Ruth Thornton
Co-head, Bacterial Respiratory Infectious Disease Group (BRIDG)
PhD
Dr Ruth Thornton (BSc, PhD) is a Passe and Williams Mid-Career Research Fellow at the University of Western Australia and Co-Lead of the Bacterial Respiratory Infectious Disease Group at the Wesfarmers Centre of Vaccines and Infectious Diseases, based at The Kids Research Institute Australia. Her research interests lie in understanding the interactions between bacteria and the host in chronic and recurrent respiratory infections including ear, nose and throat infections, and chronic lung disease.
Dr Thornton’s research into the role of bacterial biofilms, intracellular persistence, and host immunity in recurrent middle ear infections (otitis media) has changed paradigms in understanding and treating otitis media. She demonstrated that otopathogenic bacteria exist in biofilms and intracellularly in the middle ear mucosa of children with chronic and recurrent otitis media. She also demonstrated that the middle ear fluid contains host DNA which can be used by the bacteria as scaffolding to persist in the middle ear. This DNA scaffolding can be targeted to prevent recurrent ear infections and repeat surgeries following grommet surgery. This is the basis of the WA Department of Health funded ATOMIC Ears study which she currently leads, investigating the safety and effectiveness of using an anti-biofilm agent to treat recurrent and chronic otitis media.
Dr Thornton’s expertise further lies in developing paediatric focused, laboratory-based research platforms critical to unravel pathologic mechanisms of respiratory tract infections and the impact of vaccines. These include small-volume immune assays and specialist microscopy techniques which are now core techniques within her laboratory. These all contribute to her overall goal in understanding host-microbial interactions, and why certain therapies may or may not work in high-risk populations, so as to improve treatment and prevention of chronic respiratory infections.
Projects
Healthy Ears Clinical Trial: A telehealth-facilitated randomised-controlled trial utilising a health promotion intervention to resolve otitis media with effusion for children won specialist Ear, Nose and Throat (ENT) waiting lists
A telehealth-facilitated randomised-controlled trial utilising a health promotion intervention to resolve otitis media with effusion for children won specialist Ear, Nose and Throat (ENT) waiting lists
Impact of Repeat Pertussis Vaccination on Infant and Maternal Antibody Quality
Unlocking the immunology of whooping cough vaccines to guide the development of improved vaccines and schedules in Australia
Pathogens on the rise: is impaired immunity the cause of chronic ear and chest infections?
A systems biology approach to determining the risk for development of otitis media
Does mum know best? Should we be vaccinating mothers to protect their babies from ear and lung disease?
Defining the cellular immune response to vaccines for enhanced protection from invasive pneumococcal disease
Improved diagnosis, treatment and prevention of recurrent tonsillitis
ATOMIC Ears: A Phase IIB randomised controlled trial to assess safety, tolerability and acceptability of a 5-day Dornase alfa treatment as an adjunct therapy to ventilation tube insertion for otitis media in children
Pathogenesis of obstructive sleep apnoea
Microbiological and immunological factors predicting surgical outcomes for chronic otitis media
Immunogenicity of pneumococcal vaccine schedules in high-risk infants in Papua New Guinea
Evaluation of a bacterial therapy for prevention of respiratory infection including influenza and otitis media
Dornase alfa as an adjunct therapy to treat chronic ear infections
Development of molecular tools for accurate diagnosis and disease surveillance (including vaccine impact)
Defining the microbes in the middle ear and upper respiratory tract that lead to recurrent ear infections – a metagenomic study
Using the latest sequencing technology to examine the microbial composition of the middle ear & nasopharyngeal region, the site of initial colonization of OM
Published research
The Platform trial In COVID-19 vaccine priming and BOOsting (PICOBOO) booster vaccination substudy protocol
Coronavirus-2019 (COVID-19) vaccination in Australia commenced in February 2021. The first vaccines recommended for use were AZD1222 and BNT162b2, both delivered as a two-dose primary schedule. In the absence of sustained immunity following immunisation, recommendations for booster vaccination have followed. It is likely that periodic boosting will be necessary for at least some Australians, but it is unknown what the optimal booster vaccines and schedules are or for whom vaccination should be recommended.
