Direct effectiveness of pneumococcal polysaccharide vaccine against invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia in elderly population in the era of pneumococcal conjugate vaccine: A case-control study

BackgroundWhile herd effects and serotype replacement by childhood pneumococcal protein conjugated vaccines (PCVs) continues to accumulate worldwide, direct effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPV23) against pneumococcal diseases in the elderly has been challenged. We estimated the direct effectiveness of PPV23 in the elderly population.MethodsFor a hospital-based case-control study, cases of invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) (adults ≥ 65 years) were identified in 14 hospitals participated in the pneumococcal surveillance program from March 2013 to October 2015, following implementation of PPV23 national immunization program (NIP) for the elderly in the Republic of Korea. Controls matched by age, sex, and hospital were selected at ratios of 1:2 (IPD) or 1:1 (NBPP). Clinical data and vaccination records were collected. Vaccine effectiveness was calculated as (1-adjusted odds ratio) × 100.ResultsWe enrolled 148 IPD and 557 NBPP cases, and 295 IPD and 557 NBPP controls for analyses. Overall effectiveness of PPV23 against IPD was 28.5% [95% confidence interval (CI) −5.8%–51.6%] and against NBPP was 10.2% (-15.1-30.6) in all patients ≥ 65 years. However, in subgroup analysis of patients aged 65–74 years, PPV23 was protective against IPD [effectiveness 57.4% (19.4–77.5)] and against NBPP [effectiveness 35.0% (2.3–56.7)]. Furthermore, serotype-specific effectiveness of PPV23 against IPD was 90.6% (27.6–98.8) for PPV23-unique serotypes and 81.3% (38.6–94.3) for PPV23 serotypes excluding serotype 3.ConclusionsThis study indicates that PPV23 with broad serotype coverage might be beneficial in preventing IPD and NBPP due to non-PCV13 serotypes in the young-elderly, with potentially increasing effectiveness in the setting of childhood PCV NIP.     

老年人接种23价肺炎球菌多糖疫苗保护效果的Meta分析

目的 评价60岁以上老年人接种23价肺炎球菌多糖疫苗(PPV23)对侵袭性肺炎球菌疾病(IPD)和肺炎球菌肺炎(PP)的保护效果.方法 电子检索National Center for Biotechnology Information、Cochrane Library、中国生物医学文献数据库、中国期刊全文数据库和万方全文数据库等数据库,将60岁以上老年人接种PPV23流行病学保护效果的随机对照试验、队列研究、病例对照研究纳入研究.合并各项研究中关于接种组和对照组间发生IPD、PP的相对危险度(RR)或比值比(OR).在合并RR或OR有统计学意义的情况下,计算疫苗效力.使用RevMan 5.3软件进行统计分析.结果 共纳入4篇随机对照研究、5篇队列研究和8篇病例对照研究.随机对照研究合并后显示接种PPV23后对IPD和PP的疫苗效力分别是73％(95％CI:10％～92％),64％ (95％ CI:35％ ～80％);队列研究合并后显示对IPD和PP的疫苗效力分别为45％ (95％CI:15％～65％),48％ (95％CI:25％～63％);病例对照研究合并显示对IPD和PP的疫苗效力分别是59％ (95％ CI:35％～74％),45％(95％CI:27％～59％).结论 60岁以上老年人接种PPV23后对IPD和PP均有良好的保护效果,而且由于PPV23覆盖肺炎球菌血清型别较广,可以有效减少IPD、PP发病,值得在60岁以上老年人中推广使用.     

Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine

Efficacy of the new serotypes in the 13-valent pneumococcal conjugate vaccine (PCV13) against invasive pneumococcal disease (IPD) was based on a putative correlate of protection. In England and Wales, PCV13 replaced PCV7 in the 2, 4, and 13 month schedule in April 2010. Using non-vaccine type IPD cases as controls, we estimated vaccine effectiveness (VE) for the new serotypes. Among 166 IPD cases in PCV13 eligible children reported by July 2011 with known serotype and vaccination status, VE for 2 doses under a year was 78% (95% confidence interval −18% to 96%) and 77% (38-91%) for one dose over a year. VE for 7F and 19A was 76% (21-93%) and 70% (10-90%) respectively for ≥one dose. VE for serotypes 1 and 3 was 62% and 66% respectively although confidence intervals spanned zero. IPD due to PCV13-only serotypes halved in children under 2 years in the study period.     

