Prevalence of non-communicable diseases among household contacts of people with tuberculosis: A systematic review and individual participant data meta-analysis.

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.

Pediatric Profound Dengue Shock Syndrome and Use of Point-of-Care Ultrasound During Mechanical Ventilation to Guide Treatment: Single-Center Retrospective Study, 2013-2021.

OBJECTIVES: Profound dengue shock syndrome (DSS) complicated by severe respiratory failure necessitating mechanical ventilation (MV) accounts for high case fatality rates among PICU-admitted patients. A major challenge to management is the assessment of intravascular volume, which can be hampered by severe plasma leakage and the use of MV. DESIGN: Retrospective cohort, from 2013 to 2021. PATIENTS: Sixty-seven children with profound DSS supported by MV, some of whom underwent bedside point-of-care ultrasound (POCUS) for assessment and monitoring of hemodynamics and fluid administration. SETTING: PICU of the tertiary Children's Hospital No. 2 in Vietnam. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed data clinical and laboratory data during PICU stay. In particular, during use of MV (i.e., at times 0-, 6-, and 24-hr after commencement) and fluid resuscitation. The primary study outcome was 28-day in-hospital mortality, and the secondary outcomes were associations with changes in hemodynamics, blood lactate, and vasoactive-inotrope score (VIS). Patients had a median age of 7 years (interquartile range, 4-9). Use of POCUS during fluid management (39/67), as opposed to not using (28/67), was associated with lower mortality (6/39 [15%] vs. 18/28 [64%]; difference 49 % [95% CI, 28-70%], p < 0.001). Use of POCUS was associated with lower odds of death (adjusted odds ratio 0.17 [95% CI, 0.04-0.76], p = 0.02). The utilization of POCUS, versus not, was associated with greater use of resuscitation fluid, and reductions in VIS and pediatric logistic organ dysfunction (PELOD-2) score at 24 hours after MV and PICU discharge. CONCLUSIONS: In our experience of pediatric patients with profound DSS and undergoing MV (2013-2021), POCUS use was associated with lower odds of death, a higher volume of resuscitation fluid, and improvements in the blood lactate levels, VIS, and PELOD-2 score.

Towards universal health coverage in Vietnam: a mixed-method case study of enrolling people with tuberculosis into social health insurance.

BACKGROUND: Vietnam's primary mechanism of achieving sustainable funding for universal health coverage (UHC) and financial protection has been through its social health insurance (SHI) scheme. Steady progress towards access has been made and by 2020, over 90% of the population were enrolled in SHI. In 2022, as part of a larger transition towards the increased domestic financing of healthcare, tuberculosis (TB) services were integrated into SHI. This change required people with TB to use SHI for treatment at district-level facilities or to pay out of pocket for services. This study was conducted in preparation for this transition. It aimed to understand more about uninsured people with TB, assess the feasibility of enrolling them into SHI, and identify the barriers they faced in this process. METHODS: A mixed-method case study was conducted using a convergent parallel design between November 2018 and January 2022 in ten districts of Hanoi and Ho Chi Minh City, Vietnam. Quantitative data were collected through a pilot intervention that aimed to facilitate SHI enrollment for uninsured individuals with TB. Descriptive statistics were calculated. Qualitative interviews were conducted with 34 participants, who were purposively sampled for maximum variation. Qualitative data were analyzed through an inductive approach and themes were identified through framework analysis. Quantitative and qualitative data sources were triangulated. RESULTS: We attempted to enroll 115 uninsured people with TB into SHI; 76.5% were able to enroll. On average, it took 34.5 days to obtain a SHI card and it cost USD 66 per household. The themes indicated that a lack of knowledge, high costs for annual premiums, and the household-based registration requirement were barriers to SHI enrollment. Participants indicated that alternative enrolment mechanisms and greater procedural flexibility, particularly for undocumented people, is required to achieve full population coverage with SHI in urban centers. CONCLUSIONS: Significant addressable barriers to SHI enrolment for people affected by TB were identified. A quarter of individuals remained unable to enroll after receiving enhanced support due to lack of required documentation. The experience gained during this health financing transition is relevant for other middle-income countries as they address the provision of financial protection for the treatment of infectious diseases.

