PCV13-type Invasive Pneumococcal Disease Research Articles

Characteristics of Invasive Pneumococcal Diseases Cases Among U.S. Children With Hematologic Malignancies Before and After Introduction of Thirteen-valent Pneumococcal Conjugate Vaccine, 2005-2019.

Children with hematologic malignancies (HMs) are at increased risk of invasive pneumococcal disease (IPD). Data on long-term IPD trends in U.S. children with HM after 13-valent pneumococcal conjugate vaccine (PCV13) introduction are limited. We assessed IPD trends in children with HM before and after PCV13 introduction and the proportion of IPD cases caused by serotypes contained in new pneumococcal conjugate vaccines (PCV15 and PCV20, introduced after 2019). During 2005-2019, IPD cases among children aged <18 years were identified through the Active Bacterial Core surveillance. We characterized IPD cases by underlying conditions (HM, other IPD risk factors, no IPD risk factors) and time periods [pre-PCV13 (2005-2009), early-PCV13 (2010-2014) and late-PCV13 (2015-2019)]. We estimated incidence rate ratios (IRRs) in children aged <5 years with and without HM and during 2010-2019. We identified 5912 cases of IPD in children aged <18 years; 215 (3.6%) were among children with HM. The proportion of IPD cases with PCV13 serotypes decreased over time in all risk groups; however, IRRs among children with vs. without HM were 215.8 [95% confidence interval (CI): 146.1-292.4] and 240.9 (95 CI: 152.3-341.1) in early and late-PCV13 periods, respectively. In late-PCV13 period, PCV15/non-PCV13 serotypes and PCV20/non-PCV15 serotypes caused 19.4% and 4.8% of IPD cases among children with HM. The proportion of PCV13-type IPD decreased in all children after PCV13 introduction. However, children with HM remain at an increased risk of IPD. Continued monitoring of the impact of PCV15 and PCV20 use among children with HM is needed.

Characteristics of children with invasive pneumococcal disease eligible for the 1+1 compared with the 2+1 PCV13 infant immunisation schedule in England: a prospective national observational surveillance study

On Jan 1, 2020, the UK transitioned from a 2+1 to a 1+1 national infant immunisation schedule with the 13-valent pneumococcal conjugate vaccine (PCV13). We assessed whether the 1+1 PCV13 schedule had any impact on incidence, disease characteristics, or outcomes after invasive pneumococcal disease (IPD) in eligible children aged 0-3 years. The UK Health Security Agency conducts IPD surveillance and serotyping of invasive pneumococcal isolates via whole-genome sequencing in England. IPD was defined as identification of Streptococcus pneumoniae in a sterile site. We compared IPD incidence, demographics, clinical presentation, comorbidity prevalence, serotype distribution, and case-fatality rates (CFRs) in children from a single birth cohort eligible for the 1+1 schedule (born between Jan 1, 2020, and Dec 31, 2022) who developed IPD in the 2022-23 financial year (April to March) with children from three equivalent historical birth cohorts (born between Jan 1, 2015, and Dec 31, 2019) eligible for the 2+1 schedule who developed IPD during three respective pre-pandemic financial years: 2017-18, 2018-19, and 2019-20. There were a total of 702 IPD episodes in 697 children, including 158 (incidence 8·99 per 100 000 person-years) in the single 1+1 birth cohort and 544 (incidence 9·39 per 100 000 person-years) in the 2+1 birth cohorts, with no significant difference in the incidence of overall IPD (incidence rate ratio 0·96, 95% CI 0·80-1·14, p=0·63), PCV13-type IPD (1·21, 0·71-2·00, p=0·45), or pneumococcal meningitis (0·97, 0·66-1·40, p=0·88). Comorbidity prevalence, clinical presentation, and CFRs were also similar between the two cohorts, as was the percentage of cases in infants too young to be vaccinated (<2 months old) and infants aged 5-11 months who received one or two PCV13 priming doses, in the 1+1 and 2+1 cohorts respectively. After 3 years, the 1+1 schedule continues to provide direct and indirect protection against PCV13-type IPD in children, with no significant change in overall IPD incidence, serotype distribution, clinical presentation, or CFRs in children eligible for the 1+1 compared with the 2+1 schedule. Ongoing surveillance will be important to assess longer-term direct and indirect population protection. None.

Invasive pneumococcal disease 3 years after introduction of a reduced 1 + 1 infant 13-valent pneumococcal conjugate vaccine immunisation schedule in England: a prospective national observational surveillance study

