Stool processing methods for Xpert Ultra testing in childhood tuberculosis: A prospective, multi-country accuracy study.

Background: Centrifuge-free processing methods support stool Xpert Ultra testing for childhood tuberculosis (TB), but there are limited data on their accuracy, acceptability and usability.

Methods: We conducted a prospective evaluation of stool Xpert Ultra in India, South Africa, and Uganda with three methods: Stool Processing Kit (SPK), Simple One-Step (SOS), and Optimized Sucrose Flotation (OSF). Children <15 years old with presumptive TB had respiratory specimen testing with Xpert Ultra and culture.

Efficacy, Safety, and Immunogenicity of the MATISSE (Maternal Immunization Study for Safety and Efficacy) Maternal Respiratory Syncytial Virus Prefusion F Protein Vaccine Trial.

Objective: To evaluate descriptive efficacy data, exploratory immunogenicity data, and safety follow-up through study completion from the global, phase 3 MATISSE (Maternal Immunization Study for Safety and Efficacy) maternal vaccination trial of bivalent respiratory syncytial virus (RSV) prefusion F protein vaccine (RSVpreF).

Methods: MATISSE was a phase 3, randomized, double-blinded, placebo-controlled trial. Healthy pregnant participants aged 49 years or younger at 24-36 weeks of gestation were randomized (1:1) to receive a single RSVpreF 120 micrograms or placebo dose.

Preterm Birth Frequency and Associated Outcomes From the MATISSE (Maternal Immunization Study for Safety and Efficacy) Maternal Trial of the Bivalent Respiratory Syncytial Virus Prefusion F Protein Vaccine.

Objective: To describe preterm birth frequency and newborn and infant outcomes overall and among preterm children in the MATISSE (Maternal Immunization Study for Safety and Efficacy) trial of maternal vaccination with bivalent respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVpreF) to protect infants against severe RSV-associated illness.

Methods: MATISSE was a global, phase 3, randomized, double-blind trial. Pregnant individuals received single injections of RSVpreF or placebo.

Plasma proteomics for novel biomarker discovery in childhood tuberculosis.

Failure to rapidly diagnose tuberculosis disease (TB) and initiate treatment is a driving factor of TB as a leading cause of death in children. Current TB diagnostic assays have poor performance in children, and identifying novel non-sputum-based TB biomarkers to improve pediatric TB diagnosis is a global priority. We sought to develop a plasma biosignature for TB by probing the plasma proteome of 511 children stratified by TB diagnostic classification and HIV status from sites in four low- and middle-income countries, using high-throughput data-independent acquisition mass-spectrometry (DIA-PASEF-MS).

Technical variability across the 450K, EPICv1, and EPICv2 DNA methylation arrays: lessons learned for clinical and longitudinal studies.

DNA methylation (DNAm) is the most commonly measured epigenetic mechanism in human populations, with most studies using Illumina arrays to assess DNAm levels. In 2023, Illumina updated their DNAm arrays to the EPIC version 2 (EPICv2), building on prior iterations, namely the EPIC version 1 (EPICv1) and 450K arrays. Whether DNAm measurements are stable across these three generations of arrays has yet not been investigated, limiting the ability of researchers-especially those with longitudinal data-to compare and replicate results across arrays.

Innovative diagnostic technologies: navigating regulatory frameworks through advances, challenges, and future prospects.

Diagnostic tools are key to guiding patient management and informing public health policies to control infectious diseases. However, many diseases still do not have effective diagnostics and much of the global population faces restricted access to reliable, affordable testing. This limitation underscores the urgent need for innovation to enhance diagnostic availability and effectiveness.

Associations between prenatal exposure to environmental phenols and child neurodevelopment at two years of age in a South African birth cohort.

Objective: Evidence suggests that prenatal environmental phenol exposures negatively impact child neurodevelopment, however there is little research on the effects of mixtures of multiple phenol exposures. We analyzed associations between prenatal exposure to phenol mixtures and cognitive neurodevelopment at two years of age among 545 mother-child pairs from the South African Drakenstein Child Health Study.

Material And Methods: We measured maternal urine environmental phenol concentrations once during the second trimester of pregnancy.

Mycobacterium tuberculosis infection and tuberculosis disease in the first decade of life: a South African birth cohort study.

Background: Paediatric tuberculosis leads to more than 200 000 deaths annually. We aimed to investigate the incidence of Mycobacterium tuberculosis infection and tuberculosis disease in the first decade of life in the Drakenstein Child Health Study (DCHS), a South African cohort in a community with high tuberculosis and HIV incidence.

Methods: In this prospective birth cohort study, we enrolled pregnant women aged 18 years or older who were between 20 and 28 weeks' of gestation in a peri-urban setting outside of Cape Town, South Africa.

