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Background: Novel, expanded valency pneumococcal conjugate vaccines (PCVs) are in development to reduce the burden of pneumococcal disease (PD) in children. To understand the potential value of new vaccines in Germany, this study estimated the residual burden of PD in children < 16 years old from 2014 to 2019, using administrative health data from a large German claims database., Methods: Outpatient and inpatient cases of all-cause pneumonia (ACP), pneumococcal pneumonia (PP) and invasive pneumococcal disease (IPD) were identified in the InGef database. Incidence rates (IRs) with 95% confidence intervals (CI) were calculated as number of episodes/person-years (PY) at risk. The Mann-Kendall test assessed time trends in incidence., Results: There were no significant trends in IRs of IPD or PP from 2014 to 2019. For ACP, IRs declined from 2014 to 2019; 2,213 (CI 2,176-2,250) to 1,503 (CI 1,472-1,534) per 100,000 PY (p = 0.017). IRs of ACP and PP were highest among children aged 12-23 months; 4,672 (CI 4,584-4,762) and 20.8 (CI 15.3-27.5) per 100,000 PY, respectively. For IPD, children 5-11 months-old had the highest IRs, at 14.7 (CI 9.0-22.7) per 100,000 PY., Conclusions: From 2014 to 2019 there were no discernible trends in the IRs of PP or IPD, but the IRs of ACP declined in children aged < 16 years. The highest IRs of ACP, PP and IPD were observed in children < 2 years of age, highlighting the importance of infant pneumococcal vaccination in the prevention of pediatric PD. The clinical burden of pediatric PD in Germany persists. Continued surveillance of changing pneumococcal burden, serotype distribution, antimicrobial resistance and vaccination status is critical to better understand the factors driving incidence of PD and to inform future vaccination strategies., Competing Interests: Declarations. Ethics approval and consent to participate: All patient-level data in the InGef research database are de-identified to comply with German data protection regulations. Use of the study database for healthcare services research is therefore fully compliant with German federal law and, accordingly, Institutional Review Board/ethical approval and informed consent of the patient was not required. Participant consent for publication: Not applicable. Competing interests: All authors declare financial and non-financial conflicts of interest. TW, JW, MW and SM are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, who may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. TB is an employee of MSD Sharp & Dohme GmbH, Germany, who may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. TH was employed by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA at the time of this study. BP, RB and NQ are employed by OXON Epidemiology. DH is employed by WIG2. DO is employed by InGef and WG was employed by InGef at the time of this study., (© 2024. Merck & Co., Inc., Rahway, NJ, USA and its affiliates, and OXON Epidemiology & WIG2 Institute.)

Background: Characterizing strains causing noninvasive and invasive pneumococcal disease (IPD) may inform the impact of new pneumococcal conjugate vaccines (PCVs)., Methods: During 2011-2019, among children aged 6-36 months, pneumococcal serotype distribution and antibiotic nonsusceptibility of nasopharyngeal and middle ear fluid (MEF) isolates collected at onset of acute otitis media (AOM) in Rochester, New York, were compared with IPD isolates from the Active Bacterial Core surveillance (ABCs) system across 10 US sites., Results: From Rochester, 400 (nasopharyngeal) and 156 (MEF) pneumococcal isolates were collected from 259 children. From ABCs, 907 sterile-site isolates were collected from 896 children. Non-PCV serotypes 35B and 21 were more frequent among the Rochester AOM cases, while serotypes 3, 19A, 22F, 33F, 10A, and 12F contained in PCVs were more frequent among ABCs IPD cases. The proportion of antibiotic-nonsusceptible pneumococcal isolates was generally more common among IPD cases. In 2015-2019, serotype 35B emerged as the most common serotype associated with multiclass antibiotic nonsusceptibility for both the Rochester AOM and ABCs IPD cases., Conclusions: Pneumococcal isolates from children in Rochester with AOM differ in serotype distribution and antibiotic susceptibility compared to IPD cases identified through US surveillance. Non-PCV serotype 35B emerged as a common cause of AOM and IPD., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Kenya introduced Synflorix™ (GlaxoSmithKline, PCV10-GSK), a 10-valent pneumococcal conjugate vaccine, in 2011, using three primary doses and, in select areas, catch-up campaigns. Surveys conducted 1-2 years post-introduction showed a stable prevalence of pneumococcal colonization, with declines in vaccine-type carriage. However, little is known about the long-term impact of PCV10-GSK in Kenya., Methods: We conducted a cross-sectional survey of pneumococcal carriage among children aged <5 years in November-December 2017 in Kibera (Nairobi informal settlement, no catch-up) and Asembo (rural western Kenya, 2-dose catch-up for children 1-4 years), using the same methods and settings as prior annual surveys from 2009 to 2013. Participants were randomly selected from an ongoing population-based surveillance platform. Nasopharyngeal swabs were frozen in skim milk-tryptone-glucose-glycerin media within 4 h and underwent culture with broth enrichment for pneumococcus. Isolates were serotyped by polymerase chain reaction and Quellung., Results: We enrolled 504 children, including 252 from each site; >90 % of participants had received 3 doses of PCV10-GSK. Pneumococcal colonization was detected in 210 (83.3 %) participants in Kibera and 149 (59.1 %) in Asembo, which was significantly lower than the prevalence observed in 2013 (92.9 % and 85.7 %, respectively). PCV10-GSK serotypes were detected in 35/252 (13.9 %) participants in Kibera and 23/252 (9.1 %) in Asembo, respectively; these prevalences were lower, but not statistically different, from vaccine-type carriage prevalences in 2013 (17.3 % and 13.3 %, respectively). In 2017 in both sites, serotypes 3, 6A, 19A, 19F, and 35B were among the most common serotypes., Conclusion: Six years post-PCV10-GSK introduction, the prevalence of pneumococcal carriage among children has decreased, and the impact of PCV10-GSK on vaccine-type carriage has plateaued. Kenya recently changed from PCV10-GSK to Pneumosil™ (Serum Institute of India), a 10-valent PCV that includes serotypes 6A and 19A; these data provide historical context for interpreting changes in vaccine-type carriage following the PCV formulation switch., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Bacterial drug resistance is becoming increasingly serious, this study aims to investigate the relationship between the resistance rate of erythromycin-resistant Streptococcus pneumoniae (SP) and reasons for the epidemic under complex geographical and climatic factors in China. Data spanning from 2014 to 2021, including drug resistance rates, isolate rates, meteorological variables, and demographic statistics, were collected from the China Antimicrobial Resistance Monitoring System, the China Statistical Yearbook and China Meteorological Website. Our analysis involved nonparametric tests and the construction of multifaceted regression models for rigorous multivariate analysis. Single-factor analysis revealed significant differences in the resistance rate and isolate rate of erythromycin-resistant SP across different regions characterized by Hu Huanyong lines or different climate types. Multivariate regression analysis indicated positive correlations between the drug resistance rate and temperature, Subtropical climate, Gross Domestic Product (GDP), Hu Huanyong line, and the highest temperature in the past period (Tm); the isolate rate showed a positive correlation with regional GDP and a negative correlation with monsoon climate. The model developed in this study provides valuable insights into the resistance rate and potential relationships of erythromycin-resistant SP under complex meteorological conditions in China., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

BackgroundDespite widely implemented pneumococcal vaccination programmes, Streptococcus pneumoniae remains a global risk for human health. Streptococcus pneumoniae can cause invasive (IPD) or non-invasive pneumococcal disease (NIPD). Surveillance is mainly focusing on IPD, assessing the full impact of pneumococcal vaccination programmes on pneumococcal disease is challenging.AimWe aimed to prospectively investigate serotype distribution and antimicrobial resistance (AMR) of S. pneumoniae isolates from patients with NIPD and compare with data on IPD isolates and with a 2007-2008 dataset on NIPD.MethodsBetween September 2020 and April 2023, we collected isolates and patient data from patients with NIPD from 23 clinical laboratories in Belgium. Capsular typing was performed by a validated Fourier-Transform Infrared spectroscopic method, and AMR was assessed with broth microdilution, using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoints.ResultsWe received S. pneumoniae isolates from 1,008 patients with lower respiratory tract infections (n = 760), otitis media (n = 190) and sinusitis (n = 58). Serotype 3 was the most prevalent serotype among the NIPD isolates. Serotypes not included in the 20-valent pneumococcal conjugate vaccine (PCV20) were significantly more common among the NIPD than among the IPD isolates. Antimicrobial resistance levels were significantly higher among the NIPD isolates (n = 539; 2020-2022) compared with the IPD isolates (n = 2,344; 2021-2022). Resistance to several β-lactam antimicrobials had increased significantly compared with 15 years before.ConclusionsThe NIPD isolates were strongly associated with non-vaccine serotypes and with increased AMR levels. This underlines the importance of continued NIPD surveillance for informed policy making on vaccination programmes.

