Episodes Of Invasive Pneumococcal Disease Research Articles

Severe Invasive Pneumococcal Disease Caused by Serotype 19A in Children Under Five Years in Tāmaki Makaurau Auckland, Aotearoa New Zealand.

Increases in childhood invasive pneumococcal disease (IPD) have been reported in several countries following the easing of COVID-19 pandemic mitigations. In Aotearoa New Zealand (AoNZ), a surge in IPD is occurring in young children concurrent with changes in pneumococcal vaccines and declining immunization coverage. We sought to examine epidemiologic and clinical features of IPD among children under 5 years in a large urban region of AoNZ in the 3 years post-COVID-19. Demographic, clinical and laboratory data were collated from children under 5 years with Streptococcus pneumoniae identified from normally sterile sites between January 1, 2021, and December 31, 2023, in Tāmaki Makaurau Auckland, AoNZ. We identified 93 episodes of IPD (annual incidence of 18-40 cases per 100,000 population per year). Serotype was identified in 68 episodes and 46 (68%) were serotype 19A. Incidence was higher in Pacific children compared with non-Māori, non-Pacific children (incidence rate ratio: 2.3; 95% confidence interval: 1.4-3.7). Bacteremia occurred in 65 (70%) episodes, empyema in 47 (51%), meningitis in 11 (12%) and hemolytic uremic syndrome in 7 (7.5%). All cases of hemolytic uremic syndrome and empyema were only among children with serotype 19A. Two children died, both had serotype 19A, and 13/91 survivors (14%) experienced serious sequelae. The use of the pneumococcal conjugate vaccine with lower valency and easing of COVID-19 containment measures each may have contributed to an increase in IPD in AoNZ. Serotype 19A is associated with empyema and causes severe disease in young children. Urgent efforts are required to improve PCV13 coverage in AoNZ.

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.

Inborn Errors of Immunity in Children With Invasive Pneumococcal Disease: A Multicenter Prospective Study.

In settings with universal conjugate pneumococcal vaccination, invasive pneumococcal disease (IPD) can be a marker of an underlying inborn error of immunity. The aim of this study was to determine the prevalence and characterize the types of immunodeficiencies in children presenting with IPD. Multicenter prospective audit following the introduction of routinely recommended immunological screening in children presenting with IPD. The minimum immunological evaluation comprised a full blood examination and film, serum immunoglobulins (IgG, IgA and IgM), complement levels and function. Included participants were children in whom Streptococcus pneumoniae was isolated from a normally sterile site (cerebrospinal fluid, pleura, peritoneum and synovium). If isolated from blood, features of sepsis needed to be present. Children with predisposing factors for IPD (nephrotic syndrome, anatomical defect or malignancy) were excluded. Overall, there were 379 episodes of IPD of which 313 (83%) were eligible for inclusion and 143/313 (46%) had an immunologic evaluation. Of these, 17/143 (12%) were diagnosed with a clinically significant abnormality: hypogammaglobulinemia (n = 4), IgA deficiency (n = 3), common variable immunodeficiency (n = 2), asplenia (n = 2), specific antibody deficiency (n = 2), incontinentia pigmenti with immunologic dysfunction (n = 1), alternative complement deficiency (n = 1), complement factor H deficiency (n = 1) and congenital disorder of glycosylation (n = 1). The number needed to investigate to identify 1 child presenting with IPD with an immunologic abnormality was 7 for children aged under 2 years and 9 for those 2 years and over. This study supports the routine immune evaluation of children presenting with IPD of any age, with consideration of referral to a pediatric immunologist.

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.

