A randomised controlled trial of pneumococcal conjugate vaccines Synflorix and Prevenar13 in sequence or alone in high-risk Indigenous infants (PREV-IX): immunogenicity, carriage and otitis media outcomes

The bacterium pneumococcus causes invasive disease, pneumonia and otitis media in young children. Seven-valent pneumococcal conjugate vaccine (PCV7) has been provided for Aboriginal and high risk children since 2001 and all Australian children since 2005. There are two new pneumococcal conjugate vaccines to be licensed in Australia by the end of 2010. These have 10 pneumococcal serotypes in common but one also offers protection from H. influenzae infection and the other has 3 additional pneumococcal serotypes. H. influenzae causes otitis media and non-bacteraemic pneumonia but is rarely cultured from blood cultures and thus is considered a less invasive pathogen. For Aboriginal children however, H. influenzae is the major pathogen associated with perforated tympanic membranes (ear drums) and it is thought to be an important cause of pneumonia. Invasive disease caused by the additional serotypes, particularly 19A, has increased in Australian non-indigenous population. Thus it is anticipated that most jurisdictions will choose to use the PCV13. However, because Indigenous children have much higher rates of infection due to H. influenzae than non-Indigenous children, Indigenous children may benefit from both vaccines. There are no studies that directly compare these two vaccines to determine overall clinical benefit. This Randomised Controlled Trial (RCT) will directly compare the two vaccines as well as an early 3+1 combination schedule, commencing at one months of age. Immunological, microbiological and clinical outcomes will be assessed.