Incremental effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia hospitalisation among Australian Indigenous children: A record linkage study

BackgroundThe impact of pneumococcal conjugate vaccines (PCVs) on pneumonia in children is well-documented but data on 23-valent pneumococcal polysaccharide vaccine (PPV23) are lacking. Between 2001 and 2011, Indigenous children in Western Australia (WA) were recommended to receive PPV23 at 18–24 months of age following 3 doses of 7-valent PCV. We evaluated the incremental effectiveness of PPV23 against pneumonia hospitalisation.MethodsIndigenous children born in WA between 2001 and 2012 who received PCV dose 3 by 12 months of age were followed from 18 to 60 months of age for the first episode of pneumonia hospitalisation (all-cause and 3 subgroups: presumptive pneumococcal, other specified causes, and unspecified). We used Cox regression modelling to estimate hazard ratios (HRs) for pneumonia hospitalisation among children who had, versus had not, received PPV23 between 18 and 30 months of age after adjustment for confounders.Results11,120 children had 327 first episodes of all-cause pneumonia hospitalisation, with 15 (4.6%) coded as presumptive pneumococcal, 46 (14.1%) as other specified causes and 266 (81.3%) unspecified. No statistically significant reduction in all-cause pneumonia was seen with PPV23 (HR 1.11; 95% CI: 0.87–1.43), but the direction of the association differed for presumptive pneumococcal (HR 0.47; 95% CI: 0.16–1.35) and specified (HR 0.89; 95% CI: 0.49–1.62) from unspecified causes (HR 1.13; 95% CI: 0.86–1.49). During the baseline period before PPV23 vaccination (12–18 months), all-cause pneumonia risk was higher among PPV23-vaccinated than unvaccinated children (RR: 1.73; 95% CI: 1.30–2.28).ConclusionIn this high-risk population, no statistically significant incremental effect of a PPV23 booster at 18–30 months was observed against hospitalised all-cause pneumonia or the more specific outcome of presumptive pneumococcal pneumonia. Confounding by indication may explain the slight trend towards an increased risk against all-cause pneumonia. Larger studies with better control of confounding are needed to further inform PPV23 vaccination.     

Evaluation of impact of 23 valent pneumococcal polysaccharide vaccine following 7 valent pneumococcal conjugate vaccine in Australian Indigenous children

BackgroundHigh incidence and serotype diversity of invasive pneumococcal disease (IPD) in Indigenous children in remote Australia led to rapid introduction of 7-valent conjugate pneumococcal vaccine (7vPCV) at 2, 4 and 6 months in 2001, followed by 23-valent polysaccharide pneumococcal vaccine (23vPPV) in the second year of life. All other Australian children were offered 3 doses of 7vPCV without a booster from 2005. This study evaluated the impact of the unique pneumococcal vaccine schedule of 7vPCV followed by the 23vPPV booster among Indigenous Australian children.MethodsChanges in IPD incidence derived from population-based passive laboratory surveillance in Indigenous children <5 years eligible for 23vPPV were compared to non-Indigenous eligible for 7vPCV only from the pre-vaccine introduction period (Indigenous 1994–2000; non-Indigenous 2002–2004) to the post-vaccine period (2008–2010 in both groups) using incidence rate ratios (IRRs) stratified by age into serotype groupings of vaccine (7v and 13vPCV and 23vPPV) and non-vaccine types. Vaccine coverage was assessed from the Australian Childhood Immunisation Register.ResultsAt baseline, total IPD incidence per 100,000 was 216 (n = 230) in Indigenous versus 55 (n = 1993) in non-Indigenous children. In 2008–2010, IRRs for 7vPCV type IPD were 0.03 in both groups, but for 23v-non7v type IPD 1.2 (95% CI 0.8–1.8) in Indigenous versus 3.1 (95% CI 2.5–3.7) in non-Indigenous, difference driven primarily by serotype 19A IPD (IRR 0.6 in Indigenous versus 4.3 in non-Indigenous). For non-7vPCV type IPD overall, IRR was significantly higher in those age-eligible for 23vPPV booster compared to those younger, but in both age groups was lower than for non-Indigenous children.ConclusionThese ecologic data suggest a possible “serotype replacement sparing” effect of 23vPPV following 7vPCV priming, especially for serotype 19A with supportive evidence from other immunogenicity and carriage studies. Applicability post 10vPCV or 13v PCV priming in similar settings would depend on local serotype distribution of IPD.     

