Risk Of Invasive Pneumococcal Disease Research Articles

Impact of PCV13 and PPSV23 Vaccination on Invasive Pneumococcal Disease in Adults with Treated Rheumatoid Arthritis: A Population-Based Study

On-time receipt of pneumococcal vaccines is essential in patients with rheumatoid arthritis (RA) as immunosuppressive medications increase their risk of invasive pneumococcal disease (IPD). However, data regarding the impact of timely administration of these vaccines on the risk of developing IPD are lacking for RA patients. We conducted a retrospective cohort study to assess the impact of on-time vaccination for pneumococcal conjugate vaccine (PCV) 13 and pneumococcal polysaccharide vaccine (PPSV) 23 in patients treated for RA on the development of IPD using national Veterans Affairs data from 2010 to 2018. 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. A total of 33,545 patients were included in the cohort. Non-compliance with PCV recommendations was associated with an increased risk of IPD in a multivariable logistic regression model. This finding was consistent whether IPD status was ascertained by International Classification of Diseases coding (OR 2.42, 95%CI 2.14–2.73) or microbiologic data (OR 1.64, 95%CI 1.26–2.14). Providers should actively seek opportunities to provide pneumococcal vaccinations to patients with RA, as their on-time administration is associated with a decreased risk of IPD.

Epidemiology of childhood invasive pneumococcal disease in Australia: a prospective cohort study

BackgroundThe widespread use of pneumococcal conjugate vaccines (PCV) has changed the epidemiology of invasive pneumococcal disease (IPD) in children globally.MethodsMulticentre prospective audit of IPD episodes from five paediatric hospitals in...

Comparative effectiveness of pneumococcal vaccination strategies to prevent invasive pneumococcal disease: a population-based cohort study at the veterans health administration in the United States

ObjectivesComparative effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13), 23-valent polysaccharide vaccine (PPSV23), and their combinations for adults in preventing invasive pneumococcal disease (IPD) has yet to be thoroughly investigated. We aimed to estimate the comparative effectiveness of preventing IPD, using population-based data from the Veterans Health Administration (VHA) in the United States. MethodsWe included all patients who were between 65 and 74 years, had established primary care within VHA between 2005 and 2021, and had not received any prior pneumococcal vaccination. We measured time-to-event from cohort enrolment to the onset of IPD, considering death a competing risk event, and used Cox regression models to estimate cause-specific hazards. PCV13 only, PPSV23 only, PCV13 after PPSV23, and PPSV23 after PCV13 were incorporated into models as time-dependent covariates. Patient demographics and comorbidities were also included in the model. ResultsA total of 3 044 067 patients were enrolled in the cohort, with 863 958 deaths (28.4%) and 1731 cases of IPD (0.06%) during the study period. The overall incidence rate of IPD in this population was 5.36 per 100 000 patient-years. A total of 921 070 patients (30.3%) received at least one dose of effective pneumococcal vaccine. In multivariate analysis adjusted for comorbidities, PCV13 alone was not associated with the reduced risk of IPD, whereas PPSV23 had protective association with IPD incidence (adjusted hazard ratio [aHR], 0.70; 95% CI, 0.59–0.83). When combined, PCV13 followed by PPSV23 had a stronger protective association (aHR, 0.54; [0.36–0.83]) compared with PPSV23 followed by PCV13 (aHR, 0.73; [0.58–0.91]). Discussion: In this large cohort study at the VHA, the combination of PCV13 and PPSV23, particularly PCV13 followed by PPSV23, was associated with a lower risk of IPD, indicating additional benefits in combined vaccinations with potential importance in vaccination order. Further studies are needed to evaluate the effect of newer pneumococcal vaccines.

Obstructive Sleep Apnea and Acute Lower Respiratory Tract Infections: A Narrative Literature Review.