Twelve years of pneumococcal conjugate vaccination in the Netherlands: Impact on incidence and clinical outcomes of invasive pneumococcal disease

IntroductionIn 2006, the Netherlands introduced the 7-valent pneumococcal conjugate vaccine (PCV7) in their national immunisation programme. In 2011, PCV7 was replaced by the 10-valent vaccine (PCV10). We report on the impact of PCV on invasive pneumococcal disease (IPD) incidence, clinical syndromes and patient outcomes.MethodsPneumococcal isolates of hospitalised IPD patients between June 2004 and May 2018 were obtained from nine sentinel laboratories, covering 25% of the Dutch population. All isolates were serotyped. IPD incidence and clinical outcome were determined before and after introduction of PCV7 and after the switch to PCV10, stratified by age and serotype.ResultsCompared to before PCV7 introduction, significant declines in IPD incidence were observed in 2016–2018 in children <5 years (69%), 18–49 year olds (31%) and ≥65 year olds (19%). Compared to before PCV10 introduction, the IPD incidence in 2016–2018 declined in children <5 years (RR:0.68, 95%CI:0.42–1.11), 5–17 year olds (RR:0.58, 95%CI:0.29–1.14) and 18–49 year olds (RR:0.72, 95%CI:0.57–0.90), but not in 50–64 year olds (RR:0.94, 95%CI:0.81–1.10) and ≥65 year olds (RR:1.04, 95%CI:0.0.93–1.15). While the case fatality rate (CFR) decreased from 16.2% pre-PCV to 13.4% post-PCV10 (RR:0.83, 95%CI:0.70–0.99), the switch to PCV10 had no further impact on CFR (RR:1.14, 95%CI:0.96–1.36).ConclusionTwelve years of PCV in the Netherlands has resulted in a sustained reduction of IPD incidence in children and younger adults. The switch from PCV7 to PCV10 did not have additional impact on the IPD incidence in older adults and CFR due to emerging non-vaccine serotypes.     

The effect of anti-TNF treatment on the immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis

Our aim was to study the effect of anti-TNF treatment on immunogenicity and safety of the 7-valent conjugate pneumococcal vaccine in children with juvenile idiopathic arthritis. Thirty-one children (mean age:12.9 ± 4.6 years) treated with anti-TNFs plus Disease Modifying Anti-Rheumatic Drugs (DMARDs) and 32 age-matched children treated only with DMARDs were vaccinated with two doses of PCV7. After the first vaccine dose geometric mean titers (GMTs) were significantly increased for all vaccine serotypes (p < 0.0001) in both groups and were found to be protective (>0.35 μg/ml) in 87–100% of all children, depending on the serotype. Children receiving anti-TNFs achieved a significantly lower GMTs against serotypes 4, 14 and 23F (p < 0.05). A ≥4-fold increase of the baseline titers to ≥5 vaccine serotypes was observed in 50% and 75% of the anti-TNF and control patients, respectively (p = 0.0697). No patient developed vaccine-associated serious adverse events or disease flares.     

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.     

The incidence of pediatric invasive Haemophilus influenzae and pneumococcal disease in Chiba prefecture,Japan before and after the introduction of conjugate vaccines

The Haemophilus influenzae type b (Hib) vaccine and the heptavalent pneumococcal conjugate vaccine (PCV7) were introduced in Japan in 2008 and 2010, respectively. In 2011, immunization with these two vaccines was encouraged throughout Japan through a governmental program. Children treated in Chiba prefecture for culture-proven invasive H. influenzae disease (IHiD) and invasive Streptococcus pneumoniae disease (IPD) were identified in a prefectural surveillance study from 2008 to 2013. The incidence rate ratio (IRR) and its confidence interval (CI) were calculated to compare the 3 years before and after governmental financial support for vaccination. The average number of IHiD and IPD cases among children <5 years of age in 2011–2013 decreased 84% (IRR: 0.16, 95% CI: 0.09–0.26, p < 0.0001) and 51% (IRR: 0.49, 95% CI: 0.37–0.63, p < 0.0001) compared with those occurring in 2008–2010. The most common non-PCV7 serotype encountered in 2011 and 2013 was 19A. After governmental subsidization of Hib and PCV7 vaccination, IHiD and IPD decreased in Chiba prefecture, Japan. Continuous surveillance is necessary to determine the effectiveness of these two vaccines and for detection of emerging invasive serotypes.     