Economic burden of acute otitis media, pneumonia, and invasive pneumococcal disease in children in the United States after the introduction of 13-valent pneumococcal conjugate vaccines during 2014–2018

BackgroundStreptococcus pneumoniae remains a leading cause of morbidity, mortality, and healthcare resource utilization (HRU) among children. This study quantified HRU and cost of acute otitis media (AOM), pneumonia, and invasive pneumococcal disease (IPD).MethodsThe IBM MarketScan® Commercial Claims and Encounters and Multi-State Medicaid databases from 2014 to 2018 were analyzed. Children with AOM, all-cause pneumonia, or IPD episodes were identified using diagnosis codes in inpatient and outpatient claims. HRU and costs were described for each condition in the commercial and Medicaid-insured populations. National estimates of the number of episodes and total cost ($US 2019 for each condition were extrapolated using data from the US Census Bureau.ResultsApproximately 6.2 and 5.6 million AOM episodes were identified in commercial and Medicaid-insured children, respectively, during the study period. Mean cost per AOM episode was $329 (SD $1505) for commercial and $184 (SD $1524) for Medicaid-insured children. A total of 619,876 and 531,095 all-cause pneumonia cases were identified among commercial and Medicaid-insured children, respectively. Mean cost per all-cause pneumonia episode was $2304 (SD $32,309) in the commercial and $1682 (SD $19,282) in the Medicaid-insured population. A total of 858 and 1130 IPD episodes were identified among commercial and Medicaid-insured children, respectively. Mean cost per IPD episode was $53,213 (SD $159,904) for commercial and $23,482 (SD $86,209) for the Medicaid-insured population. Nationally, there were over 15.8 million cases of AOM annually, with total estimated cost of $4.3 billion, over 1.5 million cases of pneumonia annually, with total cost of $3.6 billion, and about 2200 IPD episodes annually, for a cost of $98 million.ConclusionsThe economic burden of AOM, pneumonia, and IPD among US children remains substantial. IPD and its manifestations were associated with higher HRU and costs per episode, compared to AOM and all-cause pneumonia. However, owing to their higher frequencies, AOM and all-cause pneumonia were the main contributors to the economic burden of pneumococcal disease nationally. Additional interventions, such as the development of pneumococcal conjugate vaccinees with sustained protection of existing vaccine type serotypes as well as broader inclusion of additional serotypes, are necessary to further reduce the burden of disease caused by these manifestations.

Healthcare resource utilisation and cost of pneumococcal disease from 2003 to 2019 in children ≤17 years in England.

To estimate healthcare resource utilisation (HCRU) and costs associated with pneumococcal disease (PD) in children aged ≤17 years in England from 2003-2019. A retrospective study in children aged ≤17 years was conducted using the Clinical Practice Research Datalink Gold primary care database and Hospital Episodes Statistics Admitted Patient Care database from 2003-2019. Episodes of invasive pneumococcal disease (IPD) were identified in hospital, pneumococcal pneumonia (PP) and all-cause pneumonia (ACP) episodes in primary care and in hospital, and acute otitis media (AOM) episodes in primary care. General practitioner (GP) visits and inpatient admission yearly rates were calculated per 1,000 persons. The average inpatient and primary care cost per episode were calculated. The Mann-Kendall test was used to assess monotonic time trends. 1,500,686 children were followed from 2003-2019. The highest average inpatient cost per episode [£34,255 (95%CI 27,222-41,288)] was in IPD, followed by ACP [£3,549 (95%CI 3,405-3,693)] and PP [£1,498 (95%CI 1,153-1,843)]. The highest primary care costs per episode were in AOM [£48.7 (95%CI 48.7-48.7)], followed by PP [£38.4 (95%CI 37.0-39.7)] and ACP [£28.6 (95%CI 28.2-29.1)]. The highest inpatient admission and GP visits yearly rates were observed in children aged <2 years. Across years, a significant decrease in GP visits yearly rates was observed for PP, ACP and AOM in children overall (p-value<0.001). A decrease in primary care costs was observed for ACP (p-value<0.001). There was an increasing trend in AOM primary care costs (p-value<0.001). No significant trends were observed in inpatient admission yearly rates in PP, ACP or IPD and inpatient costs per episode in PP, ACP and IPD. From 2003-2019, primary care HCRU and costs decreased (except for PP cost), but no trends in inpatient HCRU and costs were observed. The economic burden of pneumonia, IPD and AOM remains substantial in children aged ≤17 years in England.

