Rates Of Invasive Pneumococcal Disease Research Articles

Long-term effect of pneumococcal conjugate vaccines on invasive pneumococcal disease incidence among people of all ages from national, active, laboratory-based surveillance in South Africa, 2005–19: a cohort observational study

In South Africa, 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2009 and 13-valent PCV (PCV13) was introduced in 2011, both in a two plus one schedule. We evaluated the ongoing effects of PCV on the prevention of invasive pneumococcal disease (IPD) over 15 years of sustained surveillance in South Africa before the COVID-19 pandemic. We conducted national, active, laboratory-based surveillance for IPD among all ages in South Africa, including isolate serotyping and susceptibility testing. We fitted linear regression models with vaccine covariates to imputed IPD case counts each year by serotype and age to compare expected and actual IPD cases in 2019, which was the main outcome. Vaccine effects were set to zero to identify expected incidence after the introduction of PCV7 and PCV13. From Jan 1, 2005, to Dec 31, 2019, surveillance identified 52 957 IPD cases. Among the 50 705 individuals with age data available, 9398 (18·5%) were infants aged younger than 2 years. Compared with expected case numbers (no vaccination) predicted using all available data, overall IPD rates among children younger than 2 years declined by 76·0% (percentage risk difference; 95% CI -79·0 to -72·8%) in 2019; notably, PCV7 and additional PCV13 serotype IPD rates declined by 95·5% (-97·0 to -93·4%) and 93·8% (-96·2 to-90·5%), respectively, whereas non-vaccine serotypes (NVTs) did not change significantly. Among adults aged 25-44 years, overall IPD declined by 50·4% (-54·2 to -46·3%), and PCV7 and additional PCV13 serotype IPD rates declined by 86·1% (-88·7 to -83·1%) and 77·2% (-80·9 to -73·0%), respectively, whereas NVTs increased by 78·5% (56·8 to 103·4%). Individuals aged older than 64 years also benefited from declines in IPD (-30·2%; -41·9 to -16·2%), but NVTs increased (234·9%; 138·1 to 379·4%). We documented sustained direct and indirect benefits of PCV across age groups, and NVT increases in adults older than 24 years. Higher valency PCVs would have the added benefit of preventing this residual disease. National Institute for Communicable Diseases of the National Health Laboratory Service (South Africa) and US Agency for International Development Antimicrobial Resistance Initiative, US Centers for Disease Control and Prevention.

Comparative effectiveness of pneumococcal vaccination strategies to prevent invasive pneumococcal disease: a population-based cohort study at the veterans health administration in the United States

ObjectivesComparative effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13), 23-valent polysaccharide vaccine (PPSV23), and their combinations for adults in preventing invasive pneumococcal disease (IPD) has yet to be thoroughly investigated. We aimed to estimate the comparative effectiveness of preventing IPD, using population-based data from the Veterans Health Administration (VHA) in the United States. MethodsWe included all patients who were between 65 and 74 years, had established primary care within VHA between 2005 and 2021, and had not received any prior pneumococcal vaccination. We measured time-to-event from cohort enrolment to the onset of IPD, considering death a competing risk event, and used Cox regression models to estimate cause-specific hazards. PCV13 only, PPSV23 only, PCV13 after PPSV23, and PPSV23 after PCV13 were incorporated into models as time-dependent covariates. Patient demographics and comorbidities were also included in the model. ResultsA total of 3 044 067 patients were enrolled in the cohort, with 863 958 deaths (28.4%) and 1731 cases of IPD (0.06%) during the study period. The overall incidence rate of IPD in this population was 5.36 per 100 000 patient-years. A total of 921 070 patients (30.3%) received at least one dose of effective pneumococcal vaccine. In multivariate analysis adjusted for comorbidities, PCV13 alone was not associated with the reduced risk of IPD, whereas PPSV23 had protective association with IPD incidence (adjusted hazard ratio [aHR], 0.70; 95% CI, 0.59–0.83). When combined, PCV13 followed by PPSV23 had a stronger protective association (aHR, 0.54; [0.36–0.83]) compared with PPSV23 followed by PCV13 (aHR, 0.73; [0.58–0.91]). Discussion: In this large cohort study at the VHA, the combination of PCV13 and PPSV23, particularly PCV13 followed by PPSV23, was associated with a lower risk of IPD, indicating additional benefits in combined vaccinations with potential importance in vaccination order. Further studies are needed to evaluate the effect of newer pneumococcal vaccines.

