Geographical migration and fitness dynamics of Streptococcus pneumoniae.

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59-1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.

Estimating the Global and Regional Burden of Streptococcus pneumoniae Meningitis in Children: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Streptococcus pneumoniae (Spn) has been a leading cause of bacterial meningitis in children. The most recent estimation of the global burden of Spn meningitis indicates a positive trajectory in eliminating Spn through the implementation of pneumococcal conjugate vaccines. However, continuous monitoring and assessment of the disease burden are necessary due to the evidence of serotype replacement, antibiotic resistance, and the impact of the recent COVID-19 pandemic. OBJECTIVE: The aim of this systematic review is to provide an updated and focused assessment of the global and regional burden of Spn meningitis in children, which can guide policies and strategies to reduce the disease burden. METHODS: Population-based studies published from January 1, 2000, to January 1, 2022, were preliminarily searched from the electronic databases PubMed, Embase, Global Health (CABI), and CINAHL Plus without any language restrictions. Studies were included if they reported the incidence, prevalence, mortality, or case-fatality ratio (CFR) for Spn meningitis in children aged 0-4 years; meningitis was confirmed by cerebrospinal fluid culture; the study period was a minimum of 1 year; the number of reported cases was at least 10; and the study had no methodological ambiguities. The article screening process follows the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. Characteristics including study period, setting, World Health Organization region, income level, vaccination information, and participant data (age, number of cases, deaths, sequelae, and risk factors) will be extracted from the included studies. Search results will be updated and incorporated into our review prior to finalizing the extraction of data. Generalized linear mixed models meta-analysis will be performed to estimate the pooled incidence and CFR. We will further assess the risk of bias and heterogeneity, and will perform subgroup and sensitivity analyses to provide a meaningful interpretation of the current burden and literature for pneumococcal meningitis. RESULTS: Our preliminary search in December 2021 yielded 9295 articles. Out of 275 studies that were assessed with our eligibility criteria, 117 articles were included. Data extraction and analysis are expected to be complete by January 2025. We plan to publish the results from the full study, including an updated search in 2024, by March 2025. CONCLUSIONS: Given that the major burden of Spn meningitis affects children under the age of 5 years, this systematic review will provide a thorough understanding of the global burden of Spn meningitis in this vulnerable population over a span of 2 decades. Insights into incidence trends, geospatial distribution, risk factors, and sequelae will be valuable for stakeholders, policy makers, and the academic community. This information will aid in the ongoing monitoring of the disease and in enhancing targeted vaccine programs to further mitigate the impact of the disease on children worldwide. TRIAL REGISTRATION: PROSPERO CRD42021293110; https://tinyurl.com/kc3j5k4m. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50678.

Determinants of pneumococcal vaccination dropout among children aged 12-23 months in Ethiopia: a secondary analysis from the 2019 mini demographic and health survey.

Background: Vaccination is a cost-effective public health program that helps reduce significant morbidity and mortality in children under the age of five. Worldwide, the number of vaccine-preventable causes of child death has significantly decreased since the Expanded Program of Immunization (EPI) was introduced. However, for a variety of reasons, 23 million children did not have adequate access to vaccines in 2020. Therefore, this study aimed to evaluate the determinants of pneumonia conjugate vaccine (PCV) dropout among children aged 12-23 months in Ethiopia. Methods: The study analyzed cross-sectional data obtained from the 2019 mini Ethiopian demographic and health survey. Multilevel binary logistic regression analysis was utilized, and the best fit model was chosen using the Akaike Information Criteria. The study comprised a weighted sample of 989 children aged 12 to 23 months. The study presented the Adjusted Odds Ratio (AOR) along with a 95% Confidence Interval (CI) to identify the significant factors influencing PCV dropout. Results: The PCV dropout rate was reported at 20.2% in this study. In the multilevel analysis, possession of a health card (AOR = 0.076, 95% CI: 0.019, 0.04), vaccination for PCV 2 (AOR =0.002, 95% CI: 0.023, 0.263), and region 7 (AOR = 6.98, 95% CI: 10.1, 48.31) were significantly associated with children's PCV dropout. Conclusion: Having a health card, having received the PCV 2 vaccinations, and region were significant predictors of PCV dropout. Consequently, health education on immunization for all mothers and region-specific, customized public health interventions are needed to reduce the vaccination dropout rate.

