Search Results (132)

Background: Streptococcus pneumoniae (Spn) is a leading bacterial pathogen responsible for severe invasive diseases, including meningitis, sepsis, and pneumonia. Current pneumococcal vaccines, which are all based on capsular polysaccharide antigens, provide limited protection and are further compromised by post-vaccination serotype replacement. Pneumococcal surface protein A (PspA), a highly conserved virulence factor expressed across diverse serotypes, has emerged as a promising candidate antigen for novel protein-based vaccines. However, progress in this field has been hindered by the absence of standardized in vitro functional antibody assays. Methods: This study established a robust functional antibody detection method for PspA-based protein vaccines by modifying the conventional multiplex opsonophagocytic killing assay (MOPA), originally designed for polysaccharide-based vaccines. Using polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) typing, a target strain panel was selected and developed to include representative strains from PspA Family 1-Clade 2 and Family 2-Clades 3 and 4. The MOPA protocol was optimized by extending the phagocytic reaction time to enhance sensitivity. Specificity was confirmed through recombinant PspA competitive inhibition assays. Results: The assay demonstrated high linearity (R² ≥ 0.98) between opsonophagocytic index (OI) and serum dilution, along with acceptable repeatability (CV ≤ 30%) and intermediate precision (CV ≤ 50%). Both preclinical and clinical serum samples exhibited potent bactericidal activity against diverse PspA families, independent of capsule type. Conclusions: This study provided a standardized framework to support the development and regulatory assessment of protein-based pneumococcal vaccines. Full article

Background/Objectives: Streptococcus pneumoniae (S. pneumoniae) remains a leading cause of invasive bacterial disease in children worldwide. In Tunisia, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the national immunization program in 2019 for children under two years of age. This study aimed to assess molecular epidemiology, antimicrobial resistance, and vaccine impact on pediatric invasive pneumococcal disease (IPD) before and after PCV10 introduction. Methods: A retrospective study was conducted at Bechir Hamza Children’s Hospital (Tunis, Tunisia) between 2016 and 2022. IPD isolates were characterized by multiplex PCR, antimicrobial susceptibility testing, and whole-genome sequencing. Serotyping was performed using three approaches: multiplex PCR, SeroBA, and a novel cpsB gene-based algorithm. Genomic diversity and population structure were analyzed through molecular typing approaches. Incidence trends were calculated using national population data. Results: Among 150 confirmed IPD isolates, vaccine-type (VT-PCV10) strains decreased significantly from 69.8% before to 47.2% after vaccine introduction (p = 0.013), with serotype 14 showing the largest decline. Genomic analysis identified 43 sequence types and 27 global pneumococcal sequence clusters, reflecting high genetic heterogeneity. The cpsB approach demonstrated strong concordance with PCR (κ = 0.67) and SeroBA (κ = 0.85). The mean annual incidence of VT disease in children aged 0–4 years declined from 1.28 to 0.86 cases per 100,000 population, while non-vaccine serotypes showed a modest increase. Conclusions: PCV10 introduction was associated with a marked reduction in vaccine-type IPD among young children, supporting its public health benefit. Ongoing genomic surveillance remains essential to monitor serotype replacement and antimicrobial resistance in Tunisia. Full article

Background/Objectives: American Indian/Alaska Native individuals exhibit a higher prevalence of carriage of Streptococcus pneumoniae and are at increased risk of invasive pneumococcal disease compared with the general US population, driven by persistent inequities in health determinants. Although the use of pneumococcal vaccines has reduced carriage of vaccine serotypes, the prevalence of carriage of non-vaccine serotypes has increased. Methods: This study was a descriptive subgroup analysis of the PNEU-DAY study (NCT03547167; EudraCT 2017-004915-38). Safety, tolerability, and immunogenicity of sequential administration of either V114, a 15-valent pneumococcal conjugate vaccine (PCV), or 13-valent PCV (PCV13), followed 6 months later by 23-valent pneumococcal polysaccharide vaccine (PPSV23), were evaluated in pneumococcal vaccine-naïve American Indian adults with or without pre-defined risk factors for pneumococcal disease. Polymerase chain reaction testing assessed nasopharyngeal/oropharyngeal carriage of S. pneumoniae. Results: Following administration of PCV and PPSV23, the proportions of participants with adverse events were generally comparable between vaccination groups. V114 and PCV13 were immunogenic for all respective vaccine serotypes, with V114 inducing robust immune responses to the two additional serotypes not included in PCV13 (22F and 33F), based on opsonophagocytic activity geometric mean titers and immunoglobulin G geometric mean concentrations at 30 days post-vaccination. Sequential administration with PPSV23 was immunogenic in both vaccination groups. Nasopharyngeal/oropharyngeal carriage of S. pneumoniae was observed in 16.7% to 22.6% of American Indian participants across the study timepoints. Conclusions: V114 was well tolerated and immunogenic for the 15 serotypes in V114 when administered either alone or followed by PPSV23. Use of V114 has the potential to expand serotype coverage and protect against pneumococcal disease resulting from serotypes absent in PCV13 among American Indian adults. Full article