The UK transition from a 2 + 1 to a 1 + 1 infant immunisation schedule with the 13-valent pneumococcal conjugate vaccine (PCV13) on Jan 1, 2020, coincided with the start of the COVID-19 pandemic. We describe the epidemiology of invasive pneumococcal disease (IPD) in England over 6 financial years (April 1 to March 31) between 2017-18 and 2022-23. We used prospective national surveillance data, including serotyping and whole-genome sequencing of invasive isolates, to analyse IPD trends in England by age and financial year. We compared breakthrough infections and vaccine failure rates in 2022-23 among children eligible for the 1 + 1 schedule with rates in cohorts of children eligible for the 2 + 1 schedule between 2017-18 and 2019-20. We assessed genomic changes over time by comparing Global Pneumococcal Sequencing Clusters and multilocus sequence types among PCV13 serotypes causing IPD. There were 4598 laboratory-confirmed IPD cases in 2022-23, 3025 in 2021-22, 1240 in 2020-21, and 5316 in 2019-20. IPD incidence in 2022-23 was 14% lower than in 2019-20 (incidence rate ratio [IRR] 0·86, 95% CI 0·81-0·91; p<0·001). IPD incidence in 2022-23 compared with 2019-20 was 34% higher in children (aged <15 years) (378 cases vs 292 cases; IRR 1·34, 95% CI 1·08-1·68; p=0·009) and 17% lower in adults (aged 15 years and older; 4220 vs 5024; 0·83, 0·78-0·88; p<0·001). The proportion of PCV13-type IPD increased from 19·4% (95% CI 18·2-20·4; 957 of 4947) in 2019-20 to 29·7% (28·3-31·0; 1283 of 4326) in 2022-23, mainly due to serotype 3, but also serotypes 19F, 19A, and 4, alongside a decrease in non-PCV13 serotypes 8, 12F, and 9N. The increase in IPD incidence due to serotypes 3, 19A, and 19F was driven by clonal expansion of previously circulating strains, whereas serotype 4 expansion was driven by newer strains (ie, sequence types 801 and 15603). Breakthrough infections and vaccine failure rates were similar in children eligible for the 1 + 1 (1·08 per 100 000 person-years) and 2 + 1 (0·76 per 100 000 person-years; IRR 1·42, 95% CI 0·78-2·49; p=0·20) PCV13 schedules. Overall, IPD incidence in England was lower in 2022-23, 2 years after removal of pandemic restrictions, than in 2019-20. Breakthrough and vaccine failure rates were not significantly different between children who received the 1 + 1 compared with the 2 + 1 PCV13 immunisation schedule. The post-pandemic increase in childhood IPD incidence and especially PCV13-type IPD will require close monitoring. None.

Systematic Review and Meta-Analysis of the Efficacy and Effectiveness of Pneumococcal Vaccines in Adults.

New pneumococcal conjugate vaccines (PCVs), 15- and 20-valent (PCV15 and PCV20), have been licensed for use among U.S. adults based on safety and immunogenicity data compared with the previously recommended 13-valent PCV (PCV13) and 23-valent pneumococcal polysaccharide vaccines (PPSV23). We conducted a systematic review of the literature on PCV13 and PPSV23 efficacy (randomized controlled trials [RCTs]) or effectiveness (observational studies) against vaccine type (PCV13 type or PPSV23 type, respectively), invasive pneumococcal disease (IPD), and pneumococcal pneumonia (PP) in adults. We utilized the search strategy from a previous systematic review of the literature published during the period from January 2016 to April 2019, and updated the search through March 2022. The certainty of evidence was assessed using the Cochrane risk-of-bias 2.0 tool and the Newcastle-Ottawa scale. When feasible, meta-analyses were conducted. Of the 5085 titles identified, 19 studies were included. One RCT reported PCV13 efficacy of 75% (PCV13-type IPD) and 45% (PCV13-type PP). Three studies each reported PCV13 effectiveness against PCV13-type IPD (range 47% to 68%) and against PCV13-type PP (range 38% to 68%). The pooled PPSV23 effectiveness was 45% (95% CI: 37%, 51%) against PPSV23-type IPD (nine studies) and 18% (95% CI: -4%, 35%) against PPSV23-type PP (five studies). Despite the heterogeneity across studies, our findings suggest that PCV13 and PPSV23 protect against VT-IPD and VT-PP in adults.

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease Among Adults With HIV-United States, 2008-2018.

People with HIV (PWH) are at increased risk for invasive pneumococcal disease (IPD). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for use in US children in 2010 and for PWH aged 19 years or older in 2012. We evaluated the population-level impact of PCV13 on IPD among PWH and non-PWH aged 19 years or older. We identified IPD cases from 2008 to 2018 through the Active Bacterial Core surveillance platform. We estimated IPD incidence using the National HIV Surveillance System and US Census Bureau data. We measured percent changes in IPD incidence from 2008 to 2009 to 2017-2018 by HIV status, age group, and vaccine serotype group, including serotypes in recently licensed 15-valent (PCV15) and 20-valent (PCV20) PCVs. In 2008-2009 and 2017-2018, 8.4% (552/6548) and 8.0% (416/5169) of adult IPD cases were among PWH, respectively. Compared with non-PWH, a larger proportion of IPD cases among PWH were in adults aged 19-64 years (94.7%-97.4% vs. 56.0%-60.1%) and non-Hispanic Black people (62.5%-73.0% vs. 16.7%-19.2%). Overall and PCV13-type IPD incidence in PWH declined by 40.3% (95% confidence interval: -47.7 to -32.3) and 72.5% (95% confidence interval: -78.8 to -65.6), respectively. In 2017-2018, IPD incidence was 16.8 (overall) and 12.6 (PCV13 type) times higher in PWH compared with non-PWH; PCV13, PCV15/non-PCV13, and PCV20/non-PCV15 serotypes comprised 21.5%, 11.2%, and 16.5% of IPD in PWH, respectively. Despite reductions post-PCV13 introduction, IPD incidence among PWH remained substantially higher than among non-PWH. Higher-valent PCVs provide opportunities to reduce remaining IPD burden in PWH.

