Mycobacterium tuberculosis resisters despite HIV exhibit activated T cells and macrophages in their pulmonary alveoli.

Natural resistance to Mycobacterium tuberculosis (Mtb) infection in some people with HIV (PWH) is unexplained. We performed single cell RNA-sequencing of bronchoalveolar lavage cells, unstimulated or ex vivo stimulated with Mtb, for 7 PWH who were TST & IGRA positive (called LTBI) and 6 who were persistently TST & IGRA negative (called resisters). Alveolar macrophages (AM) from resisters displayed a baseline M1 macrophage phenotype while AM from LTBI did not.

PET/CT guided tuberculosis treatment shortening: a randomized trial.

Six months of chemotherapy using current agents is standard of care for pulmonary, drug-sensitive tuberculosis (TB), even though some are believed to be cured more rapidly and others require longer therapy. Understanding what factors determine the length of treatment required for durable cure in individual patients would allow individualization of treatment durations, provide better clinical tools to determine the of appropriate duration of new regimens, as well as reduce the cost of large Phase III studies to determine the optimal combinations to use in TB control programs. We conducted a randomized clinical trial in South Africa and China that recruited 704 participants with newly diagnosed, drug-sensitive pulmonary tuberculosis and stratified them based on radiographic disease characteristics as assessed by FDG PET/CT scan readers.

Exogenous binding immunoglobulin protein (BiP) enhance immune regulatory phenotype in ex-vivo Mtb infected PBMCs stratified based on QuantiFERON response.

Even though anti-tuberculosis (TB) treatment is readily available, Mycobacterium tuberculosis (Mtb) infection continues to be a global threat with a high death rate recorded from a single infectious agent. This highlights the significance of developing new strategies to curb the growing Mtb infection cases. Host-directed therapies (HDT) offer a promising approach that includes both drug discovery and drug repurposing, aimed at identifying host targets and promoting immune cell populations that can lead to better infection outcomes.

Assessing the propensity of TB clinical isolates to form viable but non-replicating subpopulations.

Current tuberculosis (TB) treatment is typically effective against drug-susceptible Mycobacterium tuberculosis, but can fail due to acquired drug resistance or phenotypic resistance. M. tuberculosis persisters, a subpopulation of viable but non-replicating (VBNR) antibiotic-tolerant bacteria, are thought to contribute to poor TB treatment outcomes.

PneumoniaCheck, a novel aerosol collection device, permits capture of airborne Mycobacterium tuberculosis and characterisation of the cough aeromicrobiome in people with tuberculosis.

Background: Tuberculosis (TB), a major cause of disease and antimicrobial resistance, is spread via aerosols. Aerosols have diagnostic potential and airborne-microbes other than Mycobacterium tuberculosis complex (MTBC) may influence transmission. We evaluated whether PneumoniaCheck (PMC), a commercial aerosol collection device, captures MTBC and the aeromicrobiome of people with TB.

Blood transcriptomic signatures for symptomatic tuberculosis in an African multicohort study.

Background: Multiple host blood transcriptional signatures have been developed as non-sputum triage tests for tuberculosis (TB). We aimed to compare the diagnostic performance of 20 blood transcriptomic TB signatures for differentiating between symptomatic patients who have TB other respiratory diseases (ORD).

Methods: As part of a nested case-control study, individuals presenting with respiratory symptoms at primary healthcare clinics in Ethiopia, Malawi, Namibia, Uganda, South Africa and The Gambia were enrolled.

A novel aerosol collection method shows the cough aeromicrobiome of people with tuberculosis is phylogenetically distinct from respiratory tract specimens.

Background: Tuberculosis (TB), a major cause of disease and antimicrobial resistance, is spread via aerosols. Aerosols have diagnostic potential and airborne-microbes other than (MTBC) may influence transmission. We evaluated whether PneumoniaCheck (PMC), a commercial aerosol collection device, captures MTBC and the aeromicrobiome of people with TB.