Both obstructive sleep apnea (OSA) and acute lower respiratory tract infections (LRTIs) are important global health issues. The pathophysiological links between OSA and LRTIs include altered immune responses due to chronic intermittent hypoxia and sleep fragmentation, increased aspiration risk, and a high burden of comorbidities. In this narrative review, we evaluated the current evidence on the association between OSA and the incidence and outcomes of acute LRTIs in adults, specifically community-acquired pneumonia and viral pneumonia caused by influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Studies have demonstrated that OSA patients are more likely to develop bacterial pneumonia and exhibit a higher risk of invasive pneumococcal disease. The risk intensifies with the severity of OSA, influencing hospitalization rates and the need for intensive care. OSA is also associated with an increased risk of contracting influenza and suffering more severe disease, potentially necessitating hospitalization. Similarly, OSA contributes to increased COVID-19 disease severity, reflected by higher rates of hospitalization, longer hospital stays, and a higher incidence of acute respiratory failure. The effect of OSA on mortality rates from these infections is, however, somewhat ambiguous. Finally, we explored antibiotic therapy for OSA patients with LRTIs, addressing care settings, empirical regimens, risks, and pharmacokinetic considerations. Given the substantial burden of OSA and its significant interplay with acute LRTIs, enhanced screening, targeted vaccinations, and optimized management strategies for OSA patients should be prioritized.

Pneumococcal carriage and serotype distribution in children with nephrotic syndrome

BackgroundPatients with nephrotic syndrome (NS) are at a higher risk of developing invasive pneumococcal disease (IPD). Pneumococcal carriage studies are helpful tools for detecting potentially infectious serotypes and guiding immunization efforts. Pneumococcal nasopharyngeal colonization is common, and IPD can easily occur in an immunosuppressed state. Limited information is available regarding the frequency of pneumococcal carriage in individuals with NS. The aim of this study was to evaluate pneumococcal carriage and serotype distribution in children with NS.MethodsPneumococcal carriage was detected by real-time PCR assays from nasopharyngeal swab samples from 98 children with NS, and 100 healthy controls. Isolates were serotyped by real-time PCR.ResultsThe pneumococcal carriage rate was 44.9% in children with NS. Regarding the recommendation about pneumococcal immunization in children with NS, the vaccination rate was low. Also, non-PCV13 serotypes have been detected in at least 25% of PCV13-vaccinated children. There is no statistically significant difference in total pneumococcal carriage rate, PCV13 serotype carriage rate, or non-PCV13 serotype carriage rate between children with NS and healthy controls (p > 0.05 for all).ConclusionsThe pneumococcal carriage rate was similar between children with NS and healthy controls. However, because children with NS have an increased risk for IPD, the serotype distribution of children with NS can demonstrate the improved protection offered by new pneumococcal vaccines. Regular monitoring for IPD is crucial for assessing the evolving sero-epidemiology of pneumococcal infections and evaluating the effectiveness of vaccines for children with NS.Graphical A higher resolution version of the Graphical abstract is available as Supplementary information

Improving Pneumococcal Vaccination Rates in Immunosuppressed Pediatric Patients with Rheumatic Disease.

Patients with rheumatic diseases are at a high risk of invasive pneumococcal disease due to immunosuppression. We conducted a quality improvement project, and the first aim was to increase the percentage of patients with systemic lupus erythematosus and mixed connective tissue disease that is up to date on pneumococcal vaccinations from 9.6% to 80% within one year. Subsequently, the second aim was to increase the percentage of patients on immunosuppression with systemic lupus erythematosus, mixed connective tissue disease, juvenile dermatomyositis and systemic vasculitis that is up to date on pneumococcal vaccinations from 62.6% to 80% within one year. Two process measures were up-to-date vaccination status on (1) 13-valent pneumococcal conjugated vaccine (PCV13) and (2) 23-valent pneumococcal polysaccharide vaccine (PPSV23). Our outcome measure was being fully up to date on both pneumococcal vaccinations. Interventions included an immunization algorithm, reporting of eligible patients, education, reminders, and pre-visit planning. There were shifts in the centerline for all quality measures in both phases of this project. The combined pneumococcal vaccination rate for Phase 1 increased from 9.6% to 91.1%, and this centerline was sustained. Pneumococcal vaccination rates also significantly increased for Phase 2: 68.8% to 93.4% for PCV13, 65.2% to 88.5% for PPSV23, and 62.6% to 86.5% for the combined pneumococcal vaccination rate. Quality improvement methodology significantly increased and sustained pneumococcal vaccination rates in our high-risk, immunosuppressed patients. We continue to prioritize this important initiative to mitigate the risk of invasive pneumococcal disease.