Combined Therapeutic Plasma Exchange and Continuous Renal Replacement Therapy in Children With Dengue-Associated Acute Liver Failure and Shock Syndrome: Single-Center Cohort From Vietnam.

OBJECTIVES: Pediatric acute liver failure (PALF) is a fatal complication in patients with severe dengue. To date, clinical data on the combination of therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT) for managing dengue-associated PALF concomitant with shock syndrome are limited. DESIGN: Retrospective cohort study (January 2013 to June 2022). PATIENTS: Thirty-four children. SETTING: PICU of tertiary Children's Hospital No. 2 in Vietnam. INTERVENTIONS: We assessed a before-versus-after practice change at our center of using combined TPE and CRRT (2018 to 2022) versus CRRT alone (2013 to 2017) in managing children with dengue-associated acute liver failure and shock syndrome. Clinical and laboratory data were reviewed from PICU admission, before and 24 h after CRRT and TPE treatments. The main study outcomes were 28-day in-hospital mortality, hemodynamics, clinical hepatoencephalopathy, and liver function normalization. MEASUREMENTS AND MAIN RESULTS: A total of 34 children with a median age of 10 years (interquartile range: 7-11 yr) underwent standard-volume TPE and/or CRRT treatments. Combined TPE and CRRT ( n = 19), versus CRRT alone ( n = 15), was associated with lower proportion of mortality 7 of 19 (37%) versus 13 of 15 (87%), difference 50% (95% CI, 22-78; p < 0.01). Use of combined TPE and CRRT was associated with substantial advancements in clinical hepatoencephalopathy, liver transaminases, coagulation profiles, and blood lactate and ammonia levels (all p values < 0.001). CONCLUSIONS: In our experience of children with dengue-associated PALF and shock syndrome, combined use of TPE and CRRT, versus CRRT alone, is associated with better outcomes. Such combination intervention was associated with normalization of liver function, neurological status, and biochemistry. In our center we continue to use combined TPE and CRRT rather than CRRT alone.

Determinants of catastrophic costs among households affected by multi-drug resistant tuberculosis in Ho Chi Minh City, Viet Nam: a prospective cohort study.

BACKGROUND: Globally, most people with multidrug-resistant tuberculosis (MDR-TB) and their households experience catastrophic costs of illness, diagnosis, and care. However, the factors associated with experiencing catastrophic costs are poorly understood. This study aimed to identify risk factors associated with catastrophic costs incurrence among MDR-TB-affected households in Ho Chi Minh City (HCMC), Viet Nam. METHODS: Between October 2020 and April 2022, data were collected using a locally-adapted, longitudinal WHO TB Patient Cost Survey in ten districts of HCMC. Ninety-four people with MDR-TB being treated with a nine-month TB regimen were surveyed at three time points: after two weeks of treatment initiation, completion of the intensive phase and the end of the treatment (approximately five and 10 months post-treatment initiation respectively). The catastrophic costs threshold was defined as total TB-related costs exceeding 20% of annual pre-TB household income. Logistic regression was used to identify variables associated with experiencing catastrophic costs. A sensitivity analysis examined the prevalence of catastrophic costs using alternative thresholds and cost estimation approaches. RESULTS: Most participants (81/93 [87%]) experienced catastrophic costs despite the majority 86/93 (93%) receiving economic support through existing social protection schemes. Among participant households experiencing and not experiencing catastrophic costs, median household income was similar before MDR-TB treatment. However, by the end of MDR-TB treatment, median household income was lower (258 [IQR: 0-516] USD vs. 656 [IQR: 462-989] USD; p = 0.003), and median income loss was higher (2838 [IQR: 1548-5418] USD vs. 301 [IQR: 0-824] USD; p < 0.001) amongst the participant households who experienced catastrophic costs. Being the household's primary income earner before MDR-TB treatment (aOR = 11.2 [95% CI: 1.6-80.5]), having a lower educational level (aOR = 22.3 [95% CI: 1.5-344.1]) and becoming unemployed at the beginning of MDR-TB treatment (aOR = 35.6 [95% CI: 2.7-470.3]) were associated with experiencing catastrophic costs. CONCLUSION: Despite good social protection coverage, most people with MDR-TB in HCMC experienced catastrophic costs. Incurrence of catastrophic costs was independently associated with being the household's primary income earner or being unemployed. Revision and expansion of strategies to mitigate TB-related catastrophic costs, in particular avoiding unemployment and income loss, are urgently required.