The Platform Trial In COVID-19 Priming and BOOsting (PICOBOO): The immunogenicity, reactogenicity, and safety of different COVID-19 vaccinations administered as a second booster
PICOBOO is a randomised, adaptive trial evaluating the immunogenicity, reactogenicity, and safety of COVID-19 booster strategies. We report data for second boosters among individuals 50-<70 years old primed with AZD1222 (50-<70y-AZD1222) until Day 84.
The Respiratory Microbiome in Paediatric Chronic Wet Cough: What Is Known and Future Directions
Chronic wet cough for longer than 4 weeks is a hallmark of chronic suppurative lung diseases, including protracted bacterial bronchitis, and bronchiectasis in children. Severe lower respiratory infection early in life is a major risk factor of PBB and paediatric bronchiectasis.
Safety, tolerability, and effect of a single aural dose of Dornase alfa at the time of ventilation tube surgery for otitis media: A Phase 1b double randomized control trial
One third of children require repeat ventilation tube insertion (VTI) for otitis media. Disease recurrence is associated with persistent middle ear bacterial biofilms. With demonstration that Dornase alfa (a DNase) disrupts middle ear effusion biofilms ex vivo, we identified potential for this as an anti-biofilm therapy to prevent repeat VTI. First, safety and tolerability needed to be measured.
ISOM 2023 research Panel 4 - Diagnostics and microbiology of otitis media
To identify and review key research advances from the literature published between 2019 and 2023 on the diagnosis and microbiology of otitis media (OM) including acute otitis media (AOM), recurrent AOM (rAOM), otitis media with effusion (OME), chronic suppurative otitis media (CSOM) and AOM complications (mastoiditis).
Biofilms and intracellular infection in otitis media
Otitis media (OM), middle ear infection, represents a significant burden on children, their families, and the healthcare system. OM is the major cause of hearing loss in children and if left untreated in children who suffer chronic and recurrent forms of OM, this disease can have serious life-long sequelae.
From guidelines to practice: A retrospective clinical cohort study investigating implementation of the early detection guidelines for cerebral palsy in a state-wide early intervention service
To report on knowledge translation strategies and outcomes from the implementation of the early detection guidelines for cerebral palsy (CP) in a state-wide tertiary early intervention (EI) service and investigate the impact of social determinants on clinical services.
Evidence of maternal transfer of antigen-specific antibodies in serum and breast milk to infants at high-risk of S. pneumoniae and H. influenzae disease
Children in low-mid income countries, and First Nations children in high-income countries, experience disproportionately high rates of Streptococcus pneumoniae and Haemophilus influenzae infections and diseases including pneumonia and otitis media.
Predominant Bacterial and Viral Otopathogens Identified Within the Respiratory Tract and Middle Ear of Urban Australian Children Experiencing Otitis Media Are Diversely Distributed
Otitis media (OM) is one of the most common infections in young children, arising from bacterial and/or viral infection of the middle ear. Globally, Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) are the predominant bacterial otopathogens. Importantly, common upper respiratory viruses are increasingly recognized contributors to the polymicrobial pathogenesis of OM.
Australian Aboriginal Otitis-Prone Children Produce High-Quality Serum IgG to Putative Nontypeable Haemophilus influenzae Vaccine Antigens at Lower Titres Compared to Non-Aboriginal Children
Nontypeable Haemophilus influenzae (NTHi) is the most common bacterial otopathogen associated with otitis media (OM). NTHi persists in biofilms within the middle ears of children with chronic and recurrent OM. Australian Aboriginal children suffer exceptionally high rates of chronic and recurrent OM compared to non-Aboriginal children.
Sleep Disordered Breathing and Recurrent Tonsillitis Are Associated With Polymicrobial Bacterial Biofilm Infections Suggesting a Role for Anti-Biofilm Therapies
The underlying pathogenesis of pediatric obstructive sleep disordered breathing (SDB) and recurrent tonsillitis (RT) are poorly understood but need to be elucidated to develop less invasive treatment and prevention strategies.
Prevalence and subtyping of biofilms present in bronchoalveolar lavage from children with protracted bacterial bronchitis or non-cystic fibrosis bronchiectasis: a cross-sectional study
Lower airway biofilms are hypothesised to contribute to poor treatment outcomes among children with chronic lung disease; however, data are scarce.
