AIM:We report the longitudinal analysis of QuantiFERON-Gold Plus (QFT-plus) results from a clinical trial conducted in three high TB/HIV burden countries, comparing three different tuberculosis preventive treatment (TPT) regimens in people living with HIV (PLHIV). METHODS:PLHIV were enrolled in Ethiopia, Mozambique and South Africa, and randomised to: (i) one course of weekly rifapentine-isoniazid for 3 months (3HP); (ii) weekly rifapentine-isoniazid for 3 months given annually for 2 years (p3HP); (iii) daily isoniazid for 6 months (6H). QFT-plus testing was performed at baseline, M12 and M24. Quantitative and qualitative results, and serial changes (conversions and reversions) were assessed. RESULTS:From baseline to M12, 13.0% (196/1502) of participants converted, with no differences between 3HP (13.1%) and 6H (12.9%). From M12 to M24 conversion occurred in 4.0% of participants receiving p3HP and 9.4% of those receiving 3HP (p-value 0.110). Overall reversions occurred in 19.0% (178/935) of participants. Reversion rates were similar across study arms and timepoints. The risk of developing TB during the study period was higher among individuals QFT-plus positive at baseline (aHR, 1.66; 95% CI, 1.41-1.89, p-value = 0.034). CONCLUSION:QFT-Plus conversions and reversions occurred frequently in PLHIV and did not differ by TPT regimen, or between those who did and did not receive a second course of TPT. The high rate of QFT-positivity, along with the large proportion of conversions despite TPT highlights the complexity of interpreting serial IGRA results in PLHIV in high-transmission scenarios.

Tuberculosis remains a major global health challenge, despite recent advances in drug and regimen development. Pragmatic randomised trials are needed to evaluate the effectiveness, safety, and tolerability of new tuberculosis treatments under routine care conditions to appropriately inform practice guidelines and facilitate uptake. In this Review, we propose guiding principles for pragmatic tuberculosis treatment trials. Using the PRECIS-2 framework, we address eligibility, recruitment, setting, organisation of care, adherence support, outcomes, follow-up, primary analysis, data collection, and monitoring. Pragmatic trials should maximise generalisability through broad inclusion criteria, integration within routine health systems, and flexible delivery approaches while maintaining appropriate standards for participant safety and data reliability. We discuss considerations for individually randomised and cluster-randomised designs, outcome definitions, risk-proportionate monitoring, and streamlined data collection. Adoption of these principles will improve the generation of real-world evidence and facilitate global implementation of effective tuberculosis treatments.

Inadequate adherence to tuberculosis (TB) treatment increases the risk of treatment failure and recurrence. Identifying factors contributing to poor adherence could refine targeting strategies and optimize resource distribution. We examined specific individual-level factors for TB treatment adherence among adults with drug-sensitive TB, including HIV status, antiretroviral therapy, time to access clinical care, and perceived stigma. Data are from the “TB Mate” cluster-randomized trial, which evaluated a TB treatment adherence intervention across 18 public health clinics in South Africa (PACTR201902681157721). Treatment adherence was measured using smart pillboxes, with pillbox opening recorded as a proxy for the dose taken. Adults in the control group, utilizing the pillbox in silent mode, were included in this analysis. We used logistic regression to model poor adherence (< 80

Mobile health (mHealth) technologies are increasingly used to support community-based healthcare. However, their real-world impact often remains unclear. Understanding implementation factors is essential for advancing their use and achieving meaningful health outcomes. We evaluated an mHealth tool (AitaHealth) after customising its modules and workflows for household Tuberculosis (TB) contact tracing and other community-based data collection by community health workers (CHWs). We describe the acceptability, feasibility, and implementation fidelity of this approach. We conducted a mixed-methods evaluation in two South African districts: uMkhanyakude and Ekurhuleni. We collected qualitative data through focus group discussions (FGDs) and in-depth interviews (IDIs) with CHWs, team leaders, and key stakeholders. We used deductive thematic analysis grounded in the Technology Acceptance Model (TAM) to assess the acceptability and implementation feasibility of the mHealth tool. We used quantitative data from the AitaHealth metadata to assess implementation fidelity. CHWs appreciated AitaHealth's efficiency, data security, and credibility. Across the two districts, 103 CHWs recorded data for 2,452 households and 10,649 household members. However, they reported challenges in ease of use, with unreliable devices, weak support, and safety concerns hindering data collection. These issues led to inconsistent engagement, with 48.5% of CHWs logging in fewer than 15 times during implementation. Despite these challenges, when used, AitaHealth ensured high-quality data collection and household coverage, with TB-related fields completed in over 94% of households, demonstrating its potential under better conditions. AitaHealth`s limitations stemmed from system constraints rather than user resistance. To achieve full impact, mHealth tools require reliable infrastructure and supportive environments for both the tools and their implementers.

