Impact of the pneumococcal conjugate vaccines on invasive pneumococcal disease in France, 2001–2012

Context and aimsVaccination with the 7-valent pneumococcal conjugate vaccine (PCV7) was recommended in France in 2003 for children <2 years. The 13-valent conjugate vaccine (PCV13) replaced PCV7 in 2010. We assessed the impact of PCVs vaccination on the incidence of invasive pneumococcal diseases (IPD) in French children (0–15 years) and adults (>15 years).MethodsIPD rates were calculated using cases reported from 2001 to 2012 to Epibac, a laboratory network. The distribution of serotypes was assessed from invasive isolates serotyped at the National reference Centre for Pneumococci. IPD incidence rates were compared between the pre-PCV7 (2001–2002), late PCV7 (2008–2009) and post PCV13 (2012) periods.ResultsThe PCVs coverage increased from 56% in the 2004 birth-cohort to 94% in the 2008 and following birth-cohorts. Following PCV7 introduction, IPD incidence decreased by 19% between 2001–2002 and 2008–2009 in children <2 years, but increased in children aged 2–15 years and adults, despite a sharp decline in PCV7-IPD in all age-groups. After PCV13 introduction, IPD incidence decreased by 34% in children <5 years, by 50% in those aged 5–15 years and 15% in adults from 2008–2009 to 2012. The incidence of PCV13-Non PCV7-IPD decreased by 74% in children <5 years and by 60% in those aged 5–15 years.ConclusionsVaccination with PCV13 was rapidly followed by a decrease in the incidence of all-type IPD in children, in relation with a sharp decrease in the incidence of PCV13-Non PCV7-IPD. Moreover, all-type IPD decreased after PCV13 introduction in older non-vaccinated age-groups, with a shift in the distribution of serotypes. Considering the whole 2001–2012 period, the vaccination with PCV7 and PCV13 resulted in a decline in the incidence of IPD in children up to the age of 5 but not in older children and adults.     

Can the success of pneumococcal conjugate vaccines for the prevention of pneumococcal diseases in children be extrapolated to adults?

Before conjugate pneumococcal vaccines (PCVs) were introduced it was estimated that Streptococcus pneumoniae caused 500,000 cases of pneumonia, 50,000 cases of bacteremia and 3000 cases of meningitis annually in the United States in both children and adults. After 10 years of routine use of the 7-valent pneumococcal conjugate vaccine (PCV7) the incidence of vaccine-type pneumococcal diseases (PDs) had significantly decreased in vaccinated children (direct effect) and unvaccinated subjects of all ages (indirect effect). Second generation, higher-valent PCVs, especially 13-valent (PCV13), routinely implemented since 2010, have reduced the incidence of PDs caused by the six additional non-PCV7 serotypes, in both vaccinated and unvaccinated subjects. The licence for this vaccine has recently been extended to include adults aged 18 to 49 in Europe. Although PCV13 has an indirect effect on IPD in adults, this will probably not achieve the same level of disease control in adults and the elderly (especially those at high risk) as that obtained in vaccinated children.     

Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in pneumococcal vaccine-naïve adults ≥50 years of age

BackgroundPneumococcal disease remains a public health priority in adults. Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine (PCV15) containing 13 serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13) plus 2 additional serotypes (22F and 33F) was evaluated in adults ≥50 years old (NCT01513551).Methods691 adults received one dose of PCV15, PCV13, or 23-valent pneumococcal polysaccharide vaccine (PPV23) and were followed 14 days for safety. Serotype-specific IgG geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) were measured immediately prior and 1-month postvaccination.ResultsSafety profiles were comparable across vaccination groups. PCV15 induced comparable levels of IgG GMCs and OPA GMTs to PCV13 and PPV23 for shared serotypes. Serotype-specific antibodies were numerically higher among recipients of PCV15 than PCV13 and PPV23 for 7 and 12 shared serotypes, respectively; and lower for 4 and 1 serotype(s), respectively. PCV15 induced higher IgG and OPA antibodies than PCV13 or PPV23 for serotypes unique to PCV15 (22F and 33F not in PCV13; 6A not in PPV23).ConclusionsPCV15 displayed an acceptable safety profile and induced IgG and OPA to all 15 serotypes included in the vaccine, at levels comparable to PCV13 and PPV23 for shared serotypes with these vaccines.Study identification: V114-002.CLINICALTRIALS.GOV identifier: NCT01513551.© 2018 Merck & Co., Inc.     

Characterization of pneumococcal meningitis before and after introduction of 13-valent pneumococcal conjugate vaccine in Niger, 2010–2018

Pneumococcal meningitis in the African meningitis belt is primarily caused by Streptococcus pneumoniae serotype 1, a serotype contained in the 13-valent pneumococcal conjugate vaccine (PCV13). In 2014, Niger introduced PCV13 with doses given at 6, 10, and 14 weeks of age. We leveraged existing meningitis surveillance data to describe pneumococcal meningitis trends in Niger.As a national reference laboratory for meningitis, Centre de Recherche Médicale et Sanitaire (CERMES) receives cerebrospinal fluid specimens from suspected bacterial meningitis cases and performs confirmatory testing for an etiology by culture or polymerase chain reaction (PCR). Specimens with S. pneumoniae detection during 2010–2018 were sent to the Centers for Disease Control and Prevention for serotyping by sequential triplex real-time PCR. Specimens that were non-typeable by real-time PCR underwent serotyping by conventional multiplex PCR. We tested differences in the distribution of pneumococcal serotypes before (2010–2012) and after (2016–2018) PCV13 introduction.During January 2010 to December 2018, CERMES received 16,155 specimens; 5,651 (35%) had bacterial etiology confirmed. S. pneumoniae accounted for 13.2% (744/5,651); 53.1% (395/744) were serotyped. During 2010–12, PCV13-associated serotypes (VT) constituted three-fourths of serotyped pneumococcus-positive specimens; this proportion declined in all age groups in 2016–18, most substantially in children aged < 5 years (74.0% to 28.1%; P < 0.05). Among persons aged ≥ 5 years, VT constituted > 50% of pneumococcal meningitis after PCV13 introduction; serotype 1 remained the most common VT among persons aged ≥ 5 years, but not among those < 5 years.VT as a group caused a smaller proportion of reported pneumococcal meningitis cases after PCV13 introduction in Niger. Serotype 1, however, remains the major cause of pneumococcal meningitis in older children and adults. Different vaccination strategies, such as changing the infant vaccination schedule or extending vaccine coverage to older children and adults, are needed, in addition to stronger surveillance.     

Sequential administration of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine–naïve adults 60–64 years of age

Background

Unlike free pneumococcal polysaccharide vaccines (PPSVs), pneumococcal conjugate vaccines (PCVs) induce a T–cell–dependent immune response. The study assessed potential influence of initial 13-valent PCV (PCV13) or 23-valent PPSV (PPSV23) on subsequent vaccine administrations.

Methods

We conducted a randomized, modified double-blind study in 720 pneumococcal vaccine–naïve adults 60–64 years of age. Subjects received either PCV13 at year 0 and PCV13 at year 1; PCV13 at year 0 and PPSV23 at year 1; or PPSV23 at year 0 and PCV13 at year 1. Antipneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after each vaccination.

Results

OPA titers following PPSV23 given 1 year after PCV13 (PCV13/PPSV23) (a) were noninferior for the 12 common serotypes and significantly higher for 6 of 12 common serotypes than those following only an initial PPSV23; and (b) were significantly higher for 11 of 12 common serotypes compared with PPSV23 followed by PCV13 (PPSV23/PCV13). In addition, PPSV23 followed 1 year later by PCV13 (PPSV23/PCV13) elicited significantly lower OPA titers than after only an initial dose of PCV13 for all 13 serotypes. Responses after a second vaccination with either PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for 9 of 13 and 8 of 12 common serotypes compared with the initial PCV13 dose.

Conclusion

In pneumococcal vaccine–naïve adults 60–64 years of age, an initial PCV13 augmented the antipneumococcal response to subsequent administration of PPSV23 for many of the serotypes in common to both vaccines. In contrast, an initial PPSV23 resulted in a diminished response to subsequent administration of PCV13 for all serotypes. With a relatively short 1-year interval between doses, responses after a second vaccination with PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for a majority of serotypes compared with the initial PCV13 dose, probably reflecting the need for a longer interval between vaccine administrations.ClinicalTrials.gov Identifier: NCT00574548.     