Aims: To compare nasopharyngeal carriage and antibiotic susceptibility of Streptococcus pneumoniae among patients with and without diabetes at Moi Teaching and Referral Hospital (MTRH) in western Kenya., Methods: A cross-sectional study was conducted at MTRH diabetes and eye clinics. Participants were selected using systematic random sampling. Sociodemographic data and risk factors were collected through interviewer-administered questionnaires. Blood samples were taken to measure random blood sugar and HbA1c levels. Nasopharyngeal swabs were cultured and tested for antibiotic susceptibility within 24 h. Data analysis was performed using STATA version 13. Associations were assessed using Pearson's chi-square, Fisher's exact test, unpaired t-test, and Wilcoxon test., Results: A total of 124 participants with diabetes and 121 without diabetes were enrolled. Overall, 7.4 % (95 % CI: 4.4, 11.4) of participants carried S. pneumoniae. Carriage was higher in diabetes (12.1 % [95 % CI: 7.0, 19.0]) than non-diabetes participants (2.48 % [95 % CI: 1.0, 7.0]), with a statistically significant difference (p = 0.004). Diabetes was associated with higher odds of carriage (adjusted OR 6.2, p = 0.012). No association was found with age, sex, cooking fuel, presence of children under 5, or prior antibiotic use. Among participants with diabetes, carriage of Streptococcus Pneumoniae was only associated with insulin use. Antibiotic resistance was highest for cotrimoxazole (94.44 %), followed by amoxicillin (16.7 %) and cefuroxime (11.1 %). No resistance to macrolides was observed., Conclusion: Nasopharyngeal carriage of S. pneumoniae is higher in patients with diabetes, with significant resistance to common antibiotics, though macrolides remain effective., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: On Jan 1, 2020, the UK transitioned from a 2+1 to a 1+1 national infant immunisation schedule with the 13-valent pneumococcal conjugate vaccine (PCV13). We assessed whether the 1+1 PCV13 schedule had any impact on incidence, disease characteristics, or outcomes after invasive pneumococcal disease (IPD) in eligible children aged 0-3 years., Methods: The UK Health Security Agency conducts IPD surveillance and serotyping of invasive pneumococcal isolates via whole-genome sequencing in England. IPD was defined as identification of Streptococcus pneumoniae in a sterile site. We compared IPD incidence, demographics, clinical presentation, comorbidity prevalence, serotype distribution, and case-fatality rates (CFRs) in children from a single birth cohort eligible for the 1+1 schedule (born between Jan 1, 2020, and Dec 31, 2022) who developed IPD in the 2022-23 financial year (April to March) with children from three equivalent historical birth cohorts (born between Jan 1, 2015, and Dec 31, 2019) eligible for the 2+1 schedule who developed IPD during three respective pre-pandemic financial years: 2017-18, 2018-19, and 2019-20., Findings: There were a total of 702 IPD episodes in 697 children, including 158 (incidence 8·99 per 100 000 person-years) in the single 1+1 birth cohort and 544 (incidence 9·39 per 100 000 person-years) in the 2+1 birth cohorts, with no significant difference in the incidence of overall IPD (incidence rate ratio 0·96, 95% CI 0·80-1·14, p=0·63), PCV13-type IPD (1·21, 0·71-2·00, p=0·45), or pneumococcal meningitis (0·97, 0·66-1·40, p=0·88). Comorbidity prevalence, clinical presentation, and CFRs were also similar between the two cohorts, as was the percentage of cases in infants too young to be vaccinated (<2 months old) and infants aged 5-11 months who received one or two PCV13 priming doses, in the 1+1 and 2+1 cohorts respectively., Interpretation: After 3 years, the 1+1 schedule continues to provide direct and indirect protection against PCV13-type IPD in children, with no significant change in overall IPD incidence, serotype distribution, clinical presentation, or CFRs in children eligible for the 1+1 compared with the 2+1 schedule. Ongoing surveillance will be important to assess longer-term direct and indirect population protection., Funding: None., Competing Interests: Declaration of interests The UKHSA Immunisation and Vaccine Preventable Diseases Division (affiliated with FA, MB, Y-WC, NJA, DJL, MER, and SNL) has provided vaccine manufacturers with post-marketing surveillance reports on pneumococcal and meningococcal infections which the companies are required to submit to the UK Licensing authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports. SNL performs contract research on behalf of St George's University of London and the UKHSA for pharmaceutical companies but receives no personal remuneration. The Respiratory and Vaccine Preventable Bacteria Reference Unit (affiliated with JCD, SE, and DJL) at UKHSA has received grant funding from vaccine manufacturers for investigator-led research projects on pneumococcal surveillance., (Copyright © 2024 Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Lower respiratory tract infections, commonly caused by respiratory syncytial virus (RSV) or Streptococcus pneumoniae (pneumococcus), pose a substantial global health burden, especially in children younger than 5 years of age. A deeper understanding of the relationship between RSV and pneumococcus would aid the development of health-care approaches to disease prevention and management. We completed a systematic review to identify and assess evidence pertaining to the relationship between RSV and pneumococcus in the pathogenesis of childhood respiratory infections. We found mechanistic evidence for direct pathogen-pathogen interactions and for indirect interactions involving host modulation. We found a strong seasonal epidemiological association between these two pathogens, which was recently confirmed by a parallel decrease and a subsequent resurgence of both RSV and pneumococcus-associated disease during the COVID-19 pandemic. Importantly, we found that pneumococcal vaccination was associated with reduced RSV hospitalisations in infants, further supporting the relevance of their interaction in modulating severe disease. Overall evidence supports a broad biological and clinical interaction between pneumococcus and RSV in the pathogenesis of childhood respiratory infections. We hypothesise that the implementation of next-generation pneumococcal and RSV vaccines and monoclonal antibodies targeting RSV will act synergistically to reduce global morbidity and mortality related to childhood respiratory infections., Competing Interests: Declaration of interests LB and RD obtained a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme (MSD) to cover the costs of Violicom's searches and screening of the data. LB is the founding chairman of the Respiratory Syncytial Virus Foundation (ReSViNET Foundation); he has regular interactions with pharmaceutical and other industrial partners, but he has not received personal fees or other personal benefits. LB reports the following funding to his institution: funding for investigator-initiated studies from AbbVie, MedImmune, AstraZeneca, Sanofi, Janssen, Pfizer, MSD, and MeMed Diagnostics; funding for the RSV GOLD study from the Bill & Melinda Gates Foundation; funding as part of the Innovative Medicines Initiative-funded RESCEU and PROMISE projects with partners GSK, Novavax, Janssen, AstraZeneca, Pfizer, and Sanofi; funding for participation in clinical studies sponsored by MedImmune and Pfizer from Julius Clinical; and consulting fees and fees for invited lectures from AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, GSK, Novavax, Pfizer, Moderna, AstraZeneca, MSD, Sanofi, and Janssen. AM has received research grants to her institution from Janssen, Merck, and the US National Institutes of Health (NIH); fees for participation on advisory boards from Janssen, Sanofi Pasteur, Merck, Pfizer, and AstraZeneca; and fees for lectures from Sanofi Pasteur and AstraZeneca. OR has received research grants to his institution from Janssen, Merck, NIH, and the Bill & Melinda Gates Foundation; fees for participation on advisory boards from Sanofi Pasteur, Merck, and Pfizer; and fees for lectures from Pfizer, Sanofi Pasteur, and AstraZeneca. DMW is supported by a grant from the NIH National Institute of Allergy and Infectious Diseases (R01AI137093) and has received consulting fees from Pfizer, Merck, and GSK/Affinivax for work unrelated to this manuscript; he is the principal investigator on grants from Pfizer and Merck to his institution for work unrelated to this manuscript. RD has received grants to his institution from Pfizer, MSD, and MedImmune/AstraZeneca; consulting fees and fees for participation on advisory boards from Pfizer and MSD; payment for speakers bureaus from Pfizer, MSD, Sanofi Pasteur, and GSK; and payment for expert testimony from Pfizer. SBB and DB declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Streptococcus pneumoniae is a major cause of mortality globally. The introduction of pneumococcal conjugate vaccines (PCVs) has reduced the incidence of the targeted serotypes significantly, but expansion of non-targeted serotypes, serotype replacement, and incomplete vaccine-targeting contribute to pneumococcal disease in the vaccine era. Here, we characterize the changing population genetic landscape of S. pneumoniae in Norway over a 41-year period (1982-2022)., Methods: Since 2018, all cases of invasive pneumococcal disease have undergone whole-genome sequencing (WGS) at the Norwegian Institute of Public Health. In order to characterize the changing population over time, historical isolates were re-cultured and sequenced, resulting in a historical WGS dataset. Isolates were assigned to global pneumococcal sequence clusters (GPSCs) using PathogenWatch and assigned to serotypes using in silico (SeroBA) and in vitro methods (Quellung reaction). Temporal phylogenetic analyses were performed on GPSCs of particular interest., Results: The availability of WGS data allowed us to study capsular variation at the level of individual lineages. We detect highly divergent fates for different GPSCs following the introduction of PCVs. For two out of eight major GPSCs, we identified multiple instances of serotype switching from vaccine types to non-vaccine types. Dating analyses suggest that most instances of serotype switching predated the introduction of PCVs, but expansion occurred after their introduction. Furthermore, selection for penicillin non-susceptibility was not a driving force for the changing serotype distribution within the GPSCs over time., Conclusions: PCVs have been major shapers of the Norwegian disease-causing pneumococcal population, both at the level of serotype distributions and the underlying lineage dynamics. Overall, the introduction of PCVs has reduced the incidence of invasive disease. However, some GPSCs initially dominated by vaccine types escaped the effect of vaccination through expansion of non-vaccine serotypes. Close monitoring of circulating lineages and serotypes will be key for ensuring optimal vaccination coverage going forward., (© 2024. The Author(s).)

Background: Nasopharyngeal carriage of S. pneumoniae is a global health problem that has been associated with the emergence of severe disease and pathogen dissemination in the community. However, summary data on the carriage rate, antimicrobial susceptibility profile, and determinant factors is lacking., Method: Articles were extensively searched in bibliographic databases and gray literature using entry terms or phrases. Studies meeting eligibility criteria were extracted in MS Excel and exported to STATA version 17 software for statistical analysis. A random-effects model was used to compute the pooled magnitude of the nasal carriage of S. pneumoniae and its multidrug resistance. The heterogeneity was quantified by using the I 2 value. Publication bias was assessed using a funnel plot and Egger's test. Sensitivity analysis was done to assess the impact of a single study on the pooled effect size., Result: Of the 146 studies identified, 8 studies containing a total of 3223 children were selected for meta-analysis of the magnitude of the nasal carriage of S. pneumoniae and its multidrug resistance. The overall pooled prevalence of nasal carriage of S. pneumoniae and its MDR status in Ethiopian children was 32.77% (95%CI: 25.1, 40.44). and 31.22% (95%CI: 15.06, 46.84), respectively. The highest resistant pattern of S. pneumoniae was against tetracycline, which was 46.27% (95%CI: 37.75, 54.79), followed by 45.68% (95%CI: 34.43, 57.28) trimethoprim-sulfamethoxazole, while the least pooled prevalence was against chloramphenicol, which was 16.2% (95%CI: 9.44, 22.95). The pooled effect of age less than 5 years old (pooled OR = 1.97; 95% CI: 1.35, 2.88, P < 0.001), co-sleeping habit with others (pooled OR = 2.36; 95% CI: 1.77, 3.66; P < 0.001), sibling (pooled OR = 1.82; 95% CI: 1.14, 2.91, P = 0.01), history of hospitalization (pooled OR = 4.39; 95% CI: 1.86, 10.34, P = 0.001), and malnutrition (pooled OR = 2.18; 95% CI: 1.49, 3.19; P < 0.001) showed a statistical association with S. pneumoniae nasal carriage rate by using the random effect Sidik-Jonkman model., Conclusion: The magnitude of the nasopharyngeal carriage rate and multi-drug resistance status of S. pneumoniae alarms the need for immediate interventions such as strengthening antimicrobial stewardship programs, undertaking national antimicrobial surveillance, one-health initiatives, and national immunization programs., (© 2024. The Author(s).)

