Tuberculosis survivors often face long-term physical, psychological, and social challenges that extend beyond microbiological cure. Post-tuberculosis complications include pulmonary damage, cardiovascular and neurological sequelae, as well as significant impacts on overall wellbeing and livelihoods. Despite increasing awareness, most care continues to focus primarily on lung disease, overlooking the multisystem and social needs of survivors. A holistic, people-centered framework that integrates medical, rehabilitative, and community-based strategies is essential for restoring health and facilitating societal participation among tuberculosis survivors.

Abstract We investigated host-genetic TB susceptibility by expression quantitative trait loci (eQTL) analysis of the tuberculin skin test (TST) as a standardised challenge model of human in vivo TB immunology. Paired genotyping with 415 RNA-sequencing profiles from day 2 and day 7 TST biopsies in 267 individuals with latent or active TB identified cis-eQTLs affecting 1,719 response genes. The strongest signal mapped to ERAP2 , and colocalisation analysis linked reduced ERAP2 expression to increased TB risk in GWAS data. Heritability was greatest in HLA class II antigen presentation and T-cell activation pathways. HLA-DR haplotypes associated with subsequent expansion of Mtb-reactive T cells, linking host genotype to antigen-specific immunity. Trans-eQTLs also identified a proliferative programme centred on NCAPD3 , implicating genetically regulated cell-cycle control as an antigen-independent determinant of T-cell immunity. These findings provide a functional framework for interpreting TB susceptibility loci and identification of candidate biomarkers for TB risk stratification and vaccine development.

Background and objectives:Tuberculosis remains a United Kingdom health concern. It occurs predominantly in people who have lived in tuberculosis endemic countries or have links there. Adherence to anti-tuberculosis treatment can be challenging, especially for people who experience severe side effects or social marginalisation. Poor adherence can lead to treatment failure. Current adherence support interventions make little difference to outcome. We identified the need for a 'manualised' approach to (1) improve case-managers' ability to detect people likely to non-adhere and (2) guide targeted adherence support. Objectives:Synthesise knowledge on drivers and interventions to support anti-tuberculosis treatment adherence Apply the Perceptions and Practicalities framework to understand poor adherence Develop a manualised intervention to identify adherence-related risks, modifiable barriers and support mechanisms Pilot the intervention and assess feasibility of data collection Evaluate implementation through fidelity and reach, and assess impact on adherence Assess intervention delivery costs to guide a full trial plus economic evaluation. Methods:The study ran April 2018-September 2022. Formative work included scoping reviews of adherence literature; National Health Service patients, caregivers, and health worker interviews; and clinic observations. A multidisciplinary group, including people with lived experience of tuberculosis, healthcare professionals, and researchers, coproduced the intervention package. We performed a (1 : 1) pilot cluster-randomised trial (N = 79 participants evaluated), randomising four London tuberculosis clinics, in preparation for a definitive cluster-randomised trial. Participants in control clinics received standard care. The primary outcome was adherence, doses taken of a possible 168 measured using evriMED boxes and other sources. We recorded treatment outcomes and changes in participants' needs, health-related beliefs and perceptions, costs, and health status. We conducted a mixed-methods process evaluation, using questionnaires, interviews, case-report forms, checklists and clinic observations. At intervention sites, additional resources were:Electronic tuberculosis needs assessment completed at all visits. Two animated videos to increase motivation and ability to take treatment. Interactive treatment guide designed around the Perceptions and Practicalities framework. Detailed manual for case managers. Results:We developed a tuberculosis needs assessment for tuberculosis services. This appeared better than standard care at identifying people requiring adherence support [e.g. at baseline 21/36 (58.3%) intervention vs. 4/43 (9.3%) control] and social support (over 24 weeks, on 29 vs. 6 occasions respectively). Cumulative dose-taking was high across the study population at 24 weeks [84% (95% confidence interval 78-91%) overall; 81% (68-93%) intervention; 88% (67-100%) control]. Dose-taking patterns were similar between arms. The videos and booklet produced short-term improvements in beliefs, necessity, concerns and practical barriers. Collecting health economic data using self-completed questionnaires was feasible; retrieving data from records more challenging. The intervention was acceptable to patients and staff though took longer than control to perform. Limitations:Study sample contained few people more likely to non-adhere. Assessments may have altered intervention's effects. Use of medication monitor in both arms may have affected results. Conclusions and future work:The intervention, a National Health Service first, is feasible to use. Its place in care and method of evaluation could be assessed in a larger, definitive study. Trial registration:This trial is registered as Current Controlled Trials ISRCTN 95243114. IRAS ID: 231542; REC reference number: 18/LO/1818. Funding:This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/88/06) and is published in full in Health Technology Assessment; Vol. 30, No. 28. See the NIHR Funding and Awards website for further award information.