1299. Epidemiology of Invasive Pneumococcal Disease (IPD) in the United States 2011-2019

Abstract Background Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for U.S. children aged &amp;lt; 5 years in February 2010 and recommended in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults aged ≥ 65 years in 2014. PCV13 has led to dramatic reductions in invasive pneumococcal disease (IPD) burden. New, higher valency PCVs (PCV15, PCV20) are expected to be licensed for adults in late 2021. We examined remaining PCV13-type IPD among children and adults and assessed IPD burden potentially preventable through PCV15 and PCV20 use. Methods IPD cases (isolation of pneumococcus from sterile sites) were identified through CDC’s Active Bacterial Core surveillance during 1998–2019. Isolates were serotyped by Quellung or whole genome sequencing. Incidence rates (cases/100,000) were calculated using U.S. Census Bureau population denominators. Results After introduction of PCV13 in children, by 2013–2014, PCV13-type IPD declined 89% (from 15 to 2 cases/100,000) in children age &amp;lt; 5 years and 67% (from 19 to 7 cases/100,000) in adults age ≥ 65 years. During 2014–2019, rates of PCV13-type IPD in children and adults remained stable. In 2018–2019, among children age &amp;lt; 5 years, serotypes 3, 19F, 19A, and 6C accounted for most of the remaining PCV13-type IPD (46%, 32%, 14% and 4% respectively) (Figure 1). Among adults age ≥ 65 years, serotypes 3, 6C, 19A, and 19F accounted for most of the remaining PCV13-type IPD (62%, 12%, 10%, and 9% respectively) (Figure 1). During 2015–2019, rates of PCV15 and PCV20-type IPD have remained stable. In 2018–2019, among adults age ≥ 65 years, PCV15 non-PCV13-type IPD rates were 3.6 cases per 100,000 and accounted for 15% of all IPD. PCV20 non-PCV13-type IPD rates were 6.8 cases per 100,000 and accounted for 29% of all IPD (Figure 2). Among children age &amp;lt; 5 years, PCV15 non-PCV13-type IPD rates were 1.6 cases per 100,000 and accounted for 17% of all IPD. PCV20 non-PCV13-type IPD rates were 2.8 cases per 100,000 and accounted for 39% of all IPD (Figure 2). Figure 1. Incidence rates of IPD among children &amp;lt; 5 years old, by pneumococcal conjugate vaccine type and individual PCV13 serotypes, 2011–2019 Figure 2. Incidence rates of IPD among adults ≥ 65 years old, by pneumococcal conjugate vaccine type and individual PCV13 serotypes, 2011–2019 Conclusion Following the dramatic reductions after PCV13 introduction, PCV13-type IPD has remained stable during the past five years. There are opportunities to prevent an additional 30% IPD burden among adults through new PCV use. Disclosures William Schaffner, MD, VBI Vaccines (Consultant) Lee Harrison, MD, GSK, Merck, Pfizer, Sanofi Pasteur (Consultant)

70. Changes in Invasive Pneumococcal Disease among Adults Living with HIV Following Introduction of 13-Valent Pneumococcal Conjugate Vaccine, 2008–2018

BackgroundPeople living with HIV (PLHIV) are at increased risk of invasive pneumococcal disease (IPD). The 13-valent pneumococcal conjugate vaccine (PCV13) was recommended for children in 2010, and for immunocompromised adults (including PLHIV) in series with 23-valent polysaccharide vaccine (PPSV23) in 2012. We evaluated changes in IPD incidence in adults ≥19 years old by HIV status after PCV13 introduction and proportion of remaining IPD due to serotypes included in the 15- (PCV15) and 20-valent (PCV20) conjugate vaccines expected to be licensed in 2021. MethodsIPD cases were identified through CDC’s Active Bacterial Core surveillance (ABCs). HIV status was obtained from medical records. Isolates were serotyped by Quellung reaction, or whole-genome sequencing and grouped into PCV13-types, PPV11-types (unique to PPSV23), or non-vaccine types. We estimated IPD incidence (cases per 100,000 people) using national projections of ABCs cases as numerators and national case-based HIV surveillance (PLHIV) or US census data (non-PLHIV) as denominators. We compared IPD incidence in 2011–12 and 2017–18 to pre-PCV13 baseline (2008–09) by serotype groups. We assessed the proportion of IPD due to serotypes included in PCV15 and PCV20. ResultsOverall IPD incidence at baseline was 306.7 for PLHIV and 15.2 for non-PLHIV. From baseline to 2017–18, IPD incidence declined in PLHIV (-40.3%; 95% CI: -47.7, -32.3%) and non-PLHIV (-28.2%; 95% CI: -30.9, -25.5%). The largest reductions were in PCV13-type IPD during both periods (-44.2% for PLHIV and -42.2% for non-PLHIV in 2011–12; -72.5% for PLHIV and -62.2% for non-PLHIV in 2017–18) compared to baseline (Figures 1, 2). In 2017–2018, overall IPD and PCV13-type rates were 16.8 (95% CI: 15.1, 18.5) and 12.6 (95% CI: 9.9, 15.3) times as high in PLHIV vs non-PLHIV, respectively; PCV13, PCV15/non-PCV13, and PCV20/non-PCV15 serotypes comprised 21.5%, 11.2% and 16.5% of IPD in PLHIV.IPD incidence rates among adults aged ≥19 years old by serotype group in PLHIV, 2008–2018 IPD incidence rates among adults aged ≥19 years old by serotype group in non-PLHIV, 2008–2018 ConclusionIPD rates declined significantly in both PLHIV and non-PLHIV during the study period due to reductions in PCV13-type IPD; however, IPD rates remained 17-fold higher in PLHIV compared to non-PLHIV, mainly due to non-PCV13 types. Higher-valent pneumococcal conjugate vaccines provide opportunities to reduce some of the remaining IPD burden in PLHIV.Disclosures William Schaffner, MD, VBI Vaccines (Consultant) Lee Harrison, MD, GSK, Merck, Pfizer, Sanofi Pasteur (Consultant)

Levels of pneumococcal conjugate vaccine coverage and indirect protection against invasive pneumococcal disease and pneumonia hospitalisations in Australia: An observational study.