After introducing pneumococcal conjugate vaccines (PCVs), serotype replacement occurred in Streptococcus pneumoniae . Predicting which pneumococcal strains will become common in carriage after vaccination can enhance vaccine design, public health interventions, and understanding of pneumococcal evolution. Invasive pneumococcal isolates were collected during 1998-2018 by the Active Bacterial Core surveillance (ABCs). Carriage data from Massachusetts (MA) and Southwest United States were used to calculate weights. Using pre-vaccine data, serotype-specific inverse-invasiveness weights were defined as the ratio of the proportion of the serotype in carriage to the proportion in invasive data. Genomic data were processed under bioinformatic pipelines to define genetically similar sequence clusters (i.e., strains), and accessory genes (COGs) present in 5-95% of isolates. Weights were applied to adjust observed strain proportions and COG frequencies. The negative frequency-dependent selection (NFDS) model predicted strain proportions by calculating the post-vaccine strain composition in the weighted invasive disease population that would best match pre-vaccine COG frequencies. Inverse-invasiveness weighting increased the correlation of COG frequencies between invasive and carriage data in linear or logit scale for pre-vaccine, post-PCV7, and post-PCV13; and between different epochs in the invasive data. Weighting the invasive data significantly improved the NFDS model's accuracy in predicting strain proportions in the carriage population in the post-PCV13 epoch, with the adjusted R 2 increasing from 0.254 before weighting to 0.545 after weighting. The weighting system adjusted invasive disease data to better represent the pneumococcal carriage population, allowing the NFDS mechanism to predict strain proportions in carriage in the post-PCV13 epoch. Our methods enrich the value of genomic sequences from invasive disease surveillance.IMPORTANCE Streptococcus pneumoniae , a common colonizer in the human nasopharynx, can cause invasive diseases including pneumonia, bacteremia, and meningitis mostly in children under 5 years or older adults. The PCV7 was introduced in 2000 in the United States within the pediatric population to prevent disease and reduce deaths, followed by PCV13 in 2010, PCV15 in 2022, and PCV20 in 2023. After the removal of vaccine serotypes, the prevalence of carriage remained stable as the vacated pediatric ecological niche was filled with certain non-vaccine serotypes. Predicting which pneumococcal clones, and which serotypes, will be most successful in colonization after vaccination can enhance vaccine design and public health interventions, while also improving our understanding of pneumococcal evolution. While carriage data, which are collected from the pneumococcal population that is competing to colonize and transmit, are most directly relevant to evolutionary studies, invasive disease data are often more plentiful. Previously, evolutionary models based on negative frequency-dependent selection (NFDS) on the accessory genome were shown to predict which non-vaccine strains and serotypes were most successful in colonization following the introduction of PCV7. Here, we show that an inverse-invasiveness weighting system applied to invasive disease surveillance data allows the NFDS model to predict strain proportions in the projected carriage population in the post-PCV13/pre-PCV15 and pre-PCV20 epoch. The significance of our research lies in using a sample of invasive disease surveillance data to extend the use of NFDS as an evolutionary mechanism to predict post-PCV13 population dynamics. This has shown that we can correct for biased sampling that arises from differences in virulence and can enrich the value of genomic data from disease surveillance and advance our understanding of how NFDS impacts carriage population dynamics after both PCV7 and PCV13 vaccination., Competing Interests: The authors declare no conflict of interest.

Background: Pneumococcal conjugate vaccines (PCVs) provide strong direct protection in children, while limited data are available on their indirect effect on mortality among older age groups. This multicountry study aimed to assess the population-level impact of pediatric PCVs on all-cause pneumonia mortality among children ≥5 years of age, and invasive pneumococcal disease (IPD) cases in Chile., Methods: Demographic and mortality data from Argentina, Brazil, Chile, Colombia, and Mexico were collected considering the ≥ 5-year-old population, from 2000 to 2019, with 1 795 789 deaths due to all-cause pneumonia. IPD cases in Chile were also evaluated. Time series models were employed to evaluate changes in all-cause pneumonia deaths during the postvaccination period, with other causes of death used as synthetic controls for unrelated temporal trends., Results: No significant change in death rates due to all-cause pneumonia was detected following PCV introduction among most age groups and countries. The proportion of IPD cases caused by vaccine serotypes decreased from 29% (2012) to 6% (2022) among people aged ≥65 years in Chile., Discussion: While an effect of PCV against pneumonia deaths (a broad clinical definition that may not be specific enough to measure indirect effects) was not detected, evidence of indirect PCV impact was observed among vaccine-type-specific IPD cases., Competing Interests: Potential conflicts of interest . D. M. W. has received consulting fees from Pfizer, Merck, Affinivax, and Matrivax for work unrelated to this article; and is Principal Investigator on grants from Pfizer and Merck to Yale University for work unrelated to this article. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in US children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts., Methods: We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national health care surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses., Results: Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval, 1.8-3.9) visits and 2.4 (95% CI, 1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (95% CI, 11.2-20.4) visits and 13.2 (95% CI, 9.9-18.0) antibiotic prescriptions annually per 1000 children. PCV15/20-additional serotypes account for 0.4% (95% CI, 0.2%-0.6%) and 2.1% (95% CI, 1.5%-3.0%) of pediatric outpatient antibiotic use., Conclusions: Compared with PCV15-additional serotypes, PCV20-additional serotypes account for > 5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use., Competing Interests: Potential conflicts of interest. L. M. K. reports consulting fees from Merck Sharpe & Dohme and Vaxcyte for unrelated work. J. A. L. reports research grants from Pfizer and Merck Sharpe & Dohme; and consulting fees from Pfizer, Merck, Sharpe & Dohme, and Vaxcyte for unrelated work. S. Y. T. reports research grants from Pfizer for unrelated work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Streptococcus pneumoniae serotype 35B, a non-vaccine type, is a major contributor to the increase in pneumococcal infection post-vaccination. We aimed to understand the mechanism of its spread by characterizing 35B. The serotype, type 1 pilus (T1P) positivity, and antimicrobial susceptibility of 319 isolates in 2018-2022 were analysed and compared with those of isolates in 2014-2017 to find the changes. 35B accounted for 40 (12.5%) isolates. T1P positivity was notably higher in 35B (87.5%) than in the other serotypes. To confirm the role of T1P, an adhesion factor, we compared adherence to A549 cells between T1P -positive 35B isolates and their T1P -deficient mutants, showing contribution of T1P to adherence. Penicillin-non-susceptible rate of 35B was 87.5%, and meropenem-resistant 35B rate was 35.0%, which increased from 14.5% of 2014-2017 ( p  = 0.009). Multilocus sequence typing was performed in 35B strains. Prevalence of clonal complex 558, harbouring T1P and exhibiting multidrug non-susceptibility, suggested the advantages of 35B in attachment and survival in the host. The emergence of ST156 isolates, T1P -positive and non-susceptible to β-lactams, has raised concern about expansion in Japan. The increase of serotype 35B in pneumococcal diseases might have occurred due to its predominant colonizing ability after the elimination of the vaccine-serotypes.