BACKGROUND:Nontuberculous mycobacteria (NTM) are associated with chronic and challenging infections, particularly pulmonary disease (NTM-PD). While clinical guidelines provide treatment recommendations for the most common disease-causing species, they offer limited guidance on managing treatment failures. This study aims to develop a consensus-based decision-making framework for addressing treatment failure in NTM-PD. METHODS:A panel of 16 international experts used the e-Delphi method to address gaps in NTM-PD management. Initial statements were derived from an open-ended questionnaire, supported by a prior systematic review. Iterative rounds of expert evaluation were conducted until a consensus was reached on treatment failure definitions, decision-making criteria, therapeutic strategies and supportive care measures. RESULTS:Consensus defined treatment failure as the absence of culture conversion after 6 months of appropriate antimycobacterial therapy, while clinical and radiological deterioration were considered additional but non-mandatory criteria. Treatment intensification or de-escalation decisions were based on patient preferences, clinical status, comorbidities, disease severity, antibiotic tolerance, resistance patterns and previous treatment history. Treatment intensification highlighted the necessity for personalised multidrug antibiotic regimens. De-escalation strategies focus on delivering optimal, patient-centred supportive care while minimising pharmacological adverse effects, by opting for simplified antibiotic regimens, intermittent antibiotic courses for symptomatic control or the cessation of antimicrobial therapy. CONCLUSION:This study offers a structured approach to managing treatment failure in NTM-PD, addressing patient selection, treatment intensification, de-escalation and supportive care, while championing individualised strategies. Future research should concentrate on validating predictive factors for treatment response, refining therapeutic regimens and investigating host-directed therapies to enhance patient outcomes.

Background The clinical and prognostic implications of asymptomatic tuberculosis remain poorly understood. Methods We conducted a multicentre prospective cohort study to evaluate the association between asymptomatic tuberculosis (TB) and treatment outcomes. Individuals with rifampicin-susceptible pulmonary TB were enrolled from the Cohort Study of Pulmonary Tuberculosis. Asymptomatic TB was defined as the absence of any TB-related symptoms at diagnosis. The primary outcome was a favourable outcome, defined as treatment success without recurrence. Multivariable logistic regression models were used to assess associations between asymptomatic TB and favourable outcomes. The Cox proportional hazards model was applied to evaluate effect of asymptomatic TB on failure to complete treatment within 1 year. Stratified analyses by symptom status and mode of detection were performed to examine stratum-specific effects. Results Of 1071 individuals with pulmonary TB, 32.7% were asymptomatic. Compared to symptomatic patients, asymptomatic individuals were younger, less likely to be underweight and more often diagnosed through population health screening rather than clinical presentation or opportunistic testing. Asymptomatic TB was associated with higher likelihood of favourable outcome in multivariable models (adjusted odds ratio (aOR) 1.50, 95% CI 1.04-2.20) and a reduced risk of failing to complete treatment within one year in survival analyses (adjusted hazard ratio 0.66, 95% CI 0.45-0.95). Asymptomatic TB detected through health screening had the most favourable outcomes (aOR 2.41, 95% CI 1.34-4.66). Conclusion Asymptomatic TB was significantly associated with treatment success without recurrence and particularly in patients identified through health screening. Our results support symptom-agnostic screening in TB control programmes.

T cells contribute to immune protection and pathogenesis in tuberculosis, but measurements of polyclonal responses have failed to resolve correlates of outcome. We report the temporal evaluation of the human in vivo clonal repertoire of Mycobacterium tuberculosis ( Mtb )-reactive T cell responses, by T cell receptor (TCR) sequencing at the site of the tuberculin skin test, as a model for a standardised antigenic challenge. Initial non-selective recruitment of T cells is followed by enrichment of Mtb -reactive clones arising from oligoclonal T cell proliferation. We introduce a modular computational pipeline, Metaclonotypist, to sensitively cluster distinct TCRs with shared epitope specificity, which we apply here to establish a catalogue of public Mtb -reactive HLA-restricted T cell metaclones. Although most in vivo Mtb -reactive T cells are private, 10 metaclones were sufficient to identify Mtb -T cell reactivity across our study population (N≥128), indicating striking population level immunodominance of specific TCR-peptide interactions that may inform patient stratification and vaccine development.

