Incidence Rate Of Invasive Pneumococcal Disease Research Articles

The impact of pneumococcal serotype replacement on the effectiveness of a national immunization program: a population-based active surveillance cohort study in New Zealand

In Aotearoa New Zealand (NZ) PCV7 was introduced in 2008, then PCV10 in 2011 and PCV13 in 2014. In 2017 PCV10 was re-introduced, replacing PCV13. In the present study, we investigate the resultant rapidly changing invasive pneumococcal disease (IPD) epidemiology. We compare the IPD incidence rate ratio (IRR) in NZ (2022 versus 2020) with other countries, and describe the IPD epidemiology (including trends in overall IPD and serotype 19A, and antimicrobial resistance) within NZ. Additionally, we performed a genomic-epidemiology investigation identifying the most common 19A sequence types and associated risk factors. Though IPD incidence rates have increased in the US and Australia (2021-22) after declines in 2020, in NZ the incidence rate is the highest since 2011 with a significantly higher IRR than US (p<0.01). Incidence rates among children <2 and adults 65 or over in 2022 are the highest since 2009, driven by significant increases of serotype 19A (p=0.01). Māori and Pacific peoples are experiencing the highest rates since 2009. Further, penicillin resistance among 19A isolates has increased from 39% (2012) to 84% (2021) (p=0.02). Genomic sequencing identified the more virulent ST-2062 as most common among 19A isolates sequenced, increasing from 5% (2010) to 55% (2022). With very high incidence rates of IPD in NZ, inadequate protection against 19A, increasing resistance, and a more virulent 19A clade, targeted public health campaigns and increased PCV13 availability are needed. The NZ Ministry of Health funds IPD surveillance and typing in NZ.

Indirect impact of childhood 13-valent pneumococcal conjugate vaccine (PCV13) in Canadian older adults: a Canadian Immunization Research Network (CIRN) retrospective observational study

Background13-valent pneumococcal conjugate vaccine (PCV13) has been part of publicly funded childhood immunisation programmes in Ontario and British Columbia (BC) since 2010. We assessed the indirect impact of infant PCV13...

Invasive Pneumococcal Disease After 2 Decades of Pneumococcal Conjugate Vaccine Use.

We sought to describe the evolving epidemiology of invasive pneumococcal disease (IPD) among children in Massachusetts, United States, over the last 2 decades during which sequential 7-valent pneumococcal conjugate vaccines (PCV7) and 13-valent PCVs (PCV13) were implemented. Cases of IPD in children aged <18 years were detected between 2002 and 2021 through an enhanced population-based, statewide surveillance system. Streptococcus pneumoniae isolates from normally sterile sites were serotyped and evaluated for antimicrobial susceptibility. IPD incidence rates and rate ratios with 95% confidence intervals (CIs) were calculated. We identified 1347 IPD cases. Incidence of IPD in children aged <18 years declined 72% over 2 decades between 2002 and 2021 (incidence rate ratios 0.28, 95% CI 0.18-0.45). IPD rates continued to decline after replacement of PCV7 with PCV13 (incidence rate ratios 0.25, 95% CI 0.16-0.39, late PCV7 era [2010] versus late PCV13 era [2021]). During the coronavirus disease 2019 pandemic years, 2020 to 2021, the rate of IPD among children aged <18 years reached 1.6 per 100 000, the lowest incidence observed over the 20 years. In PCV13 era, approximately one-third of the IPD cases in children aged >5 years had at least 1 underlying condition (98, 30.3%). Serotypes 19A and 7F contributed 342 (48.9%) of all cases before implementation of PCV13 (2002-2010). Serotype 3 (31, 8.6%), and non-PCV13 serotypes 15B/C (39, 10.8%), 33F (29, 8.0%), 23B (21, 0.8%), and 35B (17, 4.7%) were responsible for 37.8% of cases in PCV13 era (2011-2021). Penicillin nonsusceptibility continued to decline (9.8% vs 5.3% in pre-/late PCV13 era, P = .003), however has become more common among non-PCV13 serotypes compared with vaccine serotypes (14.8% vs 1.4%, P < .001). Robust ongoing surveillance networks are critical for identifying emerging serotypes and development of next-generation vaccine formulations.

