Study protocol: a pragmatic, cluster-randomized controlled trial to evaluate the effect of implementation of the Truenat platform/MTB assays at primary health care clinics in Mozambique and Tanzania (TB-CAPT CORE).

BACKGROUND: In 2020, the WHO-approved Molbio Truenat platform and MTB assays to detect Mycobacterium tuberculosis complex (MTB) and resistance to rifampicin directly on sputum specimens. This primary health care center-based trial in Mozambique and Tanzania investigates the effect of Truenat platform/MTB assays (intervention arm) combined with rapid communication of results compared to standard of care on TB diagnosis and treatment initiation for microbiologically confirmed TB at 7 days from enrolment. METHODS: The Tuberculosis Close the Gap, Increase Access, and Provide Adequate Therapy (TB-CAPT) CORE trial employs a pragmatic cluster randomized controlled design to evaluate the impact of a streamlined strategy for delivery of Truenat platform/MTB assays testing at primary health centers. Twenty-nine centers equipped with TB microscopy units were selected to participate in the trial. Among them, fifteen health centers were randomized to the intervention arm (which involves onsite molecular testing using Truenat platform/MTB assays, process process optimization to enable same-day TB diagnosis and treatment initiation, and feedback on Molbio platform performance) or the control arm (which follows routine care, including on-site sputum smear microscopy and the referral of sputum samples to off-site Xpert testing sites). The primary outcome of the study is the absolute number and proportion of participants with TB microbiological confirmation starting TB treatment within 7 days of their first visit. Secondary outcomes include time to bacteriological confirmation, health outcomes up to 60 days from first visit, as well as user preferences, direct cost, and productivity analyses. ETHICS AND DISSEMINATION: TB-CAPT CORE trial has been approved by regulatory and ethical committees in Mozambique and Tanzania, as well as by each partner organization. Consent is informed and voluntary, and confidentiality of participants is maintained throughout. Study findings will be presented at scientific conferences and published in peer-reviewed international journals. TRIAL REGISTRATION: US National Institutes of Health's ClinicalTrials.gov, NCT04568954. Registered 23 September 2020.

Perceived stigma among people with TB and household contacts.

BACKGROUND: TB-related stigma hampers access to diagnosis and treatment, making it important to understand the demographic and clinical characteristics associated with perceived TB stigma. TB stigma has not been studied in household contacts before, yet they comprise an important population for epidemic control, with high risk of infection.METHOD: A cross-sectional study was conducted among people with TB and household contacts in South Africa using a 12-item perceived TB stigma scale (score range: 0-36). Demographic and clinical characteristic data were collected using a close-ended questionnaire. A linear mixed-effects regression model was used to explore perceived TB stigma levels and its associated characteristics.RESULTS: The sample included 143 people with TB and 135 household contacts. The mean perceived TB stigma score among people with TB was 22.1 (95% CI 21.1-23.1) and 22.2 (95% CI 21.1-23.3) among household contacts. Being in the same household explained 24.3% variability in stigma perception. Residence in the urban study site (Soshanguve) and a positive HIV diagnosis were associated with higher perceived TB stigma score.CONCLUSIONS: People with TB and household contacts have similarly high prevalence of perceived TB stigma. Positive HIV status and urban location were associated with higher prevalence of perceived TB stigma.

Understanding patient-level costs of weekly isoniazid-rifapentine (3HP) among people living with HIV in Uganda.

BACKGROUND: Twelve weeks of weekly isoniazid and rifapentine (3HP) prevents TB disease among people with HIV (PWH), but the costs to people of taking TB preventive treatment is not well described.METHODS: We surveyed PWH who initiated 3HP at a large urban HIV/AIDS clinic in Kampala, Uganda, as part of a larger trial. We estimated the cost of one 3HP visit from the patient perspective, including both out-of-pocket costs and estimated lost wages. Costs were reported in 2021 Ugandan shillings (UGX) and US dollars (USD; USD1 = UGX3,587)RESULTS: The survey included 1,655 PWH. The median participant cost of one clinic visit was UGX19,200 (USD5.36), or 38.5% of the median weekly income. Per visit, the cost of transportation was the largest component (median: UGX10,000/USD2.79), followed by lost income (median: UGX4,200/USD1.16) and food (median: UGX2,000/USD0.56). Men reported greater income loss than women (median: UGX6,400/USD1.79 vs. UGX3,300/USD0.93), and participants who lived further than a 30-minute drive to the clinic had higher transportation costs than others (median: UGX14,000/USD3.90 vs. UGX8,000/USD2.23).CONCLUSION: Patient-level costs to receive 3HP accounted for over one-third of weekly income. Patient-centered approaches to averting or defraying these costs are needed.