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...

Assessing the Impact of Pneumococcal Conjugate Vaccine Immunization Schedule Change From 3+0 to 2+1 in Australian Children: A Retrospective Observational Study.

In mid-2018, the Australian childhood 13-valent pneumococcal conjugate vaccine schedule changed from 3+0 to 2+1, moving the third dose to 12 months of age, to address increasing breakthrough cases of invasive pneumococcal disease (IPD), predominantly in children aged >12 months. This study assessed the impact of this change using national IPD surveillance data. Pre- and postschedule change 3-dose 13-valent pneumococcal conjugate vaccine breakthrough cases were compared by age group, serotype, and clinical syndrome. Annual rates of breakthrough cases were calculated (per 100 000) using respective birth cohort sizes and 3-dose vaccine coverage. Using time-series modelling, observed IPD rates in children aged <12 years were compared to that expected if the 3+0 schedule were continued. Over 2012-2022, rate of 3-dose breakthrough cases in children aged >12 months was 2.8 per 100 000 (n = 557; 11 birth cohorts). Serotype 3 replaced 19A as predominant breakthrough serotype (respectively, 24% and 65% in 2013 to 60% and 20% in 2022) followed by 19F. In breakthrough cases, the most frequent clinical phenotype was bacteremic pneumonia (69%), with meningitis accounting for 3%-4%. In cohorts eligible for 2+1 versus 3+0 schedules, rate of breakthrough cases was lower for all vaccine serotypes, except type 3 (incidence rate ratio, 0.50 [95% confidence interval, .28-.84] and 1.12 [0.71-1.76], respectively). Observed compared to expected IPD was 51.7% lower (95% confidence interval, -60.9 to -40.7%) for vaccine serotypes, but the change for nonvaccine types was not significant 12% (-9.6 to 39.7). The 2+1 schedule is likely superior to 3+0 for overall IPD control, a finding that may be worth consideration for other countries considering or using 3+0 PCV schedules.

Estimating geographical spread of Streptococcus pneumoniae within Israel using genomic data.

Understanding how pathogens spread across geographical space is fundamental for control measures such as vaccination. Streptococcus pneumoniae (the pneumococcus) is a respiratory bacterium responsible for a large proportion of infectious disease morbidity and mortality globally. Even in the post-vaccination era, the rates of invasive pneumococcal disease (IPD) remain stable in most countries, including Israel. To understand the geographical spread of the pneumococcus in Israel, we analysed 1174 pneumococcal genomes from patients with IPD across multiple regions. We included the evolutionary distance between pairs of isolates inferred using whole-genome data within a relative risk (RR) ratio framework to capture the geographical structure of S. pneumoniae. While we could not find geographical structure at the overall lineage level, the extra granularity provided by whole-genome sequence data showed that it takes approximately 5 years for invasive pneumococcal isolates to become fully mixed across the country.This article contains data hosted by Microreact.

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.

Effects of PCV10 and PCV13 on pneumococcal serotype 6C disease, carriage, and antimicrobial resistance

BackgroundThe cross-protection of pneumococcal conjugate vaccines (PCV) against serotype 6C is not clearly documented, although 6C represents a substantial burden of pneumococcal disease in recent years. A systematic review by the World Health Organization that covered studies through 2016 concluded that available data were insufficient to determine if either PCV10 (which contains serotype 6B but not 6A) or PCV13 (containing serotype 6A and 6B) conferred protection against 6C. MethodsWe performed a systematic review of randomized controlled trials and observational studies published between January 2010 – August 2022 (Medline/Embase), covering the direct, indirect, and overall effect of PCV10 and PCV13 against 6C invasive pneumococcal disease (IPD), non-IPD, nasopharyngeal carriage (NPC), and antimicrobial resistance (AMR). ResultsOf 2548 publications identified, 112 were included. Direct vaccine effectiveness against 6C IPD in children ranged between 70 and 85 % for ≥ 1 dose PCV13 (n = 3 studies), was 94 % in fully PCV13 vaccinated children (n = 2), and −14 % for ≥ 1 dose of PCV10 (n = 1). Compared to PCV7, PCV13 efficacy against 6C NPC in children was 66 % (n = 1). Serotype 6C IPD rates or NPC prevalence declined post-PCV13 in most studies in children (n = 5/6) and almost half of studies in adults (n = 5/11), while it increased post-PCV10 for IPD and non-IPD in all studies (n = 6/6). Changes in AMR prevalence were inconsistent. ConclusionsIn contrast to PCV10, PCV13 vaccination consistently protected against 6C IPD and NPC in children, and provided some level of indirect protection to adults, supporting that serotype 6A but not 6B provides cross-protection to 6C. Vaccine policy makers and regulators should consider the effects of serotype 6A-containing PCVs against serotype 6C disease in their decisions.