1160. Comparative Effectiveness of Pneumococcal Vaccination Strategies to Prevent Invasive Pneumococcal Disease: A Cohort Study at the Veterans Health Administration

Abstract Background The direct impact of a combined vaccination strategy pneumococcal 13-valent conjugate vaccine (PCV13) and 23-valent polysaccharide vaccine (PPSV23) for adults in preventing pneumococcal infections has yet to be thoroughly investigated. We aimed to estimate the comparative effectiveness of preventing the most severe form of pneumococcal infections, invasive pneumococcal disease (IPD), by comparing the risk of IPD stratified by the use of PCV13, PPSV23, and their combinations. Methods We included all patients who were 65 years or older, had established primary care within the Veterans Health Administration (VHA) between 2005 and 2021, and had not received any prior pneumococcal vaccination. We measured time-to-event from cohort enrollment to the onset of culture-proven IPD, considering death a competing risk event, and constructed a Cox regression model to estimate cause-specific hazards. PCV13 only, PPSV23 only, and PCV13 + PPSV23 were incorporated into the model as a time-dependent exposure variable, and we estimated hazard ratios (HRs) associated with them. We also considered a waning effect by incorporating time-by-vaccine interaction terms in the model to estimate continuously changing time-dependent hazards. Results 5,069,917 patients were enrolled in the cohort (male: 96.5%; median age: 72 [IQR: 65-79]). 1,217,349 patients received at least one dose of pneumococcal vaccine during the study period. The overall incidence rate of IPD was 9.1 per 100,000 patient-years. In crude analysis, all pneumococcal vaccines were associated with lower HRs for IPD, and there was an additive benefit of PCV13 and PPSV23 (Tables 1 and 2). In multivariate analysis, associations between PCV13 alone and PPSV23 alone were no longer statistically significant after adjusting for age and comorbidities, but PCV13 + PPSV23 was significantly associated with lower HR for IPD. No time-by-vaccine interaction term was significant. Conclusion In this large cohort study at the VHA, neither vaccine by itself appeared to lower the risk of IPD, but the combination of PCV13 and PPSV23 was associated with a significantly lower risk. In addition, we did not observe evidence of a waning effect to prevent IPD. Further studies are needed to evaluate the effect of newer pneumococcal vaccines. Disclosures Michihiko Goto, MD MSCI, Merck &amp; Co.: Grant/Research Support

Invasive Pneumococcal Disease and Potential Impact of Pneumococcal Conjugate Vaccines Among Adults, Including Persons Experiencing Homelessness-Alaska, 2011-2020.

Adults aged ≥65 years, adults with certain underlying medical conditions, and persons experiencing homelessness are at increased risk for invasive pneumococcal disease (IPD). Two new pneumococcal conjugate vaccines, 15-valent pneumococcal conjugate vaccine (PCV15) and 20-valent pneumococcal conjugate vaccine (PCV20), were recently approved for use in US adults. We describe the epidemiology of IPD among Alaska adults and estimate the proportion of IPD cases potentially preventable by new vaccines. We used statewide, laboratory-based surveillance data to calculate and compare IPD incidence rates and 95% confidence intervals (CIs) among Alaska adults aged ≥18 years during 2011-2020 and estimate the proportion of IPD cases that were caused by serotypes in PCV15 and PCV20. During 2011-2020, 1164 IPD cases were reported among Alaska adults for an average annual incidence of 21.3 cases per 100 000 adults per year (95% CI, 20.1-22.5). Incidence increased significantly during the study period (P < .01). IPD incidence among Alaska Native adults was 4.7 times higher than among non-Alaska Native adults (95% CI, 4.2-5.2). Among adults experiencing homelessness in Anchorage, IPD incidence was 72 times higher than in the general adult population (95% CI, 59-89). Overall, 1032 (89%) Alaska adults with IPD had an indication for pneumococcal vaccine according to updated vaccination guidelines; 456 (39%) and 700 (60%) cases were caused by serotypes in PCV15 and PCV20, respectively. Use of PCV15 and PCV20 could substantially reduce IPD among adults in Alaska, including Alaska Native adults and adults experiencing homelessness.

