Does using different pneumococcal vaccines in combination work for ear health outcomes better than using them alone? (NHMRC 605810 and 1046999 CIA Leach, Morris, Mulholland, Brown, Torzillo, Lehmann, Richmond, Marsh, Smith-Vaughan, Pearson and Jeffries-Stokes).
Randomised Controlled clinical Trials (RCT) are being conducted to evaluate pneumococcal vaccine schedules and combination superiority:
PREV-IX-COMBO Trial (COMBO)
The bacterium pneumococcus causes invasive disease, pneumonia and otitis media in young children. PCV13 is now the recommended pneumococcal conjugate vaccines (PCV) in Australia. The decision to recommend PCV13 over PHiD-CV10 has been primarily driven by the increase in cases of invasive pneumococcal disease due to serotype 19A(1). However for the Northern Territory (NT), in the last 3 years there has been one case of serotype 3, 6A or 19A invasive pneumococcal disease (IPD) per year in Indigenous children less than 2 years of age. By contrast, almost 20% of young Indigenous children have perforated tympanic membranes of which 60% are associated with Non-typable H. influenzae (NTHi), compared to 3% having serotypes 3, 6A or 19A.
The PREV-IX_COMBO trial is a randomised controlled trial (RCT) of these two pneumococcal conjugate vaccines currently licensed in Australia. Participating Indigenous infants living in remote communities in 4 regions of the NT are randomised between 28 and 38 days of age and allocated to one of three groups: PHiD-CV10 at 2, 4, 6 months or PCV13 at 2,4,6 months, or an investigational group of a 4-dose combination schedule of PHiD-CV10 at 1,2, and 4 months plus PCV13 at 6 months.
PREV_IX-BOOST Trial (BOOST)
To follow on from COMBO, this study will recruit patients from COMBO to assess whether an extra dose of pneumococcal vaccine (Booster dose) will result in better outcomes for children at age 3.
The primary outcome measure will be the proportion of subjects with serotype-specific antibody above the level required for protection from IPD in each study group at 18 months of age. This will be determined in ELISA assays. Nasopharyngeal carriage or NTHi and the proportion of children with any otitis media and/or any tympanic membrane perforation will also be captured. PHiD-CV10 has potential to offer protection from NTHi but we know little of its potential selective impact on NTHi biology. The immune response to HiD (and pneumococcal proteins) must be better understood to establish immune correlates of protection in Indigenous populations and improve vaccine design.
This will be the first study to shed light on the impact of otitis media (OM) on the trajectory of early child development and education.