A vaccine emergency-when to overrule parental refusal of vaccination at birth for prevention of vertical transmission of hepatitis B virus?

Hepatitis B virus (HBV) is a potentially chronic infection that can be transmitted from mother to child with the risk of developing cirrhosis, liver failure and hepatocellular carcinoma. There is a safe and effective vaccine to prevent vertical transmission that is recommended to be given as soon as possible after birth and within 24 hours.When a woman with HBV refuses the birth dose of HBV vaccine for her baby, infectious diseases and safeguarding teams are asked to provide urgent opinions on whether this crosses the threshold for triggering child protection mechanisms.

Clinical presentation, diagnostics, and outcomes of infants with congenital and postnatal tuberculosis: a multicentre cohort study of the Paediatric Tuberculosis Network European Trials Group (ptbnet).

Background: According to estimates, globally more than 200,000 pregnant women develop tuberculosis (TB) annually. Despite this, data on perinatal TB remain scarce. This study aimed to describe perinatal TB, comprising congenital (cTB) and postnatal (pTB) TB, in a European setting.

Understanding the interaction between cytomegalovirus and tuberculosis in children: The way forward.

Over 1 million children develop tuberculosis (TB) each year, with a quarter dying. Multiple factors impact the risk of a child being exposed to Mycobacterium tuberculosis (Mtb), the risk of progressing to TB disease, and the risk of dying. However, an emerging body of evidence suggests that coinfection with cytomegalovirus (CMV), a ubiquitous herpes virus, impacts the host response to Mtb, potentially influencing the probability of disease progression, type of TB disease, performance of TB diagnostics, and disease outcome.

Defeating Paediatric Tuberculous Meningitis: Applying the WHO "Defeating Meningitis by 2030: Global Roadmap".

Children affected by tuberculous meningitis (TBM), as well as their families, have needs that lie at the intersections between the tuberculosis and meningitis clinical, research, and policy spheres. There is therefore a substantial risk that these needs are not fully met by either programme. In this narrative review article, we use the World Health Organization (WHO) "Defeating Meningitis by 2030: global roadmap" as a starting point to consider key goals and activities to specifically defeat TBM in children.

Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics.

The pathogenesis of Tuberculous meningitis (TBM) is poorly understood, but contemporary molecular biology technologies have allowed for recent improvements in our understanding of TBM. For instance, neutrophils appear to play a significant role in the immunopathogenesis of TBM, and either a paucity or an excess of inflammation can be detrimental in TBM. Further, severity of HIV-associated immunosuppression is an important determinant of inflammatory response; patients with the advanced immunosuppression (CD4+ T-cell count of <150 cells/μL) having higher CSF neutrophils, greater CSF cytokine concentrations and higher mortality than those with CD4+ T-cell counts > 150 cells/μL.

Protection against mycobacterial infection: A case-control study of mycobacterial immune responses in pairs of Gambian children with discordant infection status despite matched TB exposure.

Background: Children are particularly susceptible to tuberculosis. However, most children exposed to Mycobacterium tuberculosis are able to control the pathogen without evidence of infection. Correlates of human protective immunity against tuberculosis infection are lacking, and their identification would aid vaccine design.

Performance of metabonomic serum analysis for diagnostics in paediatric tuberculosis.

We applied a metabonomic strategy to identify host biomarkers in serum to diagnose paediatric tuberculosis (TB) disease. 112 symptomatic children with presumptive TB were recruited in The Gambia and classified as bacteriologically-confirmed TB, clinically diagnosed TB, or other diseases. Sera were analysed using H nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS).

Performance of immune-based and microbiological tests in children with tuberculosis meningitis in Europe: a multicentre Paediatric Tuberculosis Network European Trials Group (ptbnet) study.

Introduction: Tuberculous meningitis (TBM) is often diagnostically challenging. Only limited data exist on the performance of interferon-γ release assays (IGRA) and molecular assays in children with TBM in routine clinical practice, particularly in the European setting.

Methods: Multicentre, retrospective study involving 27 healthcare institutions providing care for children with tuberculosis (TB) in nine European countries.

Tuberculosis Disease in Children and Adolescents on Therapy With Antitumor Necrosis Factor-ɑ Agents: A Collaborative, Multicenter Paediatric Tuberculosis Network European Trials Group (ptbnet) Study.

Background: In adults, anti-tumor necrosis factor-α (TNF-α) therapy is associated with progression of latent tuberculosis (TB) infection (LTBI) to TB disease, but pediatric data are limited.

Methods: Retrospective multicenter study within the Paediatric Tuberculosis Network European Trials Group, capturing patients <18 years who developed TB disease during anti-TNF-α therapy.

Results: Sixty-six tertiary healthcare institutions providing care for children with TB participated.