Evaluating the effectiveness of the Play Active policy intervention and implementation support in early childhood education and care: a pragmatic cluster randomised trial protocol
Daily physical activity is critical during the early years of life for facilitating children's health and development. A large proportion of preschool children do not achieve the recommended 3 h of daily physical activity. Early childhood education and care (ECEC) services are a key setting to intervene to increase physical activity. There is a significant need for ECEC specific physical activity policy, including clearer guidelines on the amount of physical activity children should do during care, and strategies for implementation of these guidelines.
Differences in Pneumococcal and Haemophilus influenzae Natural Antibody Development in Papua New Guinean Children in the First Year of Life
Development of vaccines to prevent disease and death from Streptococcus pneumoniae, and nontypeable Haemophilus influenzae (NTHi), the main pathogens that cause otitis media, pneumonia, meningitis and sepsis, are a global priority.
Targeting host-microbial interactions to develop otitis media therapies
Otitis media (OM; middle ear infection) is the most common reason for pre-school children to visit a doctor, be prescribed antimicrobials, or undergo surgery. Recent Cochrane reviews of clinical trials have identified that antibiotics and grommet surgery are only moderately effective in treating OM, with recurrent or persistent infection observed in one-third of children. Research efforts are focusing on developing improved therapies to treat OM and prevent disease recurrence.
PCV10 elicits Protein D IgG responses in Papua New Guinean children but has no impact on NTHi carriage in the first two years of life
Nasopharyngeal colonisation with nontypeable Haemophilus influenzae (NTHi) is associated with development of infections including pneumonia and otitis media. The 10-valent pneumococcal conjugate vaccine (PCV10) uses NTHi Protein D (PD) as a carrier. Papua New Guinean children have exceptionally early and dense NTHi carriage, and high rates of NTHi-associated disease.
Optimising a 6-plex tetanus-diphtheria-pertussis fluorescent bead-based immunoassay
Small volume assays are required for large-scale research studies and in particular paediatric trials, where multiple measures are required from a single sample. Fluorescent bead-based technology (Bioplex/Luminex) allows high through-put and simultaneous quantification of multiple analytes in a single test. This technology uses sets of microspheres, each with a unique spectral address that can be coated with a different antigen of interest.
An observational study of antibody responses to a primary or subsequent pertussis booster vaccination in Australian healthcare workers
Adult pertussis vaccination is increasingly recommended to control pertussis in the community. However, there is little data on the duration and kinetics of immunity to pertussis boosters in adults. We compared IgG responses to vaccination with a tetanus, low-dose diphtheria, low-dose acellular pertussis (Tdap) booster at 1 week, 1 month and 1 year post-vaccination in whole-cell (wP)-primed Australian paediatric healthcare workers who had received an adult Tdap booster 5-12 years previously, to those who received their first Tdap booster. Tdap vaccination was well tolerated in both groups.
An observational study of antibody responses to a primary or subsequent pertussis booster vaccination in Australian healthcare workers
Adult pertussis vaccination is increasingly recommended to control pertussis in the community. However, there is little data on the duration and kinetics of immunity to pertussis boosters in adults. We compared IgG responses to vaccination with a tetanus, low-dose diphtheria, low-dose acellular pertussis (Tdap) booster at 1 week, 1 month and 1 year post-vaccination in whole-cell (wP)-primed Australian paediatric healthcare workers who had received an adult Tdap booster 5-12 years previously, to those who received their first Tdap booster.
Pneumococcal conjugate vaccine primes mucosal immune responses to pneumococcal polysaccharide vaccine booster in Papua New Guinean children
Invasive pneumococcal disease remains a major cause of hospitalization and death in Papua New Guinean (PNG) children. We assessed mucosal IgA and IgG responses in PNG infants vaccinated with pneumococcal conjugate vaccine (PCV) followed by a pneumococcal polysaccharide vaccine (PPV) booster.
