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.

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.

Invasive pneumococcal disease surveillance in Canada, 2021-2022.

Background: Invasive pneumococcal disease (IPD, Streptococcus pneumoniae) has been a nationally notifiable disease in Canada since 2000. The use of conjugate vaccines has caused a shift in the distribution of serotypes over time. This report is a summary of the demographics, serotypes and antimicrobial resistance of IPD isolates collected in Canada in 2021 and 2022. Methods: The National Microbiology Laboratory (NML) of the Public Health Agency of Canada in Winnipeg, Manitoba collaborates with provincial and territorial public health laboratories to conduct national surveillance of IPD. There were 1,999 isolates reported in 2021 and 3,775 isolates in 2022. Serotype was determined by the Quellung reaction or whole-genome sequencing (WGS). Antimicrobial susceptibilities were determined by WGS methods, broth microdilution, or data shared by collaborators in the Canadian Antimicrobial Resistance Alliance program at the University of Manitoba. Population-based IPD incidence rates were obtained through the Canadian Notifiable Disease Surveillance System. Results: The incidence of IPD in Canada was 5.62 cases per 100,000 population in 2021, decreasing from the peak of 10.86 cases per 100,000 population in 2018. Serotypes with increasing trends (p<0.05) between 2018 and 2022 included: 4 (6.1%-12.4%), 9V (1.0%-5.1%) and 12F (4.8%-5.4%). The overall prevalence of PCV13 serotypes increased over the same period (31.2%-41.5%, p<0.05) while the prevalence of non-vaccine types decreased significantly (27.3%-21.5%, p<0.0001). The highest rates of antimicrobial resistance in 2021 and 2022 were seen with clarithromycin (21%, 2021; 24%, 2022) and erythromycin (22%, 2021; 24%, 2022). Multidrug-resistant IPD continued to increase from 2018 to 2022 (6.7%-12.6%, p<0.05). Conclusion: The number of cases of IPD continued to decrease in 2021 in comparison to previous years, however, 2022 saw a return to pre-COVID-19 levels. Disease due to PCV13 serotypes 3, 4, 9V and 19F, as well as non-PCV13 serotypes 12F and 20, is increasing in prevalence. Surveillance of IPD to monitor changing serotype distribution and antimicrobial resistance is essential.

Invasive pneumococcal serotype 3 infection following pneumococcal vaccination in a hematopoietic stem cell transplant patient: A case report.

Given the high mortality rate of invasive pneumococcal disease (IPD) in hematopoietic stem cell transplant (HSCT) recipients, vaccination is recommended. These recipients respond to most vaccines; however, their immune response is typically weaker during the first months or years after transplantation, compared with that of healthy individuals. Here, we report a case of IPD with serotype 3 pneumonia and empyema in an HSCT recipient who had received three doses of the 13-valent pneumococcal conjugate vaccine (PCV) and one dose of the 23-valent pneumococcal polysaccharide vaccine; furthermore, the recipient had no relapse, graft-versus-host disease, or use of immunosuppressive agents after allogeneic HSCT for acute myeloid leukemia. Moreover, we discussed the characteristics of serotype 3 Streptococcus pneumoniae, a case series of breakthrough infections with S. pneumoniae in HSCT recipients who received pneumococcal vaccines, and the potential implications for the upcoming PCV15 and PCV20 vaccines for serotype 3.

Uptake of pneumococcal vaccines in older Australian adults before and after universal public funding of PCV13.

BACKGROUND: In 2020 Australia changed the funded universal older adult pneumococcal vaccination program from use of the 23-valent pneumococcal polysaccharide vaccine (PPV23) at age 65 to the 13-valent pneumococcal conjugate vaccine (PCV13) at age 70 years. We investigated uptake of both PCV13 and PPV23 in older adults before and after the program change. METHODS: We analysed a national dataset of records of patients attending general practices (GPs). We included regular attendees aged 65 or above in 2020. Cumulative uptake of PCV13 and monthly uptake of PPV23 was compared for the two periods before (January 2019 to June 2020) and after (July 2020 to May 2021) the program change on 1 July 2020, by age groups and presence of comorbid conditions. RESULTS: Our study included data from 192,508 patients (mean age in 2020: 75.1 years, 54.2 % female, 46.1 % with at least one comorbidity). Before July 2020, for all adults regardless of underlying comorbidities, the cumulative uptake of PCV13 was < 1 % but by May 2021, eleven months after the program changes, cumulative uptake of PCV13 had increased among those aged 70-79 years (without comorbidity: 16.3 %; with comorbidity: 21.1 %) and 80 + years (without comorbidity: 13.5 %; with comorbidity: 17.7 %), but not among those aged 65-69 years (without comorbidity: 1.3 %; with comorbidity: 3 %). Monthly uptake of PPV23 dropped following the program change across all age groups. CONCLUSIONS: Changes in uptake of PCV13 and PPV23 among those aged 70 + years were consistent with program changes. However, PCV13 uptake was still substantially lower in individuals aged 65-69 years overall and in those with comorbidities.

Pneumococci isolated from children in community-based practice differ from isolates identified by population and laboratory-based invasive disease surveillance.

BACKGROUND: Characterizing strains causing noninvasive and invasive pneumococcal disease (IPD) may inform the impact of new pneumococcal conjugate vaccines (PCVs). METHODS: During 2011-2019, among children aged 6-36 months, pneumococcal serotype distribution and antibiotic non-susceptibility of nasopharyngeal and middle ear fluid (MEF) isolates collected at onset of acute otitis media (AOM) in Rochester, New York were compared with IPD isolates from Active Bacterial Core surveillance (ABCs) across 10 U.S. sites. RESULTS: From Rochester, 400 (nasopharyngeal) and 156 (MEF) pneumococcal isolates were collected from 259 children. From ABCs, 907 sterile-site isolates were collected from 896 children. Non-PCV serotypes 35B and 21 were more frequent among the Rochester AOM cases, while serotypes 3, 19A, 22F, 33F, 10A, and 12F contained in PCVs were more frequent among ABCs IPD cases. The proportion of antibiotic non-susceptible pneumococcal isolates was generally more common among IPD cases. In 2015-2019, serotype 35B emerged as the most common serotype associated with multiclass antibiotic non-susceptibility for both the Rochester AOM and ABCs IPD cases. CONCLUSIONS: Pneumococcal isolates from children in Rochester with AOM differ in serotype distribution and antibiotic susceptibility compared to IPD cases identified through U.S. surveillance. Non-PCV serotype 35B emerged as a common cause of AOM and IPD.

Effect of pneumococcal conjugate vaccines on viral respiratory infections: a systematic literature review.

BACKGROUND: In addition to preventing pneumococcal disease, emerging evidence indicates that pneumococcal conjugate vaccines (PCVs) might indirectly reduce viral respiratory tract infections (RTI) by affecting pneumococcal-viral interactions. METHODS: We performed a systematic review of interventional and observational studies published during 2000-2022 on vaccine efficacy/adjusted effectiveness (VE) and overall effect of PCV7, PCV9, PCV10, or PCV13 against viral RTI. RESULTS: Sixteen of 1671 records identified were included. Thirteen publications described effects of PCVs against viral RTIs in children. VE against influenza ranged between 41-86% (n=4), except for the 2010-2011 influenza season. In a randomized controlled trial, PCV9 displayed efficacy against any viral RTI, human seasonal coronavirus, parainfluenza, and human metapneumovirus. Data in adults were limited (n=3). PCV13 VE ranged between 4-25% against viral lower RTI, 32-35% against COVID-19 outcomes, 24-51% against human seasonal coronavirus, and 13-36% against influenza A lower RTI, with some 95%CI spanning zero. No protection was found against adenovirus or rhinovirus in children or adults. CONCLUSIONS: PCVs were associated with protection against some viral RTI, with the strongest evidence for influenza in children. Limited evidence for adults was generally consistent with pediatric data. Restricting public health evaluations to confirmed pneumococcal outcomes may underestimate the full impact of PCVs.