Knowledge, Attitudes, and Behaviors Regarding Pneumococcal Vaccines in Adults 65 Years and Older in Primary Care in Wisconsin.

INTRODUCTION: Although shared decision-making is highly valued, its implementation in clinical practice is suboptimal. Shared decision-making was included in the Centers for Disease Control and Prevention (CDC) recommendations for the pneumococcal conjugate vaccine 13 valent for older adults. As a first step to develop and test clinician educational resources to facilitate shared decision-making for pneumococcal vaccines for older adults, we completed a needs assessment to identify knowledge gaps, attitudes, and behaviors. METHODS: Primary care clinicians, pharmacists, and patient care staff completed a questionnaire on shared decision-making and pneumococcal vaccines. After the CDC recommended new pneumococcal vaccines and eliminated the role of shared decision-making, a revised questionnaire was distributed to additional clinicians in an effort to increase the sample size. RESULTS: Knowledge of pneumococcal vaccine recommendations was high among those who responded to knowledge questions (48 of 75 respondents). Although 96% of respondents believed shared decision-making for use of pneumococcal vaccines in adults 65 years or older was feasible, 25% responded that it would be "somewhat difficult" to explain potential harms and benefits of PCV13. DISCUSSION: Although shared decision-making was reported to be feasible, challenges implementing it are ongoing. Knowledge gaps regarding pneumococcal vaccines were observed, highlighting the need for ongoing medical education with changing vaccine recommendations.

Invasive pneumococcal disease in Latin America and the Caribbean: Serotype distribution, disease burden, and impact of vaccination. A systematic review and meta-analysis.

BACKGROUND: Invasive pneumococcal diseases (IPD) are associated with high morbidity, mortality, and health costs worldwide, particularly in Latin America and the Caribbean (LAC). Surveillance about the distribution of serotypes causing IPD and the impact of pneumococcal vaccination is an important epidemiological tool to monitor disease activity trends, inform public health decision-making, and implement relevant prevention and control measures. OBJECTIVES: To estimate the serotype distribution for IPD and the related disease burden in LAC before, during, and after implementing the pneumococcal vaccine immunization program in LAC. METHODS: Systematic literature review following Cochrane methods of studies from LAC. We evaluated the impact of the pneumococcal vaccine on hospitalization and death during or after hospitalizations due to pneumococcal disease and serotype-specific disease over time. We also analyzed the incidence of serotyped IPD in pneumococcal conjugate vaccine PCV10 and PCV13. The protocol was registered in PROSPERO (ID: CRD42023392097). RESULTS: 155 epidemiological studies were screened and provided epidemiological data on IPD. Meta-analysis of invasive diseases in children <5 years old found that 57%-65% of causative serotypes were included in PCV10 and 66%-84% in PCV13. After PCV introduction, vaccine serotypes declined in IPD, and the emergence of non-vaccine serotypes varied by country. CONCLUSIONS: Pneumococcal conjugate vaccines significantly reduced IPD and shifted serotype distribution in Latin America and the Caribbean. PCV10/PCV13 covered 57-84% of serotypes in children under 5, with marked decline in PCV serotypes post-vaccination. Continuous surveillance remains crucial for monitoring evolving serotypes and informing public health action.

Adult Pneumococcal Vaccination in Ghana: Current Status and Future Recommendations - Expert Opinion.

