Immunization strategies for individuals with sickle cell anemia: A narrative review.

Sickle cell anemia (SCA) is a hereditary blood disorder characterized by the production of abnormal hemoglobin, leading to the formation of sickle-shaped red blood cells. These distorted cells can obstruct blood flow, causing vaso-occlusive crises and increasing the risk of severe infections due to functional asplenia and immune system dysregulation. Immunization is a crucial strategy to mitigate infection-related complications in individuals with SCA, necessitating a comprehensive and tailored vaccination approach. Current immunization guidelines for individuals with SCA recommend a combination of standard and additional vaccines to address their heightened susceptibility to infections. Key vaccines include pneumococcal conjugate (PCV13) and polysaccharide (PPSV23) vaccines, meningococcal conjugate (MenACWY) and serogroup B (MenB) vaccines, Haemophilus influenzae type b (Hib) vaccine, annual influenza vaccine, and hepatitis A and B vaccines. These vaccinations aim to provide broad protection against pathogens that pose significant risks to patients with SCA. Despite generally adequate immune responses, the variability in vaccine efficacy due to immune dysfunction necessitates booster doses and additional vaccinations. This narrative review highlights the importance of adhering to current immunization recommendations and addresses challenges such as access to care, vaccine hesitancy, and monitoring vaccination status.

Management of the vaccination campaign in a population of frail older outpatients affected by cognitive or endocrinological conditions: a pilot study in Italy.

Vaccination, particularly against pneumococcus and influenza, is a low-cost primary prevention, useful to avoid hard complications, particularly among frail older people. In this pilot study, we aimed to assess the effect of a strategy for influenza and pneumococcal vaccination for outpatients mainly affected by cognitive or endocrinological conditions, evaluating what could stimulate or demotivate vaccination among older people. This study was conducted during the 2023-2024 influenza season at the outpatient clinics in Palermo, Italy. A total 76 patients were included. More than half of the patients could be considered as pre-frail and about 20% frail, according to a comprehensive geriatric evaluation. Among patients, 46.05% received only vaccination against pneumococcus, 28.95% both vaccinations, and 25.0% only against influenza. Compared with the previous seasons, a 19.5% increase of influenza and 90.2% of pneumococcal vaccine uptake was observed. Side effects of vaccination were the main reason of the previous rejection, namely 76.9% for influenza and 53.8% for anti-pneumococcal vaccination. In conclusion, our study indicates how a new vaccination strategy in different settings could be feasible. Proposing influenza and pneumococcal vaccination for frail older outpatients could be an effective instrument to improve immunization coverage that is still low among older people.

Current trends in development and manufacturing of higher-valent pneumococcal polysaccharide conjugate vaccine and its challenges.

Pneumococcal conjugate vaccines (PCVs) have been developed to protect against pneumococcal diseases caused by the more than 100 serotypes of the bacterium Streptococcus pneumoniae. PCVs primarily prevent pneumococcal infections such as sepsis, bacteraemia, meningitis, otitis media, pneumonia, septicaemia, and sinusitis among infants, adults, elderly, and immunocompromised individuals. The current available PCVs only cover a limited number of serotypes, and there is an immense need for developing higher-valent PCVs that can protect against non-vaccine serotypes to overcome challenges like serotype replacement and antibiotic resistance. The main challenges for developing higher valent PCVs are the complexity of the manufacturing process comprising polysaccharide fermentation, purification, modification or sizing of multiple polysaccharides and conjugation between polysaccharides and carrier proteins, the stability of the conjugates, and the immunogenicity of the vaccine. Different manufacturing processes have been explored to produce higher valent PCVs using different serotypes of S. pneumoniae and conjugation with different carrier proteins. The global coverage of higher valent PCVs are still low, mainly due to the high cost and limited supply of the vaccine. This review focuses on the existing and emerging manufacturing processes and challenges associated with higher-valent pneumococcal PCV development.

Effectiveness of pneumococcal vaccination in adults with common immune-mediated inflammatory diseases in the UK: a case-control study.