Immune response to the 23-valent polysaccharide pneumococcal vaccine after the 7-valent conjugate vaccine in allogeneic stem cell transplant recipients: Results from the EBMT IDWP01 trial

The current recommendations for active immunization after stem cell transplant (SCT) include 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7) from 3 months after transplant, followed by a 23-valent polysaccharide pneumococcal vaccine (PPV23). However, until now, the immune response to PPV23 after PCV7 has not been assessed after SCT. In the EBMT IDWP01 trial, 101 patients received 1 dose of PPV23 at 12 or 18 months, both after 3 doses of PCV7. The efficacy of PPV23 was assessed 1 month later and at 24 months after transplant by the pneumococcal serotype 1 and 5 antibody levels. Serotype 1 and 5 are not included in PCV7. Although the geometric mean concentrations were significantly higher 1 month after PPV23, for both antigens, the response rates (≥0.15 μg/mL), in the range of 68–94%, were not different between groups independent of the assessment date. One PPV23 dose after 3 PCV7 doses, already known to increase the response to PCV7, also extends the serotype coverage given 12 or 18 months after transplant.     

Pneumococcal carriage,serotype distribution,and antimicrobial susceptibility in Papua New Guinean children vaccinated with PCV10 or PCV13 in a head-to-head trial

BackgroundChildren in Papua New Guinea (PNG) are at high risk of pneumococcal infections. We investigated pneumococcal carriage rates, serotype distribution, and antimicrobial susceptibility in PNG children after vaccination with 10-valent or 13-valent pneumococcal conjugate vaccines (PCV10; PCV13).MethodsInfants (N = 262) were randomized to receive 3 doses of PCV10 or PCV13 at 1-2-3 months of age, followed by pneumococcal polysaccharide vaccination (PPV) or no PPV at 9 months of age. Nasopharyngeal swabs (NPS) collected at ages 1, 4, 9, 10, 23 and 24 months were cultured using standard bacteriological procedures. Morphologically distinct Streptococcus pneumoniae colonies were serotyped by the Quellung reaction. Antimicrobial susceptibility was determined by Kirby-Bauer disc diffusion and minimum inhibitory concentration (MIC).ResultsS. pneumoniae was isolated from 883/1063 NPS collected at 1–23 months of age, including 820 serotypeable (64 different serotypes) and 144 non-serotypeable isolates. At age 23 months, 93.6% (95%CI 86.6–97.6%) of PCV10 recipients and 88.6% (95%CI 80.1–94.4%) of PCV13 recipients were pneumococcal carriers, with higher carriage of PCV10 serotypes by PCV10 recipients (19.8%, 95%CI 12.2–29.5) than PCV13 recipients (9.3%, 95%CI 4.1–17.3) (p = 0.049). There were no other statistically significant differences between PCV10 and PCV13 recipients and children receiving PPV or no PPV. Nearly half (45.6%) of carried pneumococci were non-susceptible to penicillin based on the meningitis breakpoint (MIC ≥ 0.12 µg/mL), but resistance was rare (1.1%) using the non-meningitis cut-off (MIC ≥ 8 µg/mL). Non-susceptibility to trimethoprim-sulfamethoxazole (SXT) was common: 23.2% of isolates showed intermediate resistance (MIC 1/19–2/38 µg/mL) and 16.9% full resistance (MIC ≥ 4/76 µg/mL). PCV serotypes 14 and 19A were commonly non-susceptible to both penicillin (14, 97%; 19A, 70%) and SXT (14, 97%; 19A, 87%).ConclusionEven after PCV10 or PCV13 vaccination, children living in a high-risk setting such as PNG continue to experience high levels of pneumococcal colonization, including carriage of highly antimicrobial-resistant PCV serotypes.The study is registered with ClinicalTrials.gov (CTN NCT01619462).     

