Vaccine-type Invasive Pneumococcal Disease Research Articles

Potential impact of replacing the 13-valent pneumococcal conjugate vaccine with 15-valent or 20-valent pneumococcal conjugate vaccine in the 1 + 1 infant schedule in England: a modelling study

Paediatric pneumococcal conjugate vaccine (PCV) programmes in England using seven-valent PCV (PCV7) in 2006 and 13-valent PCV (PCV13) in 2010 have reduced vaccine-type invasive pneumococcal disease, but the overall effect has been reduced by an increase in invasive pneumococcal disease due to non-vaccine serotypes and serotype 3. We developed pneumococcal transmission models to investigate the potential effect on invasive pneumococcal disease of higher valency PCVs covering an additional two (ie, 15-valent PCV [PCV15]) or seven serotypes (ie, 20-valent PCV [PCV20]) in England. We conducted a modelling study using realistic, age-structured, and compartmental deterministic models fitted to carriage data from before the introduction of PCVs and invasive pneumococcal disease data from before and after the introduction of PCV7 and PCV13 in England from the UK Heath Security Agency invasive pneumococcal disease surveillance system. We estimated key parameters, including PCV7 and PCV13 efficacy against vaccine-type carriage and invasiveness of PCV7 serotypes; the additional serotypes in PCV13, PCV15 and PCV20; and non-vaccine serotypes. We simulated the effect of transitioning from PCV13 to PCV15 or PCV20 in infants under the current 1 + 1 vaccination schedule and investigated the effect of reduced carriage protection against PCV13 serotypes due to attenuation of immunogenicity in higher valency vaccines. Our results suggest that PCV15 might increase overall invasive pneumococcal disease as the reduction in vaccine-type invasive pneumococcal disease would be counterbalanced by an increase in non-PCV15 invasive pneumococcal disease. By contrast, PCV20 is projected to have a substantial impact on overall invasive pneumococcal disease due to higher invasiveness of the additional serotypes covered by PCV20 than the replacing non-vaccine serotypes. Reduced carriage protection against PCV13 serotypes with higher valency vaccines would amplify these effects. Replacing PCV13 with PCV20 is likely to have a substantial public health benefit, but PCV15 could potentially increase the overall burden of disease. UK Health Security Agency and National Institute of Health Research.

Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease among children in the United States between 2010 and 2019: An indirect cohort study

BackgroundA U.S. case-control study (2010–2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes. MethodsWe used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC’s Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010–2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %). ResultsAmong 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4–96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7–93.3 %), 50.2 % (28.4–80.5 %), and 93.8 % (69.8–98.8 %) against serotypes 19A, 3, and 19F, respectively. ConclusionsAt least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance.

1718. Effectiveness of 13-valent pneumococcal conjugate vaccine for prevention of invasive pneumococcal disease among children in the United States between 2010 and 2019: an indirect cohort study

Abstract Background The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced for infant use in the United States in 2010, replacing PCV7. A U.S. case-control study (2010–2014) demonstrated vaccine effectiveness (VE) for ≥1 dose of PCV13 at 86%; however, this study lacked statistical power to examine VE by number of doses and against individual serotypes. Methods We used the indirect cohort method to estimate VE of PCV13 against vaccine-type invasive pneumococcal disease among children &amp;lt; 5 years in the U.S. from May 1, 2010 to December 31, 2019. We included IPD cases identified through CDC’s Active Bacterial Core surveillance in 10 U.S. states; during 2010 – 2014, we additionally included cases enrolled in a post-licensure matched case-control study from expanded sites. Cases and controls were defined as individuals with PCV13-type-IPD (VT-IPD) and non-PCV13-type-IPD (NVT), respectively; serotype 6C was categorized as VT. We used logistic regression to estimate the adjusted odds of prior PCV13 receipt, controlling for confounders identified a priori including age category, race/ethnicity, sex, state, year, and any immunocompromising and/or chronic conditions. Results A total of 1,161 IPD cases were identified; 223 (19.2%) were VT cases and 938 (80.8%) were non-VT controls. Of those, 108 cases (48.4%; 108/223) and 600 controls (64.0%; 600/938) had received &amp;gt;3 PCV13 doses; 47 cases (21.1%) and 53 controls (5.7%) had received no PCV doses. Serotypes 19A (N=96), 3 (N=60), and 19F (N=45) caused 90.1% (201/223) of VT-IPD. VE of &amp;gt;1 or ≥3 PCV13 doses against VT-IPD was 81.7% (95% Confidence Interval: 69.1–89.1%) and 87.8% (75.2–94.0%), respectively. VE of ≥3 PCV13 doses was 87.0% (75.8–93.0%), 54.6% (-8.8–81.0%), and 92.9% (74.4–98.0%) against serotypes 19A, 3, and 19F, respectively. VE was 87.6% (67.9-95.2%) for three primary doses before 12 months of age and 92.4% (78.2–97.2%) for three primary doses and a booster at 12 months of age or older. Vaccine effectiveness estimates against PCV13-type IPD among US children under five years of age, 2010 - 2019 Conclusion VE of ≥1 PCV13 dose against IPD was consistent with the previous estimate from the case-control study, and ≥3 doses appear to provide substantial protection. Among the most commonly circulating VT-IPD, PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance. Disclosures Lee Harrison, MD, GSK: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi: Advisor/Consultant Tamara Pilishvili, PhD MPH, GSK: Employed by GSK since February 2023. At the time of data collection and analysis for this work was employed by the CDC