Diabetes as a risk factor for pneumococcal disease and severe related outcomes and efficacy/effectiveness of vaccination in diabetic population. Results from meta-analysis of observational studies

AimsTo collect all available evidence on the effect of diabetes mellitus (DM) as a risk factor for pneumococcal disease incidence and related complications, and on the efficacy/effectiveness of vaccines in patients with DM.MethodsTwo distinct systematic searches on MEDLINE, Cochrane, ClinicalTrials.gov and EMBASE databases were performed, one for each meta-analysis, collecting all observational (cohort and case–control) studies and randomized clinical trials performed on humans up to June 1st, 2023.ResultsWe retrieved 36 observational studies comparing risk for pneumococcal disease and related complications in people with or without DM, and 11 studies (1 randomized clinical trial and 10 observational studies) assessing conjugated and polysaccaridic vaccines efficacy/effectiveness on preventing such outcomes. People with DM were at higher risk for Invasive Pneumococcal Disease (unadjusted OR 2.42 [2.00; 2.92]); Case-Fatality Rate (unadjusted OR 1.61 [1.25; 2.07], Pneumococcal pneumonia (unadjusted OR 2.98 [2.76; 3.22), and Intensive care unit admission for pneumococcal disease (unadjusted OR 2.09 [1.20; 3.66]). In diabetic individuals vaccinated with conjugated vaccine, incidence of pneumonia specific for vaccine type in a clinical trial (OR 0.237 [0.008; 0.704]), and hospitalization for overall pneumonia during the year following the polysaccharide vaccination in observational studies (unadjusted OR 0.63 [0.45–0.89]) were significantly lower in comparison with unvaccinated DM subjects, with no significant differences for other outcomes.ConclusionsPeople with diabetes mellitus are at higher risk for less favourable course of pneumococcal disease and should be therefore targeted in vaccination campaigns; more evidence needs to be collected on vaccination outcomes in people with diabetes.

Neighborhood-level disadvantages increase risk for invasive pneumococcal disease

BackgroundStreptococcus pneumoniae (Spn) infection remains common worldwide despite recent vaccine efforts. Invasive pneumococcal disease (IPD) is the most severe form of Spn infection. Known individual risk factors for IPD include male gender and African American race. However, area-level socioeconomic factors have not been assessed. We examined the association of neighborhood-level disadvantages and risk of IPD in a tertiary medical center located in a socioeconomic diverse urban area in the Southeastern United States. MethodsPatients hospitalized with culture-confirmed Streptococcus pneumoniae (Spn) infection from 01/01/2010 - 12/31/2019 were identified from electronic health record (EHR). The cohort's demographic and clinical information were obtained from EHR. Patients’ residential address was geocoded and matched to 2015 area deprivation index (ADI). The association of ADI and IPD was evaluated using logistic regression after controlling for the demographic information (age, sex, race) and clinical factors (BMI, smoking status, alcoholism, immunosuppressive status, vaccination status, comorbidities). ResultsA total of 268 patients were hospitalized with culture-positive Streptococcus pneumoniae infection and 92 (34.3%) of them had IPD. The analysis showed that higher neighborhood deprivation (ADI in 79–100) was associated with increased risk of developing IPD in younger patients with age less than 65 (p = 0.007) after controlling for the individual demographic information and clinical factors. ConclusionsADI is a risk factor for IPD in younger adults. Community-level socioeconomic risk factors should be considered when developing prevention strategies such as increasing vaccine uptake in high risk population to reduce the disease burden of IPD.

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 & Co.: Grant/Research Support

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

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. 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. 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. Use of PCV15 and PCV20 could substantially reduce IPD among adults in Alaska, including Alaska Native adults and adults experiencing homelessness.

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

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. 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. 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). 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.

Vaccinating Welders against Pneumococcus: Evidence from a Systematic Review and Meta-Analysis.