BACKGROUND: People with immune-mediated inflammatory disease are at increased risk of pneumococcal pneumonia. The effectiveness of pneumococcal vaccination in people with immune-mediated inflammatory diseases has not been evaluated. We investigated the effectiveness of pneumococcal vaccination in preventing morbidity and mortality associated with pneumonia in patients with immune-mediated inflammatory diseases. METHODS: In this matched case-control study, we used primary-care electronic health record data from the Clinical Practice Research Datalink Gold database in the UK, with linked hospitalisation and mortality data. Adults with incident common immune-mediated inflammatory diseases diagnosed between April 1, 1997, and Dec 31, 2019, were followed up from the first diagnosis date to the occurrence of an outcome or date of last follow-up. Cases (ie, those with an outcome of interest) were age-matched and sex-matched to up to ten contemporaneous controls by use of incidence density sampling. Outcomes were hospitalisation due to pneumonia, death due to pneumonia, or primary-care consultation for lower respiratory tract infection requiring antibiotics. We defined hospital admission for pneumonia using hospital discharge diagnoses, death due to pneumonia using death certification data, and lower respiratory tract infection as present when primary-care consultation and antibiotic prescription occurred on the same date. We used multivariable, unconditional, logistical regression and constructed three models to examine the association between pneumococcal vaccination as an exposure and each of the three outcomes. FINDINGS: The first nested case-control analysis included 12 360 patients (7326 [59·3%] women and 5034 [40·7%] men): 1884 (15·2%) who were hospitalised due to pneumonia and 10 476 (84·8%) who were not admitted to hospital due to pneumonia. The second analysis included 5321 patients (3112 [58·5%] women and 2209 [41·5%] men): 781 (14·7%) who died due to pneumonia and 4540 (85·3%) who were alive on the index date. The third analysis included 54 530 patients (33 605 [61·6%] women and 20 925 [38·4%] men): 10 549 (19·3%) with lower respiratory tract infection treated with antibiotics and 43 981 (80·7%) without infection. In the multivariable analysis, pneumococcal vaccination was negatively associated with hospitalisation due to pneumonia (adjusted odds ratio 0·70 [95% CI 0·60-0·81]), death due to pneumonia (0·60 [0·48-0·76]), and lower respiratory tract infection treated with antibiotics (0·76 [0·72-0·80]). INTERPRETATION: Pneumococcal vaccination is associated with protection against hospitalisation and death due to pneumonia in patients with immune-mediated inflammatory diseases, without apparent residual confounding. However, residual unmeasured confounding cannot be fully excluded in observational research, which includes nested case-control studies. These findings should also be corroborated with data from other countries, given that this study used UK-based data. FUNDING: National Institute for Health and Care Research.

Limitations in the clinical utility of vaccine challenge responses in the evaluation of primary antibody deficiency including Common Variable Immunodeficiency Disorders.

Vaccine challenge responses are an integral component in the diagnostic evaluation of patients with primary antibody deficiency, including Common Variable Immunodeficiency Disorders (CVID). There are no studies of vaccine challenge responses in primary hypogammaglobulinemia patients not accepted for subcutaneous/intravenous immunoglobulin (SCIG/IVIG) replacement compared to those accepted for such treatment. Vaccine challenge responses in patients enrolled in two long-term prospective cohorts, the New Zealand Hypogammaglobulinemia Study (NZHS) and the New Zealand CVID study (NZCS), were compared in this analysis. Almost all patients in the more severely affected SCIG/IVIG treatment group achieved protective antibody levels to tetanus toxoid and H. influenzae type B (HIB). Although there was a highly significant statistical difference in vaccine responses to HIB, tetanus and diphtheria toxoids, there was substantial overlap in both groups. In contrast, there was no significant difference in Pneumococcal Polysaccharide antibody responses to Pneumovax® (PPV23). This analysis illustrates the limitations of evaluating vaccine challenge responses in patients with primary hypogammaglobulinemia to establish the diagnosis of CVID and in making decisions to treat with SCIG/IVIG. The conclusion from this study is that patients with symptoms attributable to primary hypogammaglobulinemia with reduced IgG should not be denied SCIG/IVIG if they have normal vaccine responses.

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

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

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

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

Unswitched memory B cell deficiency in children with sickle cell disease and response to pneumococcal polysaccharide vaccine.

Early mortality in sickle cell disease (SCD) is attributed to increased infections due to loss of splenic function. Marginal zone B cells are important for initial opsonization of pathogens and can be absent in spleen histopathology in SCD. The frequency of unswitched memory B cells (UMBC), the circulating correlate of marginal zone B cells, reflects the immunologic function of the spleen. We hypothesized that asplenia in SCD is associated with alterations in the peripheral blood lymphocyte population and explored whether UMBC deficiency was associated with a clinical phenotype. We analyzed B cell subsets and clinical history for 238 children with SCD and 63 controls. The median proportion of UMBCs was lower in children with SCD compared with controls (4.7% vs. 6.6%, p < .001). Naïve B cells were higher in SCD compared with controls (80.6 vs. 76.3%, respectively, p = .02). UMBC frequency declined by 3.4% per year increase in age in SCD (95% CI: 2%, 4.7%, p < .001), but not in controls. A majority of children in all cohorts had an IgM concentration in the normal range for age and there were no differences between groups (p = .13). Subjects developed titers adequate for long-term protection to fewer serotypes in the polysaccharide vaccine than controls (14.7 vs. 19.4, p < .001). In this cohort, bacteremia was rare and specific clinical complications were not associated with UMBC proportion. In summary, UMBC deficiency occurs in SCD and is associated with age. Future studies should investigate B cell subsets prospectively and identify the mechanism of B cell loss in the spleen.

Doubly robust proximal synthetic controls.

To infer the treatment effect for a single treated unit using panel data, synthetic control (SC) methods construct a linear combination of control units' outcomes that mimics the treated unit's pre-treatment outcome trajectory. This linear combination is subsequently used to impute the counterfactual outcomes of the treated unit had it not been treated in the post-treatment period, and used to estimate the treatment effect. Existing SC methods rely on correctly modeling certain aspects of the counterfactual outcome generating mechanism and may require near-perfect matching of the pre-treatment trajectory. Inspired by proximal causal inference, we obtain two novel nonparametric identifying formulas for the average treatment effect for the treated unit: one is based on weighting, and the other combines models for the counterfactual outcome and the weighting function. We introduce the concept of covariate shift to SCs to obtain these identification results conditional on the treatment assignment. We also develop two treatment effect estimators based on these two formulas and generalized method of moments. One new estimator is doubly robust: it is consistent and asymptotically normal if at least one of the outcome and weighting models is correctly specified. We demonstrate the performance of the methods via simulations and apply them to evaluate the effectiveness of a pneumococcal conjugate vaccine on the risk of all-cause pneumonia in Brazil.

Pneumococcal vaccination and primary care presentations for acute respiratory tract infection and antibiotic prescribing in older adults.

BACKGROUND: While the 23-valent pneumococcal polysaccharide vaccine (PPV23) has demonstrated its role in preventing severe pneumococcal disease, its impact on more non-specific conditions like acute respiratory tract infection (ARI) and lower respiratory tract infections (LRTI) remains unclear. We aimed to investigate the role of PPV23 in prevention of presentations for ARI and LRTI and related antibiotic prescriptions among older adults in primary care. METHODS: Using a nationwide general practice dataset, we followed a cohort of regularly attending patients aged ≥65 years from 1 January 2014 until 31 December 2018 for presentations for ARI, LRTI, and related antibiotic prescriptions. Associations between PPV23 receipt and each outcome were assessed using a multiple failures survival model to estimate hazard ratios (HR) adjusted for age, sex, socioeconomic status, and various health measures. RESULTS: A cohort of 75,264 patients aged ≥65 years (mean 75.4, 56% female) in 2014 was followed. The incidence of presentations for ARI, ARI-related antibiotic prescription, LRTI, and LRTI-related antibiotic prescription was 157.6, 76.0, 49.6, and 24.3 per 1000 person-years, respectively. Recent PPV23 vaccine receipt was associated with a small reduction in ARI presentations (adjusted HR vaccinated vs. unvaccinated 0.96; 95%CI 0.94-0.98; p = 0.002); however, there was no reduction in ARI-related antibiotic prescription, LRTI presentation, nor LRTI-related antibiotic prescription (adjusted HR were 0.99[95%CI 0.96-1.03], 1.04[95%CI 0.99-1.09], 1.07[95%CI 1.00-1.14]). CONCLUSION: PPV23 vaccination in older adults may result in a small reduction in the incidence of total ARI presentations in primary care. However, the effect is small and residual confounding cannot be excluded.

Retrospective study on the health and economic burden of hospitalized patients due to pneumonia and invasive pneumococcal infections in Belgium settings.

INTRODUCTION: pneumococcal infections are associated with high morbidity, hospitalisation and mortality. The objective of this study was to investigate the health and economic burden of all-cause pneumonia and invasive pneumococcal disease in Belgian hospital settings, by patient's age and risk profile. METHODS: This descriptive retrospective study was conducted in 17 Belgian hospitals. Univariate and multivariate logistic linear regression models were performed. The Health Insurance and patient's cost perspectives were considered because a few studies report these costs. RESULTS: The analysis has included 4,712 hospital admissions over the year 2018. Median hospitalization costs were higher for invasive pneumococcal infection diagnosis than for all-cause pneumonia (p < 0,001), respectively 4,051€ and 3,362€. Other factors associated with higher hospitalization cost were patient's high-risk profile, admission to emergency unit, transfer from nursing home, admission to intensive care unit and length of stay. CONCLUSION: Streptococcus pneumoniae infections remain a public health problem with significant cost for the Health Insurance and poor prognosis. Invasive pneumococcal infections are associated with longer hospital stays and required more intensive care than all other causes of pneumonia, in addition to be more costly, which justifies more attention for vaccination. This study also suggests an increase of economic and health burden with age and presence of underlying conditions.

[Vaccination status and factors associated with pneumococcal vaccination in geriatric short-stay care]. / Statut vaccinal et facteurs associés à la vaccination antipneumococcique en court séjour gériatrique.

Nearly two-thirds of geriatric short-stay patients were eligible for pneumococcal vaccination. Among patients eligible for vaccination, less than 5 % had received at least one injection of pneumococcal vaccine on admission. We found no modifiable factors associated with vaccination status, but several avenues for improving vaccination coverage.

Pneumococcal Perplexity: Improving Awareness of Updated Pneumococcal Vaccination Recommendations in Two Large Military Treatment Facilities.

INTRODUCTION: Vaccinations are an essential aspect of preventive medicine. In October 2021, the pneumococcal conjugate vaccine-20 (PCV-20) and PCV-15 were authorized for use in adults by the U.S. FDA. In 2022, the Advisory Committee on Immunization Practices (ACIP) subsequently published updated pneumococcal vaccination recommendations that incorporate both PCV-20 and PCV-15. Pneumococcal vaccination is effective in reducing pneumococcal disease, particularly in high-risk patient groups such as those with chronic lung disease; however, the updated dosing schedule for pneumococcal vaccinations can be quite confusing, especially if patients have previously received "older" vaccinations, such as pneumococcal polysaccharide vaccine-23 or PCV-13. The purpose of this quality improvement project was to increase providers' knowledge of current ACIP pneumococcal vaccination recommendations, including indications and dosing schedule, and to improve pneumococcal vaccination rates among eligible adults and children. MATERIALS AND METHODS: Focused education sessions were presented to primary care and subspecialty residents, fellows, and staff at Brooke Army Medical Center and Wilford Hall Ambulatory Surgical Center regarding current ACIP pneumococcal vaccination recommendations. Sessions included information about PCV-15 and PCV-20 vaccines, indications for vaccination, and dosing schedules. Subjective knowledge of updated ACIP pneumococcal vaccination recommendations was assessed among primary care and subspecialty residents, fellows, and staff via an anonymous survey both pre- and post-intervention. Number of PCV-20 vaccinations given and estimated vaccination rates of patients aged 19 to 64 years with asthma were assessed pre- and post-intervention over a 6 month time span. RESULTS: Of surveyed providers, only 9% discussed vaccinations at every visit and 11% did not discuss vaccinations at all. There was a statistically significant increase in providers' knowledge of pneumococcal vaccination guidelines for children post-intervention (P = .01) but no statistically significant increase in knowledge for guidelines for adults, for patients that have received prior pneumococcal vaccines, or in overall confidence in recommending pneumococcal vaccines. There was a 17% increase in the number of PCV-20 vaccinations given post-intervention (198 pre-intervention, 232 post-intervention). The estimated PCV-20 vaccination rate for adults aged 19 to 64 years with asthma increased from 14.9% pre-intervention to 19.5% post-intervention (P = .33). CONCLUSIONS: There is a significant knowledge gap regarding ACIP pneumococcal vaccination recommendations among military providers and a low pneumococcal vaccination rate for adults aged 19 to 64 years with asthma at Joint Base-San Antonio MTFs. Focused education sessions were effective in increasing providers' knowledge of updated pneumococcal vaccination recommendations, confidence in recommending vaccines, total number of pneumococcal vaccinations given, and estimated pneumococcal vaccination rate for adults with asthma. The validity of conclusions drawn from our data were limited because of discordant numbers of survey respondents as well as potentially inaccurate estimates of pneumococcal vaccination rates pre- and post-intervention. Despite this, the results warrant continued education of pneumococcal vaccines, indications, and dosing schedules.