Background: Despite pre-transplantation vaccination against invasive pneumococcal disease (IPD) and hepatitis B virus (HBV), most solid organ transplant (SOT) recipients are without post-transplantation seroprotection against IPD and HBV. We aimed to determine the seroprotection rates and changes in antibody concentrations after booster vaccination against IPD and HBV in SOT recipients without post-transplantation seroprotection after pre-transplantation vaccination. Furthermore, we aimed to identify risk factors associated with non-response to booster vaccination. Methods: In this prospective cohort study, we included adult SOT recipients without post-transplantation seroprotection against IPD who then received the 23-valent pneumococcal polysaccharide vaccine (PPSV23) booster, as well as adult SOT recipients without seroprotection against HBV who then received the Engerix-B^® booster after pre-transplantation vaccination. Logistic regression models were used to analyze risk factors for non-response to booster vaccination. Results: We included 50 SOT recipients in analyses of booster vaccination against IPD and 52 SOT recipients in analyses of booster vaccination against HBV. Seroprotection rates were 52% after booster vaccination against IPD and 7.7% after booster vaccination against HBV. The median geometric mean concentration of pneumococcal antibodies increased from 0.54 µg/mL IgG (interquartile range, IQR: 0.35–0.77) to 1.21 µg/mL IgG (IQR: 0.87–1.62) after booster vaccination (p < 0.001). Having pre-transplantation seroprotection against IPD at time of listing was associated with lower odds of non-response to booster vaccination. We were not able to identify risk factors for non-response to HBV booster vaccination. Conclusions: Booster vaccination improved seroprotection against IPD, but not HBV. Further studies are needed to examine optimal vaccination strategies for SOT recipients. Full article

Streptococcus pneumoniae contributes significantly to morbidity, mortality, and healthcare costs worldwide due to severe Invasive Pneumococcal Disease (IPD), particularly among young children and vulnerable populations. This review critically examines the current state of pneumococcal disease epidemiology, the evolution of vaccine strategies, and persistent challenges to achieve global control of the disease. The implementation of Pneumococcal Conjugate Vaccines (PCVs) has yielded substantial public health gains, establishing herd protection and sharply reducing vaccine-type IPD incidence. However, this success has been fundamentally challenged by serotype replacement, where non-vaccine serotypes have subsequently emerged to cause a significant proportion of the residual disease burden. This epidemiological shift has necessitated the development and deployment of higher-valency PCVs (PCV15, PCV20, and PCV21) to expand serotype coverage. Furthermore, optimal protection requires personalized strategies for high-risk cohorts where vaccine effectiveness can be compromised. In this context, the review details how pneumococcal vaccination—and particularly PPSV23—serves as an indispensable diagnostic tool to evaluate a broad spectrum of Inborn Errors of Immunity (IEI) and in particular humoral defects. Diagnostic challenges are strained by non-standardized assays and the limited panel of unique serotypes available for testing in the PCV era. The scientific priority is now the development of universal protein-based vaccines, to provide protection against all serotypes and non-encapsulated strains by targeting conserved virulence factors. This integrated approach, combining expanded PCV coverage with novel vaccine technology, is essential to mitigate the ongoing public health burden of pneumococcal disease. Full article

