13-valent Conjugate Vaccine Research Articles

Pneumococcal Serotype-Specific Antibodies in Children with Recurrent Oto-sinopulmonary Infections.

Low titers to pneumococcal vaccine are a frequent finding in pediatric patients with recurrent oto-sinopulmonary infections. To characterize the pre- and post-immunization antibody trend for each serotype included in the pneumococcal 13-valent conjugate vaccine (PCV13), in a cohort of pediatric patients with recurrent oto-sinopulmonary infections. This retrospective review identified 182 patients with recurrent oto-sinopulmonary infections (131 required an immune workup and 99 had low pneumococcal titers leading to a PCV13 vaccine booster). Baseline pneumococcal serotype-specific antibody titers at initial visit and 6 weeks after the vaccine booster were obtained. An adequate response to the pneumococcal conjugate vaccine was deemed to be a 4-fold increase over baseline and/or a post-immunization titer of 1.3 µg/ml or greater. Overall, PCV13 booster provided a significant improvement in the number of protective titers, increasing from 3.6 serotypes at baseline to 11.1 serotypes at 6 weeks (p < 0.001). This increase correlated with improved clinical outcomes (81% showed no signs of recurrent infection after the first booster and 94% after a second booster). Post-immunization antibody concentrations were significantly higher than at baseline for all serotypes (p< 0.05) and only 8, 9N, and 12F did not exhibit a greater than 4-fold increase (p> 0.05) 6 weeks following booster. There were no differences between patients at different ages in post-immunization titer levels for all serotypes. In pediatric patients with recurrent oto-sinopulmonary infections, an additional pneumococcal booster proved to be effective in the protection of these children against further infections, across all age groups.

Current and new vaccines against pneumococci

Pneumococcal vaccination plays acrucial role in the prevention of bacterial respiratory infections caused by Streptococcus pneumoniae. Pneumococci are responsible for diseases such as pneumonia, sinusitis and acute otitis media and can cause serious invasive infections such as meningitis and bacteraemia. Pneumococcal pneumonia leads to increased morbidity and mortality, particularly in patients with chronic lung diseases such as chronic obstructive pulmonary disease (COPD). The introduction of 13-valent conjugate vaccines (pneumococcal conjugate vaccine13 [PCV13]) has significantly reduced the burden of disease. However, infections caused by serotypes not covered by PCV13 continue to occur. Current vaccines such as the 20-valent conjugate vaccine (PCV20) provide extended serotype coverage and have shown arobust immune response in clinical trials. The recently updated recommendations of the German Standing Committee on Vaccination (Ständige Impfkommission, STIKO) include the use of PCV20 for all indication categories in adults, which represents asimplified and more effective vaccination strategy. Future developments include vaccines with even broader serotype coverage and improved immunological properties; these are expected to further reduce the burden of pneumococcal disease. Improving vaccination uptake and increasing vaccination rates, particularly among at-risk groups, remain key objectives to protect public health in the long term.

Dynamics of &lt;i&gt;Streptococcus pneumoniae&lt;/i&gt; serotype structure in children for the period 2016–2022

BACKGROUND: The need for microbiological monitoring of the distribution of pneumococcal serotypes is associated with changes that occur during routine immunization of children with pneumococcal vaccines. AIM: To characterize the changes in the serotype structure of Streptococcus pneumoniae obtained from healthy preschool children between 2016 and 2022. MATERIALS AND METHODS: In total, 1250 healthy children aged 6 years attending kindergartens were examined in multicenter studies (2016–2018 and 2020–2022). Nasopharyngeal pneumococcal isolates (n=265) were obtained using the culture method. S. pneumoniae serotype was determined using polymerase chain reaction. RESULTS: Between 2016 and 2018, the prevalence of pneumococcal carriage decreased from 27.3 to 17.3%, and by 2022, it increased to 25.6%. Moreover, the correspondence of S. pneumoniae serotypes to the antigenic composition of the 13-valent pneumococcal vaccine decreased from 48.8 to 9.4% and the composition of the 20-valent vaccine from 75.6 to 39.1%. The proportion of “non-vaccine” types of pneumococcus increased from 22% in 2016 to 61% in 2022. Among the “non-vaccine” serotypes/groups, 15AF, 6CD, 23A, and 35F/47F were predominant, and new variants were also discovered: 23B and 35B. The serotypes included in the 13-valent conjugate vaccine were detected among unvaccinated children and were represented by variants 19F, 6A and 6B, 23F. Throughout the observation period, pneumococci of serotypes/groups 15BC, 11AD, and 10A were detected with high frequency. CONCLUSIONS: Because of the elimination of a significant part of S. pneumoniae “vaccine” serotypes in 2016–2022, the concordance of circulating variants with the antigenic composition of pneumococcal conjugate vaccines significantly decreased. In addition, the new types detected with high frequency are not included in existing pneumococcal vaccines, which necessitates the creation of new immunobiological drugs for pneumococcal infection prevention.

Invasive Pneumococcal Disease Epidemiology and Serotype Replacement After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Ontario, Canada, 2007-2022.

New vaccine products were recently authorized for protection against invasive pneumococcal disease (IPD) in Canada. Our aim was to determine age- and serotype-specific trends in IPD incidence and severity in Canada's largest province, Ontario. We included all confirmed IPD cases reported in Ontario and defined the pre-pneumococcal 13-valent conjugate vaccine (PCV13) era (01/2007 to 12/2010), post-PCV13 era (01/2011 to 12/2019), and coronavirus disease 2019 (COVID-19) pandemic era (01/2020 to 12/2022). We estimated incidence, hospitalization, and case fatality rate (CFR) by age. We grouped IPD cases by vaccine-specific serotypes (PCV13; PCV15-non-PCV13; PCV20-non-PCV13; PCV20-non-PCV15; polysaccharide 23-valent vaccine-non-PCV20; and non-vaccine-preventable [NVP]). We then compared incidence rates by age and serotype group in the pre- and post-PCV13 eras by calculating rate ratios (RRs) and their 95% CIs. Incidence and hospitalizations declined from the pre- to post-PCV13 era in children aged <5 years (RR, 0.7; 95% CI, 0.6-0.8; and RR, 0.8; 95% CI, 0.7-0.9, respectively), but the CFR increased (1.4% to 2.3%). Other age groups saw smaller declines or more stable incidence rates across the years; hospitalizations increased in adults aged 50-64 years (RR, 1.2; 95% CI, 1.1-1.4) and ≥65 years (RR, 1.1; 95% CI, 1.0-1.1). For all ages, IPD cases and hospitalizations attributable to PCV13 serotypes declined, and those attributable to PCV15-non-PCV13, PCV20-non-PCV13, and NVP serotypes increased. IPD incidence declined during the COVID-19 era. IPD incidence and hospitalizations due to PCV13 serotypes decreased after PCV13 introduction but increased for other serotypes. Continued surveillance is required to evaluate changes to pneumococcal vaccination programs and ongoing changes to the distribution of IPD-causing serotypes.

Severity of Exacerbation in Pneumococcal Vaccinated versus Unvaccinated Patients with Exacerbation of Chronic Obstructive Pulmonary Disease: A Post hoc Analysis of Presentation Status of the Subjects of HOPE Chronic Obstructive Pulmonary Disease Study

Background: Acute exacerbations occur with varying frequency and severity and impact the natural course of chronic obstructive pulmonary disease (COPD) patients. Pneumococcal vaccination has been shown to decrease the incidence of community-acquired pneumonia and exacerbation rate in COPD patients. There is a paucity of data on the influence of pneumococcal conjugate vaccination on the severity of COPD exacerbations. Objectives: The objectives of this study were to evaluate the severity of exacerbation in pneumococcal vaccinated (vaccinated with 13-valent conjugate vaccine) versus unvaccinated COPD subjects hospitalized with acute exacerbation. Materials and Methods: This was a post hoc analysis of the severity of exacerbation in the subjects of HOPE COPD study. This involved the collection of clinical, radiological, and laboratory data of 120 COPD patients who were hospitalized with an acute exacerbation, 60 of whom had prior pneumococcal vaccination and 60 were unvaccinated. Data of COPD patients at the time of presentation with acute exacerbation were analyzed. Comparison was made between severity parameters such as presence of fever, leukocytosis, respiratory failure, multilobar consolidation, hypotension needing inotropic support, and presence of sepsis between pneumococcal vaccinated and unvaccinated subjects. Results: The occurrence of multilobar consolidation was substantially less in the vaccinated group (60% vs. 6.7%; P = 0.0001). The incidence of fever, leukocytosis, and elevated C-reactive protein was significantly higher in the unvaccinated group. Need for intensive care unit care was higher in the unvaccinated group (58.3% vs. 30% with P = 0.019). The occurrence of new-onset respiratory failure was similar in both the groups although type 2 failure with respiratory acidosis was more in the unvaccinated group. Patients in the unvaccinated group had a higher incidence of sepsis and need for inotropic support as well as assisted ventilation. Conclusions: Prior immunization with 13-valent pneumococcal conjugate vaccine ameliorates the severity of exacerbation in COPD patients needing hospitalization. Pneumococcal vaccination may be recommended for all patients with COPD who are at risk of hospitalization with acute exacerbation.

