Introduction Nearly all existing respiratory syncytial virus (RSV) incidence estimates are based on real-time polymerase chain reaction (RT–PCR) testing of nasal or nasopharyngeal (NP) swabs. Adding testing of additional specimen types to NP swab RT–PCR increases RSV detection. However, prior studies only made pairwise comparisons and the synergistic effect of adding multiple specimen types has not been quantified. We compared RSV diagnosis by NP swab RT–PCR alone versus NP swab plus saliva, sputum, and serology. Methods This was a prospective cohort study over two study periods (27 December 2021 to 1 April 2022 and 22 August 2022 to 11 November 2022) of patients aged ≥ 40 years hospitalized for acute respiratory illness (ARI) in Louisville, KY. NP swab, saliva, and sputum specimens were collected at enrollment and PCR tested (Luminex ARIES platform). Serology specimens were obtained at acute and convalescent timepoints (enrollment and 30–60-day visit). RSV detection rate was calculated for NP swab alone and for NP swab plus all other specimen type/test. Results Among 1766 patients enrolled, 100% had NP swab, 99% saliva, 34% sputum, and 21% paired serology specimens. RSV was diagnosed in 56 (3.2%) patients by NP swab alone, and in 109 (6.2%) patients by NP swab plus additional specimens, corresponding to a 1.95 times higher rate [95% confidence interval (CI) 1.62, 2.34]. Limiting the comparison to the 150 subjects with all four specimen types available (i.e., NP swab, saliva, sputum, and serology), there was a 2.60-fold increase (95% CI 1.31, 5.17) compared to NP swab alone (3.3% versus 8.7%). Sensitivities by specimen type were: NP swab 51%, saliva 70%, sputum 72%, and serology 79%. Conclusions Diagnosis of RSV in adults was several-fold greater when additional specimen types were added to NP swab, even with a relatively low percentage of subjects with sputum and serology results available. Hospitalized RSV ARI burden estimates in adults based solely on NP swab RT–PCR should be adjusted for underestimation.

Controversy exists regarding the clinical effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for the prevention of serotype-specific community-acquired pneumonia (CAP). The objective of this study was to define the effectiveness of PPSV23 for the prevention of CAP hospitalizations due to vaccine-contained serotypes. This secondary analysis was a nested case–control, test-negative study design of adult patients hospitalized for CAP between 1 June 2014 and 31 March 2017. Cases included patients with CAP due to a S. pneumoniae serotype contained in the PPSV23. Urinary antigen detection of the 23 serotypes was performed. In the study, PPSV23 vaccination alone and no other pneumococcal vaccination was the primary exposure of interest. Vaccine effectiveness was calculated as (1-OR) × 100. Adjusted estimates were obtained from a logistic regression model that controlled for confounding variables. A total of 3686 patients were included in the analysis. The PPSV23 vaccination was documented in 608 (16%) patients, and the PPSV23-serotype CAP was detected in 48 (8%) PPSV23-vaccinated patients and in 288 (9%) non-vaccinated patients. Unadjusted vaccine effectiveness for preventing PPSV23-serotype CAP was 17% (95% CI: −13% to 40%). Adjusted estimates for preventing PPSV23-serotype CAP was 14% (95% CI: −17% to 38%). In this study, PPSV23 vaccination offered no protection against PPSV23-serotype CAP hospitalization in adults. This is the first PPSV23 vaccine effectiveness study from United States that utilized a urinary antigen detection assay as the main method for S. pneumoniae serotyping. This study highlights the need for more effective vaccines in the prevention of hospitalization due to S. pneumoniae CAP.