New advances in RSV: Is prevention attainable?

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI), hospitalization, and mortality in infants and young children globally. The greatest burden of severe disease and mortality occurs in low-middle income countries (LMICs), with large and vulnerable childhood populations. The highest rates of RSV-hospitalization occur in healthy-term infants under 3 months of age.

Subclinical Myocardial Fibrosis in South African Youth With HIV: Results From the CTAAC-Heart Study.

Background: Few data exist on myocardial fibrosis and inflammation in youth with HIV.

Methods: We performed cardiovascular magnetic resonance (CMR) on a cross section of South African youth: youth with perinatally acquired HIV (YPHIV) undergoing antiretroviral therapy (ART), youth with nonperinatally acquired HIV (YNPHIV) receiving ART, and youth without HIV. Quantile regression models were fit to assess the association between HIV status and CMR outcomes: subclinical fibrosis (late gadolinium enhancement [LGE] mass and fraction, native T1, extracellular volume) and inflammation (native T1, T2 mapping).

Early-life respiratory syncytial virus disease and long-term respiratory health.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI), hospital admission, and mortality in children worldwide. Early-life RSV LRTI has also been associated with subsequent long-term respiratory sequelae, including recurrent LRTI, recurrent wheezing, asthma, and lung function impairment, and these effects can persist into adulthood as chronic respiratory disease. New preventive measures (maternal vaccine or long-acting monoclonal antibodies) have been licensed to reduce the burden of acute RSV LRTI in infants and children at high risk through passive immunisation.

The nasopharyngeal microbiome in South African children with lower respiratory tract infection: a nested case-control study of the Drakenstein Child Health Study.

Background: Lower respiratory tract infection (LRTI) is a leading cause of infant morbidity and mortality globally. LRTI may be caused by viral or bacterial infections, individually or in combination. We investigated associations between LRTI and infant nasopharyngeal (NP) viruses and bacteria in a South African birth cohort.

Subcortical Brain Volumes and Neurocognitive Function in Children With Perinatal HIV Exposure: A Population-Based Cohort Study in South Africa.

Background: Children who are HIV-exposed and uninfected (HEU) are at risk for early neurodevelopmental impairment. Smaller basal ganglia nuclei have been reported in neonates who are HEU compared to HIV-unexposed (HU); however, neuroimaging studies outside infancy are scarce. We examined subcortical brain structures and associations with neurocognition in children who are HEU.

Asthma Inception: Epidemiologic Risk Factors and Natural History Across the Life Course.

Asthma is a descriptive label for an obstructive inflammatory disease in the lower airways manifesting with symptoms including breathlessness, cough, difficulty in breathing, and wheezing. From a clinician's point of view, asthma symptoms can commence at any age, although most patients with asthma-regardless of their age of onset-seem to have had some form of airway problems during childhood. Asthma inception and related pathophysiologic processes are therefore very likely to occur early in life, further evidenced by recent lung physiologic and mechanistic research.

The inclusion of children and adolescents in tuberculosis diagnostic development and evaluation-a consensus statement.

The diagnosis of paediatric tuberculosis remains a challenge due to the non-specificity of symptoms and the paucibacillary nature of tuberculosis in children. However, in the development of new tuberculosis diagnostics, the unique needs of children and adolescents are rarely considered in the design process, with delays in evaluation and approval. No clear guidance is available on when and how to include children and adolescents in tuberculosis diagnostic development and evaluation.

Cardioprotective effects of early versus late initiated antiretroviral treatment in adolescents with perinatal HIV-1 infection.

Whether, and how, cardioprotective effects of antiretroviral treatment (ART) in adolescents with perinatal HIV infection (APHIV) vary with age at treatment initiation is unknown. We used magnetic resonance imaging to compare cardiac status between APHIV initiated on ART at < 5 years of age (early ART, n = 37) and ≥ 5 years of age (delayed ART, n = 34) versus HIV-uninfected peers (n = 21), reporting z-score mean differences adjusted for confounders. Relative to HIV-uninfected adolescents, APHIV with early ART had higher left ventricular (LV) global circumferential strain (GCS) [adjusted mean (95%CI) z-score: 0.

Exposure to Violence and Mental Health Outcomes Among Pre-schoolers in a South African Birth Cohort.

Little is known about the relationship between violence exposure and mental health in preschoolers living in low- and middle-income countries (LMICs). Multiple regression analyses investigated associations between violence exposure and mental health in the Drakenstein Child Health Study (N = 978), a South African birth cohort. Lifetime violence exposure was assessed at age 4.

Maternal age is related to offspring DNA methylation: A meta-analysis of results from the PACE consortium.

Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals.