Drug-resistant tuberculosis treatments, the case for a phase III platform trial.

Most phase III trials in drug-resistant tuberculosis have either been underpowered to quantify differences in microbiological endpoints or have taken up to a decade to complete. Composite primary endpoints, dominated by differences in treatment discontinuation and regimen changes, may mask important differences in treatment failure and relapse. Although new regimens for drug-resistant tuberculosis appear very effective, resistance to new drugs is emerging rapidly.

TB PCR in BAL and EBUS-TBNA samples for the diagnosis of pulmonary and mediastinal lymph node TB: retrospective TRiBE study.

Introduction: The role of Xpert Ultra in bronchoalveolar lavage (BAL) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples for pulmonary and mediastinal lymph node tuberculosis (TB) remains unclear.

Methods: This was a retrospective observational service evaluation at a tertiary TB centre in a low-incidence setting. The diagnostic indices of Xpert Ultra, smear and culture (with cytology for EBUS-TBNA samples) were compared with culture positivity or a composite reference standard of clinical TB diagnosis.

Non-tuberculous mycobacterial pulmonary disease (NTM-PD): Epidemiology, diagnosis and multidisciplinary management.

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause significant disease in both immunocompromised and immunocompetent individuals. The incidence of NTM pulmonary disease (NTM-PD) is rising globally. Diagnostic challenges persist and treatment efficacy is variable.

Obesity dysregulates the pulmonary antiviral immune response.

Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses.

Silicosis, tuberculosis and silica exposure among artisanal and small-scale miners: A systematic review and modelling paper.

An estimated 44 million artisanal and small-scale miners (ASM), largely based in developing economies, face significant occupational risks for respiratory diseases which have not been reviewed. We therefore aimed to review studies that describe silicosis and tuberculosis prevalence and respirable crystalline silica (RCS) exposures among ASM and use background evidence to better understand the relationship between exposures and disease outcomes. We searched PubMed, Web of Science, Scopus and Embase for studies published before the 24th March 2023.

Vulnerability and tuberculosis treatment outcomes in urban settings in England: A mixed-methods study.

Background: Evidence on factors contributing to poor treatment outcome and healthcare priorities in vulnerable populations affected by tuberculosis (TB) in urban areas of England other than London is needed to inform setting-specific prevention and care policies. We addressed this knowledge gap in a cohort of TB patients and healthcare providers in Birmingham and Leicester, UK.

Methods: A mixed-methods study was performed.

Recovering from COVID-19: lessons learnt from an intensive secondary care follow-up service.

In response to the first COVID-19 surge in 2020, secondary care outpatient services were rapidly reconfigured to provide specialist review for disease sequelae. At our institution, comprising hospitals across three sites in London, we initially implemented a COVID-19 follow-up pathway that was in line with expert opinion at the time but more intensive than initial clinical guidelines suggested. We retrospectively evaluated the resource requirements for this service, which supported 526 patients from April 2020 to October 2020.

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination.

Background: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.

Methods: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia.

Interferon-γ release assay screening in biologics: safe and reliable, but not perfect.

Background: Systemic biologic agents can increase the risk of re-activation of latent tuberculosis (TB). Prior to initiation, screening for latent TB using an interferon-γ release assay (IGRA) is recommended. There is concern that false-negative IGRAs may be more likely in this context.

Anti-tubercular therapy in the treatment of tubercular uveitis: A systematic review and meta-analysis.

We quantitatively evaluated the efficacy of antitubercular therapy (ATT) in tubercular uveitis (TBU) patients. Main outcome measures include inflammation recurrence, inflammation reduction, complete resolution of inflammation, improved visual acuity (VA), ability to taper corticosteroids to < 10 mg/day without inflammatory progression, and use of adjunctive immunosuppressants while on ATT. This review is prospectively registered in PROSPERO (CRD42020206845).

Intestinal perforation due to miliary tuberculosis in a patient with myasthenia gravis.

A man in his early 70s presented to the emergency department with a fall, following a history of fatigue and malodorous urine. On presentation, he was feverish, tachycardic and confused and was treated for presumed urinary sepsis. A chest radiograph showed increased opacification in the left upper lobe with calcification.

Diagnosis of tuberculosis in dialysis and kidney transplant patients.

Background And Objectives: In patients with chronic kidney disease the risk of developing Tuberculosis is increased, while the presentation is often atypical making the diagnosis more difficult. The aim of this study is to describe the presentation of Tuberculosis in dialysis and kidney transplant patients, including the range of diagnostic approaches and the utility of different sample types.