Effectiveness of a 3 + 0 pneumococcal conjugate vaccine schedule against invasive pneumococcal disease among a birth cohort of 1.4 million children in Australia

BackgroundMost studies use indirect cohort or case-control methods to estimate vaccine effectiveness (VE) of 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) against invasive pneumococcal disease (IPD). Neither method can measure the benefit vaccination programs afford the unvaccinated and many studies were unable to estimate dose-specific VE. We linked Australia’s national immunisation register with health data from two states to calculate IPD incidence by vaccination status and VE for a 3 + 0 PCV schedule (doses at 2, 4, 6 months, no booster) among a cohort of 1.4 million births.MethodsBirths records for 2001–2012 were probabilistically linked to IPD notifications, hospitalisations, deaths, and vaccination history (available until December 2013). IPD rates in vaccinated and unvaccinated children <2 years old were compared using Cox proportional hazards models (adjusting for potential confounders), with VE = (1 − adjusted hazard ratio) × 100. Separate models were performed for all-cause, PCV7, PCV13 and PCV13-non-PCV7 serotype-specific IPD, and for Aboriginal and non-Aboriginal children.ResultsFollowing introduction of universal PCV7 in 2005, rates of PCV7 serotype and all-cause IPD in unvaccinated children declined 89.5% and 61.4%, respectively, to be similar to rates in vaccinated children. Among non-Aboriginal children, VEs for 3 doses were 94.2% (95%CI: 81.9–98.1) for PCV7 serotype-specific IPD, 85.6% (95%CI: 60.5–94.8) for PCV13-non-PCV7 serotype-specific IPD and 80.1% (95%CI: 59.4–90.3) for all-cause IPD. There were no statistically significant differences between the VEs for 3 doses and for 1 or 2 doses against PCV13 and PCV13-non-PCV7 serotype-specific IPD, or between Aboriginal and non-Aboriginal children.ConclusionOur population-based cohort study demonstrates that >90% coverage in the first year of a universal 3 + 0 PCV program provided high population-level protection, predominantly attributable to strong herd effects. The size of the cohort enabled calculation of robust dose-specific VE estimates for important population sub-groups relevant to vaccination policies internationally.     

Comparative impact of pneumococcal conjugate vaccines on pneumococcal meningitis according to underlying conditions

BackgroundSeveral underlying conditions increase the risk of pneumococcal meningitis (PM) in childhood. Patients with these diseases are initially considered as an important target of pneumococcal conjugate vaccines (PCVs). Limited data are available for PM in children with underlying conditions. To understand the benefits of PCV7 followed by PCV13 in this vulnerable population, we analyzed the data for a large cohort of pediatric patients with PM in France from 2001 to 2014.MethodsWe conducted hospital-based active surveillance with 227 pediatric wards working with 168 microbiology departments throughout France. Standardized inclusion criteria for PM were used and data were analyzed by a pre-PCV7, post-PCV7 and post-PCV13 period.ResultsFrom 2001 to 2014, among the 1582 cases of PM, 62.5% were reported in children less than 2 years old. Underlying conditions (n = 255, 16.1%) accounted for 7.3% of the cases in these young children versus 30.8% for children ⩾2–18 years old (p < 0.001). After PCV13 implementation, PM cases decreased by 44.0% from 2009 to 2014, mainly in children without underlying conditions. Though the number of children with underlying conditions remained stable, their proportion among overall PM cases increased by 79.1%. Among children with underlying conditions, PCV7 serotypes, 6 additional PCV13 serotypes, additional 11 serotypes in PPV23 and other serotypes accounted for 24.5%, 14.7%, 25.0% and 35.8%, respectively (p < 0.001). After PCV13 implementation, 50.0% of PM cases with underlying conditions and 37.9% without underlying conditions were caused by serotypes included in neither PCV13 nor PPV23.ConclusionBesides the reduced numbers of PM, its profile has changed, with an increase in cases in proportion of children with underlying conditions accompanied by a striking change in serotype distribution. This underlines the importance of detecting underlying conditions in children with PM in the PCV13 era.     

Immunogenicity of 13-valent pneumococcal conjugate vaccine among children with underlying medical conditions

BackgroundStreptococcus pneumoniae is a leading cause of vaccine-preventable disease in children under 5 years. Immunocompromised children and those with underlying diseases are at increased risk of severe complications from vaccine-preventable infections. We studied the humoral immune response to the 13-valent pneumococcal conjugate vaccine (PCV13) in children with HIV-infection, kidney or lung disease and compared this to the response in healthy control children.MethodsChildren aged 12–71 months with underlying conditions including HIV-infection and those with kidney and lung diseases (at-risk children), and a healthy control group were vaccinated with PCV13. The at-risk children received two doses of PCV13 and the controls received one dose. Serotype-specific antibodies for all PCV13 serotypes were measured by a luminex-based enzyme immunoassay at baseline and post-vaccination.ResultsAfter the first PCV13 dose, the fold-increase in serotype-specific antibody geometric mean concentrations (GMCs) from baseline and the percentage of participants with ≥4-fold-increase in antibody concentrations was similar between the control and at-risk children. GMCs were, however, lower for three of the 13 serotypes in HIV-infected children, higher for serotype 6B in children with kidney disease and higher for serotypes 6B and 14 in children with lung disease. After second vaccine dose HIV-infected children had an increase in GMCs from post-first dose for nine serotypes but the percentage of participants with ≥4-fold-increase from baseline was similar post-second dose compared to post-first dose except for serotypes 6A and 19F. In children with kidney or lung diseases the immune responses after second vaccine dose were similar to post-first dose. Attenuated responses were observed for serotypes 3 and 19A in all study-groups, which was especially pronounced in the at-risk groups.ConclusionAll study-groups mounted an immune response to PCV13, with the at-risk groups having responses that were mostly similar to the control children.     

Pneumococcal conjugate vaccine primes mucosal immune responses to pneumococcal polysaccharide vaccine booster in Papua New Guinean children

IntroductionInvasive pneumococcal disease remains a major cause of hospitalization and death in Papua New Guinean (PNG) children. We assessed mucosal IgA and IgG responses in PNG infants vaccinated with pneumococcal conjugate vaccine (PCV) followed by a pneumococcal polysaccharide vaccine (PPV) booster.MethodsInfants received 7-valent PCV (7vPCV) in a 0–1–2 (neonatal) or 1–2-3-month (infant) schedule, or no 7vPCV (control). At age 9 months all children received 23-valent PPV (23vPPV). IgA and IgG to 7vPCV and non-7vPCV (1, 5, 7F, 19A) serotypes were measured in saliva collected at ages 1, 2, 3, 4, 9, 10 and 18 months (131 children, 917 samples). Correlations were studied between salivary and serum IgG at 4, 10 and 18 months.ResultsSalivary IgA and IgG responses overall declined in the first 9 months. Compared to non-7vPCV recipients, salivary IgA remained higher in 7vPCV recipients for serotypes 4 at 3 months, 6B at 3 months (neonatal), and 14 at 3 (neonatal), 4 and 9 months (infant); and for salivary IgG for serotypes 4 at 3, 4 and 9 months, 6B at 9 months, 14 at 4 (neonatal) and 9 months, 18C at 3, 4, and 9 (infant) months, and 23F at 4 months. Following 23vPPV, salivary 7vPCV-specific IgA and IgG increased in 7vPCV-vaccinated children but not in controls; and salivary IgA against non-PCV serotypes 5 and 7F increased in 7vPCV recipients and non-recipients. Salivary and serum IgG against 7vPCV-serotypes correlated in 7vPCV-vaccinated children at 4 and 10 months of age.ConclusionsPCV may protect high-risk children against pneumococcal colonization and mucosal disease by inducing mucosal antibody responses and priming for mucosal immune memory that results in mucosal immune responses after booster PPV. Saliva can be a convenient alternative sample to serum to study PCV-induced systemic IgG responses.     