BACKGROUND:Tuberculosis household contacts are at elevated risk of HIV, and systematic screening for tuberculosis is an opportunity for people to know their status. We aimed to assess the coverage and positivity of HIV testing during household systematic screening for tuberculosis. METHODS:For this systematic review and meta-analysis (PROSPERO: CRD42024471979), we searched MEDLINE, Embase, Global Health, and Africa Wide databases from Jan 1, 2000, to June 24, 2025. The primary analysis population was household contacts of people with tuberculosis without known HIV. Studies were included if HIV testing was offered to household contacts, and in the primary analysis if people known to be living with HIV were excluded from the population eligible for testing. We extracted or derived coverage (proportion of people eligible for testing who received an HIV test) and positivity (proportion of people tested with a positive result) and calculated pooled proportions using random effects meta-analysis. We narratively summarised themes from qualitative reports. Meta-regression examined the association of national HIV prevalence, time period, and participant age, with coverage and positivity of HIV testing. FINDINGS:Searches identified 31 quantitative studies (110 090 people), of which 17 (40 407 people) were included in primary analyses. Seven qualitative studies reported community or provider perspectives. The pooled proportion of eligible household contacts tested for HIV was 72·9% (95% CI 60·3-83·9), ranging from 0% to 100%. Pooled positivity of testing was 5·9% (3·6-8·8) overall. Positivity was 9·7% (5·8-14·5; ten studies) in countries with ≥10% national adult HIV prevalence. Qualitative studies highlighted context-dependent facilitators and barriers of household contacts' capability, opportunity, and motivations to engage with HIV testing. INTERPRETATION:Few studies have evaluated HIV testing for tuberculosis household contacts. Coverage of testing was reasonable but varied substantially across studies. Positivity of testing was high. Further research is needed to understand and optimise acceptability and ensure feasibility of HIV testing within screening of tuberculosis among household contacts, and tuberculosis-HIV programmes in high HIV-incidence settings should consider monitoring implementation of HIV within routine tuberculosis household contact screening. FUNDING:National Institute for Health and Care Research and Wellcome Trust.

BACKGROUND:Tuberculosis preventive therapy coverage for people with advanced HIV disease (AHD) is poor. Innovative delivery strategies to increase tuberculosis preventive therapy uptake are needed; we sought to evaluate the safety and feasibility of two strategies for ultra-short course tuberculosis preventive therapy with 1 month of daily rifapentine plus isoniazid (1HP). METHODS:In this phase-3, open-label, non-inferiority, randomised controlled strategy trial (ISRCTN 18437550), we recruited consecutive adults (aged ≥18 years) admitted to hospital with AHD receiving treatment for cryptococcal meningitis who were screened for active tuberculosis during their hospitalisation from three tertiary referral hospitals in Uganda (Mulago National Specialised Hospital, Kiruddu National Referral Hospital in Kampala, and Mbarara Regional Referral Hospital). Adults without evidence of tuberculosis disease and meeting all eligibility criteria were approached for consent and inclusion. Patients were excluded if they had evidence of active hepatitis B infection, abnormal liver function tests, had known chronic liver disease, were jaundiced, were pregnant or breastfeeding, or presented with a clinical syndrome which, in the opinion of the attending clinician, put the patient at significant risk if they were to participate in the trial. After providing informed consent, we randomly assigned participants (1:1) to inpatient initiation of 1HP before hospital discharge or outpatient initiation at 6 weeks after time of cryptococcal meningitis diagnosis. 1HP was standardised across treatment groups, a 28-day course of 600 mg rifapentine plus 300 mg isoniazid daily with adjunctive pyridoxine (25 mg per day). The 1HP regimen was not dose adjusted on the basis of weight. The primary endpoint was tuberculosis disease-free survival and 1HP treatment completion at 18 weeks, powered for a 15% non-inferiority margin; analysis was by intention to treat. FINDINGS:From Jan 24, 2022, to Nov 13, 2024, 419 adults were screened after 210 were found ineligible and four died before random allocation, 205 were randomly allocated (171 in Kampala and 34 in Mbarara, Uganda): 103 to the inpatient group and 102 to the outpatient group. 119 participants (58%) were male and 86 (42%) were female. In the primary adjusted intention-to-treat analysis, 72 participants in the inpatient 1HP group (70%) had tuberculosis disease-free survival and 1HP treatment completion at 18 weeks compared with 63 (62%) in the outpatient 1HP group (adjusted risk difference 7·1%, 90% CI -3·8 to 17·9) confirming non-inferiority. Treatment completion was achieved in 78 (76%) of 103 in the inpatient 1HP group compared to 67 (66%) of 102 in the outpatient 1HP group (site-adjusted risk difference 9·7%, 95% CI -2·4 to 21·8). 170 grade 3 or 4 adverse events occurred in 99 (48%) of 205 participants. Among participants who had taken at least one dose of 1HP the frequency of adverse events across trial groups was similar apart from grade 4 anaemia, which occurred in a higher proportion of participants in the outpatient group (9% vs 2%, p=0·045). INTERPRETATION:1HP initiation before hospital discharge was non-inferior to outpatient initiation among adults with AHD and cryptococcosis. These data suggest that following exclusion of active tuberculosis disease, inpatient 1HP initiation is feasible and comparably safe compared with outpatient initiation. FUNDING:The Wellcome Trust, UK National Institute for Health and Care Research, US National Institutes of Health.