Workers occupationally exposed to welding dusts and fumes have been suspected to be at increased risk of invasive pneumococcal disease (IPD). Since the 2010s, the United Kingdom Department of Health and the German Ständige Impfkommission (STIKO) actively recommend welders undergo immunization with the 23-valent polysaccharide (PPV23) pneumococcal vaccine, but this recommendation has not been extensively shared by international health authorities. The present meta-analysis was therefore designed to collect available evidence on the occurrence of pneumococcal infection and IPD among welders and workers exposed to welding fumes, in order to ascertain the effective base of evidence for this recommendation. PubMed, Embase and MedRxiv databases were searched without a timeframe restriction for the occurrence of pneumococcal infections and IPD among welders and workers exposed to metal dusts, and articles meeting the inclusion criteria were included in a random-effect meta-analysis model. From 854 entries, 14 articles (1.6%) underwent quantitative analysis, including eight retrospective studies (publication range: 1980-2010), and six reports of professional clusters in shipbuilding (range: 2017-2020). Welders had an increased likelihood of developing IPD compared with non-welders (odds ratio 2.59, 95% CI 2.00-3.35, I2 = 0%, p = 0.58), and an increased likelihood of dying from IPD (standardized mortality ratio (SMR) 2.42, 95% CI 1.96-2.99, I2 = 0%, p = 0.58). Serotype typing was available for 72 cases, 60.3% of which were represented by serotype 4, followed by 12F (19.2%) and serotype 8 (8.2%). Although the available data derive from a limited number of studies, available results suggest that pneumococcal vaccination should be recommended for workers exposed to welding fumes, and vaccination strategies should consider the delivery of recombinant formulates in order to combine the direct protection against serotypes of occupational interest with the mucosal immunization, reducing the circulation of the pathogen in occupational settings characterized by close interpersonal contact.

Pneumococcal infections in children with sickle cell disease before and after pneumococcal conjugate vaccines

AbstractChildren with sickle cell disease (SCD) are at increased risk of invasive pneumococcal disease (IPD). Over 25 years, the Georgia Emerging Infections Program/Centers for Disease Control and Prevention Active Bacterial Core Surveillance network identified 104 IPD episodes among 3707 children with hemoglobin SS (HbSS) or HbSC aged <10 years, representing 6% of IPD in Black or African American children residing in Metropolitan Atlanta (reference population). Children with IPD and HbSS/SC were older than those with IPD in the reference population (P < .001). From 1994-1999 to 2010-2018, IPD declined by 87% in children with HbSS aged 0 to 4 years, and by 80% in those aged 5 to 9 years. However, IPD incidence rate ratios when comparing children with SCD with the reference population increased from 20.2 to 29.2 over these periods. Among children with HbSS and IPD, death declined from 14% to 3% after 2002, and meningitis declined from 16% to 8%. Penicillin resistance was more prevalent in children with SCD before 7-valent pneumococcal conjugate vaccine (PCV7) licensure. After 2010, all IPD serotypes were not included in the 13-valent PCV (PCV13). Within 3 years of vaccination, the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against non-PCV13 serotypes included in PPSV23 plus 15A/15C was 92% (95% confidence interval, 40.8- 99.0, P = .014; indirect-cohort effect adjusted for age and hydroxyurea). PPSV23 would cover 62% of non-PCV13 serotype IPD in children with SCD, whereas PCV15, PCV20, and PCV21/V116 (in development) could cover 16%, 51%, and 92%, respectively. Although less frequent, IPD remains a life-threatening risk in children with SCD. Effective vaccines with broader coverage could benefit these children.

Safety and Immunogenicity of V114 in Preterm Infants: A Pooled Analysis of Four Phase Three Studies.