Pneumococcal infections in children with sickle cell disease before and after pneumococcal conjugate vaccines

AbstractChildren with sickle cell disease (SCD) are at increased risk of invasive pneumococcal disease (IPD). Over 25 years, the Georgia Emerging Infections Program/Centers for Disease Control and Prevention Active Bacterial Core Surveillance network identified 104 IPD episodes among 3707 children with hemoglobin SS (HbSS) or HbSC aged <10 years, representing 6% of IPD in Black or African American children residing in Metropolitan Atlanta (reference population). Children with IPD and HbSS/SC were older than those with IPD in the reference population (P < .001). From 1994-1999 to 2010-2018, IPD declined by 87% in children with HbSS aged 0 to 4 years, and by 80% in those aged 5 to 9 years. However, IPD incidence rate ratios when comparing children with SCD with the reference population increased from 20.2 to 29.2 over these periods. Among children with HbSS and IPD, death declined from 14% to 3% after 2002, and meningitis declined from 16% to 8%. Penicillin resistance was more prevalent in children with SCD before 7-valent pneumococcal conjugate vaccine (PCV7) licensure. After 2010, all IPD serotypes were not included in the 13-valent PCV (PCV13). Within 3 years of vaccination, the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against non-PCV13 serotypes included in PPSV23 plus 15A/15C was 92% (95% confidence interval, 40.8- 99.0, P = .014; indirect-cohort effect adjusted for age and hydroxyurea). PPSV23 would cover 62% of non-PCV13 serotype IPD in children with SCD, whereas PCV15, PCV20, and PCV21/V116 (in development) could cover 16%, 51%, and 92%, respectively. Although less frequent, IPD remains a life-threatening risk in children with SCD. Effective vaccines with broader coverage could benefit these children.

Invasive pneumococcal disease among the elderly in the later era of paediatric pneumococcal conjugate vaccination-A longitudinal study over 10 years based on public surveillance data in the Nordics.

Pneumococcal conjugate vaccines (PCVs) have proven effective in preventing both non-invasive and invasive pneumococcal disease (IPD) in small children and in older age groups. However, long-term observations and country comparisons of IPD incidence in the elderly following introduction of PCVs in paediatric national immunisation programmes (NIPs) are scarce. We aimed to estimate and compare incidence of IPD in the elderly in Denmark, Finland, Norway, and Sweden over a 10-year time span. During the study period Denmark and Norway used PCV13 in their paediatric NIP, Sweden both PCV10 and PCV13 and Finland used PCV10. Uptake of pneumococcal vaccines for the elderly was low. We collected longitudinal data on confirmed IPD cases and their serotypes among elderly people (aged ≥65 years) 2010-2019 in the four countries of interest. Annual IPD incidence rates were calculated per country, by vaccine-associated serotypes (PCV10, PCV13, PCV15, PCV20 and PPV23) and for non-vaccine serotypes. A regression model was used to estimate average annual change in incidence in each country. Incidence rates of IPD in the elderly in 2019 ranged from 31.4 to 41.8 per 100,000 people across the countries. Denmark and Norway showed an annual average decline in IPD incidence (-3.3; 95% CI: -5.6 to -1.1; p<0.01) and (-3.3; 95% CI: -5.5 to -1.0; p<0.01) respectively from 2010 to 2019, whereas no change was seen for Sweden (-0.5; 95% CI: -1.9 to 0.8; p = 0.39) or Finland (0.9; 95% CI: -1.0 to 2.7; p = 0.32). IPD incidence due to emerging serotypes, e.g., serotypes 8 and 12F, has increased. Serotype 19A remained a major cause of IPD in countries with PCV10 in paediatric NIPs. Despite paediatric PCV programmes, a considerable vaccine preventable IPD burden remains in the elderly. Further, choice of PCV in paediatric programs was associated with differences in serotype distribution and incidence amongst the elderly. Direct vaccination of the elderly with recently approved broad coverage PCVs holds promise for meaningful impact on disease burden with PCV20 covering a majority of IPD amongst the elderly in the four studied countries. Effectiveness of new vaccines in real-life clinical practice should be followed.

