Streptococcus pneumoniae is a major cause of community-acquired pneumonia, bacteremia, and meningitis in older adults worldwide. Two pneumococcal vaccines containing S. pneumoniae capsular polysaccharides are in current use: the polysaccharide vaccine PPSV23 and the glycoconjugate vaccine PCV13. In clinical trials, both vaccines elicit similar opsonophagocytic killing activity. In contrast to polysaccharide vaccines, conjugate vaccines have shown consistent efficacy against nasopharyngeal carriage and noninvasive pneumonia overall and for some prevalent individual serotypes. Given these different clinical profiles, it is crucial to understand the differential immunological responses induced by these two vaccines. Here, we used a high-throughput systems serology approach to profile the biophysical and functional features of serum antibodies induced by PCV13 and PPSV23 at 1 month and 1 year. In comparison with PPSV23, PCV13 induced higher titers across antibody isotypes; more durable antibody responses across immunoglobulin G (IgG), IgA, and IgM isotypes; and increased antigenic breadth. Although titers measured in opsonophagocytic activity (OPA) assays were similar between the two groups, confirming what was observed in clinical studies, serum samples from PCV13 vaccinees could induce additional non-OPA antibody-dependent functions, including monocyte phagocytosis and natural killer cell activation. In a multivariate modeling approach, distinct humoral profiles were demonstrated in each arm. Together, these results demonstrate that the glycoconjugate PCV13 vaccine induces an antigenically broader, more durable, polyfunctional antibody response. These findings may help explain the increased protection against S. pneumoniae colonization and noninvasive pneumonia and the longer duration of protection against invasive pneumococcal disease, mediated by PCV13.

Vaccines remain a fundamental intervention for preventing illness and death. In the United States, suboptimal vaccine uptake in adolescents and young adults has been observed for meningococcal conjugate (MenACWY) and serogroup B meningococcal (MenB) vaccines, particularly among marginalized communities, despite current recommendations by the Advisory Committee on Immunization Practices. A systematic literature search was conducted in the MEDLINE and MEDLINE In-Process, Embase, Cochrane, PsychInfo, and CINAHL databases to identify both drivers of, and barriers to, MenACWY and MenB vaccine uptake in adolescents and young adults. A total of 34 of 46 eligible studies that presented outcomes stratified by race/ethnicity, geography, and socioeconomic status were selected for review. Results showed MenACWY and MenB vaccination coverage in adolescents and young adults is impacted by racial/ethnic, socioeconomic, and geographic disparities. Gaps also exist in insurance for, or access to, these vaccines in adolescents and young adults. Moreover, there was variability in the understanding and implementation of the shared decision-making recommendations for the MenB vaccine. Disease awareness campaigns, increased clarity in accessing all meningococcal vaccines, and further research on the relationships between measures of marginalization and its impact on vaccine coverage in adolescents and young adults are needed to reduce the incidence of severe infections.

Background: Nirmatrelvir/ritonavir (NMV/r) is an oral antiviral drug used to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in patients aged 12 years or older at high risk of progression to severe disease (eg, hospitalization and death). Despite being the preferred option for outpatient treatment in the majority of countries worldwide, NMV/r is currently underutilized in real-world clinical practice. Areas of Uncertainty: As numerous real-world studies have described patient outcomes following treatment with NMV/r, this systematic literature review provides a comprehensive summary of evidence on NMV/r effectiveness against hospitalization and mortality further organized by clinically meaningful categories, such as acute versus longer-term follow-up, age, underlying health conditions, and vaccination status, to help inform health care decision making. Data Sources: We searched Embase and PubMed (December 22, 2021–March 31, 2023) and congress abstracts (December 1, 2021–December 31, 2022) for reports describing NMV/r effectiveness. Therapeutic Advances: In total, 18 real-world studies met final selection criteria. The evidence showed that NMV/r significantly reduced postinfection risk of all-cause and COVID-19-related hospitalization and mortality in both acute (≤30 days) (21%–92%) and longer-term (>30 days) (1%–61%) follow-up. The reduction in postinfection risk was higher when treatment was received within 5 days of symptom onset. Real-world effectiveness of NMV/r treatment was observed regardless of age, underlying high-risk conditions, and vaccination status. Conclusion: The systematic literature review findings demonstrated the effectiveness of NMV/r against hospitalization and mortality during the Omicron period among individuals at high risk of progression to severe COVID-19 disease.

Background: Healthcare workers are at increased risk of exposure to respiratory pathogens including Streptococcus pneumoniae (pneumococcus). While little asymptomatic carriage has been reported in young-to-middle-aged adults, this may be due to nonsensitive diagnostic methods. The aim of the current study was to investigate the rates of pneumococcal carriage in a large cohort of healthcare workers, using saliva as a respiratory specimen. Methods: We evaluated pneumococcal carriage in convenience samples of saliva, self-collected from asymptomatic healthcare workers (Connecticut, USA) who were testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 30 March to 11 June 2020. DNA extracted from the culture-enriched saliva was later tested using quantitative polymerase chain reaction for piaB, lytA, and serotype. Saliva samples were considered positive for pneumococcus when the piaB cycle threshold value was <40. Results: Study participants were 22–74 years old (mean age, 38.5 years), 75% female, 75% white, and with occupations including registered nurses (48%), medical doctors (23%), and patient care assistants (5%). Overall, 138 of 1241 samples (11%) from 86 of 392 individuals (21%) tested piaB positive at some point during the 4-month study period, with 28 (33%) colonized individuals positive at multiple time points. Carriers reflected the overall study population. No significant demographic characteristics were associated with detection of pneumococcus. Colonized individuals primarily carried serotypes 19F (25.6%) and 3 (12.8%). Conclusions: During a period of mandatory masking, we identified a cumulative pneumococcal carriage prevalence of 21% among healthcare workers. This study highlights that healthcare workers may act as unrecognized reservoirs of pneumococcus in the population. Despite long-standing pediatric immunization programs, vaccine-targeted serotypes continue to be prevalent among the adult population.

Introduction: Community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae is a substantial cause of morbidity and mortality among older adults. This study estimated incidences of CAP, chest X-ray−confirmed CAP (CXR+CAP), S pneumoniae-positive CAP, S pneumoniae-positive CXR+CAP, and S. pneumoniae serotype distribution among 46,000 at-risk adults aged ≥ 50 years residing in Chrzanów County, Poland. Material and methods: From January 2010 to January 2012, all facilities providing ambulatory and inpatient care enrolled all consenting resident patients with suspicion of CAP. Chest X-rays, urine, blood, and sputum samples were analyzed. Annualized incidence rates were determined. Presence of S pneumoniae-positive CAP and/or S. pneumoniae serotype distribution was determined using the urine antigen detection assay (capable of detecting the serotypes in the 13-valent pneumococcal conjugate vaccine [PCV13]), BinaxNOW®, and/or microbiology cultures. Results: Among 5055 enrolled patients, 1195 (23.7%) were diagnosed with CAP and 1166 (23.4%) had CXR+CAP. S. pneumoniae was detected in 144 (12.1%) and 131 (11.2%) patients from the CAP and CXR+CAP cohorts, respectively. Annualized incidence rates of CAP, CXR+CAP, S pneumoniae-positive CAP, and S. pneumoniae-positive CXR+CAP were 12.8, 12.5, 1.6, and 1.4 per 1000 residents, respectively. Among CXR+CAP patients, 39.7% were aged 50 to 64 years and 60.3% were aged ≥ 65 years. Incidence rates generally increased with age. The most common serotypes in S. pneumoniae-positive CXR+CAP patients were 3 (n = 15), 23F (n = 10), 18C (n = 9), and 9V (n = 6). Conclusions: CAP due to PCV13 serotypes is a source of morbidity among adults >50 years and may be reduced by greater access to pneumococcal vaccines.

Background: In the United States, the invasive pneumococcal disease incidence in Indigenous populations is higher than in the general population. Molecular detection and/or specimen sampling from multiple body sites could enhance our understanding of pneumococcal carriage, a prerequisite for disease. Methods: Persons aged <5 and ≥18 years from the Navajo Nation and White Mountain Apache Tribal lands were enrolled in an observational carriage study from October 2015 through September 2017. Swabs from the nasopharynx (all participants) and oropharynx (adults only) were collected and tested by enriched culture or molecular methods (lytA and piaB polymerase chain reaction [PCR]). Cultured Streptococcus pneumoniae was serotyped by sequencing. PCR-positive samples were serotyped by 13-valent pneumococcal conjugate vaccine (PCV13)–type PCR and TaqMan array card PCR. Results: An overall 1503 participants were enrolled (age <5 years, n = 600; ≥18 years, n = 903). Among children, pneumococcal positivity was similar by culture (49.5%) and PCR (50.8%); PCV13-type carriage was 8.0% by any method. Among adults, oropharyngeal swab positivity by PCR was 18.5%, an increase when compared with cultured oropharyngeal swabs (0.6%) and nasopharyngeal swabs by culture (7.9%) or PCR (5.3%); PCV13-type carriage by any sample or method was 8.0%. Conclusions: PCV13-type carriage persists in Indigenous populations. Use of molecular methods and oropharyngeal swabs for adults increased carriage prevalence estimates.