Associate Professor Lea-Ann Kirkham

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

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

Determining the off-target effects of infant vaccines on respiratory infection outcomes in Western Australian children

Childhood pneumonia in the Eastern Highlands Province of Papua New Guinea: clinical, microbiological and immunological predictors of disease

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

Nasal Delivery of Haemophilus haemolyticus Is Safe, Reduces Influenza Severity, and Prevents Development of Otitis Media in Mice

Despite vaccination, influenza and otitis media (OM) remain leading causes of illness. We previously found that the human respiratory commensal Haemophilus haemolyticus prevents bacterial infection in vitro and that the related murine commensal Muribacter muris delays OM development in mice. The observation that M muris pretreatment reduced lung influenza titer and inflammation suggests that these bacteria could be exploited for protection against influenza/OM.

An infant mouse model of influenza-driven nontypeable Haemophilus influenzae colonization and acute otitis media suitable for preclinical testing of novel therapies

Nontypeable Haemophilus influenzae (NTHi) is a major otitis media (OM) pathogen, with colonization a prerequisite for disease development. Most acute OM is in children <5 years old, with recurrent and chronic OM impacting hearing and learning. Therapies to prevent NTHi colonization and/or disease are needed, especially for young children. Respiratory viruses are implicated in driving the development of bacterial OM in children.

Clinical predictors of hypoxic pneumonia in children from the Eastern Highlands Province, Papua New Guinea: secondary analysis of two prospective observational studies

Pneumonia is the leading cause of death in young children globally and is prevalent in the Papua New Guinea highlands. We investigated clinical predictors of hypoxic pneumonia to inform local treatment guidelines in this resource-limited setting.

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.

Pneumococcal carriage, serotype distribution, and antimicrobial susceptibility in Papua New Guinean children vaccinated with PCV10 or PCV13 in a head-to-head trial

Children in Papua New Guinea (PNG) are at high risk of pneumococcal infections. We investigated pneumococcal carriage rates, serotype distribution, and antimicrobial susceptibility in PNG children after vaccination with 10-valent or 13-valent pneumococcal conjugate vaccines (PCV10; PCV13).

Histo-blood group antigen profile of Australian Aboriginal children and seropositivity following oral rotavirus vaccination

Histo-blood group antigens (HBGAs) may influence immune responses to rotavirus vaccination.

among children with pneumonia using a causal Bayesian network

Pneumonia remains a leading cause of hospitalization and death among young children worldwide, and the diagnostic challenge of differentiating bacterial from non-bacterial pneumonia is the main driver of antibiotic use for treating pneumonia in children. Causal Bayesian networks (BNs) serve as powerful tools for this problem as they provide clear maps of probabilistic relationships between variables and produce results in an explainable way by incorporating both domain expert knowledge and numerical data.

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.

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.

An eight-plex immunoassay for Group A streptococcus serology and vaccine development

Group A Streptococcus (GAS) is a major human pathogen responsible for superficial infections through to life-threatening invasive disease and the autoimmune sequelae acute rheumatic fever (ARF). Despite a significant global economic and health burden, there is no licensed vaccine available to prevent GAS disease. Several pre-clinical vaccines that target conserved GAS antigens are in development.

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.

Lack of effectiveness of 13-valent pneumococcal conjugate vaccination against pneumococcal carriage density in Papua New Guinean infants

Papua New Guinea (PNG) introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in 2014, with administration at 1, 2, and 3 months of age. PCV13 has reduced or eliminated carriage of vaccine types in populations with low pneumococcal carriage prevalence, carriage density and serotype diversity.

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.