Dynamics of invasive pneumococcal disease in infants < 2 years old following PCV7/13 implementation using two infant and a booster dose schedule: evidence for indirect protection of young infants, Israel, 2004 to 2019.

BackgroundPneumococcal conjugated vaccine (PCV)7 and PCV13 programmes started in Israel from July 2009 and November 2010 respectively, with a 2+1 schedule (one dose at 2 months old, one at 4 months old, and a booster dose at 12 months old). Thereafter, invasive pneumococcal disease (IPD) rates substantially declined in children. Uptake of all three doses in < 2-year-olds since 2012 is > 90%. For still incompletely vaccinated infants (≤ 12 months old), how well the PCV 2+1 programme shields from IPD is not fully resolved.AimTo assess the adequacy of protection conferred by the 2+1 schedule PCV vaccination programme, particularly among incompletely-vaccinated infants.MethodsThis was a population-based, prospective, nationwide active IPD surveillance study in Israel, 2004-2019, in children < 24 months old. We estimated annual incidence rates (IR) of overall IPD, IPD caused by PCV13 serotypes (VT13), and non-PCV13 serotypes (NVT13). Annual IPD IRs were stratified by age: < 4 months (receiving ≤ 1 dose), 4-6 months (immediately post dose 2), 7-12 months (a few months post dose 2), and 13-23 months (post dose 3). Late-PCV (2004-2008) to pre-PCV13 (2016-2019) mean annual IR ratios (IRRs) were calculated.Results2,569 IPD episodes were recorded. VT13 decreased > 90% in all age groups, while NVT13 seemed to increase. All-IPD rates declined in all age groups by 56-70%. The 2+1 schedule impact on 7-12-month-old infants (pre-booster) was similar to that on 13-23-month-old children (post booster), with PCV13 IPD reductions of 97% and 98%, respectively.ConclusionsIndirect (herd) protection of infants, including < 4 month-olds with ≤ 1 PCV dose, was achieved by the 2+1 PCV schedule programme which thus seems adequate.

Comparison of the epidemiology of invasive pneumococcal disease between Australia and New Zealand in 2017–2021: an observational study based on surveillance data

The Australian immunisation schedule uses 13-valent pneumococcal conjugate vaccine (PCV13), while New Zealand (NZ) changed from PCV13 to 10-valent PCV (PCV10) in 2017. In NZ, cases of serotype 19A (not in PCV10) have been increasing since 2017. We compared invasive pneumococcal disease (IPD) epidemiology between Australia and NZ in 2017-2021. We collated IPD notification data from national surveillance systems. Between Australia and NZ, we compared IPD incidence rates and assessed the proportion of serotype 19A, and stratified for ethnicity and age. Between 2017 and 2021, the crude IPD incidence per 100,000 in Australia ranged from 4.3 to 8.4, and ranged from 6.9 to 11.4 in NZ. The highest age-adjusted IPD rates were observed in Australian Indigenous people (range: 27.3-35.5) followed by NZ Māori/Pacific peoples (range 19.7-30.4). For children <2 years, ethnicity-adjusted IPD rates were similar between Australia and NZ in 2017-2020. In 2021, however, the ethnicity-adjusted incidence in children <2 years was higher in NZ (30.2; 95% CI 21.1-39.4) than in Australia (23.3 95% CI: 19.5-27.1) (p<0.01). In Australia, the proportion of serotype 19A remained 5%, whereas in NZ serotype 19A increased from 11.5% to 29.5% with the largest increase in children <2 years and 2-4 years. Despite higher risks in Indigenous populations in Australia compared to all other groups, the overall IPD rate in NZ is increasing, particularly among children. The numbers and proportions of IPD due to serotype 19A are increasing in NZ especially in children. These data support the NZ decision from December 2022 to change to PCV13. This research received no specific funding.