Healthcare resource utilization and cost of pneumococcal disease in children in Germany, 2014–2019: a retrospective cohort study

BackgroundSince the introduction of higher valency pneumococcal conjugate vaccines in 2009, recent estimates on the economic burden of pediatric pneumococcal disease (PD) in Germany have been lacking. This study estimates healthcare resource utilization (HCRU) and medical cost associated with PDs in children < 16 years old in Germany from 2014–2019.MethodsA nationally representative sample from the Institute for Applied Health Research (InGef) German claims database was used, covering approximately 5% of the total German population. Episodes of pneumococcal pneumonia (PP), all-cause pneumonia (ACP), invasive pneumococcal disease (IPD), and acute otitis media (AOM) in children aged < 16 years were identified using ICD-10-GM codes. HCRU was estimated from annual rates of outpatient visits, outpatient antibiotic prescriptions and inpatient admissions, divided by person-years (PY) at-risk. Average direct medical costs per episode were estimated as the total cost of all HCRU, divided by the total number of episodes. The Mann–Kendall test was used to assess monotonic time trends from 2014–2019.Results During 2014–2019, 916,805 children aged < 16 years were followed up for a total of 3,608,716 PY. The average costs per episode for out-versus inpatient care associated with PP and ACP were €67 (95% CI 58–76) versus €2,606 (95% CI 1,338–3,873), and €63 (95% CI 62–63) versus €620 (95% CI 598–641), respectively. For IPD, the average medical cost per episode for out-versus inpatients were €30 (95% CI 19–42) versus €6,051 (95% CI 3,323–8,779), respectively. There were no significant trends in HCRU or costs for IPD or pneumonia over the study period, except for a significant reduction in ACP outpatient visits. A significant decrease in rate of outpatient visits and antibiotic prescribing for recurrent AOM was observed, in addition to an increase in rates of hospital admissions for simple AOM. This was paralleled by a significant increase in inpatient costs per episode for treating AOM overall, and simple AOM, over the study period.Conclusions The HCRU and cost per episode of pneumonia and IPD did not vary significantly from 2014–2019, but increased for AOM. The economic burden of pneumonia, IPD, and AOM remains substantial in Germany.

Incidence of pneumococcal disease from 2003 to 2019 in children ≤17 years in England

BackgroundPneumococcal disease is a leading cause of communicable disease morbidity and mortality globally. We aimed to estimate invasive pneumococcal disease (IPD), pneumococcal pneumonia (PP) and all-cause pneumonia (ACP) incidence rates (IRs) in children aged 0–17 years in England from 2003 to 2019.MethodsA retrospective study in children ≤17 years old from 2003 to 2019 using the Clinical Practice Research Datalink (CPRD) Gold and Hospital Episodes Statistics Admitted Patient Care (HES APC) databases. IPD episodes were identified in hospital records (HES APC). PP (caused by Streptococcus pneumoniae only) and ACP episodes (caused by any pathogen) were identified in primary care (CPRD) and in hospital records (HES APC). Annual IRs by age-group were calculated as the number of episodes/person-years (PY) at risk, with 95% confidence intervals (95% CI). Interrupted time series analyses were conducted to assess changes in IRs across the post-PCV7 (2007–2009), early post-PCV13 (2011–2014) and late post-PCV13 (2015–2019) periods compared to the pre-PCV7 period (2003–2005) using generalized linear models.Results170 IPD episodes, 769 PP episodes and 12,142 ACP episodes were identified in 1,500,686 children in 2003–2019. The overall IPD, PP and ACP IRs (per 100,000 PY) were 2.29 (95% CI 1.96–2.66), 10.34 (95% CI 9.62–11.10) and 163.37 (95% CI 160.47–166.30), respectively. The highest IPD, PP and ACP IRs were observed in children aged < 2 years compared to older children (2–4 and 5–17 years). IPD IRs decreased between the pre-PCV7 period and the late post-PCV13 period from 3.28 (95% CI 2.42–4.33) to 1.41 (95% CI 0.80–2.29), IRR 0.28 (95% CI 0.09–0.90), p-value 0.033. PP IRs declined between the pre-PCV7 period and the late post-PCV13 period from 14.65 (95% CI 12.77–16.72) to 3.87 (95% CI 2.81–5.20), IRR 0.19 (95% CI 0.09–0.38), p-value < 0.001. ACP IRs declined between the pre-PCV7 period and the late post-PCV13 period from 167.28 (95% CI 160.78–173.96) to 124.96 (95% CI 118.54–131.63), IRR 0.77 (95% CI 0.66–0.88), p-value < 0.001.ConclusionsThe clinical burden of IPD, PP and ACP declined in children in England aged 0–17 years between 2003 and 2019, especially in the late post-PCV13 period. This study highlights the importance of PCV vaccination in reducing the burden of PD and ACP in children in England.

Invasive Pneumococcal Disease in High-risk Children: A 10-Year Retrospective Study.

Despite the availability of conjugate pneumococcal vaccines, children with high-risk conditions remain vulnerable to invasive pneumococcal disease (IPD). This study sought to describe IPD prevalence, vaccination and outcomes among high-risk children. We used International Classification of Disease10 discharge and microbiology codes to identify patients hospitalized for IPD at a large pediatric hospital from January 1, 2009, to December 31, 2018. Patients were considered high-risk if they had: primary immunodeficiency, asplenia, transplant, active malignancy, sickle cell disease, cochlear implant, nephrotic syndrome, chronic lung disease, cerebrospinal fluid leak, HIV or used immunosuppressive therapy. In total 94 high-risk patients were hospitalized for IPD. The most common high-risk conditions included malignancy (n = 33, 35%), solid-organ or bone marrow transplant (n = 17, 18%) and sickle cell disease (n = 14, 15%). Bacteremia was the most common presentation (n = 81, 86%) followed by pneumonia (n = 23, 25%) and meningitis (n = 9, 10%). No deaths occurred. Of 66 patients with known pneumococcal vaccination status, 15 (23%) were unvaccinated, and 51 (77%) received at least one dose of a pneumococcal vaccine; 20 received all four recommended pneumococcal conjugate vaccine (PCV) doses. Only three children received PPSV23. Of 20 children with no or partial (<3 doses) immunization, 70% (14) of IPD episodes were due to vaccine-preventable serotypes. Of 66 known IPD serotypes, 17% (n = 11) were covered by PCV13, 39% (n = 26) were covered by PPSV23 and 39% (n = 26) were nonvaccine serotype. Despite the availability of effective pneumococcal vaccines, IPD persists among children with high-risk conditions. Improving PCV13 and PPSV23 vaccination could significantly reduce IPD; most episodes were due to vaccine-preventable serotypes in incompletely immunized patients.

Genomic features of predominant non-PCV13 serotypes responsible for adult invasive pneumococcal disease in Spain.

Although pneumococcal conjugate vaccines (PCVs) effectively prevent invasive pneumococcal disease (IPD), serotype replacement has occurred. We studied the pangenome, antibiotic resistance mechanisms and presence of mobile elements in predominant non-PCV13 serotypes causing adult IPD after PCV13 vaccine introduction in Spain. We conducted a multicentre study comparing three periods in six Spanish hospitals and analysed through whole genome sequencing representative strains collected in the pre-PCV13, early-PCV13 and late-PCV13 periods. Among 2197 cases of adult IPD identified, 110 pneumococci expressing non-PCV13 capsules were sequenced. Seven predominant serotypes accounted for 42.6% of IPD episodes in the late-PCV13 period: serotypes 8 (14.4%), 12F (7.5%), 9N (5.2%), 11A (4.1%), 22F (3.9%), 24F (3.9%) and 16F (3.6%). All predominant non-PCV13 serotypes were highly clonal, comprising one or two clonal complexes (CC). In general, CC538, CC4048, CC3016F, CC43322F and CC669N, related to predominant non-PCV13 serotypes, were antibiotic susceptible. CC15611A was associated with resistance to co-trimoxazole, penicillin and amoxicillin. CC23024F was non-susceptible to penicillin and resistant to erythromycin, clindamycin, and tetracycline. Six composite transposon structures of the Tn5252-family were found in CC23024F, CC98912F and CC3016F carrying different combinations of erm(B), tet(M), and cat. Pangenome analysis revealed differences in accessory genomes among the different CC, with most variety in CC3016F (23.9%) and more conservation in CC15611A (8.5%). We identified highly clonal predominant serotypes responsible for IPD in adults. The detection of not only conjugative elements carrying resistance determinants but also clones previously associated with vaccine serotypes (CC15611A and CC23024F) highlights the importance of the accessory genome.

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

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

Clinical and economic burden of pneumococcal disease among individuals aged 16 years and older in Germany.

This study assessed the incidence rate of all-cause pneumonia (ACP) and invasive pneumococcal disease (IPD) and associated medical costs among individuals aged ≥16 in the German InGef database from 2016 to 2019. Incidence rate was expressed as the number of episodes per 100 000 person-years (PY). Healthcare resource utilisation was investigated by age group and by risk group (healthy, at-risk, high-risk). Direct medical costs per ACP/IPD episode were estimated as the total costs of all inpatient and outpatient visits. The overall incidence rate of ACP was 1345 (95% CI 1339-1352) and 8.25 (95% CI 7.76-8.77) per 100 000 PY for IPD. For both ACP and IPD, incidence rates increased with age and were higher in the high-risk and at-risk groups, in comparison to the healthy group. ACP inpatient admission rate increased with age but remained steady across age-groups for IPD. The mean direct medical costs per episode were €8075 (95% CI 7121-9028) for IPD and €1454 (95% CI 1426-1482) for ACP. The aggregate direct medical costs for IPD and ACP episodes were estimated to be €8.5 million and €248.9 million respectively. The clinical and economic burden of IPD and ACP among German adults is substantial regardless of age.

1309. Incidence and Epidemiology of Invasive Pneumococcal Disease due to Serotype 3 in South-Central Ontario

BackgroundIn our population, the most common serotype (ST) of S. pneumoniae causing invasive pneumococcal disease (IPD) is now ST 3. We undertook an analysis of population based surveillance for IPD to examine the incidence and epidemiology of ST 3 disease over the last 25 years.MethodsThe Toronto Invasive Bacterial Diseases Network has performed population-based surveillance for IPD in Toronto/Peel region (pop’n 4.5M) since 1995. All sterile site isolates of S. pneumoniae are reported to a central study laboratory, isolates are serotyped, and clinical and vaccination data are collected via patient and physician interview and chart review. Population data are obtained from Statistics Canada.ResultsFrom 1995-2020, 11032 episodes of IPD occurred; 10015 had STs available, and 10484 clinical data. Overall, ST 3 comprised 9.2% of cases (N=931). Compared to other patients with IPD, those with ST 3 IPD were older (median age 65 vs. 58.5, P< .001), more likely to have underlying lung (22.7% v 16.0%, P< .0001) and cardiac (21.7 v 18.4, P=.02) disease and less likely to be immunocompromised (IC) (23.1% v 29.0% P< .0001). ST3 episodes were more likely to be pneumonia (81% v 65%), less likely to be bacteremia without focus (7.6% v 18.9%), and more likely to require ICU admission (42.3% v 25.1%) and to die (27.1% v 16.6%). In multivariable analysis, patients with ST 3 disease remained more likely to die (OR 1.65; 95%CI1.3-2.0). Over time, the proportion of patients with ST 3 IPD who were nursing home (NH) residents (18/171 in 1995-2000 vs. 4/215 in 2016-2020, P=.0002), and who were IC (46/169 in 1995-2000 vs 39/204 in 2016-2020, P=.007) decreased significantly; in IPD due to other STs, the proportion who were NH residents declined, but the proportion IC increased significantly. The case fatality rate (CFR) declined significantly in IPD due to ST3 but not other STs (Figure 1). Changes in incidence are shown in Figure 2.Figure 2: Incidence of serotype 3 IPD over time, Toronto/Peel, 1995-2020 The incidence of ST3 IPD in children and adults under 65 did not change significantly from 1995/96 to 2019/20. In older adults, the annual incidence of disease declined from 4.98 per 100,000 per year in 1995-2000 to 3.53 per 100,000 per year in 2001-2010 (IRR 0.71, 95%CI 0.56-0.90), then to 2.23 per 100,000 per year in 2011-2020 (IRR compared to 2001-2010 0.63, 95%CI 0.50-0.79)FIgure 2: Case fatality rate of IPD due to serotype 3 and other serotypes over time, 1995-2020, Toronto-Peel The case fatality rate of IPD due to ST3 declined from 37.6% (56/149) in 1995-2000 to 50/235 (21.3%) in 2015-2020 (P<.0001). The CFR in other serotypes did not change.ConclusionThe epidemiology of IPD due to ST3 has changed significantly over time and the CFR has declined. The incidence of ST3 disease in children and younger adults has not changed significantly, although the power to detect change is low in children. In older adults the incidence of ST3 disease declined significantly after PPV23 introduction in 1995/6 and again after PCV13 introduction for children.Disclosures All Authors: No reported disclosures

