Appropriateness, barriers, and facilitators of multi-month dispensing of tuberculosis drugs in rural eastern Uganda: A qualitative study to inform a non-inferiority randomized trial.

Multi-month dispensing of tuberculosis (TB) drugs is an innovative strategy that may reduce frequent clinic visits and travel costs among people with TB (PWTB) in rural areas. To inform a planned trial, we explored the appropriateness, barriers, and facilitators to multi-month dispensing among PWTB and healthcare providers in rural eastern Uganda. We used qualitative methods situated within the Consolidated Framework for Implementation Research to explore two refill schedules for multi-month dispensing of TB drugs-a four- or five-visit refill schedule.

AveloMask, a novel breath aerosol collection kit for airborne : a proof-of-principle assessment.

Tuberculosis (TB) remains the world's deadliest infectious disease, with many active cases missed due to challenges in sputum collection. Exhaled breath aerosols (XBA), a major route of (MTB) transmission, offer a promising non-invasive alternative. This study evaluated the diagnostic accuracy and feasibility of the AveloMask-a novel point-of-care breath aerosol collection kit-for detecting active pulmonary TB using quantitative PCR (qPCR).

The three-gene Xpert Host Response signature for pediatric tuberculosis screening: A prospective diagnostic accuracy study.

Background: Blood-based gene signatures offer potential as a near point-of-care tuberculosis (TB) screening tool. We examined the accuracy of the GeneXpert MTB Host Response (Xpert-HR) cartridge to screen for TB in children.

Methods: We enrolled children under 15 years from The Gambia and Uganda being evaluated for pulmonary TB.

Informing People-Centered Target Product Profiles for TB Diagnostics: A Multi-Country Qualitative Study.

Background: Timely and accurate tuberculosis (TB) diagnosis remains a key challenge in high-burden settings. The World Health Organization (WHO) has developed Target Product Profiles (TPPs) to guide diagnostic development, which have largely reflected the perspectives of experts, with limited input from people affected by TB. This qualitative study explored preferences and experiences to inform people-centered TB diagnostic strategies.

Multicohort assessment of plasma metabolic signatures of tuberculosis disease in children.

Current microbiological tests for tuberculosis (TB) disease in children have suboptimal accuracy and rely on respiratory samples which may be challenging to obtain. We sought to use high-resolution metabolomics (HRM) to identify blood-based biomarkers associated with TB disease in children. We analyzed plasma samples from 438 children 0-14 years being evaluated for TB disease in India, Peru, Uganda, The Gambia, and South Africa.

Addressing Stigma, Mental Well-Being, and Alcohol Use among People with Tuberculosis in Sub-Saharan Africa: A Call for an Integrated Care Model.

Tuberculosis (TB) remains a major public health challenge in sub-Saharan Africa (SSA), with stigma, mental health issues, and alcohol use significantly affecting treatment outcomes. Stigma delays TB diagnosis, reduces treatment adherence, and disrupts care continuity. Mental health conditions, such as depression and anxiety, further undermine adherence, whereas alcohol use accelerates TB disease progression and leads to poor treatment outcomes.

Plasma proteomics for biomarker discovery in childhood tuberculosis.

Failure to rapidly diagnose tuberculosis disease (TB) and initiate treatment is a driving factor of TB as a leading cause of death in children. Current TB diagnostic assays have poor performance in children, thus a global priority is the identification of novel non-sputum-based TB biomarkers. Here we use high-throughput proteomics to measure the plasma proteome for 511 children, with and without HIV, and across 4 countries, to distinguish TB status using standardized definitions.

Projecting the impact and costs of near point-of-care tuberculosis screening assays in community-based active case finding.

Background: Community-based active case finding (ACF) may reduce tuberculosis incidence and mortality but is not widely implemented due to resource constraints. How novel screening test characteristics would affect the impact and costs of ACF strategies is not clear.

Methods: We developed mathematical models of tuberculosis natural history and transmission, calibrated to data from three high tuberculosis burden countries (India, Vietnam and the Philippines) and simulated the impact of annual community-based ACF programs.

Tongue Swab Xpert MTB/RIF Ultra Testing for Tuberculosis Using a Revised Consensus Protocol: A multi-country diagnostic accuracy study.