Cost to perform door-to-door universal sputum screening for TB in a high-burden community.

BACKGROUND: Population-based active case-finding (ACF) identifies people with TB in communities but can be costly. METHODS: We conducted an empiric costing study within a door-to-door household ACF campaign in an urban community in Uganda, where all adults, regardless of symptoms, were screened by sputum Xpert Ultra testing. We used a combination of direct observation and self-reported logs to estimate staffing requirements. Study budgets were reviewed to collect costs of overheads, equipment, and consumables. Our primary outcome was the cost per person diagnosed with TB. RESULTS: Over a 28-week period, three teams of two people collected sputum from 11,341 adults, of whom 48 (0.4%) tested positive for TB. Screening 1,000 adults required 258 person-hours of effort at a cost of US$35,000, 70% of which was for GeneXpert cartridges. The estimated cost per person screened was $36 (95% uncertainty range [95% UR] 34­38), and the cost per person diagnosed with Xpert-positive TB was $8,400 (95% UR 8,000­8,900). The prevalence of TB in the underlying community was the primary modifiable determinant of the cost per person diagnosed. CONCLUSION: Door-to-door screening can be feasibly performed at scale, but will require effective triage and identification of high-prevalence populations to be affordable and cost-effective.

Alcohol use as a mediator of the effect of two alcohol reduction interventions on mental health symptoms of ART clients in Vietnam.

We aimed to examine the mediating role of alcohol use in the pathway from the interventions to depression and anxiety symptoms using data from a randomized controlled trial among people living with HIV (PWH) with hazardous alcohol use (n = 440) in Thai Nguyen, Vietnam. Participants were randomized into either a combined intervention (CoI), a brief intervention (BI) and a standard of care arm. Both interventions were based on cognitive behavioral therapy and motivational enhancement therapy. Alcohol use was measured as the percentage of days abstinent from alcohol in the last 30 days. Symptoms of depression and anxiety were measured with the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 scales. Alcohol use was a significant mediator of the effects of two alcohol interventions on depression symptoms, but not anxiety symptoms. There were significant indirect effects via alcohol use of both interventions on depression symptoms at 12 months (CoI: mean difference (MD) = -0.134; 95%CI: -0.251, -0.035); (BI: MD = -0.141; 95%CI: -0.261, -0.038). There were no significant direct or total effects of the interventions on either symptoms at 12 months. Interventions with a dual focus on mental health and alcohol disorders are needed to determine optimal ways to tackle these common comorbidities among PWH.

The impact of time at home on potential yield of home-based TB contact investigation.

BACKGROUND: The yield of TB contact tracing is often limited by challenges in reaching individuals during the screening process. We investigated the times at which index patients and household contacts were typically at home and the potential effects of expanding the timing of home-based contact investigation.METHODS: Index patients and household contacts in Kampala, Uganda, were asked about their likely availability at different day/time combinations. We calculated the "participant identification gap" (defined as the proportion of participants who reported being home <50% of the time) during business hours only. We then estimated the incremental reduction in the participant identification gap if hours were expanded to include weekday evenings, Saturdays, and Sundays. Statistical significance was assessed using McNemar´s tests.RESULTS: Nearly half of eligible individuals (42% of index patients and 52% of contacts) were not likely to be home during contact investigation conducted only during business hours. Expanding to weekday evenings, Saturdays, and Sundays would reduce this participant identification gap to 15% among index patients and 18% among contacts - while also reducing differences by sex and employment.CONCLUSIONS: Expanding hours for conducting contact investigation or other home-based health interventions could substantially reduce the number of individuals missed and address disparities in access to care.

Considering equity in priority setting using transmission models: Recommendations and data needs.