Estimating the risk of recurrent invasive pneumococcal disease in Australia, 1991–2016

BackgroundIndividuals who experience an initial episode of invasive pneumococcal disease (IPD) are at increased risk of recurrent episodes. However, the magnitude of risk has not been well-quantified in the pneumococcal conjugate vaccine era. Individuals with a previous episode of IPD are not commonly identified as a high-risk group in vaccination guidelines. MethodsAustralian residents with at least one case of IPD between 1991 and 2016 were identified using routine public health surveillance data which included identified IPD risk factors. Incidence of recurrent IPD was calculated from 2001 onwards (after IPD became nationally notifiable) using time-to-event analyses with individuals contributing person-time at risk of recurrence if they survived greater than 14 days after initial episode onset. ResultsFrom 1991 to 2016 there were 28,809 IPD episodes in 28,218 individuals. A total of 512 (1.8%) persons experienced 591 recurrent episodes. From 2001 to 2016 the incidence of recurrent IPD was 216.2 per 100,000 person-years, 27 times greater than the population rate of primary IPD during this period (8.0 per 100,000 population per year). Between 2011 and 2016, more than one-quarter of individuals experiencing recurrence had no IPD risk factors identified at first episode. ConclusionsThere is substantially increased risk of recurrent IPD after an initial episode. At least one-quarter of those with recurrent episodes have no identified risk factors at the initial episode. Given the potential preventability of future episodes, those with a previous IPD episode should be identified as a high-risk group and receive pneumococcal vaccination.

Invasive pneumococcal disease in persons with predisposing factors is dominated by non-vaccine serotypes in Southwest Sweden

BackgroundThe pneumococcal conjugate vaccine PCV7 was introduced in Southwest Sweden in the child vaccination program in 2009, followed by PCV13 in 2010 and PCV10 in 2015. In this retrospective cohort study we assessed the pneumococcal serotype distribution in relation to predisposing factors, clinical manifestations and outcome during seven years after PCV introduction.MethodsClinical data from 1278 patients with 1304 episodes of invasive pneumococcal disease (IPD) between January 2009 and December 2015 in Region Västra Götaland, Sweden, were retrospectively collected from medical records. Pneumococcal isolates were serotyped by gel diffusion and/or Quellung reactions performed at the Public Health Agency in Sweden. Associations between serotypes and clinical characteristics were statistically evaluated by use of Fisher’s exact test, Mann-Whitney U test and Logistic regression analysis, whereas IPD episodes caused by serotypes over time were analyzed by Mantel-Haenszel chi-square test.ResultsWith the exception of serotype 3, the prevalence of PCV13 serotypes decreased during the study period, from 76% (n = 157) of all IPD episodes in 2009 to 25% (n = 42) in 2015 (p < 0.001) while non-PCV13 serotypes increased, mainly among patients ≥65 years and in patients with predisposing factors, including cardiovascular disease, pulmonary disease and malignancy (p < 0.001 for all). Patients with predisposing factors, including those with malignancy, immune deficiency or renal disease, were more likely to have IPD caused by a serotype not included in PCV13 rather than a vaccine-included serotype. Serotype 3 was associated with intensive care unit admissions while serotype 1 and 7F caused IPD among healthier and younger patients. PCV13 serotypes were associated with invasive pneumonia, and non-PCV13 serotypes were associated with bacteremia with unknown focus and with manifestations other than pneumonia or meningitis.ConclusionsNon-PCV13 serotypes caused the majority of IPD cases in Southwest Sweden, especially in patients ≥65 years and in patients with predisposing factors. Serotype 3, included in PCV13, was prevalent and often caused severe disease.

