Immunogenicity, reactogenicity, and IgE-mediated immune responses of a mixed whole-cell and acellular pertussis vaccine schedule in Australian infants: A randomised, double-blind, noninferiority trial.

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.

Exploring the views of infection consultants in England on a novel delinked funding model for antimicrobials: the SMASH study.

Objectives: A novel 'subscription-type' funding model was launched in England in July 2022 for ceftazidime/avibactam and cefiderocol. We explored the views of infection consultants on important aspects of the delinked antimicrobial funding model.

Methods: An online survey was sent to all infection consultants in NHS acute hospitals in England.

Development and validation of a dynamic 48-hour in-hospital mortality risk stratification for COVID-19 in a UK teaching hospital: a retrospective cohort study.

Objectives: To develop a disease stratification model for COVID-19 that updates according to changes in a patient's condition while in hospital to facilitate patient management and resource allocation.

Design: In this retrospective cohort study, we adopted a landmarking approach to dynamic prediction of all-cause in-hospital mortality over the next 48 hours. We accounted for informative predictor missingness and selected predictors using penalised regression.

Mucosal-Associated Invariant T cells exhibit distinct functional signatures associated with protection against typhoid fever.

We have previously demonstrated that Mucosal-Associated Invariant T (MAIT) cells secrete multiple cytokines after exposure to Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever in humans. However, whether cytokine secreting MAIT cells can enhance or attenuate the clinical severity of bacterial infections remain debatable.

A controlled human infection model of Streptococcus pyogenes pharyngitis (CHIVAS-M75): an observational, dose-finding study.

Background: Streptococcus pyogenes is a leading cause of infection-related morbidity and mortality. A reinvigorated vaccine development effort calls for new clinically relevant human S pyogenes experimental infection models to support proof of concept evaluation of candidate vaccines. We describe the initial Controlled Human Infection for Vaccination Against S pyogenes (CHIVAS-M75) study, in which we aimed to identify a dose of emm75 S pyogenes that causes acute pharyngitis in at least 60% of volunteers when applied to the pharynx by swab.

Immunogenicity of a Third Scheduled Dose of Rotarix in Australian Indigenous Infants: A Phase IV, Double-blind, Randomized, Placebo-Controlled Clinical Trial.

Background: Rotarix (GlaxoSmithKline) oral rotavirus vaccine is licensed as 2 doses in the first 6 months of life. In settings with high child mortality rates, clinical protection conferred by 2 doses of Rotarix is reduced. We assessed vaccine immune response when an additional dose of Rotarix was given to Australian Aboriginal children 6 to <12 months old.

OPTIMUM study protocol: an adaptive randomised controlled trial of a mixed whole-cell/acellular pertussis vaccine schedule.

Introduction: Combination vaccines containing whole-cell pertussis antigens were phased out from the Australian national immunisation programme between 1997 and 1999 and replaced by the less reactogenic acellular pertussis (aP) antigens. In a large case-control study of Australian children born during the transition period, those with allergist diagnosed IgE-mediated food allergy were less likely to have received whole-cell vaccine in early infancy than matched population controls (OR: 0.77 (95% CI, 0.

Human Typhi exposure generates differential multifunctional cross-reactive T-cell memory responses against Paratyphi and invasive nontyphoidal .

Objective: There are no vaccines for most of the major invasive strains causing severe infection in humans. We evaluated the specificity of adaptive T memory cell responses generated after Typhi exposure in humans against other major invasive strains sharing capacity for dissemination.

Methods: T memory cells from eleven volunteers who underwent controlled oral challenge with .

Point of Care Nucleic Acid Testing for SARS-CoV-2 in Hospitalized Patients: A Clinical Validation Trial and Implementation Study.

There is an urgent need for rapid SARS-CoV-2 testing in hospitals to limit nosocomial spread. We report an evaluation of point of care (POC) nucleic acid amplification testing (NAAT) in 149 participants with parallel combined nasal and throat swabbing for POC versus standard lab RT-PCR testing. Median time to result is 2.

Whole-Cell Pertussis Vaccination and Decreased Risk of IgE-Mediated Food Allergy: A Nested Case-Control Study.

Background: Rates of food allergy have increased markedly in Australia and other high- income countries in recent years. On the basis of ecological observations, and the known immunologic characteristics of whole-cell pertussis (wP) compared with acellular pertussis (aP) vaccines, we hypothesized that wP vaccination in infancy protects against the development of food allergy.

Objective: To determine whether infants who receive wP in infancy were less likely to develop IgE-mediated food allergy than those who received aP.

The ORVAC trial protocol: a phase IV, double-blind, randomised, placebo-controlled clinical trial of a third scheduled dose of Rotarix rotavirus vaccine in Australian Indigenous infants to improve protection against gastroenteritis.

Introduction: Rotavirus vaccines were introduced into the Australian National Immunisation Program in 2007. Despite this, Northern Territory Indigenous children continue to be hospitalised with rotavirus at a rate more than 20 times higher than non-Indigenous children in other Australian jurisdictions, with evidence of waning protection in the second year of life. We hypothesised that scheduling an additional (third) dose of oral human rotavirus vaccine (Rotarix, GlaxoSmithKline) for children aged 6 to <12 months would improve protection against clinically significant all-cause gastroenteritis.