Decrease in the incidence and in hospital mortality of community-acquired pneumonia among children in Spain (2001–2014)

ObjectivesTo describe trends in the incidence and outcomes of community-acquired pneumonia (CAP) hospitalizations among Spanish children from 2001 to 2014 and to assess the effect of the pneumococcal vaccination (PCV) coverage in this period.MethodsThis study was conducted using the Spanish National Hospital Database from 2001 to 2014 including subjects <18 years. We selected discharges with a primary diagnosis of CAP.Study variable included age, sex, comorbid conditions, procedures, isolated pathogens and hospital outcome variables.In order to estimate the effect of coverage of pneumococcal vaccination in hospitalizations for CAP, we used the number of commercialized doses of PCV (PCV7 PCV10, and PCV13) for each year.Incidence rates of admissions for CAP were calculated by dividing the number of admissions per year, sex, and age group by the corresponding number of people in that population group according to the census data.ResultsWe identified 194,419 admissions for CAP. Incidence rate was highest among children younger than 2 years and decreased significantly by 3.67% per year over the study period in this age group. Among children aged 2–4 years incidence of CAP seem to decrease after year 2009. S. pneumoniae isolations decreased significantly over time but virus isolations increased. In children aged <2 years and 2–4 years increase in PVC was associated to a decrease in the incidence of CAP hospitalizations.Overall crude in hospital mortality following CAP fell significantly from 4.1‰ in 2001–2003 to 2.8‰ in 2012–2014.ConclusionsCAP incidence rates decreased significantly among children <2 years of age from 2001 to 2014. S. pneumoniae isolations decreased significantly over time but virus isolations increased. In hospital mortality paralleling CAP fell significantly in children and adolescents from 2001 to 2014. Improvement in vaccination coverage seems to have a mitigating effect on hospitalizations and outcomes for CAP in children.     

Alterations in serotype-specific B cell responses to the 13-valent pneumococcal conjugate vaccine in aging HIV-infected adults

BackgroundAdvanced age and human immunodeficiency virus (HIV) infection are associated with increased pneumococcal disease risk. The impact of these factors on cellular responses to vaccination is unknown.MethodsHIV-infected (HIV+) individuals 50–65 years old with CD4⁺ T cells/μl (CD4) >200 on antiretroviral therapy (ART) ≥1 year received either the 13-valent pneumococcal conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine (PCV/PPV) or PPV only. HIV-uninfected (HIV−) controls received PCV/PPV. Phenotype distribution and surface expression of complement receptor CD21 and tumor necrosis factor superfamily receptors (TNFRs) were compared on serotype-specific B cells postvaccination.ResultsPostvaccination serotype-specific B cell percentages were significantly lower in HIV+ PCV/PPV compared to PPV groups, but similar between HIV+ or HIV− PCV/PPV groups. Transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI)⁺ serotype-specific B cell percentages were significantly decreased in HIV+ PCV/PPV compared to PPV groups. CD21⁺ serotype-specific B cells were significantly higher in HIV− compared to HIV+ PCV/PPV groups.ConclusionsAn initial dose of PCV reduced the frequency, but not phenotype distribution, of serotype-specific B cells and also lowered TACI expression in aging HIV+ subjects postvaccination with PPV. These findings suggest that PCV does not enhance cellular responses to revaccination with PPV.     

Effectiveness of thirteen-valent pneumococcal conjugate vaccine to prevent serotype 3 invasive pneumococcal disease in Quebec in children,Canada

In the province of Quebec, Canada, a 2 + 1 dose pneumococcal conjugate vaccine (PCV) program for children was implemented in 2004. PCV7 was replaced by PCV10 in 2009, by PCV13 in 2011 and by PCV10 in 2018, without catch-up in all instances. The objective was to estimate PCV13 effectiveness to prevent serotype 3 invasive pneumococcal disease in children aged less than 5 years, using 2010–2018 mandatory notification and laboratory surveillance data, an indirect cohort design and multivariate logistic regression models. A total of 29 cases of serotype 3 and 290 non-vaccine serotype cases as controls were analysed. Overall vaccine effectiveness (≥1 dose) was estimated at 59% [-39% to 88%]. During the first year after the last dose effectivness was 88% [47% to 97%] whereas no protection was observed thereafter. There was no trend towards increased effectiveness with the number of doses. PCV13 protection against serotype 3 IPD seems to be short-lived.     