Risk of invasive pneumococcal disease is 3-fold higher in preterm versus full-term infants. V114 is a 15-valent pneumococcal conjugate vaccine (PCV) containing the 13 serotypes in PCV13 plus 2 unique serotypes, 22F and 33F. A pooled subgroup analysis was performed in preterm infants (<37 weeks gestational age) enrolled in 4 pediatric phase 3 studies evaluating the safety and immunogenicity of different 4-dose regimens of V114 or PCV13. Healthy preterm infants were randomized 1:1 to receive V114/PCV13 in the 4 studies. Safety was evaluated as the proportion of participants with adverse events (AEs) following receipt of PCV. Serotype-specific antipneumococcal immunoglobulin G (IgG) geometric mean concentrations, IgG response rates and opsonophagocytic activity geometric mean titers were measured at 30 days postdose 3, pretoddler dose and 30 days postdose 4. V114 and PCV13 were administered to 174 and 180 participants, respectively. Mean gestational age was 35.4 weeks (range: 27 - <37 weeks). Proportions of participants with AEs were comparable between vaccination groups; most AEs experienced were of short duration (≤3 days) and mild-to-moderate intensity. V114-elicited IgG geometric mean concentrations, IgG response rates and opsonophagocytic activity geometric mean titers were generally comparable to PCV13 for the 13 shared serotypes and higher for serotypes 22F and 33F at 30 days postdose 3 and postdose 4. In preterm infants, V114 was well tolerated and induced comparable immune responses to PCV13 for the 13 shared serotypes and higher immune responses to serotypes 22F and 33F. Results support the use of V114 in preterm infants.

Pneumococcal vaccination coverage among US adults enrolled in Medicaid and newly diagnosed with underlying medical conditions

ABSTRACTBackgroundAdults with chronic or immunocompromising conditions have an elevated risk of invasive pneumococcal disease, yet their pneumococcal vaccination rates remain low.MethodsThis retrospective cohort study used the IBM MarketScan® Multi-State Medicaid database to examine pneumococcal vaccination uptake among adults 19–64 years of age with underlying conditions. Gompertz accelerated failure time model was used to examine factors associated with vaccination.ResultsIn the study population of 108,159 adults, the vaccination rate was 4.1% after 1 year of follow-up and 19.4% after 10 years. The mean time from initial diagnosis to vaccination was 3.9 years. Adults aged 35–49 and 50–64 years (relative to 19–34) or those receiving an influenza vaccination were more likely to receive a pneumococcal vaccination. Adults with HIV/AIDS were more likely, while adults with chronic heart or lung disease, alcohol or tobacco dependence, or cancer were less likely to be vaccinated than adults with diabetes mellitus. Adults diagnosed by specialists were less likely to be vaccinated than those diagnosed by primary care providers.ConclusionsThe rates of pneumococcal vaccination among adults with Medicaid plans and underlying conditions were well under Healthy People Initiative targets. Insights into factors associated with vaccination can inform efforts to improve vaccination rates among this population.

Immunogenicity of the 13-Valent Pneumococcal Conjugated Vaccine Followed by the 23-Valent Polysaccharide Vaccine in Chronic Lymphocytic Leukemia.

Patients with Chronic Lymphocytic Leukemia (CLL) have a 29- to 36-fold increased risk of invasive pneumococcal disease (IPD) compared to healthy adults. Therefore, most guidelines recommend vaccination with the 13-valent pneumococcal conjugated vaccine (PCV13) followed 2 months later by the 23-valent polysaccharide vaccine (PPSV23). Because both CLL as well as immunosuppressive treatment have been identified as major determinants of immunogenicity, we aimed to assess the vaccination schedule in untreated and treated CLL patients. We quantified pneumococcal IgG concentrations against five serotypes shared across both vaccines, and against four serotypes unique to PPSV23, before and eight weeks after vaccination. In this retrospective cohort study, we included 143 CLL patients, either treated (n = 38) or naive to treatment (n = 105). While antibody concentrations increased significantly after vaccination, the overall serologic response was low (10.5%), defined as a ≥4-fold antibody increase against ≥70% of the measured serotypes, and significantly influenced by treatment status and prior lymphocyte number. The serologic protection rate, defined as an antibody concentration of ≥1.3 µg/mL for ≥70% of serotypes, was 13% in untreated and 3% in treated CLL patients. Future research should focus on vaccine regimens with a higher immunogenic potential, such as multi-dose schedules with higher-valent T cell dependent conjugated vaccines.

Chronic medical conditions associated with invasive pneumococcal diseases in inpatients in teaching hospitals in São Paulo city: Estimating antimicrobial susceptibility and serotype-coverage of pneumococcal vaccines.