Background: In early 2021, the 10-valent Pneumococcal conjugate vaccine (PCV10) was replaced with 13-valent (PCV13) by the federal directorate of immunization (FDI), Pakistan. We assessed the impact of a higher valent vaccine, PCV13, on the serotype distribution of nasopharyngeal carriage in rural Pakistan., Methods: Children <2 years were randomly selected from two rural union councils of Matiari, Sindh in Pakistan between September-October,2022. Clinical, sociodemographic and vaccination histories were recorded. Nasopharyngeal swabs were collected and processed at Infectious Disease Research Laboratory, Aga Khan University, Karachi. Whole genome sequencing was performed on the culture positive isolates., Results: Of the 200 children enrolled, pneumococcus was detected in 140(70 %) isolates. Majority of age-eligible children (60.1 %,110/183) received 3 PCV13 doses. PCV10 carriage declined from 13.2 %(78/590) in 2017/18 to 7.2 % (10/140) in 2022, additional PCV13 serotypes (3, 6A/6C and 19A) decreased from 18.5 %(109/590) to 11.4 %(16/140) while non-PCV13 serotypes increased from 68.3 %(403/590) to 81.4 %(114/140). There were 88.5 %(n = 124), 80.7 %(n = 113), 55.0 %(n = 77), and 46.0 %(n = 65) isolates predicted to be resistant to cotrimoxazole, penicillin(meningitis cut-off), tetracycline, and erythromycin respectively., Conclusion: Replacing PCV10 with PCV13 rapidly decreased prevalence of PCV13 carriage among vaccinated children in Matiari, Pakistan. Vaccine-driven selection pressure may have been responsible for the increase of non-PCV13 serotypes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for infants in Argentina's national immunization program (NIP) in a 2 + 1 schedule since 2012. Licensure of the 15-valent vaccine (PCV15) is anticipated soon, and the 20-valent vaccine (PCV20) recently received regulatory approval. This cost-effectiveness analysis examined the public health and economic implications of transitioning from PCV13 to either PCV15 or PCV20 in Argentina's pediatric NIP., Methods: A decision-analytic Markov model was used with a 10-year time horizon and a 3.0% annual discount rate for costs and benefits. Vaccine effectiveness estimates were derived from Argentinian surveillance data, PCV13 clinical effectiveness and impact studies, and PCV7 efficacy studies. Population, epidemiologic, and economic inputs were obtained from literature and Argentinian-specific data. The study adopted a healthcare system perspective; sensitivity and scenario analyses were conducted to assess input parameters and structural uncertainty., Results: Compared with PCV13, PCV20 was estimated to avert an additional 7,378, 42,884, and 172,389 cases of invasive pneumococcal disease (IPD), all-cause pneumonia, and all-cause otitis media (OM), respectively, as well as 3,308 deaths, resulting in savings of United States Dollars (USD) 50,973,962 in direct medical costs. Compared with PCV15, PCV20 was also estimated to have greater benefit, averting an additional 6,140, 35,258, and 142,366 cases of IPD, pneumonia, and OM, respectively, as well as 2,624 deaths, resulting in savings of USD 37,697,868 in direct medical costs. PCV20 was associated with a higher quality-adjusted life year gain and a lower cost (i.e., dominance) versus both PCV13 and PCV15. Results remained robust in sensitivity analyses and scenario assessments., Conclusion: Over a 10-year horizon, vaccination with PCV20 was expected to be the dominant, cost-saving strategy versus PCV13 and PCV15 in children in Argentina. Policymakers should consider the PCV20 vaccination strategy to achieve the greatest clinical and economic benefit compared with lower-valent options., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Lucila Rey-Ares reports a relationship with Pfizer Inc that includes: employment. An Ta reports a relationship with Cytel Inc that includes: employment. An Ta reports a relationship with Pfizer Inc that includes: consulting or advisory. Donata Freigofaite reports a relationship with Cytel Inc that includes: employment. Sophie Warren reports a relationship with Pfizer Inc that includes: employment. Mercedes Mac Mullen reports a relationship with Pfizer Inc that includes: employment. Carolina Carballo reports a relationship with Pfizer Inc that includes: employment. Liping Huang reports a relationship with Pfizer Inc that includes: employment. The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: LRA, CC, and LH are employees of Pfizer Inc. SW and MM were employed by Pfizer Inc. at the time of manuscript development. AT received consulting fees from Pfizer Inc. for the study and manuscript development and is an employee of Cytel Inc. DF was employed by Cytel Inc. at the time of manuscript development. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: The COVID-19 pandemic led to the institution of public health measures in many countries which reduced respiratory infections. We aimed to identify and characterize changes in pediatric (<18 years) invasive pneumococcal disease (pIPD) in Portugal in 2018-2023., Methods: pIPD cases were identified by culture and molecular methods and stratified by age and serotype. When available the susceptibility of the isolates to antimicrobials was evaluated., Results: pIPD cases were markedly reduced in the last trimester of 2019-2020 and the entire 2020-2021 season. While 2021-2022 was in line with pre-pandemic seasons, in 2022-2023, the number of pIPD cases exceeded those found pre-pandemic. Molecular tests were responsible for identifying and serotyping 30% of cases, highlighting their importance in evaluating pIPD. Among the 316 pIPD cases, 37 different serotypes were detected, of which serotypes 3 (n = 85, 26.9%), 8 (n = 25, 7.9%), 10A (n = 21, 6.6%) and 24F (n = 20, 6.3%) were the most frequent. The post-pandemic serotype distribution reflected mostly pre-pandemic trends and the rebound was not driven by particular serotypes. We identified many vaccine failures, most (n = 37) representing serotype 3 infections. Penicillin non-susceptibility increased from 14% pre-pandemic to 29%, with serotype 24F becoming particularly significant., Conclusions: The higher number of cases of pIPD post-COVID-19 in Portugal raises the possibility of a higher burden of pneumococcal disease in Europe post-pandemic. The relatively stable serotype distribution and the current availability of the higher valency conjugate vaccines PCV15 and PCV20, potentially preventing a large proportion of pIPD (43% and 67%, respectively), offer an opportunity to control this increase., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JM-C received research grants administered through his university and received honoraria for serving on the speakers bureaus of Pfizer and Merck Sharp and Dohme. MR received honoraria for serving on the speakers bureau of Pfizer and Merck Sharp and Dohme, for serving in expert panels of Merck Sharp and Dohme, support for attending meetings from Pfizer, and received research grants administered through his university from Merck Sharp and Dohme. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Lower respiratory infections and invasive disease caused by Streptococcus pneumoniae serotype 3 remain major clinical challenges around the world, despite widespread availability of updated vaccines., Methods: As part of CANWARD, antimicrobial susceptibility testing and serotyping were performed on all S. pneumoniae isolates from 2007 to 2021. A subset of 226/264 (85.6%) serotype 3 isolates were selected for WGS to determine sequence type (ST)/clonal cluster (CC) and correspondence of antimicrobial resistance determinants (erm, mefAE, tetM, cat, folA, folP) with resistance phenotype., Results: Of the 3,039 S. pneumoniae isolates obtained from 2007 to 2021, 8.7% (n = 264) were serotype 3, with 64.0% of respiratory origin and 36.0% from blood. Of 226 sequenced serotype 3 isolates, 184 (81.4%) were ST180 (GPSC12). The proportion of ST8561 (single locus variant of ST180) increased from 7.2% to 16.6% during the study period. An increasing proportion of serotype 3 isolates had phenotypic resistance (P = 0.0007) and genetic resistance determinants (P = 0.004), comparing 2017-21 to 2007-11, largely due to a recently expanded ST180 clade with cat, tetM and mef determinants., Conclusions: S. pneumoniae serotype 3 from GPSC12 continues to dominate throughout Canada, with an increase in the proportion of ST8561. The proportion of serotype 3 isolates that are phenotypically resistant and with genetic resistance determinants is increasing over time, reflecting a global increase in GPSC12 genotypes with known resistance determinants. Phylogenomic characterization of isolates collected over time and from around the world may facilitate improved treatment and enhanced prevention strategies, including new vaccines with activity against S. pneumoniae serotype 3., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Objectives: This study aims to understand the magnitude of and mechanisms underlying the development of cardiovascular events (CVEs) in patients with invasive pneumococcal disease (IPD). We aimed to identify factors that contribute to the occurrence of CVEs within 1 year after admission and discuss implications for patient care., Methods: A multicentered cohort study included adult patients from four Dutch hospitals who had a positive blood culture for Streptococcus pneumoniae and any type of clinical manifestation between 2012 and 2020. Disease characteristics and microbiological data were systematically collected from electronic patient files. The main outcome measures were the occurrence of stroke and acute coronary syndromes (ACS)., Results: Of 914 eligible patients, 4.2% experienced a CVE within 1 year after admission for IPD. ACS mainly occurred in the first 2 weeks, whereas stroke developed throughout follow-up. Although ACS was positively associated with disease severity, the sole independent predictor was alcohol abuse (odds ratio [OR] 3.840, 95% confidence interval [CI] 1.108-13.303). Although stroke occurred in 6.3% of meningitis cases, the best clinical predictor of stroke was a body temperature >39.5 °C at admission (OR 3.117 [1.154-8.423]). In the adult IPD population aged <70 years, pneumococcal serotypes were the primary predictors of ACS (7F; OR 15.733 [1.812-136.632]) and stroke (22F; OR 7.320 [1.193-44.903])., Conclusions: Adverse CVEs were not uncommon after IPD diagnosis and deserve attention, especially in the high-risk groups we identified in our study population. Whether specific serotypes play a role in the development of CVE requires substantiation in further research., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Patients with nephrotic syndrome (NS) are at a higher risk of developing invasive pneumococcal disease (IPD). Pneumococcal carriage studies are helpful tools for detecting potentially infectious serotypes and guiding immunization efforts. Pneumococcal nasopharyngeal colonization is common, and IPD can easily occur in an immunosuppressed state. Limited information is available regarding the frequency of pneumococcal carriage in individuals with NS. The aim of this study was to evaluate pneumococcal carriage and serotype distribution in children with NS., Methods: Pneumococcal carriage was detected by real-time PCR assays from nasopharyngeal swab samples from 98 children with NS, and 100 healthy controls. Isolates were serotyped by real-time PCR., Results: The pneumococcal carriage rate was 44.9% in children with NS. Regarding the recommendation about pneumococcal immunization in children with NS, the vaccination rate was low. Also, non-PCV13 serotypes have been detected in at least 25% of PCV13-vaccinated children. There is no statistically significant difference in total pneumococcal carriage rate, PCV13 serotype carriage rate, or non-PCV13 serotype carriage rate between children with NS and healthy controls (p > 0.05 for all)., Conclusions: The pneumococcal carriage rate was similar between children with NS and healthy controls. However, because children with NS have an increased risk for IPD, the serotype distribution of children with NS can demonstrate the improved protection offered by new pneumococcal vaccines. Regular monitoring for IPD is crucial for assessing the evolving sero-epidemiology of pneumococcal infections and evaluating the effectiveness of vaccines for children with NS., (© 2024. The Author(s).)

Background: Bacterial etiologies of acute otitis media (AOM) have shifted from the introduction of pneumococcal conjugate vaccines (PCVs), antibiotic selection and competition among species. We characterized Streptococcus pneumoniae ( Spn ), Haemophilus influenzae ( Hflu ) and Moraxella catarrhalis ( Mcat ) in the nasopharynx during well-child healthy visits and at the onset of AOM, and in middle ear fluid (MEF) of children with AOM to assess anticipated effects of higher-valency PCVs (PCV15 and PCV20)., Methods: From September 2021 to September 2023, we conducted a prospective longitudinal cohort study of PCV13 immunized children 6-36 months old. MEF was collected via tympanocentesis. Serotyping and antibiotic susceptibility testing were performed on Spn , Hflu and Mcat isolates., Results: We obtained 825 nasopharyngeal and 216 MEF samples from 301 children. The order of frequency of nasopharyngeal colonization was Mcat , Spn and Hflu ; Hflu was the predominant otopathogen in MEF. Among Spn isolates, non-PCV15, non-PCV20 serotypes predominated in the nasopharynx and in MEF; the most frequent serotype was 35B. Among MEF samples, 30% of Spn isolates were amoxicillin nonsusceptible; 23% of Hflu isolates and 100% of Mcat isolates were β-lactamase-producing., Conclusion: The majority of Spn isolates among young children were non-PCV15, non-PCV20 serotypes, especially serotype 35B; therefore, the impact of higher-valency PCVs in reducing pneumococcal colonization or AOM is expected to be limited. Hflu continues to be the most frequent AOM pathogen. Antibiotic susceptibility data suggest a high dose of amoxicillin/clavulanate or alternative drugs that are effective against contemporary mix of otopathogens could be considered for optimal empiric selection to provide the best efficacy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Adults living with human immunodeficiency virus (ALWHIV) receiving antiretroviral therapy (ART) exhibit higher pneumococcal carriage prevalence than adults without HIV (HIV-). To assess factors influencing high pneumococcal carriage in ALWHIV, we estimated pneumococcal carriage acquisition and clearance rates in a high transmission and disease-burdened setting at least 10 years after introducing infant PCV13 in routine immunisation., Methods: We collected longitudinal nasopharyngeal swabs from individuals aged 18-45 in Blantyre, Malawi. The study group included both HIV- individuals and those living with HIV, categorised based on ART duration as either exceeding 1 year (ART > 1y) or less than 3 months (ART < 3 m). Samples were collected at baseline and then weekly for 16 visits. To detect pneumococcal carriage, we used classical culture microbiology, and to determine pneumococcal serotypes, we used latex agglutination. We modelled trajectories of serotype colonisation using multi-state Markov models to capture pneumococcal carriage dynamics, adjusting for age, sex, number of under 5 year old (< 5y) children, social economic status (SES), and seasonality., Results: We enrolled 195 adults, 65 adults in each of the study groups. 51.8% were females, 25.6% lived with more than one child under 5 years old, and 41.6% lived in low socioeconomic areas. The median age was 33 years (IQR 25-37 years). The baseline pneumococcal carriage prevalence of all serotypes was 31.3%, with non-PCV13 serotypes (NVT) at 26.2% and PCV13 serotypes (VT) at 5.1%. In a multivariate longitudinal analysis, pneumococcal carriage acquisition was higher in females than males (hazard ratio [HR], NVT [1.53]; VT [1.96]). It was also higher in low than high SES (NVT [1.38]; VT [2.06]), in adults living with 2 + than 1 child < 5y (VT [1.78]), and in ALWHIV on ART > 1y than HIV- adults (NVT [1.43]). Moreover, ALWHIV on ART > 1y cleared pneumococci slower than HIV- adults ([0.65]). Residual VT 19F and 3 were highly acquired, although NVT remained dominant., Conclusions: The disproportionately high point prevalence of pneumococcal carriage in ALWHIV on ART > 1y is likely due to impaired nasopharyngeal clearance, which results in prolonged carriage. Our findings provide baseline estimates for comparing pneumococcal carriage dynamics after implementing new PCV strategies in ALWHIV., (© 2024. The Author(s).)

Invasive pneumococcal disease (IPD) due to non-vaccine serotypes after the introduction of pneumococcal conjugate vaccines (PCV) remains a global concern. This study used pathogen genomics to evaluate changes in invasive pneumococcal lineages before, during and after vaccine introduction in South Africa. We included genomes (N = 3104) of IPD isolates from individuals aged <18 years (2005-20), spanning four periods: pre-PCV, PCV7, early-PCV13, and late-PCV13. Significant incidence reductions occurred among vaccine-type lineages in the late-PCV13 period compared to the pre-PCV period. However, some vaccine-type lineages continued to cause invasive disease and showed increasing effective population size trends in the post-PCV era. A significant increase in lineage diversity was observed from the PCV7 period to the early-PCV13 period (Simpson's diversity index: 0.954, 95% confidence interval 0.948-0.961 vs 0.965, 0.962-0.969) supporting intervention-driven population structure perturbation. Increases in the prevalence of penicillin, erythromycin, and multidrug resistance were observed among non-vaccine serotypes in the late-PCV13 period compared to the pre-PCV period. In this work we highlight the importance of continued genomic surveillance to monitor disease-causing lineages post vaccination to support policy-making and future vaccine designs and considerations., (© 2024. The Author(s).)