Surveillance of pneumococcal colonization and invasive pneumococcal disease reveals shift in prevalent carriage serotypes in Massachusetts’ children to relatively low invasiveness

BackgroundFollowing the introduction of pneumococcal conjugate vaccines (PCV), overall nasopharyngeal colonization rates have not changed significantly, however a dramatic and sustained decline in invasive pneumococcal disease (IPD) in children was observed in every setting where the PCVs were implemented. We aimed to describe the differences in invasive disease potential of serotypes that are common colonizers in pre- and post-vaccine eras in order to provide further insight in our understanding of dynamic epidemiology of pneumococcal diseases.MethodsUsing data from surveillance of nasopharyngeal carriage and enhanced surveillance for IPD, a serotype specific “invasive capacity (IC)” was computed by dividing the incidence of IPD due to serotype x by the carriage prevalence of that same serotype in children <7 years of age in Massachusetts. We have evaluated the serotype specific invasive capacity in two periods; pre-PCV13 (2001/02, 2003/04, 2006/07, 2008/09) and post-PCV13 (2010/11 and 2013/14), and by age groups; <24 months vs. ≥24 months.ResultsAn approximate 50-fold variation in the point estimate was observed between the serotypes having the highest (7F, 38, 19A, 3, 33F) and the lowest (6C, 35B, 21, 11A, 23B and 23A) computed serotype specific invasive disease potential. In the post-PCV13 era (6C, 35B, 11A, 23B and 23A), 5 of the 7 most common serotypes colonizing the nasopharynx were serotypes with the lowest invasive capacity. Serotype specific invasive capacity trended down in older children for majority of the serotypes, and serotypes 3, 10A and 19A had significantly lower invasive capacity in children older than 24 months of age compared to younger children.ConclusionInvasive capacity differs among serotypes and likely by age. Point estimates of IC for most of the common serotypes colonizing children in Massachusetts in post-PCV13 era were low and likely explain the continued reduction in IPD from the pre-PCV era in the absence of specific protection against these serotypes.     

Invasive pneumococcal disease in Canada 2010–2017: The role of current and next-generation higher-valent pneumococcal conjugate vaccines

BackgroundIn 2010–2011, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7- or 10-valent vaccine (PCV7 and PCV10, respectively) in pediatric immunization programs across Canada. For adults aged ≥65 years, the 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been publicly funded for several decades; PCV13 funding was not recommended in this population, partly due to expected ongoing vaccine-serotype disease decline stemming from herd effects of the pediatric program. Higher-valent PCVs (ie, 15- and 20-valent PCVs [PCV15 and PCV20, respectively]) currently in development may become available in Canada in the coming years.MethodsUsing the National Microbiology Laboratory surveillance reports, annual case counts and serotype distribution of invasive pneumococcal disease (IPD) from 2010 to 2017 in Canada were examined to assess the impact of existing programs on PCV13-serotype IPD and determine the proportion of IPD that can potentially be prevented by current and forthcoming higher-valent PCVs.ResultsThe percentages of PCV13-serotype IPD decreased from 55% [1492/2708] in 2010 to 30% [902/3006] in 2017 in all age groups combined, including a decline from 67% [221/331] to 18% [40/219] in children aged <5 years and from 50% [487/967] to 23% [287/1238] in adults aged ≥65 years. Overall, IPD cases declined mainly before 2014 and have plateaued since then. In 2017, PCV15- and PCV20-serotypes (inclusive of PCV13 serotypes) accounted for 42% and 58% of IPD cases, respectively, in all ages.ConclusionsIn Canada, publicly funded pediatric PCV13 use was associated with large declines in IPD due to vaccine serotypes. Substantial residual PCV13-serotype IPD proportions observed among all ages imply limits to indirect protection afforded by the pediatric PCV13 program at the current uptake level and suggest the adult PPSV23 program alone is insufficient. Higher-valent PCVs have the potential to address a substantial proportion of remaining IPD cases among all age groups.     

Trends in serotype prevalence in invasive pneumococcal disease before and after infant pneumococcal vaccination in Belgium, 2002–2010

Objectives

We evaluated the effect of the infant 7-valent pneumococcal conjugate vaccine (PCV7) program on the serotype distribution in invasive pneumococcal disease in the Belgian population.

Methods

Serotyping was performed on 13,998 bacteraemic and pleural fluid isolates sent to the National Reference Laboratory between 2002 and 2010. We compared the distribution of serogroups (SGs) between the pre- (2002–2004) and post-PCV7 (2007–2010) era for children (<18 years), adults (18–59 years) and older individuals (≥60 years).