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

Panel 4: Recent advances in understanding the natural history of the otitis media microbiome and its response to environmental pressures

Advances in understanding bacterial dynamics in the upper airway microbiome are driving development of microbiota-modifying therapies to prevent or treat disease

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

Production of IgG2 Antibodies to Pneumococcal Polysaccharides After Vaccination of Treated HIV Patients May Be Augmented by IL-7Rα Signaling in ICOS + Circulating T-Cells

Our findings suggest that utilization of IL-7 by cTFH cells affects production of IgG2 antibodies to PPV23 antigens in some HIV patients

Safety and immunogenicity of pneumococcal conjugate vaccines in a high-risk population: a randomised controlled trial of PCV in Papua New Guinean infants

Infant vaccination with 3 doses of PCV10 or PCV13 is safe and immunogenic in a highly endemic setting

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

Immunogenicity and Immune Memory after a Pneumococcal Polysaccharide Vaccine Booster in a High-Risk Population Primed with Pneumococcal Conjugate Vaccine

PPV is immunogenic in 9-month-old children at high risk of pneumococcal infections and does not affect the capacity to produce protective immune responses

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

Moraxella catarrhalis Restriction-Modification Systems Are Associated with Phylogenetic Lineage and Disease

We observed an association between Type III DNA methyltransferase presence and Otitis Media-associated middle ear isolates

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

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.

Rationale and methods of a randomized controlled trial of immunogenicity, safety and impact on carriage of pneumococcal conjugate and polysaccharide vaccines in infants in Papua New Guinea

Vaccination trials in high endemicity areas are needed to provide evidence and guidance on idea strategies to protect children in these areas against infections

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

Increased CTLA-4+ T cells may contribute to impaired T helper type 1 immune responses in patients with chronic obstructive pulmonary disease

Chronic inflammation may expand sub-populations of T cells expressing CTLA-4 in COPD patients and therefore impair T-cell function

Production of IgG antibodies to pneumococcal polysaccharides is associated with expansion of ICOS+ circulating memory T follicular-helper cells which is impaired by HIV infection

Dysfunction of T follicular-helper cells is a possible cause of impaired germinal centre and IgG antibody responses in individuals with HIV

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.

No evidence for impaired humoral immunity to pneumococcal proteins in Australian Aboriginal children with otitis media

Conserved vaccine candidate proteins from S.pneumoniae induce serum and salivary antibody responses in Aboriginal and non-Aboriginal children with history of OM

Duplex quantitative PCR assay for detection of haemophilus influenzae that distinguishes fucose-and protein d-negative strains

Developed a specific Haemophilus influenzae quantitative PCR (qPCR) that also identifies fucose-negative and protein D-negative strains

Chronic HIV-1 infection induces B-cell dysfunction that is incompletely resolved by long-term antiretroviral therapy

B-cell dysfunction persists in patients with HIV receiving long-term antiretroviral therapy. the causes and consequences of this require further investigation.

Molecular tools for differentiation of non-typeable Haemophilus influenzae from Haemophilus haemolyticus

The molecular approaches that have been developed for differentiation of NTHi from H. haemolyticus, with the advantages and disadvantages of each target

A PCR-high-resolution melt assay for rapid differentiation of nontypeable Haemophilus influenzae and Haemophilus haemolyticus

We have developed a PCR-high-resolution melt (PCR-HRM) assay to discriminate nontypeable Haemophilus influenzae (NTHi) colonies from Haemophilus haemolyticus

Diversity of Nontypeable Haemophilus influenzae strains colonizing Australian Aboriginal and non-Aboriginal children

Nontypeable Haemophilus influenzae (NTHI) strains are responsible for respiratory-related infections which cause a significant burden of disease in...

High pneumococcal serotype specific IgG, IgG1 and IgG2 levels in serum and the middle ear of children with recurrent acute otitis media

Recurrent acute otitis media (AOM), frequently caused by Streptococcus pneumoniae, is a major paediatric health problem.

Neutrophil Extracellular Traps and Bacterial Biofilms in Middle Ear Effusion of Children with Recurrent Acute Otitis Media

Bacteria persist within biofilms on the middle ear mucosa of children with recurrent and chronic otitis media however the mechanisms by which these...

Children with otitis media mount a pneumococcal serotype specific serum IgG and IgA response comparable to healthy controls after pneumococcal conjugate vaccination

We investigated the suggestion that otitis-prone children have an impaired antibody response in the context of pneumococcal vaccination.

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