Social network interventions (SNIs) can leverage influential individuals within personal networks to amplify health behavior adoption and intervention diffusion. While SNIs are potentially effective in enhancing uptake of HIV prevention and other interventions, identifying optimal peer leaders remains challenging. This study assessed how social network-based approaches can improve peer leader identification compared to non-structural approaches (i.e., those that do not use network data for promoter selection). Between 8 th October 2024 and 31 st March 2025, we mapped the social connections among fishermen in two communities in Mangochi, Malawi. The communities had previously participated in a cluster-randomized trial (FISH), which aimed to create demand among fishermen for HIV and schistosomiasis services via peer-nominated leaders. Using Network Canvas and a photographic census, we conducted a network survey, capturing ties, support roles and interaction frequency. Whole-network maps were constructed, centrality measures and the key player problem positive (KPP-POS) algorithm were applied to identify the highest-ranking individuals as potential promoters. We compared the reach (i.e., proportion of nodes within two steps of a promoter) of peer-nominated leaders selected by FISH to these sociometric methods . We recruited 370 of 397 eligible fishermen (mean age 34.8years [SD 13.11]). Both communities exhibited sparse, low-reciprocity networks with long path lengths. One network had two dense cores, while the other featured a single core. There was no evidence of assortative mixing by education, age or village of residence. FISH trial peer leaders were not consistently central in the constructed maps. The KPP-POS algorithm identified alternative, more dispersed nodes, achieving the highest reach (66% in F001; 75% in F024) versus in-degree (58%, 67%), closeness (58%, 68%), betweenness (58%, 69%) and eigenvector (60%, 68%) promoter sets. Our findings highlight that strategically identified promoters can achieve good reach within social networks, crucial for effective public health programming in complex settings like fishing communities.

Background:Tuberculosis remains the leading infectious cause of death worldwide. In the WHO African region, declining incidence has coincided with antiretroviral therapy (ART) scale-up, though whether this reflects reduced progression to disease or reduced transmission is unclear. We evaluated how ART and symptom status influence within-household Mycobacterium tuberculosis complex (MTBC) transmission risk. Methods:We conducted a case-contact household study in rural South Africa, enrolling index adults with bacteriologically-confirmed pulmonary tuberculosis. MTBC immunoreactivity was measured in all child household contacts (aged 2-14 years) as a proxy measure of within-household transmission. We assessed the influence of index person ART status and symptom status and explored effect-measure modification of the association between index person HIV status and transmission risk by sex. Results:Among 755 child contacts of 296 index persons, effective ART was not associated with within-household MTBC transmission risk (risk ratio [RR], 1.07; 95% CI, 0.66-1.74). Among PLHIV engaged in ART care, WHO TB four-symptom screen (WHO4SS) status was not associated with transmission risk (RR, 0.80; 95% CI, 0.43-1.47), although absence of reported cough reduced risk (RR, 0.61; 95% CI, 0.38-0.96). A pronounced interaction between sex and HIV status was observed: HIV-negative women had the highest within-household MTBC transmission risk (30.5% vs. 14.3% in women with HIV) whereas risks were similar between HIV-positive and HIV-negative men. Conclusions:We found no evidence that effective ART or WHO4SS status influenced within-household MTBC transmission risk, though confidence intervals were wide. Absence of reported cough was associated with lower risk, and transmission risk was highest among child contacts of HIV-negative women. These findings suggest reported cough is a useful marker of transmission risk and that routine tuberculosis screening within ART care may reduce transmission from PLHIV; intensified efforts are nonetheless needed to achieve earlier tuberculosis detection in HIV-negative individuals.