576. Burden of Pneumococcal Disease Due to Serotypes Covered by the 13-Valent and New Higher-Valent Pneumococcal Conjugate Vaccines in All Children and Children at Risk in the United States

Abstract Background Routine vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) in infants along with a catch-up option with PCV13/PPSV23 in children with underlying medical conditions (UMC) have considerably reduced invasive pneumococcal disease (IPD) and non-invasive pneumococcal disease (PD), including community acquired pneumonia (CAP) and acute otitis media (AOM), in the United State (US). However, a rise in IPD and non-invasive PD caused by non-PCV13 serotypes has been observed. A 15-valent PCV (PCV15) and 20-valent PCV (PCV20), containing additional serotypes to PCV13, are anticipated for children soon. The objective of the study was to estimate the annual cases, deaths, and economic burden of disease attributable to PCV13, PCV15, and PCV20 serotypes in children &amp;lt; 18 years old overall and those with UMC in the US. Methods Estimated annual cases, deaths and direct medical costs associated with PD caused by PCV13, PCV15 and PCV20 serotypes were calculated based on published incidence rates of IPD, CAP, and AOM, along with age-group specific serotype coverage, case fatality rates, and disease-related costs (Table 1). The PD burden in those with UMC were extrapolated based on incidence rate ratios of those with UMC vs. those without UMC. The results were reported for 0-17 years and were further stratified into 2 age groups: 0-4 and 5-17 years. Table 1:Source Data for the Calculation Results The estimated annual PD cases attributable to PCV13, PCV15, and PCV20 serotypes in those 0-17 years were 768,301, 1,275,187, and 1,656,716 and in those with UMC were 23,209, 43,579, 63,949 (Table 2.1), respectively. The estimated direct medical costs were $494, $833, $1,103 million in those 0-17 years, and $76, $127, and $186 million in those with UMC, respectively (Table 3.1). The total estimated IPD cases in children with UMC were 18% (PCV13), 20% (PCV15) and 23% (PCV20) of all estimated IPD cases in all children. Conclusion This study demonstrates that the clinical and economic burden associated with new serotypes included in higher valent PCVs are substantial and higher in children with UMCs. The result shows that PCV20 will offer broader PCV coverage in the prevention of PD in ages &amp;lt; 18 years overall and those specifically with UMC. Disclosures Alejandro D. Cane, MD, PhD, Pfizer: Full time employee|Pfizer: Stocks/Bonds Johnna Perdrizet, MPH, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Adriano Arguedas, Medical director, Pfizer: Stocks/Bonds.

Molecular epidemiology of paediatric invasive pneumococcal disease in Andalusia, Spain.

This study aimed to assess the impact of the introduction of pneumococcal conjugate vaccine 13 (PCV13) on the molecular epidemiology of invasive pneumococcal disease (IPD) in children from Andalusia. A population-based prospective surveillance study was conducted on IPD in children aged <14 years from Andalusia (2018-2020). Pneumococcal invasive isolates collected between 2006 and 2009 in the two largest tertiary hospitals in Andalusia were used as pre-PCV13 controls for comparison of serotype/genotype distribution. Overall IPD incidence rate was 3.55 cases per 100 000 in 2018; increased non-significantly to 4.20 cases per 100 000 in 2019 and declined in 2020 to 1.69 cases per 100 000 (incidence rate ratio 2020 vs. 2019: 0.40, 95% confidence interval (CI) 0.20-0.89, P = 0.01). Proportion of IPD cases due to PCV13 serotypes in 2018-2020 was 28% (P = 0.0001 for comparison with 2006-2009). Serotypes 24F (15%) and 11A (8.3%) were the most frequently identified non-PCV13 serotypes (NVT) in 2018-2020. Penicillin- and/or ampicillin-resistant clones mostly belonged to clonal complex 156 (serotype 14-ST156 and ST2944 and serotype 11A-ST6521). The proportion of IPD cases caused by PCV13 serotypes declined significantly after the initiation of the PCV13 vaccination programme in 2016. Certain NVT, such as serotypes 24F and 11A, warrant future monitoring in IPD owing to invasive potential and/or antibiotic resistance rates.

