The introduction of the 7-valent pneumococcal vaccine (PCV7) in Canada was very effective in reducing invasive pneumococcal disease (IPD) in children; however, increases of non-PCV7 serotypes have subsequently offset some of these reductions. A 13-valent pneumococcal vaccine (PCV13) targeting additional serotypes was implemented between 2010 and 2011, and in 2012 changes in the incidence of disease and the distribution of IPD serotypes began to emerge. The incidence of IPD in children <5 years of age declined from 18.0 to 14.2 cases per 100 000 population between 2010 and 2012; however, the incidence in ages ≥5 years remained relatively unchanged over the 3-year period, at about 9.7 cases per 100 000 population. From 2010 to 2012, PCV13 serotypes declined significantly from 66% (224/339) to 41% (101/244, p < 0.001) in children <5 years of age, and from 54% (1262/2360) to 43% (1006/2353, p < 0.001) in children ≥5 years of age. Serotypes 19A, 7F, 3, and 22F were the most common serotypes in 2012, with 19A decreasing from 19% (521/2727) to 14% (364/2620, p < 0.001), 7F decreasing from 14% (389/2727) to 12% (323/2620, p = 0.04), and 22F increasing from 7% (185/2727) to 11% (279/2620, p < 0.001) since 2010. Serotype 3 increased from 7% (23/339) to 10% (24/244) in <5-year-olds (p = 0.22) over the 3-year period. The highest rates of antimicrobial resistance were observed with clarithromycin (23%), penicillin using meningitis breakpoints (12%), clindamycin (8%), and trimethoprim-sulfamethoxazole (6%). Shifts in the distribution of IPD serotypes and reductions in the incidence of disease suggest that current immunization programs in Canada are effective in reducing the burden of IPD in children. While we acknowledge the limited data on the effectiveness of the PCV13 vaccine, to our knowledge, this study represents one of the first descriptions of the potential impact of the PCV13 vaccine in the Canadian population. Continued surveillance will be important to recognize replacement serotypes, to determine the extent of herd immunity effects in nonpaediatric populations, and to assess the overall effectiveness of PCV13 in reducing IPD in Canada.
A baseline serotype distribution was established by age and region for 2058 invasive Streptococcus pneumoniae isolates collected during the implementation period of the 13-valent pneumococcal conjugate vaccine (PCV13) program in many parts of Canada in 2010. Serotypes 19A, 7F, and 3 were the most prevalent in all age groups, accounting for 57% in <2 year olds, 62% in 2-4 year olds, 45% in 5-14 year olds, 44% in 15-49 year olds, 41% in 50-64 year olds, and 36% in ≥65 year olds. Serotype 19A was most predominant in Western and Central Canada representing 15% and 22%, respectively, of the isolates from those regions, whereas 7F was most common in Eastern Canada with 20% of the isolates. Other prevalent serotypes include 15A, 23B, 12F, 22F, and 6C. PCV13 serotypes represented 65% of the pneumococci isolated from <2 year olds, 71% of 2-4 year olds, 61% of 5-14 year olds, 60% of 15-49 year olds, 53% of 50-64 year olds, and 49% of the ≥65 year olds. Continued monitoring of invasive pneumococcal serotypes in Canada is important to identify epidemiological trends and assess the impact of the newly introduced PCV13 vaccine on public health.
Antimicrobial resistance in
Streptococcus pneumoniae
represents a threat to public health and monitoring the dissemination of resistant strains is essential to guiding health policy. Multiple-variable linear regression modeling was used to determine the contributions of molecular antimicrobial resistance determinants to antimicrobial minimum inhibitory concentration (MIC) for penicillin, ceftriaxone, erythromycin, clarithromycin, clindamycin, levofloxacin, and trimethoprim/sulfamethoxazole. Training data sets consisting of Canadian
S. pneumoniae
isolated from 1995 to 2019 were used to generate multiple-variable linear regression equations for each antimicrobial. The regression equations were then applied to validation data sets of Canadian (n=439) and USA (n=607 and n=747) isolates. The MIC for β-lactam antimicrobials were fully explained by amino acid substitutions in motif regions of the penicillin binding proteins PBP1a, PPB2b, and PBP2x. Accuracy of predicted MICs within one doubling dilution to phenotypically determined MICs for penicillin was 97.4%, ceftriaxone 98.2%; erythromycin 94.8%; clarithromycin 96.6%; clindamycin 98.2%; levofloxacin 100%; and trimethoprim/sulfamethoxazole 98.8%; with an overall sensitivity of 95.8% and specificity of 98.0%. Accuracy of predicted MICs to the phenotypically determined MICs was similar to phenotype-only MIC comparison studies. The ability to acquire detailed antimicrobial resistance information directly from molecular determinants will facilitate the transition from routine phenotypic testing to whole genome sequencing analysis and can fill the surveillance gap in an era of increased reliance on nucleic acid assay diagnostics to better monitor the dynamics of
S. pneumoniae
.
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