Letter to the Editor: Women Doctors' Preferences Toward Neurosurgery Residency in Latin America— A Peruvian Perspective

The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine immunization program in Uruguay in March 2008 with a 2-dose primary series (given at 2 and 4 months) plus a booster (at 12 months) and a catch-up campaign (two doses given at 15 and 17 months). We used a case–control methodology and existing laboratory surveillance and immunization registry data from Uruguay to evaluate PCV7 effectiveness against vaccine-type invasive pneumococcal disease (VT-IPD). Cases of VT-IPD (with pneumococcus obtained from a normally sterile site) were identified through the National Reference Laboratory. Age- and neighborhood-matched controls were obtained through a national immunization registry in which all children are enrolled at birth regardless of vaccine receipt; all eligible controls were included. Immunization status of cases and controls was assessed through the immunization registry, and conditional logistic regression was used to calculate PCV7 effectiveness. Between April 2008 and February 2010, 44 cases of VT-IPD among children < 5 years were identified; 43 (98%) of those children were located in the registry. Among located case patients, 7 (16.3%) were age-eligible to have received at least one dose of PCV7. A total of 637 matched controls were included. Vaccine effectiveness was 91.3% (95% CI: 46.4, 98.6) for ≥1 PCV7 doses and 94.8% (95% CI: 43.1, 99.5) for ≥2 PCV7 doses. Using existing data we demonstrated high effectiveness of PCV7 against VT-IPD in Uruguay–a middle-income country using a 2-dose primary series plus a booster dose and a limited catch-up campaign. These data also highlight the utility of surveillance and high-quality immunization registries for evaluating the effectiveness of vaccines.

Historical Population-Level Impact of Infant 13-Valent Pneumococcal Conjugate Vaccine (PCV13) National Immunization Programs on Invasive Pneumococcal Disease in Australia, Canada, England and Wales, Israel, and the United States

This study estimates the annual population-level impact of 13-valent pneumococcal conjugate vaccine (PCV13) infant national immunization programs (NIPs) on vaccine-type and non-vaccine type invasive pneumococcal disease (IPD) incidence across all ages using national surveillance data. We identified countries (Australia, Canada, England and Wales, Israel, and the US) with national IPD active surveillance data that introduced the seven-valent PCV (PCV7) followed by PCV13, which also reported annual serotype- and age group-specific incidence. We extracted IPD incidence by serotype groupings [PCV13 minus PCV7 (PCV13-7) serotypes; PCV13-7 serotypes excluding serotype 3; non-PCV13 serotypes; and the 20-valent (PCV20) minus PCV13 (PCV20-13) serotypes] and by age groups (< 2years, 2-4years, 5-17years, 18-34years, 35-49years, 50-64years, and ≥ 65years). For each country, we calculated the annual relative change in IPD incidence (percent change), and the corresponding incidence rate ratio (IRR), for 7 years post introduction compared to the year prior to PCV13 program initiation. PCV13-7 vaccine-type IPD incidence consistently decreased over time following introduction of PCV13 across countries, reaching an approximate steady state after 3-4years in ages < 5years, with roughly 60-90% decrease (IRRs = 0.1-0.4) and after 4-5years in ages ≥ 65years with approximately 60-80% decrease (IRRs = 0.2-0.4). Incidence declines were more substantial for the PCV13-7 grouping when excluding serotype 3. Non-PCV13 serotype incidence was variable by country and age group, ranging from virtually no serotype replacement compared to the PCV7 period across ages in the US to increases for other countries ranging from 10 to 204% (IRRs = 1.10-3.04) in children < 5years and 41% to 123% (IRRs = 1.41-2.23) in ages ≥ 65years. Countries with longstanding PCV13 infant NIPs have observed substantial direct and indirect benefits, which are demonstrated in this study by the reduction in PCV13-7 IPD incidence compared to PCV7 period in all age groups. Over time, non-PCV13 serotypes have emerged in response to the reduction of incidence of PCV13-unique serotypes. Higher-valent PCVs are needed to address this emerging pneumococcal disease burden as well as the direct vaccination of both pediatric and adult populations against the most prevalent circulating serotypes.

