Incidence Of Pneumococcal Disease Research Articles

Diabetes as a risk factor for pneumococcal disease and severe related outcomes and efficacy/effectiveness of vaccination in diabetic population. Results from meta-analysis of observational studies.

To collect all available evidence on the effect of diabetes mellitus (DM) as a risk factor for pneumococcal disease incidence and related complications, and on the efficacy/effectiveness of vaccines in patients with DM. Two distinct systematic searches on MEDLINE, Cochrane, ClinicalTrials.gov and EMBASE databases were performed, one for each meta-analysis, collecting all observational (cohort and case-control) studies and randomized clinical trials performed on humans up to June 1st, 2023. We retrieved 36 observational studies comparing risk for pneumococcal disease and related complications in people with or without DM, and 11 studies (1 randomized clinical trial and 10 observational studies) assessing conjugated and polysaccaridic vaccines efficacy/effectiveness on preventing such outcomes. People with DM were at higher risk for Invasive Pneumococcal Disease (unadjusted OR 2.42 [2.00; 2.92]); Case-Fatality Rate (unadjusted OR 1.61 [1.25; 2.07], Pneumococcal pneumonia (unadjusted OR 2.98 [2.76; 3.22), and Intensive care unit admission for pneumococcal disease (unadjusted OR 2.09 [1.20; 3.66]). In diabetic individuals vaccinated with conjugated vaccine, incidence of pneumonia specific for vaccine type in a clinical trial (OR 0.237 [0.008; 0.704]), and hospitalization for overall pneumonia during the year following the polysaccharide vaccination in observational studies (unadjusted OR 0.63 [0.45-0.89]) were significantly lower in comparison with unvaccinated DM subjects, with no significant differences for other outcomes. People with diabetes mellitus are at higher risk for less favourable course of pneumococcal disease and should be therefore targeted in vaccination campaigns; more evidence needs to be collected on vaccination outcomes in people with diabetes.

State of pneumococcal vaccine immunity.

Like the other invasive encapsulated bacteria, Streptococcus pneumoniae is also covered with a polysaccharide structure. Infants and elderly are most vulnerable to the invasive and noninvasive diseases caused by S. pneumoniae. Although antibodies against polysaccharide capsule are efficient in eliminating S. pneumoniae, the T cell independent nature of the immune response against polysaccharide vaccines renders them weakly antigenic. The introduction of protein conjugated capsular polysaccharide vaccines helped overcome the weak immunogenicity of pneumococcal polysaccharides and decreased the incidence of pneumococcal diseases, especially in pediatric population. Conjugate vaccines elicit T cell dependent response which involve the interaction of specialized CD4+ T cells, called follicular helper T cells (Tfh) with germinal center B cells in secondary lymphoid organs. Despite their improved immunogenicity, conjugate vaccines still need to be administered three to four times in infants during the first 15 month of their life because they mount poor Tfh response. Recent studies revealed fundamental differences in the generation of Tfh cells between neonates and adults. As the portfolio of pneumococcal conjugate vaccines continues to increase, better understanding of the mechanisms of antibody development in different age groups will help in the development of pneumococcal vaccines tailored for different ages.

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.

Impact of Demographic Developments and PCV13 Vaccination on the Future Burden of Pneumococcal Diseases in Germany—An Integrated Probabilistic Differential Equation Approach

Streptococcus pneumonia is the primary cause of morbidity and mortality in infants and children globally. Invasive pneumococcal disease (IPD) incidence is affected by various risk factors such as age and comorbidities. Additionally, this bacterium is a major cause of community-acquired pneumonia (CAP), leading to higher rates of hospitalization, especially among older adults. Vaccination with pneumococcal conjugate vaccines (PCVs) has proven effective, but the demographic transition in Germany poses a challenge. This study introduces a novel stochastic approach by integrating a population forecast model into a transmission dynamic model to investigate the future burden of pneumococcal diseases in three age groups (0–4, 5–59, and 60 and older). Our simulations, presented through mean predictions and 75% prediction intervals, indicate that implementing PCV13 (13-valent pneumococcal conjugate vaccine) until the year 2050 results in reduced cases of IPD and CAP in all age groups compared to scenarios without infant vaccination. However, cases with non-vaccine serotypes may persist at higher levels compared to scenarios without infant vaccination. Consequently, there may be a need for improvement in the current national vaccine policy, such as implementing the use of higher-valent PCVs and strengthening adult vaccination uptake.

