Colonization with 19F and other pneumococcal conjugate vaccine serotypes in children in St. Louis, Missouri, USA.

BACKGROUND: The epidemiology of nasopharyngeal (NP) pneumococcal carriage varies with geography and has changed in response to pneumococcal conjugate vaccine (PCV): a low prevalence (3% or less of colonizing isolates) of colonization by vaccine-type (VT) pneumococcal serotypes after PCV introduction has been reported. The primary goal of this study was to determine the VT serotype prevalence of NP pneumococcal colonization of children residing in the St. Louis, MO, USA metropolitan area following introduction of the 13-valent PCV in 2010. The secondary goal of this study was to identify characteristics associated with NP pneumococcal carriage of any serotype. METHODS: Between July 2013 and April 2016, we enrolled 397 healthy children, aged 0-17years, who required sedation for procedures or minor surgeries at St. Louis Children's Hospital. NP swabs were collected after sedation or anesthesia and cultured for pneumococcus. Vaccine records were obtained from primary care providers or from state immunization databases. Parents/guardians completed a questionnaire to provide demographics, past medical history and household characteristics. RESULTS: Of the 88 pneumococcal isolates recovered from 84 colonized subjects (21.2% of all enrolled subjects; 95% CI 17.2-25.2%), 16 were VT. Eleven isolates were serotype 19F (12.5%), four (4.5%) were 6A and one (1.1%) was 19A. Prevalence of VT among colonizing isolates was thus 18.2% (CI 10.1-26.1%) in our cohort, despite complete PCV vaccination in 87% of colonized children. Factors associated with pneumococcal colonization by any serotype included younger age and daycare attendance. CONCLUSION: Children in St. Louis exhibit a higher prevalence of VT serotypes among pneumococcal carriage isolates than has been reported in other areas in the US, demonstrating the necessity of ongoing surveillance of local epidemiology and providing evidence that serotype 19F can remain prevalent in a pediatric population despite high vaccine uptake.

L-Plastin promotes podosome longevity and supports macrophage motility.

Elucidating the molecular regulation of macrophage migration is essential for understanding the pathophysiology of multiple human diseases, including host responses to infection and autoimmune disorders. Macrophage migration is supported by dynamic rearrangements of the actin cytoskeleton, with formation of actin-based structures such as podosomes and lamellipodia. Here we provide novel insights into the function of the actin-bundling protein l-plastin (LPL) in primary macrophages. We found that podosome stability is disrupted in primary resident peritoneal macrophages from LPL-/- mice. Live-cell imaging of F-actin using resident peritoneal macrophages from LifeACT-RFP+ mice demonstrated that loss of LPL led to decreased longevity of podosomes, without reducing the number of podosomes initiated. Additionally, macrophages from LPL-/- mice failed to elongate in response to chemotactic stimulation. These deficiencies in podosome stabilization and in macrophage elongation correlated with impaired macrophage transmigration in culture and decreased monocyte migration into murine peritoneum. Thus, we have identified a role for LPL in stabilizing long-lived podosomes and in enabling macrophage motility.

Prevalence of nasopharyngeal pneumococcal colonization in children and antimicrobial susceptibility profiles of carriage isolates.

Nasopharyngeal (NP) pneumococcal carriage predisposes children to pneumococcal infections. Defining the proportion of pneumococcal isolates that are antibiotic-resistant enables the appropriate choice of empiric therapies. The antibiogram of NP carriage isolates derived from a pediatric population following the introduction of the 13-valent pneumococcal conjugate vaccine was defined in this study.