Faculty Bibliography

Using CDC's Active Bacterial Core surveillance data, we observed increasing incidence of rare group B Streptococcus serotypes VI and VIII, from 0.007 and 0 cases per 100,000 in 2007 to 0.14 and 0.13 in 2023, respectively. These serotypes disproportionally impacted American Indian/Alaska Native, Asian, and Native Hawaiian/Pacific Islander populations.

Group B Streptococcus (GBS) intestinal colonization is critical for the pathogenesis of late-onset disease in infants. Using a murine model, we explore the role of rodA, which encodes a peptidoglycan polymerase RodA, belonging to the shape, elongation, division, and sporulation family that participates in peptidoglycan synthesis and maintenance of cell wall integrity. We investigated the contribution of rodA to GBS gastrointestinal (GI) colonization using a wild-type strain (A909 WT) and an isogenic in-frame deletion mutant of rodA (A909ΔrodA). Morphological differences between the two strains were examined by transmission electron microscopy (TEM), and the contribution of rodA to GI colonization was assessed in a murine model through monocolonization and cocolonization experiments. We evaluated the growth of the mutant strain under intestinal physiological stress conditions and characterized its interactions with host epithelial cells in vitro. A909ΔrodA showed a unique chaining/aggregation phenotype compared to the A909 WT strain, with the presence of capsule confirmed via TEM and immunoblotting. In murine cocolonization experiments, A909 WT outcompeted A909ΔrodA; however, monocolonization experiments exhibited comparable colonization and bacterial burden across the GI tract. In vitro experiments revealed impaired growth in bile and an increase in adhesion to intestinal epithelial cells by the ΔrodA mutant. rodA plays a role in GBS intestinal colonization. Deletion of rodA increases sensitivity to gastrointestinal stressors in vitro and causes a pronounced defect in competition in vivo, suggesting that the presence of rodA increases the fitness of GBS in the gut.

Many medical providers in the United States have never seen a case of measles. This situation will likely change if decreases in childhood vaccination rates and increases in multi-state measles outbreaks continue. Measles can lead to hospitalization and severe disease, especially for high-risk groups including young children and people who are pregnant or immunocompromised. In-hospital transmission of measles can occur prior to diagnosis, as patients are infectious for approximately 4 days prior to the onset of rash. Review of the diagnosis and management of measles is essential for the hospitalist to ensure timely responses to this highly contagious virus.

UNLABELLED:. Our findings are consistent with interspecies HGT as a mechanism underlying emergence of serotype VIII GBS. IMPORTANCE/OBJECTIVE:, in the production of GBS serotype VIII and the complementation of its function by orthologs from other streptococci. Our work demonstrates GBS's ability to utilize genes from other streptococci to produce functional capsular polysaccharide. HGT could generate further capsule diversity beyond the 10 current serotypes, potentially increasing the number of strains capable of vaccine escape. Surveillance for such events is warranted.

Staphylococcus aureus is a global health concern, resulting in significant disease burden in both hospital and community settings. To establish infection, the bacteria must contend with a multitude of host defense mechanisms, including "nutritional immunity", in which nutrients are sequestered away from invading pathogens. Importantly, S. aureus requires iron for growth during infection, which it acquires through the lysis of erythrocytes (hemolysis). HlgAB, a secreted bi-component pore forming toxin, contributes to the ability of S. aureus to lyse erythrocytes to release heme iron. HlgAB consists of two subunits, the S-subunit HlgA and the F-subunit HlgB. Prior work has shown that the hemolytic activity of HlgAB is dependent on the binding of HlgA to the host receptor Duffy Antigen Receptor for Chemokines (DARC). Here we show that HlgB binds the surface of erythrocytes independently of DARC or HlgA. Our comparative genomic analysis reveals high conservation of hlgA and hlgB genes across S. aureus lineages. By performing structure-function studies, we identified a series of loops within the rim domain of HlgB that are required for the binding of HlgB to erythrocytes and erythrocyte lysis by HlgAB. The importance of HlgB-mediated host targeting was validated in a tissue culture model of S. aureus-mediated lysis of primary human erythrocytes, in an in vivo murine model of intoxication, and during in vivo systemic infection. Altogether, these findings expand our mechanistic insights into how S. aureus overcomes nutritional immunity, and the role of HlgB in S. aureus pathophysiology.