Quality Improvement Interventions to Enhance Vaccine Uptake in Cancer Patients: A Systematic Review.

INTRODUCTION: Cancer patients, because of their compromised immune responses, face a higher risk of preventable infections, leading to increased morbidity and mortality. Despite this, vaccination rates among these patients are suboptimal, and research on effective interventions to improve vaccination rates is limited. METHODS: We conducted a comprehensive search in PubMed and Cochrane Library for studies investigating quality improvement (QI) interventions targeting vaccine uptake in cancer patients. Two authors independently screened, extracted data, and analyzed studies, resolving any discrepancies through consensus. RESULTS: Thirteen studies met the inclusion criteria, published between 2014 and 2022. Seven studies focused on the influenza vaccine, five on the pneumococcal vaccine, and one on both. Twelve studies used multiple interventions, whereas one used a single intervention. Most interventions aimed to enhance patient and family knowledge and identify eligible patients before their appointments. All studies demonstrated improved vaccine uptake after implementing the interventions. CONCLUSIONS: A variety of QI interventions have effectively increased pneumococcal and influenza vaccine uptake among cancer patients. Future research should address roadblocks to implementation and explore the effect of these interventions on other vaccines.

Real-World Coverage With Influenza, Pneumococcal, and Herpes Zoster Vaccines Among Patients With Rheumatic Diseases in a Nationwide Healthcare Plan.

OBJECTIVE: Vaccination against preventable infections is important for the management of rheumatic diseases (RDs). This study assessed the vaccination coverage and predictors among patients with RDs using real-world data from Israel. METHODS: This retrospective cross-sectional study, based on a Maccabi Healthcare Services database, included adult patients diagnosed with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and systemic lupus erythematosus (SLE), as of April 30, 2019. Age-specific vaccination coverage for influenza (past year), pneumococcal (23-valent pneumococcal polysaccharide vaccine [PPSV23] and/or 13-valent pneumococcal conjugate vaccine [PCV13]), and live-attenuated herpes zoster (HZ) vaccines (past 5 years) was reported. Logistic regression was used to investigate predictors of vaccination. RESULTS: The study included 14,528 patients (RA: n = 6932; PsA: n = 4395; SLE: n = 1951; > 1 condition: n = 1250). Influenza vaccine coverage among patients with RA, PsA, and SLE was 45.1%, 36.2%, and 33.7%, respectively. For PPSV23, corresponding rates were 19.6%, 16.2%, and 12.6%, respectively. In the elderly population (≥ 65 years), 63.2% had influenza vaccine in the past year and 83.4% had a PPSV23 vaccine in the past 5 years or at age ≥ 65. For PCV13 and HZ, coverage in the overall study population was low at 4.8% and 3.6%, respectively. Central residence and treatment with corticosteroids and biologic or targeted synthetic disease-modifying antirheumatic drugs within the past 5 years were significant predictors of vaccination coverage across all vaccines (P < 0.05). Other predictors varied by vaccine, including female sex (influenza, PPSV23, PCV13), age (influenza, PPSV23), chronic comorbidities (influenza, PPSV23, PCV13), shorter disease duration (PCV13), and high socioeconomic status (PCV13, HZ). CONCLUSION: This study demonstrated suboptimal coverage of influenza, pneumococcal, and HZ vaccination in patients with RA, PsA, and SLE, in particular among younger adults in Israel.