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)

1180. Comparing Changes in Pneumococcal Meningitis Incidence to all Invasive Pneumococcal Disease Following Introduction of PCV10 and PCV13: The PSERENADE Project

BackgroundThe introduction of higher valency pneumococcal conjugate vaccines (PCV10 and PCV13) has reduced invasive pneumococcal disease (IPD) incidence. It is unknown whether the degree of reduction differs for pneumococcal meningitis, a small subset of pneumococcal disease but a major cause of severe childhood morbidity and mortality globally. We compared the impact of PCV10/13 on pneumococcal meningitis and all IPD by estimating the changes in incidence following the introduction of PCV10/13 among children < 5 years of age.MethodsData on confirmed positive cases for pneumococcus in cerebrospinal fluid (CSF) were obtained directly from surveillance sites. PCV10/13 impact on all-serotype pneumococcal meningitis and all IPD were estimated using site-specific incidence rate ratios (IRRs) at each post-PCV10/13 year relative to the pre-PCV period, using Bayesian multi-level, mixed effects Poisson regression. All-site weighted average IRRs were estimated using linear mixed-effects regression. Results were stratified by product (PCV10 vs. PCV13) and amount of prior PCV7 use (none; some (1-3 years or 4-5 years with < 70% uptake); or many (≥ 4 years with ≥ 70% uptake).Results40 surveillance sites (9 PCV10, 31 PCV13) in 28 countries, primarily high-income (82%) that had both CSF and IPD data were included in analyses. CSF+ accounted for 9.0% of IPD cases (IQR across sites: 6.2%-15.6%). The rate and amount of decline was generally similar between meningitis and IPD across all strata. At 5 years after PCV10/13 introduction, the IRRs across PCV7-use strata were 0.28-0.32 for pneumococcal meningitis and 0.22-0.43 for all IPD at PCV10-using sites, and 0.27-0.41 and 0.21-0.32, respectively, for PCV13-using sites. Only one site from the African meningitis belt contributed eligible data, which lacked pre-PCV data to estimate IRRs, but incidence rate of both IPD and meningitis decreased following PCV introduction. Figure 1. All-Site Weighted Average Incidence Rate Ratios, Children < 5 years * Total sites indicate the number of sites with incidence rate data included and pre/post sites indicate the number of sites with both pre− and post−PCV data to estimate site−specific IRRs for each outcome. The size of point estimates is relative to the number of sites with both pre− and post− data. ** Year 0 indicates the year of PCV10/13 introduction and year −1 indicates the last year of PCV7 use prior to PCV10/13 introduction.ConclusionNet declines in all-serotype IPD and CSF+ meningitis in children < 5 years were similar on average for both PCV10 and PCV13. Data from low-income, high-burden, and meningitis-belt regions were limited. Disclosures Maria Deloria Knoll, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)

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)

Burden of Pneumococcal Meningitis and Bacteremia, Serotype Distribution and Antibiotic Resistance in Healthy Children After Conjugated Pneumococcal Vaccine Implementation: Single Center Experience