Effectiveness of 7-Valent Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease in Medically At-Risk Children in Australia: A Record Linkage Study.

BackgroundChildren with chronic medical conditions are at higher risk of invasive pneumococcal disease (IPD), but little is known about the effectiveness of the primary course of pneumococcal conjugate vaccine (PCV) in these children.MethodsA cohort born in 2001–2004 from two Australian states and identified as medically at-risk (MAR) of IPD either using ICD-coded hospitalizations (with conditions of interest identified by 6 months of age) or linked perinatal data (for prematurity) were followed to age 5 years for notified IPD by serotype. We categorized fully vaccinated children as either receiving PCV dose 3 by <12 months of age or ≥1 PCV dose at ≥12 months of age. Cox proportional hazard modeling was used to estimate hazard ratios (HRs), adjusted for confounders, and vaccine effectiveness (VE) was estimated as (1-HR) × 100.ResultsA total of 9220 children with MAR conditions had 53 episodes of IPD (43 vaccine-type); 4457 (48.3%) were unvaccinated and 4246 (46.1%) were fully vaccinated, with 1371 (32.3%) receiving dose 3 by 12 months and 2875 (67.7%) having ≥1 dose at ≥12 months. Estimated VE in fully vaccinated children was 85.9% (95% CI: 33.9–97.0) against vaccine-type IPD and 71.5% (95% CI: 26.6–88.9) against all-cause IPD.ConclusionThis is the first population-based study evaluating the effectiveness of PCV in children with MAR conditions using record linkage. Our study provides evidence that the VE for vaccine-type and all-cause IPD in MAR children in Australia is high and not statistically different from previously reported estimates for the general population. This method can be replicated in other countries to evaluate VE in MAR children.

1173. Changes in Invasive Pneumococcal Disease Incidence Following Introduction of PCV10 and PCV13 Among Children &amp;lt; 5 Years: The PSERENADE Project

BackgroundHigher valency pneumococcal conjugate vaccines (PCV10 and PCV13) replaced PCV7, and an updated global analysis of PCV impact on invasive pneumococcal disease (IPD) incidence is needed. We aimed to estimate the change in vaccine-type (VT), non-VT type and all-serotype (ST) IPD incidence following introduction of PCV10/13 among children < 5 years of age.MethodsIPD ST-specific incidence or cases and population denominators were obtained directly from surveillance sites. IPD incidence rate ratios (IRRs) for each site were estimated comparing the pre-any PCV incidence to each post-PCV10/13 year using Bayesian multi-level, mixed effects Poisson regressions. All-site weighted average IRRs were estimated using linear mixed-effects regressions. Results were stratified by product (PCV10 vs. PCV13) and years of prior PCV7 use (none, some [1-3 years or 4-5 years if < 70% PCV uptake], or many [≥ 4 years with ≥ 70% uptake]).ResultsAnalyses included 45 surveillance sites from 31 countries, primarily high-income (80%). Thirty surveillance sites had pre- and post-PCV data (PCV10: no prior PCV7=5 sites, some=2, many=2; PCV13: no prior PCV7=3, some=5, many=13). Five years after PCV10/13 introduction, the all-site IRRs in children < 5 years were generally similar across products and prior PCV7 use strata for all-serotype IPD (range 0.23-0.41), PCV7 STs (0.01-0.13), PCV10non7 STs (1, 5, and 7F; 0.05-0.20), and ST6A (0.01-0.18). IRRs for ST19A were lower for PCV13 sites (range by PCV7 use: 0.09-0.31) than for PCV10 sites (1.1-1.4). ST3 IRRs were dynamic, differing by product at year 5 (range for PCV13 sites=0.86-1.02; PCV10 sites=1.55-1.78), but converging by year 7. NonPCV13 STs increased across all strata (range 1.9-2.6), except one strata with a single African site that declined.Figure 1. All-Site Weighted Average Incidence Rate Ratios, Children <5> * Total sites indicates number of sites with incidence rate data included and pre/post sites indicates number of sites with both pre- and post-PCV data to estimate IRRs for each outcome. ** Year 0 indicates the year of PCV10/13 introduction and year -1 indicates the last year of PCV7 use prior to PCV10/13 introduction.ConclusionAll-serotype IPD in children < 5 years declined following both PCV10 and PCV13 use, driven by substantial declines in VT serotypes and offset by increases in nonPCV13 STs. ST19A decreased among PCV13-sites, mitigating replacement disease occurring after PCV7 use, but increased, on average, among PCV10-sites. Changes in ST3 were heterogeneous, increasing in some sites and no change from baseline in others. Data from low-income and high-burden settings were limited.Disclosures Julia C. Bennett, MSPH, Pfizer (Research Grant or Support) Maria Deloria Knoll, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)

Dynamics of Invasive Pneumococcal Disease in Israel in Children and Adults in the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Era: A Nationwide Prospective Surveillance.