Adult non-invasive pneumococcal pneumonia in Portugal is dominated by serotype 3 and non-PCV13 serotypes 3-years after near universal PCV13 use in children.

Non-invasive pneumococcal pneumonia (NIPP) is possibly the most frequent infection by Streptococcus pneumoniae in adults. However, the herd effect of vaccinating children in adult NIPP (aNIPP) remains poorly characterized. We determined the serotype distribution and antimicrobial susceptibility of isolates causing aNIPP (>18 years) in 2016-2018 in Portugal; 3 years with near universal vaccination of children with the 13-valent conjugate vaccine (PCV13), following over a decade of significant PCV use in children in the private market. Among the 1,149 aNIPP isolates, the most frequent serotypes detected were: 3 (n = 168, 14.6%), 11A (n = 102, 8.9%), 19F (n = 70, 6.1%), 23A and 23B (n = 62, 5.4% each), 9N (n = 60, 5.2%), 8 and 29/35B (n = 43, 3.7% each); together accounting for 53% of all isolates. The serotype distribution causing aNIPP was stable in 2016-2018, with the serotypes included in PCV7 still being important causes of disease and serotype 3, a PCV13 serotype, remaining the leading cause of aNIPP. There was an increase in penicillin non-susceptibility from 17% in 2016 to 24% in 2018 (p = 0.018). Some PCV13 serotypes, such as 14, 19A and 19F were associated to resistance, which may have contributed to their persistence. The fact that close to 20% of aNIPP is caused by four non-vaccine serotypes (23A, 23B, 9N, and 29/35B) and that there were significant differences in serotype distribution relative to invasive disease, stress the importance of maintaining the surveillance of these infections. The lack of a continued herd effect from vaccinating children and the significant fraction of aNIPP potentially preventable by PCV13 (30%), PCV15 (34%), PCV20 (53%) and the 23-valent polysaccharide vaccine (61%) underscore the importance of considering the broader use of pneumococcal vaccines in adults.

Ten-year analysis of the efficacy of vaccination against pneumococcal infection in patients with chronic obstructive pulmonary disease

Major problems in the course of chronic obstructive pulmonary disease (COPD) include frequent exacerbations and related deaths. The use of pneumococcal vaccines, primarily a 13-valent polysaccharide conjugate vaccine, is a generally recognized tool for reducing the number of exacerbations.The aim of the study was to analyze the prospective clinical efficacy of vaccine prophylaxis with conjugated pneumococcal vaccine Prevenar-13 (PCV13) in patients with COPD over 10 years.Methods. A total of 362 male patients who were treated or monitored at the Regional Pulmonological Center of Chelyabinsk in 2012 – 2022 were enrolled in the study. The main efficacy endpoints of observation over 10 years were: the dynamics of dyspnea (mMRC score), forced expiratory volume in 1st second, the number of exacerbations, hospitalizations, the number of pneumonias. After confirming the diagnosis of COPD, the patients were divided into two observation groups. The first group (n = 150) included patients vaccinated with PCV13. The second group (n = 212) included patients with COPD who had not received pneumococcal vaccination for various reasons.Results. Severe forms of the disease and frequent exacerbations predominated in both groups. 96 (27%) deaths were recorded in the PCV13-vaccinated group, and 171 (47%) deaths in the unvaccinated group. The difference between vaccinated and unvaccinated is statistically significant (p &lt; 0.05). In the unvaccinated patients, there was a steady progression of shortness of breath with an increase by 12% compared to baseline (p &lt; 0.05) by the 10th year. A positive trend in FEV1 was noted in patients vaccinated with PCV13. They also showed a significant decrease in BODE prognostic index.Conclusion. The use of PCV13 allows for stabilization of the main clinical and functional indicators of the respiratory system in patients with COPD in the long term (at least 10 years of follow-up). Vaccination maintains a low risk of adverse events according to the BODE index; an increase in patient survival was noted over a 10-year horizon (odds ratio – 2.35; 95% confidence interval – 1.45; 3.77), including cases with acute viral damage with COVID-19 (COronaVIrus Disease 2019).

1160. Comparative Effectiveness of Pneumococcal Vaccination Strategies to Prevent Invasive Pneumococcal Disease: A Cohort Study at the Veterans Health Administration

Abstract Background The direct impact of a combined vaccination strategy pneumococcal 13-valent conjugate vaccine (PCV13) and 23-valent polysaccharide vaccine (PPSV23) for adults in preventing pneumococcal infections has yet to be thoroughly investigated. We aimed to estimate the comparative effectiveness of preventing the most severe form of pneumococcal infections, invasive pneumococcal disease (IPD), by comparing the risk of IPD stratified by the use of PCV13, PPSV23, and their combinations. Methods We included all patients who were 65 years or older, had established primary care within the Veterans Health Administration (VHA) between 2005 and 2021, and had not received any prior pneumococcal vaccination. We measured time-to-event from cohort enrollment to the onset of culture-proven IPD, considering death a competing risk event, and constructed a Cox regression model to estimate cause-specific hazards. PCV13 only, PPSV23 only, and PCV13 + PPSV23 were incorporated into the model as a time-dependent exposure variable, and we estimated hazard ratios (HRs) associated with them. We also considered a waning effect by incorporating time-by-vaccine interaction terms in the model to estimate continuously changing time-dependent hazards. Results 5,069,917 patients were enrolled in the cohort (male: 96.5%; median age: 72 [IQR: 65-79]). 1,217,349 patients received at least one dose of pneumococcal vaccine during the study period. The overall incidence rate of IPD was 9.1 per 100,000 patient-years. In crude analysis, all pneumococcal vaccines were associated with lower HRs for IPD, and there was an additive benefit of PCV13 and PPSV23 (Tables 1 and 2). In multivariate analysis, associations between PCV13 alone and PPSV23 alone were no longer statistically significant after adjusting for age and comorbidities, but PCV13 + PPSV23 was significantly associated with lower HR for IPD. No time-by-vaccine interaction term was significant. Conclusion In this large cohort study at the VHA, neither vaccine by itself appeared to lower the risk of IPD, but the combination of PCV13 and PPSV23 was associated with a significantly lower risk. In addition, we did not observe evidence of a waning effect to prevent IPD. Further studies are needed to evaluate the effect of newer pneumococcal vaccines. Disclosures Michihiko Goto, MD MSCI, Merck &amp; Co.: Grant/Research Support

Vaccination against Streptococcus pneumoniae in Children Born between 2015 and 2018 in Poland-How Has the Introduction of Free Compulsory Pneumococcal Vaccination Affected Its Uptake?

Starting from 2017, pneumococcal vaccination was added to the Polish vaccination calendar as mandatory for all children born after 2016. The 10-valent conjugate vaccine was selected as mandatory and therefore free of charge. This paper aims to examine the impact of introducing mandatory vaccination on vaccine uptake. For this purpose, an analysis was conducted for 1595 vaccination record sheets from outpatient clinics in Wrocław and surrounding villages for children born 2015-2018. After the introduction of compulsory vaccination, the percentage of children fully vaccinated against pneumococcus increased (60.4% vs. 84.8%, p < 0.001). A significant decrease in the number of children who did not receive any dose of the vaccine was observed (27.8% to 3.3%, p < 0.001). The introduction of compulsory vaccination did not affect the completion of the pneumococcal schedule (11.8% vs. 11.9%). Compulsory PCV10 vaccination resulted in the less frequent choice of the 13-valent vaccine (72.3% vs. 19.9%, p < 0.001). More children in rural outpatient clinics were vaccinated against pneumococcus compared to urban outpatient clinics (84.8% vs. 70.8%, p < 0.001). The introduction of free pneumococcal vaccination increased the proportion of children vaccinated, although it did not affect the rate of discontinuation of the initiated schedule. In Poland, the increased popularity of the 10-valent vaccine at the expense of the 13-valent one translated into a change in the proportion of pneumococcal serotypes causing invasive pneumococcal disease.

