Invasive Pneumococcal Disease Cases Research Articles

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.

Invasive Pneumococcal Disease Characterization in Adults and Subgroups aged < 60 years and ≥ 60 years in Bogota, Colombia

There is scarce information on the burden of invasive pneumococcal disease (IPD) among adults in low- and middle-income countries. This study aimed to describe the clinical outcomes and microbiological characteristics associated with IPD in adults and subgroups aged 18-59 years and ≥60 years in Colombia. A retrospective chart review study was conducted in five institutions of Bogotá from January 2011 to December 2017. Analyses were carried out for overall population and stratified by age group (18-59; ≥ 60 years). There were 169 IPD cases; median age was 58 years, 51.5% were male, and 80.5% had at least one comorbidity. Bacteremic pneumonia was the most common presentation (63.9%). The median length of hospital stay was 12 days with high healthcare resource utilization (HCRU): 58.6% required ICU and 53.3% inotropic support. Overall case-fatality rate (CFR) was 41.4%. Clinical outcomes were worse in patients ≥60 years old with significantly higher CFR and HCRU (ICU admission, mechanical ventilation, and inotropic support) compared to those aged 18-59 years. The most frequent serotypes were 3, 6 A/C, 14, and 19A. The sensitivity to penicillin in meningitis and non-meningitis isolates were 75% and 89.1% respectively. IPD was associated with a substantial burden in adults and worse clinical outcomes and HCRU in older adults in Colombia. Surveillance data combined with clinical outcomes have the potential to inform age-based pneumococcal vaccination policies.

Health and economic burden associated with 15-valent pneumococcal conjugate vaccine serotypes in Korea and Hong Kong

ABSTRACT Use of pneumococcal conjugate vaccines (PCVs) has greatly reduced the incidence of invasive pneumococcal disease (IPD). V114 (VAXNEUVANCE™, Merck Sharp & Dohme Corp. a subsidiary of Merck & Co. Inc. Kenilworth, NJ, USA) is a 15-valent PCV currently approved in adults in the United States, containing the 13 serotypes in licensed PCV13 and 2 additional serotypes (22F and 33F) which are important contributors to residual pneumococcal disease. This study quantified the health and economic burden of IPD attributable to V114 serotypes in hypothetical birth cohorts from Korea and Hong Kong. A Markov model was used to estimate the case numbers and costs of IPD in unvaccinated birth cohorts over 20 years. The model was applied to 3 scenarios in Korea (pre-PCV7, pre-PCV13, and post-PCV13) and to 2 scenarios in Hong Kong (pre-PCV7 and post-PCV13). For Korea, the model predicted 62, 26, and 8 IPD cases attributable to V114 serotypes in the pre-PCV7, pre-PCV13, and post-PCV13 scenarios, respectively. Costs of V114-type IPD fell from $1.691 million pre-PCV7 to $.212 million post-PCV13. For Hong Kong, the model estimated 62 V114-associated IPD cases in the pre-PCV7 scenario and 46 in the post-PCV13 scenario. Costs attributed to all V114 serotypes were $2.322 million and $1.726 million in the pre-PCV7 and post-PCV13 periods, respectively. Vaccine-type serotypes are predicted to cause continuing morbidity and cost in Korea (19A) and Hong Kong (3 and 19A). New pediatric pneumococcal vaccines must continue to protect against serotypes in licensed vaccines to maintain disease reduction, while extending coverage to non-vaccine serotypes.

Clinical characteristics, antimicrobial resistance, and risk factors for mortality in paediatric invasive pneumococcal disease in Beijing, 2012\u20132017