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

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

All-oral longer regimens are effective for the management of multidrug-resistant tuberculosis in high-burden settings.

BACKGROUND: Recent World Health Organization guidance on drug-resistant tuberculosis treatment de-prioritised injectable agents, in use for decades, and endorsed all-oral longer regimens. However, questions remain about the role of the injectable agent, particularly in the context of regimens using new and repurposed drugs. We compared the effectiveness of an injectable-containing regimen to that of an all-oral regimen among patients with drug-resistant tuberculosis who received bedaquiline and/or delamanid as part of their multidrug regimen. METHODS: Patients with a positive baseline culture were included. 6-month culture conversion was defined as two consecutive negative cultures collected >15 days apart. We derived predicted probabilities of culture conversion and relative risk using marginal standardisation methods. RESULTS: Culture conversion was observed in 83.8% (526 out of 628) of patients receiving an all-oral regimen and 85.5% (425 out of 497) of those receiving an injectable-containing regimen. The adjusted relative risk comparing injectable-containing regimens to all-oral regimens was 0.96 (95% CI 0.88-1.04). We found very weak evidence of effect modification by HIV status: among patients living with HIV, there was a small increase in the frequency of conversion among those receiving an injectable-containing regimen, relative to an all-oral regimen, which was not apparent in HIV-negative patients. CONCLUSIONS: Among individuals receiving bedaquiline and/or delamanid as part of a multidrug regimen for drug-resistant tuberculosis, there was no significant difference between those who received an injectable and those who did not regarding culture conversion within 6 months. The potential contribution of injectable agents in the treatment of drug-resistant tuberculosis among those who were HIV positive requires further study.

What makes community health worker models for tuberculosis active case finding work? A cross-sectional study of TB REACH projects to identify success factors for increasing case notifications.

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.

Socio-protective effects of active case finding on catastrophic costs from tuberculosis in Ho Chi Minh City, Viet Nam: a longitudinal patient cost survey.

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 (VND1 = 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 < 0.001) and lower median total costs (US$279 vs. US$894; p < 0.001). Fewer ACF patients incurred catastrophic costs (15 % vs. 30 %) and had lower odds of catastrophic cost (aOR = 0.17; 95 % CI: [0.05, 0.67]; p = 0.011), especially during the intensive phase (OR = 0.32; 95 % CI: [0.12, 0.90]; p = 0.030). ACF patient experienced less social exclusion (OR = 0.41; 95 % CI: [0.18, 0.91]; p = 0.030), but more often resorted to financial coping mechanisms (OR = 5.12; 95 % CI: [1.73, 15.14]; p = 0.003). CONCLUSIONS: ACF can be effective in reaching vulnerable populations and mitigating the socioeconomic burden of TB, and can contribute to achieving the WHO End TB Strategy goals. Nevertheless, as TB remains a catastrophic life event, social protection efforts must extend beyond ACF.

Tuberculosis among economic migrants: a cross-sectional study of the risk of poor treatment outcomes and impact of a treatment adherence intervention among temporary residents in an urban district in Ho Chi Minh City, Viet Nam.

