Our survey of 1720 young children in remote communities two and four years after commencement of a government funded schedule for Indigenous children of 7PCV at 2, 4 and 6 months followed by a booster 23PPV at 18 months of age, provides a valuable source of pneumococcal serotype and susceptibility data for the region. Two major influences have had the potential to impact on pneumococcal carriage in this population; pneumococcal vaccination and antimicrobial prescribing. In three communities studied extensively in the 1990s, around 50% children carried 7PCV serotypes. Predominant pre-7PCV serotypes were 6B, 19F, 23F, 19A, 16F and 6A (unpublished data from 3 of the communities also in these surveys). Retrospective PCR analysis confirms one of 20 pre-7PCV 6A isolates was 6C. A similar serotype distribution was found in cultures of discharge from acute perforations of the tympanic membrane.
In general, this survey found small differences between 2003 and 2005. Vaccine uptake (at least 2 doses of 7PCV) was around 87% in 2003 and increased to 96% in 2005. By 2005, 84% age-eligible children had received 23PPV. Between 2003 and 2005 we detected small but statistically significant reductions in pneumococcal carriage (-6%). This trend was consistent across all age groups. Similarly for 7PCV types (-4%). There was a small reduction in 6A. Overall, carriage of 23PPV-non-7PCV types was significantly reduced (-5%), including serotype 19A (-4%), but other 23PPV-non-7PCV types (20 and 9N) increased. Non-vaccine serotypes (not in 23PPV) increased by 10%, mainly attributable to serotypes 23B, 34 and 10F. Serotypes 6C and 16F remained unchanged.
Among the group of children not vaccinated, 19A, 16F and 6A and 6C were the predominant serotypes and 7PCV type carriage was less than 10%, indicating a herd effect. Similarly, in very young non-vaccinated infants (mean age 1.9 months) carriage was around 58% and only 8% carried 7PCV vaccine types. Serotypes were diverse and no dominant emerging serotype was evident in this young group.
There is no strong evidence from 23PPV studies to suggest that 23PPV has an impact on NP carriage Our immunogenicity study showed 23PPV to be an effective booster for 7PCV-primed serotypes, and that modest responses to some additional serotypes in 23PPV also occurred. Whether the antibody concentrations achieved would prevent pneumococcal acquisition in the nasopharynx was not assessed. In this survey we did detect a 5% reduction in 23PPV-non-7PCV serotype carriage between 2003 and 2005, at a time when uptake of 23PPV as a booster dose increased from 35% to 62%. In the age group eligible for 23PPV booster, carriage of serotypes unique to 23PPV was actually higher in 23PPV-vaccinated than non-vaccinated children, but only in 2003. We are unable to explain this observation which was not present in 2005. Whether this is related to lack of effect of 23PPV on carriage, or timing of the swabbing in relation to 23PPV vaccination, or other factors cannot be assessed from this study. Further studies of 23PPV seem warranted as is large-scale surveillance of 23PPV-non-7PCV serotypes in this population.
Beta-lactam prescribing did not change significantly between 2003 and 2005, however the region with highest prescribing also had higher carriage of penicillin non-susceptible strains. Serotypes 19A and 16F accounted for a considerable proportion of beta-lactam- non-susceptible strains, as did remaining 7PCV serotypes. The finding that penicillin non-susceptibility is linked to the major endemic replacement serotypes indicates a need for ongoing monitoring to assess trends over coming years. High level penicillin resistance was very uncommon in 2005 (1 isolate). The clinical impact of penicillin resistance will be much greater if high level resistance increases over time. In the 2008 report by Roche, serotype 19A caused the majority (36%) of penicillin non-susceptible IPD cases in Australia in 2006.
Macrolide prescribing was low, but increased significantly between 2003 and 2005, mainly due to recent mass azithromycin use in one community. At the time of our survey in that community there was no statistically significant difference in pneumococcal carriage or carriage of azithromycin resistant strains between children recently prescribed azithromycin and those not (RD = 6% [-5, 18]). Our previous longitudinal study had shown that azithromycin reduces carriage of pneumococci, providing resistant strains with a selective advantage that allows spread within the community. Over time, and in the absence of further azithromycin use or selective pressure, susceptible stains re-populate and the proportion of the population carrying resistant strains declines. The present cross-sectional study does not capture this dynamic process and therefore does not allow any conclusions regarding the relationship between mass azithromycin use and carriage. In Central Australia, recent macrolide prescribing was rare, but carriage of azithromycin resistant strains was clearly higher than other regions. We suggest that this higher background of resistance may be related to a longer period of exposure to azithromycin for trachoma and STI (sexually transmitted infection) eradication programs, in the central Australian region. Data to support this are lacking; the 2006 Trachoma surveillance report identified that azithromycin treatment was recommended but was poorly documented in the Northern Territory
Whilst carriage prevalence does not fully predict IPD serotypes (particularly outbreak or epidemic serotypes such as serotypes 1 or 5), the majority of annual IPD cases are caused by the serotypes most prevalent in the carriage population. In Australia, rates of IPD caused by serotype 19A in Indigenous children have fluctuated over recent years and serotype 6A became the most common non-vaccine IPD serotype in Indigenous children and the second most common in non-Indigenous children. Hanna compared IPD serotypes in under 5 year old Indigenous children living in far North Queensland pre- and post-7PCV implementation. They concluded that there was no evidence of non-7PCV serotype replacement. However, the pre-vaccine non-7PCV cases were inflated by a serotype 1 outbreak. Excluding type 1 cases, there was a risk difference in non-7PCV IPD of 55% [95%CI 30,80]. Reporting of pneumococcal epidemiology needs to consider the epidemic and endemic nature of various serotypes and that serotype-specific data are needed to best describe and prepare for shifts over time and in response to vaccines and antibiotic selective pressures.
Otitis media (OM) serotypes closely align with carriage serotype profile, and for Aboriginal children OM is a common and serious infection often resulting in chronic suppurative OM (CSOM). This study showed that the serotypes colonising infants at 2 months of age, and therefore the serotypes most likely causing early OM, are no longer 7PCV-types. Vaccines that are effective in preventing early onset of ear disease (and pneumonia) are urgently needed.