BackgroundTo analyse clinical characteristics, antibiotic susceptibility, and risk factors for mortality in paediatric invasive pneumococcal disease (IPD) in Beijing.MethodsPaediatric IPD patients in our hospital were retrospectively collected from 2012 to 2017. Clinical manifestations, laboratory tests, antimicrobial susceptibility and serotype of isolates, and risk factors for mortality of IPD were analysed.ResultsOverall, 186 IPD cases were enrolled. The major manifestations were meningitis (76), pneumonia with bacteraemia (60), bacteraemia without focus (21), and pneumonia with empyaema (22). Of 72 cases with underlying diseases, leukaemia (18.0%), congenital heart disease (15.3%), primary immunodeficiency disease (12.5%), nephrotic syndrome (12.5%), and cerebrospinal fluid leakage (12.5%) were most common. In total 96.9% of isolates would have been covered by the pneumococcal conjugate vaccine (PCV13), including 19F (32.8%), 19A (23.4%), 4 (17.2%), and 23F (9.4%). Nonsusceptibility rates of penicillin, cefotaxime, and cefepime among nonmeningitis patients increased between 2012 and 2017; The mortality rate was 21.5%. Meningitis, respiratory failure, multiple organ failure, and white blood cell count < 4000 cells/μL were independent risk factors for mortality.ConclusionMeningitis was the most common clinical manifestation of IPD, and was frequently associated with death. Strains in the PCV13 vaccine would cover most of the cases, and so wider use of PCV13 should be considered.

Recalibrated estimates of non-bacteremic and bacteremic pneumococcal community acquired pneumonia in hospitalized Canadian adults from 2010 to 2017 with addition of an extended spectrum serotype-specific urine antigen detection assay

Objective(s)In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017. MethodsS. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16–49, 50–64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)]. Results11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50–64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP. Conclusion(s)Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.

Cumulative occupational exposure to inorganic dust and fumes and invasive pneumococcal disease with pneumonia

PurposeOccupational exposure to inorganic dust and fumes in the year preceding disease has been associated with increased pneumococcal pneumonia risk, but the impact of prior cumulative exposure has not been characterized.MethodsWe studied 3184 cases of invasive pneumococcal disease with pneumonia. The case index date was the day the infection was diagnosed. We selected six controls for each case from the Swedish population registry; each control was assigned the index date of their corresponding case. We linked job histories to a job-exposure matrix to calculate a cumulative exposure index, intensity-years, by multiplying the duration (maximum 5 years) of each exposure with the level of exposure (0 for unexposed, 1 for low and 4 for high). We used conditional logistic analyses to estimate the odds ratio (OR) of invasive pneumococcal disease with pneumonia adjusted for comorbidities, educational level, income and other occupational exposures.ResultsTaking other occupational exposures into account, greater than 5 intensity-years of exposure to silica dust or to fumes was each associated with increased odds for invasive pneumococcal disease with pneumonia (OR 2.53, 95% CI 1.49–4.32) and (OR 2.24, 95% CI 1.41–3.55), respectively. Five intensity-years or less of exposure to silica dust or fumes manifested lower odds (OR 1.45, 95% CI 1.20–1.76) and (OR 1.05, 95% CI 0.94–1.16), respectively.ConclusionThis study adds evidence that the risk of pneumococcal pneumonia increases with increasing cumulative exposure to dust and fumes, indicating the importance of cumulative exposure.

Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network.

Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate. This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0-16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada. The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers. The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.

Invasive Pneumococcal Disease Case Series in Pediatric Inpatients: A Clinical Experience from South India

Invasive Pneumococcal Disease Case Series in Pediatric Inpatients: A Clinical Experience from South India

Reemergence of Invasive Pneumococcal Disease in Germany During the Spring and Summer of 2021.

BackgroundThe incidence of invasive pneumococcal disease (IPD) decreased worldwide in 2020 and the first quarter of 2021, concurrent with nonpharmaceutical interventions (NPIs) intended to stymie transmission of SARS-CoV-2. In 2021, the stringency of these NPI strategies has varied. We investigated age- and serotype-specific variations in IPD case counts in Germany in 2020–2021.MethodsIPD cases through 30 November 2021 were stratified by age group, serotype, or geographic location. IPD surveillance data in 2020–2021 were compared with (1) IPD surveillance data from 2015–2019, (2) mobility data during 2020 and 2021, and (3) NPI stringency data in 2020 and 2021.ResultsIPD incidence began to return toward baseline among children 0–4 years old in April 2021 and exceeded baseline by June 2021 (a 9% increase over the average monthly values for 2015–2019). Children aged 5–14 years and adults aged 15–34 or ≥80 years showed increases in IPD cases that exceeded baseline values starting in July 2021, with increases also starting in spring 2021. The age distribution and proportion of vaccine-serotype IPD remained comparable to those in previous years, despite lower overall case counts in 2020 and 2021. The percentage change in IPD incidence compared with the previous 5 years was correlated with changes in mobility and with NPI stringency.ConclusionsIPD levels began to return to and exceed seasonal levels in spring and summer 2021 in Germany, following sharp declines in 2020 that coincided with NPIs related to the coronavirus disease 2019 pandemic. Proportions of vaccine serotypes remained largely consistent throughout 2020–2021.