Non-invasive pneumococcal serotypes and antimicrobial susceptibilities in a paediatric hospital in the era of conjugate vaccines

To evaluate the effects of 7-valent pneumococcal conjugate vaccine (PCV7) introduction to the routine childhood immunisation schedule in 2008 and its replacement by PCV13 in 2010 in Ireland, we surveyed the serotypes and antimicrobial susceptibilities of 339 pneumococci associated with carriage and non-invasive infection (NII) in a Dublin paediatric hospital from 2009 to 2012. Furthermore, we compared the distribution of pneumococcal serotypes collected from 2009 to 2012 to 105 NII pneumococci isolated in 2007, the year before conjugate vaccine introduction. PCV7 serotypes declined from 2007 to 2012 as follows: carriage, 67–23% (p = 0.0004); conjunctivitis, 58–0% (p < 0.0001); non-bacteraemic lower respiratory tract infection, 50–19% (p = 0.0363) and otitis media 54–27%. Notably, antimicrobial resistant (AMR) PCV7 serotypes showed a significant decrease by the end of the study period (i.e. 2012) (p < 0.0001). Compared with 2007 the overall occurrence of serotype 19A increased from 1.9 to 10% in 2010 (p = 0.0132) and to 15% in 2011 (p = 0.0005). Importantly, serotype 19A declined significantly from 2011 levels to an overall prevalence of 4.8% in 2012 (p = 0.0243). Most striking was the significant reduction of AMR 19A (p = 0.0195). Conversely, increases were observed in non-vaccine type (NVT) pneumococci in 2009–2012, of which serotypes 11A (n = 30), 15B/C (n = 17), 22F (n = 14), 35Bn = 13), non-typeable pneumococci (n = 13) and 23A (n = 12) were the most prevalent. Moreover, an increase in NVT non-susceptible to at least one antimicrobial in 2009–2012 was noted, attributable to serotypes 35B (n = 10) and 15A (n = 7). In summary, this study has shown that PCV7 and PCV13 introduction has had a positive impact on their target serotypes and antimicrobial resistance amongst pneumococci within a paediatric hospital within a short time period. However, the increase in NVT prevalence highlights the need for continued surveillance.     

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine compared to a 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine-naive adults

Background

Streptococcus pneumoniae is a major cause of morbidity and mortality among adults 50 years of age and older in the United States. Pneumococcal conjugate vaccines are efficacious against pneumococcal disease in children and may also offer advantages in adults.

Methods

We performed a randomized, modified double-blind trial that compared a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in 831 pneumococcal vaccine naive adults 60–64 years of age. An additional group of 403 adults 50–59 years of age received open-label PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured at baseline, and at 1 month and 1 year after vaccination.

Results

In the randomized trial, the month 1 post-vaccination OPA geometric mean titers in the PCV13 group were statistically significantly higher than in the PPSV23 group for 8 of the 12 serotypes common to both vaccines and for serotype 6A, a serotype unique to PCV13, and were comparable for the other 4 common serotypes. The immune response to PCV13 was generally greater in adults 50–59 years of age compared to adults 60–64 years of age. OPA titers declined from 1 month to 1 year after PCV13 administration but remained higher than pre-vaccination baseline titers.

Conclusions

PCV13 induces a greater functional immune response than PPSV23 for the majority of serotypes covered by PCV13, suggesting that PCV13 could offer immunological advantages over PPSV23 for prevention of vaccine-type pneumococcal infection.     