Background:Streptococcus pneumoniae is a well-known pathogen responsible for respiratory and invasive diseases; however, central nervous system (CNS) involvement in the form of bacterial myelitis is exceedingly rare, particularly in immunocompetent adults. Moreover, the association between pneumococcal infections and reactive arthritis is scarcely documented. We report an unusual case of pneumococcal myelitis complicated by reactive arthritis in an elderly patient with no evident immunosuppression. Case Presentation: A 68-year-old man with a medical history of hypertension, benign prostatic hyperplasia, multiple disc herniations, and a resected pancreatic neuroendocrine tumour presented to the emergency department with acute urinary retention and fever (38.5 °C). The neurological examination revealed lower limb weakness and decreased deep tendon reflexes. Spinal magnetic resonance demonstrated T2 hyperintense lesions suggestive of longitudinally transverse myelitis. Cerebrospinal fluid (CSF) analysis showed pleocytosis with elevated protein levels; the polymerase chain reaction (PCR) test resulted positive result for Streptococcus pneumoniae. The patient received intravenous antimicrobial and corticosteroid therapy with partial neurological improvement. Within days, he developed acute monoarthritis of the right ankle. Joint aspiration revealed sterile inflammatory fluid, negative for crystals and cultures, supporting a diagnosis of reactive arthritis. The articular symptoms resolved with the use of prednisone. An extensive immunological work-up was negative, and no other infectious or autoimmune triggers were identified. The patient underwent a structured rehabilitation program with gradual improvement in motor function over the following weeks. Conclusions: This case illustrates a rare clinical scenario of pneumococcal myelitis associated with reactive arthritis in a patient without overt immunosuppression. It highlights the importance of considering bacterial aetiologies in cases of acute transverse myelitis and the potential for unusual systemic immune responses such as reactive arthritis. Early recognition and the administration of appropriate antimicrobial and supportive therapies are crucial for improving neurological and systemic outcomes. To our knowledge, this is one of the first reported cases describing the co-occurrence of these two conditions in the context of S. pneumoniae infection. Full article

This study assessed the epidemiological and microbiological invasive pneumococcal disease (IPD) changes that occurred before and after the emergence of COVID-19 in Italy. All IPD cases reported through the nationwide surveillance system during 2018–2023 were included. IPD incidence and serotype distributions were analyzed by age group. IPD incidence in 2020–2021 declined in all age groups compared with 2018–2019, especially in children less than 2 years of age and elderly people aged > 64 years. A resurgence of IPD cases was observed from late 2022 onwards, with values in children exceeding those seen before the pandemic. The post COVID-19 increase in children was mainly driven by some PCV13 serotypes, such as 3, 19A, and 19F, but also non-vaccine serotypes, including 10A, 8, and 24F, while in the elderly population, a predominance of serotypes 3 and 8 was observed. In conclusion, a steep drop in IPD incidence was observed during the peak of the COVID-19 pandemic, followed by a subsequent upsurge of cases, especially in children. Continuous national surveillance is necessary to monitor the dynamics and evolution of IPD and the impact of new higher-valency vaccines in Italy over the next few years. Full article

Background/Objectives: Streptococcus pneumoniae is a major human pathogen causing illnesses that range from mild respiratory infections to severe invasive diseases. More than 100 known S. pneumoniae serotypes differ in their virulence, prevalence, and levels of drug resistance. Additionally, different clonal types within the same serotype may exhibit varying disease potential and genetic characteristics. This study aimed to determine phenotypic and molecular characteristics of S. pneumoniae isolated from patients with invasive pneumococcal disease (IPD). Methods: The serotypes of invasive S. pneumoniae isolates collected between 2022 and 2025 from adult patients hospitalized in a tertiary hospital were determined. Multilocus sequence typing (MLST) was performed on isolates with reduced susceptibility to penicillin to assess their molecular epidemiology. Results: Serotype 3 was the most common among all invasive isolates (29/85; 34.1%), followed by serotype 19A (22/85; 25.9%). Most penicillin-resistant isolates belonged to serotypes 19A and 19F. Three of the eight 19A isolates with reduced penicillin susceptibility were assigned to ST320 (37.5%), a clinically significant clone due to its high virulence and antibiotic resistance. While 15.3% of all isolates were multidrug-resistant (MDR), nearly half of the isolates with reduced penicillin susceptibility were MDR, most frequently exhibiting the erythromycin–clindamycin–tetracycline resistotype. Conclusions: This study highlights the predominance of serotype 19A, particularly the highly virulent and resistant ST320 clone, among invasive isolates with reduced penicillin susceptibility. These findings underscore the ongoing threat of antimicrobial resistance in IPD and the importance of continued surveillance of serotype distribution and resistance patterns to guide treatment strategies and vaccination policy decisions. Full article