Background: Tongue swabs are a promising specimen for tuberculosis (TB) diagnosis. In a previous study using a consensus protocol, tongue swabs tested with Xpert MTB/RIF Ultra (Xpert Ultra, Cepheid, USA) outperformed sputum smear microscopy, but a substantial proportion (6.1%) of results were non-actionable (e.

Identifying gaps in tuberculosis preventive care for non-U.S.-born persons at community health clinics in the United States.

Background: Treating asymptomatic tuberculosis (TB) infection prevents TB disease and is critical for TB elimination in the United States (U.S.).

Preferences for Tongue Swab versus Sputum Collection for Tuberculosis Testing: A Multi-Country Survey.

Background: Sputum collection for tuberculosis (TB) diagnosis poses challenges for children, people living with HIV, and those who struggle with sputum production. Tongue swab-based molecular testing offers a promising non-invasive alternative, but person-centered research on acceptability is limited.

Methods: We conducted a pragmatic survey across eight countries (Vietnam, Philippines, South Africa, Nigeria, Zambia, India, Uganda, Peru) among people with presumptive TB attending primary care facilities.

Multi-month dispensing of tuberculosis medications in sub-Saharan Africa: A feasible, person-centered care model.

The treatment success rate among people with tuberculosis in sub-Saharan Africa is suboptimal despite the availability of shortened and efficacious TB regimens. Barriers such as long travel distances and frequent clinic visits for medication refills hinder access to care and compromise treatment adherence and completion. Multi-month dispensing of anti-retroviral drugs has proved successful in improving treatment adherence and viral load suppression among people living with human immunodeficiency virus.

Stool processing methods for Xpert Ultra testing in childhood tuberculosis: A prospective, multi-country accuracy study.

Background: Centrifuge-free processing methods support stool Xpert Ultra testing for childhood tuberculosis (TB), but there are limited data on their accuracy, acceptability and usability.

Methods: We conducted a prospective evaluation of stool Xpert Ultra in India, South Africa, and Uganda with three methods: Stool Processing Kit (SPK), Simple One-Step (SOS), and Optimized Sucrose Flotation (OSF). Children <15 years old with presumptive TB had sputum testing with Xpert Ultra and culture.

Importance of confirmatory test characteristics in optimizing community-based screening for tuberculosis: An epidemiological modeling analysis.

Background: Current active case-finding (ACF) efforts for tuberculosis (TB) are limited by the costs, operational barriers, and sensitivity of available tools to confirm a TB diagnosis. However, it is not well understood which of these limitations has the greatest epidemiological relevance and might therefore warrant prioritization in test development.

Methods: We developed a state-transition model of a one-time, community-based ACF intervention, with a fixed budget of one million United States dollars for screening and confirmatory testing.

A Prospective Evaluation of a Three-Gene Host Response Signature to Classify Tuberculosis Severity in Children.

Background: Children with non-severe TB may benefit from short-course treatment, but point-of-care tools are needed to stratify disease severity. We prospectively evaluated the Cepheid Xpert MTB-Host Response (HR) prototype cartridge for distinguishing TB severity in children with pulmonary TB (PTB) in The Gambia and Uganda.

Methods: We included children <15 with microbiologically confirmed or clinically diagnosed unconfirmed PTB.

Causal inference methodologies to assess the effect of missed clinic visits on treatment success rate among people with tuberculosis in rural Uganda.

Background: Although randomized controlled trials are the gold standard design for cause-effect analysis, high costs and challenges around practicability, feasibility, and ethics may limit their use. In such situations, causal inference methods can improve the rigor of cause-effect analysis using observational data but such methods have infrequently been applied in tuberculosis (TB) research. We conducted a parallel comparison across three causal inference methods in order to assess the causal association between missed clinic visit/s and treatment success among people with drug-susceptible bacteriologically confirmed pulmonary TB.

The Accuracy of the Uganda National Tuberculosis and Leprosy Program diagnostic algorithm and the World Health Organisation treatment decision algorithms for childhood tuberculosis: A retrospective analysis.

Diagnosing childhood pulmonary tuberculosis (TB) is a challenge. This led the Uganda National Tuberculosis and Leprosy Program (NTLP) to develop a clinical treatment decision algorithm (TDA) for children. However, there is limited data on its accuracy, and how it compares to new World Health Organization (WHO) TB TDAs for children.

Sex differences in systematic screening for tuberculosis among antiretroviral therapy naïve people with HIV in Kampala, Uganda.