Identification of the determinants of incomplete vaccination in Australian children.

Background And Aims: We aimed to understand the risk factors associated with incomplete vaccination, which may help to identify and prioritise opportunities to intervene.

Methods: Consenting parents of children <6 years old attending an outpatient clinic completed a questionnaire, which captured demographic information and their level of agreement with belief statements about vaccination using a 7-point Likert scale. Vaccination status was determined from the Australian Childhood Immunisation Register and deemed either "complete" (no doses overdue) or "incomplete" (1 or more doses overdue) at the time of questionnaire completion.

Controlled human infection for vaccination against Streptococcus pyogenes (CHIVAS): Establishing a group A Streptococcus pharyngitis human infection study.

Group A Streptococcus (GAS) is a highly-adapted and human-restricted pathogen responsible for a high global burden of disease across a diverse clinical spectrum. Vaccine development has been impeded by scientific, regulatory, and commercial obstacles. Human infection studies (HIS) are increasingly contributing to drug, diagnostics, and vaccine development, reducing uncertainty at early stages, especially for pathogens with animal models that incompletely reproduce key elements of human disease.

Perinatal Risk Factors Associated With Gastroenteritis Hospitalizations in Aboriginal and Non-Aboriginal Children in Western Australia (2000-2012): A Record Linkage Cohort Study.

Background: Gastroenteritis is a leading cause of childhood morbidity worldwide. We aimed to assess the maternal and infant characteristics and population attributable fractions associated with childhood gastroenteritis-related hospitalizations.

Methods: We conducted a whole-of-population retrospective birth cohort study of 367,476 children live-born in Western Australia 2000-2012.

The NICE-GUT trial protocol: a randomised, placebo controlled trial of oral nitazoxanide for the empiric treatment of acute gastroenteritis among Australian Aboriginal children.

Introduction: Diarrhoeal disease is the second leading cause of death in children under 5 years globally, killing 525 000 annually. Australian Aboriginal and Torres Strait Islander (hereafter Aboriginal) children suffer a high burden of disease. Randomised trials in other populations suggest nitazoxanide accelerates recovery for children with , amoebiasis, gastroenteritis, as well as in cases where no enteropathogens are found.

Protocol for Pertussis Immunisation and Food Allergy (PIFA): a case-control study of the association between pertussis vaccination in infancy and the risk of IgE-mediated food allergy among Australian children.

Introduction: Atopic diseases, including food allergy, have become a predominant cause of chronic illness among children in developed countries. In Australia, a rise in hospitalisations among infants coded as anaphylaxis to foods coincided with the replacement of whole-cell pertussis (wP) vaccine with subunit acellular pertussis (aP) vaccine on the national immunisation schedule in the late 1990s. Atopy is characterised by a tendency to mount T helper type 2 (Th2) responses to otherwise innocuous environmental antigens.

Assessment and Translation of the Antibody-in-Lymphocyte Supernatant (ALS) Assay to Improve the Diagnosis of Enteric Fever in Two Controlled Human Infection Models and an Endemic Area of Nepal.

New diagnostic tests for enteric fever are urgently needed to assist with timely antimicrobial treatment of patients and to measure the efficacy of prevention measures such as vaccination. In a novel translational approach, here we use two recently developed controlled human infection models (CHIM) of enteric fever to evaluate an antibody-in-lymphocyte supernatant (ALS) assay, which can detect recent IgA antibody production by circulating B cells in mononuclear cell culture. We calculated the discriminative ability of the ALS assay to distinguish diagnosed cases in the two CHIM studies in Oxford, prior to evaluating blood culture-confirmed diagnoses of patients presenting with fever to hospital in an endemic areas of Kathmandu, Nepal.

Challenge of Humans with Wild-type Serovar Typhi Elicits Changes in the Activation and Homing Characteristics of Mucosal-Associated Invariant T Cells.

Gastrointestinal infections by serovar Typhi (. Typhi) are rare in industrialized countries. However, they remain a major public health problem in the developing world with an estimated 26.

Importance of Typhi-Responsive CD8+ T Cell Immunity in a Human Typhoid Fever Challenge Model.

Typhoid fever, caused by the human-restricted organism serovar Typhi (. Typhi), constitutes a major global health problem. The development of improved attenuated vaccines is pressing, but delayed by the lack of appropriate preclinical models.

Evaluation of the Clinical and Microbiological Response to Salmonella Paratyphi A Infection in the First Paratyphoid Human Challenge Model.

Background: To expedite the evaluation of vaccines against paratyphoid fever, we aimed to develop the first human challenge model of Salmonella enterica serovar Paratyphi A infection.

Methods: Two groups of 20 participants underwent oral challenge with S. Paratyphi A following sodium bicarbonate pretreatment at 1 of 2 dose levels (group 1: 1-5 × 103 colony-forming units [CFU] and group 2: 0.

Blood culture-PCR to optimise typhoid fever diagnosis after controlled human infection identifies frequent asymptomatic cases and evidence of primary bacteraemia.

Background: Improved diagnostics for typhoid are needed; a typhoid controlled human infection model may accelerate their development and translation. Here, we evaluated a blood culture-PCR assay for detecting infection after controlled human infection with S. Typhi and compared test performance with optimally performed blood cultures.