Streptococcus pneumoniae carriage studies are crucial to monitor changes induced by use of pneumococcal conjugate vaccines and inform vaccination policies. In this cross-sectional study, we examined changes within the pneumococcal population following introduction of PCV13 in 2015 in the National Immunization Program (NIP), in Portugal. In 2018-2020 (NIP-PCV13), we obtained 1450 nasopharyngeal samples from children ≤6 years attending day-care. We assessed serotypes, antimicrobial resistance, and genotypes (MLST and GPSC) and compared findings with earlier periods: 2009-2010 (pre-PCV13), 2011-2012 (early-PCV13), and 2015-2016 (late-PCV13). Pneumococcal carriage prevalence remained stable at 60.2 %. Carriage of PCV13 serotypes was 10.7 %, markedly reduced compared to pre-PCV13 period (47.6 %). The most prevalent PCV13 serotypes were 19F, 3, and 19A all showing a significant decreasing trend compared to the pre-PCV13 period (from 7.1 % to 4.7 %, 10.1 % to 1.8 %, and 14.1 % to 1.8 %, respectively), a notable observation given the described limited effectiveness of PCV13 against serotype 3. Non-vaccinated children and children aged 4-6 years were more likely to carry PCV13 serotypes (2.5-fold, 95 %CI [1.1-5.6], and 2.9-fold, 95 %CI [1.3-6.8], respectively). The most prevalent non-PCV13 serotypes were 15B/C, 11A, 23B, 23A, and NT, collectively accounting for 51.9 % of all isolates. In total, 30.5 % of all pneumococci were potentially covered by PCV20. Resistance to penicillin (low-level) and macrolides increased significantly, from 9.3 % and 13.4 %, respectively, in the late-PCV13 period, to approximately 20 % each, mostly due to lineages expressing non-PCV13 serotypes, nearing pre-PCV13 levels. An expansion of lineages traditionally associated with PCV13 serotypes, like CC156-GPSC6 (serotype 14) and CC193-GPSC11 (serotype 19F), but now predominantly expressing non-PCV13 serotypes (11A, 15B/C, and 24F for GPSC6; and 15A and 21 for GPSC11) was noted. These findings indicate that the pneumococcal population is adapting to the pressures conferred by PCV13 and antimicrobial use and indicate the need to maintain close surveillance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RSL has received consulting and speaking fees from Pfizer and Merck Sharp & Dome. RSL has received funds for unrestricted research grants from Pfizer and Merck Sharp & Dome, paid directly to her institution. ABA has received consulting and speaking fees from Pfizer and Merck Sharp & Dome. All other authors declare they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pneumococcal disease in older adults in the United Kingdom is rising despite immunisation. A key gap in the literature is the clinical effectiveness of revaccination with the pneumococcal polysaccharide vaccine (PPV23)., Methods: A cohort study was performed in England, using electronic medical records in the Clinical Practice Research Datalink. Individuals aged ≥64 years and vaccinated with PPV23 were included. Rates of hospitalised pneumonia (HP) and invasive pneumococcal disease (IPD) were compared between individuals receiving a single PPV23 dose versus those receiving two doses using multi-level Cox proportional hazards models. Propensity score weighting was performed to minimise the effect of confounding covariates across the comparison groups., Results: Between 2006 and 2019, there were 462 505 eligible participants. Of those, 6747 (1·5 %) received revaccination. Two doses compared to one dose was associated with an increased risk of HP (adjusted Hazard Ratio [aHR] 1·95; 95 %CI 1·74-2·20) and IPD (aHR 1·44; 95 %CI 1·41-1·46). In participants aged 64-74 years PPV23 revaccination was associated with more IPD (aHR 2·02; 95 %CI 1·75-2·33) and HP (aHR 1·46; 95 %CI 1·42-1.49). In those aged ≥75 years PPV23 revaccination was associated with more HP (aHR 1·12; 95 %CI 1·08-1·16) with no statistically significant difference detected in risk of IPD (aHR 1·20; 95 %CI 0·94-1·52)., Conclusions: No clear benefit of PPV23 revaccination was measured in older adults in this observational study. The small proportion of revaccinated subjects limits the strength of the conclusions. Further research evaluating the clinical effectiveness of PPV23 revaccination is required., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: NF and DH are currently in receipt of grant support from Seqirus UK Ltd. for the evaluation of influenza vaccines in the UK. NF and DH have previously received research-initiated and industry-initiated research grant support from GlaxoSmithKline (GSK) Biologicals for evaluation of rotavirus vaccination in the UK. DH has also received grants from GSK, Sanofi Pasteur, and Merck & Co (Kenilworth, New Jersey, USA) for rotavirus strain surveillance. KD, VD, LB, SA, NB and KF have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate the cost-effectiveness of the 20-valent pneumococcal conjugate vaccine (PCV20) compared to 13-valent pneumococcal conjugate vaccine (PCV13) for the pediatric population in Korea, where the four-dose vaccine coverage rate is over 97%., Methods: We constructed a Markov model to calculate the cost and quality-adjusted life-years (QALYs) over 10 years. The health states were susceptible states; disease states, which included invasive pneumococcal diseases such as meningitis, bacteremia, pneumonia, and acute otitis media; and death attributable to pneumococcal disease. The annual incidence and mortality due to pneumococcal diseases were estimated based on the serotypes covered by PCV13 and PCV20, vaccine coverage rate, vaccine effectiveness, and population size. Vaccine, administration, and disease costs were included in the model., Results: In the total population (n = 51,431,305), PCV20 prevented more pneumococcal diseases and deaths, resulting in a gain of 74,855 QALY over PCV13. Meanwhile, the PCV20 group spent $275,136,631 less than the PCV13 group. As PCV20 gained more QALYs but spent less on total medical costs than PCV13, PCV20 was dominant over PCV13., Conclusions: In the Korean population, PCV20 is a cost-effective and dominant option over PCV13. Our findings provide evidence for decision-making regarding the introduction of PCV20 in countries with high vaccine coverage., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sun-Kyeong Park reports financial support was provided by Pfizer Korea Ltd. Young June Choe reports financial support was provided by Pfizer Korea Ltd. Ju-Yeon Lee reports financial support was provided by Pfizer Korea Ltd. In-Ae Suk reports financial support was provided by Pfizer Korea Ltd. Young-Soo Kim reports financial support was provided by Pfizer Korea Ltd. Hak-Yeon Kim reports financial support was provided by Pfizer Korea Ltd. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Streptococcus pneumoniae, a medically important opportunistic bacterial pathogen of the upper respiratory tract, is a major public health concern, causing a wide range of pneumococcal illnesses, both invasive and noninvasive. It is associated with significant global morbidity and mortality, including pneumonia, meningitis, sepsis, and acute otitis media. The major purpose of this study was to determine the molecular epidemiology of Streptococcus pneumoniae strains that cause invasive and noninvasive infections in Ethiopia. A prospective study was undertaken in two regional hospitals between January 2018 and December 2019. Whole-genome sequencing was used to analyze all isolates. Serotypes and multilocus sequence types (MLST) were derived from genomic data. The E-test was used for antimicrobial susceptibility testing. Patient samples obtained 54 Streptococcus pneumoniae isolates, 33 from invasive and 21 from noninvasive specimens. Our findings identified 32 serotypes expressed by 25 Global Pneumococcal Sequence Clusters (GPSCs) and 42 sequence types (STs), including 21 new STs. The most common sequence types among the invasive isolates were ST3500, ST5368, ST11162, ST15425, ST15555, ST15559, and ST15561 (2/33, 6% each). These sequence types were linked to serotypes 8, 7 C, 15B/C, 16 F, 10 A, 15B, and 6 A, respectively. Among the noninvasive isolates, only ST15432, associated with serotype 23 A, had numerous isolates (4/21, 19%). Serotype 14 was revealed as the most resistant strain to penicillin G, whereas isolates from serotypes 3, 8, 7 C, and 10 A were resistant to erythromycin. Notably, all serotype 6 A isolates were resistant to both erythromycin and penicillin G. Our findings revealed an abnormally significant number of novel STs, as well as extremely diversified serotypes and sequence types, implying that Ethiopia may serve as a breeding ground for novel STs. Recombination can produce novel STs that cause capsular switching. This has the potential to influence how immunization campaigns affect the burden of invasive pneumococcal illness. The findings highlight the importance of continuous genetic surveillance of the pneumococcal population as a vital step toward enhancing future vaccine design., (© 2024. The Author(s).)

Introduction: Pneumococcal disease is a serious global public health concern. The primary causative agent of severe illnesses such as pneumonia, meningitis, acute otitis media, and bacteremia is the pneumococcus bacterium. The pneumococcal conjugate vaccine is a key strategy to reduce the burden of pneumococcal disease. Understanding the spatial distribution of complete childhood pneumococcal conjugate vaccine utilization and its associated factors is crucial for designing strategies to improve vaccination implementation. Therefore, this study aimed to determine the spatial distribution of complete childhood pneumococcal conjugate vaccination coverage and identify its determinants in Ethiopia., Method: A spatial and multilevel analysis was conducted using data from the 2019 Ethiopian Mini Demographic and Health Survey. The analysis included a total of 2,055 weighted children. The association between the outcome variable and the explanatory variables was determined by calculating adjusted odds ratios at a 95% confidence interval. Explanatory variables were considered significantly associated with the outcome if the p-value was less than 0.05., Result: The prevalence of complete childhood pneumococcal conjugate vaccination in Ethiopia was 53.94% (95% CI: 51.77, 56.08). Higher complete childhood pneumococcal vaccination coverage was observed in the Addis Ababa, Tigray, Amhara, Benishangul-Gumuz, and Oromia regions, while lower coverage was seen in the Afar, Somali, and SNNPR regions of Ethiopia. Factors significantly associated with complete childhood pneumococcal conjugate vaccination included maternal age, antenatal care visits, place of delivery, region, community women's literacy level, community poverty level, and community antenatal care utilization., Conclusion: The distribution of complete childhood pneumococcal conjugate vaccination exhibited spatial variability across Ethiopia. Approximately half of children aged twelve to thirty-five months received the full dose of the childhood pneumococcal conjugate vaccine in the country. Several factors were identified as statistically significant determinants of complete childhood pneumococcal conjugate vaccination, including maternal age, antenatal care visits, place of delivery, region, community women's literacy level, community poverty level, and community ANC utilization. Therefore, policies and strategies aimed at combating pneumococcal disease should consider these determinants and address areas with low vaccination coverage., (© 2024. The Author(s).)