Low vaccination coverage of pneumococcal conjugate vaccines (PCVs) in Shanghai,China: A database analysis based on birth cohorts from 2012 to 2020

BackgroundPneumococcal vaccines have been developed to protect infants and young children from pneumococcal diseases. Vaccination coverage studies are important in determining a population’s vaccination status and strategically adjusting national immunization programs (NIP). In this paper, we aim to describe the coverage of pneumococcal conjugate vaccines (PCVs) immunization for birth cohorts from 2012 to 2020 and discussed the factors influencing the coverage.MethodsVaccination data were collected via the vaccination information database in Shanghai, China, for children born from 2012 to 2020. The population data used in this study were collected from each community from 2012 to 2020. The coverage of initial immunization (1^st dose), basic immunization (three doses) and full immunization (3 + 1 doses) for PCVs was calculated according to the number of doses received. As vaccination coverage was assessed each year, Annual Growth Rate (AGR) was used to describe the variation trend of vaccination coverage. Immunization time and completeness of different PCVs were also analyzed.ResultsThe total number of births from 2012 to 2020 was 38,268 in Huangpu District, Shanghai, China. The initial immunization coverage of PCVs increased from 12.26% in 2012 to 49.65% in 2020, and the highest coverage was 50.61% in 2019. The cumulative vaccination coverage of PCVs was 19.4% for initial immunization and 16.8% for basic immunization from 2012 to 2020. And cumulative full immunization coverage of PCVs was 12.3% from 2012 to 2019. The PCVs coverage of most vaccination statuses showed an obvious upward trend from 2017 to 2020.ConclusionsDespite an upward trend in vaccination coverage of PCVs, the vaccination coverage of initial, basic and full immunization among children is still low. And given the heavy burden of Streptococcus pneumoniae (Sp) among children in China and the fact that the current vaccination coverage cannot effectively protect children, it is recommended that the government include PCVs into the NIP as soon as possible.     

Immunogenicity and safety of double dosage of pneumococcal vaccines in adult kidney transplant recipients and waiting list patients: A non-blinded,randomized clinical trial

BackgroundPneumococcal prime-boost vaccination is recommended for solid organ transplant recipients, but is not thoroughly tested in this population. Furthermore, a pneumococcal vaccine dose effect has never been investigated, though observed in healthy adults. To assess whether a double dose of 13-valent pneumococcal conjugate vaccine (PCV13) and of 23-valent pneumococcal polysaccharide vaccine (PPV23) increases the immunogenicity of prime-boost vaccination in kidney transplant recipients (KTRs) and patients on the kidney transplant waiting list (WLPs), a phase 3, randomized, non-blinded trial was conducted.MethodsKTRs and WLPs were in parallel groups assigned either normal or double dosage of both vaccines 12 weeks apart. A ′protective response′ was an average geometric mean concentration ≥ 1 mg/L based on 12 vaccine shared serotype-specific IgG antibodies. Furthermore, number of antibodies with ≥ 2-fold rises and individual serotype-specific antibody concentrations were evaluated. Follow-up was 48 weeks.ResultsSeventy-four KTRs and 65 WLPs were enrolled. In WLPs, double dosage resulted in a significantly higher proportion of participants with a ′protective response′ (66.7%), 5 weeks after PPV23, compared to normal dosage (35.5%), p = 0.015. KTRs exhibited no dose effect. After PPV23, all four groups had increased their number of serotypes with ≥ 2-fold rises (p ≤ 0.05 for both WLPs groups; p ≤ 0.01 for both KTRs groups). Vaccines were safe, well tolerated and still immunogenic at week 48.ConclusionsData suggests that double dosage of pneumococcal vaccines used according to the prime-boost strategy might be recommendable for WLPs. Furthermore, our data supports PPV23?s additive effect to PCV13 in KTRs and WLPs. (EudraCT: 2016–004123-23)     