Results

The proportion of cases caused by PCV7-SGs in subjects <18 years decreased from 69% pre-PCV7 to 26% post-PCV7 (p < 0.005) and the majority of cases caused by PCV7-SGs were caused by SG 19. Post-PCV7, the prevalence of PCV7-SGs decreased from 38% to 29% and from 57% to 35% in subjects in the age groups 18–59 and ≥60 years, respectively (p < 0.005). Post-PCV7 the prevalence of SGs 1, 7 and 19 increased significantly in subjects aged <18 years. The increase of SG19 was caused by an increase of serotype 19A in this age group (p < 0.005). After the introduction of infant PCV7 the largest rise in prevalence occurred for SGs 7, 12 and 22 (p < 0.005) in the two older age categories. Post PCV7, the overall PCV13 and 23-valent pneumococcal polysaccharide vaccine coverage rates decreased from 85% to 69% and from 96% to 93%, respectively (p < 0.005).

Conclusions

PCV7 has an impact on SG distribution of invasive pneumococcal disease isolates of vaccinated and unvaccinated subjects. SG replacement forms a major threat to the success of PCV7. PCV13, including several additional replacement serotypes (STs 1, 7F, 19A), represents an attractive alternative.     

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 18–49 years of age,naive to 23-valent pneumococcal polysaccharide vaccine

BackgroundBased on the success of vaccination with pneumococcal conjugate vaccines (PCVs) in children, recent studies have focused on PCVs in adults. Data from a randomized, double-blind study comparing the immunogenicity, tolerability, and safety of the 13-valent PCV (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in PPSV23-naive adults 60–64 years of age have been published. The same study also included a cohort of adults aged 18–49 years that received open-label PCV13. The purpose of this cohort was to examine the immunogenicity, safety, and tolerability of PCV13 in adult subjects 18–49 years of age compared with adults 60–64 years of age for whom PCV13 is approved.MethodsAdults naive to PPSV23 were grouped by age into 2 cohorts: 18–49 years (n = 899; further stratified by age into 3 subgroups 18–29, 30–39, and 40–49 years) and 60–64 years (n = 417). All subjects received 1 dose of PCV13. In both age groups, immunogenicity was assessed by antipneumococcal opsonophagocytic activity (OPA) geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) 1 month after vaccination. Safety and tolerability were evaluated.ResultsIn adults aged 18–49 years, OPA GMTs and IgG GMCs were noninferior for all 13 serotypes and statistically significantly higher for all except 1 serotype (OPA GMT) and 5 serotypes (IgG GMCs) compared with adults 60–64 years. Immune responses were highest in the youngest age subgroup (18–29 years). Local reactions and systemic events were more common in adults 18–49 years compared with 60–64 years and were self-limited.ConclusionImmune responses to PCV13 are robust in adults ≥18 years of age, with highest responses observed in the youngest subgroup. Based on its safety and immunologic profile, PCV13 may serve an important therapeutic role in younger adults, particularly those with underlying medical conditions who have an increased risk of serious pneumococcal infections.     

Estimating the risk of recurrent invasive pneumococcal disease in Australia, 1991–2016

BackgroundIndividuals who experience an initial episode of invasive pneumococcal disease (IPD) are at increased risk of recurrent episodes. However, the magnitude of risk has not been well-quantified in the pneumococcal conjugate vaccine era. Individuals with a previous episode of IPD are not commonly identified as a high-risk group in vaccination guidelines.MethodsAustralian residents with at least one case of IPD between 1991 and 2016 were identified using routine public health surveillance data which included identified IPD risk factors. Incidence of recurrent IPD was calculated from 2001 onwards (after IPD became nationally notifiable) using time-to-event analyses with individuals contributing person-time at risk of recurrence if they survived greater than 14 days after initial episode onset.ResultsFrom 1991 to 2016 there were 28,809 IPD episodes in 28,218 individuals. A total of 512 (1.8%) persons experienced 591 recurrent episodes. From 2001 to 2016 the incidence of recurrent IPD was 216.2 per 100,000 person-years, 27 times greater than the population rate of primary IPD during this period (8.0 per 100,000 population per year). Between 2011 and 2016, more than one-quarter of individuals experiencing recurrence had no IPD risk factors identified at first episode.ConclusionsThere is substantially increased risk of recurrent IPD after an initial episode. At least one-quarter of those with recurrent episodes have no identified risk factors at the initial episode. Given the potential preventability of future episodes, those with a previous IPD episode should be identified as a high-risk group and receive pneumococcal vaccination.     

