Effectiveness of the primary Bacillus Calmette-Guérin vaccine against the risk of Mycobacterium tuberculosis infection and tuberculosis disease: a meta-analysis of individual participant data.

Background: Tuberculosis vaccine trials using disease as the primary endpoint are large, time consuming, and expensive. An earlier immunological measure of the protection against disease would accelerate tuberculosis vaccine development. We aimed to assess whether the effectiveness of the Bacillus Calmette-Guérin (BCG) vaccine for prevention of Mycobacterium tuberculosis infection was consistent with that for prevention of tuberculosis disease.

Implications of subclinical tuberculosis for vaccine trial design and global effect.

Tuberculosis is a leading cause of death from an infectious agent globally. Infectious subclinical tuberculosis accounts for almost half of all tuberculosis cases in national tuberculosis prevalence surveys, and possibly contributes to transmission and might be associated with morbidity. Modelling studies suggest that new tuberculosis vaccines could have substantial health and economic effects, partly based on the assumptions made regarding subclinical tuberculosis.

Development, assessment and educational impact of a blended e-learning training program on pharmacovigilance implemented in four African countries.

Introduction: Efforts to improve medication access in low-and middle-income countries, particularly in Sub-Saharan Africa, have made progress, especially in the fight against infectious diseases such as tuberculosis. However, challenges exist in establishing effective pharmacovigilance systems. The PhArmacoVIgilance Africa (PAVIA) project was committed to enhancing pharmacovigilance in Tanzania, Eswatini, Nigeria, and Ethiopia, with an emphasis on anti-tuberculosis drugs, utilizing various methods, including training.

Prevalence of subclinical pulmonary tuberculosis in adults in community settings: an individual participant data meta-analysis.

Background: Subclinical pulmonary tuberculosis, which presents without recognisable symptoms, is frequently detected in community screening. However, the disease category is poorly clinically defined. We explored the prevalence of subclinical pulmonary tuberculosis according to different case definitions.

Aerosolization of viable bacilli by tuberculosis clinic attendees independent of sputum-Xpert Ultra status.

Potential () transmission during different pulmonary tuberculosis (TB) disease states is poorly understood. We quantified viable aerosolized from TB clinic attendees following diagnosis and through six months' follow-up thereafter. Presumptive TB patients (n=102) were classified by laboratory, radiological, and clinical features into Group A: Sputum-Xpert Ultra-positive TB (n=52), Group B: Sputum-Xpert Ultra-negative TB (n=20), or Group C: TB undiagnosed (n=30).

Estimating the contribution of subclinical tuberculosis disease to transmission: An individual patient data analysis from prevalence surveys.

Background: Individuals with bacteriologically confirmed pulmonary tuberculosis (TB) disease who do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to () transmission is unknown, especially compared to individuals who report symptoms at the time of diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare.

Methods: We reviewed the literature to identify studies where surveys of infection were linked to population surveys of TB disease.

Target product profiles: tests for tuberculosis treatment monitoring and optimization.

The World Health Organization has developed target product profiles containing minimum and optimum targets for key characteristics for tests for tuberculosis treatment monitoring and optimization. Tuberculosis treatment optimization refers to initiating or switching to an effective tuberculosis treatment regimen that results in a high likelihood of a good treatment outcome. The target product profiles also cover tests of cure conducted at the end of treatment.

Reply: Tuberculosis screening in migrants to the EU/EEA and UK.

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Monocyte to lymphocyte ratio and hemoglobin level to predict tuberculosis after antiretroviral therapy initiation.

Objective: To determine the performance of the baseline monocyte to lymphocyte ratio (MLR), baseline anemia severity and combination of these biomarkers, to predict tuberculosis (TB) incidence in people with HIV (PWH) after antiretroviral therapy (ART) initiation.

Design: Multicenter, retrospective cohort study.

Methods: We utilized the data from study A5175 (Prospective Evaluation of Antiretroviral Therapy in Resource-limited Settings: PEARLS).

An Aspiration to Radically Shorten Phase 3 Tuberculosis Vaccine Trials.

A new tuberculosis vaccine is a high priority. However, the classical development pathway is a major deterrent. Most tuberculosis cases arise within 2 years after Mycobacterium tuberculosis exposure, suggesting a 3-year trial period should be possible if sample size is large to maximize the number of early exposures.