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 (ß6) and post-intervention trend (ß7). 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 < 0.001) than permanent residents. Intra-province migrants were similarly more likely to be lost to follow-up (aOR = 1.86 [95% CI: 1.03-3.36], p = 0.041). There was evidence that patients > 55 years of age (aRR = 0.93 [95% CI: 0.89-0.96], p < 0.001), relapse patients (aRR = 0.89 [95% CI: 0.84-0.94], p < 0.001), and retreatment patients (aRR = 0.62 [95% CI: 0.52-0.75], p < 0.001) had lower treatment success rates. TB/HIV co-infection was also associated with lower treatment success (aRR = 0.77 [95% CI: 0.73-0.82], p < 0.001) and higher loss to follow-up (aOR = 2.18 [95% CI: 1.55-3.06], p < 0.001). The provision of treatment adherence support increased treatment success (IRR(ß6) = 1.07 [95% CI: 1.00, 1.15], p = 0.041) and reduced loss to follow-up (IRR(ß6) = 0.17 [95% CI: 0.04, 0.69], p = 0.013) in the intervention districts. Loss to follow-up continued to decline throughout the post-implementation period (IRR(ß7) = 0.90 [95% CI: 0.83, 0.98], p = 0.019). CONCLUSIONS: Economic migrants, particularly those crossing provincial borders, have higher risk of poor treatment outcomes and should be prioritized for tailored adherence support. In light of accelerating urbanization in many regions of Asia, implementation trials are needed to inform evidence-based design of strategies for this vulnerable population.

A comparative impact evaluation of two human resource models for community-based active tuberculosis case finding in Ho Chi Minh City, Viet Nam.

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.

Expanding molecular diagnostic coverage for tuberculosis by combining computer-aided chest radiography and sputum specimen pooling: a modeling study from four high-burden countries.

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. Supplementary Information: The online version contains supplementary material available at 10.1186/s44263-024-00081-2.

Study protocol: diagnostic accuracy study comparing Cy-Tb and STANDARD F TB-Feron FIA tests for tuberculosis infection diagnosis in Vietnam.

INTRODUCTION: The large reservoir of tuberculosis (TB) infections is one of the main reasons for the persistent incidence of TB. Accurate diagnostic tests are crucial to correctly identify and treat people with TB infection, which is vital to eliminate TB globally. The rdESAT-6 and rCFP-10 (Cy-Tb) injection ('Cy-Tb'), a TB-specific antigen skin test and STANDARD F TB-Feron FIA ('Standard F TB') measuring interferon-gamma by fluorescence immunoassay assay are two novel tools for the diagnosis of TB infection which offer advantages compared with current tests in low-resource settings and reduced costs to both health systems and TB-affected people. The proposed study aims to evaluate the diagnostic accuracy of these two new tests for TB infection diagnosis. METHODS AND ANALYSIS: This cross-sectional study aims to assess the diagnostic accuracy for TB infection of the Cy-Tb skin test and Standard F TB assay (investigational tests) compared with the QuantiFERON-TB Gold Plus (QFT-Plus) assay as the immunological reference standard. Three different cohorts of study participants will be recruited at the Vietnam National Lung Hospital: adults with bacteriologically confirmed pulmonary TB (n=100), household contacts of people with TB (n=200) and people without TB infection (n=50). All consenting participants will undergo simultaneous testing with Cy-Tb, Standard F TB and QFT-Plus. The primary endpoint is the diagnostic accuracy of the Cy-Tb skin test and Standard F TB assay, expressed as sensitivity and specificity against the reference standard. ETHICS AND DISSEMINATION: Ethical approval was granted by the Vietnam National Lung Hospital Institutional Review Board (65/23/CN-HDDD-BVPTU) and the Swedish Ethical Review Authority (Dnr 2023-04271-01). Study results will be disseminated to the scientific community and policymakers through scientific publications. TRIAL REGISTRATION NUMBER: NCT06221735.

Ensuring Continuity of Tuberculosis Care during Social Distancing through Integrated Active Case Finding at COVID-19 Vaccination Events in Vietnam: A Cohort Study.

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.

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

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

Mapping protein-exopolysaccharide binding interaction in Staphylococcus epidermidis biofilms by live cell proximity labeling.