Following 13-valent pneumococcal conjugate vaccine (PCV13) implementation in infants worldwide, overall and vaccine-type invasive pneumococcal disease (IPD) rates declined in children, with variable indirect impact on adults. A population-based, prospective, nationwide active surveillance of IPD in Israel, 2004-2019 (for adults ≥18 years, 2009-2019). The 7-valent PCV (PCV7)/PCV13 were implemented in Israel in July 2009/November 2010, respectively, with >90% uptake in children <2 years. The 23-valent pneumococcal polysaccharide vaccine (PPV-23) uptake among those >65 years was ~75%. For pre-PCV episodes with missing serotype, extrapolations were applied. Overall, PCV13 serotypes (VT13) and non-VT13 (NVT) incidence rate ratios (IRRs) comparing pre-PCV (2004-2008), early-PCV (2009-2011), and late-PCV13 (2016-2019) periods were calculated for different age groups. Overall, 8614 IPD cases were recorded. IPD rates declined by 67% in children <5 and 5-17 years, comparing late-PCV13 versus pre-PCV periods (IRR [95% CI]: .33 [.27-.40] and .33 [.21-.50], respectively). For adults, comparing late-PCV13 with early-PCV periods, rates significantly declined by 53% in those aged 18-44, while rates did not decline significantly in other age groups. VT13 rates significantly declined in all ages, with decline rates ranging between 94% in children <5 years and 60% in adults ≥85 years. NVT rates significantly increased in <5-, 50-64-, and ≥65-year age groups. In the late-PCV13 period, serotypes 3, 14, and 19A remained the predominant VT13, while serotypes 8 and 12F emerged as predominant NVTs. Continuous monitoring of circulating serotypes in all ages demonstrated direct and indirect PCV effects, which are essential for the development of new vaccination strategies.

Impact of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease and pneumonia in The Gambia: 10 years of population-based surveillance

SummaryBackgroundThe Gambia introduced seven-valent pneumococcal conjugate vaccine (PCV7) in August 2009, followed by PCV13 in May, 2011, using a schedule of three primary doses without a booster dose or catch-up immunisation. We aimed to assess the long-term impact of PCV on disease incidence.MethodsWe did 10 years of population-based surveillance for invasive pneumococcal disease (IPD) and WHO defined radiological pneumonia with consolidation in rural Gambia. The surveillance population included all Basse Health and Demographic Surveillance System residents aged 2 months or older. Nurses screened all outpatients and inpatients at all health facilities using standardised criteria for referral. Clinicians then applied criteria for patient investigation. We defined IPD as a compatible illness with isolation of Streptococcus pneumoniae from a normally sterile site (cerebrospinal fluid, blood, or pleural fluid). We compared disease incidence between baseline (May 12, 2008–May 11, 2010) and post-vaccine years (2016–2017), in children aged 2 months to 14 years, adjusting for changes in case ascertainment over time.FindingsWe identified 22 728 patients for investigation and detected 342 cases of IPD and 2623 cases of radiological pneumonia. Among children aged 2–59 months, IPD incidence declined from 184 cases per 100 000 person-years to 38 cases per 100 000 person-years, an 80% reduction (95% CI 69–87). Non-pneumococcal bacteraemia incidence did not change significantly over time (incidence rate ratio 0·88; 95% CI, 0·64–1·21). We detected zero cases of vaccine-type IPD in the 2–11 month age group in 2016–17. Incidence of radiological pneumonia decreased by 33% (95% CI 24–40), from 10·5 to 7·0 per 1000 person-years in the 2–59 month age group, while pneumonia hospitalisations declined by 27% (95% CI 22–31). In the 5–14 year age group, IPD incidence declined by 69% (95% CI −28 to 91) and radiological pneumonia by 27% (95% CI −5 to 49).InterpretationRoutine introduction of PCV13 substantially reduced the incidence of childhood IPD and pneumonia in rural Gambia, including elimination of vaccine-type IPD in infants. Other low-income countries can expect substantial impact from the introduction of PCV13 using a schedule of three primary doses.FundingGavi, The Vaccine Alliance; Bill & Melinda Gates Foundation; UK Medical Research Council; Pfizer Ltd.

The Impact of Pneumococcal Conjugate Vaccine (PCV) Coverage Heterogeneities on the Changing Epidemiology of Invasive Pneumococcal Disease in Switzerland, 2005-2019.