Design, Setting, Participants, And Measurements: In this retrospective study, case records of dialysis and kidney transplant patients were reviewed, including all those treated for Tuberculosis between January 2009 and December 2020.

Evaluating the clinical impact of routine whole genome sequencing in tuberculosis treatment decisions and the issue of isoniazid mono-resistance.

Background: The UK has implemented routine use of whole genome sequencing (WGS) in TB diagnostics. The WHO recommends addition of a fluoroquinolone for isoniazid mono-resistance, so early detection may be of use. The aim of this study was to describe the clinical utility and impact of WGS on treatment decisions for TB in a low incidence high resource clinical setting.

Review: The Nose as a Route for Therapy. Part 2 Immunotherapy.

The nose provides a route of access to the body for inhalants and fluids. Unsurprisingly it has a strong immune defense system, with involvement of innate (e.g.

BTS clinical statement for the diagnosis and management of ocular tuberculosis.

The BTS clinical statement for the diagnosis and management of ocular tuberculosis (TB) draws on the expertise of both TB and and ophthalmic specialists to outline the current understanding of disease pathogenesis, diagnosis and management in adults. Published literature lacks high-quality evidence to inform clinical practice and there is also a paucity of data from animal models to elucidate mechanisms of disease. However, in order to improve and standardise patient care, this statement provides consensus points with the currently available data and agreed best practice.

Effectiveness of nationwide programmatic testing and treatment for latent tuberculosis infection in migrants in England: a retrospective, population-based cohort study.

Background: In low-incidence countries, tuberculosis mainly affects migrants, mostly resulting from reactivation of latent tuberculosis infection (LTBI) acquired in high-incidence countries before migration. A nationwide primary care-based LTBI testing and treatment programme for migrants from high-incidence countries was therefore established in high tuberculosis incidence areas in England. We aimed to assess the effectiveness of this programme.

Utility of Esophageal Ultrasound-guided Biopsy of Mediastinal Lymph Nodes in Diagnosis of Childhood Tuberculosis.

A 6-year-old boy with autistic spectrum disorder was diagnosed with tuberculosis infection following contact tracing of his mother who had isoniazid-resistant pulmonary tuberculosis. He progressed to develop mediastinal lymphadenopathy causing a persistent cough. He was too small to undergo endobronchial ultrasound-guided biopsy.

Monitoring prolongation of QT interval in patients with multidrug-resistant tuberculosis and non-tuberculous mycobacterium using mobile health device AliveCor.

Multidrug resistant tuberculosis and non-tuberculous mycobacterium infections present challenges due to complex treatment regimens. Extended treatment regimes expose patients to higher risks of toxic side-effects. A high drug toxicity profile necessitates closer monitoring.

Genomic signatures of pre-resistance in Mycobacterium tuberculosis.

Recent advances in bacterial whole-genome sequencing have resulted in a comprehensive catalog of antibiotic resistance genomic signatures in Mycobacterium tuberculosis. With a view to pre-empt the emergence of resistance, we hypothesized that pre-existing polymorphisms in susceptible genotypes (pre-resistance mutations) could increase the risk of becoming resistant in the future. We sequenced whole genomes from 3135 isolates sampled over a 17-year period.

Personalised Medicine for Tuberculosis and Non-Tuberculous Mycobacterial Pulmonary Disease.

Personalised medicine, in which clinical management is individualised to the genotypic and phenotypic data of patients, offers a promising means by which to enhance outcomes in the management of mycobacterial pulmonary infections. In this review, we provide an overview of how personalised medicine approaches may be utilised to identify patients at risk of developing tuberculosis (TB) or non-tuberculous mycobacterial pulmonary disease (NTM-PD), diagnose these conditions and guide effective treatment strategies. Despite recent technological and therapeutic advances, TB and NTM-PD remain challenging conditions to diagnose and treat.

Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts.

Background: The success of case isolation and contact tracing for the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission depends on the accuracy and speed of case identification. We assessed whether inclusion of additional symptoms alongside three canonical symptoms (CS), fever, cough and loss or change in smell or taste, could improve case definitions and accelerate case identification in SARS-CoV-2 contacts.

Methods: Two prospective longitudinal London (UK)-based cohorts of community SARS-CoV-2 contacts, recruited within 5 days of exposure, provided independent training and test datasets.