Introduction Managing patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) unresponsive to guideline-based therapy remains challenging due to limited treatment options and complex disease progression. This study systematically reviewed existing literature on management strategies and emerging therapeutic approaches for refractory NTM-PD.Methods We systematically reviewed studies on NTM-PD treatment failure published from inception until 31 January 2024, examining associated factors, intensification strategies, and supportive measures. Twenty-five studies met the inclusion criteria, mostly retrospective and observational, focusing on pulmonary disease by Mycobacterium avium complex and Mycobacterium abscessus species. Findings were synthesised qualitatively because of substancial heterogeneity in study design and outcomes.Results Before treatment intensification or de-escalation, the impact of antibiotics on health-related quality of life and microbiological factors, including acquired resistance and pathogen shifts, should be assessed. Severe baseline radiological findings and multiple prior regimen modifications were associated with lower treatment success. Evidence for supportive interventions—such as nutritional counselling, respiratory rehabilitation, and psychosocial support—remains limited. Intermittent intravenous antibiotics may aid symptom control. Depending on NTM species, additional antibiotics have been explored to intensify treatment, though evidence is largely observational. Surgical resection may be considered for localised disease, but recurrence risk remains substantial, particularly with preoperative positive cultures. Novel therapeutic approaches remain under investigation as potential alternatives.Discussion This systematic review underscores the complexity of managing refractory NTM-PD, highlighting the role of treatment intensification, symptom control, supportive measures, and knowledge gaps. While no standardised approach exists, individualised strategies incorporating clinical, microbiological, and radiological factors remain essential for optimising patient outcomes.

Antiretroviral therapy (ART) has transformed HIV into a manageable health condition with normal life expectancy. However, people with HIV continue to have poorer mental health compared to background populations, which may be linked to stigma, lack of social support, or socioeconomic challenges. Personalised care aims to improve the outcomes of people with long-term health conditions and the National Health Service (NHS) Long Term Plan looks to implement this (including access to health coaching and social prescribing). The SPHERE trial aims to assess whether a health and well-being coaching and social prescribing intervention improves patient-reported health and well-being among people living with HIV who have psychosocial needs. SPHERE will be conducted across seven HIV outpatient clinics in England and is a pragmatic, two-arm, parallel group randomised controlled trial (RCT) embedding a routine assessment of psychosocial needs in HIV care. Eligibility criteria are people living with HIV aged 18 or older, available for the duration of study follow-up and scoring 16 or more on an assessment of psychosocial need: “Positive-Outcomes-11” (PO-11), covering physical, psychological, social and socioeconomic aspects of health and well-being. The RCT requires 568 participants who will be individually randomised in a 1:1 ratio to either a health and well-being coaching and social prescribing intervention or usual care. The intervention consists of up to eight coaching sessions that will be delivered by health professionals (e.g. HIV nurses) who have received specialist training to become health and well-being coaches. The trial will also include an internal pilot phase, process evaluation (to evaluate intervention feasibility, acceptability and mechanisms of action), economic evaluation (to assess the cost-effectiveness of the intervention and impact on NHS resource use) and parallel observational study (to assess subsequent development of psychosocial needs among those not initially eligible for the trial). The primary outcome is defined as achieving a reduction in PO-11 score of at least 40

[This corrects the article DOI: 10.1016/j.lanepe.2025.101416.].

Introduction:Treatment of non-tuberculous mycobacterial pulmonary disease (NTM-PD) is often complex, relying on long treatment courses with multiple antibiotics, which are associated with treatment intolerance and failure. Current guidelines provide limited insight into non-pharmacological treatment, which is believed to be an important component of symptom control and is related to treatment outcomes with an established evidence base in other chronic respiratory diseases. Methods:The authors conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify studies on non-pharmacological interventions for NTM-PD, focusing on airway clearance techniques, pulmonary rehabilitation, nutritional support and psychological care. Results:There was little evidence regarding the impact of non-pharmacological interventions in NTM-PD. We identified three studies that described a positive impact of airway clearance techniques, including oscillating positive expiratory pressure, chest physical therapy with devices such as Acapella and Flutter, as well as chest oscillatory techniques (e.g. Vest) and hypertonic saline nebulisation. We found no relevant studies in NTM-PD reporting the use of nutrition, pulmonary rehabilitation or psychological care as interventions in this group of patients. Conclusions:Non-pharmacological interventions show potential in managing NTM-PD, although significant evidence gaps remain. This review highlights the importance of expanding high-quality studies on the use of these interventions to people with NTM-PD.