Serotype replacement and an increase in non-encapsulated isolates among community-acquired infections of Streptococcus pneumoniae during post-vaccine era in Japan

ObjectivesIt is feared that the serotype replacement of Streptococcus pneumoniae occurred by the introduction of pneumococcal vaccines as periodical inoculation leads to reduced efficacy of the approved vaccines and altered antimicrobial susceptibility. MethodsWe determined serotypes of 351 S. pneumoniae isolates collected at a commercial clinical laboratory in Hokkaido prefecture, Japan, from December 2018 to February 2019 by using the polymerase chain reaction procedure of the US Centers for Disease Control and Prevention. Antimicrobial susceptibility and resistance gene profiles were also examined. ResultsVaccine coverage rates were 7.9% for 13-valent conjugate vaccine, and 32.5% for 23-valent polysaccharide vaccine, respectively. Non-typable strains were 19.7%. cpsA-positive isolates (group I), and null capsule clade (NCC)1, NCC2 and NCC3 (group II) comprised 31.3%, 28.4%, 32.8%, and 7.5% of the 69 non-typable strains, respectively. No penicillin-resistant/intermediate isolates were found; however, serotypes 35B and 15A/F showed low susceptibility to β-lactams. Only five strains (1.4%) were levofloxacin-resistant, and all were from the older persons, and three strains were serotype 35B. ConclusionThe progression of serotype replacement in non-invasive pneumococcal infections has occurred during the post-vaccine era in Japan, and non-encapsulated isolates, such as NCC, have increased. Antimicrobial susceptibility is not worsened.

Changes in serotype distribution of &lt;i&gt;Streptococcus pneumonia&lt;/i&gt; circulating among children in the Russian Federation after 13-valent pneumococcal conjugate vaccine introduction.

During a prospective multicenter non-interventional observational study, a comparative assessment was made of the serotype structure of pneumococci circulating among healthy children under the age of 5 years and children of the same age group with signs of respiratory infections in the periods 2016-2018 and 2020-2022. Data on the serotype structure of pneumococci in the period from 2016-2018 were obtained from our previous works. In 2020-2022 the study included 2066 healthy children and 603 children with respiratory infections. Streptococcus pneumoniae and their DNA were detected in nasopharyngeal swabs by classical culture and molecular methods. Typing was carried out by molecular methods. On the territory of the Russian Federation, pneumococci belonging to the serotypes included in the 13-valent vaccine are being forced out of circulation and replaced by non-vaccine serotypes. Before the introduction of mass antipneumococcal vaccination (until 2015), the 13-valent conjugate vaccine covered from 66.2% to 92% of pneumococci, after the start of mass anti-pneumococcal vaccination in the period 2016-2018, coverage decreased to 57.3%. Between 2020 and 2022, coverage was less than 40%. The main “non-vaccine” serotypes/serogroups circulating in the Russian Federation are 15AF, 11AD, 23A, 9LN and 16F.

Update of the consensus document on the aetiology, diagnosis and treatment of acute otitis media and sinusitis

Update of the consensus on acute otitis media (AOM) (2012) and sinusitis (2013) following the introduction of pneumococcal vaccines in the immunization schedule, and related changes, such as epidemiological variation, colonization by of nonvaccine serotypes and emerging antimicrobial resistances. A majority of studies show that the introduction of the pneumococcal 13-valent conjugate vaccine has been followed by a reduction in the nasopharyngeal carriage of pneumococcus, with an increase in the proportion of drug-resistant nonvaccine serotypes. The diagnosis of AOM is still clinical, although more stringent criteria are proposed, which are based on the visualization of abnormalities in the tympanic membrane and the findings of pneumatic otoscopy performed by trained clinicians. The routine diagnosis of sinusitis is also clinical, and the use of imaging is restricted to the assessment of complications. Analgesia with acetaminophen or ibuprofen is the cornerstone of AOM management; watchful waiting or delayed antibiotic prescription may be suitable strategies in select patients. The first-line antibiotic drug in children with AOM and sinusitis and moderate to severe disease is still high-dose amoxicillin, or amoxicillin-clavulanic acid in select cases. Short-course regimens lasting 5–7 days are recommended for patients with uncomplicated disease, no risk factors and a mild presentation. In allergic patients, the selection of the antibiotic agent must be individualized based on severity and whether or not the allergy is IgE-mediated. In recurrent AOM, the choice between watchful waiting, antibiotic prophylaxis or surgery must be individualized based on the clinical characteristics of the patient.

Temporal progression of the distribution of Streptococcus pneumoniae serotypes causing invasive pneumococcal disease in Galicia (Spain) and its relationship with resistance to antibiotics (period 2011–2021)

IntroductionStreptococcus pneumoniae causes serious diseases in the susceptible population. The 13-valent pneumococci conjugate vaccine (PCV13) was included in the children’s calendar in 2011. The objective of the study was to analyze the evolution of pneumococcal serotypes and their resistance after PCV13. MethodsThis study included the pneumococci serotyped in Galicia in 2011–2021. Antibiotic susceptibility was analyzed following EUCAST criteria. The data was analyzed in 3 sub-periods: initial (2011–2013), middle (2014–2017) and final (2018–2021). The prevalence of serotypes and their percentage of resistance to the most representative antibiotics were calculated. ResultsA total of 2.869 isolates were included. Initially, 42.7% isolates presented capsular types included in PCV13, compared to 15.4% at the end. Those included in PCV20 and not in PCV13 and PCV15 were 12.5% at baseline and 41.3% at the end; 26.4% of the isolates throughout the study had serotypes not included in any vaccine. The prevalence of serotype 8 multiplied almost by 8 and that of 12F tripled. The 19A serotype was initially the most resistant, while the resistance of serotypes 11A and 15A increased throughout the study. ConclusionsThe introduction of PCV13 in the pediatric population determined a change in pneumococcal serotypes towards those included in PCV20 and those not included in any vaccine. Serotype 19A was initially the most resistant and the 15A, not included in any vaccine, deserves special follow-up. Serotype 8, which increased the most, did not show remarkable resistance.

Actualización del documento de consenso sobre etiología, diagnóstico y tratamiento de la otitis media aguda y sinusitis

Update of the consensus on acute otitis media (AOM) (2012) and sinusitis (2013) following the introduction of pneumococcal vaccines in the immunization schedule, and related changes, such as epidemiological variation, colonization by of nonvaccine serotypes and emerging antimicrobial resistances. A majority of studies show that the introduction of the pneumococcal 13-valent conjugate vaccine has been followed by a reduction in the nasopharyngeal carriage of pneumococcus, with an increase in the proportion of drug-resistant nonvaccine serotypes. The diagnosis of AOM is still clinical, although more stringent criteria are proposed, which are based on the visualization of abnormalities in the tympanic membrane and the findings of pneumatic otoscopy performed by trained clinicians. The routine diagnosis of sinusitis is also clinical, and the use of imaging is restricted to the assessment of complications. Analgesia with acetaminophen or ibuprofen is the cornerstone of AOM management; watchful waiting or delayed antibiotic prescription may be suitable strategies in select patients. The first-line antibiotic drug in children with AOM and sinusitis and moderate to severe disease is still high-dose amoxicillin, or amoxicillin-clavulanic acid in select cases. Short-course regimens lasting 5–7 days are recommended for patients with uncomplicated disease, no risk factors and a mild presentation. In allergic patients, the selection of the antibiotic agent must be individualized based on severity and whether or not the allergy is IgE-mediated. In recurrent AOM, the choice between watchful waiting, antibiotic prophylaxis or surgery must be individualized based on the clinical characteristics of the patient.

Pneumococcal bacteraemia in adults over a 10-year period (2011-2020): a clinical and serotype analysis.

Streptococcus pneumoniae (pneumococcus) is a human nasopharyngeal tract coloniser responsible for invasive pneumococcal disease, which is largely vaccine preventable. Vaccination is recommended from birth for all, and through adulthood for those with risk conditions. To describe the clinical and serotype analysis of pneumococcus bacteraemia over a 10-year period. A 10-year (February 2011-December 2020) retrospective review was performed on all adult (age ≥18 years) pneumococcus bacteraemia presenting to the four public hospitals in Western Sydney, Australia. Comorbidities and risk factors were recorded. Three hundred unique episodes of S. pneumoniae bloodstream infection (SPBI) were identified during the study period. The median age for SPBI was 63 years with 31.7% aged 70 years or older. A 94.7% had one or more risks factors for SPBI. Pneumonia was reported in 80% of all SPBI, whereas meningitis was reported in 6% and infective endocarditis in <1%. Asplenia was noted in 2.4%. Seven- and 30-day mortality was 6.6% and 11.9%, with a higher 30-day mortality in those aged ≥70 years (24.4%). The serotype distribution showed 7-valent conjugate vaccine covered 11.0% of all isolates, whereas 13-valent conjugate vaccine (13vPCV) and a 23-valent polysaccharide vaccine (23vPPV) covered 41.7% and 69.0% respectively. Immunisation details were available for 110 individuals, of whom, only 7.3% had received pneumococcal vaccination. Most patients with pneumococcal bacteraemia had age- or comorbidity-related risk factors but were not vaccinated. Two-thirds of cases occurred in people aged <70 years. 13vPCV and 23vPPV covered 41.7% and 69.0% of bacteraemic isolates.

Nasopharyngeal colonization by Streptococcus pneumoniae in children and adults before the introduction of the 10-valent conjugate vaccine, Paraguay.

Streptococcus pneumoniae is a cause of invasive diseases such as pneumonia, meningitis, and other serious infections among children and adults in Paraguay. This study was conducted to establish S. pneumoniae baseline prevalence, serotype distribution, and antibiotic resistance patterns in healthy children aged 2 to 59 months and adults ≥60 years of age prior to the introduction of PCV10 in the national childhood immunization program in Paraguay. Between April and July 2012, a total of 1444 nasopharyngeal swabs were collected, 718 from children aged 2 to 59 months and 726 from adults ≥60 years of age. The pneumococcal isolation, serotyping, and antibiotic susceptibility testing were performed using standard tests. Pneumococcal colonization prevalence was 34.1% (245/718) in children and 3.3% (24/726) in adults. The most frequent pneumococcal vaccine-types (VT) detected in the children were 6B (42/245), 19F (32/245), 14 (17/245), and 23F (20/245). Carriage prevalence with PCV10 serotypes was 50.6% (124/245) and PCV13 was 59.5% (146/245). Among colonized adults, prevalence of PCV10 and PCV13 serotypes were 29.1% (7/24) and 41.6% (10/24), respectively. Colonized children were more likely to share a bedroom, have a history of respiratory infection or pneumococcal infection compared to non-colonized children. no associations were found in adults. However, no significant associations were found in children and neither in adults. Vaccine-type pneumococcal colonization was highly prevalent in children and rare in adults in Paraguay prior to vaccine introduction, supporting the introduction of PCV10 in the country in 2012. These data will be useful to evaluate the impact of PCV introduction in the country.

The safety of pneumococcal vaccines at the time of sequential schedule: data from surveillance of adverse events following 13-valent conjugated pneumococcal and 23-valent polysaccharidic pneumococcal vaccines in newborns and the elderly, in Puglia (Italy), 2013-2020.

Nowadays, two types of anti-pneumococcal vaccine are available: pneumococcal 13-valent conjugate vaccine (PCV13), first licensed in the United States (US) in 2013, and pneumococcal 23-valent polysaccaridic vaccine (PPSV23), first licensed in the US in 1999. These vaccines are recommended in Italy for the immunization of newborns and of the elderly, using a combined sequential schedule for the latter. This report aims to describe the PCV13- and PPSV23-related AEFIs notified in Puglia in 2013-2020, in order to design these products' safety profile in a real-life scenario, three years after the official recommendation about the sequential schedule for people over 60 years of age. This is a retrospective observational study. Data were gathered from the list of AEFIs notified following PCV13 and PPSV23 administration in Puglia in 2013-2020. The number of administered vaccine doses was obtained from the regional immunization database. AEFIs were classified according to WHO's algorithm, and causality assessment was carried out in case of serious AEFIs. From January 2013 to December 2020, 764,183 doses of PCV13 and 40,382 doses of PPSV23 were administered in Puglia. In the same period, 71 PCV13 AEFIs (Reporting Rate: 9.29 x100,000 doses) and 5 PPSV23 AEFIs (Reporting Rate: 12.4 x100,000 doses) were reported. The overall male/female ratio in AEFIs was 0.85. The majority of AEFIs occurred in subjects aged less than 2 (64/76, 84.2%), while 10 out of 76 (13.2%) occurred in patients aged 60 or older. 22 AEFIs were classified as serious and for 12 (54.5%) causality assessment showed a consistent relationship with immunization. The most commonly reported symptoms were fever (Reporting Rate: 4.72 x100,000 doses) and neurological symptoms (Reporting Rate: 3.23 x100,000 doses). Only one death was notified, classified as non-vaccine-related. The benefit of pneumococcal vaccination appears to be greater than the risk of AEFIs for both PCV13 and PPSV23. In fact, AEFIs occur in less than 0.1‰ of patients and the majority of AEFIs are mild and self-limiting.