Pneumococcal conjugate vaccines (PCVs) have lowered the incidence of invasive pneumococcal disease (IPD) worldwide. However, the influence of regional vaccine uptake differences on the changing epidemiology of IPD remains unclear. We aimed to examine the overall impact of both seven- and 13-valent PCVs (PCV7 and PCV13) on IPD in Switzerland. Three-year periods from 2005–2010 and 2011–2019 were considered, respectively, as (early and late) PCV7 eras and (early, mid and late) PCV13 eras. Vaccine coverage was estimated from a nationwide survey according to east (German-speaking) and west (French/Italian-speaking) regions for each period. Reported incidence rate ratios (IRRs) were compared between successive periods and regions using nationwide IPD surveillance data. Overall IPD incidence across all ages was only 16% lower in the late PCV13 era compared to the early PCV7 era (IRR 0.83, 95% CI 0.79–0.88), due to increasing incidence of non-PCV-type IPD (2.59, 2.37–2.83) in all age groups, except children <5 years. PCV uptake rates in swiss children were slightly higher in the west than the east (p < 0.001), and were accompanied by lower IPD incidences across all age groups in the former region. Post-PCV13, non-PCV serotypes 8, 22F and 9N were the major cause of IPD in adults ≥65 years. Increased PCV coverage in both areas of Switzerland resulted in a decrease in vaccine-type and overall IPD incidence across all age groups, in a regionally dependent manner. However, the rising incidence of non-vaccine-type IPD, exclusive to older adults, may undermine indirect beneficial effects.

1404. Twenty-year impact of Pneumococcal Conjugate Vaccines (PCV) on the burden of invasive pneumococcal disease in US children less than 5 years of age

BackgroundClinical trials of PCV7 demonstrate significant reductions in vaccine-type (VT) invasive pneumococcal disease (IPD), clinically diagnosed pneumonia in children less than 5 years of age and VT acute otitis media in children < 2 years of age. Observational, population-based studies demonstrate a reduction in overall IPD in US children following the introduction of PCV7 and PCV13. The cumulative impact of PCV on IPD syndromes over the 20 years following introduction into the US national immunization program has not been detailed.MethodsPublished and unpublished data from the Active Bacterial Core (ABC) surveillance network were used to calculate annual incidence rates of IPD and the proportional distribution by syndrome in children < 5 years of age. Cases averted were calculated from published incidence for each IPD syndrome and population data, for the pre-PCV, PCV7, and PCV13 eras. Cases averted over 2000-2009 were assumed due to PCV7 only, and those averted from 2010-2019 were assumed due to PCV13 only. It was assumed that in the absence of PCVs, disease incidence would have remained constant.ResultsAnnual cases of overall IPD, pneumococcal meningitis, and bacteremic pneumonia each declined more than 85% between the pre PCV7 incidence and the estimated incidence for 2019 (table 1). Overall, we estimated 282,600 cases of IPD, including 30,500 cases of meningitis and 78,400 cases of bacteremic pneumonia were averted. We calculated a reduction of ~ 287,600 VT cases of IPD minimally offset by an increase of ~5,000 non-VT cases. Deaths per 100,000 children < 5 years of age attributable to IPD declined by 67% in 2009 and by 64% in 2019 compared to 1997-1999. In total, 1,628 deaths in children < 5 years were averted between 2000 and 2019.Table 1. Annual Cases of IPD by syndrome in US Children Less than 5 years of age ConclusionThe substantial public health impact of PCVs over the last two decades, as measured in cases and deaths averted in children less than 5 years, re-enforces the important role vaccines play in reducing the burden of serious disease in children.DisclosuresRotem Lapidot, MD, MSCI, Pfizer (Consultant) Ruth Chapman, MSc, PhD, Evidera, Inc, (Evidera, Inc. received the funding to conduct this study.) (Consultant) Kelly Sutton, PhD, Evidera (Employee) Desmond Dillon-Murphy, MSc, PhD, Evidera, Inc. (Evidera, Inc. received the funding to conduct this study.) (Consultant) Shreeya Patel, PhD, Evidera, Inc, (Evidera, Inc. received the funding to conduct this study.) (Consultant) Erica Chilson, PharmD, Pfizer (Employee, Shareholder) Vincenza Snow, MD, Pfizer (Employee) Raymond Farkouh, PhD, Pfizer (Employee) Matthew Wasserman, MSc., Pfizer Inc. (Employee) Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant)

Incidence of invasive pneumococcal disease after introduction of the 13-valent conjugate pneumococcal vaccine in British Columbia: A retrospective cohort study.

