The pneumococcal capsule is thought to be the main determinant of carriage prevalence and invasiveness and hence the determinant of prevalence amongst disease isolates [11] and [12]. However, it has been speculated that increases in serotype 19A IPD in particular are perhaps attributable to a capsular switch event after being found associated with a sequence

type (ST), ST695, previously only linked with vaccine serotype 4 [13] and [14]. Other studies have documented increases due to the expansion of multi-drug resistant STs such as ST276 and ST320 [15] and [16]. Thus, it is increasingly important to examine both STs and serotypes involved in IPD to determine the potential effectiveness of serotype-specific pneumococcal vaccinations. In September 2006, PCV7 was introduced to the National Health Service childhood immunisation 3-MA nmr schedule in the UK

in a three dose programme at age 2, 4, and 13 months, with a catch-up for those aged up to 2 years. In 2010, 94% of PFI-2 the targeted group had received three doses of PCV7 [17]. This study examines trends in serotype and ST distributions prior to PCV7 use in Scotland, adding to existing reports on the pre-vaccine period in Scotland [18] and [19]; the effect of PCV7 on IPD incidence; trends in serotype and ST distribution post-vaccination; and the association between serotype and ST pre- and post-vaccination. The Scottish Invasive Pneumococcal Disease Enhanced Surveillance (SPIDER) database contains all cases of IPD, identified by blood or cerebrospinal fluid, in Scotland from 1999–2010. The serogroup responsible for each case of disease was available for all years; serotype and ST information was available from 2002.

Clinical isolates (from blood or cerebrospinal fluid) of S. pneumoniae were sent to the Scottish Haemophilus, Legionella, Meningococcus and Pneumococcus Reference Laboratory (SHLMPRL) after identification at diagnostic microbiology laboratories. These were grown on Columbia blood agar Carnitine palmitoyltransferase II (Oxoid, UK) at 37 °C under anaerobic conditions using an anaerobic pack (Oxoid, UK) and after a single subculture were stored at −80 °C on Protect beads (M-Tech Diagnostics, UK). Isolates were serotyped by a coagglutination method [20]. Multi-locus sequence typing was performed as described previously [21], [22] and [23]. Epidemiological years from winter of one year to the end of autumn of the next were used ensuring winter seasons were grouped together since IPD predominantly occurs in winter. Serotypes and STs were classified according to their joint occurrence prior to PCV7 use (1999–2005) and emergence post-PCV7 (2006–2010). STs were classified as associated with PCV7 serotypes if they occurred at least once in conjunction with a PCV7 serotype (labelled PCV7-ST); otherwise they were classified as not associated (NonPCV7-ST). STs which only occurred following PCV7 use were classified as PostPCV7-ST.