Development of an effective tuberculosis (TB) vaccine has been challenged by incomplete understanding of specific factors that provide protection against (Mtb) and the lack of a known correlate of protection (CoP). Using a combination of samples from a vaccine showing efficacy (DarDar [NCT00052195]) and Bacille Calmette-Guerin (BCG)-immunized humans and nonhuman primates (NHP), we identify a humoral CoP that translates across species and vaccine regimens. Antibodies specific to the DarDar vaccine strain () sonicate (MOS) correlate with protection from the efficacy endpoint of definite TB.
View Article and Find Full Text PDFThe intestinal microbiota plays a critical role in host immunity and might contribute to the significant variation between individuals' vaccine responses. A systematic search was done using MEDLINE and Embase to identify original human studies investigating the association between intestinal microbiota composition and humoral and cellular vaccine responses. In total, 30 publications (26 studies, 14 in infants, 12 in adults), were included.
View Article and Find Full Text PDFBackground: Antibiotics are the most commonly prescribed drugs during pregnancy. The long-term health risks to children associated with prenatal antibiotic exposure are uncertain.
Objective: To identify the association between prenatal antibiotics and adverse long-term health outcomes in children.
Introduction: Emergency surgical admissions represent the most unwell patients admitted to any hospital. Frailty and body composition independently identify risk of adverse outcomes but are seldom combined to predict outcomes in emergency patients. We aim to determine the relationships between frailty, body composition analyses (BCA) and mortality in an undifferentiated emergency general surgical patient population.
View Article and Find Full Text PDFBackground: Cefalexin, a first-generation cephalosporin, is commonly used as oral continuation therapy for paediatric bone and joint infections (BJIs). The standard four times daily cefalexin dose makes treatment adherence challenging. A pharmacokinetic modelling study found that a cefalexin dose of 45 mg/kg (maximum 1.
View Article and Find Full Text PDFBackground: The gold standard for diagnosis of meningitis is the isolation of a pathogen from cerebrospinal fluid (CSF) by culture or PCR. However, treatment is routinely commenced based on CSF findings prior to microbiological results. This study determined the predictive value of CSF parameters for diagnosing bacterial and viral meningitis in young infants.
View Article and Find Full Text PDFBackground: Children are the age group with the highest exposure to antibiotics (ABX). ABX treatment changes the composition of the intestinal microbiota. The first few years of life are crucial for the establishment of a healthy microbiota and consequently, disturbance of the microbiota during this critical period may have far-reaching consequences.
View Article and Find Full Text PDFObjectives: The immune response in children elicited by SARS-CoV-2 Omicron infection alone or in combination with COVID-19 vaccination (hybrid immunity) is poorly understood. We examined the humoral and cellular immune response following SARS-CoV-2 Omicron infection in unvaccinated children and children who were previously vaccinated with COVID-19 mRNA vaccine.
Methods: Participants were recruited as part of a household cohort study conducted during the Omicron predominant wave (Jan to July 2022) in Victoria, Australia.
Pediatr Infect Dis J
September 2024
Perspect Biol Med
September 2024
This article explores three different comics by creators with brain tumors: Rick, written and drawn by Gordon Shaw; Going Remote, written by Adam Bessie and drawn by Peter Glanting; and Parenthesis, written and drawn by Élodie Durand. It examines how the affordances of the comics medium enables the creators to present an experience of subjective time that is multiple, diffuse, and contradictory, in contrast to the regular apportioning of time via calendars, schedules, and pathways essential to institutional neuro-oncology. The question of time here is significant because the side effects of brain tumors can include blackouts, seizures, and periods of extreme fatigue, during which the experience of time can be significantly disrupted.
View Article and Find Full Text PDFBackground: Some individuals have a persistence of symptoms following both COVID-19 (post-acute COVID-19 syndrome; PACS) and other viral infections. This study used prospectively collected data from an international trial to compare symptoms following COVID-19 and non-COVID-19 respiratory illness, to identify factors associated with the risk of PACS, and to explore symptom patterns before and after COVID-19 and non-COVID-19 respiratory illnesses.
Methods: Data from a multicentre randomised controlled trial (BRACE trial) involving healthcare workers across four countries were analysed.
Objectives: Bacille Calmette-Guérin (BCG) vaccine has immunomodulatory effects that may provide protection against unrelated infectious diseases. We aimed to determine whether BCG vaccination protects adults against COVID-19.
Design: Phase III double-blind randomised controlled trial.
An accelerated local injection site reaction following Bacille Calmette-Guérin (BCG) vaccination has been associated with underlying active tuberculosis (TB) in high TB-prevalence settings. The clinical significance of this accelerated BCG reaction in individuals without TB symptoms, particularly in low TB-prevalence countries, is unclear. Using safety surveillance data and baseline interferon-gamma release assays (IGRA) within an international randomised trial of BCG vaccination in healthcare workers (the BRACE trial), we aimed to determine the incidence, and investigate for clinical implications, of an accelerated BCG reaction in asymptomatic adults in low and high TB-prevalence settings.
View Article and Find Full Text PDFBackground: The beneficial off-target effects of Bacille Calmette-Guérin (BCG) vaccination potentially include protection against allergy.
Objective: In the MIS BAIR trial, we aimed to determine whether neonatal BCG vaccination reduces atopic sensitisation and clinical food allergy in infants.
Methods: In this randomised controlled trial, 1272 neonates were allocated to BCG-Denmark vaccine (0.
Background: As the population ages, more older adults are presenting for surgery. Age-related declines in physiological reserve and functional capacity can result in frailty and poor outcomes after surgery. Hence, optimizing perioperative care in older patients is imperative.
View Article and Find Full Text PDFBackground: Fcγ-receptor (FcγR)-independent enhancement of SARS-CoV-2 infection mediated by N-terminal domain (NTD)-binding monoclonal antibodies (mAbs) has been observed , but the functional significance of these antibodies is less clear.
Methods: We characterized 1,213 SARS-CoV-2 spike (S)-binding mAbs derived from COVID-19 convalescent patients for binding specificity to the SARS-CoV-2 S protein, VH germ-line usage, and affinity maturation. Infection enhancement in a vesicular stomatitis virus (VSV)-SARS-CoV-2 S pseudovirus (PV) assay was characterized in respiratory and intestinal epithelial cell lines, and against SARS-CoV-2 variants of concern (VOC).
Background: In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule.
View Article and Find Full Text PDFBackground: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults.
Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom.