State of pneumococcal vaccine immunity.

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

Potential serotype-specific effectiveness against IPD of pneumococcal conjugate vaccines V114 and PCV20 in children given a 2+1 dosing regimen.

BACKGROUND: Next generation, higher valency pneumococcal conjugate vaccines (PCVs) are assessed and licensed by comparing the immune response across serotypes shared with the PCVs that are standard of care for prevention of pneumococcal disease. METHODS: Using a previously qualified method we predicted the serotype-specific vaccine effectiveness (VE) against invasive pneumococcal disease of V114 and PCV20 for the serotypes shared with PCV13 in an EU, Russian, and Australian pediatric population that is recommended to receive a 2 + 1 dosing regimen. RESULTS: The estimated protective antibody concentrations ranged from 0.03 (serotype 23F) to 1.49 µg/mL (serotype 19F). Predicted VE values for V114 ranged from 79% (serotype 5) to 100% (serotype 23F). V114 had comparable effectiveness to PCV13 for all but one of shared serotypes, with predicted higher effectiveness (in V114) against serotype 3 (93% vs. 65%). Predicted VE values for PCV20 ranged from 47% (serotype 3) to 91% (serotype 14). PCV20 predicted VE was lower than PCV13's for serotypes 4, 19F, 23F, 1, 3, 5, 6A, 7F, and 19A. CONCLUSIONS: Predicted serotype-specific VE values suggest that, with a 2 + 1 dosing regimen, V114 will have greater effectiveness than PCV20 against PCV13 serotypes, particularly for the still-prevalent serotype 3. Real-world VE studies will ultimately provide clarity on the effectiveness of novel PCVs and support further confidence in and/or improvements to modeling efforts.

Pediatric pneumococcal conjugate vaccines (PCVs) were first introduced in Europe in the early 2000s and their incorporation into national immunization programs has helped decrease the incidence of invasive pneumococcal disease (IPD) in Europe and globally. However, some IPD persists, due both to the emergence of non-vaccine pneumococcal serotypes and to the persistence of certain vaccine-targeted serotypes. Higher valency vaccines have been developed to help prevent IPD arising from these serotypes. The goal of the present study is to employ a previously developed model to predict the serotype-specific vaccine effectiveness of higher valency PCVs in a pediatric population that is recommended to receive a 2 + 1 dosing schedule.

Serotype Distribution and Antimicrobial Susceptibility Pattern of Streptococcus pneumoniae in COVID-19 Pandemic Era in Brazil.

Despite the introduction of the pneumococcal vaccine, Streptococcus pneumoniae remains a cause of invasive diseases in Brazil. This study provides the distribution of serotypes and antimicrobial susceptibility patterns for pneumococcal isolates before and during the years of the COVID-19 pandemic in two age groups, <5 and ≥50 years. This is a national laboratory-based surveillance study that uses data from the Brazilian national laboratory for invasive S. pneumoniae from the pre-COVID-19 (January 2016 to January 2020) and COVID-19 (February 2020 to May 2022) periods. Antimicrobial resistance was evaluated by disk diffusion and minimum inhibitory concentration. The year 2020 was marked by a 44.6% reduction in isolates received and was followed by an upward trend from 2021 onwards, which became evident in 2022. No differences were observed in serotypes distribution between the studied periods. The COVID-19 period was marked by the high prevalence of serotypes 19A, 3, and 6C in both age groups. Serotypes 19A and 6C were related to non-antimicrobial susceptibility. We observed a reduction in S. pneumoniae, without changes in serotypes distribution and epidemiological capsular switch during the COVID-19 period. We observed elevated resistance rates, mainly to penicillin and ceftriaxone for non-meningitis cases in children under 5 years of age.

Pneumococcal serotypes and risk factors in adult community-acquired pneumonia 2018-20; a multicentre UK cohort study.

Background: Higher-valency pneumococcal vaccines are anticipated. We aimed to describe serotype distribution and risk factors for vaccine-serotype community-acquired pneumonia (CAP) in the two years pre-SARS-CoV-2 pandemic. Methods: We conducted a prospective cohort study of adults hospitalised with CAP at three UK sites between 2018 and 2020. Pneumococcal serotypes were identified using a 24-valent urinary-antigen assay and blood cultures. Risk factors associated with vaccine-type pneumonia caused by serotypes in the 13-, 15- and 20-valent pneumococcal conjugate vaccines (PCV13, PCV15, PCV20) and 23-valent pneumococcal polysaccharide vaccine (PPV23) were determined from multivariable analysis. Findings: Of 1921 adults hospitalised with CAP, 781 (40.7%, 95% confidence intervals (CI) 38.5-42.9%) had pneumococcal pneumonia. A single PCV13-serotype was detected in 242 (31.0%, 95% CI 27.8-34.3%) pneumococcal CAP patients, mostly serotype 3 (171/242, 70.7%, 95% CI 64.5-76.0%). The additional two PCV15-serotypes were detected in 31 patients (4%, 95% CI 2.8-5.6%), and PCV20-non13-serotypes in 192 (24.6%), with serotype 8 most prevalent (123/192, 64.1%, 95% CI 57.1-70.5%). Compared to PCV13-serotype CAP, people with PCV20-non13 CAP were younger (median age 62 versus 72 years, p < 0.001) and less likely to be male (44% versus 61%, p = 0.01). PPV23-non13-serotypes were found in 252 (32.3%, 95% CI 29.1-35.6%) pneumococcal CAP patients. Interpretation: Despite mature infant pneumococcal programmes, the burden of PCV13-serotype pneumonia remains high in older adults, mainly due to serotype 3. PCV20-non13-serotype pneumonia is more likely in younger people with fewer pneumococcal risk factors. Funding: Unrestricted investigator-initiated research grant from Pfizer, United Kingdom; support from National Institute for Health Research (NIHR) Biomedical Research Centre, Nottingham.

Multiple antigen presenting system (MAPS): state of the art and potential applications.

INTRODUCTION: Technological innovations have been instrumental in advancing vaccine design and protective benefit. Improvements in the safety, tolerability, and efficacy/effectiveness profiles have profoundly reduced vaccine-preventable global disease morbidity and mortality. Here we present an original vaccine platform, the Multiple Antigen Presenting System (MAPS), that relies on high-affinity interactions between a biotinylated polysaccharide (PS) and rhizavidin-fused pathogen-specific proteins. MAPS allows for flexible combinations of various PS and protein components. AREAS COVERED: This narrative review summarizes the underlying principles of MAPS and describes its applications for vaccine design against bacterial and viral pathogens in non-clinical and clinical settings. EXPERT OPINION: The utilization of high-affinity non-covalent biotin-rhizavidin interactions in MAPS allows for combining multiple PS and disease-specific protein antigens in a single vaccine. The modular design enables a simplified exchange of vaccine components. Published studies indicate that MAPS technology may support enhanced immunogenic breadth (covering more serotypes, inducing B- and T-cell responses) beyond that which may be elicited via PS- or protein-based conjugate vaccines. Importantly, a more detailed characterization of MAPS-based candidate vaccines is warranted, especially in clinical studies. It is anticipated that MAPS-based vaccines could be adapted and leveraged across numerous diseases of global public health importance.

Existing conjugate vaccines, consisting of pathogen-derived polysaccharides (PSs) and carrier proteins unrelated to the target pathogen, have helped to significantly reduce morbidity and mortality of several bacterial diseases. However, the worldwide burden of infectious diseases targeted by conjugate vaccines is still high. This is mainly due to high pathogen diversity and ongoing evolution, and innovative approaches are needed to respond to these challenges. Multiple Antigen Presenting System (MAPS) is an original vaccine technology that relies on strong molecular interactions between biotin and rhizavidin. MAPS is highly adaptable, as different PS and protein components can be precisely combined and easily exchanged, with limited damage to immunogenic epitopes (PS and protein features recognized by the immune system). Unlike existing conjugate vaccines, MAPS complexes contain pathogen-specific proteins, able to elicit broad immune responses directed against the pathogen. To date, investigational MAPS-based vaccines have been evaluated in several non-clinical studies; one candidate pneumococcal vaccine has been evaluated in early phase clinical studies in healthy children and adults (including older adults). In these clinical studies, the MAPS-based vaccine candidate was well tolerated and induced robust immune responses. If the favorable profile of MAPS-based vaccines is confirmed in further studies, these vaccines could be used against infectious diseases associated with significant morbidity and mortality.

Pneumococcal Vaccination Lowers the Risk of Alzheimer's Disease: A Study Utilizing Data from the IBM® MarketScan® Database.

Previous studies demonstrated an association between influenza vaccination and the likelihood of developing Alzheimer's disease. This study was aimed at assessing whether pneumococcal vaccinations are associated with a lower risk of Alzheimer's disease based on analysis of data from the IBM® MarketScan® Database. Vaccinated and unvaccinated matched cohorts were generated using propensity-score matching with the greedy nearest-neighbor matching algorithm. The conditional logistic regression method was used to estimate the relationship between pneumococcal vaccination and the onset of Alzheimer's disease. There were 142,874 subjects who received the pneumococcal vaccine and 14,392 subjects who did not. The conditional logistic regression indicated that the people who received the pneumococcal vaccine had a significantly lower risk of developing Alzheimer's disease as compared to the people who did not receive any pneumococcal vaccine (OR=0.37; 95%CI: 0.33-0.42; P-value < .0001). Our findings demonstrated that the pneumococcal vaccine was associated with a 63% reduction in the risk of Alzheimer's disease among US adults aged 65 and older.

Multicountry Review of Streptococcus pneumoniae Serotype Distribution Among Adults With Community-Acquired Pneumonia.

BACKGROUND: Nonbacteremic community-acquired pneumonia (CAP) is a leading presentation of severe pneumococcal disease in adults. Serotype-specific urinary antigen detection (UAD) assay can detect serotypes causing pneumococcal CAP, including nonbacteremic cases, and guide recommendations for use of higher valency pneumococcal conjugate vaccines (PCVs). METHODS: Adult CAP serotype distribution studies that used both Pfizer UADs (UAD1, detects PCV13 serotypes; UAD2, detects PCV20 non-PCV13 serotypes plus 2, 9N, 17F, and 20) were identified by review of an internal study database and included if results were published. The percentages of all-cause radiologically confirmed CAP (RAD + CAP) due to individual or grouped (PCV13, PCV15, and PCV20) serotypes as detected from culture or UAD were reported. RESULTS: Six studies (n = 2, United States; n = 1 each, Germany, Sweden, Spain, and Greece) were included. The percentage of RAD + CAP among adults ≥18 years with PCV13 serotypes equaled 4.6% to 12.9%, with PCV15 serotypes 5.9% to 14.5%, and with PCV20 serotypes 7.8% to 23.8%. The percentage of RAD + CAP due to PCV15 and PCV20 serotypes was 1.1-1.3 and 1.3-1.8 times higher than PCV13 serotypes, respectively. CONCLUSIONS: PCV13 serotypes remain a cause of RAD + CAP among adults even in settings with pediatric PCV use. Higher valency PCVs among adults could address an important proportion of RAD + CAP in this population.

Invasive Pneumococcal Disease and Potential Impact of Pneumococcal Conjugate Vaccines Among Adults, Including Persons Experiencing Homelessness-Alaska, 2011-2020.

BACKGROUND: Adults aged ≥65 years, adults with certain underlying medical conditions, and persons experiencing homelessness are at increased risk for invasive pneumococcal disease (IPD). Two new pneumococcal conjugate vaccines, 15-valent pneumococcal conjugate vaccine (PCV15) and 20-valent pneumococcal conjugate vaccine (PCV20), were recently approved for use in US adults. We describe the epidemiology of IPD among Alaska adults and estimate the proportion of IPD cases potentially preventable by new vaccines. METHODS: We used statewide, laboratory-based surveillance data to calculate and compare IPD incidence rates and 95% confidence intervals (CIs) among Alaska adults aged ≥18 years during 2011-2020 and estimate the proportion of IPD cases that were caused by serotypes in PCV15 and PCV20. RESULTS: During 2011-2020, 1164 IPD cases were reported among Alaska adults for an average annual incidence of 21.3 cases per 100 000 adults per year (95% CI, 20.1-22.5). Incidence increased significantly during the study period (P < .01). IPD incidence among Alaska Native adults was 4.7 times higher than among non-Alaska Native adults (95% CI, 4.2-5.2). Among adults experiencing homelessness in Anchorage, IPD incidence was 72 times higher than in the general adult population (95% CI, 59-89). Overall, 1032 (89%) Alaska adults with IPD had an indication for pneumococcal vaccine according to updated vaccination guidelines; 456 (39%) and 700 (60%) cases were caused by serotypes in PCV15 and PCV20, respectively. CONCLUSIONS: Use of PCV15 and PCV20 could substantially reduce IPD among adults in Alaska, including Alaska Native adults and adults experiencing homelessness.

Predicted serotype-specific effectiveness of pneumococcal conjugate vaccines V114 and PCV20 against invasive pneumococcal disease in children.

BACKGROUND: Next-generation, higher-valency pneumococcal conjugate vaccines (PCVs), 15-valent PCV V114 and 20-valent PCV (PCV20), have been assessed by comparing their immune responses across serotypes shared with the 13-valent PCV (PCV13). Without efficacy or real-world vaccine effectiveness (VE) it becomes important to relate IgG titers to VE to aid in the interpretation of the immune response elicited by V114 and PCV20. METHODS: We estimated the protective antibody concentrations for each serotype in 7-valent PCV (PCV7) and PCV13 which were then used to predict the serotype-specific VE for each PCV7 and PCV13 non PCV7 serotype present in V114 and PCV20. RESULTS: The predicted effectiveness of V114 was comparable to PCV7 and PCV13 for 11 of the 13 shared serotypes (1, 4, 5, 6B, 7F, 9 V, 14, 18C, 19A, 19F, and 23F), with improved effectiveness against serotype 3 and decreased effectiveness against serotype 6A. PCV20 had predicted effectiveness comparable to PCV7 and PCV13 for 7 of the 13 shared serotypes (5, 6A, 7F, 9 V, 18C, 19F, and 23F), with decreased effectiveness against the remaining serotypes (1, 3, 4, 6B, 14, and 19A). CONCLUSIONS: Prediction of serotype-specific VE values suggests that V114 retains greater effectiveness than PCV20 toward most serotypes present in PCV7 and PCV13.

Pediatric pneumococcal conjugate vaccines (PCVs) first became available in 2000, when the seven-valent PCV (PCV7) was approved. Since then, PCV7 has been replaced by higher-valency vaccines, including the ten-valent (PCV10) and thirteen-valent (PCV13) vaccines and, more recently, fifteen- and twenty-valent vaccines (V114 and PCV20, respectively). The increase in valency provides broader serotype coverage against invasive pneumococcal disease (IPD) in children. However, IPD due to serotypes contained in PCV7 and PCV13 continue to be observed. In the current study, we used a previously published method to estimate the vaccine effectiveness of V114 and PCV20 in a US and Puerto Rican pediatric population that is recommended to receive a 3 + 1 dosing schedule.

Summary of the NACI Statement on Public Health Level Recommendations on the Use of Pneumococcal Vaccines in Adults, Including the Use of 15-valent and 20-valent Conjugate Vaccines.

Background: Age and certain medical/social conditions are risk factors for invasive pneumococcal disease (IPD). For prevention of IPD, the National Advisory Committee on Immunization (NACI) has recommended the 23-valent polysaccharide pneumococcal vaccine, PNEU-P-23, for adults 65 years of age and older and adults over 18 years of age living with certain underlying conditions. NACI has also recommended 13-valent conjugate pneumococcal vaccine, PNEU-C-13, for adults; however, in publicly funded programs, this recommendation is limited to individuals with risk factors for IPD. Two new conjugate vaccines, PNEU-C-15 and PNEU-C-20, have been authorized by Health Canada for prevention of IPD in adults. This article summarizes NACI public health recommendations for pneumococcal vaccines in adults given these new conjugate vaccines that provide additional serotype coverage over PNEU-C-13. Methods: Key studies evaluating the immunogenicity and safety of PNEU-C-15 and PNEU-C-20 were reviewed. The Grading of Recommendations, Assessment, Development and Evaluations framework methodology was used to assess the certainty of evidence. Results: The PNEU-C-15 and PNEU-C-20 vaccines showed comparable immune responses, and safety profiles for all mild, moderate, and severe adverse events, to the currently used vaccines. No data were available on the efficacy or effectiveness of PNEU-C-15 or PNEU-C-20. Economic evidence and feasibility assessments supported the use of the PNEU-C-20 vaccine. Conclusion: NACI recommends PNEU-C-20 for adults 65 years of age and older, 50-64 years of age and living with factors placing them at higher risk of pneumococcal disease, and 18-49 years of age with immunocompromising conditions, with PNEU-C-15+PNEU-P-23 an alternative.

Penicillin Prophylaxis in Patients With Sickle Cell Disease Beyond Age 5 Years.

OBJECTIVE: Patients with sickle cell disease (SCD) are at increased risk for invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Immunization and antimicrobial prophylaxis may prevent this complication, and landmark clinical trials support discontinuation of antimicrobial prophylaxis at age 5 years. However, antimicrobial prophylaxis continues in some patients indefinitely. The objective of this study was to evaluate the incidence of culture-positive IPD and other infections in the setting of penicillin prophylaxis in the pediatric SCD population. METHODS: This was a single-center, retrospective cohort study of patients with SCD who continued antimicrobial prophylaxis with penicillin, compared with those whose antimicrobial prophylaxis was discontinued. Included patients were aged 5 to 18 years during the study period and had no history of IPD or surgical splenectomy. Patient charts were reviewed for demographics, immunizations, penicillin prescription history, and microbiologic culture data. RESULTS: Antimicrobial prophylaxis continued beyond age 5 years in 65% of patients, a higher percentage of whom had hemoglobin SS or S beta-zero disease. No patients whose antimicrobial prophylaxis was discontinued experienced IPD; 1 patient who continued antimicrobial prophylaxis died of S pneumoniae sepsis. Rates of other infections were comparable between groups (21% in prophylaxis versus 18% in no prophylaxis). CONCLUSIONS: These results support appropriate de-prescribing of antimicrobial prophylaxis in patients with SCD who are not at high risk for IPD. Further multicenter studies are needed to evaluate consequences of antimicrobial prophylaxis with alternative agents on antibiotic resistance, examine provider rationale for continuation of antimicrobial prophylaxis, and assess quality of life effects (e.g., medication adherence, adverse drug reactions) of antimicrobial prophylaxis.

Racial, Ethnic, and Geographic Disparities in Immunization Rates Among Patients With Inflammatory Bowel Disease.

Background and Aims: Racial and ethnic disparities exist in the treatment of IBD. These disparities exist in adult vaccine uptake among the general population and may extend to patients with IBD. The primary aim of this study was to determine whether racial, ethnic, or geographic disparities existed in influenza vaccine uptake among patients with IBD. Methods: We performed a multicenter, retrospective cohort study evaluating adult vaccine uptake among patients with IBD seen at two tertiary referral centers between September 2019 and February 2020. The primary outcome was to determine if racial/ethnic and geographic disparities existed in influenza vaccine uptake for the two prior seasons. Our secondary outcomes were to determine if disparities existed for pneumococcal, zoster, or hepatitis B vaccines. Results: Among the 2453 patients who met the inclusion criteria, most identified as non-Hispanic White (89.9%), were on immunosuppressive therapy (74.5%), and received the influenza vaccine in both seasons (56.0%). Older age (prevalence ratio (PR) 0.98; 95% confidence interval (95%CI) 0.98-0.99; P < .001) and non-Hispanic White patients (PR 0.76, 95%CI 0.59-0.98, P < 0.03) were significantly more likely to be immunized. Black patients (PR 1.37; 95%CI 1.18-1.59; P < .001) and those living in underserved geographic areas (PR 1.35; 95%CI 1.17-1.56; P < 0.001) were less likely to be immunized. Racial/ethnic and geographic disparities were identified for pneumococcal, zoster, and hepatitis B vaccine uptake. Conclusions: Racial and ethnic vaccination uptake disparities exist among patients with IBD; patients from medically underserved areas are also vulnerable to these disparities Studies identifying patient, provider, and system-level opportunities to address these disparities are needed.

Indirect impact of PCV10 children vaccination on the serotype distribution and antimicrobial resistance of Streptococcus pneumoniae causing invasive disease in adults over 50 in Colombia, 2005-2019: Observational analysis.

INTRODUCTION: The introduction of pneumococcal conjugate vaccine (PCV) into childhood vaccination programmes has reduced the prevalence of vaccine serotypes (VTs) that cause invasive pneumococcal disease (IPD) in children. In the elderly population, an impact has also been seen through indirect protection (herd effect). The aim of this study was to estimate the changes in serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae isolates recovered from adult IPD and to evaluate the indirect effect of immunization with PCV10 based on laboratory records by analyzing the period from 2005 to 2019 for six years before and eight years after the universal PCV10 administration to Colombian children. METHODS: A total of 2204 S. pneumoniae isolates from adults (≥50 years) with IPD were analyzed. The analysis examined the percentage changes in proportions (prevalence) and percentage variations in population rates (annual reported rates - ARR) of VTs between the pre-PCV10 (2005-2009) and post-PCV10 (2015-2019) periods. RESULTS: The findings were (1) evidence of a significant percentage decrease of pneumococcal VT10 causing IPD in adults (50% pre-PCV10 and 16% post-PCV10); (2) significant increase of serotype 19A (from 1.6% to 14.8%) and less important increase of serotype 3 (from 10.5% to 14.5%) and non-vaccine serotypes (NVT) (from 21.4% to 38.4%) non-significant; and (3) meningitis and non-meningitis multidrug resistant isolates associated with serotype 19A. An improvement in the surveillance system is associated with the immunization of children, as noted by the increased ARRs across the analysis period. CONCLUSIONS: Our results show the indirect impact of PCV10 vaccination in children on the VT10 distribution and antimicrobial resistance of S. pneumoniae causing IPD in Colombian adults over 50 when comparing the pre-PCV10 (2005-2009) and post-PCV10 (2015-2019) periods.

Evaluating immune responses to pneumococcal vaccines.

Streptococcus pneumoniae (pneumococcus) is a significant cause of bacterial infections ranging from mild infections affecting the respiratory tract such as otitis media and sinusitis to severe diseases including bacteremia, pneumonia, and invasive pneumococcal disease (IPD) (eg, meningitis, septic arthritis, and endocarditis). Pneumococcal vaccines were first developed in the 1970s as capsular pneumococcal polysaccharide vaccines, which were T-cell independent and hence lacked immunologic memory. Subsequently in the year 2000, pneumococcal conjugate vaccines (PCV) conjugated to a protein to increase immunogenicity were developed and made commercially available. The increasing number of pneumococcal serotypes identified and the expanding pipeline of PCV vaccines with improved immunogenicity have significantly reduced the morbidity and mortality associated with IPD in high-risk patients. Pneumococcal vaccines also play an important role in the diagnosis and immunophenotyping of children and adults with inborn errors of immunity (IEI) given the increasing diversity/heterogeneity of IEI presenting with primary and/or specific antibody deficiency. Other than the quantitation of serotype levels in routine clinical care, other measurements of immune response including the functional activity of antibodies, antibody avidity, cell-mediated immunity, and immunological memory remain limited to clinical trials during vaccine development.

Assessing the utilization of antimicrobial agents in pediatric pneumonia during the era of the 13-valent pneumococcal conjugate vaccine: A retrospective, single-center study.

BACKGROUND AND PURPOSE: Pneumonia and bronchopneumonia are the most common infectious diseases in children. This study aimed to analyze changes in causative pathogens and antibiotic use for bronchopneumonia or pneumonia after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in children. METHODS: This retrospective study was conducted from 2009 to 2019. Hospitalized children aged 6 months-3 years with a discharge diagnosis of bronchopneumonia or pneumonia were included to analyze changes in the potential mismatch between the diagnosed pathogen and antibiotic use. RESULTS: The cohort comprised 1100 patients, including 648 (59%) and 452 (41%) with a discharge diagnosis of bronchopneumonia and pneumonia, respectively. The trend of viral pneumonia increased every year (rs = 0.101, p < 0.05) Antibiotics were administered in 97% patients, with an increasing annual trend in macrolide use (rs = 0.031, p = 0.009). Regarding antibiotic utilization, no significant variations were observed in the days of therapy (DOT) (rs = 0.076, p = 0.208) or length of therapy (LOT) (rs = -0.027, p = 0.534) per patient-year throughout the study duration. Interestingly, the LOT for combined therapy with macrolides and first-line beta-lactams was high (rs = 0.333, p = 0.028). In viral pneumonia treatment, neither the DOT nor LOT exhibited significant variations (rs = -0.006, p = 0.787 and rs = -0.156, p = 0.398). CONCLUSION: After the introduction of PCV13 in Taiwan, no decrease in antibiotic use has been observed among children aged 6 months-3 years with a discharge diagnosis of bronchopneumonia and pneumonia.