Exploring factors shaping antibiotic resistance patterns in Streptococcus pneumoniae during the 2020 COVID-19 pandemic.

Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.

Pneumococcal Diseases in Colombia: Epidemiological Analysis Before and During the Universal Children Immunization against Streptococcus pneumoniae in the Light of a Vaccine Change in 2022

Streptococcus pneumoniae causes meningitis, pneumonia and bacteremia, mainly in children under 5 years of age and in the elderly. Pneumococcal conjugate vaccines (PCVs) have been administered globally since the year 2000, contributing to substantially reduce the incidence of pneumococcal diseases (PDs). In 2012, Colombia implemented universal vaccination with PCV10 in children under 2 years of age, achieving a decrease and stabilization of the incidence of PDs. However, since 2014, replacement of vaccine serotypes by non-vaccine serotypes, such as 3 and 19A, predominantly, has been observed. Likewise, in 2019, there was an increase in the incidence of meningitis, coinciding with the increase of multi-resistant 19A clones. In July 2022, the vaccine formulation was changed to PCV13, which also has the potential to control serotypes 3, 6A, and 19A. This paper reviews the epidemiology of pneumococcus in Colombia, before and during the universal PCV10 vaccination.

Age-Specific Resurgence in Invasive Pneumococcal Disease Incidence in the COVID-19 Pandemic Era and Its Association With Respiratory Virus and Pneumococcal Carriage Dynamics: A Time-Series Analysis.

Using multiple national surveillance systems, we found an increase in the incidence of invasive pneumococcal disease during after the relaxation of non-pharmaceutical interventions against COVID-19, which strongly varied by age. Age groups with higher incidence of respiratory syncytial virus and influenza also experienced higher increase in invasive pneumococcal disease incidence, with no change in pneumococcal carriage.

1693. Incidence of Pneumococcal Disease in Children ≤48 Months Old in the United States: 2010-2019

Abstract Background Pneumococcal disease (PD) leads to considerable morbidity, mortality, and healthcare resource utilization in children. This study estimated incidence rates (IRs) for invasive PD (IPD), all-cause pneumonia (ACP), and acute otitis media (AOM) among children ≤ 48 months old, between 2010 and 2019 in the US. Methods This was a retrospective observational study using MarketScan® Commercial Claims and Encounters (CCAE) and Multi-State Medicaid databases (2010-2019). Date of birth was imputed using dates of live-birth claims for accurate age determination. IPD, ACP, and AOM claims in children ≤48 months old were identified using International Classification of Diseases (ICD) versions 9 and 10 diagnosis codes. Episodes were defined as one or more PD-related claims, with a gap of 90 days between two IPD or ACP claims, and 14 days between two AOM claims. IRs were defined as number of episodes per 100,000 person-years (PY) for IPD and ACP, and per 1,000 PY for AOM. Annual IRs were stratified by age (0-6, 7-12, 13-24, and 25-48 months), and reported separately for CCAE and Medicaid populations. Results Overall IPD IRs declined between 2010-2019 from 11 to 7 episodes per 100,000 PY in CCAE and from 20 to 9/100,000 PY in Medicaid; IPD IRs were highest in children 0-6 months old, followed by 7-12 months old, in both populations (Fig. 1). Overall ACP IRs changed little between 2010-2019 from 3,996 to 3,952/100,000 PY in CCAE and declined from 6,225 to 4,521 per 100,000 PY in Medicaid; ACP IRs were highest in CCAE among children aged 13-24 and 25-48 months, and in Medicaid among children aged 13-24 and 7-12 months. (Fig. 2). Overall AOM IRs changed little between 2010-2019 from 723 to 738/1,000 PY in 2018 in CCAE and decreased from 773 to 624/1,000 PY in Medicaid (Fig. 3). AOM IRs were highest for children 7-12 months in both populations.Figure 1.IPD incidence in commercially and Medicaid-insured children ages 0 - 48 months, episodes per 100,000 patient-years (2010 - 2019)Figure 2.ACP incidence in commercially and Medicaid-insured children ages 0 - 48 months, episodes per 100,000 patient-years (2010 - 2019)Figure 3.AOM incidence in commercially and Medicaid-insured children ages 0 - 48 months, episodes per 1,000 patient-years (2010 - 2019) Conclusion IPD, ACP, and AOM IRs disease burden remains substantial with a disproportionately high impact of the most severe disease manifestations (IPD and inpatient ACP) among infants in the first year of life, despite marked declines following the introduction of PCV13. Disease IRs were generally higher in Medicaid children, particularly at the start of the study period, but also declined more significantly over time compared to IRs in CCAE children. Disclosures Salini Mohanty, DrPH, MPH, Employee of Merck & Co., Inc.: Stocks/Bonds Nicolae Done, PhD, Merck & Co., Inc.: Grant/Research Support Qing liu, PhD, Merck & Co., Inc.: Advisor/Consultant Yan Song, PhD, Merck & Co., Inc.: Grant/Research Support Katherine Gaburo, n/a, Merck & Co., Inc.: I am an employee of Analysis Group, Inc., which received consulting fees for participation in this research Travis Wang, MS, MBBS, Merck & Co., Inc.: Grant/Research Support Meghan White, PharmD, Merck: Employee|Merck: Stocks/Bonds Jessica P. Weaver, PhD, Employee of Merck & Co., Inc.: Stocks/Bonds James Signorovitch, PhD, Merck & Co., Inc.: Grant/Research Support Thomas Weiss, DrPH, MPH, Employee of Merck & Co., Inc.: Stocks/Bonds

