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Clin Microbiol Infect 2011; 17: 1246-1253 Abstract The prevalence of the newly discovered pneumococcal serotype 6C has increased in some countries since the introduction of seven-valent conjugate pneumococcal vaccine (PCV7). The distribution of invasive serogroup 6 serotypes, in Australia, including 6C and 6D, has not been reported previously. During the period 1999 to 2008, 6097 isolates were referred to the New South Wales Pneumococcal Reference Laboratory for serotyping. Of these, 847 were identified by Quellung reaction as belonging to serogroup 6 and 702 were available for further study. Serotypes were determined by serotype-specific PCR as follows: 6A, 197 (28.1%); 6B, 452 (64.4%); 6C, 52 (7.4%) and one 6D. The average numbers of invasive serogroup 6 isolates, per annum, fell from 62.2 before (2000-2005) to 49.7 after (2006-2008) the introduction of PCV7. The proportions of invasive 6B fell (from 72.4% to 47.3%, p 0.03), those of 6C rose (from 3.3% to 17%, p 0.02) significantly and those of 6A remained fairly constant (24.3% vs 27%, p 0.69) between the two periods. All 6C and 6D and selected 6A and 6B isolates were further characterized by multilocus sequence typing and sequence analysis of cps genes cpsA-cpsB ( wzg-wzh) and wchA-wciN beta -wciO, wciP. Results showed considerable diversity within serotype 6C, apparently as a result of both mutation and recombination. Sequence typing indicates that, in Australia, 6C has been largely derived from 6A. The genetic diversity and rapid increase in incidence of serotype 6C causing invasive pneumococcal disease has potential implications for vaccine efficacy. [ABSTRACT FROM AUTHOR]