Otitis media (middle ear infection – OM) is one of the most common reasons a child will visit their general practitioner and be prescribed antibiotics. One in 4 children experience recurrent acute OM (rAOM) or chronic OM with effusion (cOME) also known as “glue ear” by 3 years of age. Antibiotics are ineffective at preventing disease recurrence or reducing the persistence of the “glue”. Final treatment is usually surgical requiring grommet insertion. Up to 50% of children that require one set of grommets will require repeat surgery due to OM recurrence. This recalcitrance is due to the persistence of bacteria within biofilms both on the middle ear mucosa and within the middle ear fluid.
We are currently conducting a clinical trial (ATOMIC ears study) assessing the use of Dornase alfa as an adjunct therapy to grommet surgery. This is administered at the time of surgery and for 5 days following to break down the middle ear “glue”. We are aiming to determine if this treatment can prevent complications such as discharging and blocked grommets and ultimately if it can prevent the need for repeat surgery. We are also assessing biofilm-specific immune responses to the nontypeable Haemophilus influenzae, the most common pathogen causing chronic and recurrent OM. We have demonstrated that children undergoing surgery for grommets have reduced antibody titres to important proteins involved in adherence and biofilm formation/maintenance (rsPilA, ChimV4 and Protein D). This deficiency is particularly enhanced in Australian First Nations children, who suffer from the highest burden of disease. These antigens may represent ideal vaccine candidates to help prevent or treat OM in high-risk populations.
Together these approaches represent novel treatment and preventative strategies that specifically target the underlying bacterial persistence mechanisms, an approach which has not yet been assessed and which may be relevant for other chronic respiratory infections.