AbstractOtitis media (OM) is inflammation and infection of the middle ear, behind the tympanic membrane. OM most often occurs in early childhood, and resolves with little ill-effect. Unfortunately, for some ‘at-risk’ children, perforation, chronic discharge and hearing impairment are common outcomes. OM is predominantly associated with the respiratory pathogens Streptococcus pneumoniae, non-typeable Haemophilus influenzae (NTHi), and Moraxella catarrhalis.
OM research Northern Territory (NT) of Australia began in the early 1990s. Data were combined from all available randomised controlled trials (RCTS), cohort studies and surveillance studies from 1995-2018 into an expandable data asset (BIGDATA). BIGDATA will facilitate analysis of long-term trends in ear health, nasopharyngeal (NP) carriage, and pneumococcal conjugate vaccine (PCV) immunisation impacts.
From BIGDATA, an analysis of S. pneumoniae serotypes was undertaken. Since the introduction of PCVs the dynamic of serotype carriage has changed dramatically in the NT, in both Aboriginal and non-Aboriginal children. NP carriage of vaccine-type (VT) pneumococci was reduced; replaced by non-vaccine types. There was minimal impact on overall carriage. Increasing valency vaccines have maintained the low levels of VT carriage, whilst impacting the carriage of unique vaccine serotypes as the infant schedule shifted from PCV7 to PHiDCV10 to PCV13. Reduction in PCV types also reduced β-lactam non-susceptibility, however macrolide resistance is increasing in non-VT serotypes. VT carriage in children with AOM also decreased over the eras.
PHiD-CV10 differs in carrier proteins to PCV7 and PCV13, with 8 of 10 serotypes conjugated to protein D, a lipoprotein from H.influenzae. Protein D was expected to impact H. influenzae carriage and disease, as it promotes an immune response. If immune response to protein D occurs, hypothetically NTHi which did not have the gene encoding for protein D would be selected for by PHiD-CV10 use. By testing for the presence of the gene in NTHi from the three vaccine eras it was determined that it was not the case for NP carriage NTHi, although whether NTHi isolated from ear discharge was impacted differently was not able to be determined (published).
With the impact of PHiD-CV10 unclear, a RCT was designed comparing an early start mixed primary schedule of PHiD-CV10 at 1, 2 and 4 months and PCV13 at 6 months to either vaccine alone at 2, 4 and 6 months (the infant schedule at the time). In the 425 Aboriginal infants randomised there no difference at the primary endpoint of 7 months. This lack of carriage difference in infants is consistent with international data; reporting impact on NP carriage post booster dose only. For ear discharge swabs there was a statistically significant difference between the PHiD-CV10 and mixed schedule group, with a lower proportion positive in the PHiD-CV10 at 7 months of age. However, due to the low number of children with perforation no strong conclusions can be drawn. Overall, perforations most often had NTHi cultured, and very young babies with discharge also had Staphylococcus aureus isolated. There were no differences between the groups at any age for the carriage of the PCV13 unique serotypes 3, 6A and 19A (published).
This PhD program describes the impact of pneumococcal conjugate vaccines on the NP and ear discharge microbiology of Aboriginal children in Northern and Western Australia as three PCVs have been incorporated into the infant immunisation schedule in the NT, with specific focus on the impact on S. pneumoniae and NTHi. Remote living Aboriginal children still experience unacceptably high rates of OM. Interventions should be aimed at carriage prevention and delay for infants, to shift the burden from the first months of life, to reduce the long-term impact of recurrent and chronic OM.
|Date of Award||Aug 2022|
|Supervisor||Heidi Smith-Vaughan (Supervisor) & Amanda Leach (Supervisor)|