Chronic conditions both drive development of and are consequences of tuberculosis (TB). While there is growing awareness of chronic lung disease, data on other health conditions post-TB are limited. In this cross-sectional study in Zimbabwe, we offered adults with pulmonary TB an integrated health check at or after treatment completion, assessing uptake and yield. Members of the same households were also offered the intervention. Selecting household members without prior or current TB as a comparator, we calculated odds ratios (OR) for HIV, diabetes, hypertension, underweight, anaemia, symptoms of mental health disorders, self-reported memory difficulty, vision impairment, chronic lung disease and multimorbidity (two or more of the above); and compared health-related quality of life (HRQoL; EQ-5D value). Of 229 people with TB invited, 96 (42%) participated (median age 38 years, 54% men, median 356 days from diagnosis). Common reasons for non-participation were migration and work. Among people with TB, chronic conditions were common and, other than HIV, mostly undiagnosed. Ninety-one percent of people with recent TB had at least one chronic condition; almost two-thirds had two or more. Compared to 285 household comparators (median age 34 years, 71% female) and after adjustment for age and sex, people with recent TB were more likely to have at least one chronic condition (OR 2.30 [95% confidence interval 1.03-5.11]) but not multimorbidity (1.55 [0.86-2.78]). People with recent TB had greater odds of HIV (1.77 [1.03-3.04]), symptoms of mental health disorders (1.57 [0.96-2.56]), self-reported memory difficulty (2.13 [1.19-3.80]), impaired lung function (3.24 [1.46-7.20] among 39/92 people with TB and 155/285 household comparators with data available), and underweight (5.15 [2.28-11.61]) compared to household comparators without prior TB; hypertension was less common (0.40 [0.20-0.79]) and HRQoL was worse (p = 0.005). Uptake of chronic disease screening among people with recent TB was low, but prevalence of chronic conditions was high. Holistic approaches to treatment which identify and address these conditions are needed. The contribution of post-TB multimorbidity to morbidity and mortality among TB survivors should be included in global disease estimates. Whilst comparison to household controls aimed to reduce confounding by socio-economic status, a limitation of this approach is externality, whereby the health status of the person with TB influenced that of their household members.

To end the tuberculosis (TB) epidemic, the WHO recommends implementing active case-finding to increase TB detection, as well as the provision of TB preventive treatment (TPT) in contacts of people with TB. However, the scale-up of both strategies remains limited in high TB-burden countries such as Thailand. Despite the country’s highly decentralised healthcare system, significant inequalities remain in access to care, particularly in vulnerable populations. We designed an intervention study investigating the effectiveness and feasibility of a novel strategy combining active case-finding and the implementation of short-course TPT in households of newly diagnosed adults with TB in Thailand. This is a pragmatic phase IV stepped-wedge cluster-randomised trial conducted in 20 provincial hospitals (clusters). The study population comprises household members who were exposed within the last 3 months to adults with newly detected bacteriologically confirmed TB. The intervention combines an educational video to the index TB case, provision of an invitation card to household contacts for free TB screening at the facility, with a transport voucher, and support from village or urban health volunteers. Household contacts without active TB are offered TPT regimens according to age: 1-month rifapentine-isoniazid (1HP), 3-month rifapentine-isoniazid (3HP) or 3-month rifampicin-isoniazid (3HR). In the control phase, TB staff implement the current standard of care, including verbal information to persons newly diagnosed with TB on the need to screen their household contacts and provision of standard TPT. Hospitals shift from the control to the intervention phase every 3 months in four randomised sequences until all clusters apply the intervention. Generalised linear mixed models will be used to compare the intervention outcomes versus the standard of care, controlling for clustering and confounding by time. Active case-finding and systematic TPT in at-risk populations is currently limited in Thailand. This protocol incorporates pragmatic design features with a participant-centred approach to assess the effectiveness, feasibility and acceptability of a combined strategy including systematic screening of household contacts, active case-finding and TPT provision. If successful, this strategy will likely contribute to TB elimination in Thailand and beyond. The study is registered at ClinicalTrials.gov NCT05581212 on April 3rd, 2024, and is currently recruiting.