A significant reduction in invasive pneumococcal disease (IPD) has been reported, across all ages, following the implementation of 7-valent conjugate pneumococcal vaccine (PCV7) globally, as part of infant immunization programs. We explored the additional impact of PCV13 on IPD over a 14-year period. Using provincial laboratory surveillance and hospitalization data (N = 5791), we calculated the annual incidence of IPD following the implementation of PCV13 vaccine. Poisson regression was used to evaluate changes in the overall incidence of IPD, and serotype-specific IPD between PCV7 (2004-10) and PCV13 (2011-2015) eras. Overall, IPD rates have seen a modest decline in the PCV13 compared to the PCV7 era (IRR 0.84; 95% CI: 0.79-0.89); this was seen in children ≤2 years of age, and the majority of the adult cohort. Rates of vaccine-type IPD (PCV7 and PCV13) also decreased in the PCV13 era. In contrast, IPD incidence related to non-PCV13 (IRR: 1.56; 95%CI:1.43-1.72) and non-vaccine serotypes (IRR: 2.12; 95%CI:1.84-2.45) increased in the PCV13 era compared to the PCV7 era. A modest reduction in IPD from the PCV13 vaccine was observed, with gains limited to the immunized cohort and adults. However, a significant increase in non-vaccine serotypes emphasizes the need for continued surveillance.

Pneumococcal vaccine and serotype replacement in England: the bias of increased reporting

Abstract Background Increased incidence of invasive pneumococcal disease (IPD) attributable to non-vaccine serotypes (NVT) has been reported in several countries following introduction of PCV7 and PCV13 vaccines, concurrently with a reduction in vaccine-type IPD. Such serotype replacement has, importantly, emerged in England, offsetting the benefit of PCV introduction. We scrutinise most recent findings to assess if the estimated increase in NVT disease might result from surveillance artefacts. Methods Using IPD surveillance for 2000-2018, we estimate the impact of PCV7 and PCV13 introduction on age-serotype-specific incidence rates through a synthetic control regression model, building counterfactuals by combining age-specific incidences reported for pathogens unaffected by PCVs. Results Following the introduction of PCV7 and PCV13 (pre-2006 vs post-2011), total IPD incidence declined by 57% and by 76% in children younger than 5. PCV7-IPD decreased by 93% in all age groups, whereas PCV13-IPD declined by 68% since PCV13 was introduced. Importantly, NVT-IPD increased by 43% after PCV7, with non-significant statistical increases in most age groups. Conclusions Through appropriate statistical modelling, we disentangled the impact of vaccine and improved surveillance on the changes in IPD incidence rates. By controlling for the confounding effects of improved surveillance, we are able to estimate a lower serotype replacement. Key messages Pneumococcal vaccine has been beneficial despite serotype replacement. Adequate statistical methods are needed to disentangle the two phenomena.

Efficacy and Effectiveness of the PCV-10 and PCV-13 Vaccines Against Invasive Pneumococcal Disease.

Pneumococcal conjugate vaccines (PCVs) (pneumococcal 13-valent conjugate vaccine [PCV-13] and pneumococcal 10-valent conjugate vaccine [PCV-10]) are available for prevention of pneumococcal infections in children. To determine the vaccine effectiveness (VE) of PCV-13 and PCV-10 in preventing invasive pneumococcal disease (IPD) and acute otitis media (AOM) in children <5 years. Systematic searches of Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and Cochrane. Eligible studies examined the direct effectiveness and/or efficacy of PCV-10 and PCV-13 in reducing the incidence of disease in healthy children <5 years. Two reviewers independently conducted data extraction and methodologic quality assessment. Significant effectiveness against vaccine-type IPD in children ≤5 years was reported for ≥1 dose of PCV-13 in the 3 + 1 (86%-96%) and 2 + 1 schedule (67.2%-86%) and for PCV-10 for the 3 + 1 (72.8%-100%) and 2 + 1 schedules (92%-97%). In children <12 months of age, PCV-13 VE against serotype 19A post-primary series was significant for the 3 + 1 but not the 2 + 1 schedule. PCV-10 crossprotection against 19A was significant in children ≤5 years with ≥1 dose (82.2% and 71%). Neither PCVs were found effective against serotype 3. PCV-13 was effective against AOM (86%; 95% confidence interval [CI]: 61 to 94). PCV-10 was effective against clinically defined (26.9%; 95% CI: 5.9 to 43.3) and bacteriologically confirmed AOM (43.3%; 95% CI: 1.7 to 67.3). Because of the large heterogeneity in studies, a meta-analysis for pooled estimates was not done. Both PCVs afford protection against pneumococcal infections, with PCV-10 protecting against 19A IPD, but this VE has not been verified in the youngest age groups.

Age-stratified burden of pneumococcal community acquired pneumonia in hospitalised Canadian adults from 2010 to 2015

BackgroundIn Canada, 13-valent pneumococcal conjugate vaccine (PCV13) is recommended in childhood, in individuals at high risk of invasive pneumococcal disease (IPD) and in healthy adults aged ≥65 years for protection...