Funding and financial sustainability of pharmacovigilance: suggested models for funding pharmacovigilance in resource-limited African countries.

Background: An important factor hindering the growth of pharmacovigilance (PV) in resource-limited settings is the lack of adequate funds to establish a functional National Pharmacovigilance System. Consequently, the crucial function of monitoring and ensuring the availability of safe medicines in these settings cannot be guaranteed considering the peculiarities of diseases and medicines used.

Objectives: The objective of this paper is to provide an overview as to the availability of potential sources of funds, which could be explored to ensure Medicine Safety and to proffer a potential framework likely to ensure sustainable funding of PV in Africa.

Digital health for all: How digital health could reduce inequality and increase universal health coverage.

Digital transformation in health care has a lot of opportunities to improve access and quality of care. However, in reality not all individuals and communities are benefiting equally from these innovations. People in vulnerable conditions, already in need of more care and support, are often not participating in digital health programs.

Measuring indirect transmission-reducing effects in tuberculosis vaccine efficacy trials: why and how?

Tuberculosis is the leading bacterial cause of death globally. In 2021, 10·6 million people developed symptomatic tuberculosis and 1·6 million died. Seven promising vaccine candidates that aim to prevent tuberculosis disease in adolescents and adults are currently in late-stage clinical trials.

Drivers determining tuberculosis disease screening yield in four European screening programmes: a comparative analysis.

Background: The World Health Organization End TB Strategy emphasises screening for early diagnosis of tuberculosis (TB) in high-risk groups, including migrants. We analysed key drivers of TB yield differences in four large migrant TB screening programmes to inform TB control planning and feasibility of a European approach.

Methods: We pooled individual TB screening episode data from Italy, the Netherlands, Sweden and the UK, and analysed predictors and interactions for TB case yield using multivariable logistic regression models.

Influence of Sex and Sex-Based Disparities on Prevalent Tuberculosis, Vietnam, 2017-2018.

To assess sex disparities in tuberculosis in Vietnam, we conducted a nested, case-control study based on a 2017 tuberculosis prevalence survey. We defined the case group as all survey participants with laboratory-confirmed tuberculosis and the control group as a randomly selected group of participants with no tuberculosis. We used structural equation modeling to describe pathways from sex to tuberculosis according to an a priori conceptual framework.

The natural history of untreated pulmonary tuberculosis in adults: a systematic review and meta-analysis.

Stages of tuberculosis disease can be delineated by radiology, microbiology, and symptoms, but transitions between these stages remain unclear. In a systematic review and meta-analysis of studies of individuals with untreated tuberculosis who underwent follow-up (34 cohorts from 24 studies, with a combined sample of 139 063), we aimed to quantify progression and regression across the tuberculosis disease spectrum by extracting summary estimates to align with disease transitions in a conceptual framework of the natural history of tuberculosis. Progression from microbiologically negative to positive disease (based on smear or culture tests) in participants with baseline radiographic evidence of tuberculosis occurred at an annualised rate of 10% (95% CI 6·2-13·3) in those with chest x-rays suggestive of active tuberculosis, and at a rate of 1% (0·3-1·8) in those with chest x-ray changes suggestive of inactive tuberculosis.

Clinical trials of tuberculosis vaccines in the era of increased access to preventive antibiotic treatment.

Approximately 10·6 million people worldwide develop tuberculosis each year, representing a failure in epidemic control that is accentuated by the absence of effective vaccines to prevent infection or disease in adolescents and adults. Without effective vaccines, tuberculosis prevention has relied on testing for Mycobacterium tuberculosis infection and treating with antibiotics to prevent progression to tuberculosis disease, known as tuberculosis preventive treatment (TPT). Novel tuberculosis vaccines are in development and phase 3 efficacy trials are imminent.

Quantifying progression and regression across the spectrum of pulmonary tuberculosis: a data synthesis study.

Background: Prevalence surveys show a substantial burden of subclinical (asymptomatic but infectious) tuberculosis, from which individuals can progress, regress, or even persist in a chronic disease state. We aimed to quantify these pathways across the spectrum of tuberculosis disease.

Methods: We created a deterministic framework of untreated tuberculosis disease with progression and regression between three states of pulmonary tuberculosis disease: minimal (non-infectious), subclinical (asymptomatic but infectious), and clinical (symptomatic and infectious).