AbstractType I interferon responses have been considered detrimental to host protection in tuberculosis (TB). We provide novel data to challenge this paradigm, derived from transcriptional profiling of human in vivo immune responses to discover associations with radiographic disease severity in pulmonary TB, combined with mechanistic studies to test causality for observed associations using a zebrafish larval mycobacterial infection model. Type I interferon activity in tissue samples from the site of a standardised mycobacterial challenge, the tuberculin skin test, was associated with less severe human TB disease. Abrogation of type I interferon signalling, by CRISPR-mediated mutagenesis ofstat2, led to increased burden and dissemination ofMycobacterium marinuminfection in zebrafish larvae. The mechanism for increased severity of mycobacterial infection in zebrafish involves reduced recruitment of myeloid cells required to restrict bacterial growth. Our data support a clear host protective role for type I interferon responses in mycobacterial infection, with potential applications for risk-stratification of adverse outcomes and development of a host-directed therapy to mitigate against severe disease.

BACKGROUND:Tuberculosis (TB) incidence and mortality in people living with HIV can be reduced by TB preventive treatment (TPT). However, low levels of screening and uptake, poor adherence, and loss to follow-up considerably reduce its effectiveness. We therefore aimed to assess the losses within all steps of the screening and treatment cascade. METHODS:We carried out a comprehensive, global systematic review of the TPT cascade of care in people living with HIV (PROSPERO: CRD42020162396). To enhance data generalisability we included articles which reported the proportion of people living with HIV completing any step of the TPT cascade in low and high TB burden countries published before March 2024. Random effects meta-analysis produced pooled estimates of the proportion proceeding to the next step along the cascade. Results were explored through subgroup analyses and meta-regression. RESULTS:Data from 368 cohorts containing 2.7 million participants were included. High levels of heterogeneity in outcomes were seen. Most participants were from Africa (80.6%). Isoniazid monotherapy was used for TPT in 92.6% of cohorts, usually for 6 months. Substantial loss to follow-up was found throughout the treatment cascade, with more than one in six patients lost at the following steps: initial screening, immunological testing, treatment start and completion. Regimens lasting <6 months had higher completion rates (88.4%) than those lasting 6-9 months (74.4%) or >9 months (61.6%). CONCLUSIONS:Our analysis highlights substantial loss to follow-up at multiple steps during the care cascade. This may significantly lower the reported effectiveness of TPT in real-world settings. Research and policy should focus on simplified care pathways and novel, shorter treatment regimens that optimise retention in care.

OBJECTIVES:To measure severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibody seroprevalence within a cohort of adults with HIV and correlate demographics with response rates to SARS CoV-2 vaccination. DESIGN:Initial vaccine trials for SARS CoV-2 did not examine efficacy in people with HIV. We undertook the SCAPE-HIV study from April 2021 to November 2022 to focus on vaccine response in this population to guide future vaccine scheduling. METHODS:Participants completed a retrospective questionnaire. Nucleocapsid and spike antibodies to SARS CoV-2 (anti-N and anti-S) were tested. Demographic and HIV factors (CD4 + cell count, viral load) were correlated with quantitative serological outcomes. Anti-S titres less than 400 U/ml were considered low level. Follow-up was performed in a subset post third vaccination. RESULTS:Six hundred and twelve participants completed the study questionnaire, 520 were included in the final analysis. Most participants received either ChAdOx1-S recombinant vaccine or the BNT162b2 mRNA vaccine for the first two doses. Almost all participants (99.2%) in the main group had an anti-S antibody detected above the assay cutoff (>0.8 U/ml). Most participants (77.3%) had anti-S titres greater than 400 U/ml, with the median titre 1734 U/ml. Age over 60 years was significantly associated with lower (<400 U/ml) anti-S antibody titre ( P  < 0.0001). CONCLUSION:We demonstrate a high rate of anti-S seropositivity following SARS-CoV-2 vaccination in people with HIV. Age over 60 was the only parameter found to be associated with a lower anti-S antibody titre. Our findings suggest that COVID-19 vaccine scheduling should target older persons with HIV in line with the general population.