There is limited empiric evidence on the coverage of pneumococcal conjugate vaccines (PCVs) required to generate substantial indirect protection. We investigate the association between population PCV coverage and indirect protection against invasive pneumococcal disease (IPD) and pneumonia hospitalisations among undervaccinated Australian children. Birth and vaccination records, IPD notifications, and hospitalisations were individually linked for children aged <5 years, born between 2001 and 2012 in 2 Australian states (New South Wales and Western Australia; 1.37 million children). Using Poisson regression models, we examined the association between PCV coverage, in small geographical units, and the incidence of (1) 7-valent PCV (PCV7)-type IPD; (2) all-cause pneumonia; and (3) pneumococcal and lobar pneumonia hospitalisation in undervaccinated children. Undervaccinated children received <2 doses of PCV at <12 months of age and no doses at ≥12 months of age. Potential confounding variables were selected for adjustment a priori with the assistance of a directed acyclic graph. There were strong inverse associations between PCV coverage and the incidence of PCV7-type IPD (adjusted incidence rate ratio [aIRR] 0.967, 95% confidence interval [CI] 0.958 to 0.975, p-value < 0.001), and pneumonia hospitalisations (all-cause pneumonia: aIRR 0.991 95% CI 0.990 to 0.994, p-value < 0.001) among undervaccinated children. Subgroup analyses for children <4 months old, urban, rural, and Indigenous populations showed similar trends, although effects were smaller for rural and Indigenous populations. Approximately 50% coverage of PCV7 among children <5 years of age was estimated to prevent up to 72.5% (95% CI 51.6 to 84.4) of PCV7-type IPD among undervaccinated children, while 90% coverage was estimated to prevent 95.2% (95% CI 89.4 to 97.8). The main limitations of this study include the potential for differential loss to follow-up, geographical misclassification of children (based on residential address at birth only), and unmeasured confounders. In this study, we observed substantial indirect protection at lower levels of PCV coverage than previously described-challenging assumptions that high levels of PCV coverage (i.e., greater than 90%) are required. Understanding the association between PCV coverage and indirect protection is a priority since the control of vaccine-type pneumococcal disease is a prerequisite for reducing the number of PCV doses (from 3 to 2). Reduced dose schedules have the potential to substantially reduce program costs while maintaining vaccine impact.

Invasive pneumococcal disease due to 22F and 33F in England: A tail of two serotypes

BackgroundA 15-valent pneumococcal conjugate vaccine (PCV15) aims to protect against serotype 22F and 33F in addition to the serotypes within the 13-valent PCV (PCV13) which was introduced to the UK childhood immunisation programme in April 2010. Little is known about the specific epidemiology, clinical features or outcomes of invasive pneumococcal disease (IPD) due to these two serotypes. MethodsPublic Health England (PHE) conducts enhanced IPD surveillance in England. Hospital laboratories routinely submit invasive pneumococcal isolates to PHE for serotyping and enhanced clinical information is collected through questionnaires sent to general practitioners. IPD due to serotypes 22F and 33F diagnosed during 2014/15–2018/19 were compared with IPD due to PCV13 serotypes and remaining serotypes. ResultsIn total, 25,415 isolates (93.4%) were serotyped and questionnaires were completed for 22,097 (86.9%) cases. Serotype 22F was responsible for 1,788 (7.0%) and serotype 33F for 893 (3.5%) cases compared to 19.9% (n = 5,047) for PCV13 and 69.6% (n = 17,687) for the remaining serotypes. IPD incidence increased for both serotypes since 2005/06, especially in older adults, but plateaued after PCV13 introduction. Comorbidity prevalence was 68.7% (n = 1,037) for serotype 22F and 67.2% (n = 505) for serotype 33F, with invasive pneumonia being the most common clinical presentation 1,067/1,482; 72.0%, and 514/755; 68.1%, respectively. There were 3,617 deaths within 30 days of disease onset, including 236 (CFR, 15.4%) among 22F, 128 (CFR, 16.5%) among 33F and 21.3% (925/4,350) among PCV13-type IPD cases. When compared with PCV13-type IPD, serotype 22F (aOR 0.58, 95%CI 0.49–0.68, p < 0.001) and 33F (aOR 0.73, 95%CI 0.59–0.91, p = 0.004) were independently associated with lower odds of death. The major circulating sequence types (STs) in 22F (ST 433, ST698) and 33F (ST717, ST100, ST673) were not associated with an increased risk of death compared to the other STs. ConclusionsSerotype 22F and 33F-type IPD are associated with a lower risk of death compared to PCV13-type, with those presenting with septicaemia more likely to have a fatal outcome compared to pneumonia. PCV15 has the potential to prevent up to an additional 10% of IPD cases in England.

