Abstract

The decline in invasive pneumococcal disease (IPD), following the introduction of the 7-valent pneumococcal conjugate vaccination (PCV-7), was tempered by emergence of non-vaccine serotypes, particularly 19A. In Australia, three years after PCV-7 was replaced by PCV-13, containing 19A and 19F antigens, serogroup 19 was still a prominent cause of IPD in children under five. In this study we examined the evolution of serogroup 19 before and after introduction of paediatric vaccines in New South Wales (NSW), Australia. Genomes of 124 serogroup 19 IPD isolates collected before (2004) and after introduction of PCV-7 (2008) and PCV-13 (2014), from children under five in NSW, were analysed. Eleven core genome sequence clusters (cgSC) and 35 multilocus sequence types (ST) were identified. The majority (78/124) of the isolates belonged to four cgSCs: cgSC7 (ST199), cgSC11 (ST320), cgSC8 (ST63) and cgSC9 (ST2345). ST63 and ST2345 were exclusively serotype 19A and accounted for its predominantly intermediate penicillin resistance; these two clusters first appeared in 2008 and largely disappeared after introduction of PCV-13. Serogroup 19 was responsible for the highest proportion of vaccine failures in NSW. Relatively low immunogenicity of serogroup 19 antigens and Australia’s three-dose vaccine schedule could affect the population dynamics of this serogroup.

Highlights

  • Streptococcus pneumoniae is a highly recombinant Gram positive bacterium which can be a commensal or pathogen in the respiratory tract[1]

  • There were no significant differences in the age, clinical syndromes or immunisation histories of children with serogroup 19 invasive pneumococcal disease (IPD) diagnosed in the three time periods of the study (Table 3)

  • In this study we have shown that the evolution of serogroup 19, after the introduction of PCV vaccines was different in Australia, from that described in some other countries[5,17,23] and was associated with less antibiotic resistance[11]

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Summary

Introduction

Streptococcus pneumoniae is a highly recombinant Gram positive bacterium which can be a commensal or pathogen in the respiratory tract[1]. In Australia IPD notifications in children under five fell from 55.4 to 16.8 cases per 100,000 population between 2004 and 20086,7 This success was tempered by an increase in the absolute numbers and proportions of non-vaccine serotypes causing IPD, 19A. Following introduction of PCV-7, ‘serotype switching’ or ‘capsular switch’ recombination was reported, in serogroup 1917 These ‘capsular switch’ recombination events occurred when multi-drug resistant (MDR) clones recombined to switch their vaccine capsular (19F) to a non-vaccine, capsular type (19A)[16,17,18,19]. These recombination events were facilitated by genomic ‘hotspots’ on either side of the cps locus, which is flanked by the penicillin binding protein genes, pbp1a and pbp2x20, enabling pneumococci to evade both vaccine and antibiotic pressure. WGS provides higher resolution strain typing and can identify recombination and genomic variability more effectively than multilocus sequence typing (MLST) or multilocus variable number of tandem repeats analysis (MLVA)

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