Background: Streptococcus pneumoniae, a major contributor to global morbidity and mortality, disproportionately affects children, the elderly, and immunocompromised individuals. Despite vaccination efforts, the challenge of serotype replacement highlights the ongoing struggle against invasive pneumococcal diseases (IPD) in Morocco, emphasizing the need for updated public health strategies and vaccine efficacy assessments., Methods: This study was conducted at the Ibn Rochd University Hospital Center and the Mohammed VI University Hospital Center from 2019 to 2022, focusing on hospitalized children. It involved the analysis of 74 strains of IPD, assessing the distribution of pneumococcal serotypes and their antibiotic sensitivity in the post-vaccination era., Results: The prevalence of meningitis or meningo-encephalitis was found to be 66% among the study subjects, with the most frequent serotypes being 3, 19A, 6B, 14, and 11. These serotypes varied significantly by age and location. Coverage rates for the pneumococcal conjugate vaccines, PCV-10 and PCV-13, were 20.27% and 56.75%, respectively. Notably, 43% of the strains were non-vaccine serotypes, with serotypes 3 and 19 accounting for 36% of the infections in children, indicating a lack of vaccine efficacy against these types. Additionally, 31.3% of the strains were Penicillin non-susceptible Streptococcus pneumoniae (PNSP), with 81.25% associated with non-vaccine serotypes., Conclusions: This study highlights the persistence of IPD in Moroccan children, revealing significant challenges despite vaccination efforts. With the reintroduction of PCV-13, concerns about the efficacy against non-vaccine serotypes, particularly 3 and 19A, remain. Continuous surveillance and adaptable vaccination strategies are essential to combat these serotype replacements and ensure the effectiveness of future preventive measures.

Background: 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., Methods: 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., Findings: 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%)., Interpretation: 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., Funding: 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., Competing Interests: Declaration of interests SAM has received grant funds from MSD, Pfizer, GSK, and the Bill and Melinda Gates Foundation; and honoraria from GSK, related to this work. CvM declares grant funds from Pfizer. CvM and VC declare honoraria from MSD and Pfizer. CC declares grant funds from Sanofi and the Bill and Melinda Gates Foundation. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Streptococcus pneumoniae has been estimated to cause 9·18 million cases of pneumococcal pneumonia, meningitis, and invasive non-pneumonia non-meningitis disease and 318 000 deaths among children younger than 5 years in 2015. We estimated the potential impact and cost-effectiveness of pneumococcal conjugate vaccine (PCV) introduction., Methods: We updated our existing pseudodynamic model to estimate the impact of 13-valent PCV (PCV13) in 112 low-income and middle-income countries by adapting our previously published pseudodynamic model with new country-specific evidence on vaccine coverage, burden, and post-introduction vaccine impact from WHO-UNICEF estimates of national immunisation coverage and a global burden study. Deaths, disability-adjusted life-years (DALYs), and cases averted were estimated for children younger than 5 years born between 2000 and 2030. We used specific PCV coverage in each country and a hypothetical scenario in which coverage increased to diphtheria-tetanus-pertussis (DTP) levels. We conducted probabilistic uncertainty analyses., Findings: Using specific vaccine coverage in countries, we estimated that PCV13 could prevent 697 000 (95% credibility interval 359 000-1 040 000) deaths, 46·0 (24·0-68·9) million DALYs, and 131 (89·0-172) million cases in 112 countries between 2000 and 2030. PCV was estimated to prevent 5·3% of pneumococcal deaths in children younger than 5 years during 2000-30. The incremental cost of vaccination would be I$851 (510-1530) per DALY averted. If PCV coverage were increased to DTP coverage in 2020, PCV13 could prevent an additional 146 000 (75 500-219 000) deaths., Interpretation: The inclusion of real-world evidence from lower-income settings revealed that delays in PCV roll-out globally and low PCV coverage have cost many lives. Countries with delays in vaccine introduction or low vaccine coverage have experienced many PCV-preventable deaths. These findings underscore the importance of rapidly scaling up PCV to achieve high coverage and maximise vaccine impact., Funding: Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance., Competing Interests: Declaration of interests MJ and CC received funding from the Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance (INV-009125/OPP1157270) for this study. MJ received research grants to his institution from UK National Institute for Health and Care Research (NIHR), Resuscitation Council UK, Bill & Melinda Gates Foundation, WHO, Gavi, Wellcome Trust, European Commission, InnoHK, Task Force for Global Health, and US Centers for Disease Control and Prevention. JAGS has received research grants from Gavi, the UK Medical Research Council, Wellcome Trust, NIHR, Bill & Melinda Gates Foundation, and Emory University to his institution. CC has received research grants to her institution from the Singapore Ministry of Health's National Medical Research Council (HCSAINV22jul-0005; PHRGOC22Jul-0020), the Ministry of Education (MOE2018-T2–2-070), Singapore Food Agency, Jurong Health Fund, Woodlands Health Campus, and the Thai Health Promotion Foundation. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: I declare no competing interests.

Competing Interests: BK declares funding to their organisation Medical Research Council Unit, The Gambia, at the London School of Hygiene and Tropical Medicine for pneumococcal research from PATH and Bill & Melinda Gates Foundation; funding to their organisation Medical Research Council Unit Gambia for vaccine research from Pfizer; and participation in a data safety monitoring board for Johnson & Johnson for COVID-19 vaccines. BT declares no competing interests.

Competing Interests: We declare no competing interests.

Background: Paediatric pneumococcal conjugate vaccine (PCV) programmes in England using seven-valent PCV (PCV7) in 2006 and 13-valent PCV (PCV13) in 2010 have reduced vaccine-type invasive pneumococcal disease, but the overall effect has been reduced by an increase in invasive pneumococcal disease due to non-vaccine serotypes and serotype 3. We developed pneumococcal transmission models to investigate the potential effect on invasive pneumococcal disease of higher valency PCVs covering an additional two (ie, 15-valent PCV [PCV15]) or seven serotypes (ie, 20-valent PCV [PCV20]) in England., Methods: We conducted a modelling study using realistic, age-structured, and compartmental deterministic models fitted to carriage data from before the introduction of PCVs and invasive pneumococcal disease data from before and after the introduction of PCV7 and PCV13 in England from the UK Heath Security Agency invasive pneumococcal disease surveillance system. We estimated key parameters, including PCV7 and PCV13 efficacy against vaccine-type carriage and invasiveness of PCV7 serotypes; the additional serotypes in PCV13, PCV15 and PCV20; and non-vaccine serotypes. We simulated the effect of transitioning from PCV13 to PCV15 or PCV20 in infants under the current 1 + 1 vaccination schedule and investigated the effect of reduced carriage protection against PCV13 serotypes due to attenuation of immunogenicity in higher valency vaccines., Findings: Our results suggest that PCV15 might increase overall invasive pneumococcal disease as the reduction in vaccine-type invasive pneumococcal disease would be counterbalanced by an increase in non-PCV15 invasive pneumococcal disease. By contrast, PCV20 is projected to have a substantial impact on overall invasive pneumococcal disease due to higher invasiveness of the additional serotypes covered by PCV20 than the replacing non-vaccine serotypes. Reduced carriage protection against PCV13 serotypes with higher valency vaccines would amplify these effects., Interpretation: Replacing PCV13 with PCV20 is likely to have a substantial public health benefit, but PCV15 could potentially increase the overall burden of disease., Funding: UK Health Security Agency and National Institute of Health Research., Competing Interests: Declaration of interests The Immunisation and Vaccine Preventable Diseases Division of the UK Health Security Agency provides vaccine manufacturers with post-marketing surveillance reports on pneumococcal and meningococcal infections, which the companies are required to submit to the Medicines and Healthcare Products Regulatory Agency in compliance with the companies' risk management strategy. A cost recovery charge is made for these reports. SNL performs contract research on behalf of St George's University of London and the UK Health Security Agency for pharmaceutical companies but receives no personal remuneration. The Respiratory and Vaccine Preventable Bacteria Reference Unit of the UK Health Security Agency has received grant funding from vaccine manufacturers for investigator-led research projects on pneumococcal surveillance. EM receives support from the National Institute for Health Research (NIHR) Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England (Grant Reference NIHR200929). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

This narrative review describes pneumococcal serotype prevalence for invasive disease and carriage and antibiotic resistance among specimens collected from children in countries across South and Southeast Asia from 2012 to 2024. Literature search retrieved 326 articles; 96 were included. The prevalence of pneumococcal serotypes varied geographically and over time after introduction of pneumococcal conjugate vaccine. Serotypes common in both pneumococcal carriage and disease were 6A, 6B, 14, 15B/15C, 19F, and 23F; serotypes 1, 3, 5, 19A, 15A, 10A, and 35B were also common in disease. Most of these serotypes are included in the 13-valent and 10-valent PCV. Carriage and disease isolates remained generally highly susceptible to vancomycin (mostly 100%) and levofloxacin (mostly >97%). These findings indicate that vaccine-preventable serotypes contribute significantly to pneumococcal disease burden in children in South and Southeast Asia. Consistency of national immunization programs with World Health Organization recommendations may reduce rates of pneumococcal disease in this region.

Reductions in all-cause otitis media (OM) following widespread pneumococcal conjugate vaccine use have plateaued. Granular burden of disease data are needed to guide evaluation and implementation of new measures targeting OM prevention. We conducted a retrospective study to assess the incidence and treatment costs of OM, tympanostomy tube placement (TTP), and hearing loss in children aged <5 years in the United States (US). OM episodes and TTP between 2016 and 2017 were identified in IBM MarketScan Commercial Claims and Encounters, Medicare Supplemental and Coordination of Benefits, and Multi-Medicaid databases using diagnosis codes (ICD-10). The incidence rate per 100,000 person-years (IR) of OM in <5-year-olds was 62,726 in Commercial/Medicare databases and 55,874 in Medicaid. IRs peaked at 9-<12 months (115,552 and 110,960, respectively). Approximately 5% and 4% of OM episodes in the respective databases had TTP (IR 3233 and 2404). Around 2% of children with OM had hearing loss (IR 1468 and 1109, respectively), of whom 41% had TTP. We estimated that there were 11.1 million OM episodes in 2020 costing USD 4.8 billion. 243,618 children were estimated to have OM with hearing loss at a direct total cost of USD 637 million, or 13% of the overall cost. The clinical and economic burden attributable to OM in the US was high in children aged <5 years during the study period. Novel approaches are needed to improve and broaden vaccine-induced protection against OM and its complications. The study results could guide policymakers considering age-specific interventions to reduce the OM burden.