OBJECTIVES: Disease transmission models are used in impact assessment and economic evaluations of infectious disease prevention and treatment strategies, prominently so in the COVID-19 response. These models rarely consider dimensions of equity relating to the differential health burden between individuals and groups. We describe concepts and approaches which are useful when considering equity in the priority setting process, and outline the technical choices concerning model structure, outputs, and data requirements needed to use transmission models in analyses of health equity. METHODS: We reviewed the literature on equity concepts and approaches to their application in economic evaluation and undertook a technical consultation on how equity can be incorporated in priority setting for infectious disease control. The technical consultation brought together health economists with an interest in equity-informative economic evaluation, ethicists specialising in public health, mathematical modellers from various disease backgrounds, and representatives of global health funding and technical assistance organisations, to formulate key areas of consensus and recommendations. RESULTS: We provide a series of recommendations for applying the Reference Case for Economic Evaluation in Global Health to infectious disease interventions, comprising guidance on 1) the specification of equity concepts; 2) choice of evaluation framework; 3) model structure; and 4) data needs. We present available conceptual and analytical choices, for example how correlation between different equity- and disease-relevant strata should be considered dependent on available data, and outline how assumptions and data limitations can be reported transparently by noting key factors for consideration. CONCLUSIONS: Current developments in economic evaluations in global health provide a wide range of methodologies to incorporate equity into economic evaluations. Those employing infectious disease models need to use these frameworks more in priority setting to accurately represent health inequities. We provide guidance on the technical approaches to support this goal and ultimately, to achieve more equitable health policies.

"I refused to drink but they still forced me": A mixed-methods approach to understanding the pathways to reduce alcohol use among Vietnamese people with HIV.

AIMS: This study explores the effects of two evidence-based alcohol reduction counseling interventions on readiness to change, alcohol abstinence self-efficacy, social support, and alcohol abstinence stigma among people with HIV (PWH) who have hazardous alcohol use in Vietnam. METHODS: PWH receiving antiretroviral therapy (ART) were screened for hazardous drinking and randomized to one of three study arms: combined intervention (CoI), brief intervention (BI), and standard of care (SOC). A quantitative survey was conducted at baseline (N = 440) and 3-month post-intervention (N = 405), while in-depth interviews were conducted with a subset of BI and CoI participants at baseline (N = 14) and 3 months (N = 14). Data was collected from March 2016 to August 2017. A concurrent mixed-methods model was used to triangulate quantitative and qualitative data to cross-validate findings. RESULTS: At 3 months, receiving the BI and CoI arms was associated with 2.64 and 3.50 points higher in mean readiness to change scores, respectively, compared to the SOC group (BI: ß = 2.64, 95% CI: 1.17-4.12; CoI: ß = 3.50, 95% CI 2.02-4.98). Mean alcohol abstinence self-efficacy scores were 4.03 and 3.93 points higher among the BI and CoI arm at 3 months, compared to SOC (BI: ß = 4.03, 95% CI: 0.17-7.89; CoI: ß = 3.93, 95% CI: 0.05-7.81). The impacts of the interventions on social support and alcohol abstinence stigma were not significant. Perceived challenges to refusing drinks at social events remained due to strong alcohol abstinence stigma and perceived negative support from family and friends who encouraged participants to drink posed additional barriers to reducing alcohol use. CONCLUSIONS: Both the CoI and BI were effective in improving readiness to change and alcohol abstinence self-efficacy among PWH. Yet, participants still faced significant barriers to reducing their drinking due to social influences and pressure to drink. Interventions at different levels addressing social support and alcohol abstinence stigma are warranted.

Time to care-seeking for TB symptoms.

BACKGROUND: Early presentation to healthcare facilities is critical for early diagnosis and treatment of TB. We studied self-reported time to care-seeking from the onset of TB symptoms among primary healthcare clinic (PHC) attendees in Limpopo Province, South Africa.METHODS: We used data from participants enrolled in a cluster-randomized trial of TB case finding in 56 PHC clinics across two health districts. We fitted log-normal accelerated failure time regression models and we present time ratios (TRs) for potential risk factors.RESULTS: We included 2,160 participants. Among the 1,757 (81%) diagnosed with active TB, the median time to care-seeking was 30 days (IQR 14-60); adults sought care later than children/adolescents (adjusted TR aTR 1.47, 95% CI 1.10-1.96). Among those not diagnosed with TB, the median was 14 days (IQR 7-60); being HIV-positive (aTR 1.57, 95% CI 1.03-2.40); having less than grade 8 education and currently smoking were associated with longer time to care-seeking. In the combined analysis, living with HIV and having underlying active TB was associated with faster care-seeking (TB status x HIV interaction: TR 0.68, 95% CI 0.48-0.96).CONCLUSION: Delay in care-seeking was associated with age, lower education and being a current smoker. TB awareness campaigns targeting these population groups may improve care-seeking behavior and reduce community TB transmission.