Background: On the basis of recent clinical trial data for the treatment of drug-susceptible and drug-resistant tuberculosis (TB), the American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America have updated clinical practice guidelines for TB treatment in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. Methods: A Joint Panel representing multiple interdisciplinary perspectives convened with American Thoracic Society methodologists to review evidence and make recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and GRADE-ADOLOPMENT (adoption, adaptation, and, as needed, de novo development of recommendations) methodology. Results: New drug-susceptible TB recommendations include the use of a novel 4-month regimen for people with pulmonary TB and a shortened 4-month regimen for children with nonsevere TB. Drug-resistant TB recommendation updates include the use of novel regimens containing bedaquiline, pretomanid, and linezolid with or without moxifloxacin. Conclusions: All-oral, shorter treatment regimens for TB are now recommended for use in eligible individuals

Background: Latent TB infection (LTBI) screening and treatment of population groups at high risk for TB is part of England's Tuberculosis Action Plan, which has succeeded in increasing testing volumes. However, analysis of the cost-effectiveness is hampered by a lack of detailed information on health service costs. Methods: We surveyed clinics with large volumes of activity, located in the London, West Midlands, South East & South West, and North West England TB Control Board areas. These represent three-quarters of England's TB diagnoses. We mapped clinical pathways and determined costs of staff time, testing, and drugs. Results: The clinics use interferon gamma release assays (IGRAs) (Quantiferon-TB Gold Plus, T-SPOT.TB, or both) for LTBI testing, and the most common outcomes of the testing pathways are asymptomatic patients testing negative (costing GBP64.11 per patient, range: GBP49.08-GBP81.02) or positive (costing GBP142.86(GBP120.95-GBP174.68)). Symptomatic patients, testing positive or negative, have higher costs (GBP124.35(GBP101.29-GBP138.23)). The estimated cost per patient diagnosed with LTBI is GBP458.32(GBP362.49-GBP571.47). Treatment costs depend on the regimen and the amount of monitoring the patient requires, e.g. 3 months daily Isoniazid and Rifampicin costs GBP192.86(GBP140.43-GBP255.32) for most patients, and GBP238.62(GBP157.47-GBP346.03) for those requiring more monitoring. 6 months daily Isoniazid costs GBP407.71(GBP342.56-GBP474.25). 4 months daily Rifampicin costs GBP226.98(GBP190.16-GBP270.73). One clinic uses 3 months of weekly Isoniazid and Rifapentine for some patients, costing GBP559.05. Discussion: These are the first detailed cost estimates of latent TB screening and treatment, and will enable improved assessment of cost-effectiveness, and allocation of resources. ### Competing Interest Statement PJW has received payment from Pfizer for teaching of mathematical modeling of infectious disease transmission and vaccination, and from the Dutch National Institute for Public Health and the Environment (RIVM) for participation in an audit committee on COVID-19 data analytics and modeling. All other authors report no potential conflicts. ### Funding Statement This work was funded by NIHR Health Technology Assessment grant NIHR127459. It was also supported by the UK MRC Centre for Global Infectious Disease Analysis (grant number MR/X020258/1); this award comes under the Global Health EDCTP3 Joint Undertaking. Support also come from the NIHR Health Protection Research Unit in Modelling and Health Economics, which is a partnership between the UKHSA, Imperial College London, and the London School of Hygiene & Tropical Medicine (grant code NIHR200908). RKG is funded by National Institute for Health Research (NIHR303184) and by NIHR Biomedical Research Funding to UCL and UCLH. IA is funded by the European Union under grant agreement no. 101046314 and the UK National Institute for Health and Care Research (NIHR) under grant NF-SI-0616-10037. The funding sources had no involvement in study design, analysis and interpretation of data, writing of the report, or the decision to submit the article for publication. The views expressed are those of the authors and not necessarily those of the UK Department of Health and Social Care; Foreign, Commonwealth and Development Office; European Union; UK Medical Research Council (MRC); National Institute for Health and Care Research (NIHR); or UK Health Security Agency (UKHSA). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Objectives: To measure SARS-CoV-2 antibody seroprevalence within a cohort of adults living with HIV and correlate demographics with response rates to SARS CoV-2 vaccination. Design: Initial vaccine trials for SARS CoV-2 did not examine efficacy in people with HIV. We undertook the SCAPE-HIV study from April 2021 to November 2022 to focus on vaccine response in this population to guide future vaccine scheduling. Methods: Participants completed a retrospective questionnaire. Nucleocapsid and spike antibodies to SARS CoV-2 (anti-N and anti-S) were tested. Demographic and HIV factors (CD4, viral load) were correlated with quantitative serological outcomes. Anti-S titres less than 400U/mL were considered low level. Follow-up was performed in a subset post third vaccination. Results: Six hundred and twelve participants completed the study questionnaire, 520 were included in the final analysis. Most participants received either ChAdOx1-S recombinant vaccine or the BNT162b2 mRNA vaccine for the first 2 doses. Almost all participants (99.2%) in the main group had an anti-S antibody detected above the assay cutoff (>0.8U/mL). Most participants (77.3%) had anti-S titres greater than 400U/mL, with the median titre 1734U/mL. Age over 60 years was significantly associated with lower (<400U/mL) anti-S antibody titre (p < 0.0001). Conclusions: We demonstrate a high rate of anti-S seropositivity following SARS-CoV-2 vaccination in people with HIV. Age over 60 was the only parameter found to be associated with a lower anti-S antibody titre. Our findings suggest that COVID-19 vaccine scheduling should target older persons living with HIV in line with the general population.