In Turkey, the seven-valent pneumococcal conjugated vaccine (PCV7) was included in the childhood national immunization programme in April 2008 and was replaced by the 13-valent pneumococcal conjugated vaccine (PCV13) in April 2011. In this retrospective, single-center study, it was aimed to determine the serotype distribution and antimicrobial resistance in Streptococcus pneumoniae isolates of pediatric patients with invasive pneumococcal disease (IPD) after the introduction of PVC7 and PVC13. Fifty pediatric patients diagnosed with meningitis and sepsis/bacteremia between October 2009 and October 2019 were included in the study. The pediatric patient group consisted of previously healthy patients diagnosed with meningitis and sepsis/bacteremia with S.pneumoniae isolated in their blood or cerebrospinal fluids. Patients with pneumonia-associated bacteremia and empyema were not included in the study. Serotyping of the isolates was performed by Quellung reaction using specific antisera (Statens Serum Institute, Denmark) and antibiotic (penicillin and ceftriaxone) susceptibility was determined by antibiotic gradient method based on Clinical Laboratory Standards Institute (CLSI) criteria. Of the children, 29 (58%) were boys and 21 (42%) were girls. The median age of the patients was 19 months (1 month-18 year). When the children under the age of five were evaluated, it was found that 30 (79%) patients were diagnosed with occult bacteremia/sepsis and 8 (21%) with meningitis. The overall annual incidence rate of IPD among the healthy children aged <5 years decreased significantly from 9.35/100000 to 0.83/100000 (p< 0.001). Serotype identification was determined for 44 of 50 pneumococcal isolates . However, since six patients with underlying disease were not included in the evaluation, the remaining 38 isolates were found to be one of the serotypes included in PCV7 and PCV13 at a rate of 28.9% (n= 11) and 44.7% (n= 17), respectively. While the rate of PCV13 serotypes seen in the PCV7 period was 81.8%, this rate decreased to 29.6% within eight years after PCV13 administration. The rate of non-vaccine serotypes was determined as 54.5% in PCV7 period and 70.3% in PCV13 period. The rate of non-vaccine serotypes in patients under 5 years was 60% in the period of PCV7 and 75% in the period of PCV13. The proportion of non-vaccine serotypes has increased over time. However, this difference was not statistically significant (p> 0.05). The most common serotypes detected in isolates were 19F, 23F, 7F, 31 and 24B. According to the minimum inhibitory concentration values of the isolates recovered from patients with meningitis, penicillin and ceftriaxone resistance rates were found as 43.9% and 9.8%, respectively. In conclusion, our study showed that there was a 91.1% decrease in the incidence of IPD in healthy children aged under five years after the implementation of PCV7 and PCV13. It was determined that while the rate of serotypes in vaccine content decreased, there was an increase in non-vaccine serotypes. In addition no significant change was observed in antibiotic resistance rates over the years.

Effectiveness of the 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease in Greenland

The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in 2010 to the childhood vaccination program in Greenland. This study aimed to estimate the effectiveness of the PCV13 on the incidence of invasive pneumococcal disease (IPD) in children and in adults in Greenland. IPD cases from the pre-PCV13 period (January 1995–September 2010) were compared with the post-PCV13 period (September 2010–October 2020). Register data were collected from laboratory records, IPD reports, the national registry on admissions, and medical files. A total of 295 IPD cases were identified in the study period. Overall IPD incidence rate (IR) declined from the pre-PCV13 period to the post-PCV13 period (IR 23.3 to 15.3 per 100,000 person years). Overall IPD incidence among children decreased significantly, whereas overall IPD incidence among the elderly increased significantly. During the post-PCV13 period, the incidence of vaccine serotype (VT) IPD decreased in all ages, while the incidence of non-vaccine serotype (NVT) IPD increased. This increase was most substantial among elderly ≥60 years. In conclusion, the PCV13 has reduced incidence rates of IPD in Greenland. However, the increase in NVT IPD among the elderly is noteworthy, and sup-ports continued surveillance of IPD in the population of Greenland.

Changes in Invasive Pneumococcal Disease Caused by Streptococcus pneumoniae Serotype 1 Following Introduction of PCV10 and PCV13: Findings from the PSERENADE Project.

Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococcal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containing ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) comparing the pre-PCV10/13 period to each post-PCV10/13 year by site using a Bayesian multi-level, mixed-effects Poisson regression and all-site IRRs using a linear mixed-effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all-site IRR was 0.05 (95% credibility interval 0.04–0.06) for all ages, 0.05 (0.04–0.05) for <5 years of age, 0.08 (0.06–0.09) for 5–17 years, 0.06 (0.05–0.08) for 18–49 years, 0.06 (0.05–0.07) for 50–64 years, and 0.05 (0.04–0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3 + 0 schedule constrains generalizability and data from these settings are needed.