An Auto-luminescent Fluorescent BCG Whole Blood Assay to Enable Evaluation of Paediatric Mycobacterial Responses Using Minimal Blood Volumes.

Understanding protective human immunity against mycobacteria is critical to developing and evaluating new vaccines against tuberculosis. Children are the most susceptible population to infection, disease, and death from tuberculosis, but also have the strongest evidence of BCG-inducible protection. Limited amounts of blood can be obtained for research purposes in paediatrics and therefore there is a need for high-yield, low-volume, human immunology assays.

Tuberculosis susceptibility and protection in children.

Children represent both a clinically important population susceptible to tuberculosis and a key group in whom to study intrinsic and vaccine-induced mechanisms of protection. After exposure to Mycobacterium tuberculosis, children aged under 5 years are at high risk of progressing first to tuberculosis infection, then to tuberculosis disease and possibly disseminated forms of tuberculosis, with accompanying high risks of morbidity and mortality. Children aged 5-10 years are somewhat protected, until risk increases again in adolescence.

Evaluating UK National Guidance for Screening of Children for Tuberculosis. A Prospective Multicenter Study.

Rationale: To identify infected contacts of tuberculosis (TB) cases, the UK National Institute for Health and Care Excellence (NICE) recommended the addition of IFN-γ release assays (IGRA) to the tuberculin skin test (TST) in its 2006 TB guidelines. Treatment for TB infection was no longer recommended for children who screened TST-positive but IGRA-negative.

Objectives: We performed a cohort study to evaluate the risk of TB disease in this group.

Diagnostic Performance of Tuberculosis-Specific IgG Antibody Profiles in Patients with Presumptive Tuberculosis from Two Continents.

Background: Development of rapid diagnostic tests for tuberculosis is a global priority. A whole proteome screen identified Mycobacterium tuberculosis antigens associated with serological responses in tuberculosis patients. We used World Health Organization (WHO) target product profile (TPP) criteria for a detection test and triage test to evaluate these antigens.

Why the Convention on the Rights of the Child must become a guiding framework for the realization of the rights of children affected by tuberculosis.

Background: Until recently, paediatric tuberculosis (TB) has been relatively neglected by the broader TB and the maternal and child health communities. Human rights-based approaches to children affected by TB could be powerful; however, awareness and application of such strategies is not widespread.

Discussion: We summarize the current challenges faced by children affected by TB, including: consideration of their family context; the limitations of preventive, diagnostic and treatment options; paucity of paediatric-specific research; failure in implementation of interventions; and stigma.

Plasma Membrane Profiling Reveals Upregulation of ABCA1 by Infected Macrophages Leading to Restriction of Mycobacterial Growth.

The plasma membrane represents a critical interface between the internal and extracellular environments, and harbors multiple proteins key receptors and transporters that play important roles in restriction of intracellular infection. We applied plasma membrane profiling, a technique that combines quantitative mass spectrometry with selective cell surface aminooxy-biotinylation, to Bacille Calmette-Guérin (BCG)-infected THP-1 macrophages. We quantified 559 PM proteins in BCG-infected THP-1 cells.

How to use: interferon γ release assays for tuberculosis.

Diagnosis and treatment of latent tuberculosis infection (LTBI) is important to reduce risk of progression to active tuberculosis (TB) disease. For the past century the tuberculin skin test (TST) has been used as a measure of exposure to Mycobacterium tuberculosis (MTB), but this test has limitations in test performance, sensitivity and specificity. Interferon γ release assays (IGRA), like TST, measure host immune response to MTB.

Identifying predictors of interferon-γ release assay results in pediatric latent tuberculosis: a protective role of bacillus Calmette-Guerin?: a pTB-NET collaborative study.

Rationale: Interferon-γ (IFN-γ) release assays are widely used to diagnose latent infection with Mycobacterium tuberculosis in adults, but their performance in children remains incompletely evaluated to date.

Objectives: To investigate factors influencing results of IFN-γ release assays in children using a large European data set.

Methods: The Pediatric Tuberculosis Network European Trials group pooled and analyzed data from five sites across Europe comprising 1,128 children who were all investigated for latent tuberculosis infection by tuberculin skin test and at least one IFN-γ release assay.

Current understanding of the immune response to tuberculosis in children.

Purpose Of Review: Even in the era of promising molecular diagnostics for tuberculosis, understanding of the immune response remains urgent and fundamental to combating paediatric tuberculosis, given its paucibacillary nature.

Recent Findings: Significant advances have been made in unravelling the contributions of previously underappreciated components of the immune response to Mycobacterium tuberculosis. Research into the role of the 'innate' immune system such as neutrophils alongside 'adaptive' cells such as CD4(+), CD8(+), polyfunctional and regulatory T cells has highlighted the complexity of their interactions.