Prevalence of prolonged otitis media with effusion among 2 to 3 years old Cameroonian children in the era of 13-valent pneumococcal conjugate vaccines.

Objectives: There is data scarcity on the overall effects of pneumococcal conjugate vaccines (PCVs) on otitis media (OM) in low- and middle-income countries. The impact of the 13-valent PCV (PCV13) program on OM was evaluated in Cameroon where infant vaccination was implemented in July 2011 using a 3-dose primary series at 6, 10 and 14 weeks of age. Methods: Through community-based surveillance, we used a retrospective cohort study design to assess OM prevalence among PCV13-vaccinated children aged 24 to 36 months in 2015. This was compared with a 2013 age-matched cohort of PCV13-unvaccinated children. OM was diagnosed by clinical inspection for chronic suppurative OM (CSOM) and tympanometry for OM with effusion (OME). CSOM was defined as draining of the middle ear with duration of more than 2 weeks and prolonged OME was defined as a flat 'type B' tympanogram. PCV13-vaccinated and PCV13-unvaccinated cohorts were compared by calculating prevalence odds ratios for OM and baseline characteristics. Results: Altogether, 111 OM cases were identified; 42/433 (9.7%) in the PCV13-unvaccinated in 2013 and 69/413 (16.7%) in the PCV13-vaccinated cohort in 2015. In the 2013 baseline survey, 3/433 (0.7%) children were identified with unilateral CSOM compared to 9/413 (2.2%) in the PCV13-vaccinated cohort in 2015. Bilateral prolonged OME was diagnosed in 7/433 (1.6%) PCV13-unvaccinated children and in 12/413 (2.9%) in PCV13-vaccinated children. Proportions of children with unilateral prolonged OME were 31/433 (7.2%) in the PCV13-unvaccinated group compared with 48/413 (11.6%) in the PCV13-vaccinated group. Multivariate logistic regression analysis showed evidence that PCV13-vaccinated children in 2015 had 40% less risk of contracting OM compared to PCV13-unvaccinated children in 2013 (adjusted prevalence odds ratios = 0.60 [95% confidence interval: 0.38 to 0.94], P = 0.025). Additionally, attributable proportion estimates show that, 58% of OM infections among the PCV13-vaccinated group would still have occurred despite PCV13 vaccination. Conclusion: Our findings provide significant evidence on the effect of PCV13 in decreasing OM or OME among children in this age group. It also supports justification for government's continuation of PCV13 immunization program in the absence of GAVI's funding. Further research is needed to assess the long-term impact of the PCV13 program on in OM Cameroon.

Effects of PCV10 and PCV13 on pneumococcal serotype 6C disease, carriage, and antimicrobial resistance.

BACKGROUND: The cross-protection of pneumococcal conjugate vaccines (PCV) against serotype 6C is not clearly documented, although 6C represents a substantial burden of pneumococcal disease in recent years. A systematic review by the World Health Organization that covered studies through 2016 concluded that available data were insufficient to determine if either PCV10 (which contains serotype 6B but not 6A) or PCV13 (containing serotype 6A and 6B) conferred protection against 6C. METHODS: We performed a systematic review of randomized controlled trials and observational studies published between January 2010 - August 2022 (Medline/Embase), covering the direct, indirect, and overall effect of PCV10 and PCV13 against 6C invasive pneumococcal disease (IPD), non-IPD, nasopharyngeal carriage (NPC), and antimicrobial resistance (AMR). RESULTS: Of 2548 publications identified, 112 were included. Direct vaccine effectiveness against 6C IPD in children ranged between 70 and 85 % for ≥ 1 dose PCV13 (n = 3 studies), was 94 % in fully PCV13 vaccinated children (n = 2), and -14 % for ≥ 1 dose of PCV10 (n = 1). Compared to PCV7, PCV13 efficacy against 6C NPC in children was 66 % (n = 1). Serotype 6C IPD rates or NPC prevalence declined post-PCV13 in most studies in children (n = 5/6) and almost half of studies in adults (n = 5/11), while it increased post-PCV10 for IPD and non-IPD in all studies (n = 6/6). Changes in AMR prevalence were inconsistent. CONCLUSIONS: In contrast to PCV10, PCV13 vaccination consistently protected against 6C IPD and NPC in children, and provided some level of indirect protection to adults, supporting that serotype 6A but not 6B provides cross-protection to 6C. Vaccine policy makers and regulators should consider the effects of serotype 6A-containing PCVs against serotype 6C disease in their decisions.

Effect of Pneumococcal Conjugate Vaccine on Pneumonia Incidence Rates among Children 2-59 Months of Age, Mongolia, 2015-2021.

Starting in June 2016, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced into the routine immunization program of Mongolia by using a 2+1 dosing schedule, phased by district. We used prospective hospital surveillance to evaluate the vaccine's effect on pneumonia incidence rates among children 2-59 months of age over a 6-year period. Of 17,607 children with pneumonia, overall adjusted incidence rate ratios showed decreased primary endpoint pneumonia, very severe pneumonia, and probable pneumococcal pneumonia until June 2021. Results excluding and including the COVID-19 pandemic period were similar. Pneumonia declined in 3 districts that introduced PCV13 with catch-up campaigns but not in the 1 district that did not. After PCV13 introduction, vaccine-type pneumococcal carriage prevalence decreased by 44% and nonvaccine-type carriage increased by 49%. After PCV13 introduction in Mongolia, the incidence of more specific pneumonia endpoints declined in children 2-59 months of age; additional benefits were conferred by catch-up campaigns.

Validation and comprehensive analysis of Streptococcus pneumoniae IgG WHO enzyme-linked immunosorbent assay in an Indian reference laboratory.

Monitoring serotype-specific IgG levels against pneumococci is crucial for assessing immunity, vaccine efficacy, and evaluating vaccination programs. The WHO ELISA for pneumococci is a standardized assay ensuring consistency in testing and comparability of results across laboratories. It involves a rigorous testing process to confirm accurate, precise and reliable detection of antibodies. We validated the protocol for 13 pneumococcal serotypes by assessing its specificity, reproducibility (coefficient of variation ≤15%), repeatability (coefficient of variation ≤20%), accuracy, lower limit of quantification, stability, and robustness. We found these parameters were within acceptable ranges and showed excellent performance. Our findings imply that the method employed is appropriate for evaluating 13 valent pneumococcal conjugate vaccine which is introduced in the national immunization program by comparing pre-and post-vaccination IgG response.

Safety, tolerability and immunogenicity of a novel 24-valent pneumococcal vaccine in toddlers: A phase 1 randomized controlled trial.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) significantly reduced pneumococcal disease burden. Nevertheless, alternative approaches for controlling more serotypes are needed. Here, the safety, tolerability, and immunogenicity of a 24-valent (1/2/3/4/5/6A/6B/7F/8/9N/9V/10A/11A/12F/14/15B/17F/18C/19A/19F/20B/22F/23F/33F) pneumococcal vaccine based on Multiple Antigen-Presenting System (MAPS) technology (Pn-MAPS24v) was assessed in toddlers. METHODS: In this phase 1, blinded, dose-escalation, active-controlled multicenter study conducted in the United States (September/2020-April/2022), 12-15-month-old toddlers primed with three doses of 13-valent PCV (PCV13) were randomized 3:2 to receive a single dose of one of three Pn-MAPS24v dose levels (1 µg/2 µg/5 µg per polysaccharide) or PCV13 intramuscularly. Reactogenicity (within 7 days), treatment-emergent adverse events (TEAEs, within 180 days), serious/medically attended adverse events (SAEs/MAAEs, within 180 days), and immunogenicity (serotype-specific anti-capsular polysaccharide immunoglobulin G [IgG] and opsonophagocytic activity [OPA] responses at 30 days post-vaccination) were assessed. RESULTS: Of 75 toddlers enrolled, 74 completed the study (Pn-MAPS24v 1 µg/2 µg/5 µg: 15/14/16, PCV13: 29). Frequencies of local (60 %/67 %/31 %) and systemic events (67 %/67 %/75 %) in the Pn-MAPS24v 1 µg/2 µg/5 µg and the PCV13 (55 %, 79 %) groups were in similar ranges. TEAEs were reported by 47 %/40 %/63 % of Pn-MAPS24v 1 µg/2 µg/5 µg recipients and 52 % of PCV13 recipients. No vaccine-related SAE was reported. At 30 days post-vaccination, for each of the 13 common serotypes, ≥93 % of participants in each group had IgG concentrations ≥0.35 µg/mL; >92 % had OPA titers ≥lower limit of quantitation (LLOQ), except for serotype 1 (79 %). For 7/11 unique serotypes (2/8/9N/11A/17F/22F/33F), at all dose levels, ≥78 % of Pn-MAPS24v recipients in each group had IgG concentrations ≥0.35 µg/mL and 80 %-100 % had OPA titers ≥LLOQ. CONCLUSIONS: In 12-15-month-old toddlers, a single dose of Pn-MAPS24v showed an acceptable safety profile, regardless of dose level; AEs were reported at similar frequencies by Pn-MAPS24v and PCV13 recipients. Pn-MAPS24v elicited IgG and OPA responses to all common and most unique serotypes. These results support further clinical evaluation in infants.

Effects of sequential vs single pneumococcal vaccination on cardiovascular diseases among older adults: a population-based cohort study.

BACKGROUND: Recommendations around the use of 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13) seldom focus on potential benefits of vaccine on comorbidities. We aimed to investigate whether sequential vaccination with PCV13 and PPSV23 among older adults would provide protection against cardiovascular diseases (CVD) compared with using a single pneumococcal vaccine. METHODS: We conducted a Hong Kong-wide retrospective cohort study between 2012 and 2020. Adults aged ≥65 years were identified as receiving either a single or sequential dual vaccination and followed up until the earliest CVD occurrence, death or study end. To minimize confounding, we matched each person receiving a single vaccination to a person receiving sequential vaccination according to their propensity scores. We estimated the hazard ratio (HR) of CVD risk using Cox regression and applied structural equation modelling to test whether the effect of sequential dual vaccination on CVD was mediated via the reduction in pneumonia. RESULTS: After matching, 69 390 people remained in each group and the median (interquartile range) follow-up time was 1.89 (1.55) years. Compared with those receiving a single vaccine, those receiving sequential dual vaccination had a lower risk of CVD [HR (95% CI): 0.75 (0.71, 0.80), P < 0.001]. Post-hoc mediation analysis showed strong evidence that the decreased CVD risk was mediated by the reduction in all-cause pneumonia. CONCLUSIONS: Sequential dual pneumococcal vaccination was associated with lower risk of CVD compared with single-dose PCV13 or PPSV23 in older adults. Such additional CVD benefits should be considered when making decisions about pneumococcal vaccination.

Mortality of Invasive Pneumococcal Disease following Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Greenland.