Vaccination programs have proven successful in the prevention and control of infectious diseases among children on a global scale, but the majority of adult populations remain unvaccinated. immunocompromised adults as well as older adults aged low-income countries as Streptococcus pneumoniae infections are associated with substantial morbidity and mortality among 65 years and above. Despite the introduction of pneumococcal conjugate vaccines (PCVs), the burden of vaccine-type serotypes remains high in there are no clear policies for adult vaccination. As per the Global Burden of Disease 2019 report, about 120,000 individuals aged 70 years and older died as a result of LRTIs) in sub-Saharan Africa. A medical advisory board meeting was conducted in April 2022 to discuss the burden of pneumococcal diseases in adults, the current status of policies and practices of adult vaccination, unmet needs, and challenges in Ghana. This expert opinion paper outlines the pneumococcal epidemiology and burden of disease in Ghana, as well as the rationale for adult pneumococcal vaccination. It also highlights the potential barriers to adult vaccination and offers recommendations to overcome these obstacles and enhance vaccine acceptance in Ghana.

Les programmes de vaccination ont prouvé leur succès dans la prévention et le contrôle des maladies infectieuses chez les enfants à l'échelle mondiale, mais la majorité des populations adultes restent non vaccinées. Les infections à Streptococcus pneumoniae sont associées à une morbidité et une mortalité substantielles chez les adultes immunodéprimés ainsi que chez les personnes âgées de 65 ans et plus. Malgré l'introduction des vaccins conjugués contre le pneumocoque (VCP), la charge des sérotypes vaccinaux reste élevée dans les pays à faible revenu car il n'existe pas de politiques claires en matière de vaccination des adultes. Selon le rapport sur la charge mondiale de morbidité de 2019, environ 120 000 personnes âgées de 70 ans et plus sont décédées des suites d'infections des voies respiratoires inférieures (IVRI) en Afrique subsaharienne. Une réunion du conseil consultatif médical a eu lieu en avril 2022 pour discuter du fardeau des maladies pneumococciques chez les adultes, de l'état actuel des politiques et pratiques de vaccination des adultes, des besoins non satisfaits et des défis au Ghana. Cet article d'opinion d'experts présente l'épidémiologie pneumococcique et le fardeau de la maladie au Ghana, ainsi que les arguments en faveur de la vaccination pneumococcique des adultes. Il met également en lumière les obstacles potentiels à la vaccination des adultes et propose des recommandations pour surmonter ces obstacles et améliorer l'acceptation des vaccins au Ghana. MOTS-CLÉS: Maladie pneumococcique, Fardeau de la maladie, Vaccin conjugué contre le pneumocoque, Vaccination des adultes, Streptococcus pneumoniae, Ghana, Défis de la vaccination, Immunisation des adultes, VCP-13, Pneumonie acquise en communauté.

Vaccination Open Day: A Cross-Sectional Study on the 2023 Experience in Lombardy Region, Italy.

BACKGROUND: Vaccination is a highly effective tool for controlling infectious diseases, particularly in populations at high risk of contagion due to clinical conditions or occupational exposure, such as healthcare workers. The purpose of this study is to present the open day event that marked the beginning of the influenza and anti-COVID-19 vaccination campaign in the Lombardy region and to describe the experience of an Istituto di Ricovero e Cura a Carattere Scientifico in Milan. METHODS: During the vaccination open day, eligible individuals received free vaccinations for influenza, COVID-19, pneumococcal disease, and shingles, as provided by the Lombardy Agenzia per la Tutela della Salute. In celebration of the centenary of the Università degli Studi di Milano, the Fondazione Ca'Granda Ospedale Policlinico, a contracted hospital of the university, created a special electronic diary for a total of 150 individuals, equally divided between children aged 2-6, pregnant women, and university staff. RESULTS: At the regional level, a total of 6634 influenza vaccines, 2055 anti-COVID-19 vaccines, 108 anti-pneumococcal vaccines, and 37 anti-zoster vaccines were administered. A total of 3134 (47.3%) influenza vaccines, 1151 (56%) anti-COVID-19 vaccines, and 77 (62%) anti-pneumococcal vaccines, were given to individuals aged 60-79. No differences were observed between the total number of male and female vaccinees (1017 and 1038, respectively), who received the anti-COVID-19 vaccine. At the Policlinico Foundation, out of 150 available booking slots, 154 vaccines were administered, including 117 influenza vaccines. CONCLUSIONS: The establishment of vaccine open days is a beneficial way to increase vaccine compliance. Co-administration of little-known vaccinations outside of healthcare settings could also be a useful tool.