Background/Objectives: This study analyzes the epidemiology of invasive pneumococcal disease (IPD) and the dynamics of Streptococcus pneumoniae (SP) serotypes in the Comunidad Valenciana (CV) region, Spain, over a 10-year period (2014–2024), with particular focus on vaccine coverage of PCV13 compared to the newer PCV20 and PCV21 formulations. Methods: A total of 2.014 isolates of SP obtained from sterile fluids were included, with available serotype, demographic data, and vaccination status, which were collected from the Epidemiological Surveillance System (AVE) and the Microbiological Surveillance Network of the CV region (RedMIVA). Results: Overall vaccination coverage was low (22.4%), with the highest rates observed in children under 10 years (78%) compared to only 16% in those aged 10–64 years and 22% in those over 64. Serotype distribution revealed 120 distinct serotypes, with serotype 8 (17.6%) and serotype 3 (14.7%) being the most frequent. Serotype 8 predominated among unvaccinated individuals, while serotype 3 remained highly prevalent despite inclusion in PCV13. Other relevant serotypes included 22F, 9N, 19A, 6C, and 23A. Temporal analysis showed that serotype 3 has continued to increase in recent years, whereas serotype 8 rose during the pandemic period but has remained stable in the most recent interval, while 19A, 15A, and 11A significantly declined. Among serotypes with <2% incidence, some, such as 4, 24F, and 38, showed upward trends. Conclusions: The findings suggest that PCV20 currently provides broad coverage of dominant serotypes, but PCV21 may offer advantages should serotypes like 23A, 9N, or 15A increase further due to serotype replacement. Continuous epidemiological surveillance is essential to guide evidence-based vaccine policy and anticipate future vaccine reformulations. Full article

Streptococcus pneumoniae has been a PCV10 vaccine-preventable agent in Bulgaria since 2010. Our objective is to determine the phylogenetic structure of 170 invasive and non-invasive pneumococcal isolates, focusing on their serotypes and antimicrobial susceptibility. Serotyping was performed using latex agglutination, capsular swelling reaction, and serotype-specific PCRs. Antibiotic susceptibilities were assessed by broth microdilution. MLST was conducted to define the clonal composition. The non-PCV10 serotypes accounted for 88.2%. The predominant invasive pneumococcal disease (IPD) serotypes were 19A (39.3%), 19F (21.4%), 6C (10.7%), 7F (7.1%), and 3 (7.1%). The prevalent NIPD serotypes were 19A (18.3%), 6C (15.5%), 3 (10.6%), 15A (7.7%), and 6A (6.3%). The overall antimicrobial non-susceptibility rates were: benzylpenicillin (55.2%), ceftriaxone (15.2%), cefuroxime (35.8%), amoxicillin-clavulanic acid (38.8%), erythromycin (60.5%), clindamycin (57.0%), tetracycline (43.5%), trimethoprim-sulfamethoxazole (62.9%), and chloramphenicol (13.5%). The multidrug resistance (MDR) strains were 60.5%. The predominant clone CC320, represented 20.0% MDR 19A and 19F strains linked to Taiwan^19F-14 and GPSC1. CC273/Greece^6B-22 and CC386 accounted for 5.3% 6A and 6C isolates. Most serotype 3 isolates are associated with CC505, associated with Netherlands³-31 and GPSC12. Switching to a conjugate vaccine with broader serotype coverage could reduce the incidence of 19A, 6C, and 15A MDR S. pneumoniae clones in our country. Full article

Background: Hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) therapy have markedly improved survival in pediatric patients with hematological malignancies. However, these treatments cause profound immunosuppression, leading to significant susceptibility to vaccine-preventable diseases (VPDs), including invasive pneumococcal disease and measles. Timely and tailored immunization strategies are crucial to mitigate infectious risks in this vulnerable population. Methods: We conducted a narrative review of the English-language literature from 2000 to 2024, including clinical guidelines, surveys, and original studies, to evaluate immune reconstitution and vaccination practices in pediatric patients undergoing HCT and CAR-T therapy. Literature searches in PubMed, Scopus, and Web of Science used disease-specific, therapy-specific, and pathogen-specific terms. Data synthesis focused on vaccine schedules, immune recovery markers, and adherence challenges. Results: Profound immune deficits post-HCT and CAR-T therapy compromise both innate and adaptive immunity, often necessitating revaccination. Key factors influencing vaccine responses include time since therapy, graft source, immunosuppressive treatments, and chronic graft-versus-host disease. Although inactivated vaccines are generally safe from three to six months post-HCT, live vaccines remain contraindicated until documented immune recovery. CAR-T therapy introduces unique challenges due to prolonged B-cell aplasia and hypogammaglobulinemia, leading to delayed or reduced vaccine responses. Despite established guidelines, real-world adherence to vaccination schedules remains suboptimal, driven by institutional, logistic, and patient-related barriers. Conclusions: Effective vaccination strategies are essential for reducing infectious morbidity in pediatric HCT and CAR-T recipients. Personalized vaccine schedules, immune monitoring, and multidisciplinary coordination are critical to bridging gaps between guidelines and practice, ultimately improving long-term outcomes for immunocompromised children. Full article