In September 2023, 10-valent pneumococcal conjugate vaccine (PCV) was replaced by 15-valent PCV (PCV15) in Sweden's pediatric national immunization program. Following European approval of 20-valent PCV (PCV20) in March 2024, we assessed the cost-effectiveness of PCV20 versus PCV15, both under 2 + 1 schedule, among Sweden's pediatric population. A Markov state-transition model evaluated the economic and health benefits of PCV20 versus PCV15 among all ages over a 10-year time horizon. The base case adopted a Swedish payer perspective with an annual cycle length and 3.0% discount rate for costs and outcomes. Country-specific data informed population size, epidemiology, costs, and quality of life estimates. PCV15/PCV20 effect estimates were informed by PCV13 clinical effectiveness and impact studies plus PCV7 efficacy studies. Sensitivity analyses evaluated model robustness, including PCV20 under a 3 + 1 schedule. PCV20 was associated with higher quality-adjusted life year gains versus PCV15, averting an estimated 3,116 invasive pneumococcal disease cases 21,109 inpatient pneumonia cases, 6,618 outpatient pneumonia cases, and 36,209 otitis media cases, plus 3,281 pneumococcal disease-related deaths. PCV20 yielded substantial cost savings exceeding 5.4 billion SEK over a 10-year time horizon, primarily attributed to reduced direct medical costs due to improved health outcomes compared with PCV15. The findings confirmed the dominance of PCV20 in the base case, which remained robust across deterministic and probabilistic sensitivity analyses as well as scenario assessments. PCV20 was the dominant strategy versus PCV15 over 10 years. The broader serotype coverage of PCV20 suggests superior clinical and economic advantages over PCV15, warranting inclusion in Sweden's pediatric immunization program.

Pneumonia, predominantly caused by Streptococcus pneumoniae , remains a leading cause of global mortality. The 23-valent Pneumococcal polysaccharide vaccine (PPSV23) and conjugate vaccines (PCVs) are vital measures to fight against it. This paper discussed the changes in pneumococcal vaccination strategies, particularly for older adults, as vaccine effectiveness and epidemiological patterns shift. While PPSV23 maintains effectiveness against invasive pneumococcal disease (IPD), its effectiveness against pneumococcal pneumonia is declining. Conversely, PCV13 consistently demonstrates effectiveness against both IPD and pneumonia. Consequently, the US Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends using PCVs, notably PCV20 and PCV15, over PPSV23. Japanese studies indicate a change in the efficacy/effectiveness of PPSV23 following PCV introduction in children, likely owing to serotype replacement and herd immunity. Additionally, recent data reveals a plateau in the reduction of PCV13 and PPSV23-covered serotypes, posing a challenge to current strategies. This paper indicates a paradigm shift in pneumonia management, acknowledging its chronic nature and potential to exacerbate other diseases. The future of pneumococcal vaccination lies in broader serotype coverage through PCVs, adapting to serotype changes driven by childhood vaccination programs. Furthermore, continuous research and vaccine development are crucial in this evolving field.

Colorectal cancer (CRC) long-term survivor is a rapid enlarging group. However, the effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) on this group is unknown. This nationwide population-based study in Taiwan was designed to examine the effect of PPSV23 on incidence rate ratio (IRR) of pneumonia hospitalization, cumulative incidence, and overall survival rate for these long-term CRC survivors. This cohort study was based on the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database from 2000-2017. After individual exact matching to covariates with 1:1 ratio, there were a total of 1,355 vaccinated and 1,355 unvaccinated survivors. After adjusted by multivariate Poisson regression model, vaccinated group had a non-significantly lower pneumonia hospitalization risk than unvaccinated, with an adjusted IRR of 0.879 ( p  = .391). Besides, vaccinated group had both lower cumulative incidence rate and higher overall survival time than unvaccinated.

Background: Invasive pneumococcal disease (IPD) remains a significant concern among children under 5, despite vaccination efforts. This study assessed IPD prevalence and associated risks in pediatric population., Methods: An observational, retrospective, multicenter study in Comunidad Valenciana, Spain, of IPD cases in children under 13 from January 2012 to September 2022. Data from the CV Microbiology Surveillance Network (RedMIVA) and medical records were reviewed., Results: A total of 379 IPD cases in 377 patients were analyzed, predominantly males (54.11 %) under 5 (81.17 %). PCV13 vaccination notably reduced PCV13-serotypes IPD (p=0.0002), except serotype 3. Pneumonia was common, with half having underlying conditions (50.40 %). Worse outcomes occurred in patients with neurological disorders (ANOVA, p=0.57). Vaccine failures often involved underlying conditions (63 %) and serotypes 3 and 19A. Immunodeficiencies may relate to recurrent IPD, but evidence is limited., Conclusion: Despite vaccination, IPD still impacts children, influenced by immunological status, affecting severity and mortality., Competing Interests: Declaration of competing interest Marta Garrido-Jareño (MGJ): conceived of the presented idea and wrote the manuscript. Francisco Javier Roig-Sena (FJRS): provided part of the epidemiological data of the patients to carry out the study. Elvira Pérez-Pérez (EPP): provided part of the epidemiological data of the patients to carry out the study. Ana Gil-Brusola (AGB): conceived of the presented idea and were involved in planning and supervised the work. José Luis López-Hontangas (JLLH): discussed the results and contributed to the final manuscript. Eulogio Valentín-Gómez (EVG): discussed the results and contributed to the final manuscript. Antonio Pineda-Lucena (APL): discussed the results and contributed to the final manuscript. Javier Pemán (JP): conceived the study and were in charge of overall direction and planning. Discussed the results and contributed to the final manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to provide data for the clinical features of invasive pneumococcal disease (IPD) and the molecular characteristics of Streptococcus pneumoniae isolates from paediatric patients in China. We conducted a multi-centre prospective study for IPD in 19 hospitals across China from January 2019 to December 2021. Data of demographic characteristics, risk factors for IPD, death, and disability was collected and analysed. Serotypes, antibiotic susceptibility, and multi-locus sequence typing (MLST) of pneumococcal isolates were also detected. A total of 478 IPD cases and 355 pneumococcal isolates were enrolled. Among the patients, 260 were male, and the median age was 35 months (interquartile range, 12-46 months). Septicaemia (37.7%), meningitis (32.4%), and pneumonia (27.8%) were common disease types, and 46 (9.6%) patients died from IPD. Thirty-four serotypes were detected, 19F (24.2%), 14 (17.7%), 23F (14.9%), 6B (10.4%) and 19A (9.6%) were common serotypes. Pneumococcal isolates were highly resistant to macrolides (98.3%), tetracycline (94.1%), and trimethoprim/sulfamethoxazole (70.7%). Non-sensitive rates of penicillin were 6.2% and 83.3% in non-meningitis and meningitis isolates. 19F-ST271, 19A-ST320 and 14-ST876 showed high resistance to antibiotics. This multi-centre study reports the clinical features of IPD and demonstrates serotype distribution and antibiotic resistance of pneumococcal isolates in Chinese children. There exists the potential to reduce IPD by improved uptake of pneumococcal vaccination, and continued surveillance is warranted.

Objective: To describe the profile of Streptococcus pneumoniae , identify research gaps, and provide in-depth insights into various aspects related to the pathogen. Methods: Google Scholar, PubMed, and ScienceDirect were searched for all studies on the pneumococcus in Ghana that reported on specimen collected, population and sample size, carriage prevalence, incidence of pneumococcal diseases, age of the study population, types of test performed, serotypes identified, antimicrobial susceptibilities, or molecular analysis on the pneumococci for data extraction. Results: Overall, a total of 7954 results were obtained from the three-database search, and of this, 24 articles were selected after screening. A total of 924 isolates were accounted for by serotyping/serogrouping. The prevalence of pneumococcal carriage in Ghana ranges from 11.0% to 51.4% in the population depending on the age (≤ 24-80 years), sickle cell disease (SCD), human immunodeficiency virus (HIV) status, or health of the study population, and penicillin (Pen)-nonsusceptible isolates ranged from 17% to 63%. The prevalence of pneumococci found as the etiologic agent of diseases among Ghanaians ranges from 3.4% for otitis media to 77.7% for meningitis. Overall, the 13-valent pneumococcal conjugate vaccine (PCV) (PCV-13) carriage serotypes accounted for 28.4% of the reported pneumococcal isolates. PCV-13 invasive serotypes accounted for 22.4% of the reported isolates. The non-PCV-13 carriage serotypes accounted for most (43.9%) of the reported isolates. In the pre-PCV-13 era, the nontypeable (NT) (5.5%) and other nonvaccine types (NVTs) (6.4%) were reported as being predominant. The non-PCV-13 serotypes accounted for 4.4% of the reported isolates in invasive pneumococcal disease (IPD) cases. Multidrug resistance (MDR) ranged from 7.8% to 100%. Conclusion: Predicting the invasiveness of pneumococci using molecular typing is the way to go in the future as this will provide answers to the extent to which capsular switching is contributing to the pneumococcal disease burden in Ghana almost a decade after introducing PCV-13. Continuous monitoring of antibiotic resistance patterns at both phenotypic and genotypic levels, along with serotyping and molecular typing, should be a standard practice in the surveillance of pneumococcal disease burden in Ghana., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Reuben E. Arhin et al.)