Effectiveness of 10 and 13-valent pneumococcal conjugate vaccines against invasive pneumococcal disease in European children: SpIDnet observational multicentre study

BackgroundPneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010–11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet).MethodsWe compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012–2018. We calculated pooled effectiveness as (1-vaccination odds ratio)*100, and measured effectiveness over time since booster dose.ResultsThe PCV13 and PCV10 studies included 2522 IPD cases from ten sites and 486 cases from four sites, respectively. The effectiveness of ≥ 1 PCV13 dose was 84.2% (95 %CI: 79.0–88.1) against PCV13 serotypes (n = 2353) and decreased from 93.1% (87.8–96.1) < 12 months to 85.1% (72.0–92.1) ≥ 24 months after booster dose. PCV13 effectiveness of ≥ 1 dose was 84.7% (55.7–94.7) against fatal PCV13 IPD, 64.5% (43.7–77.6), 83.2% (73.7–89.3) and 85.1% (67.6–93.1) against top serotypes 3, 19A and 1, respectively, and 85.4% (62.3–94.4) against 6C. Serotype 3 and 19A effectiveness declined more rapidly. PCV10 effectiveness of ≥ 1 dose was 84.8% (69.4–92.5) against PCV10 serotypes (n = 370), 27.2% (-187.6 to 81.6) and 85.3% (35.2–96.7) against top serotypes 1 and 7F, 32.5% (-28.3 to 64.5) and ?14.4% (-526.5 to 79.1) against vaccine-related serotypes 19A and 6C, respectively.ConclusionsPCV10 and PCV13 provide similar protection against IPD due to the respective vaccine serotype groups but serotype-specific effectiveness varies by serotype and vaccine. PCV13 provided individual protection against serotype 3 and vaccine-related serotype 6C IPD. PCV10 effectiveness was not significant against vaccine-related serotypes 19A and 6C. PCV13 effectiveness declined with time after booster vaccination. This multinational study enabled measuring serotype-specific vaccine effectiveness with a precision rarely possible at the national level. Such large networks are crucial for the post-licensure evaluation of vaccines.     

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.     

Changes in Capsule and Drug Resistance of Pneumococci after Introduction of PCV7, Japan, 2010–2013

We aimed to clarify changes in serotypes and genotypes mediating β-lactam and macrolide resistance in Streptococcus pneumoniae isolates from Japanese children who had invasive pneumococcal disease (IPD) after the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into Japan; 341 participating general hospitals conducted IPD surveillance during April 2010–March 2013. A total of 300 pneumococcal isolates were collected in 2010, 146 in 2011, and 156 in 2012. The proportion of vaccine serotypes in infectious isolates decreased from 73.3% to 54.8% to 14.7% during the 3 years. Among vaccine serotype strains, genotypic penicillin-resistant S. pneumoniae strains also declined each year. Among nonvaccine serotype strains, 19A, 15A, 15B, 15C, and 24 increased in 2012. Increases were noted especially in genotypic penicillin-resistant S. pneumoniae isolates of serotypes 15A and 35B, as well as macrolide resistance mediated by the erm(B) gene in 15A, 15B, 15C, and 24.     

The 13-valent pneumococcal conjugate vaccine (PCV13) elicits cross-functional opsonophagocytic killing responses in humans to Streptococcus pneumoniae serotypes 6C and 7A

The introduction of a 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 dramatically reduced the incidence of invasive pneumococcal disease (IPD) caused by the seven serotypes covered by the vaccine. Following the introduction of PCV7, which contains a serotype 6B conjugate, some decrease in IPD due to serotype 6A was noted suggesting that the serotype 6B conjugate provided some partial cross-protection against serotype 6A. However, no effect on serotype 6C was observed. In 2010, a pneumococcal conjugate vaccine with expanded serotype coverage (PCV13) was introduced that expanded the serotype coverage to 13 serotypes including serotype 6A. To assess whether the 6A conjugate in PCV13 could potentially induce functional anti-6C antibody responses, an opsonophagocytic assay (OPA) for serotype 6C was developed. Randomly chosen subsets of immune sera collected from infants receiving three doses of PCV7 or PCV13 were tested in OPA assays for serotype 6A, 6B and 6C. PCV7 immune sera demonstrated strong OPA responses, defined as percentage of subjects having an OPA titer ≥1:8, to serotype 6B (100% responders), partial responses to serotype 6A (70% responders) but only minimal responses to serotype 6C (22% responders). In contrast, PCV13 immune sera showed strong OPA responses to serotypes 6A (100% responders), 6B (100% responders) and 6C (96% responders). Furthermore, during pre-clinical work it was observed that serotype 7F (included in PCV13) and serotype 7A (not included in PCV13) shared serogroup-specific epitopes. To determine whether such epitopes also may be eliciting cross-functional antibody, PCV13 immune sera were also tested in serotype 7A and 7F OPA assays. All PCV13 immune sera demonstrated OPA responses to both of these serotypes. Taken together these results suggest that immunization with PCV13 has the potential to induce cross-protective responses to related serotypes not directly covered by the vaccine.     