Expansion of pneumococcal serotype 23F and 14 lineages with genotypic changes in capsule polysaccharide locus and virulence gene profiles post introduction of pneumococcal conjugate vaccine in Blantyre, Malawi.

Since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Malawi in 2011, there has been persistent carriage of vaccine serotype (VT) Streptococcus pneumoniae, despite high vaccine coverage. To determine if there has been a genetic change within the VT capsule polysaccharide (cps) loci since the vaccine's introduction, we compared 1022 whole-genome-sequenced VT isolates from 1998 to 2019. We identified the clonal expansion of a multidrug-resistant, penicillin non-susceptible serotype 23F GPSC14-ST2059 lineage, a serotype 14 GPSC9-ST782 lineage and a novel serotype 14 sequence type GPSC9-ST18728 lineage. Serotype 23F GPSC14-ST2059 had an I253T mutation within the capsule oligosaccharide repeat unit polymerase Wzy protein, which is predicted in silico to alter the protein pocket cavity. Moreover, serotype 23F GPSC14-ST2059 had SNPs in the DNA binding sites for the cps transcriptional repressors CspR and SpxR. Serotype 14 GPSC9-ST782 harbours a non-truncated version of the large repetitive protein (Lrp), containing a Cna protein B-type domain which is also present in proteins associated with infection and colonisation. These emergent lineages also harboured genes associated with antibiotic resistance, and the promotion of colonisation and infection which were absent in other lineages of the same serotype. Together these data suggest that in addition to serotype replacement, modifications of the capsule locus associated with changes in virulence factor expression and antibiotic resistance may promote vaccine escape. In summary, the study highlights that the persistence of vaccine serotype carriage despite high vaccine coverage in Malawi may be partly caused by expansion of VT lineages post-PCV13 rollout.

Hearing loss in Australian First Nations children at 6-monthly assessments from age 12 to 36 months: Secondary outcomes from randomised controlled trials of novel pneumococcal conjugate vaccine schedules.

BACKGROUND: In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations. METHODS AND FINDINGS: In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size. CONCLUSIONS: In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation. TRIAL REGISTRATION: ClinicalTrials.gov NCT01735084 and NCT01174849.

[Vaccines in adults : an underestimated pillar of cardiovascular disease prevention]. / Les vaccins de l'adulte : un pilier sous-estimé de la prévention des maladies cardiovasculaires.

This brief article focuses on vaccines targeted against five infectious agents that are linked to an increased cardiovascular risk in adults: COVID-19, influenza, pneumococcus, respiratory syncytial virus, and varicella-zoster virus. The article is divided into three parts. Firstly, it outlines the mechanisms responsible for cardiovascular events that occur during and after infections. Secondly, it discusses the principles of vaccine protection in this context. The third part is dedicated to clinical studies that specifically demonstrate the cardiovascular protection afforded by the vaccines. Vaccines targeting the five aforementioned infectious agents should undoubtedly be considered key elements in the prevention of cardiovascular risk.

Ce bref article est consacré aux vaccins dirigés contre cinq agents infectieux impliqués dans un accroissement du risque cardiovasculaire de l'adulte : COVID-19, influenza, pneumocoque, virus respiratoire syncytial et virus varicelle-zona. L'article est divisé en trois parties. Nous rappelons d'abord les mécanismes responsables des événements cardiovasculaires qui surviennent pendant et après les infections. Nous abordons ensuite les principes de la protection vaccinale en la matière. La troisième partie est consacrée à des études cliniques qui démontrent spécifiquement la protection cardiovasculaire conférée par les vaccins. Les vaccins dirigés contre les cinq agents infectieux cités plus haut devraient indiscutablement être considérés comme des éléments-clés de la prévention du risque cardiovasculaire.

Knowledge, attitudes and practices survey towards pneumococcal infection and vaccination among primary health care physicians, Ukraine, 2021.