During the COVID-19 pandemic, a significant decline in Mycoplasma pneumoniae was observed; however, M. pneumoniae re-emerged globally in 2023. Here, we describe a current outbreak of M. pneumoniae infections in the United States (US). More than 287 million patient records from all 50 states in the US were reviewed to identify patients with a M. pneumoniae diagnosis between 1 January 2017 and 30 September 2024. A c-chart was created by calculating the mean and standard error (SE) of cases during the pre-COVID-19 pandemic period, with the upper control limit (UCL) set at 3 SE above the mean. The presence of an outbreak was defined as counts above the UCL. Cumulative excess cases were used to estimate the magnitude of the outbreak, and the fold increase was calculated. A US outbreak of M. pneumoniae began at the end of 2023, resulting in 9708 excess cases corresponding to a 9.0-fold increase over the baseline UCL. The outbreak is ongoing, affects both children and adults, and includes patients with M. pneumoniae community-acquired pneumonia requiring hospitalization. This US outbreak of M. pneumoniae has significant implications for the management of patients with respiratory infections during the current pneumonia season.

Background: Most epidemiologic studies and clinical testing use single nasal/nasopharyngeal swab (NPS) for respiratory syncytial virus (RSV) detection. Studies document that RSV detection improves if another specimen is added to NPS, but the impact of using multiple specimen types has not been assessed. We quantified RSV detection increase using multiple-specimen testing versus NPS alone. Methods: Hospitalized adults aged ≥40 years with acute respiratory illness were prospectively enrolled in 7 US/Canadian hospitals. NPS, saliva, sputa, and acute/convalescent sera were collected and tested. Results: Among 3669 participants, 100% had NPS, 97.7% saliva, 33.0% sputum, and 33.4% paired serology. RSV detection was 112% higher (95% CI, 86%–141%) using all specimen types as compared with NPS alone. Serology test sensitivity was the highest (73.0%; 95% CI, 65.1%–80.8%), followed by sputum (70.1%; 95% CI, 62.1%–78.0%), saliva (61.4%; 95% CI, 55.4%–67.5%), and NPS (47.2%; 95% CI, 41.1%–53.4%). Among those with congestive heart failure exacerbations, additional specimens increased detection by 267% (95% CI, 85%–625%), and saliva detected more infections than NPS. Among 1013 participants with paired NPSs from different time points, specimens collected on average 1 day later detected 30% fewer RSV infections. Conclusions: RSV detection increased >100% using 4 specimen types, suggesting a 2-fold correction factor is appropriate for incidence and prevalence studies relying on NPS alone. Saliva was more sensitive than NPS, warranting further study, particularly in cardiac cases.

Background: The epidemiology and outcomes of community-acquired pneumonia (CAP) in immunocompromised hosts (ICHs) are not well defined. The objective of this study was to define the epidemiology and outcomes of CAP in ICHs as compared with non-ICHs. Methods: This ancillary study included a prospective cohort of hospitalized adult Louisville residents with CAP from 1 June 2014 to 31 May 2016. An ICH was defined per the criteria of the Centers for Disease Control and Prevention. Geospatial epidemiology explored associations between ICHs hospitalized with CAP and income level, race, and age. Mortality for ICHs and non-ICHs was evaluated during hospitalization and 30 days, 6 months, and 1 year after hospitalization. Results: A total of 761 (10%) ICHs were identified among 7449 patients hospitalized with CAP. The most common immunocompromising medical conditions or treatments were advanced-stage cancer (53%), cancer chemotherapy (23%), and corticosteroid use (20%). Clusters of ICHs hospitalized with CAP were found in areas associated with low-income and Black or African American populations. Mortality by time point for ICHs vs non-ICHs was as follows: hospitalization, 9% vs 5%; 30 days, 24% vs 11%; 6 months, 44% vs 21%; and 1 year, 53% vs 27%, respectively. Conclusions: Approximately 1 in 10 hospitalized patients with CAP is immunocompromised, with advanced-stage cancer being the most frequent immunocompromising condition, as seen in half of all patients who are immunocompromised. Risk for hospitalization may be influenced by socioeconomic disparities and/or race. ICHs have a 2-fold increase in mortality as compared with non-ICHs.