Prospective epidemiologic surveillance of invasive pneumococcal disease and pneumonia in children in San José, Costa Rica

Background

Streptococcus pneumoniae (SP) is the leading cause of vaccine-preventable death in children <5 years of age, globally. This surveillance determined incidence rates of invasive pneumococcal disease (IPD), clinical and chest radiograph-confirmed pneumonia (CXR + Pn); and SP serotype distribution and antimicrobial susceptibility in children in San José, Costa Rica.

Methods

This was a 2-year prospective, population-based surveillance conducted in 2007–2009 in children aged 28 days to 36 months presenting to participating healthcare centers. Eligibility criteria for study inclusion were as follows: temperature ≥ 39.0 °C within 24 h and/or clinical suspicion of IPD or pneumonia.

Results

8801 subjects were enrolled. Median age: 14.5 months. A total of 25 children had invasive pneumococcal disease with S. pneumoniae isolated from nonduplicative cultures (22) or detected solely by PCR and a clinical picture consistent with IPD (3). Sources of positive cultures (some children had >1 positive culture) were: blood (20), pleural fluid (4), and cerebrospinal fluid (3). Of the 3 cases detected solely by PCR, 2 were from cerebrospinal fluid and 1 from pleural fluid. The overall IPD incidence rates for culture-positive only cases for children aged 28 days to <3 years was 33.7/100,000 per year for years 1 and 2 combined. Age stratification of culture-positive only subjects showed a peak during year 1 (106.8/100,000) in children 28 days to <6 months of age group, and in year 2 (45.5/100,000) in children 12 months to <24 months of age group. Most common serotypes were 14 (28.6%), followed by 3, 4, 6A, 19A, and 22F (9.5% each). Of 22 nonduplicative IPD isolates, 42.9% were penicillin- and trimethoprim/sulfamethoxazole nonsusceptible isolates. Consideration of PCR-positive cases increases the incidence of IPD for children aged 28 days to <3 years to 46.0/100,000. Overall incidence of clinical pneumonia and CXR + Pn was 1968/100,000 and 551/100,000, respectively.

Conclusions

There is a considerable burden of IPD and pneumonia in children in San José. These epidemiologic data serve as a baseline to evaluate the effectiveness of the incorporation of new conjugate pneumococcal vaccines into the National Immunization Program in Costa Rican children.     

Does pneumococcal vaccine reduce influenza morbidity in humans?

A retrospective study was conducted to verify the possibility that people immunized with pneumococcal vaccine (PV) show lower morbidity not only for pneumonia but also for influenza. A total of 450 individuals were enrolled between 1999 and 2003 and allocated to one of the following groups: (A) not vaccinated; (B) immunized with PV during 1999; (C) immunized with anti-influenza vaccine (Flu-V) each year; and (D) immunized with PV once in 1999 and Flu-V every consecutive year. People from group B showed significantly lower percentage of influenza-related diseases during the year 2000 in comparison with those from group A (p<0.01), whereas in the course of 2001 the morbidity of patients from group B was lower compared with the other groups (p<0.01). The results point to a way to decrease the morbidity of influenza-related diseases by immunization with PV only, at least for 2-3 years, avoiding Flu-V administration and permitting considerable saving for health care providers. Therefore, it is concluded that PV can reduce the morbidity of influenza at a greater rate than the Flu-V.     

Issues in pneumococcal disease and pneumococcal conjugate vaccines: Highlights of the 27th meeting of ESPID,Brussels, Belgium,June 9–13, 2009

The 27th annual meeting of the European Society for Paediatric Infectious Diseases (ESPID), held in Brussels, Belgium, addressed serious bacterial infections. The scientific program included international experts who provided insights into and discussions on the epidemiology, diagnosis, prevention, treatment, and clinical presentation of important pediatric infectious diseases. This conference report offers highlights of presentations addressing pneumococcal disease and pneumococcal conjugate vaccines.     

Has the seven-valent pneumococcal conjugate vaccine had an impact on invasive pneumococcal disease in Western Australia?