BACKGROUND: The Ukrainian Ministerial Order (UMO) recommends pneumococcal vaccine (PCV) in risk groups but not free-of-charge resulting in coverage <5% (crude estimation). In 2022, the vaccination calendar will include PCV for children <5years. Doctors' pneumococcal knowledge, attitudes and practices (КAP) are paramount to successful roll-out but unexplored. We surveyed doctors aiming to assess their KAP to address gaps and misconceptions and support PCV implementation. METHODS: In March 2021, we selected and surveyed primary care doctors using simple random sampling and structured self-administered online questionnaire. We measured attitudes (importance, effectiveness, safety) and practices using 5-point Likert-type questions. We defined pneumococcal disease (PD) knowledge as low/moderate (<80%) and high (≥80%), PCV and overall knowledge as low (≤50%) and moderate/high (51-100%) and PCV attitudes and practices as negative/neutral (1.0-3.4) and positive (3.5-5.0). We calculated prevalence ratios (PRs) and 95% confidence intervals (95%CI) using Poisson regression. RESULTS: The response rate was 46% (286/628). Females represented 85% (243/285); the median age was 47 (interquartile range: 33-59, N = 281) years. Twenty-six percent (72/277) had high PD knowledge associated with age (>47 years: PR = 0.52, 95%CI: 0.30-0.90) and child-related UMO awareness (PR = 1.78, 95%CI: 1.04-3.08); 65% (182/278) had moderate/high PCV knowledge associated with positive attitudes towards PCV effectiveness (PR = 2.08, 95%CI: 1.20-3.59). Overall knowledge was moderate/high in 69% (188/271); 83% (220/265) had positive PCV attitudes; 52% (135/258) had positive practices associated with female sex (PR = 2.11, 95%CI: 1.09-4.09), positive attitudes (PR = 3.40, 95%CI: 1.23-9.39) and perception of vaccine supply as medium/big barrier (PR = 1.66, 95%CI: 1.02-2.72). CONCLUSION: We observed moderate pneumococcal knowledge, especially in older doctors, positive PCV attitudes and neutral practices. Females and doctors with positive attitudes recommended PCV more. For successful PCV implementation, we recommend proper planning and prior educational activities targeting patients and primary care doctors, especially older males, to improve knowledge, introduce PCV and address concerns while ensuring uninterrupted vaccine supply.

Spatial variation and predictors of incomplete pneumococcal conjugate vaccine (PCV) uptake among children aged 12-35 months in Ethiopia: spatial and multilevel analyses.

Background: Despite the Ethiopian government included the Pneumococcal Conjugate Vaccine (PCV) in the national expanded program for immunization in 2011, only 56% of children aged 12-23 months received the full dose of PCV. Despite some studies on PCV uptake in Ethiopia, there was a dearth of information on the geographical distribution and multilevel factors of incomplete PCV uptake. Hence, this study aimed to identify the spatial variations and predictors of incomplete PCV uptake among children aged 12-35 months in Ethiopia. Methods: The study was based on an in-depth analysis of 2016 Ethiopia Demographic Health Survey data, using a weighted sample of 3,340 women having children aged 12-35 months. Arc-GIS version 10.7 and SaTScan version 9.6 statistical software were used for the spatial analysis. To explore spatial variation and locate spatial clusters of incomplete PCV, the Global Moran's I statistic and Bernoulli-based spatial scan (SaTScan) analysis were carried out, respectively. A multilevel mixed-effect multivariable logistic regression was done by STATA version 16. Adjusted odds ratio (AOR) with its corresponding 95% CI was used as a measure of association, and variables with a p < 0.05 were deemed as significant determinants of incomplete PCV. Results: The overall prevalence of incomplete PCV in Ethiopia was found to be 54.0% (95% CI: 52.31, 55.69), with significant spatial variation across regions (Moran's I = 0.509, p < 0.001) and nine most likely significant SaTScan clusters. The vast majority of Somali, southeast Afar, and eastern Gambela regions were statistically significant hot spots for incomplete PCV. Lacking ANC visits (AOR = 2.76, 95% CI: 1.91, 4.00), not getting pre-birth Tetanus injections (AOR = 1.84, 95% CI: 1.29, 2.74), home birth (AOR = 1.72, 95% CI: 1.23, 2.34), not having a mobile phone (AOR = 1.64, 95% CI: 1.38, 1.93), and residing in a peripheral region (AOR = 4.63; 95% CI: 2.34, 9.15) were identified as statistically significant predictors of incomplete PCV. Conclusion: The level of incomplete PCV uptake was found to be high in Ethiopia with a significant spatial variation across regions. Hence, the federal and regional governments should collaborate with NGOs to improve vaccination coverage and design strategies to trace those children with incomplete PCV in peripheral regions. Policymakers and maternal and child health program planners should work together to boost access to maternal health services like antenatal care and skilled delivery services to increase immunization coverage.