Point-of-care C-reactive protein and Xpert MTB/RIF Ultra for tuberculosis screening and diagnosis in unselected antiretroviral therapy initiators: a prospective, cross-sectional, diagnostic accuracy study.

Background: Tuberculosis, a major cause of death in people living with HIV, remains challenging to diagnose. Diagnostic accuracy data are scarce for promising triage and confirmatory tests such as C-reactive protein (CRP), sputum and urine Xpert MTB/RIF Ultra (Xpert Ultra), and urine Determine TB LAM Ag (a lateral flow lipoarabinomannan [LF-LAM] test), without symptom selection. We evaluated novel triage and confirmatory tests in ambulatory people with HIV initiating antiretroviral therapy (ART).

Mycobacterium tuberculosis resisters despite HIV exhibit activated T cells and macrophages in their pulmonary alveoli.

To understand natural resistance to ( ) infection, we studied people living with HIV (PLWH) in an area of high transmission. Given that alveolar leukocytes may contribute to this resistance, we performed single cell RNA-sequencing of bronchoalveolar lavage cells, unstimulated or stimulated with . We obtained high quality cells for 7 participants who were TST & IGRA positive (called LTBI) and 6 who were persistently TST & IGRA negative (called resisters).

Improved patient safety with a simplified operating room to pediatric intensive care unit handover tool (PATHQS).

Introduction: Patient handover is a crucial transition requiring a high level of coordination and communication. In the BC Children's Hospital (BCCH) pediatric intensive care unit (PICU), 10 adverse events stemming from issues that should have been addressed at the operating room (OR) to PICU handover were reported into the patient safety learning system (PSLS) within 1 year. We aimed to undertake a quality improvement project to increase adherence to a standardized OR to PICU handover process to 100% within a 6-month time frame.

Acute Effects of a Warm-Up Intervention on Pain, Productivity, Physical Capacities and Psychological Perceptions Among Vineyard Workers: a Cluster Randomized Trial.

Purpose: Agriculture is one of the sectors that are the most concerned by musculoskeletal disorders (MSDs). Workplace physical activity programs are one of the most promising solutions to prevent adverse consequences of MSDs such as pain or impairment in physical capacities. The aims of this study were twofold: (1) to investigate the acute effect of a warm-up session on pain, work performance, physical capacities and psychosocial perceptions among vineyard workers; (2) to determine the most beneficial warm-up modality for vineyard workers.

Suppressive myeloid cells in SARS-CoV-2 and co-infection.

Epidemiologic data show that both current and previous tuberculosis (TB) increase the risk of in-hospital mortality from coronavirus disease-2019 (COVID-19), and there is a similar trend for poor outcomes from (Mtb) infection after recent SARS-CoV-2. A shared dysregulation of immunity explains the dual risk posed by co-infection, but the specific mechanisms are being explored. While initial attention focused on T cell immunity, more comprehensive analyses revealed a dysfunctional innate immune response in COVID-19, characterized by reduced numbers of dendritic cells, NK cells and a redistribution of mononuclear phagocytes towards intermediate myeloid subsets.

Immunologic and vascular biomarkers of mortality in critical COVID-19 in a South African cohort.

Introduction: Biomarkers predicting mortality among critical Coronavirus disease 2019 (COVID-19) patients provide insight into the underlying pathophysiology of fatal disease and assist with triaging of cases in overburdened settings. However, data describing these biomarkers in Sub-Saharan African populations are sparse.

Methods: We collected serum samples and corresponding clinical data from 87 patients with critical COVID-19 on day 1 of admission to the intensive care unit (ICU) of a tertiary hospital in Cape Town, South Africa, during the second wave of the COVID-19 pandemic.

High resolution imaging and five-year tuberculosis contact outcomes.

Background: The evolution of tuberculosis (TB) disease during the clinical latency period remains incompletely understood.

Methods: 250 HIV-uninfected, adult household contacts of rifampicin-resistant TB with a negative symptom screen underwent baseline F-Fluorodeoxyglucose positron emission and computed tomography (PET/CT), repeated in 112 after 5-15 months. Following South African and WHO guidelines, participants did not receive preventive therapy.