Changes in empyema among U.S. children in the pneumococcal conjugate vaccine era

BackgroundParapneumonic empyema, a serious complication of pneumonia, started increasing among U.S. children before the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000, and continued afterwards. This increase was due in part to pneumococcal serotypes not included in PCV7 that were included in the new 13-valent (PCV13) vaccine introduced in 2010. We assessed changes in the incidence of empyema hospitalizations among U.S. children after PCV13 introduction.MethodsWe calculated annualized empyema hospitalization rates among U.S. children <18 years using Nationwide Inpatient Sample and Census data (1997–2013) for four periods based on PCV7 and PCV13 introductions. Relative rates (RR) and 95% confidence intervals (CI) were calculated by age group and sex, comparing PCV7 [early-PCV7 (2001–2005) and late-PCV7 (2006–2009)] and PCV13 (2011–2013) periods with the pre-PCV7 period (1997–1999). Secondary analyses examined changes in pneumococcal, streptococcal, staphylococcal and unspecified empyema.ResultsAmong children <18 years of age, annualized empyema hospitalization rates peaked at 3.6 per 100,000 in the late-PCV7 period compared with 2.1 per 100,000 in the pre-PCV7 period [RR: 1.70 (95% CI: 1.11–2.60)]. However, annualized rates in the post-PCV13 period declined to 2.0 per 100,000, similar to rates in the pre-PCV7 period. Empyema rates among children <2 years were lower in the post-PCV13 period compared to the pre-PCV7 period [RR: 0.77 (95% CI: 0.61–0.96)], but rates in the two periods among children 2–4 and 5–17 years were similar. Most empyema were of unspecified etiology. Pneumococcal and unspecified empyema declined after PCV13 introduction.ConclusionsAlthough empyema hospitalization rates among U.S. children peaked after PCV7 introduction, rates decreased substantially following the introduction of PCV13.     

Effectiveness of three pneumococcal conjugate vaccines to prevent invasive pneumococcal disease in Quebec,Canada

BackgroundIn Quebec, a pneumococcal conjugate vaccine (PCV) program was implemented in December 2004. The recommended schedule is 2 + 1 doses for low-risk infants. PCV-7 was first used (including catch-up for children <5 years of age), replaced by PCV10 in June 2009, and by PCV13 in January 2011 (no catch-up in both instances). From the beginning, >90% of children received the recommended number of doses.ObjectiveTo assess the effectiveness of the three PCVs sequentially used to prevent invasive infectious disease (IPD).MethodsIPD cases in children 2–59 months during the years 2005–2013 were eligible. Controls were randomly identified in the provincial health insurance registry. Parents were interviewed and immunization records reviewed. Vaccine effectiveness (VE) was computed using multivariate logistic regression models.ResultsOut of 889 IPD cases reported, full participation was obtained for 516 cases (58%) and for 1767 controls. Against vaccine-type IPD, VE (≥1 dose) was 90% (82–95%) for PCV7, 97% (84–99%) for PCV10 and 86% (62–95%) for PCV13. Against 19A IPD, VE was, respectively, 42% (−9% to 69%), 71% (24–89%), and 74% (11–92%). VE (≥2 doses) against PCV13-type IPD was 85% for PCV10 (66–94%), 85% for PCV13 (55–94%), and 89% (58–97%) for a mixed PCV10 + PCV13 schedule.ConclusionsAll three PCV vaccines showed high level of protection against IPD caused by serotypes included in their formulation and there was a high level of cross-protection against 19A for PCV10. No substantial difference was seen between PCV10, PCV13, or a mixed PCV10 + PCV13 schedule.     