BACKGROUND:Recent trials have demonstrated that shortened 4-month treatment durations are effective for the majority of people with tuberculosis (TB). However, there is a population of patients with TB who require longer treatment durations. Prospectively identifying those who require shorter versus longer treatment durations would support evaluation and implementation of optimized regimens. METHODS:We analyzed data from the RIFASHORT TB treatment-shortening noninferiority trial to define a TB phenotype classification. The RIFASHORT trial primary outcome was reanalyzed using the protocol-defined noninferiority criterion of 8 percentage points, stratifying by those classified as having limited or extensive disease. RESULTS:Xpert MTB/RIF semiquantitative bacterial burden in combination with TB disease involvement grading on chest X-ray achieved the strongest differentiation between relapse and nonrelapse. The extensive disease TB phenotype (high semiquantitative bacterial burden and extensive TB disease on X-ray) accounted for one-quarter of the RIFASHORT trial population and more than half of all posttreatment TB relapses (13/23). For the limited TB disease phenotype (a semiquantitative bacterial burden other than high or no extensive TB disease on X-ray), the experimental 4-month 1200-mg rifampicin-containing regimen met the protocol-defined noninferiority criterion in both modified intention-to-treat (adjusted risk difference: -1.3%; 95% CI, -6.7% to 4.0%) and per protocol analyses (1.7%; 95% CI, -3.8% to 7.1%). CONCLUSIONS:The TB phenotype classification derived here successfully identified three-quarters of RIFASHORT trial participants for whom a 4-month 1200-mg rifampicin regimen was noninferior to the 6-month standard of care. A definitive phase III randomized trial of disease-stratified rifampicin-based TB treatment is justified.

Background Globally, over one-third of pulmonary tuberculosis (TB) disease diagnoses are made based on clinical criteria after a negative bacteriological test result. There is limited information on the factors that determine clinicians’ decisions to initiate TB treatment when initial bacteriological test results are negative. Methods and findings We performed a systematic review and individual patient data meta-analysis using studies conducted between January 2010 and December 2022 (PROSPERO: CRD42022287613). We included trials or cohort studies that enrolled individuals evaluated for TB in routine settings. In these studies, participants were evaluated based on clinical examination and routinely used diagnostics and were followed for ≥1 week after the initial test result. We used hierarchical Bayesian logistic regression to identify factors associated with treatment initiation following a negative result on an initial bacteriological test (e.g., sputum smear microscopy (SSM), Xpert MTB/RIF). Multiple factors were positively associated with treatment initiation: male sex [adjusted odds ratio (aOR) 1.61 (1.31, 1.95)], history of prior TB [aOR 1.36 (1.06, 1.73)], reported cough [aOR 4.62 (3.42, 6.27)], reported night sweats [aOR 1.50 (1.21, 1.90)], and having HIV infection but not on ART [aOR 1.68 (1.23, 2.32)]. Treatment initiation was substantially less likely for individuals testing negative with Xpert [aOR 0.77 (0.62, 0.96)] compared to smear microscopy and declined in more recent years. We were not able assess why clinicians made treatment decisions, as these data were not available. Conclusions Multiple factors influenced decisions to initiate TB treatment despite negative test results. Clinicians were substantially less likely to treat in the absence of a positive test result when using more sensitive, PCR-based diagnostics.