Pneumococcal Vaccine Breakthrough and Failure in Infants and Children: A Narrative Review.

Globally, Streptococcus pneumoniae is a leading cause of vaccine-preventable morbidity and mortality in infants and children. In recent decades, large-scale pediatric immunization programs have substantially reduced the incidence of invasive pneumococcal disease. Despite this, residual vaccine-type pneumococcal disease remains in the form of vaccine breakthrough and vaccine failure. This targeted literature review aims to discuss aspects of vaccine breakthrough and failure in infants and children, including disease epidemiology, clinical presentation, risk factors, vaccination schedules, vaccine serotypes, correlates of protection, comorbidities, disease surveillance, and potential implications for future vaccine development.

Genomic analysis of penicillin-binding proteins and recombination events in an emerging amoxicillin- and meropenem-resistant PMEN3 (Spain9V-3, ST156) variant in Taiwan and comparison with global descendants of this lineage.

From 2008 to 2020, the Taiwan National Notifiable Disease Surveillance System database demonstrated that the incidence of non-vaccine serotype 23A invasive pneumococcal disease (IPD) approximately doubled. In this study, 276 non-repetitive pneumococcal clinical isolates were collected from two medical centers in Taiwan between 2019 and 2021. Of these 267 pneumococci, 60 were serotype 23A. Among them, 50 (83%) of serotype 23A isolates belonged to the sequence type (ST) 166 variant of the Spain9V-3 clone. Pneumococcal 23A-ST166 isolates were collected to assess their evolutionary relationships using whole-genome sequencing. All 23A-ST166 isolates were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299, the newly identified PBP2x-299 in Taiwan. Transformation of the pbp1a, pbp2b, and pbp2x alleles into the β-lactam-susceptible R6 strain revealed that PBP2x-299 and PBP2b-11 increased the MIC of ceftriaxone and meropenem by 16-fold, respectively. Prediction analysis of recombination sites in PMEN3 descendants (23A-ST166 in Taiwan, 35B-ST156 in the United States, and 11A-ST838/ST6521 in Europe) showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM, and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displayed an evolutionary capacity for global dissemination and persistence, increasing IPD incidence, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases, and contributing to high antibiotic resistance.A clonal shift with a highly β-lactam-resistant non-vaccine serotype 23A, from ST338 to ST166, increased in Taiwan. ST166 is a single-locus variant of the Spain9V-3 clone, which is also called the PMEN3 lineage. All 23A-ST166 isolates, in this study, were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299. PBP2x-299 and PBP2b-11 contributed to the increasing MIC of ceftriaxone and meropenem, respectively. Prediction analysis of recombination sites in PMEN3 descendants showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM, and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displays the evolutionary capacity for dissemination, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases and contributing to high antibiotic resistance.

Changes in Invasive Pneumococcal Disease in the Paediatric Population in the Second COVID-19 Pandemic Year.