1475. Impact of a Routine Infant PCV Program on the Serotype Distribution of Episodes of Invasive Pneumococcal Disease (IPD) and Non-bacteremic Pneumococcal Pneumonia in Adults

BackgroundHerd immunity from pediatric pneumococcal conjugate vaccine (PCV) programs has resulted in substantial reductions in IPD due to PCV serotypes (ST). We assessed whether similar changes in ST distribution occur in non-bacteremic pneumococcal pneumonia (NBPP).MethodsThe Toronto Invasive Bacterial Diseases Network performs population-based surveillance for IPD and hospitalized, culture-confirmed NBPP in Toronto/Peel Region, Canada (Pop 4.5M). Patient data are collected by interview/chart review; illness associated with respiratory isolates is categorized using Musher criteria.ResultsSince 2002, 6627 episodes of IPD, and 7323 non-bacteremic episodes with a respiratory isolate of S. pneumoniae (2180 meeting modified Musher criteria for NBPP) have occurred in adults. Distributions of vaccine-type serotypes in IPD and NBPP pre-PCV7 (2002-2004), post-PCV7 (2006-2009) and late post-PCV13 (2014-2019) are shown in the Figure. There were no significant changes in distribution of vaccine serotype groups from 2014-2019 in IPD or NBPP. From 2014-2019, serotypes included in PCV13 and PCV20 were associated with 33% and 59% of IPD cases, and 29% and 49% of NBPP cases in adults..Figure. distribution of serotype groups included in different pneumococcal vaccines in cases of IPD and non-bacteremic pneumonia ConclusionEight years post routine infant PCV13 implementation, PCV13 type IPD and NBPP persists in adults. The distribution of vaccine-type strains is similar in IPD and NBPP; although non-vaccine-type strains are more common in NBPP.Disclosures Allison McGeer, MD, FRCPC, GlaxoSmithKline (Advisor or Review Panel member, Research Grant or Support)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Research Grant or Support)

Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease After Introduction Into Routine Pediatric Use.

BackgroundIn 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced 7-valent PCV (PCV7) for protection against invasive pneumococcal disease (IPD). This study used laboratory surveillance data to examine the effect of PCV13 on IPD before and after PCV13 introduction among children aged 6 weeks to <6 years and those aged ≥6 weeks.MethodsObservational laboratory-based IPD surveillance data were compared for the periods May 2010–April 2018 and May 2008–April 2010 (the PCV7 period) using a database of Kaiser Permanente Northern California (KPNC) members with laboratory-confirmed IPD.ResultsAmong children aged 6 weeks to 6 years, overall IPD incidence decreased from 11.57 per 100 000 during the PCV7 period to 4.09 per 100 000 after PCV13 introduction; PCV13-type IPD incidence decreased from 5.12 to 0.84 per 100 000. Non-PCV13−serotype IPD did not change significantly in this age group (PCV7 period, 1.71 per 100 000 and after PCV13, 2.52 per 100 000). Of cases occurring in this group, bacteremia was the most common clinical diagnosis. Across all ages, IPD decreased from 9.49 to 6.23 per 100 000 and PCV13-type IPD decreased from 4.67 to 1.89 per 100 000, changes being mostly due to decreases in serotypes 19A and 7F. IPD caused by non-PCV13 serotypes did not change (3.34 and 3.35 per 100 000). Overall, pneumococci isolated after PCV13 introduction had increased susceptibility to penicillin, cefotaxime, and ceftriaxone.This prospective, laboratory-based surveillance study in Kaiser Permanente Northern California members examined annual IPD incidence before and after PCV13 introduction. In children aged 6 weeks to <6 years, IPD caused by PCV13 serotypes decreased significantly (84%) during the surveillance period.ConclusionsIPD incidence decreased further in every age group after PCV13 introduction, suggesting both direct vaccination effects in the infant population and indirect effects in adults. Clinical Trials RegistrationNCT01128439.

2706. Indirect Effects of Infant 13-valent Conjugate Pneumococcal Vaccination Program on Invasive Pneumococcal Disease in Adults in British Columbia, Canada

BackgroundMany jurisdictions report a significant reduction in invasive pneumococcal disease (IPD) in adults following implementation of the pneumococcal conjugate vaccines, 7-valent (PCV7) and 13-valent (PCV13) in childhood immunization programs. This study evaluates the indirect effect of conjugate vaccines on IPD in British Columbia, Canada over a 14 year period (2002–2015).MethodsUsing provincial IPD laboratory surveillance data, we calculated the annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) in adults 18 years of age and older. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–2010) and pre-PCV7 (2002–2003) baselines for overall and age-specific IPD rates using Poisson regression.ResultsA total of 3793 cases were reported over the 14 year period. The overall annual incidence increased from 4.32 cases per 100,000 population in 2002 to 8.61 cases per 100,000 population in 2015. Overall, IPD has increased by 80% (IRR: 1.80; 95% CI: 1.59–2.04) compared with baseline, especially in adults ≥ 85 years of age (PCV13 vs baseline: IRR: 1.90; 95% CI: 1.25–03.05). This increase was the highest after introduction of PCV7 (IRR: 1.87; 95% CI: 1.65–2.11); the incremental change after introduction of PCV13 was non-significant (IRR 0.96; 95% CI: 0.90–1.03). While PCV7 type IPD plummeted by 76% (IRR 0.24; 95% CI: 0.18–0.31) since introduction of PCV7 compared with baseline, a modest decline in PCV13 type IPD of 20% was seen (IRR 0.80; 95% CI: 0.71–0.89) since introduction of PCV13.ConclusionAlthough PCV7-type IPD has decreased substantially, only a modest reduction in IPD from the additional 6 serotypes in the PCV13 vaccine was observed.Disclosures All authors: No reported disclosures.