Estimates of the Health and Economic Burden of Pneumococcal Infections Attributable to the 15-Valent Pneumococcal Conjugate Vaccine Serotypes in the USA.

IntroductionDespite the availability of vaccines, pneumococcal disease (PD) is associated with high clinical and economic burden, mainly caused by non-vaccine serotypes and certain vaccine-type serotypes. V114 is a 15-valent pneumococcal conjugate vaccine (PCV) that contains two epidemiologically important serotypes, 22F and 33F, in addition to the 13 serotypes in 13-valent PCV (PCV13). This study quantified the epidemiologic and economic burden of PD attributable to V114 serotypes among adults in the USA.MethodsA Markov model was used to estimate the burden of V114 serotypes in a hypothetical, non-vaccinated cohort of US adults ≥ 19 years of age who were tracked from 2019 until death. The model calculated all the invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) cases, deaths, and costs. Economic burden was estimated from a healthcare payer perspective (2019 US dollars) and discounted at 3%.ResultsThe model estimated 415,229 and 10.3 million lifetime cases of V114-type IPD and NBPP, respectively. Serotypes 22F and 33F caused approximately 33% of IPD cases and 20% of NBPP cases, while serotype 3 accounted for approximately 36% of IPD cases and 13% of NBPP cases. V114 serotypes caused 472,063 total lifetime deaths. Total discounted lifetime costs attributable to V114 serotypes were $44.8 billion US dollars.ConclusionsIn this hypothetical model of a non-vaccinated cohort of US adults, V114 serotypes were associated with a substantial health and economic burden, the majority of which was attributable to serotypes 3, 22F, and 33F. The addition of V114 to the national vaccination recommendations may help to reduce the epidemiologic and economic burden associated with PD in adults ≥ 19 years of age in the USA by providing increased coverage of these serotypes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-022-00588-x.

The impact of 10-valent pneumococcal vaccine introduction on invasive disease in Fiji

SummaryBackgroundIn 2012, Fiji introduced the 10-valent pneumococcal conjugate vaccine (PCV10). We assessed the impact of PCV10 on invasive pneumococcal disease (IPD), probable bacterial or pneumococcal meningitis (PBPM), meningitis and sepsis 3-5 years post-introduction.MethodsLaboratory-confirmed IPD and PBPM cases were extracted from national laboratory records. ICD-10-AM coded all-cause meningitis and sepsis cases were extracted from national hospitalisation records. Incidence rate ratios were used to compare outcomes pre/post-PCV10, stratified by age groups: 1-23m, 2-4y, 5-9y, 10-19y, 20-54y, ≥55y. To account for different detection and serotyping methods in the pre-and post-PCV10 period, a Bayesian inference model estimated serotype-specific changes in IPD, using pneumococcal carriage and surveillance data.FindingsThere were 423 IPD, 1,029 PBPM, 1,391 all-cause meningitis and 7,611 all-cause sepsis cases. Five years post-PCV10 introduction, IPD declined by 60% (95%CI: 37%, 76%) in children 1-23m months old, and in age groups 2-4y, 5-9y, 10-19y although confidence intervals spanned zero. PBPM declined by 36% (95%CI: 21%, 48%) among children 1-23 months old, and in all other age groups, although some confidence intervals spanned zero. Among children <5y of age, PCV10-type IPD declined by 83% (95%CI; 70%, 90%) and with no evidence of change in non-PCV10-type IPD (9%, 95%CI; -69, 43%). There was no change in all-cause meningitis or sepsis. Post-PCV10, the most common serotypes in vaccine age-eligible and non-age eligible people were serotypes 8 and 23B, and 3 and 7F, respectively.InterpretationsOur study demonstrates the effectiveness of PCV10 against IPD in a country in the Asia-Pacific of which there is a paucity of data.FundingThis study was support by the Department of Foreign Affairs and Trade of the Australian Government and Fiji Health Sector Support Program (FHSSP). FHSSP is implemented by Abt JTA on behalf of the Australian Government.