Incidence of invasive pneumococcal disease (IPD) decreased worldwide in 2020, coinciding with the implementation of measures to reduce COVID-19 transmission. We evaluated the impact of the COVID-19 pandemic on healthcare demand and IPD in children in 2021 compared to the pre-pandemic period (2018-2019) and the early pandemic period (2020) in a study carried out during 2018-2021 in Catalonia. Incidence rates were compared by calculating the incidence rate ratio (IRR), and expressing percentage changes in IRR as (1-IRR)x100. Compared to 2018-2019, emergency room (ER) visits declined by 21% in 2021 (p < 0.001), mainly in the first quarter (-39%), and compared to 2020, ER visits increased by 22% in 2021 (p < 0.001), except in the first quarter. IPD incidence overall was 11.0 in 2018-2019 and 4.6 in 2021 (-58%, p < 0.001); the reduction in incidence was similar in the 0-4 age group and was higher in the first quarters. Compared to 2020, in 2021, IPD incidence decreased during the first quarter (-86%, p < 0.001), but increased from 0.0 to 1.2 in the second quarter (p = 0.02) and from 0.6 to 2.1 (p=0.03) in the fourth quarter. The decreased IPD incidence observed in 2021 compared to 2018-2019 (most especially in the first quarter) was greater than the decrease in healthcare demand and PCR test requests. Compared to 2020, IPD incidence decreased in the first quarter when a second state of alarm was in force. In 2021, compared to 2018-2019, there was a greater reduction in PCV13 serotypes than in non-PCV13 serotypes.

Impact of the progressive uptake of pneumococcal conjugate vaccines on the epidemiology and antimicrobial resistance of invasive pneumococcal disease in Gipuzkoa, northern Spain, 1998-2022.

To analyze the impact of pneumococcal conjugate vaccines (PCVs) on the incidence of invasive pneumococcal diseases (IPDs) and pneumococcal antibiotic resistance in Gipuzkoa, northern Spain for a 25 years period. All cases of IPD confirmed by culture between 1998 and 2022 in a population of around 427,416 people were included. Pneumococci were serotyped and antimicrobial susceptibility was assessed by the EUCAST guidelines. Overall, 1,516 S. pneumoniae isolates were collected. Annual IPD incidence rates (per 100,000 people) declined from 19.9 in 1998-2001 to 11.5 in 2017-19 (42.2% reduction), especially in vaccinated children (from 46.7 to 24.9) and non-vaccinated older adult individuals (from 48.0 to 23.6). After PCV13 introduction, the decrease in the incidence of infections caused by PCV13 serotypes was balanced by the increase in the incidence of non-PCV13 serotypes. In the pandemic year of 2020, IPD incidence was the lowest: 2.81. The annual incidence rates of penicillin-resistant isolates also decreased, from 4.91 in 1998-2001 to 1.49 in 2017-19 and 0.70 in 2020. Since 2017, serotypes 14, 19A, and 11A have been the most common penicillin-resistant types. The incidence of erythromycin-resistant strains declined, from 3.65 to 1.73 and 0.70 in the same years. PCV use was associated with declines in the incidence of IPD and the spread of non-vaccine serotypes, that balanced the beneficial effect off PCV13, some of them showing high rates of antibiotic resistance.

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.

Predictors of serological non-response to the 13-valent pneumococcal conjugate vaccine followed by the 23-valent polysaccharide vaccine among adults living with HIV

BackgroundPeople living with HIV (PLWH) have higher incidence of pneumococcal disease compared to people without HIV. Immunization with pneumococcal vaccines is recommended, but serological non-response to pneumococcal vaccination is common for largely unknown reasons. MethodsPLWH on antiretroviral treatment and no prior pneumococcal vaccination received the 13-valent pneumococcal conjugate vaccine (PCV13) followed 60 days later by the 23-valent polysaccharide vaccine (PPV23). Serological response was evaluated 30 days post-PPV23 by antibodies against 12 serotypes covered by both PCV13 and PPV23. Seroprotection was defined as a ≥2-fold rise to a level above 1.3 µg/ml in geometric mean concentration (GMC) across all serotypes. Associations with non-responsiveness were evaluated by logistic regression. ResultsFifty-two virologically suppressed PLWH (median age of 50 years (IQR 44–55) and median CD4 count of 634 cells/mm3 (IQR 507–792)) were included. Forty-six percent (95 % CI 32–61, n = 24) achieved seroprotection. Serotypes 14, 18C and 19F had the highest, and serotypes 3, 4 and 6B the lowest GMCs. Pre-vaccination GMC levels less than 100 ng/ml were associated with increased odds of non-responsiveness compared to levels above 100 ng/ml (adjusted OR 8.7, 95 % CI 1.2–63.6, p = 0.0438). ConclusionLess than half of our study population achieved anti-pneumococcal seroprotective levels following PCV13 and PPV23 immunization. Low pre-vaccination GMC levels were associated with non-response. Further research is required to optimize vaccination strategies that achieve higher seroprotection in this high-risk group.