Nasal delivery of a commensal Pasteurellaceae species inhibits nontypeable Haemophilus influenzae colonisation and delays onset of otitis media in mice
We have demonstrated that a single dose of a closely related commensal can delay onset of NTHi otitis media in vivo
Panel 8: Vaccines and immunology
Review and highlight of the significant advances made towards vaccine development and understanding of the immunology of otitis media
February 2020
Panel 7 – Pathogenesis of otitis media – A review of the literature between 2015 and 2019
The most urgent areas appear to be to continue monitoring the emergence of novel otopathogens, and the need to develop prevention and preventative therapies
Bacterial Reservoirs in the Middle Ear of Otitis-prone Children Are Associated With Repeat Ventilation Tube Insertion
Presence of bacterial otopathogen in the middle ear during ventilation tube insertion was a predictor of children at-risk of repeat ventilation tube insertion
High concentrations of middle ear antimicrobial peptides and proteins are associated with detection of middle ear pathogens in children with recurrent acute otitis media
Elevated antimicrobial proteins and peptides and cytokines in middle ear effusion are a marker of inflammation and bacterial persistence
The Contribution of Geogenic Particulate Matter to Lung Disease in Indigenous Children
The aim of this study was to assess the relationship between dust levels and health in Indigenous children in Western Australia
Combination of clinical symptoms and blood biomarkers can improve discrimination between bacterial or viral community-acquired pneumonia in children
Combining elevated CRP with the presence or absence of clinical signs/ symptoms differentiates definite bacterial from presumed viral pneumonia better than CRP alone
The contribution of viruses and bacteria to community-acquired pneumonia in vaccinated children: A case - Control study
Respiratory viruses, particularly respiratory syncytial virus and human metapneumovirus, are major contributors to pneumonia in Australian children
Pcv7-and pcv10-vaccinated otitis-prone children in new zealand have similar pneumococcal and haemophilus influenzae densities in their nasopharynx and middle ear
PCV10 did not reduce NTHi density in the nasopharynx or middle ear, and was associated with increased pneumococcal nasopharyngeal density
Evidence of functional cell-mediated immune responses to nontypeable Haemophilus influenzae in otitis-prone children
These data provide evidence that otitis-prone children do not have impaired functional cell mediated immunity
Role of viral and bacterial pathogens in causing pneumonia among Western Australian children: A case-control study protocol
We aim to determine the contribute of bacteria and virus to childhood CAP to inform further development of effective strategies.
Bacillus licheniformis in geogenic dust induces inflammation in respiratory epithelium
We have previously demonstrated that mice exposed to geogenic dust PM10 experienced an exacerbation of inflammatory responses to influenza A virus.
Role of viral and bacterial pathogens in causing pneumonia among Western Australian children: A case-control study protocol
Pneumonia is the leading cause of childhood morbidity and mortality globally.
Immunogenicity and safety of single-dose, 13-valent pneumococcal conjugate vaccine in pediatric and adolescent oncology patients
All children who are receiving therapy for cancer should receive a single dose of PCV13 as soon as possible after diagnosis, regardless of prior PCV exposure.
Understanding the aetiology and resolution of chronic otitis media from animal and human studies
This Clinical Puzzle article describes our current knowledge of chronic otitis media and the existing research models for this condition
Australian Aboriginal children with otitis media have reduced antibody titers to specific nontypeable Haemophilus influenzae vaccine antigens
decreased serum IgG responses to NTHi outer membrane proteins may contribute to the development of chronic and severe OM in Australian Aboriginal children
Otitis-prone children produce functional antibodies to pneumolysin and pneumococcal polysaccharides
The production of functional antipneumococcal antibodies in otitisprone children demonstrates that they respond to the current pneumococcal conjugate vaccine (PCV)and are likely to respond to pneumolysin-based vaccines as effectively as healthy children.
Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children
Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis.
Genetic and functional evidence for a role for SLC11A1 in susceptibility to otitis media in early childhood in a Western Australian population
Otitis media (OM) is a common disease in early childhood characterised by inflammation of the middle ear.
Are you listening? The inaugural OMOZ Workshop - towards a better understanding of otitis media
Are you listening? The inaugural OMOZ Workshop - towards a better understanding of otitis media
The role of chronic infection in children with otitis media with effusion: Evidence for intracellular persistence of bacteria
Demonstrate mucosal bacterial infection in children with otitis media with effusion (OME).