Enhanced surveillance for invasive pneumococcal disease (IPD) has been ongoing in Western Australia since 1996. We describe the epidemiology of invasive pneumococcal disease in children aged <2 years between 1996 and 2005. Pneumococcal conjugate vaccine has been offered to Aboriginal children and other high-risk children since July 2001 and to all Australian children since January 2005. A total of 1655 IPD cases were reported of whom 361 (55 Aboriginal) were aged <2 years. From 1996-2001 to 2002-2005, IPD incidence declined from 192 to 124/100,000/annum in Aboriginal children and from 70 to 56/100,000/annum in non-Aboriginal children. Incidence of IPD due to vaccine serotypes (VT) declined from 118 to 43/100,000/annum (p=0.05) in Aboriginal children and from 59 to 45/100,000/annum in non-Aboriginal children (p<0.001), with no increased incidence of disease due to non-vaccine serotypes. Continued surveillance is essential to measure the impact of the childhood pneumococcal conjugate vaccination program on IPD incidence and to identify the emergence of disease due to non-vaccine serotypes.     

Secular trends (1990–2013) in serotypes and associated non-susceptibility of S. pneumoniae isolates causing invasive disease in the pre-/post-era of pneumococcal conjugate vaccines in Spanish regions without universal paediatric pneumococcal vaccination

This study analyzed temporal trends of non-susceptibility/serotypes in invasive pneumococci from Spanish regions where pneumococcal conjugate vaccines (PCVs) were not included in paediatric immunization programmes. All invasive pneumococcal isolates voluntarily sent to the Spanish Reference Laboratory for Pneumococci (January 1990–December 2013) from hospitals located in target study regions were analyzed by age group. The PCV estimated coverage in children <24 months was correlated with 13-valent PCV (PCV13) serotypes trends. A total of 28,124 invasive isolates were analyzed: 3138 (11.2%) from children <24 months, 2161 (7.7%) from children 24–59 months, 781 (2.8%) from children 5–14 years, and 22,044 (78.4%) from adults. The estimated coverage increased from 17.6% (2002) to around 40% (2010–2013). The percentage of PCV13 serotypes among all isolates over time followed a cubic significant trend (R² = 0.884), with an increasing trend up to 2001 followed by a decrease (more prominent from 2010 onwards). The estimated PCVs coverage was significantly correlated with the decrease in the percentage of PCV13 isolates in children <24 months (r² = 0.824) and in adults (r² = 0.786), mainly due to decreases in serotypes 1 and 7F in adults, and in serogroup 6 and serotypes 7F and 19A in children <24 months. None of the non-PCV13 serotypes stood out with substantial increases in the last period. This study showed that the different serotypes (and its associated non-susceptibility trends) were not equally affected by low PCVs disposition. Lack of impact in certain serotypes as serotype 1 (in children 24–59 months), 6C (in all age groups), and 19A (in adults) suggests the need for increasing vaccine coverage in the target vaccine population to increase direct and indirect protection.     

Trends in serotypes and sequence types among cases of invasive pneumococcal disease in Scotland, 1999–2010

Introduction

The 7-valent pneumococcal conjugate vaccine (Prevenar^®, Wyeth; PCV7) was introduced to the UK paediatric immunisation schedule in 2006. This study investigates trends in serotypes and multi locus sequence types (STs) among cases of invasive pneumococcal disease (IPD) in Scotland prior to, and following, the introduction of PCV7.

Methods

Scottish Invasive Pneumococcal Disease Enhanced Surveillance has records of all cases of IPD in Scotland since 1999. Cases diagnosed from blood or cerebrospinal fluid isolates until 2010 were analysed. Logistic and poisson regression modelling was used to assess trends prior to and following the introduction of PCV7.

Results

Prior to PCV7 use, on average 650 cases of IPD were reported each year; 12% occurred in those aged <5 years and 35% affected those aged over 65 years. Serotypes in PCV7 represented 47% of cases (68% in <5 year olds). The serotype and ST distribution was relatively stable with only serotype 1 and associated ST 306 showing an increasing trend. PCV7 introduction was associated with a 69% (95% CI: 50%, 80%) reduction in the incidence of IPD among those aged <5 years, a 57% (95% CI: 47%, 66%) reduction among those aged 5–64 years but no significant change among those aged 65 years and over where increases in non-PCV7 serotypes were observed. Serotypes which became more prevalent post-PCV7 are those which were associated with STs related to the PCV7 serotypes.

Conclusions

Routine serotyping and sequence typing in Scotland allowed the assessment of the relationship between the capsule and the clones in the post vaccination era. Changes in the distribution of serotypes post PCV7 introduction appear to be driven by associations between serotypes and STs prior to PCV7 introduction. This has implications for the possible effects of the introduction of higher valency vaccines and could aid in predicting replacement serotypes in IPD.     