Background: 13-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 programmes on invasive pneumococcal disease (IPD) and all-cause pneumonia hospitalisation in older adults (aged ≥65 years) using a retrospective observational study., Methods: We extracted monthly IPD and all-cause pneumonia cases from laboratory and health administrative databases between January 2005 and December 2018. Using a quasi-experimental difference-in-differences design, we calculated the ratio of risk ratios (RRRs) using incidence rates of IPD or all-cause pneumonia cases before (pre-PCV13 period) and after (PCV13 period) 2010 with rates of fractures as controls., Results: The rates of all IPD or PCV serotype-specific IPD for older adults in both Ontario and BC did not change in 8 years after childhood PCV13 programme implementation. All-cause pneumonia increased in Ontario (RRR 1.38, 95% CI 1.11 to 1.71) but remained unchanged in BC., Conclusions: Indirect community protection of older adults from hospitalisation with pneumococcal disease stalled despite maturation of childhood PCV13 vaccination programmes in two Canadian provinces., Competing Interests: Competing interests: The Centre for Vaccine Preventable Diseases is operated by the Dalla Lana School of Public Health, which receives funding from government, philanthropic, not-for-profit and private sector organisation, including vaccine manufacturers. This includes a donation from Merck to the institution that supported the salary of SAF from April 2020 to February 2023. SAF does not receive funding directly from Merck or any personal payment or direct funds from vaccine manufacturers to support her research. Other authors declare no conflicts of interest. MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Moderna, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines. All funds have been paid to his institute, and he has not received any personal payments., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Growing evidence indicates antimicrobial resistance disproportionately affects individuals living in socially vulnerable areas. This study evaluated the association between the CDC/ATSDR Social Vulnerability Index (SVI) and Streptococcus pneumoniae (SP) antimicrobial resistance (AMR) in the United States., Methods: Adult patients ≥18 years with 30-day nonduplicate SP isolates from ambulatory/hospital settings from January 2011 to December 2022 with zip codes of residence were evaluated across 177 facilities in the BD Insights Research Database. Isolates were identified as SP AMR if they were non-susceptible to ≥1 antibiotic class (macrolide, tetracycline, extended-spectrum cephalosporins, or penicillin). Associations between SP AMR and SVI score (overall and themes) were evaluated using generalized estimating equations with repeated measurements within county to account for within-cluster correlations., Results: Of 8008 unique SP isolates from 574 US counties across 39 states, the overall proportion of AMR was 49.9%. A significant association between socioeconomic status (SES) theme and SP AMR was detected with higher SES theme SVI score (indicating greater social vulnerability) associated with greater risk of AMR. On average, a decile increase of SES, indicating greater vulnerability, was associated with a 1.28% increased risk of AMR (95% confidence interval [CI], .61%, 1.95%; P = .0002). A decile increase of household characteristic score was associated with a 0.81% increased risk in SP AMR (95% CI, .13%, 1.49%; P = .0197). There was no association between racial/ethnic minority status, housing type and transportation theme, or overall SVI score and SP AMR., Conclusions: SES and household characteristics were the SVI themes most associated with SP AMR., Competing Interests: Potential conflicts of interest. S. M., N. C., M. W., and K. P. K. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and may own stock/stock options in Merck & Co., Inc., Rahway, NJ, USA. C. S. and K. C. Y., are employees of Becton, Dickinson & Company, which was contracted by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, to conduct the study. G. Y. and V. G. were employees of Becton, Dickinson, & Company at the time of the study. K. C. Y. and V. G. own stock in Becton, Dickson & Company. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Most pneumococcal disease occurs among infants and older adults and is thought to be driven by the transmission of Streptococcus pneumoniae from young children to these vulnerable age groups. However, pneumococcal disease outbreaks also affect non-elderly adults living or working in congregate, close-contact settings. Little is known about pneumococcal carriage in such populations. From July to November 2020, we collected saliva from low-income adult farmworkers in Monterey County, California, and tested for pneumococcal carriage following culture enrichment via quantitative PCR assays targeting the pneumococcal lytA and piaB genes. Participants were considered to carry pneumococci if lytA and piaB cycle threshold values were both below 40. Among 1,283 participants enrolled in our study, 117 (9.1%) carried pneumococci. Carriers tended more often than non-carriers to be exposed to children aged <5 years [odds ratio (OR) = 1.45 (0.95-2.20)] and overcrowding [OR = 1.48 (0.96-2.30) and 2.84 (1.20-6.73), respectively, for participants in households with >2-4 and >4 persons per bedroom vs ≤2 persons per bedroom]. Household overcrowding remained associated with increased risk of carriage among participants not exposed to children aged <5 years [OR = 2.05 (1.18-3.59) for participants living in households with >2 vs ≤2 persons per bedroom]. Exposure to children aged <5 years and overcrowding were each associated with increased pneumococcal density among carriers [ piaB c T difference of 2.04 (0.36-3.73) and 2.44 (0.80-4.11), respectively]. While exposure to young children was a predictor of pneumococcal carriage, associations of overcrowding with increased prevalence and density of carriage in households without young children suggest that transmission also occurs among adults in close-contact settings.IMPORTANCEAlthough infants and older adults are the groups most commonly affected by pneumococcal disease, outbreaks are known to occur among healthy, working-age populations exposed to overcrowding, including miners, shipyard workers, military recruits, and prisoners. Carriage of Streptococcus pneumoniae is the precursor to pneumococcal disease, and its relation to overcrowding in adult populations is poorly understood. We used molecular methods to characterize pneumococcal carriage in culture-enriched saliva samples from low-income adult farmworkers in Monterey County, CA. While exposure to children in the household was an important risk factor for pneumococcal carriage, living in an overcrowded household without young children was an independent predictor of carriage as well. Moreover, participants exposed to children or overcrowding carried pneumococci at higher density than those without such exposures, suggesting recent transmission. Our findings suggest that, in addition to transmission from young children, pneumococcal transmission may occur independently among adults in overcrowded settings., Competing Interests: J.A.L. discloses receipt of grant funding from Pfizer, Inc. and Merck, Sharp & Dohme and consulting honoraria from Pfizer, Inc.; Merck, Sharp & Dohme; and VaxCyte, Inc. A.L.W. discloses receipt of grant funding from Pfizer, Inc.; Merck, Sharp & Dohme; SalivaDirect, Inc.; Valvi.io; and Shield T3 and consulting honoraria from Pfizer, Inc.; Merck, Sharp & Dohme; Diasorin; PPS Health; Co-Diagnostics; and Global Diagnostic Systems. All other authors declare no competing interests.

The Southampton pneumococcal carriage study of children under 5 years old continued during the coronavirus disease 2019 (COVID-19) pandemic. Here, we present data from October 2018 to March 2023 describing prevalence of pneumococci and other pathobionts during the winter seasons before, during, and after the introduction of non-pharmaceutical interventions (NPIs) to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Nasopharyngeal swabs were collected from children attending outpatient clinics at a secondary care hospital and community healthcare sites. Pre-NPIs, in 2019/2020, the carriage prevalence of pneumococci at the hospital site was 32% ( n = 161 positive/499 participants). During NPIs, this fell to 19% ( n = 12/64), although based on fewer participants compared to previous years due to COVID-19 restrictions on health-care attendance. In 2021/2022, after NPIs had eased, prevalence rebounded to 33% ( n = 15/46) [compared to NPIs period, χ 2 (1, N = 110) =2.78, P = 0.09]. Carriage prevalence at community healthcare sites fell significantly from 27% ( n = 127/470) in 2019/2020 to 19% during the NPI period ( n = 44/228) in 2020/2021 [ χ 2 (1, N = 698) =4.95, P = 0.026]. No rebound was observed in 2021/2022 [19% ( n = 56/288)]. However, in a multivariate logistic regression model, neither site had a significantly lower carriage prevalence during the NPI period compared to the post NPI period. A reduction in serotype diversity was observed in 2020/2021. Carriage of Haemophilus influenzae was particularly affected by NPIs with a significant reduction observed. In conclusion, among children under 5 years of age, transient, modest, and statistically non-significant alterations in carriage of both Streptococcus pneumoniae and H. influenzae were associated with SARS-CoV-2 NPIs.IMPORTANCE Streptococcus pneumoniae (the pneumococcus) continues to be a major contributor to global morbidity and mortality. Using our long-running pediatric study, we examined changes in pneumococcal carriage prevalence in nearly 3,000 children under the age of 5 years between the winters of 2018/2019 and 2022/2023. This period coincided with the severe acute respiratory syndrome coronavirus 2 pandemic and, in particular, the implementation of national strategies to limit disease transmission in the UK. We observed a transient reduction of both Streptococcus pneumoniae and Haemophilus influenzae in these populations during this period of non-pharmaceutical interventions. This aligned with the reduction in invasive pneumococcal disease seen in the UK and is therefore a likely contributor to this phenomenon., Competing Interests: D.W.C. was a post-doctoral researcher on GSK-funded projects in 2014/2915 and currently receives grant support from Pfizer. S.N.F. receives support from the National Institute for Health Research funding via the NIHR Southampton Clinical Research Facility and the NIHR Southampton Biomedical Research Centre. S.N.F. and S.C.C. act as principal investigators for clinical trials and other studies conducted on behalf of University Hospital Southampton NHS Foundation Trust/University of Southampton that are sponsored by vaccine manufacturers. No personal payments are received from them. S.N.F. and S.C.C. have participated in advisory boards for vaccine manufacturers but receive no personal payments for this work. S.N.F. and S.C.C. have received financial assistance from vaccine manufacturers to attend conferences. All grants and honoraria are paid into accounts within the respective NHS Trusts or Universities or to independent charities. J.C., M.L., K.H., J.S., and B.D.G. are employees of Pfizer and may hold stock and/or stock options.

Limited data from Asia are available on long-term effects of pneumococcal conjugate vaccine introduction on pneumococcal carriage. Here we assess the impact of 13-valent pneumococcal conjugate vaccine (PCV13) introduction on nasopharyngeal pneumococcal carriage prevalence, density and antimicrobial resistance. Cross-sectional carriage surveys were conducted pre-PCV13 (2015) and post-PCV13 introduction (2017 and 2022). Pneumococci were detected and quantified by real-time PCR from nasopharyngeal swabs. DNA microarray was used for molecular serotyping and to infer genetic lineage (Global Pneumococcal Sequence Cluster). The study included 1461 infants (5-8 weeks old) and 1489 toddlers (12-23 months old) enrolled from family health clinics. We show a reduction in PCV13 serotype carriage (with non-PCV13 serotype replacement) and a reduction in the proportion of samples containing resistance genes in toddlers six years post-PCV13 introduction. We observed an increase in pneumococcal nasopharyngeal density. Serotype 15 A, the most prevalent non-vaccine-serotype in 2022, was comprised predominantly of GPSC904;9. Reductions in PCV13 serotype carriage will likely result in pneumococcal disease reduction. It is important for ongoing surveillance to monitor serotype changes to potentially inform new vaccine development., (© 2024. The Author(s).)

Introduction: In 2023 in France, 15 valent- pneumococcal conjugate vaccines (PCV15) have been recommended as alternatives to PCV13 for children < 2 years. PCV20 has been recommended for at-risk adults but not yet for infants, while PCV21 targets older adults. We endeavored to estimate the potential benefit of new pneumococcal vaccines in preventing invasive pneumococcal infections by comparing serotype extension to PCV13., Patients and Methods: The National Reference Centre for Pneumococci distributed S. pneumoniae IPD serotypes from children and adults., Results: In 2022, for children under 24 months, PCV15 and PCV20 ensured 10 % and 36 % more coverage against IPD than PCV13. For adults, PCV15, PCV20, and PCV21 covered up to 3 %, 26 %, and 50 % more IPD cases than PCV13., Conclusion: The new generation of pneumococcal vaccines could reduce the burden of invasive pneumococcal infections through serotype extension. Additional studies are needed in parallel to optimize their utilization and improve vaccine coverage in France., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [RC received personal fees and non-financial support from GSK, Merck, MSD, Pfizer, and Sanofi, outside the submitted work. CL received personal fees and non-financial support from Merck, MSD, Pfizer, outside the submitted work. Emmanuelle Varon reports personal fees and non-financial support from Merck, MSD, Pfizer and personal fees from GSK outside the submitted work.]., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: High fevers, especially in young children, often alarm clinicians and prompt extensive evaluation based on perceptions of increased risk of serious bacterial infection (SBI), and even brain damage or seizure disorders., Objective: The aim of this study was to determine the prevalence of SBI in infants aged 3-36 months with fever ≥40.5°C in a population of infants offered universal pneumococcal conjugate vaccine 13 and Haemophilus influenzae B immunization., Methods: This study is a retrospective review of all infants aged 3-36 months with temperature ≥40.5°C presenting to a tertiary care pediatric emergency department over a 30-month period in an era of universal pneumococcal conjugate 13 and H. influenzae B immunization., Results: SBI was recorded in 54 (21.8%) of 247 study infants, most commonly pneumonia 30 patients (12.1%) and urinary tract infection 16 patients (6.5%). Two patients had positive blood cultures, yielding a bacteremia rate of 0.8%. Patients with SBI had a significantly higher WBC count ( P < 0.0001) and C-reactive protein levels ( P < 0.0001), and were significantly more likely to be hospitalized ( P < 0.0001)., Discussion: Although SBI was common (21.8%) in our cohort of hyperpyrexic infants universally offered vaccination with pneumococcal conjugate 13 and H. influenzae B vaccines, bacteremia was a rare finding (0.8%)., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)