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.

2716. Persistence of 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Serotypes in Invasive Pneumococcal Disease in Adults in Southern Ontario Canada Despite Routine Pediatric Vaccination

BackgroundIn Ontario, Canada, PCV13 is covered for immunocompromised (IC) adults over 50y. PCV13 programs are thought not to be cost-effective in other adults because it is assumed that herd immunity from pediatric vaccination programs (PCV7 since 2005; PCV13 since 2010) will reduce PCV13 disease burden dramatically in adults. We analyzed data from the Toronto Invasive Bacterial Diseases Network (TIBDN) to ask whether PCV13-type invasive pneumococcal disease (IPD) in adults persists in our population.MethodsTIBDN performs population-based surveillance for IPD in Toronto+Peel Region, Ontario (pop4.1M). All microbiology laboratories receiving specimens from residents report cases of IPD and submit isolates to a central study lab for serotyping; annual audits are conducted. Demographic, medical and vaccination information are obtained from patients, families and physicians. Population data are from Statistics Canada.ResultsSince 1995, 10,365 episodes of IPD have been identified; detailed medical information was available for 9,801 (95%) and serotyping for 9411 (91%). Among 8658 adult cases, 4,273 (49%) were in those aged 15–64 years, and 4,285 (51%) in those aged >645 years. The most common diagnoses were pneumonia (5,978/8,025, 74%) and bacteremia without focus (1,030, 13%); 470 (4.6%) cases had meningitis; the case fatality rate (CFR) was 21%. The incidence of disease due to STs in PCV13 in adults declined from 7.0/100,000/year 2001 to 2.9/100,000/year in 2015–2018 and was stable from 2015–2018 (Figure 1). The incidence was > 5/100,000/year in non-IC patients over 65 years, and younger patients with cancer and kidney disease (Figure 2). In IPD from 2015 to 2018, adult patients with PCV13 ST disease were younger (median age 64 years vs. 67 years, P = .03) than other patients; there was no significant difference in the proportion with at least one underlying chronic condition (253, 69% PCV13ST, vs. 541,74% other ST, P = 0.08), or in CFR (59, 16% PCV13 vs. 145, 20% other, P = 0.13). The ST distribution of cases due to PCV13 STs is shown in Figure 3.ConclusionA significant burden of IPD due to PCV13 serotypes persists in adults in our population despite 8 years of routine pediatric PCV13 vaccination. This burden needs to be considered in assessing the value and cost-effectiveness of PCV programs for adults. Disclosures All authors: No reported disclosures.

2728. Proportion of Invasive Pneumococcal Disease Potentially Covered by Current and Next-Generation of Higher-Valency Pneumococcal Conjugate Vaccines in Canada, 2010–2016

BackgroundIn Canada, routine pediatric immunization with 7-valent pneumococcal conjugate vaccine (PCV7) was introduced between 2002 and 2006. Two of ten provinces transitioned to PCV10 in 2009; by mid-2011, following a national preferential recommendation, PCV13 replaced PCV7/PCV10 across Canada. PCV13 also has been recommended for immunocompromised adults since 2013, and immunocompetent adults aged ≥65 years on an individual basis since 2016. Immunization with 23-valent polysaccharide vaccine (PPV23) is recommended in adults with certain comorbidities, and routinely in those aged ≥65 years. Two higher-valency PCVs, PCV15, and PCV20 are currently under development.MethodsCase counts of invasive pneumococcal disease (IPD) by serotype and age group were obtained from published annual reports of passive laboratory-based national IPD surveillance conducted by the National Microbiology Laboratory (NML) since April 2010.ResultsIn all ages, the proportion of IPD due to PCV13 serotypes declined from 55% in 2010 to 31% in 2016 (Figure 1); in children age < 5 years, from 66% to 19%; in adults age 50–64 years, from 52% to 34%, and in adults age > 65 years from 51% to 25%. While most age groups have experienced declines in the proportion of PCV13-type IPD, this proportion has plateaued since 2014 in all age groups except 2–4 years old. During 2016, among all ages, the proportions of IPD due to PCV13, PCV15, and PCV20 types were 31%, 43%, and 58%, respectively; among children age < 5 years 19%, 35%, and 50%, respectively, among adults 50–64 years, 34%, 47%, and 61%, respectively, and among adults age ≥65 years, 25%, 38%, and 53%, respectively.ConclusionThe proportion of PCV13-type IPD has declined across all ages since the introduction of PCV13 in children. The plateau in this proportion observed across most age groups since 2014 suggests that herd effect may have been maximized, and additional reductions could be expected primarily from direct PCV13 adult immunization. PCV20 could potentially protect against a large proportion of the remaining IPD burden in Canada. Disclosures All authors: No reported disclosures.

Early Impact of 13-Valent Pneumococcal Conjugate Vaccine Use on Invasive Pneumococcal Disease Among Adults With and Without Underlying Medical Conditions-United States.