Chronic conditions increase the risk of invasive pneumococcal diseases (IPD). Pneumococcal vaccination remarkably reduced IPD morbimortality in vulnerable populations. In Brazil, pneumococcal vaccines are included in the National Immunization Program (PNI): PCV10 for < 2 years-old, and PPV23 for high risk-patients aged ≥ 2 years and institutionalized ≥ 60 years. PCV13 is available in private clinics and recommended in the PNI for individuals with certain underlying conditions. A retrospective study was performed using clinical data from all inpatients from five hospitals with IPD from 2016 to 2018 and the corresponding data on serotype and antimicrobial-non-susceptibility of pneumococcus. Vaccine-serotype-coverage was estimated. Patients were classified according to presence of comorbidities: healthy, without comorbidities; at-risk, included immunocompetent persons with specific medical conditions; high-risk, with immunocompromising conditions and others RESULTS: 406 IPD cases were evaluated. Among 324 cases with information on medical conditions, children < 5 years were mostly healthy (55.9%), while presence of comorbidity prevailed in adults ≥ 18 years old (> 82.0%). Presence of ≥1 risk condition was reported in ≥ 34.8% of adults. High-risk conditions were more frequent than at-risk in all age groups. Among high-risk comorbidity (n=211), cancer (28%), HIV/AIDS (25.7%) and hematological diseases (24.5%) were the most frequent. Among at-risk conditions (n=89), asthma (16.5%) and diabetes (8.1%) were the most frequent. Among 404 isolates, 42.9% belonged to five serotypes: 19A (14.1%), 3 (8.7%), 6C (7.7%), 4 and 8 (6.2% each); 19A and 6C expressed antimicrobial-non-susceptibility. The vaccine-serotype-coverage was: PCV10, 19.1%, PCV13, 43.8%; PCV15, 47.8%; PCV20, 62.9%; PCV21, 65.8%, and PPV23, 67.3%. Information on hospital outcome was available for 283 patients, of which 28.6% died. Mortality was 54.2% for those with meningitis. Vaccine with expanded valence of serotypes is necessary to offer broad prevention to IPD. The present data contribute to pneumococcal vaccination public health policies for vulnerable patients, mainly those with comorbidity and the elderly.

604 - Low socioeconomic status is linked to increased risk of invasive pneumococcal disease

604 - Low socioeconomic status is linked to increased risk of invasive pneumococcal disease

EPH29 Metformin Use Is Associated with Reduced Incidence of Invasive Pneumococcal Disease after a Pneumococcal Vaccine in Adults with Type 2 Diabetes: A Retrospective Cohort Study

Metformin, a first-line agent for type 2 diabetes mellitus (T2DM) has been shown to have immunomodulating properties in vaccine efficacy, aging and infections, including pneumonia. This study evaluated whether metformin-use associated with lower risk for invasive pneumococcal disease (IPD) post receipt of a pneumococcal vaccine (PNV).

A quality improvement study: Optimizing pneumococcal vaccination rates in children with cochlear implants

Children with cochlear implants are at increased risk of invasive pneumococcal disease, with national and international guidelines recommending additional pneumococcal vaccines for these children.This study aimed to examine the pneumococcal immunization status and rate of invasive pneumococcal disease in children with cochlear implants at a tertiary paediatric hospital over a 12-year period. Additionally, the impacts of vaccination reminders and a dedicated immunization clinic on pneumococcal vaccination rates were assessed.This quality improvement study included 200 children who had received a cochlear implant through the Children’s Hearing Implant Program at a tertiary paediatric hospital servicing the state of Western Australia. The majority of children (88%) were not up to date with additionally recommended pneumococcal vaccinations. Over the 12-year study period, 2% of children developed invasive pneumococcal disease associated with cochlear implant infections. Generic and personalized electronic immunization reminders improved pneumococcal vaccine up-take in this paediatric cochlear implant setting from 12% (19/153) at baseline to 49% (75/153, p < 0.0001) post implementation. The value of a nurse-led dedicated immunization clinic was also demonstrated with all children (42/42, 100%) up to date with Prevenar13 and the majority (34/42, 81%) up to date with Pneumovax23 post initiation of this referral pathway. These data support the expansion of this model to other medically-at-risk paediatric groups that have been highlighted consistently to be under-vaccinated.