Background: Systematic tuberculosis (TB) screening is recommended for all people with HIV (PWH) because of its potential to improve TB outcomes through earlier diagnosis and treatment initiation. As such, systematic screening may be particularly important for men, who experience excess TB prevalence and mortality compared to women. We assessed sex differences among PWH undergoing systematic TB screening, including TB prevalence and severity, diagnostic accuracy of screening tools, and TB outcomes.

Predicted choice and acceptability of regimens for tuberculosis preventive treatment among people living with HIV in Uganda - a discrete choice experiment.

Introduction: Little is known about how people living with HIV would choose if offered different tuberculosis preventive treatment (TPT) regimens, and under which conditions they would accept treatment. Actionable evidence regarding preference for TPT is needed to inform policy and the development of novel TPT regimens.

Methods: Adults engaged in care at an HIV clinic in Kampala, Uganda, completed a discrete choice experiment survey with nine random choice tasks.

Identifying mechanisms by which social determinants of health impact TB diagnostic evaluation uptake in Uganda: a qualitative study.

Background: Social and structural determinants of health (SDoH) are associated with tuberculosis (TB) outcomes but often unaddressed in TB care programs. We sought to describe the mechanism by which SDoH impact completion of TB diagnostic evaluation in Uganda using an implementation science framework rooted in behavioral theory.

Methods: Trained research staff interviewed 24 purposively sampled adults undergoing TB diagnostic evaluation at six community health centers in Uganda between February-August 2019.

Protocol for the effectiveness of multimonth refill of antituberculosis drugs (MORAD) on treatment success among people with drug-susceptible tuberculosis in rural eastern Uganda: a non-inferiority randomised trial.

Introduction: Multimonth dispensing of antituberculosis (TB) drugs reduces frequent visits and costs associated with longer travel distances to a TB clinic. We will evaluate the effectiveness of multimonth dispensing of anti-TB drugs on treatment success in individuals with drug-susceptible TB in rural eastern Uganda, and explore its relevance and appropriateness from the stakeholders' perspectives.

Methods And Analysis: In this open-label, non-inferiority, individually randomised trial, we will randomise 260 participants to either the intervention (multimonth dispensing of anti-TB drugs) or control arm (routine care) and follow-up for 6 months.

Stool processing methods for Xpert Ultra testing in childhood tuberculosis: A prospective, multi-country accuracy study.

Background: Centrifuge-free processing methods support stool Xpert Ultra testing for childhood tuberculosis (TB), but there are limited data on their accuracy, acceptability and usability.

Methods: We conducted a prospective evaluation of stool Xpert Ultra in India, South Africa, and Uganda with three methods: Stool Processing Kit (SPK), Simple One-Step (SOS), and Optimized Sucrose Flotation (OSF). Children <15 years old with presumptive TB had respiratory specimen testing with Xpert Ultra and culture.

Plasma proteomics for novel biomarker discovery in childhood tuberculosis.

Failure to rapidly diagnose tuberculosis disease (TB) and initiate treatment is a driving factor of TB as a leading cause of death in children. Current TB diagnostic assays have poor performance in children, and identifying novel non-sputum-based TB biomarkers to improve pediatric TB diagnosis is a global priority. We sought to develop a plasma biosignature for TB by probing the plasma proteome of 511 children stratified by TB diagnostic classification and HIV status from sites in four low- and middle-income countries, using high-throughput data-independent acquisition mass-spectrometry (DIA-PASEF-MS).

Impact of a multicomponent strategy including decentralized molecular testing for tuberculosis on mortality: planned analysis of a cluster-randomized trial in Uganda.

Background: Rapid diagnosis of tuberculosis (TB) is important for improving outcomes and reducing transmission. Previous studies assessing the impact of Xpert MTB/RIF (Xpert), a molecular assay that provides results within 2 h, on mortality have been inconclusive. In this planned analysis of a pragmatic cluster-randomized trial in Uganda, we assessed whether a multicomponent strategy, including decentralized Xpert testing, decreased mortality among adults evaluated for TB.

C-Reactive Protein-based Screening of People with Tuberculosis Symptoms: A Diagnostic Accuracy Study.

C-reactive protein (CRP)-based tuberculosis (TB) screening is recommended for people with HIV. However, its performance among people without HIV and in diverse settings is unknown. In a multicountry study, we aimed to determine whether CRP meets the minimum accuracy targets (sensitivity ⩾ 90%, specificity ⩾ 70%) for an effective TB screening test.