INTRODUCTION:HIV remains a global health challenge with a reported 39 million people living with HIV (PLHIV) in 2022. Sub-Saharan Africa, Asia and the Pacific are home to 82% of PLHIV, where limited access to healthcare resources underscores the urgency of innovative strategies to combat the epidemic effectively. Social network interventions (SNIs) hold promise for improving HIV testing and linkage services by engaging populations at greatest risk. This review evaluates the key design features and effectiveness of SNIs for HIV testing and linkage in low- and middle-income countries (LMICs). METHODS:We searched four databases (Medline, Embase, Global Health, Web of Science) for the period from 1st January 2003 until 16th June 2023. A combination of the terms "Social Network," "HIV," "testing" and "linkage" with an LMIC filter was used. We included interventional study designs that compared an SNI for HIV testing and/or linkage to care against non-network comparator approaches. Narrative synthesis and random effects meta-analyses were conducted to synthesize the results. RESULTS:Of the 6763 records, 13 studies met the inclusion criteria; eight were randomized controlled trials, and five were non-randomized designs. Nine studies engaged key populations. The most common strategy involved recruiting and training seeds, who then delivered HIV services to network members. The use of networks varied significantly across the papers. The network approaches used were induction (n = 11), alteration (n = 1) and a combination of individual and segmentation approaches (n = 1). The pooled estimates showed that SNIs had a modest effect on the uptake of HIV testing RR 1.12 [95% CI 1.08-1.17) but the directionality of effect for the proportion newly diagnosed positive (RR 0.88 [95% CI 0.74-1.04]) and linkage to care (RR 0.98 [95% CI 0.86-1.08]) was towards the null. DISCUSSION:SNIs improved the uptake of HIV testing and exhibit important variability in their design. CONCLUSIONS:There is a need for more studies designed to capture the complex relational dynamics of network interventions and to provide strong evidence on their isolated effects. Additionally, it is necessary to expand the use of network approaches to other priority populations. PROSPERO NUMBER:CRD42023434770.

Background New 6-month rifampicin-resistant tuberculosis treatment regimens containing bedaquiline, pretomanid, and linezolid (BPaL) with or without moxifloxacin or clofazimine, could improve treatment efficacy, safety, and tolerability, and free up resources within the health system. Following a change to WHO rifampicin-resistant tuberculosis treatment guidelines, countries are facing difficult decisions about when and how to incorporate new drug regimens into national guidelines. We aimed to assess the probability of BPaL-based regimens being cost-saving using data collected in the TB-PRACTECAL trial. Methods This economic evaluation using a cost-utility analysis was embedded in five TB-PRACTECAL trial sites in Belarus, Uzbekistan, and South Africa. Between Nov 19, 2020, and Sept 27, 2022, we collected detailed primary unit cost data in six hospitals and four ambulatory health facilities and collected data on patient-incurred costs from 73 trial participants. The primary efficacy endpoint of the main trial, a composite of unfavourable outcomes (death, disease recurrence, treatment failure, early discontinuation of therapy, withdrawal, or loss to follow-up) and clinically important safety outcomes by 72 weeks of follow-up were incorporated into the analysis. Societal perspective cost data and effect outcome data were input into a Markov model to estimate the cost per disability-adjusted life-year (DALY) averted by BPaL-based regimens compared with the standard of care over a 20-year time horizon. We conducted a range of univariate and probabilistic sensitivity analyses to test our findings. Findings BPaL-based regimens averted a mean of 128 DALYs and saved a mean of US$14868 (SD 291) per person from the provider perspective compared with standard-of-care regimens over 20 years. Patient-incurred costs were reduced by a mean of $172 (SD 084) in BPaL-based regimen groups compared with standard of care. The main cost drivers for both providers and patients were inpatient bed-days; the duration of the inpatient period varied across countries. Varying a range of model parameters affected the degree of cost savings but did not change the finding that BPaL-based regimens are cost-saving compared with standard of care. Interpretation This trial-based evidence adds to consistent indications from modelling studies that BPaL-based regimens are cost-saving for both the patient and health system. Urgent implementation of BPaL-based regimens in countries with a high burden of tuberculosis could improve treatment of rifampicin-resistant tuberculosis, reduce pill burden, and free up desperately needed resources within the health system.

Intensified tuberculosis (TB) case finding is recommended for people living with HIV (PLHIV) at every clinical encounter using the World Health Organization (WHO) screening tool (W4SS), comprising any of current cough, fever, night sweats or weight loss. We determined the frequency of W4SS symptoms at repeat visits among individuals without TB attending for HIV care in Gauteng province, South Africa. In a cohort study, we enrolled PLHIV (adults) attending clinics for routine HIV care. At enrolment, patients were screened using W4SS, and categorised into high (cough, body mass index (BMI) ≤ 18.5, CD4 < 100 cells/mm3, fever ≥ 3 weeks, and unintentional weight loss ≥ 10