Chronic Disease and Immunosuppression Increase the Risk for Nonvaccine Serotype Pneumococcal Disease: A Nationwide Population-based Study.

BackgroundDemography is changing, with people living longer with comorbidities. In this nationwide population-based study, we investigated the serotype-specific invasive pneumococcal disease (IPD) risk in individuals with comorbidities, and effects of the pneumococcal conjugated vaccine (PCV) child immunization program.MethodsCases included 14 096 IPD episodes in Sweden during 2006–2015. Controls (n = 137 289), matched to cases by age, sex, region, and calendar time, were selected from the general population. Comorbidity data was obtained through health registers and grouped as immunocompromising (IC) or chronic medical conditions (CMC).ResultsThe prevalence of CMC and IC among elderly cases was 33.9% and 39.4%. New risks identified for IPD were sarcoidosis, inflammatory polyarthropathies, systemic connective tissue, and neurological diseases. The odds ratio (OR) for IPD caused by non-PCV13 compared with PCV13 serotypes was higher in individuals with CMC/IC. Serotypes associated with the highest risk were 16F, 15C, 35F, 19F, and 23A (OR 3–5 for CMC, >10 for IC). Most comorbidities increased post-vaccination, and absolute increases of IPD caused by non-PCV13, PPV23–non-PCV13, and non-PCV13/non-PPV23 serotypes were higher in individuals with IC/CMC compared with healthy persons. Non-PCV13 serotypes 6C, 9N, 11A, 22F, 23A and 35F increased more in those with comorbidities. Mortality due to non-PCV13 serotypes increased in individuals with IC/CMC, while remaining stable in persons without comorbidities.ConclusionsThe PCV child immunization program associates with an increased disease burden of non-vaccine serotypes in individuals with comorbidities. These data are important for vaccine design and optimization of current vaccination strategies.

Changes in vaccination strategies contribute to the development of invasive pneumococcal disease in allogeneic hematopoietic stem cell transplantation recipients: a retrospective study for promoting vaccination

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients are at high risk of developing invasive pneumococcal disease (IPD) with substantial morbidity and mortality. Pneumococcal polysaccharide vaccine (PPSV23) and pneumococcal conjugate vaccine (PCV13) are the primary prevention strategy. The difference between the Japanese and international guidelines is limited except when to start PCV13. However, Japanese data regarding the incidence of IPD after allo-HSCT that include vaccination status are limited. Therefore, we aimed to study the clinical characteristics of patients with IPD following allo-HSCT, focusing on unvaccinated patients. We retrospectively reviewed allo-HSCT recipients between April 2005 and December 2018 at Komagome Hospital. Among 1,091 recipients, 11 (1008/100,000 recipients) developed 13 episodes of IPD. The median period from the first allo-HSCT to the first IPD episode was 686days (10-3040days). Ten patients developed IPD before vaccination, and seven of these unvaccinated patients with late-onset IPD were ineligible for vaccination based on domestic guidelines. Although appropriate treatments resulted in a good short-term prognosis, most episodes of IPD developed in unvaccinated allo-HSCT recipients. Our data support the promotion of better adherence to the current guidelines and the importance of pneumococcal vaccination even years after allo-HSCT to protect against late-onset IPD.