POSC103 Pneumococcal Vaccination with 13-Valent Polysaccharide Conjugate Vaccine for Older Adults with Chronic Conditions: Budget Impact Analysis in Colombia

To determine the budget impact analysis of pneumococcal vaccination with 13-valent polysaccharide conjugate vaccine (PCV13) in adults 60 years of age and older with chronic conditions in Colombia A decision tree was developed comparing vaccinated adults 60 years of age and older with chronic risk conditions for pneumococcal diseases with no vaccination. The age-specific annual rates for outpatient and inpatient pneumonia, meningitis, bacteremia caused by Streptococcus pneumoniae were extracted from the literature for patients with chronic obstructive pulmonary diseases (COPD), diabetes, cardiovascular diseases, and cancer. The frequency of the medical conditions considering of the model was based on the national report. The effectiveness of PCV13 were estimated from the clinical trial in adults 65 years of age or older. The health care resources of the events were obtained for published national studies and the cost of vaccine dose was estimated from national database. Time horizon in the analysis was 10 years. Subgroup analysis was conducted for relevant risk group. The cost and events were discount with annual rate of 3%. The exchange rate used was 3.600 Colombian pesos/1 USD. Simulating a cohort of 25.000 patients, PCV13 prevent 185 cases of inpatient pneumonia, 3 cases of outpatient pneumonia, 118 cases of invasive pneumococcal diseases and 41 deaths compared to no vaccination. The savings associated to medical care would be 771.114 USD characterized mainly by inpatient pneumonia and bacteremia. The vaccination cost may vary 500.000 and 875.000 USD. The net savings would be 83.614 USD which can vary according to the price of the vaccine. The highest return on investment is were obtained in COPD patients due to the high risk of invasive pneumococcal disease and pneumonia. PCV13 immunization is most likely to lead substantial cost savings in the following 10 years after vaccination with high impact in the public health.

POSA198 Clinical and Economic Burden Attributable to Serotypes Included in Current and Future Pneumococcal Conjugate Vaccines in Argentinean Children Under Five Years of Age

After the 13-valent pneumococcal conjugate vaccine (PCV13) introduction into the National Immunization Program in Argentina for children in 2012, a significant reduction of pneumococcal disease was observed. PCVs in development, 15-valent (PCV15) and 20-valent (PCV20), are expected to expand pneumococcal disease coverage and address more pneumococcal disease burden due to inclusion of additional serotypes. Our objective was to estimate the annual clinical and economic burden caused by the serotypes included in currently licensed and investigational PCVs among Argentinean children under five years. A decision analytic model was used to calculate the burden of disease caused by serotypes contained in four PCVs. Epidemiologic, clinical, and cost data were estimated from published sources for children under five based on 2021 population figures. Invasive pneumococcal disease (IPD) serotype distribution by PCV formulation was derived from SIREVA II and used to extrapolate outcomes. Clinical outcomes included annual cases of IPD, inpatient and outpatient pneumonia, and acute otitis media (AOM), as well as deaths associated with IPD and outpatient pneumonia. Economic outcomes included direct costs by disease state and by each payer subsector. Based on reported serotype coverage, PCV20 is estimated to cover 55% of current pneumococcal disease, with 10-valent (PCV10), PCV13, and PCV15 covering 19%, 36% and 40%, respectively. Based on our assumptions, PCV20 serotypes caused more disease compared to other PCVs, causing a total of 352,973 annual cases. Of these, IPD represented an estimated 0.05%. Total direct attributable annual subsector costs were 29.1 million USD for private, 26.9 million USD for social security, and 22.3 million USD for public. Investigational PCVs that offer the broader serotype coverage will continue to protect infants against serotypes contained in current vaccines. PCV20 has the potential to deliver additional public health impact and economic value across all subsectors in Argentina.

Epidemiological characteristics in serotype 24 paediatric invasive pneumococcal disease according to an 11-year population-based study in Japan.