The immunogenicity and safety of pneumococcal conjugate vaccine in human immunodeficiency virus-infected Thai children

Background

HIV-infected children have high risk of invasive pneumococcal disease (IPD) despite receiving highly active antiretroviral therapy (HAART). This study aimed to determine the immunogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV-7) in Thai HIV-infected children compared to HIV-exposed uninfected children.

Methods

A prospective study was conducted among children 2 months to 9 years. The number of PCV-7 doses depended upon age and HIV status; 2-6 months of age: 3 doses; 7-23 months of age: 2 doses; HIV-infected child ≥24 months: 2 doses and HIV-exposed child ≥24 months: 1 dose. Serotype-specific pneumococcal IgG antibody concentrations were measured at baseline and 28 days after complete vaccination. The primary end point was the proportion of children who achieved serotype-specific IgG antibody concentration at a cut off level ≥0.35 μg/mL. Secondary end points were a 4-fold increase in serotype-specific IgG antibody, rates of adverse events and predictors for seroconversion among HIV-infected children.

Results

Fifty-nine HIV-infected and 30 HIV-exposed children were enrolled. The median (IQR) age was 97 (67-111) and 61 months (51-73), respectively (p < 0.001). Among HIV-infected children, current and nadir CD4 counts were 1079 cell/mm³ and 461 cell/mm³, respectively. The proportion of children who achieved pneumococcal IgG ≥0.35 μg/mL was in the range of 85-98% in HIV-infected and 83-100% in HIV-exposed children depending on serotype. The lowest response was to serotype 6B in both groups. The 4-fold increase in serotype-specific IgG concentrations was similar between HIV-infected and HIV-exposed groups, except for serotype 9V (p = 0.027). HIV-infected children who had a history of AIDS had a lower antibody response to serotype 23F (p = 0.025). Seven (12%) HIV-infected children had a grade 3 local reaction.

Conclusion

PCV-7 is highly immunogenic and safe among HIV-infected children treated with HAART. The use of the pneumococcal conjugate vaccine among HIV-infected children is encouraged in order to prevent IPD.     

Ten years of experience with the pneumococcal conjugate 7-valent vaccine in children

In children, pneumococcus became the predominant infectious agent, after the routine use of the Hib conjugate vaccine dramatically decreased Haemophilus Influenzae type b prevalence. The incidence of invasive pneumococcal infections (IPI) and of non-invasive infections due to vaccine serotypes (VS) decreased by 80% in Europe along with a 30–40% decrease in the global incidence of IPI in this age group, after the implementation of Prevenar 7^® routine immunization in children below 2 years of age. The decrease of IPI due to VS in other age groups was an indirect benefit. The moderate increase of non-vaccinal serotype IPI incidence did not impede the benefit of the overall program. Serotype 19A was the most frequent and carried resistance to antibiotics. Prevenar 13^®, a second-generation vaccine with six new serotypes, replaced Prevenar 7^® in most countries after 2010, with available evidence of its effectiveness (United Kingdom, US, France).     

Early effectiveness of heptavalent conjugate pneumococcal vaccination on invasive pneumococcal disease after the introduction in the Danish Childhood Immunization Programme

We evaluated the effectiveness of the heptavalent pneumococcal conjugate vaccine (PCV7) on invasive pneumococcal disease (IPD) 1 year after PCV7's introduction in the childhood immunization programme through a nationwide cohort study based on laboratory surveillance data. There was a decline in the overall incidence of IPD from 19.4 to 17.1 cases per 100,000 population (incidence rate ratios (IRR) 0.87; 95% confidence interval (CI) [0.81–0.96]), and of meningitis from 1.56 to 1.16 (IRR 0.74; 95% CI [0.57–0.97]) comparing pre-PCV7 (years 2000–2007) and PCV7 (year 2008) periods. In children <2 years, the incidence decreased from 54 to 23 cases per 100,000 (IRR 0.43; 95% CI [0.29–0.62]) and for vaccine-serotypes from 36.7 to 7.7 (IRR 0.20; 95% CI [0.09–0.38]). The incidence of IPD declined ∼10% (IRR 0.90; 95% CI [0.84–0.97]) in patients aged ≥2 years. The case fatality was 17% in both periods. The administration of PCV7 was followed by a marked decline in the incidence of IPD in both vaccinated and non-vaccinated individuals.     