Progresión temporal de la distribución de los serotipos de Streptococcus pneumoniae productores de enfermedad neumocócica invasiva en Galicia (España) y su relación con la resistencia a antibióticos (periodo 2011-2021)

IntroductionStreptococcus pneumoniae causes serious diseases in the susceptible population. The 13-valent pneumococci conjugate vaccine (PCV13) was included in the children's calendar in 2011. The objective of the study was to analyze the evolution of pneumococcal serotypes and their resistance after PCV13. MethodsThis study included the pneumococci serotyped in Galicia in 2011-2021. Antibiotic susceptibility was analyzed following EUCAST criteria. The data was analyzed in 3 sub-periods: initial (2011-2013), middle (2014-2017) and final (2018-2021). The prevalence of serotypes and their percentage of resistance to the most representative antibiotics were calculated. ResultsA total of 2.869 isolates were included. Initially, 42.7% isolates presented capsular types included in PCV13, compared to 15.4% at the end. Those included in PCV20 and not in PCV13 and PCV15 were 12.5% at baseline and 41.3% at the end; 26.4% of the isolates throughout the study had serotypes not included in any vaccine. The prevalence of serotype 8 multiplied almost by 8 and that of 12F tripled. The 19A serotype was initially the most resistant, while the resistance of serotypes 11A and 15A increased throughout the study. ConclusionsThe introduction of PCV13 in the pediatric population determined a change in pneumococcal serotypes towards those included in PCV20 and those not included in any vaccine. Serotype 19A was initially the most resistant and the 15A, not included in any vaccine, deserves special follow-up. Serotype 8, which increased the most, did not show remarkable resistance.

Serotype 19A and 6C Account for One-Third of Pneumococcal Carriage Among Belgian Day-Care Children Four Years After a Shift to a Lower-Valent PCV.

Pneumococcal conjugate vaccines (PCVs) effectively reduce infection and asymptomatic carriage of Streptococcus pneumoniae vaccine serotypes. In 2016, Belgium replaced its infant PCV13 program by a 4-year period of PCV10. Concomitantly, S. pneumoniae serotype carriage was monitored together with the carriage of other nasopharyngeal pathogens in children attending day-care centers. From 2016 to 2019, a total of 3459 nasopharyngeal swabs were obtained from children aged 6-30 months. Culture and qPCR were used for the identification of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus and for serotyping and antimicrobial susceptibility assessment of S. pneumoniae strains. S. pneumoniae colonization was frequent and stable over the study years. H. influenzae and M. catarrhalis were more frequently carried (P < .001) than S. pneumoniae, by, respectively, 92.3% and 91.0% of children. Prevalence of all PCV13 serotypes together increased significantly over time from 5.8% to 19.6% (P < .001) and was attributable to the increasing prevalence of serotype 19A. Coincidently, non-vaccine serotype 6C increased (P < .001) and the overall pneumococcal non-susceptibility to tetracycline and erythromycin. Non-susceptibility to cotrimoxazole decreased (P < .001). The switch to a PCV program no longer covering serotypes 19A, 6A, and 3 was associated with a sustained increase of serotypes 19A and 6C in healthy children, similarly as in invasive pneumococcal disease. This resulted in a re-introduction of the 13-valent conjugate vaccine during the summer of 2019.

Invasive pneumococcal disease in patients from a pediatric hospital in Peru, 2017-2020.

Motivation for the study: there are few reports describing cases of invasive pneumococcal disease after the introduction of the 13-valent conjugate vaccine in Peru. Main findings: cases of invasive pneumococcal disease are still reported in children, more frequently in children under five years of age. The most frequent clinical form was bacteremia and there was greater antibiotic resistance to erythromycin, trimethoprim-sulfamethoxazole, and penicillin. Implications: our findings suggest the need to maintain epidemiological surveillance of invasive pneumococcal disease and to measure the impact of vaccination against pneumococcus in children. This study aimed to describe the clinical characteristics, serotypes, and antibiotic susceptibility in patients with invasive pneumococcal disease (IPD). The medical records of patients with IPD who were hospitalized at the Instituto Nacional de Salud del Niño-Breña (Lima, Peru) were reviewed. We evaluated 29 patients. The median age was 1.9 years (interquartile range: 1 to 4 years). Of the sample, 51.7% were women and the most frequent clinical form of IPD was bacteremia in 18 (62.1%) patients; 65.5% had a complete vaccination schedule, according to the Peruvian Ministry of Health. Germ isolation was performed from blood samples in 82.8% of patients. Antibiotic resistance to erythromycin (55.2%) was the most frequent, followed by resistance to trimethoprim-sulfamethoxazole (48.3%) and penicillin (24.1%). The isolated serotypes were 6C, 19A, 23A and 24F. One patient died of meningitis. In conclusion, IPD was more frequent in children aged one to five years and the most frequent clinical form was bacteremia. Five serotypes reported in previous studies were found to be resistant to penicillin and erythromycin.