After the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), serotype replacement has occurred in Japan, and serotype 24 has become the most common serotype in paediatric invasive pneumococcal disease (IPD). To understand the characteristics of serotype 24-IPD in Japanese children in the post-PCV13 era, we conducted a retrospective study in children aged ≤15 years from 2010 to 2020 using a database of paediatric IPD surveillance in Chiba prefecture, Japan. We identified a total of 357 IPD cases and collected clinical information on 225 cases (24: 32 cases, non-24: 193 cases). Compared with the non-serotype 24-IPD, serotype 24-IPD was independently related to be <2 years of age [odds ratio (OR) 3.91, 95% confidence interval (CI) 1.47-10.44; P = 0.0064] and bacteremia (OR 2.28, 95% CI 1.01-5.13; P = 0.0475), as a result of the multivariate regression analysis. We also conducted a bacterial analysis, and the isolates of serotype 24-IPD had tendencies of PCG-susceptible (24: 100.0%, non-24: 61.3%; P < 0.0001) and macrolide-resistance (24: 100.0%, non-24: 87.3%; P = 0.0490). Their multilocus sequence typing was mostly ST2572 and the variants, which were unique to Japan. This tendency might have been a result of the progress made in the Japanese PCV13 immunisation programme.

Estimation of the incidence of hospitalization for non-invasive pneumococcal pneumonia in the Norwegian population aged 50 years and older.

Abstract The purpose of this study was to estimate simple measures of the burden of non-invasive pneumococcal pneumonia (PnPn) hospitalisations in those aged 50 years and older (50+) in Norway. We conducted a retrospective register-based study and used discharge codes from the Norwegian Patient Register (NPR). We identified episodes of non-invasive PnPn in 2015 to 2016 and predicted its incidence from 2015 to 2019 based on the trend found in notified invasive pneumococcal disease cases. Overall, we identified 45–46 hospital episodes per 100 000 population of non-invasive PnPn in 2015 and 2016, each episode taking 6–8 days, and with increasing incidence with higher age. Among all identified PnPn episodes, 3 out of 4 were classified as non-invasive. We predicted that the monthly number of non-invasive PnPn episodes ranges from 39 [95% confidence interval (CI) 24–55] in August to 97 (95% CI 74–134) in December. No annual trend was identified. This study indicates that the burden of non-invasive PnPn hospitalisation has a substantial impact on the health and health care use of the 50+ population in Norway, despite the childhood immunisation programme. Many hospitalisations may be prevented through vaccination.

Childhood Invasive Bacterial Disease in Kathmandu, Nepal (2005-2013).

Invasive bacterial disease (IBD; including pneumonia, meningitis, sepsis) is a major cause of morbidity and mortality in children in low-income countries. We analyzed data from a surveillance study of suspected community-acquired IBD in children <15 years of age in Kathmandu, Nepal, from 2005 to 2013 before introduction of pneumococcal conjugate vaccines (PCV). We detailed the serotype-specific distribution of invasive pneumococcal disease (IPD) and incorporated antigen and PCR testing of cerebrospinal fluid (CSF) from children with meningitis. Enhanced surveillance of IBD was undertaken during 2005-2006 and 2010-2013. During enhanced surveillance, a total of 7956 children were recruited of whom 7754 had blood or CSF culture results available for analysis, and 342 (4%) had a pathogen isolated. From 2007 to 2009, all 376 positive culture results were available, with 259 pathogens isolated (and 117 contaminants). Salmonella enterica serovar Typhi was the most prevalent pathogen isolated (167 cases, 28% of pathogens), followed by Streptococcus pneumoniae (98 cases, 16% pathogens). Approximately, 73% and 78% of pneumococcal serotypes were contained in 10-valent and 13-valent PCV, respectively. Most cases of invasive pneumococcal disease (IPD) were among children ≥5 years of age from 2008 onward. Antigen and PCR testing of CSF for pneumococci, Haemophilus influenzae type b and meningococci increased the number of these pathogens identified from 33 (culture) to 68 (culture/antigen/PCR testing). S. enterica serovar Typhi and S. pneumoniae accounted for 44% of pathogens isolated. Most pneumococcal isolates were of serotypes contained in PCVs. Antigen and PCR testing of CSF improves sensitivity for IBD pathogens.