Impact of the COVID-19 Pandemic on Community Consumption of Antibiotics for Systemic Use and Resistance of Invasive Streptococcus pneumoniae in Slovenia.

The present study aims to investigate the impact of the COVID-19 pandemic on community antibiotic consumption and the resistance of invasive Streptococcus pneumoniae (2015-2022) to penicillin in Slovenia. During the pandemic in 2020 and 2021, the total use of antibiotics for systemic use decreased by 23.5% and 24.3%, expressed in defined daily doses per 1000 inhabitants per day (DID), while the use of penicillins, macrolides and broad-spectrum penicillins decreased by 30%, 20% and by 17.5%, respectively, and that of broad-spectrum macrolides fell by 17.1%. The incidence of invasive pneumococcal diseases (IPD) in Slovenia had a large decline during the pandemic. Decreased resistance to macrolides was significantly associated with decreased use of macrolides, while for penicillins the correlation could not be statistically confirmed. The proportion of PCV13 serotypes in IPD in Slovenia decreased after the introduction of the vaccine in the national programme, falling from 81.6% in 2015 to 45.5% in 2022. We noticed a decrease in the serotypes 1, 14, 9V, 7F, 4, 6A and an increase in the serotypes 3, 8, 22F, 11A, 23A and 15A. National interventions during the COVID-19 pandemic substantially decreased outpatients' antibiotic consumption, as well as incidence and resistance of invasive S. pneumoniae.

Changes in the Incidence of Invasive Pneumococcal Disease in Calgary, Canada, during the SARS-CoV-2 Pandemic 2020-2022.

We describe the impact of non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic on invasive pneumococcal disease (IPD) in Calgary. IPD declined significantly worldwide during 2020 and 2021. This may be due to the reduced transmission of and decrease in circulating viruses that often co-infect with the opportunistic pneumococcus. Pneumococcus has not been shown to frequently co-infect or cause secondary infection with SARS-CoV-2. We examined and compared incidence rates in Calgary per quarter in the pre-vaccine, post-vaccine, 2020 and 2021 (pandemic) and 2022 (late pandemic) eras. We also conducted a time series analysis from 2000-2022 allowing for change in trend at introduction of vaccines and for initiation of NPIs during the COVID-19 pandemic. Incidence declined in 2020/2021 but by the end of 2022 had begun to rapidly recover to near pre-vaccine rates. This recovery may be related to the high rates of viral activity in the winter of 2022 along with childhood vaccines being delayed during the pandemic. However, a large proportion of the IPD caused in the last quarter of 2022 was serotype 4, which has caused outbreaks in the homeless population of Calgary in the past. Further surveillance will be important to understand IPD incidence trends in the post-pandemic landscape.

Public health impact and cost-effectiveness of 15-valent pneumococcal conjugate vaccine use among the pediatric population of the United States.

Although use of the 13-valent pneumococcal conjugate vaccine (PCV13) among children has reduced incidence of pneumococcal disease, a considerable burden of disease remains. PCV15 is a new vaccine that contains pneumococcal serotypes 22F and 33F in addition to serotypes contained in PCV13. To inform deliberations by the Advisory Committee on Immunization Practices on recommendations for PCV15 use among U.S. children, we estimated the health impact and cost-effectiveness of replacing PCV13 with PCV15 within the routine infant immunization program in the United States. We also assessed the impact and cost-effectiveness of a supplementary PCV15 dose among children aged 2-5years who have already received a full PCV13 series. We estimated the incremental number of pneumococcal disease events and deaths averted, costs per quality adjusted life-year (QALY) gained, and costs per life-year gained under different vaccination strategies using a probabilistic model following a single birth cohort of 3.9 million individuals (based on 2020 U.S. birth cohort). We assumed that vaccine effectiveness (VE) of PCV15 against the two additional serotypes was the same as the VE of PCV13. The cost of PCV15 use among children was informed from costs of PCV15 use among adults and from discussions with the manufacturer. Our base case results found that replacing PCV13 with PCV15 prevented 92,290 additional pneumococcal disease events and 22 associated deaths, while also saving $147 million in costs. A supplementary PCV15 dose among children aged 2-5years who were fully vaccinated with PCV13 prevented further pneumococcal disease events and associated deaths but at a cost of more than $2.5 million per QALY gained. A further decrease in pneumococcal disease in conjunction with considerable societal cost savings could be expected from replacing PCV13 with PCV15 within the routine infant immunization program in the United States.