Evolution, Clinical and Microbiological Characteristics of Invasive Pneumococcal Disease since the Introduction of the Pneumococcal Conjugate Vaccine 13-Valent in Adults over 18 Years Old.

Invasive pneumococcal disease (IPD) presents high mortality in the population at risk. The aim of this work is to know the evolution, clinical and microbiological characteristics of IPD in the adult population of Majorca, since the introduction of a public funded program for pneumococcal conjugate vaccine (PCV-13) in the pediatric population in the Balearic Islands in 2016. For this purpose, a retrospective multicenter study was carried out in which all episodes of IPD in adult patients from the four hospitals of the public health system of Majorca were included, comparing the periods between 2012 and 2015 and between 2016 and 2019. Clinical variables, serotypes and antibiotic sensitivity were collected. There were 498 cases of IPD; 56.8% were male with a mean age of 67 (standard deviation: 16). Most infections were bacterial pneumonias (73.7%). Of the total cases, 264 (53%) presented complications. Of the 498 cases, 351 strains were obtained, of which 145 (41.3%) belong to vaccinal serotypes (included in the PCV-13 vaccine) and 206 (58.7%) to non-vaccinal serotypes (not included in the PCV-13 vaccine). The percentage of IPD caused by vaccinal serotypes was lower in the second period (47.8% vs. 34.5%; p = 0.012).

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

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

295. Is Herd Immunity from Pneumococcal Conjugate Vaccines Changing the Clinical Features of Invasive Pneumococcal Disease in Adults?

BackgroundNumerous factors that affect the presentation and severity of pneumococcal disease. Several studies in the pre-PCV era demonstrated that organism characteristics, including serotype, are associated with variability in disease presentation and severity. We undertook an analysis of population based surveillance for invasive pneumococcal disease (IPD) to assess whether herd immunity from PCVs will change the presentation and severity of IPD in adultsMethodsTIBDN has performed population-based surveillance for IPD in Toronto and Peel region (pop’n 4.5M) since 1995. All sterile site isolates of S. pneumoniae are reported to a central study laboratory, isolates are serotyped, and clinical and vaccination data are collected via patient and physician interview and chart review. Population data are obtained from Statistics Canada. Backwards stepwise logistic regression assessed patient characteristics, illness features, and isolate factors associated with clinical presentation and case fatality.ResultsBetween 1995 and 2018, 8815 episodes of IPD were identified in adults. Patients infected with PCV10not7 serotypes were younger, more likely male and without underlying illness. Patients with infections due to non-vaccine types were more likely to be immunocompromised. Case fatality in IPD declined from 177/754 in 1995/6 to 113/554 in 2017/8; OR 0.67, 95%CI0.51-0.86, P< .0001) and in all serotype groups (Figure). In multivariable models adjusted for host factors, relative to infections caused PCV7 serotypes, those caused by PCV10not7 were less likely to be fatal (OR 0.65, 95%CI 0.46–0.91); those caused by PCV13not10 were more likely to be fatal (OR 1.6, 95%CI 1.3–1.9). Bacteremic pneumonia as a proportion of presentations is highest in IPD due to PCV10not7 and PCV13not10 serotypes (85% and 83%, respectively), and lowest in IPD due to non-vaccine serotypes and PCV20not15 (59% and 68%, P< .0001). Meningitis is least common in IPD due to PCV10not7 serotypes (2.6%), and highest in cases due to non-vaccine types and PCV20not15 (9.0% and 8.0%, respectively, P< .0001).FIgure ConclusionIn our population, herd immunity from PCVs will result in a higher proportion of adult IPD occurring in immunocompromised cases, and a shift from bacteremic pneumonia to bacteremia without focus and meningitis.Disclosures Allison McGeer, MD, FRCPC, GlaxoSmithKline (Advisor or Review Panel member, Research Grant or Support)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Research Grant or Support)