Effects of Two Alcohol Reduction Interventions on Depression and Anxiety Symptoms of ART Clients in Vietnam.

Little is known about the potential mental health impacts of cognitive behavioral therapy and motivational interviewing interventions that focus on alcohol reduction among people with HIV (PWH). Our study aimed to assess the impact of two evidence-based alcohol reduction interventions on depression and anxiety symptoms of antiretroviral therapy (ART) clients with hazardous alcohol use. We conducted a secondary data analysis of data from a three-arm randomized controlled trial among ART clients in Thai Nguyen, Vietnam that evaluated the impacts of two alcohol reduction interventions in Vietnam. ART clients 18 years old or more with hazardous alcohol use (based on the Alcohol Use Disorders Identification Test-Consumption) were enrolled and randomized into one of three arms: Combined intervention, Brief intervention, and Standard of care (SOC). Symptoms of depression, measured with the Patient Health Questionnaire-9, and anxiety, measured with the Generalized Anxiety Disorder-7 scale, were assessed at baseline and 3, 6, and 12 months post-intervention. Generalized estimating equations were used to evaluate the effects of the interventions on depression and anxiety symptoms. The prevalence of depression and anxiety symptoms at baseline was 25.1% and 16.1%, respectively. Decreases in depression and anxiety symptoms were observed in all three arms from baseline to 12-month follow-up. There were no significant differences in depression and anxiety symptoms among participants receiving either intervention, relative to the SOC. Interventions with a dual focus on alcohol and mental health are needed to achieve more pronounced and sustainable improvements in depression and anxiety symptoms for PWH with hazardous alcohol use.

Geographic mobility and time to seeking care among people with TB in Limpopo, South Africa.

SETTING: Human mobility contributes to the spread of infectious diseases. South Africa has a long history of internal labor migration and a high burden of TB.METHODS: People newly diagnosed with TB in the Vhembe and Waterberg Districts of Limpopo answered a questionnaire regarding geographic movement over the past year. Participants were classified as 'highly mobile' (spending more than 30 nights at a residence other than their primary residence in the past year, or being ≥250 km from their primary residence at the time of the interview) or 'less mobile'. We explored associations between sociodemographic characteristics and high mobility, and between mobility and time to presentation at a clinic.RESULTS: Of the 717 participants included, 185 (25.7%) were classified as 'highly mobile'. Factors associated with high mobility included living with someone outside of Limpopo Province, HIV-positive status (men only), and current smoking (men only). Highly mobile individuals had similar care-seeking behavior as less mobile individuals (adjusted time ratio 0.9, 95% CI 0.6-1.2, P = 0.304)CONCLUSION: Highly mobile people with TB in Limpopo Province were more likely to live with people from outside the province, smoke, and have HIV. These patients had similar delays in seeking care as less mobile individuals.

Determining the value of TB active case-finding: current evidence and methodological considerations.

Active case-finding (ACF) is an important component of the End TB Strategy. However, ACF is resource-intensive, and the economics of ACF are not well-understood. Data on the costs of ACF are limited, with little consistency in the units and methods used to estimate and report costs. Mathematical models to forecast the long-term effects of ACF require empirical measurements of the yield, timing and costs of case detection. Pragmatic trials offer an opportunity to assess the cost-effectiveness of ACF interventions within a 'real-world´ context. However, such analyses generally require early introduction of economic evaluations to enable prospective data collection on resource requirements. Closing the global case-detection gap will require substantial additional resources, including continued investment in innovative technologies. Research is essential to the optimal implementation, cost-effectiveness, and affordability of ACF in high-burden settings. To assess the value of ACF, we must prioritize the collection of high-quality data regarding costs and effectiveness, and link those data to analytical models that are adapted to local settings.