Elsevier

Vaccine

Volume 36, Issue 31, 25 July 2018, Pages 4701-4707
Vaccine

Serotype distribution of invasive Streptococcus pneumoniae in adults 65 years of age and over after the introduction of childhood 13-valent pneumococcal conjugate vaccination programs in Canada, 2010–2016

https://doi.org/10.1016/j.vaccine.2018.06.018Get rights and content

Highlights

Abstract

The 13-valent conjugate vaccine (PCV13) was recommended for childhood immunization programs in 2010 in Canada and has decreased the incidence of invasive pneumococcal disease (IPD) in children and changed the epidemiology of IPD in adults. This study investigated the epidemiology of IPD in adults 65 years of age and older in Canada. A total of 7282 invasive S. pneumoniae isolated from adults ≥65 years old were serotyped from 2010 to 2016 and antimicrobial susceptibility was performed on 2527 isolates. Serotyping was performed by Quellung reaction using commercial antisera and antimicrobial susceptibilities were determined by broth microdilution. PCV7 serotypes decreased non-significantly from 2010 to 2016 from 9.1% (n = 96) to 6.7% (n = 72) while the additional six PCV13 serotypes declined significantly from 39.5% (n = 418) to 18.6% (n = 201) (p < 0.05). The 23-valent pneumococcal polysaccharide vaccine (PPV23) and non-vaccine (NVT) serotypes increased from 26.3% (n = 278) to 36.2% (n = 393) (p < 0.05), and from 25.1% (n = 266) to 38.4% (n = 416) (p < 0.05), respectively. There were no significant changes in antimicrobial resistance rates from 2011 to 2016: 24.1% of the IPD from adults ≥65 years were resistant to clarithromycin (n = 609), 10.0% to doxycycline (n = 254), 11.8% to penicillin (n = 299), 5.2% to cefuroxime (n = 131), 6.6% to clindamycin (n = 168), 6.0% to trimethoprim-sulfamethoxazole (n = 152), and 0.5% (n = 12) to ceftriaxone. Although overall incidence of IPD in adults ≥65 years has remained relatively constant from 2010 to 2016, childhood PCV13 vaccination programs have been successful in indirectly reducing IPD caused by PCV13 serotypes in adults through herd immunity effects.

Introduction

Streptococcus pneumoniae is a common microorganism of the human nasopharynx which can cause severe invasive pneumococcal disease (IPD) such as bacteraemia and meningitis. Globally it has caused an estimated 1.6 million deaths annually primarily among young children and seniors [1].

A small number of the 97 currently recognized pneumococcal serotypes [2] cause the majority of disease and vaccines targeting the capsule polysaccharide (CPS) of these strains have been very successful in directly reducing the burden of IPD in children, and indirectly in adults through herd immunity effects [3], [4], [5], [6], [7], [8]. Beginning in 2002 a 7-valent conjugate vaccine became available in the Canadian market, followed in 2009 by a 10-valent product [9]. A 13-valent pneumococcal conjugate vaccine (PCV13) targeting serotypes 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 3, 5, 7F and 19A, was recommended for use in Canada in 2010 [10] and all provinces and territories incorporated the vaccine into their routine pediatric immunization schedule program between June 2010 and January 2011. Although there may be some regional variability, overall Canadian survey data for children suggest high coverage of this vaccine with over 80% of children having received full series of PCV13 by 2 years of age [11]. Despite wide spread reports of the emergence of non-vaccine serotypes (NVT) through serotype replacement or capsule switch events [12], [13], [14], [15], [16], there has not been an overall increase in disease to pre-PCV13 levels in children [12], [13], [14], [17], [18], [19].

Adult vaccines for pneumococcal disease include the 23-valent pneumococcal polysaccharide vaccine (PPV23), which has been available since 1996 with efficacy in preventing invasive disease but has limited effectiveness with respiratory disease [7], [20], [21]. PPV23 is not licenced for routine use in young children and has little efficacy on carriage, an important reservoir for the transmission and spread of invasive disease [5], [22], [23], [24]. PPV23 has also had little effect on IPD prevalence rates of constituent serotypes in adults, possibly due to low coverage, or due to the lower effectiveness of a non-conjugated polysaccharide vaccine [22], [25], [26], [27]. In a 2014 Canadian immunization coverage survey only 36.5% of adults over the age of 65 years have been immunized with PPV23 [28].

PCV13 was approved for use in adults ≥50 years of age in early 2012 based on its non-inferiority with PPV23 [24], [29], [30]. An adult PCV13 vaccine trial, Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA), showed a reduced number of invasive infections caused by PCV13 serotypes as well as 49% efficacy to other serotypes [24], [31], and sustained immunity for at least 5 years has been reported [32]. The efficacy data presented in the CAPiTA study led the Advisory Committee on Immunization Practices (ACIP) in the USA and a variety of European countries to introduce a single dose of PCV13 prior to PPV23 [33], [34]. The cost effectiveness of PCV13 vaccinations may however be tempered by assumptions made about herd immunity effects and effectiveness metrics related to non-invasive disease [35] and some modelling work has suggested that over time, the indirect effects in older adults may result in near elimination of PCV13 serotypes when PCV13 is part of the routine childhood immunization programs [8].

This study reports current trends of IPD and shifts in the distribution of S. pneumoniae serotypes in adults ≥65 years of age following the introduction of the childhood PCV13 vaccine programs in Canada.

Section snippets

Materials and methods

A total of 7282 isolates of S. pneumoniae from normally sterile clinical sites (blood, central nervous system tissue/fluid, peritoneal fluid, pericardial fluid, synovial fluid, or other deep abscesses and tissues) [36] and pleural fluid from people aged 65 years and older were serotyped from 2010 to 2016. National IPD serotype surveillance in Canada consists primarily of a passive laboratory based system where all invasive isolates from all provincial/territorial public health laboratories are

Results

Ages associated with the 7282 invasive S. pneumoniae isolates ranged from 65 to 109 years of age with a mean and mode of 76 and 65 years, respectively. There were 3117 (42.8%) isolates from people 65–74 years of age, 2424 (33.3%) from those aged 75–84 years and 1741 (23.9%) from people ≥85 years of age. Gender information was provided for 7161 (98.3%) isolates and 50.6% (n = 3625) were from male patients. Blood sources accounted for 94.6% of the isolates (n = 6887), cerebral spinal fluid

Discussion

Following the introduction of pediatric PCV13 vaccination programs in Canada in 2010, the incidence of IPD among children <5 years of age has declined dramatically from 18.2 to 10.8 cases per 100,000 population from 2010 to 2016 [46]. The ≥60 year old age group however had the highest incidence rate which has declined marginally from 22.3 to 20.3 cases per 100,000 population [46]. During this time period shifts in the distribution of pneumococcal serotypes in adults ≥65 years of age have

Acknowledgements

We thank the contributors and collaborators at the Toronto Invasive Bacterial Diseases Network – Agron Plevneshi, Sylvia Pong-Porter, Karen Green, Kenny Wong, and the site investigators and staff in TIBDN laboratories, infection control programs, and public health units. Financial support for the antimicrobial resistance portion of this study performed at the University of Manitoba was provided in part by Pfizer (Wyeth).

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