Invasive pneumococcal disease among adults with hematological and solid organ malignancies: A population-based cohort study

ObjectivesTo determine the risk of invasive pneumococcal disease (IPD) in adult cancer patients stratified by type of underlying malignancy, age, and capsular serotype and to assess herd effects of childhood pneumococcal vaccination. MethodsAll adult IPD cases reported to the Dutch pneumococcal surveillance system between 2004 and 2016 were included in this study. IPD incidence rates (IR) stratified by subtype of malignancy were calculated per 100 000 patient-years of follow-up. Incidence rate ratios (IRR) were calculated to compare IRs between groups. ResultsA total of 7167 IPD cases were included, of which 1453 were in patients with malignancies. For patients with hematological malignancies (HM) and solid organ malignancies (SOM), IRs were 482/100 000 and 79/100 000, respectively, compared with 15/100 000 in controls. The highest incidence was observed among patients with multiple myeloma, non-Hodgkin lymphoma, chronic lymphocytic leukemia, pancreatic cancer, and lung cancer (3299/100 000, 2717/100 000, 538/100 000, 559/100 000, and 393/100 000, respectively), and in patients ≥50 years old. Among HM patients, the incidence of IPD declined significantly after the implementation of infant pneumococcal vaccination (IRR 0.65, 95% confidence interval 0.51–0.84); among SOM patients, the decline was not statistically significant (IRR 0.88, 95% confidence interval 0.72–1.07). ConclusionsThe IPD disease burden in cancer patients remains high. Large differences in IPD incidence between the different types of cancer demand tailored guidance regarding pneumococcal vaccination.

911. Assessment of Representativeness of IPD Surveillance Conducted by the National Microbiology Laboratory of Canada

BackgroundUnderstanding the evolving epidemiology of Streptococcus pneumoniae serotypes is important for assessing the current and potential future immunization programs. In Canada, Invasive pneumococcal disease (IPD) is mandatory reportable to provincial/territorial public health. Provinces and territories voluntarily submit annual IPD data to the Canadian Notifiable Disease Surveillance System (CNDSS), which publishes information on IPD cases and incidence rates, however serotype data are not available. Provinces/territories also voluntarily submit IPD isolates to the National Microbiology laboratory (NML) for serotyping; provinces that conduct their own serotyping submit this information. The NML produces comprehensive IPD surveillance reports including serotype distribution; due to lack of population denominator, no incidence rates are available. The two surveillance programs are not linked. The objective of the study is to assess the representativeness of the NML surveillance as compared to the CNDSS and provincial reportable diseases databases.MethodsOver the study time period (2010-2017), we compared annual IPD case counts between the NML and CNDSS reports. Due to the difference in age grouping between CNDSS and NML, comparison was limited to these groups: all age, < 5, 5-14 and > 15 years. In addition, the IPD counts from NML were compared to data from four largest provinces.ResultsFor < 5 group, NML reported 91% of CNDSS case count whereas for 5-14 and > 15 years of age, it was 81% and 79%, respectively. Compared to the corresponding provincial databases, NML reported 91%, 97%, and 93% case counts for Ontario, British Columbia, and Alberta, respectively, while it was only 47% for Quebec. Further analysis revealed that the discrepancy in Quebec is the result of under-representation of >5 populations.Figure 1: Comparison of age stratified IPD case counts between CNDSS and NML Figure 2. Comparison of all age IPD case counts between NML and provincial databases ConclusionIPD surveillance conducted by NML has been instrumental to gain insight into the evolving epidemiology of S. pneumoniae serotypes in Canada. Comparisons of IPD counts from NML surveillance reports with reportable disease databases revealed different levels of concordance across provinces and age groups. The limitations of NML surveillance including incomplete or inconsistent reporting should be taken into consideration when interpreting the data.DisclosuresRajeev M. Nepal, PhD, Pfizer (Employee) Stephane B. Dion, PhD, Pfizer (Employee) Ana Gabriela Grajales, MD, Pfizer (Employee) Maria Major, B.Sc., MPH, Pfizer (Employee) Alejandro Cane, MD, Pfizer (Employee) Jelena Vojicic, MD, Pfizer (Employee)