Long-term population impact of infant 10-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in adults in Finland

BackgroundLimited data are available on long-term indirect effects of ten-valent pneumococcal conjugate vaccine (PCV10) programmes. We evaluated changes in invasive pneumococcal disease (IPD) incidence, mortality, and serotype distribution in adults up to 9 years after infant PCV10 introduction.MethodsCulture-confirmed IPD cases ≥18 years (n = 5610; 85% were pneumonia) were identified through national, population-based laboratory surveillance; data were linked with population registry to conduct nationwide follow-up study. In a time-series model, we compared serotype-specific IPD incidence and associated 30-day mortality rates before and after PCV10 by using negative binomial regression models.ResultsDuring pre-PCV10 period (7/2004–6/2010), overall IPD incidence in adults ≥18 years increased yearly by 4.8%. After adjusting for trend and seasonality, the observed PCV10 serotype IPD incidence in 7/2018–6/2019 was 90% (12/100,000 person-years) lower than the expected rate without PCV10 program. Non-PCV10 serotype incidence was 40% (4.4/100,000 person-years) higher than expected; serotypes 3, 19A, 22F, and 6C accounted for most of the rate increase. However, incidence of non-PCV10 IPD levelled off by end of follow-up. The observed-expected incidence rate-ratio (IRR) was 0·7 (95 %CI 0·5–0.8) for all IPD and 0·7 (95 %CI 0·3–1·3) for IPD-associated 30-day mortality. Case-fatality proportion decreased from 11·9% to 10.0% (p < 0.01). In persons ≥65 years, the IRR was 0·7 (95 %CI 0·5–0.95).ConclusionsSignificant indirect effects were seen for vaccine-serotype IPD and for overall IPD in all adult age groups. For non-vaccine IPD, the incidence stabilized 5 years after infant PVC10 program introduction, resulting in a steady state in which non-vaccine IPD accounted for nearly 90% of overall IPD. Substantial pneumococcal disease burden remains in older adults.     

Decreased immune response to pneumococcal conjugate vaccine after 23-valent pneumococcal polysaccharide vaccine in children

Background

Pneumococcal polysaccharide vaccine (PPV) is used in children at high risk of IPD. PPV is generally not considered to induce immunologic memory, whereas pneumococcal conjugate vaccines (PCVs) elicit protective antibody responses in infants and induce immunologic memory. Little is known about the characteristics of immune responses to PCV in children who previously received PCV and PPV in series.

Objective

To characterize immune responses to 13-valent pneumococcal CRM₁₉₇ conjugate vaccine (PCV13; serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in children vaccinated in infancy with 9-valent pneumococcal–meningococcal C-CRM₁₉₇ conjugate combination vaccine (PCV9-MnCC), followed by a toddler dose of PCV9-MnCC or 23-valent pneumococcal polysaccharide vaccine (PPV23).

Methods

Children (n = 89) who received PCV9-MnCC in infancy and PPV23 or PCV9-MnCC at age 12 months in a previous (2002–2003) study were vaccinated at age 7.5 years with PCV13; groups PPV23/PCV13 (n = 50) and PCV9/PCV13 (n = 39). Immunoglobulin (Ig)G antibodies, avidity, and opsonophagocytic activity (OPA) were measured before and at 1 and 4 weeks postvaccination.

Results

One week postvaccination, IgG levels increased significantly for all serotypes in both groups, and >97% of vaccinees achieved IgG ≥0.35 μg/ml 4 weeks after PCV13 vaccination. The PCV9/PCV13 group had higher IgG responses compared with the PPV23/PCV13 group. The upper limits of the 95% confidence intervals of the PPV23/PCV13:PCV9/PCV13 IgG geometric mean concentration ratios were <1.0 for serotypes 1, 4, 5, 9V, 18C, and 23F at 1 week. OPA and avidity results supported these findings.