Historical Population-Level Impact of Infant 13-Valent Pneumococcal Conjugate Vaccine (PCV13) National Immunization Programs on Invasive Pneumococcal Disease in Australia, Canada, England and Wales, Israel, and the United States

This study estimates the annual population-level impact of 13-valent pneumococcal conjugate vaccine (PCV13) infant national immunization programs (NIPs) on vaccine-type and non-vaccine type invasive pneumococcal disease (IPD) incidence across all ages using national surveillance data. We identified countries (Australia, Canada, England and Wales, Israel, and the US) with national IPD active surveillance data that introduced the seven-valent PCV (PCV7) followed by PCV13, which also reported annual serotype- and age group-specific incidence. We extracted IPD incidence by serotype groupings [PCV13 minus PCV7 (PCV13-7) serotypes; PCV13-7 serotypes excluding serotype 3; non-PCV13 serotypes; and the 20-valent (PCV20) minus PCV13 (PCV20-13) serotypes] and by age groups (< 2years, 2-4years, 5-17years, 18-34years, 35-49years, 50-64years, and ≥ 65years). For each country, we calculated the annual relative change in IPD incidence (percent change), and the corresponding incidence rate ratio (IRR), for 7 years post introduction compared to the year prior to PCV13 program initiation. PCV13-7 vaccine-type IPD incidence consistently decreased over time following introduction of PCV13 across countries, reaching an approximate steady state after 3-4years in ages < 5years, with roughly 60-90% decrease (IRRs = 0.1-0.4) and after 4-5years in ages ≥ 65years with approximately 60-80% decrease (IRRs = 0.2-0.4). Incidence declines were more substantial for the PCV13-7 grouping when excluding serotype 3. Non-PCV13 serotype incidence was variable by country and age group, ranging from virtually no serotype replacement compared to the PCV7 period across ages in the US to increases for other countries ranging from 10 to 204% (IRRs = 1.10-3.04) in children < 5years and 41% to 123% (IRRs = 1.41-2.23) in ages ≥ 65years. Countries with longstanding PCV13 infant NIPs have observed substantial direct and indirect benefits, which are demonstrated in this study by the reduction in PCV13-7 IPD incidence compared to PCV7 period in all age groups. Over time, non-PCV13 serotypes have emerged in response to the reduction of incidence of PCV13-unique serotypes. Higher-valent PCVs are needed to address this emerging pneumococcal disease burden as well as the direct vaccination of both pediatric and adult populations against the most prevalent circulating serotypes.

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.].

Cost-Effectiveness Analysis of the South African Infant National Immunization Program for the Prevention of Pneumococcal Disease.

Pneumococcal disease, which presents a substantial health and economic burden, is prevented through pneumococcal vaccination programs. We assessed the impact of switching from a 13-valent-based (PCV13) to lower 10-valent-based (PCV10-GlaxoSmithKline [GSK] or PCV10-Serum Institute of India [SII]) or higher-valent (PCV15 or PCV20) vaccination programs in South Africa. A previously published decision-analytic model was adapted to a South African setting. Historical invasive pneumococcal disease (IPD) incidence data were used to project IPD incidence over time for each vaccination program on the basis of serotype coverage. Historical incidence (IPD, pneumonia, otitis media), mortality, costs, and utilities were obtained from the published literature. Cases of disease, direct medical costs (i.e., vaccination, IPD, pneumonia, and otitis media costs) (in 2022 South African rands), life-years, quality-adjusted life-years (QALY), and incremental cost per QALY were estimated over a 5- and 10-year horizon for PCV13 and the PCV10 vaccines. Additionally, a public health impact analysis was conducted comparing PCV13, PCV15, and PCV20. Continuing use of PCV13 would substantially reduce disease incidence over time compared with switching to either of the PCV10 lower-valent vaccines. Cases of IPD were reduced by 4.22% and 34.70% when PCV13 was compared to PCV10-GSK and PCV10-SII, respectively. PCV13 was also found to be cost saving over 5- and 10-year time horizons compared with PCV10-SII and to be cost-effective over a 5-year time horizon and cost-saving over a 10-year time horizon compared with PCV10-GSK. PCV20 was consistently estimated to prevent more cases than the PCV10 vaccines, PCV13, or PCV15. Switching from a higher-valent to a lower-valent vaccine may lead to disease incidence re-emergence caused by previously covered serotypes. Maintaining PCV13 was estimated to improve public health further by averting additional pneumococcal disease cases and saving more lives and also to reduce total costs in most scenarios. Higher-valent PCVs can achieve the greatest public health impact in the pediatric vaccination program in South Africa.