1181. Serotype Distribution by Age of Remaining Invasive Pneumococcal Disease After Long-Term PCV10/13 Use: The PSERENADE Project

BackgroundPneumococcal conjugate vaccines (PCV) have reduced invasive pneumococcal disease (IPD) (see other PSERENADE abstract), of which > 70% was vaccine-type pre-PCV. We described the serotype (ST) distribution of remaining IPD in countries with mature infant PCV10/13 programs.MethodsIPD ST distribution data were obtained directly from surveillance sites, supplemented with published literature. Mature programs were defined as exclusive use of PCV10 or PCV13 for at least 5-7 years (depended on if prior PCV7 use and/or PCV10/13 catch-up) with primary series uptake > 70%. The distribution was estimated using a multinomial Dirichlet regression, stratified by PCV product and age (< 5 years, ≥ 50 years).ResultsSerotyped IPD cases from 42 PCV13- (n=78,912) and 12 PCV10-using sites (n=8,429) in 41 countries were analyzed. Most sites were from high-income countries (67%) and used a booster dose schedule (81%). For low- and middle-income countries, only 5 and 7 sites had more than 20 eligible cases for children and adults, respectively. In PCV10 sites, 10.0% (95% CI: 6.3-12.9%) and 15.5% (95% CI: 13.4-19.3%) of the remaining IPD during the mature period was PCV10-type among children and adults, respectively (Figure 1). For PCV13 sites, PCV13-type was 26.4% (95% CI: 21.3-30.0%) among children and 29.5% (95% CI: 27.5-33.0%) among adults. PCV20-, PCV24-, and PPV23-type cases ranged from 62-72% across all age and PCV-use groups. ST 19A was the leading ST at PCV10 sites, though more so for children (30.6%, 95% CI: 18.2-43.1%) than adults (14.8%, 95% CI: 11.9-17.8%; Figure 2). ST 3 was a top ST in both PCV10 and PCV13 sites, causing about 9% of cases in children and 14% in adults. ST 6C was the third most common ST in PCV10 sites, causing 6% of cases in both age groups. Some top non-PCV13 STs are included in higher-valent investigational PCVs (15BC, 12F, 22F, 8, 9N) but others are not (24F, 23B, 23A, 15A). Figure 1. Percentage of IPD cases in the mature PCV10/13 period due to serotypes included in current and upcoming products. Serotype (ST) 3 is illustrated separately in lighter purple in the bars corresponding to products that include ST3 due to the uncertain effectiveness against ST3 in current products. ST6C is illustrated in grey above the bars where ST6A is included. Although ST6C is not included in PCV10 or PCV13, PCV13 offers cross-protection through ST6A. ST6A also benefits from cross-protection with ST6B, included in both PCV10 and PCV13. Therefore, ST6A causes a very small fraction of disease in both settings and age groups, and it is not shown. Confidence intervals do not include ST6C, as this serotype is not included in PCV10/13. PCV13 is Pfizer’s Prevnar13/Prevenar13; PCV10 is GSK’s Synflorix.Figure 2. Serotype-specific distribution of IPD in the mature PCV10/13 period. Serotypes are colored by the lowest valency PCV product they are included in. The “x” in the PCV legend represents the extra serotypes included in that product relative to the next lower product (i.e., PCV13x includes serotypes 3, 6A, and 19A not in PCV10). Serotype (ST) 6C is colored separately because, although it is not included in any product, it is covered through cross-protection with PCV13-type serotype 6A. PCV13 is Pfizer’s Prevnar13/Prevenar13; PCV10 is GSK’s Synflorix.ConclusionIPD due to vaccine STs was low for both children and adults in countries with mature PCV programs. ST distribution of remaining IPD differed between PCV10 and PCV13 sites and between age groups. Higher-valency PCVs under evaluation target over half of remaining IPD cases, but some prevalent STs are not included in known investigational products.Disclosures Maria Deloria Knoll, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)