Before the incorporation of the 13-valent pneumococcal conjugate vaccine (PCV13) into the childhood vaccination regimen in Greenland in 2010, Inuit populations experienced a substantial prevalence of invasive pneumococcal disease (IPD). The PCV13 introduction has been shown to markedly reduce the incidence of IPD. This current study estimated the impact of PCV13 introduction on IPD mortality in Greenland. This was a nationwide register-based study using all available data on IPD cases 1995-2020 in Greenland. Thirty-one-day IPD case fatality rates (CFR), and all-cause and mortality rates associated with IPD during the period before the introduction of PCV13 (January 1995 to September 2010) were compared with those observed in the post-PCV13 era (September 2010 to October 2020). Standardized mortality ratios (SMRs) expressed differences in mortality by sex, age, region, ethnicity, comorbidity, and serotype. IPD CFR decreased with 24.5% from the pre- to the post-PCV13 period. SMR in IPD patients decreased by 57% (95% CI, 36-75%), and a reduction occurred in all age groups. While SMR in IPD persons ≥60 years remained virtually unchanged, there were no IPD-related deaths in persons ≤39 years in the post-PCV13 period. In conclusion, IPD-related mortality has decreased in Greenland following PCV13 introduction in 2010 in the country.

Compliance with recommended pneumococcal vaccination schedule in patients treated for rheumatoid arthritis: A retrospective cohort study in the Veterans Affairs population.

INTRODUCTION: Invasive pneumococcal disease (IPD) is a leading cause of death. Rheumatoid arthritis (RA) patients are at risk of IPD due to immunosuppressant medications. Up until 2022, two pneumococcal vaccines, the 13-valent Pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23), were recommended. Despite the recommendation change to give a single 20-valent PCV vaccine (PCV20), some still require multiple vaccinations. There is a need to identify barriers to vaccine uptake. METHODS: We conducted a retrospective cohort study to assess the on-time vaccination rates for PCV13 and PPSV23 in treated RA patients between 2010 and 2018 using national Veterans Affairs data. Patients > 18 years of age diagnosed with RA and newly initiated on RA treatment were included. Pneumococcal vaccine compliance was assessed by measuring on-time receipt of PCV13 and PPSV23 vaccinations. We identified factors using multivariate logistic regression and described the occurrence of these factors using descriptive statistics. RESULTS: A total of 39,243 patients were included in the study. Most patients were white (75.8 %), male (85.4 %), on methotrexate therapy (41.4 %). The average age was 62.3 years. The proportion of patients considered vaccine compliant is 43.9 %. The primary independent risk factors for vaccine non-compliance were black/African American race (Odds Ratio [OR] 1.26, 95 % Confidence Interval [CI] 1.19-1.34) or missing/unknown race (OR 1.45, 95 % CI 1.31-1.61), missing/unknown ethnicity (OR 1.21, 1.02-1.43), never married (OR 1.10, 95 % CI 1.02-1.19) or widowed (OR 1.23, 95 % CI 1.12-1.34), diagnosed with congestive heart failure (OR 1.10, 95 % CI 1.00-1.22), or dementia (OR 1.48, 95 % CI 1.16-1.91). The proportion of patients who were non-compliant in patients who were vaccine naïve was 32.1 % and the non-compliance rate for non-naïve patients was 65.3 %. CONCLUSIONS: Providers should identify barriers to pneumococcal vaccination in RA patients to improve compliance. Efforts to increase vaccination should be tailored to specific high-risk groups.

Effect of Pneumococcal Conjugate 13 Valent and Polysaccharide 23 Valent Vaccination on Anti-Pneumococcal Antibody Titer of Hemodialysis Patients: A Randomized Clinical Trial.