Pneumococcal carriage in young children after introduction of PCV13 in Hong Kong

ObjectivesPneumococcal conjugate vaccine (PCV) has been included in Hong Kong’s Childhood Immunization Programme since 2009. This study aimed to assess nasopharyngeal pneumococcal carriage rate, serotypes and antimicrobial resistance pattern in young children after the introduction of 13-valent PCV (PCV13).Study designA community-based, cross-sectional surveillance study was performed on healthy infants attending eleven Maternal and Child Health Centres across different parts of Hong Kong. Nasopharyngeal swabs were obtained from healthy children aged 2, 12 and 18 months during their visit to the centers for immunization from June 2013 to June 2014. Pneumococcal isolates were serotyped and tested for antimicrobial resistance. Details of the demographics, family composition, vaccination history and medical history was obtained through interview of the guardians.Results1541 children were recruited. The overall carriage rate was 5.5%. Children aged 12 and 18 months were more likely to have pneumococcal colonization (12 months OR: 2.88; 95% CI: 1.41–5.87 and 18 months OR: 2.19, 95% CI: 1.05–4.57). Recent respiratory symptoms and presence of siblings younger than 6 years were independently associated with pneumococcal carriage. Eighty-four pneumococcal isolates were serotyped. The most prevalent serogroup/types were 15 (15B/C, 16.7%; 15A/F, 9.5%), 6C (15.5%) and 23A (13.1%). Overall, 2.4% of the isolates were heptavalent PCV serotypes, 10.7% were PCV13 serotypes and 89.3% were non-PCV13 serotypes. The proportions of penicillin, cefotaxime and erythromycin non-susceptible isolates were 7.3%, 13.4% and 79.3% respectively.ConclusionThe rate of pneumococcal carriage was low in young children in Hong Kong and compared to previous local studies there appears to have been an overall reduction in the carriage rate after the introduction of PCV. Likely serotype replacement was noted with a predominance of non-vaccine serotypes in pneumococcal carriage with the emergence of serogroup/type 15 and 6C.     

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.     

Clinical effectiveness of 13-valent and 23-valent pneumococcal vaccination in middle-aged and older adults: The EPIVAC cohort study, 2015–2016

BackgroundClinical benefits using the 23-valent pneumococcal polysaccharide vaccine (PPsV23) or the 13-valent pneumococcal conjugate vaccine (PCV13) in adults are controversial. This study investigated clinical effectiveness for both PPsV23 and PCV13 in preventing pneumonia among middle-aged and older adults.MethodsPopulation-based cohort study involving 2,025,730 persons ≥50 years in Catalonia, Spain, who were prospectively followed between 01/01/2015 and 31/12/2016. Primary outcomes were hospitalisation from pneumococcal or all-cause pneumonia and main explanatory variable was PCV13/PPsV23 vaccination status. Multivariable Cox regression models were used to estimate vaccination effectiveness adjusted for age and baseline-risk conditions.ResultsCohort members were followed for 3,897,151 person-years (17,496 PCV13 vaccinated and 1,551,502 PPsV23 vaccinated), observing 3259 pneumococcal pneumonias (63 in PCV13 vaccinated, 2243 in PPsV23 vaccinated) and 24,079 all-cause pneumonias (566 in PCV13 vaccinated, 17,508 in PPsV23 vaccinated). Global incidence rates (per 100,000 person-years) were 83.6 for pneumococcal pneumonia (360.1 in PCV13 vaccinated, 144.6 in PPsV23 vaccinated) and 617.9 for all-cause pneumonia (3235.0 in PCV13 vaccinated, 1128.5 in PPsV23 vaccinated). In the multivariable analyses, the PCV13 appeared significantly associated with an increased risk of pneumococcal pneumonia (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.17–1.97; p = 0.002) and all-cause pneumonia (HR: 1.76; 95% CI: 1.61–1.92; p < 0.001) whereas the PPsV23 did not alter the risk of pneumococcal pneumonia (HR: 1.08; 95% CI: 0.98–1.19; p = 0.132) and slightly increased the risk of all-cause pneumonia (HR: 1.17; 95% CI: 1.13–1.21; p < 0.001). In stratified analyses focused on specific target population subgroups (i.e., elderly people, at-risk and high-risk individuals), protective effects of vaccination did not emerge either.ConclusionData does not support clinical benefits from pneumococcal vaccination (nor PCV13 neither PPsV23) against pneumonia among Catalonian adults in the current era of universal PCV’s childhood immunisation.     

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.