Incidence of pneumococcal disease in children ≤48 months old in the United States: 1998–2019

BackgroundPneumococcal disease (PD) is a major cause of morbidity and mortality among children, particularly in the youngest age groups. This study aimed to assess the incidence of PD over time by age group in young children with commercial or Medicaid coverage in the US. MethodsEpisodes of invasive pneumococcal disease (IPD), all-cause pneumonia (ACP), and acute otitis media (AOM) were identified in the MarketScan® Commercial and Medicaid claims databases using diagnosis codes among children aged ≤ 48 months with confirmed date of birth (DoB), at any time during the study period (1998–2019). DoB was assigned using diagnosis codes for birth or delivery using the child’s or mother’s medical claims to ensure accurate age determination. Annual incidence rates (IRs) were calculated as number of disease episodes/100,000 person-years (PY) for IPD and ACP and episodes/1,000 PY for AOM, for children aged 0–6, 7–12, 12–24, and 25–48 months. ResultsAnnual IPD IRs declined from 53 to 7 episodes/100,000 PY between 1998 and 2019 in commercially-insured and 58 to 9 episodes/100,000 PY between 2001 and 2019 in Medicaid-insured children. Annual ACP IRs declined from 5,600 to 3,952 episodes/100,000 PY, and from 6,706 to 4,521 episodes/100,000 PY, respectively, over these periods. In both populations, children aged 0–6 months had the highest incidence of IPD and inpatient ACP. Annual AOM IRs declined from 1,177 to 738 episodes/1,000 PY (commercially-insured) and 633 to 624 episodes/1,000 PY (Medicaid-insured), over these periods. IRs were higher in rural vs. urban areas for all disease manifestations. ConclusionsIncidence rates of IPD, ACP, and AOM decreased in children with commercial insurance and Medicaid coverage from 1998 to 2019. However, burden of disease remained substantial, with higher annual IRs for IPD and ACP for Medicaid-insured vs. commercially-insured children. IPD and inpatient ACP were most common in the youngest children 0–6 months old, followed by the 7–12-month age group.

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

Outcomes of pediatric community-acquired pneumonia before and after national pneumococcal immunization in Taiwan.

In Taiwan, the incidence of invasive pneumococcal disease (IPD) in children declined after the catch-up primary vaccination programs and the full national immunization program (NIP) with PCV13. The objective of the study was to investigate the clinical outcomes of pediatric community-acquired pneumonia (CAP) before and after the NIP. The study included patients aged 3 months to 17 years who were diagnosed with CAP and treated at the National Taiwan University Hospital between 2007 and 2019. Patients were assigned to three birth cohorts according to their birth years and vaccination eligibility: non-NIP, catch-up, and full NIP. We compared the rates of severe outcomes, including case fatality and pathogens. A total of 6557 patients who met the CAP criteria were enrolled during the study period. The case-fatality rate decreased from 3.2% (94/2984) in the non-NIP cohort to 0.3% (7/2176) in the catch-up cohort and 0.8% (11/1397) in the full NIP cohort (p < 0.001). Furthermore, there was a significant decrease in invasive ventilation from the non-NIP (17.9%) to both catch-up (6.8%) and full NIP cohorts (9.1%). The rate of IPD declined from the non-NIP cohort to the catch-up cohort (1.8% vs. 0.6%, p < 0.001) and from the catch-up to the full NIP cohort (0.6% vs. 0.07%, p = 0.014). In contrast, the rates of infections with other pathogens increased after NIP. The introduction of PCV13 showed significant reduction in case-fatality and IPD rates. The increasing rates of other pathogens warrant further surveillance for their clinical significance.