Surveillance of pneumococcal serotypes in adults hospitalised with acute lower respiratory tract infection in Bristol, UK.

INTRODUCTION: Pneumococcus remains a major cause of adult lower respiratory tract infections (LRTI). Few data exist on the relative contribution of serotypes included in pneumococcal vaccines to community-acquired pneumonia (CAP) and non-pneumonic (NP) LRTI. We measured the burden of all and vaccine-serotype pneumococcal respiratory infection following SARS-CoV-2 emergence to inform evidence-based vaccination policy. METHODS: A prospective cohort study at two Bristol hospitals (UK) including all adults age ≥ 18-years hospitalised with acute lower respiratory tract disease (aLRTD) from Nov2021-Nov2022. LRTI patients were classified as: a) radiographically-confirmed CAP (CAP+/RAD+), b) clinically-diagnosed CAP without radiological confirmation (CAP+/RAD-), or c) NP-LRTI. Pneumococcus was identified by blood culture, BinaxNOW™and serotype-specific urine antigen detection assays (UAD). RESULTS: Of 12,083 aLRTD admissions, 10,026 had LRTI and 2,445 provided urine: 1,097 CAP + RAD+; 207 CAP + RAD-; and 1,141 NP-LRTI. Median age was 71.1y (IQR57.9-80.2) and Charlson comorbidity index = 4 (IQR2-5); 2.7 % of patients required intensive care, and 4.4 % died within 30-days of hospitalisation. Pneumococcus was detected in 280/2445 (11.5 %) participants. Among adults aged ≥ 65y and 18-64y, 12.9 % (198/1534) and 9.0 % (82/911), respectively, tested pneumococcus positive. We identified pneumococcus in 165/1097 (15.0 %) CAP + RAD+, 23/207 (11.1 %) CAP + RAD-, and 92/1141 (8.1 %) NP-LRTI cases. Of the 280 pneumococcal cases, 102 (36.4 %) were due to serotypes included in PCV13 + 6C, 115 (41.7 %) in PCV15 + 6C, 210 (75.0 %) in PCV20 + 6C/15C and 228 (81.4 %) in PPV23 + 15C. The most frequently identified serotypes were 8 (n = 78; 27.9 % of all pneumococcus), 7F (n = 25; 8.9 %), and 3 (n = 24; 8.6 %). DISCUSSION: Among adults hospitalised with respiratory infection, pneumococcus is an important pathogen across all subgroups, including CAP+/RAD- and NP-LRTI. Despite 20-years of PPV23 use in adults ≥ 65-years and herd protection due to 17-years of PCV use in infants, vaccine-serotype pneumococcal disease still causes a significant proportion of LRTI adult hospitalizations. Direct adult vaccination with high-valency PCVs may reduce pneumococcal disease burden.

The potential impact of PCV-13, PCV-15 and PCV-20 vaccines in Colombia.

PURPOSE: To provide information about which pneumococcal vaccine could have greater coverage in Colombia. METHODS: This is a retrospective analysis of patients diagnosed with invasive pneumococcal disease (IPD) between 2015 and 2019 in Bogotá, Colombia. We compared the theoretical serotype coverage of the available anti-pneumococcal vaccines (i.e., PCV-10, PCV-10 SII, PCV-13, PCV-15, PCV-20, PCV-21, PCV24, PPSV-23) and the non-vaccine-covered serotypes stratified by age. RESULTS: 690 IPD cases were included. In children ≤5 y/o, of the approved vaccines PCV-20 showed the most theoretical protection (71.3 % [149/209]), while in adults aged 18-64 y/o was PCV-20 (61.8 % [164/265]), and in those ≥65 y/o was PPSV-23 (58.1 % [100/172]) followed by PCV-20 (55.2 % [95/172]). The non-covered serotypes represented one-third of the cohort (33.9 % [234/690]), being 6C (20.5 % [48/234]), 15A (12.8 % [30/234]), and 23A (11.5 % [27/234]) the most prevalent. CONCLUSION: Introducing PCV-20 for children and PCV-20 along with a PPSV-23 booster in adults may reduce IPD frequency in all ages in Colombia. The inclusion of non-covered serotypes is required for future vaccines.