Recently, there has been an increase in invasive pneumococcal disease (IPD) caused by serotype 1 Streptococcus pneumoniae throughout Europe. Serotype 1 IPD is associated with bacteremia and pneumonia in Europe and North America, especially in neonates, and is ranked among the top five most prevalent pneumococcal serotypes in at least 10 countries. The currently licensed pediatric pneumococcal vaccine does not afford protection to this serotype. Upon screening of 252 clinical isolates of S. pneumoniae, we discovered mutations in the pneumolysin gene of two out of the four serotype 1 strains present in the study group. Analysis of an additional 28 serotype 1 isolates from patients with IPD from various Scottish Health Boards, revealed that >50% had mutations in their pneumolysin genes. This resulted in the expression of nonhemolytic forms of pneumolysin. All of the strains producing nonhemolytic pneumolysin were sequence type 306 (ST306), whereas those producing "wild-type" pneumolysin were ST227. The mutations were in a region of pneumolysin involved in pore formation. These mutations can be made in vitro to give the nonhemolytic phenotype. Pneumolysin is generally conserved throughout all serotypes of S. pneumoniae and is essential for full invasive disease; however, it appears that serotype 1 ST306 does not require hemolytically active pneumolysin to cause IPD.

Based on the invasive pneumococcal isolates referred to reference laboratories in Scotland in 1988-99, we identified the distribution of serotypes/groups and their antimicrobial resistance patterns in order to evaluate the coverage of polysaccharide and the new pneumococcal conjugate vaccines. A total of 5659 invasive isolates were included. Of these, 5124 (90.5%) were blood isolates, 308 (5.5%) were CSF isolates, 143 (2.5%) were blood and CSF and 84 (1.5%) were other normally sterile isolates. The most prevalent 11 serotypes/groups were 14, 9, 19, 6, 23, 1, 3, 4, 7, 8 and 18, in numerical order. These accounted for 84% of total serotypes/groups. The serotypes/groups included in the 23 and 14-valent polysaccharide vaccines accounted for 96% and 88% of all isolates. Both vaccines accounted for 98% of penicillin non-susceptible and 100% of erythromycin non-susceptible isolates. The 7, 9, and 11-valent conjugate vaccines covered 61, 68 and 80% of invasive isolates respectively. The coverage of these vaccines was substantially higher in youngest age group with 84, 86 and 93% of invasive isolates in children < 2 years included in the 7, 9 and 11-valent conjugate vaccines compared with 58, 64 and 77% in adults > or = 65 years of age. The serotype/group distribution of invasive isolates in Scotland varied from year to year over the period 1993-9. The coverage of the 23-valent vaccine remained above 95% in each year but the coverage of the 7, 9 and 11-valent conjugate vaccines showed more marked fluctuation with coverage as low as 53, 60 and 75% in some years. Continued surveillance of invasive pneumococcal isolates is required to inform the development of appropriate vaccine strategies to prevent pneumococcal disease in Scotland.

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A review of the epidemiology of invasive pneumococcal disease in Scotland was carried out using data from laboratory-based systems during the period 1988–99. This comprised 5456 (90·8%) isolates of Streptococcus pneumoniae from blood, 467 (7·8%) from cerebrospinal fluid (CSF) and 84 (1·4%) from other sterile sites. The mean annual incidence of invasive disease was 9·8/105 population (9·0/105 for bacteraemia and 0·8/105 for meningitis). Invasive disease was highest in children <2 years of age and in the elderly [ges ]65 years (44·9/105 and 28·4/105 population in these age groups respectively). The highest incidence of pneumococcal meningitis, 11·8/105 persons occurred in children <2 years of age. Males had a higher incidence of pneumococcal bacteraemia and meningitis than females (male[ratio ]female = 1·2[ratio ]1 for bacteraemia (RR = 1·17, 95% CI 1·11, 1·24) and 1·5[ratio ]1 for meningitis (RR = 1·41, 95% CI 1·18, 1·70)). Pneumococcal disease was highest in winter periods and coincided with influenza activity. The proportion of penicillin and erythromycin non-susceptible isolates increased from 4·2% in 1992 to 12·6% in 1999 and from 5·6% in 1994 to 16·3% in 1999 respectively. Our data confirm the substantial and increasing disease burden from pneumococcal disease and rise in prevalence of antibiotic non-susceptibility among pneumococci in Scotland. Continued surveillance of groups at increased risk for pneumococcal disease and the antibiotic susceptibility and serotype distribution of isolates are important to develop appropriate policies for the prevention of pneumococcal disease in Scotland.