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.

Persistence of Pneumococcal Carriage among Older Adults in the Community despite COVID-19 Mitigation Measures.

Reported rates of invasive pneumococcal disease were markedly lower than normal during the 2020/2021 winter in the Northern Hemisphere, the first year after the start of the COVID-19 pandemic. However, little is known about rates of carriage of pneumococcus among adults during this period. Between October 2020-August 2021, couples in the Greater New Haven Area, USA, were enrolled if both individuals were aged 60 years and above and did not have any individuals under the age of 60 years living in the household. Saliva samples and questionnaires regarding social activities and contacts and medical history were obtained every 2 weeks for a period of 10 weeks. Following culture-enrichment, extracted DNA was tested using qPCR for pneumococcus-specific sequences piaB and lytA. Individuals were considered positive for pneumococcal carriage when Ct values for piaB were ≤40. Results. We collected 567 saliva samples from 95 individuals (47 household pairs and 1 singleton). Of those, 7.1% of samples tested positive for pneumococcus, representing 22/95 (23.2%) individuals and 16/48 (33.3%) households. Study participants attended few social events during this period. However, many participants continued to have regular contact with children. Individuals who had regular contact with preschool and school-aged children (i.e., 2 to 9 year olds) had a higher prevalence of carriage (15.9% versus 5.4%). Despite COVID-19-related disruptions, a large proportion of older adults continued to carry pneumococcus. Prevalence was particularly high among those who had contact with school-aged children, but carriage was not limited to this group. IMPORTANCE Carriage of Streptococcus pneumoniae (pneumococcus) in the upper respiratory tract is considered a prerequisite to invasive pneumococcal disease. During the first year of the COVID-19 pandemic, markedly lower rates of invasive pneumococcal disease were reported worldwide. Despite this, by testing saliva samples with PCR, we found that older adults continued to carry pneumococcus at pre-pandemic levels. Importantly, this study was conducted during a period when transmission mitigation measures related to the COVID-19 pandemic were in place. However, our observations are in line with reports from Israel and Belgium where carriage was also found to persist in children. In line with this, we observed that carriage prevalence was particularly high among the older adults in our study who maintained contact with school-aged children.

Control and Prevention of Invasive Pneumococcal Disease: A Current and Historical Perspective.

Although significant progress has been made in reducing the incidence of invasive pneumococcal disease (IPD) in children, IPD remains a continued threat. Since the introduction of pneumococcal conjugate vaccines (PCVs), rates of IPD and non-IPD have substantially decreased. However, serotype replacement reversed some of the benefits of PCV7 and, more recently, PCV13. Several replacement serotypes are antibiotic resistant, which is a cause of concern for providers. The introduction of the higher-valency conjugate vaccines PCV15 and PCV20 is expected to provide greater serotype coverage; unfortunately, these vaccines do not include some of the recently emerged serotypes. Recommendations for the use of the 23-valent polysaccharide vaccine in high-risk populations may be modified because of the effectiveness of the newer PCVs. Pediatricians must be aware of the new vaccine strategies for the prevention of IPD and the manifestations of IPD so that prompt empirical therapy can be initiated when treatment is required. [Pediatr Ann. 2023;52(3):e96-e101.].

Increase of invasive pneumococcal disease in children temporally associated with RSV outbreak in Quebec: a time-series analysis