BACKGROUND:People with human immunodeficiency virus (PHIV) admitted to the hospital have high mortality, with tuberculosis (TB) being the major cause of death. Systematic use of new TB diagnostics could improve TB diagnosis and might improve outcomes. METHODS:We conducted a cluster randomized trial among adult PHIV admitted to Zomba Central Hospital, Malawi. Admission days were randomly assigned to: enhanced TB diagnostics using urine lipoarabinomannan (LAM) antigen tests (SILVAMP-LAM, Fujifilm, Japan and Determine-LAM, Alere/Abbot, USA), digital chest X-ray with computer-aided diagnosis (dCXR-CAD, CAD4TBv6, Delft, Netherlands), plus usual care ("enhanced TB diagnostics"); or usual care alone ("usual care"). The primary outcome was TB treatment initiation during admission. Secondary outcomes were 56-day mortality, TB diagnosis within 24 hours, and undiagnosed TB at discharge, ascertained by culture of one admission sputum sample. FINDINGS:Between 2 September 2020 and 15 February 2022, we recruited 419 people. Four were excluded postrecruitment, leaving 415 adults recruited during 207 randomly assigned admission days in modified intention-to-treat analysis. At admission, 90.8% (377/415) were taking antiretroviral therapy with a median CD4 cell count of 240 cells/mm3. In the enhanced diagnostic arm, median CAD4TBv6 score was 60 (interquartile range: 51-71), 4.4% (9/207) had SILVAMP-LAM-positive and 14.4% (29/201) had Determine-LAM-positive urine with 3 samples positive by both urine tests. TB treatment was initiated in 46/207 (22.2%) in the enhanced TB diagnostics arm and 24/208 (11.5%) in the usual care arm (risk ratio, 1.92; 95% confidence interval [CI]: 1.20-3.08). There was no difference in mortality by 56 days (enhanced TB diagnosis: 54/207, 26.1%; usual care: 52/208, 25.0%; hazard ratio. 1.05; 95% CI: .72-1.53); TB treatment initiation within 24 hours (enhanced TB diagnosis: 8/207, 3.9%; usual care: 5/208, 2.4%; risk ratio, 1.61; 95% CI: .53-4.71); or undiagnosed microbiological-confirmed TB at discharge (enhanced TB diagnosis, 0/207 [0.0%], usual care arm 2/208 [1.0%]; P = .50. INTERPRETATION:Urine SILVAMP-LAM/Determine-LAM plus dCXR-CAD diagnostics identified more hospitalized PHIV with TB than usual care. The increase in TB treatment appeared mainly because of greater use of Determine-LAM, rather than SILVAMP-LAM or dCXR-CAD. Poor concordance between Determine-LAM and SILVAMP-LAM urine tests requires further investigation. Inpatient mortality for adults with human immunodeficiency virus remains unacceptability high.

Social networks play a vital role in influencing individual and collective health behaviors and facilitating the diffusion of health interventions. Fishing communities in sub-Saharan Africa face socio-cultural and occupational challenges such as low literacy rates and high mobility. However, their high social cohesion creates a unique social environment for spreading health interventions. We explored the role of social relationships in mediating health intervention adoption in these communities, to inform future intervention strategies. We conducted an exploratory phenomenological qualitative study between September and October 2024 nested within a large community cluster randomized trial (the FISH trial) in fishing communities in Mangochi district on the southern tip of Lake Malawi. We conducted four focus group discussions (N = 47) and 16 in-depth interviews. Data were analyzed thematically using a hybrid deductive and inductive data coding approach. Fishermen's social networks included fishing friendships, kin and broader community connections that facilitated knowledge exchange, resource sharing and support provision. Familiarity, trust, desire to conform to community norms and shared community ties enabled health knowledge exchange and encouraged uptake of targeted interventions for HIV and schistosomiasis, despite fishermen's mobility. Other facilitators at individual level included perceived susceptibility and financial incentives. Occasionally, negative rumors spread through peer networks, e.g., a link between blood sample collection and malign government agenda, contributed to disengagement with health interventions. Other factors including HIV-related stigma and prohibitive traditional beliefs interacted with social networks to hinder uptake. Fishermen's health decisions are deeply embedded within their social structures. However, other factors operating at the individual and community level were noted to be crucial catalysts of the decision-making process. This study highlights the potential of leveraging social networks in public health strategies for mobile communities so long as they account for critical individual factors that influence health service engagement.