The 13-valent pneumococcal vaccine (PCV13) was introduced for US children in 2010 and for immunocompromised adults ≥19 years old in series with the 23-valent polysaccharide vaccine (PPSV23) in 2012. We evaluated PCV13 indirect effects on invasive pneumococcal disease (IPD) among adults with and without PCV13 indications. Using Active Bacterial Core surveillance and the National Health Survey, using Active Bacterial Core surveillance and the National Health Interview Survey, we estimated and compared IPD incidence in 2013-2014 and 2007-2008, by age and serotype group (PCV13, PPSV23-unique, or nonvaccine types [NVTs]), among adults with and without PCV13 indications. IPD incidence declined among all adults. Among adults 19-64 years, PCV13-type IPD declined 57% (95% confidence interval [CI], -68% to -43%) in adults with immunocompromising conditions (indication for PCV13 use), 57% (95% CI, -62% to -52%) in immunocompetent adults with chronic medical conditions (CMCs, indications for PPSV23 use alone), and 74% (95% CI, -78% to -70%) in adults with neither vaccine indication. Among adults aged ≥65 years, PCV13-type IPD decreased 68% (95% CI, -76% to -60%) in those with immunocompromising conditions, 68% (95% CI, -72% to -63%) in those with CMCs, and 71% (95% CI, -77% to -64%) in healthy adults. PPSV23-unique types increased in adults 19‒64 years with CMCs, and NVTs did not change among adults with or without PCV13 indications. From 2013 to 2014, non-PCV13 serotypes accounted for 80% of IPD. IPD incidence among US adults declined after PCV13 introduction in children. Similar reductions in PCV13-type IPD in those with and without PCV13 indications suggest that observed benefits are largely due to indirect effects from pediatric PCV13 use rather than direct use among adults.

Limited indirect effects of an infant pneumococcal vaccination program in an aging population.

BackgroundA general recommendation for adult pneumococcal vaccination with 23-valent polysaccharide vaccine (PPV23) for adults 60 and older has been in place in Germany since 1998, but uptake has been low. Just over a decade after the implementation of an infant pneumococcal conjugate vaccine recommendation, we examined indirect protection effects on adult invasive pneumococcal disease (IPD) in Germany.Methods and findingsReported IPD cases decreased in children under two years of age from 11.09 per 100,000 in 2003–2006 to 5.94 per 100,000 in 2017/18, while in adult age groups, reported IPD cases rose across the board, most dramatically in adults 60 years of age and over, from 1.64 to 10.08 cases per 100,000. PCV13-type IPD represents 31% of all cases in this age group, the lion’s share of which is due to the rapid increase of serotype 3 IPD, which, by itself, has reached 2.11 reported cases per 100,000 and makes up 21% of all IPD cases in this age group. The two vaccine formulations currently in development (PCV15 and PCV20) would increase current (PCV13) coverage by 8.5% points and 28.0% points in children, while in adults coverage would increase by 10.4% points and 21.9% points, respectively.ConclusionsWhile original models predicted that indirect effects of childhood vaccination would suffice for adults, it seems that the herd protection effect has reached its limit, with vaccine serotypes 4, 19F, and 19A IPD persisting in adults after initial reductions, and serotype 3 IPD not showing any herd protection effect at all.

Streptococcus pneumoniae serotype 3 is masking PCV13-mediated herd immunity in Canadian adults hospitalized with community acquired pneumonia: A study from the Serious Outcomes Surveillance (SOS) Network of the Canadian immunization research Network (CIRN)

BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV13) was recently shown to be effective against PCV13-type invasive pneumococcal disease (IPD) and pneumococcal community acquired pneumonia (CAPSpn) in healthy adults aged ≥65 years, prompting many countries to re-assess adult immunization. In Canada, the potential benefits of adult PCV13 immunization were unclear given anticipated herd immunity from PCV13 childhood immunization introduced since 2010. This study describes the serotype distribution and clinical outcomes of Canadian adults aged ≥16 years, who were hospitalized with CAPSpn and IPD from 2010 to 2015. MethodsActive surveillance for CAP and IPD was performed in adult hospitals across five Canadian provinces. IPD was identified when Streptococcus pneumoniae was isolated from sterile sites. Bacteremic and non-bacteremic CAPSpn were identified using blood culture, and sputum culture or PCV13-specific urine antigen detection (UADPCV13), respectively. Serotype was assigned using Quellung reaction, PCR, or UADPCV13. ResultsOf 6687 CAP cases where a test was performed, S. pneumoniae positivity decreased from 15.9% in 2011 to 8.8% in 2014, but increased to 12.9% in 2015. CAPSpn attributed to PCV13 serotypes followed a similar trend, dropping from 8.3% in 2010 to 4.6% in 2014, but increasing to 6.3% in 2015. The decline was primarily attributed to serotypes 7F and 19A, and the proportional increase to serotype 3. Similar trends were noted for bacteremic and non-bacteremic CAPSpn. Serious outcomes such as 30-day mortality, intensive care unit admission, and requirement for mechanical ventilation were prominent in CAPSpn and IPD cases, but remained unchanged over the study years. ConclusionHerd immunity afforded primarily by serotypes 7F and 19A appears to be partly masked by a concomitant proportional increase of serotype 3. Despite evidence of herd immunity, these PCV13 serotypes remain persistent in Canadian adults hospitalized with CAPSpn, and represent between 5 and 10% of all CAP in this patient population.