Field evaluation of a point-of-care triage test for active tuberculosis (TriageTB).

Background: To improve tuberculosis (TB) diagnosis, the World Health Organisation (WHO) has called for a non-sputum based triage test to focus TB testing on people with a high likelihood of having active pulmonary tuberculosis (TB). Various host or pathogen biomarker-based testing devices are in design stage and require validity assessment. Host biomarkers have shown promise to accurately rule out active TB, but further research is required to determine generalisability.

Point-of-care C-reactive protein and Xpert MTB/RIF Ultra for tuberculosis screening and diagnosis in unselected antiretroviral therapy initiators: a prospective diagnostic accuracy study.

Background: Tuberculosis (TB), a major cause of death in people living with HIV (PLHIV), remains challenging to diagnose. Diagnostic accuracy data are lacking for promising triage tests, such as C-reactive protein (CRP), and confirmatory tests, such as sputum and urine Xpert MTB/RIF Ultra (Ultra), and urine LAM, without prior symptom selection.

Methods: 897 PLHIV initiating antiretroviral therapy were consecutively recruited in settings with high TB incidence, irrespective of symptoms.

Optimising the yield from bronchoalveolar lavage on human participants in infectious disease immunology research.

Bronchoalveolar lavage (BAL) is becoming a common procedure for research into infectious disease immunology. Little is known about the clinical factors which influence the main outcomes of the procedure. In research participants who underwent BAL according to guidelines, the BAL volume yield, and cell yield, concentration, viability, pellet colour and differential count were analysed for association with important participant characteristics such as active tuberculosis (TB) disease, TB exposure, HIV infection and recent SARS-CoV-2 infection.

Optimising the yield from bronchoalveolar lavage on human participants in infectious disease immunology research.

Bronchoalveolar lavage (BAL) is becoming a common procedure for research into infectious disease immunology. Little is known about the clinical factors which influence the main outcomes of the procedure. In research participants who underwent BAL according to guidelines, the BAL volume yield, and cell yield, concentration, viability, pellet colour and differential count were analysed for association with important participant characteristics such as active tuberculosis (TB) disease, TB exposure, HIV infection and recent SARS-CoV-2 infection.

Effects of a warm-up intervention at the workplace on pain, heart rate, work performance and psychological perception among vineyard workers.

Objectives: Warm-up sessions before physical activity are widely used in sports to help prevent injury and improve performance. Nowadays, companies assume that the effects observed in a sport context can be transferred to the workplace, particularly among workers exposed to biomechanical strain. Yet research on the use of warm-up interventions at the workplace is rather scarce and, when available, leads to conflicting results due to the low quality of the studies.

Understanding the biology, morbidity and social contexts of adolescent tuberculosis: a prospective observational cohort study protocol (Teen TB).

Introduction: A considerable burden of the tuberculosis (TB) epidemic is found in adolescents. The reasons for increased susceptibility to TB infection and higher incidence of TB disease in adolescence, compared with the 5-10 years old age group, are incompletely understood. Despite the pressing clinical and public health need to better understand and address adolescent TB, research in this field remains limited.

Neutrophil degranulation, NETosis and platelet degranulation pathway genes are co-induced in whole blood up to six months before tuberculosis diagnosis.

Mycobacterium tuberculosis (M.tb) causes tuberculosis (TB) and remains one of the leading causes of mortality due to an infectious pathogen. Host immune responses have been implicated in driving the progression from infection to severe lung disease.

Exploring acute effects of workplace warm-up intervention on pain, physical capacities, and productivity in agriculture: A study protocol.

Background: Physical activity programs at the workplace have shown positive results on physical capacities and pain for several years. Due to the duration of the training session or the need for an instructor, these supervised programs are rather difficult to implement. For this reason, numerous companies, especially companies in manual sectors, are turning to another solution, i.