The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations for use. The ACIP Work Groups (WG) conduct an in-depth review of the available scientific information regarding specific FDA-licensed vaccines, or important vaccines in advanced stages of clinical development that are under consideration for FDA licensure and then present the information and their recommendation to the ACIP for a vote. If a recommendation receives a majority vote, it moves to the CDC Director for approval and, if approved, it is published in the CDC Morbidity and Mortality Weekly Report (MMWR). At that point the ACIP recommendation represents the official CDC recommendation for U.S. immunizations. The ACIP met on April 16-17, 2025, to discuss influenza vaccines, chikungunya vaccines, coronavirus disease (COVID-19) vaccines, RSV immunizations, meningococcal vaccines, human papillomavirus (HPV) vaccines, Mpox vaccines, and cytomegalovirus (CMV) vaccines. This update summarizes the proceedings of these meetings, with an emphasis on topics that are most relevant to the pediatric population. Major updates for pediatric clinicians include information regarding HPV and meningococcal vaccination considerations, and updates regarding RSV immunization in infants which will likely be voted on during upcoming ACIP meetings.

Vaccine-preventable diseases that have yet to be eliminated are important to review for the practicing clinician. Haemophilus influenzae type b (Hib) was once the leading cause of bacterial meningitis in young children and now causes rare invasive disease in young children and the elderly. Patients with immunodeficiency and impaired complement response to encapsulated organisms (e.g., sickle cell disease; asplenia) are at particular risk of invasive Hib disease. Recognition of a potential case, prompt management and reporting, and inpatient vaccine administration and education are crucial actions for hospitalists in the management of Hib disease and prevention.

IMPORTANCE:SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity. OBJECTIVE:To characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease. DESIGN, SETTING, AND PARTICIPANTS:This secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax. Participants were SARS-CoV-2 negative at baseline and acquired COVID-19 during the blinded phase of the trials. The setting included the US, Brazil, South Africa, Colombia, Argentina, Peru, Chile, and Mexico; start dates were July 27, 2020, to December 27, 2020; data cutoff dates were March 26, 2021, to July 30, 2021. Statistical analysis was performed from November 2022 to June 2023. MAIN OUTCOMES AND MEASURES:Linear regression was used to assess the association of demographic and clinical characteristics, viral variant, and trial with polymerase chain reaction-measured log10 VL in nasal and/or nasopharyngeal swabs taken at the time of COVID-19 diagnosis. RESULTS:Among 1667 participants studied (886 [53.1%] male; 995 [59.7%] enrolled in the US; mean [SD] age, 46.7 [14.7] years; 204 [12.2%] aged 65 years or older; 196 [11.8%] American Indian or Alaska Native, 150 [9%] Black or African American, 1112 [66.7%] White; 762 [45.7%] Hispanic or Latino), median (IQR) log10 VL at diagnosis was 6.18 (4.66-7.12) log10 copies/mL. Participant characteristics and viral variant explained only 5.9% of the variability in VL. The independent factor with the highest observed differences was trial: Janssen participants had 0.54 log10 copies/mL lower mean VL vs Moderna participants (95% CI, 0.20 to 0.87 log10 copies/mL lower). In the Janssen study, which captured the largest number of COVID-19 events and variants and used the most intensive post-COVID surveillance, neither VL at diagnosis nor averaged over days 1 to 28 post diagnosis was associated with COVID-19 severity. CONCLUSIONS AND RELEVANCE:In this study of placebo recipients from 4 randomized phase 3 trials, high variability was observed in SARS-CoV-2 VL at the time of COVID-19 diagnosis, and only a fraction was explained by individual participant characteristics or viral variant. These results suggest challenges for future studies of interventions seeking to influence VL and elevates the importance of standardized methods for specimen collection and viral load quantitation.