183. Decrease in Invasive Pneumococcal Disease in 7 United States Children’s Hospitals during the COVID-19 Pandemic

BackgroundDuring the 2020 SARS-CoV-2 pandemic, physical distancing and mask use guidelines were implemented resulting in a decline in the number of infections caused by influenza, respiratory syncytial virus and otitis media. A surveillance analysis from England and Taiwan showed a decline in invasive pneumococcal disease (IPD) (Clin Infect Dis. 2021;72: e65-75 and J Infect. 2021;82:296-297). We hypothesized that COVID mitigation efforts resulted in a decrease in incidence of pediatric IPD within the U.S. during 2020 compared to previous years.MethodsWe reviewed all cases of IPD among 7 children’s hospitals from the U.S. Pediatric Multicenter Pneumococcal Surveillance Group from 2017-2020. IPD was defined by the isolation of Streptococcus pneumoniae from normally sterile sites (eg. blood, cerebrospinal, pleural, synovial or peritoneal fluid). Pneumococcal pneumonia was defined as an abnormal chest radiograph in the presence of a positive blood, pleural fluid or lung culture. Mastoiditis was identified by positive middle ear, subperiosteal abscess or mastoid bone culture. Serotypes were determined by the capsular swelling method. Hospital admission numbers were obtained for incidence calculations. Statistical analyses were performed using STATA11. A p< 0.05 was considered significant.ResultsA total of 410 IPD cases were identified. The cumulative incidence of IPD (0-22 years of age) decreased from 99.2/100,000 admissions in 2017-2019 to 53.8/100,000 admissions in 2020 (risk ratio 0.54, CI: 0.40-0.72, p< 0.00001). Pneumococcal bacteremia and pneumonia decreased significantly in 2020 (p< 0.05), and although not statistically significant, there were fewer cases of meningitis and mastoiditis when compared to previous years (p=0.08) (Figure 1). Sex, race, age or presence of comorbidities were not significantly different between groups. Most common serotypes in 2020 were 35B, 3 and 15B/C (Figure 2). ConclusionThe observed decline in IPD cases during the first year of the SARS-CoV-2 pandemic is likely associated with mask use and physical distancing limiting transmission of S. pneumoniae via droplets and viral infections frequently preceding IPD. These precautions might be useful in the future to decrease IPD, especially in high-risk patients.Disclosures Sheldon L. Kaplan, MD, Pfizer (Research Grant or Support) Tina Q. Tan, MD, GSK (Individual(s) Involved: Self): Advisor or Review Panel member, Grant/Research Support; ILiAD (Individual(s) Involved: Self): Advisor or Review Panel member; Merck (Individual(s) Involved: Self): Advisor or Review Panel member, Grant/Research Support; Moderna (Individual(s) Involved: Self): Advisor or Review Panel member; Pfizer (Individual(s) Involved: Self): Advisor or Review Panel member Pia S. Pannaraj, MD, MPH, Pfizer (Grant/Research Support)Sanofi-Pasteur (Advisor or Review Panel member)Seqirus (Advisor or Review Panel member) Larry Givner, MD, AstraZeneca (Advisor or Review Panel member) Kristina G. Hulten, PhD, Pfizer (Research Grant or Support)

1325. Recalibrating Estimates of Pneumococcal Disease in Hospitalized Canadian adults from 2010 to 2017 with Use of an Extended Spectrum Serotype-specific Urine Antigen Detection