Pneumococcal Conjugate Vaccine Breakthrough Infections: 2001-2016.

Mostcountries use 3-dose pneumococcal conjugate vaccine (PCV) schedules; a 4-dose (3 primary and 1 booster) schedule is licensed for US infants. We evaluated the invasive pneumococcal disease (IPD) breakthrough infection incidence in children receiving 2 vs 3 primary PCV doses with and without booster doses (2 + 1 vs 3 + 1; 2 + 0 vs 3 + 0). We used 2001-2016 Active Bacterial Core surveillance data to identify breakthrough infections (vaccine-type IPD in children receiving≥1 7-valent pneumococcal conjugate vaccine [PCV7] or 13-valent pneumococcal conjugate vaccine [PCV13] dose) among children aged <5 years. We estimated schedule-specific IPD incidence rates (IRs) per 100 000 person-years and compared incidence by schedule (2 + 1 vs 3 + 1; 2 + 0 vs 3 + 0) using rate differences (RDs) and incidence rate ratios. We identified 71 PCV7 and 49 PCV13 breakthrough infections among children receiving a schedule of interest. PCV13 breakthrough infection rates were higher in children aged <1 year receiving the 2 + 0 (IR: 7.8) vs 3 + 0 (IR: 0.6) schedule (incidence rate ratio: 12.9; 95% confidence interval: 4.1-40.4); PCV7 results were similar. Differences in PCV13 breakthrough infection rates by schedule in children aged <1 year were larger in 2010-2011 (2 + 0 IR: 18.6; 3 + 0 IR: 1.4; RD: 16.6) vs 2012-2016 (2 + 0 IR: 3.6; 3 + 0 IR: 0.2; RD: 3.4). No differences between schedules were detected in children aged≥1 year for PCV13 breakthrough infections. Fewer PCV breakthrough infections occurred in the first year of life with 3 primary doses. Differences in breakthrough infection rates by schedule decreased as vaccine serotypes decreased in circulation.

2711. Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease in Older Adults

BackgroundRoutine use of 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for infants since early 2010 and for adults ≥65 years since 2014 when KPNC began routine use of PCV13 in adults. PCV13 vaccine effectiveness (VE) against vaccine-type invasive pneumococcal disease (IPD) has been demonstrated; however, recent surveillance data have been interpreted as showing limited population-level impact of PCV13 on serotype 3 IPD. We estimated PCV13 VE against IPD due to vaccine serotypes at Kaiser Permanente Northern California (KPNC).MethodsThe study period spanned September 2014 through September 2018. The cohort included KPNC members who were aged ≥65 years with no record of pneumococcal polysaccharide vaccine (PPV23) receipt before age 65 years. We compared IPD cases with KPNC members who were the same age on the date of the positive pneumococcal culture using conditional logistic regression, conditioned on age and date, and controlled for sex, race, KPNC service area and membership history, prior season influenza vaccine receipt, PPV23 receipt after age 65 years, risk factors for IPD, and healthcare utilization.ResultsFrom September 2014 to September 2018, PCV13 vaccine coverage among persons ≥65 years old increased from < 1% to 77%. During the same period, there was a total of 245 IPD cases. For a variety of reasons, we did not have serotype results for 57 (23%) IPD cases, which were excluded from the analysis. There were 61 (25%) PCV13-type IPD cases included in the analysis, of which 33 (14%) were serotype 3. PCV13 VE against PCV13-type serotypes was 68.0% (95% CI: 37.7%, 83.6%; P-value < 0.01), and 53.4% (95% CI: −10.0%, 80.3%; P = 0.08) against serotype 3.ConclusionDuring the first 4 years of PCV13 vaccination implementation in adults ≥65 years of age at KPNC, PCV13 provided significant protection against PCV13-type IPD. Further surveillance will allow for more precise estimation of PCV13 VE on overall and serotype 3 IPD over time.Disclosures All authors: No reported disclosures.

2715. Pneumococcal Community-Acquired Pneumonia Attributed to PCV13 Serotypes in Hospitalized Adults: Comparison of the 50–64 and 65+ Age Groups