Epidemiología del derrame pleural paraneumónico en la infancia durante la implementación de la vacuna antineumocócica conjugada de 13 serotipos / Epidemiology of pediatric parapneumonic pleural effusion during 13-valent pneumococcal conjugate vaccine implementation

Introducción: La incidencia del derrame pleural paraneumónico, incluyendo el empiema, ha sufrido variaciones en las últimas décadas, que se han relacionado con la implantación de distintos tipos de vacuna antineumocócica conjugada. Métodos: Se han revisado retrospectivamente los datos de los 10 hospitales públicos de la provincia de Alicante (España), que abarcan una población de 279.000 niños menores de 15 años, entre 2010 y 2018. Se desglosaron los derrames menores de 10mm (DP−) y los de 10mm o más (DP+). Resultados: Se han analizado 366 episodios de derrame pleural paraneumónico, 178 DP− (48,6%) y 188 DP+ (51,4%), con una mediana de edad de 4 años (rango intercuartílico: 2-7 años) y una evidente estacionalidad con máximo en invierno y mínimo en verano. Se identificó al agente etiológico por cultivo en 34 pacientes (9,3%), destacando Streptococcus pneumoniae (24 pacientes) seguido por Streptococcus pyogenes (7 pacientes). El serotipo de S. pneumoniae más frecuente fue el 19A (6 pacientes) y se han identificado 3 fallos vacunales. La tasa anual media de incidencia fue de 14,3 casos por 100.000 menores de 15 años (7,0 para DP− y 7,3 para DP+), sin cambios significativos a lo largo del tiempo, aunque sí se apreciaron diferencias marcadas de la incidencia entre los distintos departamentos sanitarios. Conclusiones: No hemos encontrado variaciones temporales en la incidencia del derrame paraneumónico pese a la implementación de la vacuna antineumocócica conjugada de 13 serotipos. Es destacable la variabilidad de la incidencia entre departamentos vecinos sin motivo aparente.(AU)

Introduction: The reported incidence of parapneumonic pleural effusion, including empyema, has shown fluctuations in the last decades. It has been related to the implementation of different types of conjugate pneumococcal vaccines. Methods: We have retrospectively reviewed data from all 10 public hospitals in Alicante Province (Spain) covering a population of 279,000 children under 15 years of age, between 2010 and 2018. Effusions less than 10mm (PE−) and those of 10mm or more (PE+) were separated. Results: A total of 366 episodes of parapneumonic pleural effusion have been analyzed, 178 PE− (48.6%) and 188 PE+ (51.4%), with a median age of 4 years (interquartile range: 2-7 years) and marked seasonality with the maximum in winter and the minimum in summer. A culture proven bacterial agent was identified in 34 patients (9.3%), mainly Streptococcus pneumoniae (24 patients) followed by Streptococcus pyogenes (7 patients). The most frequent S. pneumoniae serotype was 19A (6 patients) and 3 vaccine failures were observed. The mean annual incidence rate was 14.3 cases per 100,000 children under 15 years of age (7.0 for PE− and 7.3 for PE+). No significant changes were observed in incidence over time, but noticeable differences in incidence were observed in different health departments. Conclusions: We have not found temporal variations in incidence of parapneumonic effusion despite the implementation of the 13-valent pneumococcal conjugate vaccine. The unexplained disparity in incidence between close departments is noteworthy.(AU)

Neumonía bacteriana en niños en Ecuador: una mirada al impacto de las vacunas

Introducción: La neumonía adquirida en la comunidad es una de las enfermedades con mayor prevalencia en la comunidad pediátrica en nuestro país. De las diferentes etiologías que pueden causarlas, la neumonía ocasionada por Streptococcus pneumoniae puede ser prevenida con el uso de inmunización. Actualmente se disponen de tres tipos de vacunas antineumocócicas conjugadas autorizadas de uso pediátrico de forma sistemática. Objetivo: Identificar la prevalencia de neumonía bacteriana en niños bajo 5 años de edad, que requirieron hospitalización comparando la vacuna neumocócica recibida: 10 valente (PCV10) versus 13 valente (PCV13). Pacientes y Métodos: Estudio de descriptivo, retrospectivo. Se incluyeron pacientes hospitalizados bajo 5 años de edad, con diagnóstico de neumonía bacteriana mediante codificación CIE10 en un hospital de tercer nivel de la ciudad de Quito-Ecuador, durante el año 2019. Resultados: Se estudiaron 175 pacientes de los cuales 74 cumplieron con criterios clínicos de neumonía, de estos 46 recibieron PCV10 y 28 recibieron vacuna PCV13. Discusión y Conclusiones: La prevalencia de neumonía bacteriana fue mayor en los pacientes inmunizados con PCV10 lo que sugiere una relación de menor probabilidad de neumonía con el uso de la vacuna PCV13.