Respiratory viruses have been previously suspected to trigger invasive pneumococcal disease (IPD). After progressive non-pharmaceutical interventions (NPI) lifting, an unusual RSV outbreak has been observed in the Fall 2021, raising concerns about the possible consequences on IPD. We aimed to analyse the evolution of IPD incidence across age-groups since NPI lifting, and its temporal association with respiratory viral infections. We conducted a time-series analysis using 1) population-based IPD surveillance data and 2) statistics from the laboratory surveillance network of respiratory viruses in the province of Quebec, Canada, from January 2013 to January 2022. The monthly IPD incidence was analysed by quasi-Poisson regression models across age-groups. The fraction of IPD incidence change potentially attributable to different viruses in 2021-2022 was estimated. A total of 7712 IPD cases were included. After a major decrease in IPD incidence from April 2020, IPD rate started to increase in <5-year-old children in October 2021, exceeding the pre-NPI trend (+62%). This was temporally associated with an unusual surge in RSV cases (+53% versus pre-NPI trend). During this 2021-22 surge, the fraction of IPD attributable to RSV dynamics in children was 77% (95% CI [33-100]). By contrast, the IPD incidence in older age-groups remained low, and was temporally associated with influenza dynamics. These results provide new evidence on the role of respiratory viruses in driving IPD dynamics, with possible differences between children and adults. In the coming future, the potential benefit of interventions targeting RSV, such as vaccines, for IPD prevention should be considered. The study was supported by a grant from the Quebec Ministry of Health and Social Services ('ministère de la Santé et des Services sociaux du Québec'). Publication was supported by a grant from "Fondation de l'Assistance Publique - Hôpitaux de Paris et de l'Alliance«Tous Unis contre le Virus » (Fondation de France/Institut Pasteur/APHP)". N.O. was supported by the ESPID (European Society of Pediatric Infectious Diseases) 2021-2023 Fellowship Award and the 2022 ISPPD (International Symposium on Pneumococci and Pneumococcal Diseases) Robert Austrian Research award.

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.

Impact of national pneumococcal vaccination program on invasive pneumococcal diseases in South Korea

Following the introduction of pneumococcal conjugate vaccines (PCVs), the rate of invasive pneumococcal disease (IPD) declined, however, IPDs replaced by serotypes that are not included in the vaccine have emerged. We describe the epidemiology of IPD in South Korea over a 4.5-year period, encompassing the impact following introduction of PCV10/13 and PPSV23 into the public immunization program, and assess serotype dynamics in pediatric and adult population. This was a nationwide, retrospective review of surveillance of all IPD cases in Korea between September 2014 to December 2019. We analyzed VT13 (serotypes included in 13-valent conjugate vaccine) and NVT (nonvaccine type) cases by age, sex, IPD type, vaccination status, and deaths. A total of 893 cases with serotype data were included; 306 (34%) VT13 cases and 587 (66%) NVT cases. Serotype 3 (n = 155) was the most common VT13 serotype, followed by serotypes 19A (n = 70) and 14 (n = 28). Among the NVTs, serotype 10A (n = 74) was the most common serotype, followed by serotypes 23A (n = 60) and 34 (n = 58). Persons who had PCV13 vaccination were at lower risk (aOR = 0.11, 95% CI 0.02–0.73, P = 0.022) of death compared to unvaccinated persons. Introduction of PCV10/13 and PPSV23 vaccination program has had different impacts on the serotype-specific IPD across age groups. The most common serotypes included serotypes 3 and 19A (VT13), and 10A, 23A, and 34 (NVT). Our findings suggest continued monitoring in the midst of new vaccine development, and a need to develop novel strategies to mitigate the IPDs from emerging pneumococcal serotypes.

Invasive Pneumococcal Disease and Long-Term Mortality Rates in Adults, Alberta, Canada.

The relationship between increased short-term mortality rates after invasive pneumococcal disease (IPD) has been frequently studied. However, the relationship between IPD and long-term mortality rates is unknown. IPD patients in Alberta, Canada, had clinical data collected that were linked to administrative databases. We used Cox proportional hazards modeling, and the primary outcome was time to all-cause deaths. First IPD events were identified in 4,522 patients, who had a median follow-up of 3.2 years (interquartile range 0.8‒9.1 years). Overall all-cause mortality rates were consistently higher among cases than controls at 30 days (adjusted hazard ratio [aHR] 3.75, 95% CI 3.29–4.28), 30‒90 days (aHR 1.56, 95% CI 1.27‒1.93), and >90 days (aHR 1.43, 95% CI 1.33–1.54). IPD increases risk for short, intermediate, and long-term mortality rates regardless of age, sex, or concurrent conditions. These findings can help clinicians focus on postdischarge patient plans to limit long-term effects after acute IPD infection.