Conclusions

PPV23 vaccination of toddlers may compromise subsequent responses to pneumococcal conjugate vaccines. The clinical relevance of this finding is unclear.     

The effectiveness of pneumococcal polysaccharide vaccine 23 (PPV23) in the general population of 50 years of age and older: A systematic review and meta-analysis

Two pneumococcal vaccines currently exist and have been recommended for the prevention of pneumococcal infection in adults 65 years of age and older: the 23-valent polysaccharide (PPV23) and the conjugate 13-valent (PCV13) vaccine.ObjectiveTo evaluate and summarize the results from all studies reporting on the vaccine effectiveness of PPV23 in preventing invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) in individuals over the age of 50.MethodsSystematic database searches were completed in PubMed, Medline, Embase, CINAHL, Web of Science, and Cochrane. Google Scholar and hand searches of seminal articles and past systematic reviews were employed. Studies were included if they independently evaluated the effect of PPV23 on IPD and/or CAP in adults (50+). Data extraction and quality assessment were both completed independently by two researchers. Quality was assessed using the National Advisory Committee on Immunization methodology for quality assessment. All conflicts were resolved by consensus.ResultsThe vaccine effectiveness for PPV23 in preventing IPD was 50% (95% CI: 21%–69%) for cohort studies and 54% (95% CI: 32%–69%) for case-control studies. The VE estimates for CAP were 4% (95% CI: -26%–26%) for trials, 17% (95% CI: -26%–45%) for cohort studies, and 7% (95% CI: -10%–21%) for case-control studies.ConclusionsThe vaccine effectiveness of PPV23 in preventing IPD and all-cause CAP was consistent with past systematic reviews and similar to the estimates that were reported in the CAPiTA trial evaluating the vaccine effectiveness of PCV13. Consistent benefits were also reported across ecological studies and reports of surveillance data for the general population 50 years and older. The results suggests that the current practice of vaccinating the adults 65 years of age and older with PPV23 would have similar benefits to PCV13 in preventing potential cases of all-serotype IPD and all-cause CAP.     

Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine in 23-valent pneumococcal polysaccharide vaccine-naïve and previously immunized adult patients with severe chronic kidney disease

Individuals with chronic kidney disease (CKD) are at high risk of pneumococcal infections and recommended to receive the 23-valent pneumococcal polysaccharide vaccine (PPV23). Although the 13-valent pneumococcal conjugate vaccine (PCV13) has been found to have higher immunogenicity compared to PPV23 in adults with some immunocompromising conditions, previous PPV23 immunization may decrease the immunogenicity of PCV13. We assessed immunogenicity and safety of PCV13 in 74 PPV23-naïve and 58 previously PPV23-immunized (>1 year ago) patients with severe (stage 4–5) CKD. Serum IgG, IgM, and IgA specific to seven serotypes, i.e. 3, 6B, 9V, 14, 19A, 19F, 23F were quantified pre- and 4 weeks and one year post-immunization.Baseline concentrations for most serotype-specific IgG and IgM, and serotype 3-specific IgA were higher in previously PPV23-immunized compared to PPV23-naïve patients. Immunization with PCV13 significantly increased almost all serotype-specific IgG, all IgA and some IgM; an increase in some serotype-specific IgG and IgM lasted for one year. Fold increases in antibody concentrations and the proportion of individuals with >2-fold increase post-immunization were generally larger in PPV23-naïve than previously immunized patients for most serotype-specific IgG and some IgA. The data show that in patients with CKD who received previous PPV23 immunization over one year ago, the antibody response to PCV13 was inferior compared to pneumococcal vaccine naïve study participants. In both groups, the lowest response to PCV13 was found for serotype 3. Patients of Indigenous ethnic background demonstrated a superior immune response to PCV13 compared to the non-Indigenous counterpart that could partially be related to Indigenous study participants' younger age. Although we found that previous PPV23 immunization could contribute to the more frequent occurrence of systemic adverse events post PCV13 immunization, those did not exceed the mild to moderate range.