BackgroundPneumococcal vaccine recommendations in Canada include both age- and risk-based guidance. This study aimed to describe the burden of vaccine-preventable pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) by age in hospitalized adults. MethodsActive surveillance for all-cause CAP and IPD in hospitalized adults was performed from 2010 to 2017, including laboratory results, patient demographics, and outcomes. Streptococcus pneumoniae was detected using blood and sputum culture, or urine antigen detection (UAD). Serotype was assigned using Quellung reaction, PCR, or serotype-specific UADs spanning the 24 serotypes in PCV13 and PPV23 vaccines. Data were categorized by age (16-49, 50-64, 65+, and 50+ years) and over time. Results11129 ACP cases and 216 cases of IPD (non-CAP) were identified. A laboratory test for S. pneumoniae was performed in 8912 of ACP cases, identifying 1264 (14.2%) as pCAP. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These serious outcomes, as well as mortality, were more prominent in bacteremic pCAP and IPD. Risk factors for death in pCAP included aged 75+ years, immune compromising conditions, and BMI < 18.5. When categorized by age, the proportion of individuals aged 65+ years for pCAP and IPD was 49.8% and 48.6%, and the 50-64 year age cohort represented 31.3% and 29.9%, respectively. The contributions of PCV13 and PPV23 serotypes remained relatively stable over time, and overall represented 57.6% and 90.9% for pCAP, and 35.0% and 72.0% for IPD, respectively. ConclusionSeven years following infant PCV13 immunization programs in Canada, PCV13 and PPV23 serotypes in pCAP and IPD remained predominant causes of pneumococcal disease. Serious outcomes were particularly evident in adults 50+, suggesting pneumococcal vaccines should be encouraged in this age group.Disclosures Jason J. LeBlanc, PhD, FCCM, D[ABMM], GSK (Research Grant or Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support) Todd F Hatchette, MD, GSK (Grant/Research Support)Pfizer (Grant/Research Support) Melissa K. Andrew, MD, PhD, GSK (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member)Sanofi (Consultant, Grant/Research Support, Advisor or Review Panel member)Seqirus (Advisor or Review Panel member) Allison McGeer, MSc,MD,FRCPC,FSHEA, GlaxoSmithKline (Advisor or Review Panel member)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Louis Valiquette, MD, M.Sc., Cubist (Consultant)GSK (Grant/Research Support)Merck (Consultant)Optimer (Consultant)Pfizer (Grant/Research Support) Shelly McNeil, FRCPC, MD, GSK (Grant/Research Support)Pfizer (Grant/Research Support)Sinofi Pasteur (Grant/Research Support)

21. Systematic Review and Meta-Analysis of Pneumococcal Vaccine Effectiveness against Invasive Pneumococcal Disease among Adults

Abstract Background Two new pneumococcal conjugate vaccines (PCVs), PCV15 and PCV20, are anticipated to be licensed for use in U.S. adults in 2021. To help inform the U.S. Advisory Committee on Immunization Practices’ discussions on pneumococcal vaccine use among adults, we conducted a systematic review and meta-analysis. We specifically looked at efficacy or effectiveness of PCV13 and pneumococcal polysaccharide vaccine (PPSV23) against invasive pneumococcal disease (IPD) in adults. Methods We conducted a search of English literature published from 1998 – February 2021 on PCV13 and PPSV23 efficacy or effectiveness studies using eight major databases. Studies targeting adults with immunocompromising conditions were excluded. Title and abstract screening of identified studies and data abstraction were performed by two reviewers. Results were stratified by vaccine product, outcome evaluated (vaccine type (VT) or all IPD), study design, and effect measure. Random effects models were used to pool estimates by stratum. Results Of 3,422 citations reviewed, we identified 26 IPD studies; 4 on PCV13, 22 on PPSV23, 18 with all IPD, and 17 with VT-IPD (Table) as an outcome. Only one randomized-controlled trial (RCT) was identified for PCV13 with an efficacy of 52% (95% CI: 22%, 77%) against all IPD and 75% (95% CI: 41%, 91%) against VT-IPD. A pooled vaccine effectiveness (VE) estimate from three observational studies evaluating PCV13 was 56% (95% CI: 32%, 71%; I2 =12.8) against VT-IPD. Two RCTs evaluating PPSV23 reported efficacies against all IPD ranging between 79-86%; an additional RCT reported no IPD cases during RCT. Vaccine effectiveness estimates from 14 observational studies evaluating PPSV23 ranged between 29-76% against all IPD. Pooled VE estimates from 12 observational studies showed PPSV23 effectiveness against VT-IPD was 38% (95% CI: 28% to 46%; I2 =40.8). Table. Efficacy and effectiveness studies against vaccine-type invasive pneumococcal disease Conclusion Evidence suggests both pneumococcal vaccines are effective against VT-IPD in adults. Given that PCV15 and PCV20 are expected to be licensed based on immunogenicity data and no clinical efficacy data are available for these new vaccines, the findings from this review will help inform policy discussions on use of the new PCVs among adults. Disclosures All Authors: No reported disclosures