Background/Objectives: Pneumococcal conjugate vaccines (PCVs) have significantly reduced invasive pneumococcal disease (IPD) globally. We conducted a systematic review to assess whether serotype and antimicrobial resistance trends in the Middle East and North Africa (MENA) reflect global patterns post-PCV introduction. Methods: We searched the CINAHL, MEDLINE, PUBMED, EMBASE, Global Health, Global Index Medicus, EBSCO, Scopus, and Cochrane databases for articles published from inception to 24 January 2024. Eligible studies were original articles in English or French, reporting IPD serotype distribution or antimicrobial susceptibility in the MENA region. Risk of bias was assessed using the STROBE checklist. Results: Eighty-nine studies from 18 countries were included. A decline in PCV7 serotypes was observed following the introduction of PCV10 or PCV13, which was more pronounced in PCV10-era studies. Serotype 3 increased post-PCV13 era, while 19A declined only after PCV10. An expansion in PCV20 serotypes and non-vaccine types (NVTs) was noted in PCV13-implementing countries. Antimicrobial resistance data were insufficient to provide a reliable trend. Limitations: There was limited AMR data and variable surveillance quality across countries. Conclusions: PCV introduction resulted in a modest decrease in PCV7 serotypes and a variable impact on PCV13 serotypes. This, along with the increase in PCV20 serotypes, indicates that higher-valency PCVs might provide better serotype coverage in the region. The study highlights the need for more robust surveillance across the region. Registration: CRD42018104529. Full article

Streptococcus pneumoniae remains a leading cause of invasive diseases, particularly affecting young children and the elderly. Currently, two main types of pneumococcal vaccines are commercially available: polysaccharide vaccine (PPSV23) and conjugate vaccines (e.g., PCV20). Of over 100 identified pneumococcal serotypes, vaccines targeting 24 serotypes covered by PPSV23 and PCV20 (19 serotypes overlap between the two vaccines) have been developed, with serotype distribution varying by geography, age, and time. The immune response to pneumococcal vaccines differs across serotypes, vaccine types (polysaccharide vs. conjugate), and host factors. Quantitative methods for antibody assessment—particularly newer high-throughput assays—have emerged since 2000 to address limitations in conventional approaches. However, these methods have not been comprehensively reviewed. This scoping review aimed to systematically map the existing literature on quantitative methods used to assess antibody responses to pneumococcal vaccines. Specific objectives included the following: 1. summarizing conventional and novel quantitative immunoassays; 2. evaluating the current state of validation and application of these methods; 3. identifying knowledge gaps and methodological challenges. We followed the PRISMA-ScR guidelines. We included the following: 1. peer-reviewed, open-access papers related to immunoassays used for pneumococcal antibody assessment; 2. articles written in English; 3. Studies published between 2000 and 2023. We excluded the following: 4. studies focusing on other pathogens, employing different analytical methods, or using animal models. Articles meeting the eligibility criteria were primarily retrieved from PubMed and Scopus. If free full-text versions were unavailable there, Google Scholar or the original journal databases were consulted. All references were exported to EndNote 20 for further management. At the beginning of the review, a data-charting form was developed based on prior studies and commonly addressed themes. Additional charts were created to accommodate newly identified variables during the review. All charting tools were reviewed and finalized through discussion among all research team members. The included studies were classified into five thematic groups: 1. general descriptions of quantitative assessment methods, 2. assay development and validation, 3. comparative studies, 4. technical details of assay development, 5. interpretation of assay application findings. Of 1469 articles from PubMed and 2946 articles from Scopus initially identified, 55 articles met the inclusion criteria. The earliest methods included radioimmunoassays, later replaced by WHO-standardized ELISA. While ELISA remains the gold standard, it is limited by labor, cost, and throughput. Multiplex immunoassays (MIAs), including Luminex-based platforms, have demonstrated advantages in efficiency and scalability. However, many MIAs did not initially meet WHO validation criteria. More recent assays show an improved performance, yet interlaboratory variability and lack of standardized protective thresholds remain major limitations. This review provides the first comprehensive mapping of quantitative antibody assessment methods for pneumococcal vaccines. Although ELISA continues to serve as the benchmark, MIAs represent a promising next-generation approach. Continued efforts are needed to harmonize assay validation protocols and establish global standards for protective thresholds, which will enhance the reliability of vaccine efficacy monitoring across diverse populations. Full article