Have changing pneumococcal vaccination programmes impacted disease in Ontario?

Background

Publicly funded infant 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in Ontario, Canada in 2005 and was replaced by 10- and 13-valent vaccines (PCV10, PCV13) in October 2009 and November 2010, respectively. Among adults ≥ 65 years, a 23-valent polysaccharide vaccine (PPV23) has been universally available since 1996. In January 2012, PCV13 was approved for adults  ≥ 50 years. This study examines the impact of publicly funded vaccination programmes on invasive pneumococcal disease (IPD).

Methods

Laboratory data from population-based surveillance for IPD conducted at the Toronto Invasive Bacterial Disease Network and from Public Health Ontario Laboratories between January 1, 2008 and December 31, 2010 were analyzed.

Results

Between 2008 and 2010 there were 3259 cases of IPD; overall incidence was 7.4/9.3/8.3 per 100,000 in 2008/9/10, respectively. Incidence increased significantly among adults 65+ years during the period; this group had the highest incidence (21.5–25.6/100,000). The second highest incidence in 2008 and 2009 was in infants <1 year, whereas in 2010 it was in children 1–4 years. Among children <5 years, 68% and 19% of serotypes were covered by PCV13 and PCV10, respectively, between 2008 and 2010. In 2009, 6 cases with the 3 additional PCV10 serotypes were reported in infants compared with 2 in 2010. Among persons eligible for PCV7 (born ≥ 2004), there was a 77% decrease in the rate of IPD due to PCV7 serotypes between 2008 and 2010 and a 60% decrease in PCV7 serotypes among persons not vaccine-eligible (born < 2004). There was a 15% difference in serotype coverage between PCV13 and the 23-valent polysaccharide vaccine in adults ≥ 50 years.

Conclusions

During Ontario's PCV7 programme, serotype-specific decreases in IPD were observed, suggesting vaccine programme success, including herd immunity. Our results also suggest some early impact among infants from PCV10 introduction. A substantial burden of disease was also observed among older adults.     

Could a single dose of pneumococcal conjugate vaccine in children be effective? Modeling the optimal age of vaccination

Using incidence rates from CDC's Active Bacterial Core surveillance and immunogenicity data from the Navajo/Apache trial of pneumococcal conjugate vaccine (PCV), we used Markov modeling to predict the optimal age to give a single dose of PCV. Antibody concentration thresholds of 0.35 and 1.0 mcg/ml were considered protective. Our outcome was vaccine serotype-specific invasive pneumococcal disease (IPD) incidence at 24 months. The models predicted the optimal age to vaccinate is 5-7 months with vaccine-induced immunologic memory and 8-10 months without memory. IPD reduction ranged from 15 to 62%, depending on model parameters. A single PCV dose in infants could prevent substantial IPD.     

The effect of various types of patients’ reminders on the uptake of pneumococcal vaccine in adults: A randomized controlled trial

BackgroundInvasive pneumococcal disease is one of the most important vaccine-preventable diseases threatening the adult community due to missed opportunities for vaccination. This study compares the effect of three different types of patient reminder system on adulthood Streptococcus pneumoniae immunization in a primary care setting.MethodsThe study targeted patients aged 40 and older eligible for pneumococcal vaccine, but did not receive it yet (89.5% of 3072 patients) based on their electronic medical records in a family medicine center in Beirut. The sample population was randomized using an automated computer randomization system into six equal groups, receiving short phone calls, short text messaging system (sms-text) or e-mails each with or without patient education. Each group received three identical reminders spaced by a period of four weeks. Documentation of vaccine administration was then added to the longitudinal electronic patient record. The primary outcome was the vaccine administration rate in the clinics.ResultsOf the eligible patients due for the pneumococcal 23-polyvalent vaccine, 1380 who had mobile phone numbers and e-mails were randomized into six equal intervention groups. The various reminders increased vaccination rate to 14.9%: 16.5% of the short phone calls group, 7.2% of the sms-text group and 5.7% of the e-mail group took the vaccine. The vaccination rate was independent of the age, associated education message and the predisposing condition.ConclusionUse of electronic text reminders via e-mails and mobile phones seems to be a feasible and sustainable model to increase pneumococcal vaccination rates in a primary care center.