Background: Community-acquired pneumonia is one of the most prevalent diseases in the pediatric community in our country, of the different etiologies that can cause them, pneumonia caused by Streptococcus pneumoniae can be prevented with the use of immunization. Currently there are three types of authorized pneumococcal conjugate vaccines for pediatric use in a systematic way. Aim: To identify the prevalence of bacterial pneumonia in children under 5 years of age who required hospitalization by comparing the pneumococcal vaccine received: 10 valent (PCV10) versus 13 valent (PCV13). Methods: Descriptive, retrospective study. Hospitalized patients under 5 years of age with a diagnosis of bacterial pneumonia by ICD10 coding in a third level hospital in the city of Quito - Ecuador during 2019 were included. Results: 175 patients were studied, of which 74 patients met clinical criteria for pneumonia, of these 46 received PCV10 and 28 received PCV13 vaccine. Discussion and Conclusions: The prevalence of bacterial pneumonia was higher in patients immunized with PCV10, suggesting a relationship of lower probability of pneumonia with the use of the PCV13 vaccine.

Pneumococcal vaccine uptake among Medicare Beneficiaries aged ≥65 years following the shared clinical decision-making recommendation for 13-valent pneumococcal conjugate vaccine in 2019.

BACKGROUND: In November 2019, the US Advisory Committee on Immunization Practices recommended shared clinical decision-making (SCDM) for use of 13-valent pneumococcal conjugate vaccine (PCV13) among immunocompetent elderly adults. The impact of SCDM on PCV13 use in this population, immunocompromised persons, and vulnerable subgroups has not been well documented. METHODS: Using Medicare Research Identifiable Files (01/2018 - 09/2020), monthly uptake of pneumococcal vaccine (PCV13, 23-valent pneumococcal polysaccharide vaccine [PPSV23]) was identified among fee-for-service beneficiaries aged ≥ 65 years with Part B coverage and no evidence of prior PCV13. Uptake was stratified by vaccine, risk profile, and demographics. RESULTS: Among the > 12 M beneficiaries included each month, PCV13 uptake declined from > 70% of pneumococcal vaccinations before SCDM to < 60% after SCDM (02/2020). Reductions in PCV13 uptake were consistent across vulnerable subgroups as well as immunocompromised persons. CONCLUSIONS: PCV13 use decreased among immunocompetent and immunocompromised persons alike, despite continued routine PCV13 recommendation for the latter group.

Impacts of the COVID-19 pandemic on immunization with pneumococcal vaccines in children and older adults in Brazil.

The COVID-19 pandemic has profoundly impacted individuals, resulting in long-lasting consequences. One of the effects has been a decline in vaccine adherence attributed to physical distancing measures, potentially contributing to the resurgence of preventable diseases, and posing diagnostic challenges. Consequently, monitoring immunization rates becomes crucial as an indicator for health promotion campaigns and to mitigate the strain on healthcare systems. This study aims to assess the effects of the COVID-19 pandemic on immunization with pneumococcal vaccines in children and older adults in Brazil from 2018 to 2021. Data was collected from the Department of Informatics of the Unified Health System, focusing on the number of doses administered and vaccination coverage with pneumococcal vaccines across the country. A total of 21,780,450 doses were administered, with a decline of 19.97% in vaccine coverage throughout the evaluation period. An overall negative trend was observed in the time series analysis for all states in Brazil. However, not all showed a statistically significant change associated with the pandemic. Therefore, it is essential for states that experienced a decline in vaccination rates during the COVID-19 pandemic to closely monitor changes in pneumococcal vaccination. Failure in the process may lead to an increase in pneumococcal infections and place an additional burden on the healthcare system.