Background:The Global Lung Function Initiative (GLI) and American Thoracic Society recently endorsed a race-composite spirometry reference equation ("GLI Global"). Africa (outside North Africa) is not represented in the underlying dataset; GLI Global has not been evaluated in the region. We evaluated the fit and diagnostic implications of GLI and African (identified by scoping review) reference equations in three East/Southern African countries. Methods:Among healthy participants from a tuberculosis household contact cohort study in Mozambique, Tanzania and Zimbabwe (age ≥10 years) with post-bronchodilator spirometry we calculated forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC z-scores using different equations, the proportion of people with obstructive airways disease or preserved-ratio-impaired spirometry by different equations. We compared these measures across reference equations. Results:In total, 806 healthy people had good-quality post-bronchodilator spirometry. Across GLI equations, "African American" fitted best (mean±sd FEV1 z-score -0.12±1.20, mean FVC z-score -0.35±1.19). Compared with "African American", GLI Global resulted in twice as many people being identified as having preserved-ratio impaired spirometry (22% versus 11%) with a similar proportion having obstruction (4.2% versus 3.8%). Reference equations developed in Africa conferred similar fit compared with the GLI African American equation. Conclusions:Reference equations have clinical and public health implications that demand careful consideration, particularly in resource-constrained environments. Use of GLI Global may result more people being identified as having lung function impairment. Further work that includes clinical outcomes is needed to ensure that GLI Global is globally representative. The key limitation of this work is the potential for people with undiagnosed respiratory disease to have been included in the analysis.

Digital adherence technologies (DATs) could improve the person-centeredness of tuberculosis (TB) treatment. DATs are found to be acceptable, though evidence of their effectiveness is varied. Our objective was to understand the fidelity of DAT interventions within five cluster-randomized trials. Two DATs (smart pillbox, medication labels) were assessed, with real-time adherence data available to healthcare providers (HCPs) on a digital platform in Ethiopia, the Philippines, South Africa, Tanzania, and Ukraine. A framework assessed four components of implementation: inputs (training, support, mobile access), processes (SMS, home visits, platform usage), outputs (DAT engagement, manual dosing), and outcomes (people with TB (PwTB)–HCP relationship). Fidelity was evaluated by quantitative indicators, and content analysis of qualitative sub-studies supplemented some indicators. Engagement with DATs was high among PwTB. Pillbox users showed high levels of sustained engagement (box opening), with digitally recorded doses ranging from 82% to 91%. Differences were observed in login frequency by HCPs to the adherence platform. In Ethiopia, Tanzania, and Ukraine, there was at least one login to the platform on 71% of weekdays per facility compared with the Philippines and South Africa at 42% and 52%, respectively. Intervention fidelity varied among countries, suggesting a need for future work on optimizing implementation.

Globally, tuberculosis incidence and mortality is driven by syndemic interactions of tuberculosis with other chronic conditions including HIV, diabetes and undernutrition in a deleterious social and structural context, often characterised by poverty. Systematic screening for tuberculosis among household contacts is a core element of the WHO tuberculosis strategy but is hampered in high-tuberculosis incidence settings by health system constraints and low participation by household members of people with tuberculosis. Reframing screening as a health check, informed by the syndemic framework, could improve uptake and address proximate determinants of tuberculosis. Within a larger research study aimed at evaluating new tuberculosis diagnostic tests we developed and, using mixed methods, evaluated an integrated health check in a prospective cohort of tuberculosis household contacts in Zimbabwe. This included screening for a range of health conditions, health education and counselling, and on-site treatment or referral. Of 836 identified household contacts, 700 (84%) participated in tuberculosis screening. Of those, 467 people (67% women, median age 28 years) were invited to the health check; all participated in the intervention. One percent (n = 5/459) were diagnosed with tuberculosis. Almost two thirds (n = 288) had at least one unmet health need (either undiagnosed or uncontrolled diabetes, hypertension, HIV, anaemia, undernutrition, common mental health disorders, vision impairment, or tuberculosis). Of those referred following the health check, 66% accessed care for at least one condition, with variation across conditions. In-depth interviews with participants (n = 28), informed development of a refined explanatory theory, illustrating the benefits of a syndemic theory-based approach to tuberculosis screening for household contacts. Members of tuberculosis affected households have multiple, intersecting and unmet health needs. A holistic approach to systematic screening of household contacts guided by the syndemic framework could improve the health of these vulnerable people, advancing progress towards both tuberculosis and sustainable development goals.