Antibody responses after sequential vaccination with PCV13 and PPSV23 in patients with moderate to severe plaque psoriasis under immunosuppressive therapy.

A crucial step in lowering the risk of invasive pneumococcal illness in high-risk populations, such as individuals with plaque psoriasis, is pneumococcal vaccination. The serologic response to the sequential vaccination with Prevenar 13 (PCV13) and Pneumovax 23 (PPSV23) in psoriasis patients under immunosuppressive therapy is still poorly characterized despite national recommendations suggesting vaccination for immunocompromised patients. In this prospective study, we investigated the serological response in 57 patients under active systemic treatment for moderate to severe plaque psoriasis who underwent sequential vaccination with PCV13 followed by PPSV23. Our analysis focused on global and serotype-specific anti-pneumococcal antibody responses over a 7-month period post-vaccination. Our findings reveal a robust serological response in patients with plaque psoriasis under systemic therapy. When comparing our results with a cohort of kidney transplant recipients who completed a similar sequential vaccination protocol, psoriasis patients showed higher antibody concentrations. In psoriasis patients, the mean levels of all global antibody classes tested (IgG, IgG2, IgA, IgM) increased more than 4-fold (P < 0.0001) and serotype-specific antibodies more than 1.9-fold (P < 0.01). In addition to providing strong evidence of the safety and effectiveness of sequential pneumococcal vaccination in individuals with plaque psoriasis, our work sheds light on the complex interactions that exist between immunosuppressive treatment, vaccination schedule, and antibody responses in various risk groups. IMPORTANCE: To protect against severe courses of infection with Streptococcus pneumoniae, the national guidelines recommend sequential vaccination for these patients. However, there are only studies on the efficacy of a single administration of these vaccines in this particular risk group. The immunological responses to the vaccine were correlated with clinical patient data. In summary, our study shows for the first time that sequential vaccination is immunogenic in patients with moderate to severe plaque psoriasis.

Surveillance of invasive pneumococcal disease in Spain exploring the impact of the COVID-19 pandemic (2019-2023).

OBJECTIVES: Dynamic trends of invasive pneumococcal disease (IPD) including the evolution of prevalent serotypes are very useful to evaluate the impact of current and future pneumococcal conjugate vaccines (PCVs) and the rise of non-vaccine serotypes. In this study, we include epidemiological patterns of S. pneumoniae before and after COVID-19 pandemic. METHODS: We characterized all national IPD isolates from children and adults received at the Spanish Pneumococcal Reference Laboratory during 2019-2023. RESULTS: In the first pandemic year 2020, we found a general reduction in IPD cases across all age groups, followed by a partial resurgence in children in 2021 but not in adults. By 2022, IPD cases in children had returned to pre-pandemic levels, and partially in adults. In 2023, IPD rates surpassed those of the last pre-pandemic year. Notably, the emergence of serotype 3 is of significant concern, becoming the leading cause of IPD in both pediatric and adult populations over the last two years (2022-2023). Increase of serotype 4 in young adults occurred in the last epidemiological years. CONCLUSIONS: The COVID-19 pandemic led to a temporary decline in all IPD cases during 2020 attributable to non-pharmaceutical interventions followed by a subsequent rise. Employing PCVs with broader coverage and/or enhanced immunogenicity may be critical to mitigate the marked increase of IPD.