151. Evaluation of Pneumococcal Vaccine Effectiveness Against Invasive Pneumococcal Disease Among US Medicare Beneficiaries ≥65 Years Old

BackgroundPneumococcal conjugate vaccine (PCV13) was recommended in series with PPSV23 for all US adults ≥65 years in late 2014. We evaluated effectiveness of PCV13 against invasive pneumococcal disease (IPD) among Medicare beneficiaries ≥65 years old to assess this new policy.MethodsWe linked records for IPD cases (pneumococcus isolated from sterile sites) in persons ≥65 years old identified through Active Bacterial Core surveillance with those of Medicare beneficiaries. Isolates were serotyped and classified as PCV13 (with or without cross-reacting type 6C), and nonvaccine types. We selected Medicare beneficiaries with no record of IPD or pneumonia as controls, and matched to cases on age, residence census tract, and length of Medicare enrollment; we included all eligible controls. Vaccination and medical histories were obtained through Medicare. We estimated vaccine effectiveness (VE) as 1 minus the IPD odds ratio for vaccinated (PCV13) vs. unvaccinated (no PCV13 or PPSV23) persons using conditional logistic regression, adjusted for sex and underlying conditions.ResultsFrom 2,246 IPD cases identified in 2015–2016, 1,017 (45%) were matched to Medicare beneficiaries. After excluding cases in persons residing in long-term care facilities or with <1 year of Medicare enrollment, we included 699 eligible cases and 10,152 controls in our analysis. PCV13-types (+6C) accounted for 164 (23%) cases, and serotype 3 was the most common PCV13-type. Case patients were more likely than controls to have one or more chronic (88% vs. 58%) or immunocompromising (54% vs. 32%) conditions present. Fourteen percent, 22%, and 8% of case patients, and 18%, 21%, and 8% of controls received PCV13 only, PPSV23 only, or both vaccines, respectively. PCV13-only VE against PCV13-types was 36% (95% CI −18, 65%). When we included type 6C with PCV13-types, VE was 67% (95% CI 11, 88%). PCV13 showed similar effectiveness against PCV13 type (+6C) IPD among adults >75 years of age (VE 61%, 95% CI 14, 82). VE was 26% (95% CI −58, 65%) against serotype 3 and 67% (95% CI 11, 88%) against other PCV13-types (+6C). PCV13 was not effective against nonvaccine types.ConclusionPCV13 was effective in preventing IPD caused by PCV13 types when excluding type 3; no effectiveness was demonstrated against serotype 3.Disclosures W. Schaffner, Merck: Member, Data Safety Monitoring Board, Consulting fee. Pfizer: Member, Data Safety Monitoring Board, Consulting fee. Dynavax: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. SutroVax: Consultant, Consulting fee. Shionogi: Consultant, Consulting fee.

1436. Risk Factors for Invasive Pneumococcal Disease in Adults ≥65 Years Old Following Pneumococcal Conjugate Vaccine Recommendation

BackgroundIn 2014, pneumococcal conjugate (PCV13) and polysaccharide (PPSV23) vaccines were recommended in series for all US adults ≥65 years. We conducted a case–control study to evaluate risk factors for invasive pneumococcal disease (IPD) among adults ≥65 years old.MethodsIPD cases (isolation of pneumococcus from sterile sites) were identified through Active Bacterial Core surveillance during 2015–2018. Isolates were serotyped using whole genome sequencing. Four controls, identified through a commercial database, were matched per case by age and zip code. We obtained vaccination and medical histories from providers, vaccine registries and participant interviews. A functional status score was calculated based on participant interview. We calculated IPD odds ratios using multivariable conditional logistic regression.ResultsWe enrolled 328 IPD cases and 1,280 matched controls. Fifty percent of case-patients and 55% of controls received a dose of PCV13. Case-patients were more likely than controls to have a chronic condition (heart, liver, or lung disease, diabetes, cochlear implant, alcohol abuse, smoking; 82% vs. 59%), immunosuppression (60% vs. 32%), poor functional status (score of ≥ 3; 71% vs. 50%), annual household income <$30,000 (38% vs. 25%) and education level of high school or less (36% vs. 25%). In a multivariable model, case-patients were more likely than controls to have a chronic condition (OR 2.48, 95% CI 1.72, 3.58), immunosuppression (OR 2.56, 95% CI 1.92,3.42), poor functional status (OR 3.66, 95% CI 2.42, 5.54), and primary or secondary smoking exposure (OR 3.09, 95% CI 1.32, 7.2). In analysis limited to PCV13-type cases and matched controls, adjusting for PCV13 receipt, measures of association were no longer significant for chronic conditions (OR 1.45, 95% 0.71, 2.95), immunosuppression (OR 1.51, 95% CI 0.83, 2.74), or poor functional status (OR 1.98, 95% CI 0.91, 4.3).ConclusionChronic and immunosuppressive conditions remain IPD risk factors for adults in the era of PCV13 use; poor functional status was also identified as a risk factor. Targeted evaluation of adults with poor functional status could inform IPD prevention strategies. PCV13 may reduce the risk of PCV13-type IPD associated with chronic conditions and poor functional status.Disclosures W. Schaffner, Merck: Member, Data Safety Monitoring Board, Consulting fee; Pfizer: Member, Data Safety Monitoring Board, Consulting feeDynavax: Consultant, Consulting fee; Seqirus: Consultant, Consulting fee; SutroVax: Consultant, Consulting fee; Shionogi: Consultant, Consulting fee.