Background/Objectives: Pneumococcal serotypes 1 and 5 are associated with invasive pneumococcal disease (IPD). However, data on the circulation of these serotypes in Asia following the introduction of the pneumococcal conjugate vaccine (PCV) is limited. The Lao People’s Democratic Republic (Lao PDR) introduced PCV13 into its national immunisation programme in 2013. We undertook a serosurvey to assess the IgG responses to serotypes 1 and 5 from a convenience sample of children aged under 5 years in Vientiane, Lao PDR. Methods: This cross-sectional analysis used a convenience sample of the close contacts of children under five years old who had been hospitalised with acute respiratory infections between 2013 and 2016 in Vientiane, Lao PDR. Serotype-specific IgG concentrations to serotypes 1 and 5 were measured using a modified WHO ELISA method. Results: A total of 214 participants were included, 130 of whom were unvaccinated and 84 were vaccinated with PCV13. Compared to unvaccinated participants, a higher number of PCV-vaccinated participants met the IgG threshold for IPD (≥0.35 μg/mL) [41.5% (54/130) vs. 71.4% (60/84)] for serotype 1. In contrast, for serotype 5, a similar number of participants in the PCV-vaccinated and unvaccinated group met the IgG threshold for IPD (85.7% (72/84) vs. 82.3% (107/130). Among unvaccinated children, serotype 1 IgG levels peaked at 12 and 23 months at 0.49 µg/mL (95% CIs: 0.25–0.96), while serotype 5 IgG levels were similar across age groups, ranging from 0.55 to 0.79 µg/mL. Conclusions: Our findings indicate the considerable circulation of serotypes 1 and 5 within the community in Lao PDR. Ongoing surveillance is important for informing PCV vaccination strategies. Full article

Background: Pneumococcal disease is a significant health burden, particularly among older adults and individuals with chronic conditions. Sequential pneumococcal vaccination (PCV13 followed by PPSV23) has been recommended in Italy since 2017 for its demonstrated efficacy, safety, and cost-effectiveness in preventing invasive pneumococcal disease (IPD). Nevertheless, limited data are available on the sequential pneumococcal vaccination coverage in Italy. This study aimed to evaluate the coverage and trends of sequential pneumococcal vaccination among individuals who turned 65 years old within the Viterbo Local Health Authority between 2018 and 2023. Methods: A retrospective cohort study was conducted using data from the Regional Vaccination Registry (AVR), a comprehensive digital vaccination dataset. Vaccination coverage was calculated based on individuals completing the sequential pneumococcal vaccination within two years after turning 65 years old. Trends as well as subgroup variations based on sex, citizenship, district of residence, and municipality size were analyzed. Results: Among 27,657 individuals who turned 65 years of age during the study period, only 2.32% completed the sequential pneumococcal vaccination. Coverage increased steadily from 2018 (0.60%) to a peak in 2020 (3.27%), followed by a plateau and a decline in 2023 (2.53%). Coverage varied across demographic and geographic subgroups: females (2.58%) had higher coverage than males (2.04%), Italian citizens (2.45%) exceeded foreign residents (0.64%), and residents in District C (3.03%) led over District A (1.08%). Smaller municipalities (≤10,000 inhabitants) showed higher coverage (2.52%) than larger ones (1.98%). Conclusions: Adherence to sequential pneumococcal vaccination has been very low throughout the considered study period. This is highly relevant information to consider in the view of new available pneumococcal vaccines for immunization of the elderly. Furthermore, geographic and demographic differences highlight the need for targeted public health interventions. Full article