Background: Pneumococcal infections are a life- threatening disease in hemodialysis patients and vaccination against pneumococcus is an effective prevention. The current study aims to evaluate the immune response and maintenance of the anti-pneumococcal antibody titer in hemodialysis patients to the 23 valent pneumococcal polysaccharide vaccine alone and 13 valent conjugated with 23 valent polysaccharide vaccine. Materials and Methods: This study is a randomized clinical trial that was performed at Loghman Hakim Hospital in Tehran, Iran in 2017. A total of 70 patients undergoing hemodialysis were randomly assigned to intervention (22 patients) and control (23 patients). In the control group, only one dose of the PPSV23 vaccine while patients in the intervention group were injected initially with PCV13, and then after at least 8 weeks PPSV23 vaccine. The outcome of this study is first and sixth-month antibody titer after injection of the PPSV23 vaccine. Results: The obtained result showed no significant difference between the two groups in the first month and sixth months. The results indicate that both the intervention group (treated with PCV13+PPSV23) and the control group (treated with PPSV23 only) experienced a significant impact from the first to the sixth month. Additionally, there was a noticeable effect on the levels of anti pneumococcal antibodies during the first to sixth month between the intervention and control groups. In addition, the difference between the antibody titer of the first month and the sixth month was not significant in the two groups. Conclusion: The anti-pneumococcal antibody titer in hemodialysis patients does not show a clear difference after two vaccine injections and one vaccination.

Comparison of pneumococcal immunogenicity elicited by the PCV13 and PCV15 vaccines in adults 18 through 49 years of age.

AIM: Pneumococcal conjugate vaccines (PCV13, PCV15, PCV20) effectively target the capsular polysaccharides of the most common disease-causing Streptococcus pneumoniae serotypes. In this short communication, we analyzed healthy participants who received PCV13 and PCV15 vaccines as part of a recently concluded exploratory clinical trial and report antibody responses to the 13 shared serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) as well as functional OPA responses to serotype 3. METHODS: Sera from 87 adult participants (18 through 49 years of age) randomized to receive either PCV13 or PCV15 were collected (n = 46 or n = 41, respectively), from 17 study centers in the US. IgG concentrations of the 13 shared serotypes and serotype 3-specific OPA titers were analyzed before and 1 month after vaccination using internally validated assays. RESULTS: At 1 month after vaccination, IgG GMCs of the 13 shared serotypes in PCV13 were similar to those for PCV15. Specifically, serotype 3 OPA GMTs and 95% CIs were similar 1 month after vaccination for PCV13 (62.9 [48.9, 80.9]) and PCV15 (71.1 [50.9, 99.2]). CONCLUSION: In healthy participants who received either PCV13 or PCV15, similar serotype-specific responses were observed between all shared serotypes when a uniform validated internal assay was used. Of note, data from this study suggest that both vaccines induce similar functional antibody responses against pneumococcal serotype 3.

A multicenter study on the epidemiology of complicated parapneumonic effusion in the era of currently available pneumococcal conjugate vaccines.

BACKGROUND: Parapneumonic effusion (PPE) is a common complication of pneumonia. Streptococcus pneumoniae is the most common cause of bacterial pneumonia. A reduction in pneumonia hospitalizations has been observed since the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). Despite this apparent benefit, an increase in the incidence of PPE was recorded in some countries following PCV7 implementation. As the 13-valent pneumococcal conjugate vaccine (PCV13) was expected to provide a wider protection against PPE, the aim of the present study was to evaluate the impact of PCV13 introduction on the epidemiology of complicated parapneumonic effusion (c-PPE) among children in the Athens greater area. METHODS: All cases of community-acquired pneumonia (CAP) with PPE requiring chest tube insertion (complicated PPE, c-PPE) hospitalized in the 3 public Children's hospitals in Athens between 01/01/2004 and 31/12/2019 were included in the study. RESULTS: A total of 426 cases of c-PPE associated with pneumonia were recorded of which 198 were admitted during 2004-2010 (period A, prePCV13/PCV -7 introduction period) and 228 during 2011-2018 (period B, post - PCV13 period). A definite bacterial etiology was established in 44.4 % of all cases and of those 25.4 % were caused by S. pneumoniae. An increasing trend in c-PPE incidence was observed during period A; although, a significant decrease on c-PPE annual rates was observed during the period B (p = 0.011), a remarkable increase in serotype 3 cases was recorded. CONCLUSION: A decreasing time trend in c-PPE cases among children was shown after the introduction of PCV13 in our area. However, serotype 3 is nowadays a common cause of PPE. Hence, continuous surveillance is imperative in order to follow c-PPE epidemiology over time.

Effectiveness of 13-valent pneumococcal conjugate vaccine on all-cause pneumonia in children under 5 years in Shanghai, China: An observational study.

BACKGROUND: Streptococcus pneumoniae (Spn) is a common respiratory pathogen and the main cause of bacterial pneumonia, meningitis, and bacteremia, acute otitis media. Imported 13-valent pneumococcal conjugate vaccine (PCV13) was licensed in China and introduced in Shanghai in 2017. We aim to describe PCV13 vaccination trends and pneumonia incidence of children under 5 from 2017 to 2020, then estimate the effectiveness of PCV13 against community-acquired pneumonia (CAP) in children under 5 in Shanghai, China. METHODS: By calculating propensity scores with logistic regression, a comparison group was formed by frequency matching one unvaccinated child to one vaccinated child. For matching, we used the nearest-neighbor matching algorithm and exact matching, and then created distinct matched analysis sets for two cohorts. A Kaplan-Meier analysis was conducted to measure the cumulative incidence of all-cause pneumonia in both groups and used the log-rank test to assess the differences between the two cumulative incidence curves. Cox proportional hazards regression was used to compare the adjusted hazard ratios (HR) of differences in all-cause pneumonia between the two groups. RESULTS: Children received three or more doses PCV13 accounted for 85.7% of all vaccinated children. The incidence of pneumonia in Shanghai's Songjiang district decreased rapidly from 2017, when PCV13 vaccination presented an overall increasing trend. The estimated vaccine effectiveness against visits for all-cause pneumonia was 19% (95% CI: 3 to 32) after the first dose in children vaccinated with at least one dose of PCV13. The protective effectiveness of PCV13 was found to be higher for hospitalized pneumonia (30%, 95% CI: 5% to 49%) than for outpatient pneumonia (19%, 95% CI: 4% to 32%). CONCLUSIONS: PCV13 vaccination among children aged 0-5 years substantially reduced the incidence of all-cause pneumonia. Direct immunization of children under 5 years is an effective strategy to combat outpatient pneumonia, and hospitalized pneumonia.

A Nationwide Digital Multidisciplinary Intervention Aimed at Promoting Pneumococcal Vaccination in Immunocompromised Patients.

Immunocompromised patients (IPs) are at high risk for infections, some of which are vaccine-preventable. The Israeli Ministry of Health recommends pneumococcal conjugate vaccine 13 (PCV13) and pneumococcal polysaccharide vaccine 23 (PPSV23) for IP, but vaccine coverage is suboptimal. We assessed the project's effectiveness in improving the pneumococcal vaccination rate among IP. An automated population-based registry of IP was developed and validated at Maccabi Healthcare Services, an Israeli health maintenance organization serving over 2.6 million members. Included were transplant recipients, patients with asplenia, HIV or advanced kidney disease; or those receiving immunosuppressive therapy. A personalized electronic medical record alert was activated reminding clinicians to consider vaccination during IP encounters. Later, IP were invited to get vaccinated via their electronic patient health record. Pre- and post-intervention vaccination rates were compared. Between October 2019 and October 2021, overall PCV13 vaccination rates among 32,637 IP went up from 11.9% (n = 3882) to 52% (n = 16,955) (p < 0.0001). The PPSV23 vaccination rate went up from 39.4% (12,857) to 57.1% (18,652) (p < 0.0001). In conclusion, implementation of targeted automated patient- and clinician-facing alerts, a remarkable increase in pneumococcal vaccine uptake was observed among IP. The outlined approach may be applied to increase vaccination uptake in large health organizations.