeks) and group 4 (1200 mg·day-1 for 25 weeks). Proportions of patients achieving treatment success were 59.1%, 90.4%, 91.3% and 96.0%, respectively. Compared with group 2, group 1 (adjusted sub-distribution hazard ratio (SHR) 0.24, 95% CI 0.08-0.71) and group 3 (adjusted SHR 0.36, 95% CI 0.16-0.81) had lower success rates. While group 4 showed no significant difference in treatment success versus group 2 (adjusted SHR 0.57, 95% CI 0.23-1.43), it had a higher rate of adverse events of grade 3 and higher (adjusted SHR 2.29, 95% CI 1.37-3.83). CONCLUSION:A dosing strategy of 600 mg·day-1 linezolid for 16 weeks then 300 mg·day-1 for 8 weeks could be optimal for treating multidrug-resistant and rifampicin-resistant tuberculosis when considering effectiveness and safety.