BackgroundIn healthy adults aged ≥65 years, direct immunization with the 13-valent pneumococcal conjugate vaccine (PCV13) was shown effective at preventing vaccine-type pneumococcal community-acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD). Although PCV13 was licensed for use in Canadian adults aged >50 years, it was recommended for immunocompromised individuals who are at highest risk of IPD. In 2016, a recommendation was issued for use of PCV13 in immunocompetent adults aged ≥65 years, for the prevention of pCAP and IPD. This study aimed to compare pCAP cases attributed to PCV13 serotypes in adults aged 50–64 and ≥65 years.MethodsActive surveillance for CAP and IPD was performed from 2010 to 2015 in adult hospitals across five Canadian provinces. To identify pCAP, blood culture, sputum culture, or a PCV13 serotype-specific urine antigen detection (ssUAD) were used. Serotype was assigned using Quellung reaction, PCR, or ssUAD. All pCAP cases were categorized by serotype and age groups. Patient demographics and outcome data were collected.ResultsOver years 2010–2015, 6687 CAP cases were tested. 835 pCAP cases were identified, of which 418 (50%) caused by a PCV13 serotype. The majority (74%) of PCV13-associated pCAP occurred in the adults aged ≥50 years, whereas only 41.4% (173/418) were in adults ≥65 years. PCV13 pCAP cases declined over the years, likely through herd immunity from childhood immunization. The yearly proportion of pCAP attributed to PCV13 serotypes for ages ≥50 remained high (67.5 to 80.6%), compared those occurring in the ≥65 age groups (35.1 to 49.4%). Compared with test-negative controls, pCAP cases in both age groups were more likely to be admitted to ICU, require mechanical ventilation, and had higher mortality. Of pCAP deaths, 61.4% and 82.3% were in the ≥65 and ≥50 age cohorts, respectively.ConclusionFrom year 2010 to 2015, adults hospitalized with PCV13 pCAP in the ≥65 age cohort accounted for less than half of the cases, whereas including the 50–64 age cohort increased the proportion to 74%. Similarly, the proportion of PCV13 pCAP deaths that occurred in adults aged ≥50 years was 82%, compared with 61% in the ≥65 age cohort. Expansion of PCV13 recommendations to include adults 50–64 years of age should be considered.Disclosures All authors: No reported disclosures.

Protective effect of PCV vaccine against experimental pneumococcal challenge in adults is primarily mediated by controlling colonisation density

Widespread use of Pneumococcal Conjugate Vaccines (PCV) has reduced vaccine-type nasopharyngeal colonisation and invasive pneumococcal disease. In a double-blind, randomised controlled trial using the Experimental Human Pneumococcal Challenge (EHPC) model, PCV-13 (Prevenar-13) conferred 78% protection against colonisation acquisition and reduced bacterial intensity (AUC) as measured by classical culture. We used a multiplex qPCR assay targeting lytA and pneumococcal serotype 6A/B cpsA genes to re-assess the colonisation status of the same volunteers. Increase in detection of low-density colonisation resulted in reduced PCV efficacy against colonisation acquisition (29%), compared to classical culture (83%). For experimentally colonised volunteers, PCV had a pronounced effect on decreasing colonisation density. These results obtained in adults suggest that the success of PCV vaccination could primarily be mediated by the control of colonisation density. Studies assessing the impact of pneumococcal vaccines should allow for density measurements in their design.

Regional variations in serotype distribution and vaccination status in children under six years of age with invasive pneumococcal disease in Germany.

OverviewThe protective effect of infant pneumococcal conjugate vaccine (PCV) recommendation can be seen in Germany as a whole and in smaller regional groups. Comparisons between population-normalized geographic regions of Germany show different serotype distributions after program implementation, particularly in non-vaccine serotypes. The prior distinct differences in serotype distribution in children between the former East and former West German federal states have vanished. Children under six remain a vulnerable group, but the occurrence of vaccine-type (VT) invasive pneumococcal disease (IPD) in children correctly vaccinated (using a three-dose primary series plus one booster dose) with PCV13 was low (9 out of 374 cases, 2.4%). However, only 18.4% of children in Germany with IPD were correctly vaccinated with PCV13 according to the recommended schedule. Continued surveillance and better schedule adherence are essential to definitively establish the most effective PCV administration schedule.Vaccination effectsFor all PCV products used in Germany (PCV7, PCV10, and PCV13), vaccination status was the most common statistically significant predictor of infection with a particular serotype: Unvaccinated children old enough to have received at least one dose of vaccine in the PCV7 group had significantly higher odds (OR: 6.84, 95%CI: 2.66–22.06, adjusted for per capita income and residence in the northeastern federal states) of contracting VT IPD. In the PCV10 group, VT IPD had an OR of 4.52 (95% CI: 1.60–15.62, adjusted for year of infection, median household size, and residence in the southern federal states) in unvaccinated children, and in the PCV13 group, unvaccinated children continued to have higher odds (OR: 6.21, 95%CI: 3.45–11.36, adjusted for year of infection, age of child, per capita income, residence in the southern federal states, and percentage of children using public daycare) of getting vaccine-type IPD. Being unvaccinated was the most frequent significant indicator for infection with vaccine-type serotypes for each analysis group, while geographic groupings showed more limited potential to predict serotype of infection in early childhood IPD in Germany.