Bacterial biofilms consist of cells encased in an extracellular polymeric substance (EPS) composed of exopolysaccharides, extracellular DNA, and proteins that are critical for cell-cell adhesion and protect the cells from environmental stress, antibiotic treatments, and the host immune response. Degrading EPS components or blocking their production have emerged as promising strategies for prevention or dispersal of bacterial biofilms, but we still have little information about the specific biomolecular interactions that occur between cells and EPS components and how those interactions contribute to biofilm production. Staphylococcus epidermidis is a leading cause of nosocomial infections as a result of producing biofilms that use the exopolysaccharide poly-(1→6)-ß-N-acetylglucosamine (PNAG) as a major structural component. In this study, we have developed a live cell proximity labeling approach combined with quantitative mass spectrometry-based proteomics to map the PNAG interactome of live S. epidermidis biofilms. Through these measurements we discovered elastin-binding protein (EbpS) as a major PNAG-interacting protein. Using live cell binding measurements, we found that the lysin motif (LysM) domain of EbpS specifically binds to PNAG present in S. epidermidis biofilms. Our work provides a novel method for the rapid identification of exopolysaccharide-binding proteins in live biofilms that will help to extend our understanding of the biomolecular interactions that are required for bacterial biofilm formation.

A qualitative assessment on the acceptability of providing cash transfers and social health insurance for tuberculosis-affected families in Ho Chi Minh City, Vietnam.

To achieve the Sustainable Development Goal's targets of universal health coverage (UHC) and poverty reduction, interventions are required that strengthen and harmonize both UHC and social protection. Vietnam is committed to achieving financial protection and over 90% of the general population has enrolled in its social health insurance (SHI) scheme. However, an estimated 63% of tuberculosis (TB)-affected households in Vietnam still face catastrophic costs and little is known about the optimal strategies to mitigate the costs of TB care for vulnerable families. This study assessed the acceptability of a social protection package containing cash transfers and SHI using individual interviews (n = 19) and focus group discussions (n = 3 groups). Interviews were analyzed through framework analysis. The study's main finding indicated that both conditional and unconditional cash transfers paired with SHI were acceptable, across six dimensions of acceptability. Cash transfers were considered beneficial for mitigating out-of-pocket expenditure, increasing TB treatment adherence, and improving mental health and general well-being, but the value provided was inadequate to fully alleviate the economic burden of the illness. The conditionality of the cash transfers was not viewed by participants as inappropriate, but it increased the workload of the TB program, which brought into question the feasibility of scale-up. SHI was viewed as a necessity by almost all participants, but people with TB questioned the quality of care received when utilizing it for auxiliary TB services. Access to multiple sources of social protection was deemed necessary to fully offset the costs of TB care. Additional research is needed to assess the impact of cash transfer interventions on health and economic outcomes in order to create an enabling policy environment for scale-up.

Comparative performance evaluation of QIAreach QuantiFERON-TB and tuberculin skin test for diagnosis of tuberculosis infection in Viet Nam.

Current WHO-recommended diagnostic tools for tuberculosis infection (TBI) have well-known limitations and viable alternatives are urgently needed. We compared the diagnostic performance and accuracy of the novel QIAreach QuantiFERON-TB assay (QIAreach; index) to the QuantiFERON-TB Gold Plus assay (QFT-Plus; reference). The sample included 261 adults (≥ 18 years) recruited at community-based TB case finding events. Of these, 226 underwent Tuberculin Skin Tests and 200 returned for interpretation (TST; comparator). QIAreach processing and TST reading were completed at lower-level healthcare facilities. We conducted matched-pair comparisons for QIAreach and TST with QFT-Plus, calculated sensitivity, specificity and area under a receiver-operating characteristic curve (AUC), and analyzed concordant-/discordant-pair interferon-gamma (IFN-γ) levels. QIAreach sensitivity and specificity were 98.5% and 72.3%, respectively, for an AUC of 0.85. TST sensitivity (53.2%) at a 5 mm induration threshold was significantly below QIAreach, while specificity (82.4%) was statistically equivalent. The corrected mean IFN-γ level of 0.08 IU/ml and corresponding empirical threshold (0.05) of false-positive QIAreach results were significantly lower than the manufacturer-recommended QFT-Plus threshold (≥ 0.35 IU/ml). Despite QIAreach's higher sensitivity at equivalent specificity to TST, the high number of false positive results and low specificity limit its utility and highlight the continued need to expand the diagnostic toolkit for TBI.

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

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

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

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