Background In low tuberculosis (TB)-endemic countries, tuberculosis preventive therapy (TPT) is recommended for immunocompromised individuals with a positive immunodiagnostic test. This study aimed to assess the performance of the QuantiFERON-TB Gold Plus (QFT+) assay and predictive power for future tuberculosis in immunocompromised individuals. Methods In this prospective observational study, immunocompromised adults >= 18 years of age including people living with HIV (PLHIV), chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, and immunocompetent adults with and without TB-disease were recruited at 21 sites in 11 European countries and tested with the QFT+ assay. Individuals without TB-disease were followed up for the development of tuberculosis. TB incidence rates (IR) were calculated, stratified by QFT+ results and acceptance of TPT. This study is registered with Clinicaltrials.gov, NCT02639936. Findings A total of 2663 individuals (1115 female, 1548 male) were enrolled from 03/11/2015 to 29/03/2019. Persons without tuberculosis were followed up for at least two years. Among 1758 immunocompromised individuals without active tuberculosis, 13.6% had positive QFT+ results. Sensitivity and specificity for TB-disease were 70.0% (52.1-83.3%) and 91.4% (89.6-92.9%), respectively, in immunocompromised, and 81.4% (76.6-85.3%) and 96.0% (92.5-97.9%), respectively, in immunocompetent individuals. During 2457 cumulative years of follow-up among 932 individuals with chronic renal failure, rheumatoid arthritis, solid-organ transplantation or stem-cell transplantation, including 83 persons with a positive QFT+ test without TPT, no-one developed active tuberculosis. In contrast, among 642 PLHIV without TPT, one with an indeterminate QFT+ and 3/30 individuals with a positive QFT+ developed active tuberculosis; all had detectable HIV-replication and low CD4 T-cell counts (incidence 4.1 (95% CI (1.3-12.4) per 100 person-years). No individuals receiving TPT developed active tuberculosis during 269 years of follow-up. Interpretation In immunocompromised individuals in low TB-endemic countries, the 2-year-risk for active tuberculosis was highest among PLHIV with detectable HIV-replication and low CD4-counts. In this study, the QFT+ assay did not strongly predict progression to active tuberculosis, which emphasises the need to incorporate additional risk factors. Funding None. Copyright (c) 2025 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Fluoroquinolones are increasingly important for anti-tuberculosis (TB) treatment. Identifying fluoroquinolone resistance (FR) is essential. Using sequencing data from over 16 000 unselected isolates, this first English survey of FR, found it present in 1.4% overall and 23.9% of multidrug-resistant TB. Routine sequencing allows clinically-relevant resistance surveillance and should be widely adopted.

Receipt of nebulised pentamidine in people with HIV was audited to identify if individuals were appropriately receiving nebulised pentamidine, and whether national guidelines were being followed when prophylaxis was commenced and discontinued. Of 76 people with who received nebulised pentamidine, the main indication for starting nebulised pentamidine was a co-trimoxazole adverse drug reaction. Co-trimoxazole desensitization was not attempted before starting nebulised pentamidine. The main indication for stopping nebulised pentamidine prophylaxis was when immune reconstitution occurred. This single centre audit revealed that national guidelines were being followed in most cases. The lack of information regarding the reason for starting or stopping nebulised pentamidine prophylaxis, or detail of the clinician’s concerns about potential poor adherence with oral regimens of prophylaxis as a reason for choosing nebulised pentamidine prophylaxis, identifies a need for improved documentation of clinicians’ decision-making. Introduction of pharmacist-led interventions/alerts using patients’ electronic records, similar to those used in primary care, would enable the specialist pharmacy team to identify when and if co-trimoxazole desensitization has been offered and discussed/declined before a clinician prescribes nebulised pentamidine as well as enabling identification of those in who pentamidine prophylaxis has been continued, despite “immune reconstitution”.