Synthetic BSA-conjugated disaccharide related to the Streptococcus pneumoniae serotype 3 capsular polysaccharide increases IL-17A Levels, γδ T cells, and B1 cells in mice.

The disaccharide (ß-D-glucopyranosyluronic acid)-(1→4)-ß-D-glucopyranoside represents a repeating unit of the capsular polysaccharide of Streptococcus pneumoniae serotype 3. A conjugate of the disaccharide with BSA (di-BSA conjugate) adjuvanted with aluminum hydroxide induced - in contrast to the non-adjuvanted conjugate - IgG1 antibody production and protected mice against S. pneumoniae serotype 3 infection after intraperitoneal prime-boost immunization. Adjuvanted and non-adjuvanted conjugates induced production of Th1 (IFNγ, TNFα); Th2 (IL-5, IL-13); Th17 (IL-17A), Th1/Th17 (IL-22), and Th2/Th17 cytokines (IL-21) after immunization. The concentration of cytokines in mice sera was higher in response to the adjuvanted conjugate, with the highest level of IL-17A production after the prime and boost immunizations. In contrast, the non-adjuvanted conjugate elicited only weak production of IL-17A, which gradually decreased after the second immunization. After boost immunization of mice with the adjuvanted di-BSA conjugate, there was a significant increase in the number of CD45+/CD19+ B cells, TCR+ γδ T cell, CD5+ В1 cells, and activated cells with MHC II+ expression in the spleens of the mice. IL-17A, TCR+ γδ T cells, and CD5+ В1 cells play a crucial role in preventing pneumococcal infection, but can also contribute to autoimmune diseases. Immunization with the adjuvanted and non-adjuvanted di-BSA conjugate did not elicit autoantibodies against double-stranded DNA targeting cell nuclei in mice. Thus, the molecular and cellular markers associated with antibody production and protective activity in response to immunization with the di-BSA conjugate adjuvanted with aluminum hydroxide are IL-17A, TCR+ γδ T cells, and CD5+ В1 cells against the background of increasing MHC II+ expression.

Pneumococcal antibody response in children with recurrent respiratory tract infections: A descriptive study.

BACKGROUND: The pneumococcal antibody response after vaccination with unconjugated pneumococcal vaccine can be evaluated as part of the diagnostic work-up of children with recurrent respiratory tract infections to detect an underlying polysaccharide antibody deficiency. Little is known about the prevalence of polysaccharide antibody deficiency in this population and its therapeutic consequences. OBJECTIVES: This study aimed to investigate the prevalence of polysaccharide antibody deficiency in children with recurrent respiratory tract infections and to correlate polysaccharide responsiveness with clinical severity. In addition, we aimed to evaluate differences in the immunoglobulin (Ig)G2/IgG ratio, IgA level, and age in relation to the number of deficient serotype-specific antibody responses. METHODS: Polysaccharide antibody titers for pneumococcal serotypes 8, 9N, and 15B; clinical characteristics; and immunoglobulin levels of 103 children with recurrent respiratory tract infections were retrospectively assessed. American Academy of Allergy, Asthma, and Immunology guidelines were used for the interpretation of the polysaccharide antibody response. RESULTS: Overall, 28 children (27.2 %) were diagnosed with polysaccharide antibody deficiency. No correlation was found between the number of deficient serotype-specific antibody responses and clinical severity. The study participants with a normal response to all three serotypes had a higher IgG2/IgG ratio than those with one or more deficient responses (p < 0.003). No significant correlation between IgA levels and polysaccharide responsiveness was found. The median age of children with normal polysaccharide responsiveness for the three tested serotypes was higher than that of children with a deficient response to one or more serotypes (p < 0.0025). CONCLUSION: For a large group of children (18.4 %) with recurrent respiratory tract infections, an underlying mechanism for their susceptibility was defined thanks to diagnostic unconjugated pneumococcal polysaccharide vaccination. Further research is needed to formulate age-specific normal values for polysaccharide responsiveness and to investigate the usefulness of the IgG2/IgG ratio in determining the need for diagnostic unconjugated pneumococcal polysaccharide vaccination.